Delayed sequential abdominal wall closure in pediatric liver transplantation to overcome "large for size" scenarios.

BACKGROUND: Primary abdominal wall closure after pediatric liver transplantation (PLT) is neither always possible nor advisable, given the graft-recipient size discrepancy and its potential large-for-size scenario. Our objective was to report the experience accumulated with delayed sequential closure (DSC) guided by Doppler ultrasound control. METHODS: Retrospective analysis of DSC performed from 2013 to March 2020. RESULTS: Twenty-seven DSC (26.5%) were identified out of 102 PLT. Transplant indications and type of grafts were similar among both groups. In patients with DSC, mean weight and GRWR were 9.4 ± 5.5 kg (3.1-26 kg) and 4.7 ± 2.4 (1.9-9.7), significantly lower and higher than the primary closure cohort, respectively. The median time to achieve definitive closure was 6 days (range 3-23 days), and the median number of procedures was 4 (range 2-9). Patients with DSC had longer overall PICU (22.5 ± 16.9 vs. 9.1 ± 9.7 days, p < .05) and hospital stay (33.4 ± 19.1 vs 23, 9 ± 19.8 days (p < .05). These differences are less remarkable if the analysis is performed in a subgroup of patients weighing less than 10 kg. Two patients presented vascular complications (7.4%) within DSC group. No differences were seen when comparing overall, 3-year graft and patient survival (96% and 96% in the DSC group). CONCLUSIONS: DSC is a simple and safe technique to ensure satisfactory clinical outcomes to overcome "large for size" scenarios in PLT. In addition, we were able to avoid using a permanent biological material for closing the abdomen.

Impact of COVID-19 on Families of Pediatric Solid Organ Transplant Recipients.

OBJECTIVE: The COVID-19 pandemic and lockdown measures have had a clear psychological impact on families, and specifically those with children with chronic illnesses have reported greater overloads and exhaustion. The objective of this study was to evaluate the exposure, impact and experience of the pandemic on families of pediatric solid organ transplant (SOT) recipients compared to families of healthy children and adolescents. METHODS: We recruited 96 families, 48 with a pediatric SOT recipient and 48 healthy controls, matched by child age and gender. A primary caregiver from each family responded to an online sociodemographic questionnaire and the COVID-19 Exposure and Family Impact Survey (CEFIS), which explores the exposure, impact and experience of the pandemic and lockdown on families. RESULTS: Exposure to the pandemic was greater in families of healthy children and adolescents. The impact was mostly negative in both groups: caregivers reported increased anxiety (76%) and mood disturbances (71.9%) and hindered quality of sleep (64.6%) and health habits (58.3%). On the positive side, family relationships improved. Qualitatively, the SOT group positively perceived isolation and established hygienic measures as protective and destigmatizing, although they reported fear of virus transmission to their child. CONCLUSIONS: The psychological impact of the pandemic has been similar in both groups, although families of transplant recipients have protected themselves more, probably because they are used to prevention measures and they see contagion as a graver risk. Additionally, SOT recipients' families presented some idiosyncratic elements, especially a decrease in their perception of stigma associated with the medical condition.

Endoscopic variceal ligation as primary prophylaxis for upper GI bleeding in children.

BACKGROUND AND AIMS: Variceal hemorrhage can be a life-threatening adverse event of chronic liver disease. In contrast to the well-described guidelines for the management of portal hypertension (PH) in adults, there is limited evidence about the optimal prophylactic management of variceal bleeding in children. This study was carried out to assess the efficacy of endoscopic variceal ligation (EVL) as primary prophylaxis to prevent upper GI bleeding in children with PH. METHODS: From January 2014 to April 2018, all pediatric patients with PH disease and medium to large esophageal varices or reddish spots, regardless of the grade of the varix, were prospectively included in the protocol of primary prophylaxis with EVL. A second retrospective group of patients was made after reviewing medical records of 32 pediatric patients with PH that presented esophageal varices in the upper endoscopy and had received propranolol as primary prophylaxis. RESULTS: Twenty-four patients (75%) reached varices eradication in the EVL group, with a median of 2 procedures (range, 1-4) before eradication and a median time to eradication of 3.40 months (range, 1.10-13.33). No EVL-related adverse events were observed. Statistically significant differences were observed in the bleeding rate at 3 years between propranolol and EVL groups (6/32 [21.9%] vs 1/32 [3.2%], P < .02). The hazard ratio for bleeding for patients treated with propranolol compared with those treated with EVL was 2.6 (95% confidence interval, 1.53-3.67). CONCLUSIONS: EVL is a safe and effective treatment to prevent upper GI bleeding in pediatric patients with PH. (Clinical trial registration number: NCT03943784.).

Endotipsitis as an indication for pediatric liver transplantation.

Endotipsitis is a rare but severe complication of transjugular intrahepatic portosystemic shunt (TIPS), a device widely used to treat portal hypertension in adults, but sparsely used in children. We report a case of endotipsitis in a 3-year-old child affected of biliary atresia. She underwent a Kasai procedure at 3 months of age but, although the bile flow was restored, she presented upper gastrointestinal bleeding due to portal hypertension 1.5 years later. A TIPS was placed in order to control the hemorrhage. A year after TIPS placement, she started presenting repeated episodes of cholangitis. Blood cultures were positive to Enterobacter cloacae. Even with long antibiotic courses, adjusted to blood cultures, infectious signs were observed after antibiotic withdrawal. Device infection was demonstrated through Positron emission tomography-Computed tomography scan. The patient was listed for liver transplantation, and intravenous antibiotic treatment was maintained until stent removal during the liver transplant 8 months later. No infectious complications were demonstrated after the surgery. To the best of our knowledge, this is the first case report of endotipsitis described in a pediatric patient.

The Role of Liver Transplantation in Propionic Acidemia.

Despite optimal medical treatment and strict low-protein diet, the prognosis of propionic acidemia (PA) patients is generally poor. We aim to report our experience with liver transplantation (LT) in the management of PA patients. Six patients with PA received a LT at a mean age of 5.2 years (1.3-7.5 years). The indications for LT were frequent metabolic decompensations in the first 4 patients and preventative in the last 2 patients. Two patients presented hepatic artery thromboses that were solved through an interventional radiologist approach. These patients showed a very high procoagulant state that was observed by thromboelastography. Arterial vasospasm without thrombus was observed in 2 patients during the LT surgery. In order to avoid hepatic artery thrombosis, an arterial conduit from the recipient aorta to the hepatic artery of the donor was used in the fifth patient. After LT, patients presented improvement in propionyl byproducts without complete normalization, but no decompensations have been observed. In conclusion, LT could be a good therapeutic option to improve the metabolic control and the quality of life of PA patients. Improved surgical strategies along with new techniques of interventional radiology allow us to perform the LT minimizing the complications derived from the higher risk of hepatic artery thrombosis.

Role of Biodegradable Stents as Part of Treatment of Biliary Strictures after Pediatric and Adult Liver Transplantation: An Observational Single-Center Study.

This brief report presents the results of 20 adult and pediatric patients treated with the use of biodegradable SX-Ella biliary stents placed by means of a transhepatic approach for the treatment of benign biliary strictures after liver transplantation. Stent insertions were always feasible (100%), and only 1 case of acute pancreatitis was observed (5%). The overall clinical success rate of the procedure, including anastomotic and nonanastomotic strictures, was 75%, and was higher in the anastomotic stricture group (81.25%) than in the nonanastomotic stricture group (50%).

Conversion from twice-daily to once-daily tacrolimus formulation in pediatric liver transplant recipients - a long-term prospective study.

To assess the safety and efficacy of conversion from twice-daily tacrolimus to once-daily tacrolimus in pediatric liver transplant recipients. Conversion from twice-daily to once-daily tacrolimus was made in stable pediatric liver transplant recipients. Doses and serum levels of tacrolimus, liver, and renal function were recorded on the day before the conversion and at days 5, 30, 90, and 180 postconversion. Patients were controlled every 2-3 months thereafter. Fifty-five patients were enrolled in the study. The mean age at conversion was 10.2 ± 3.6 years. The mean tacrolimus trough level was 4.7 ± 1.9 ng/dl preconversion, followed by a significant decline to 4.2 ± 1.7 30 days after the switch (P < 0.004). Mean daily tacrolimus dose was 0.09 ± 0.046 mg/Kg preconversion with a significant increase to 0.11 ± 0.060 3 months postconversion (P < 0.001). Fifteen patients with calculated glomerular filtration rate between 60 to 80 ml/min/m2 preconversion showed a significant improvement one and 3 years after the switch (73 ± 4.1, 83 ± 4.3 and 90.3 ± 7.3 ml/min/m2 , respectively (P < 0.001). The mean follow-up was 5.2 ± 2.4 years. Conversion to once-daily tacrolimus is safe and effective in a cohort of stable pediatric liver transplant patients.

Energy efficiency and color quality limits in artificial light sources emulating natural illumination.

We present in this work a calculation of the theoretical limits attainable for natural light emulation with regard to the joint optimization of the Luminous Efficacy of Radiation and color fidelity by using multiple reflectance spectra datasets, along with an implementation of a physical device that approaches these limits. A reduced visible spectrum of blackbody radiators is introduced and demonstrated which allows lamps designed to emulate natural light to operate with excellent color fidelity and higher efficiency as compared to full visible spectrum sources. It is shown that even though 3,000K and 5,500K blackbody sources have maximum efficacies of 21 lm/W and 89 lm/W, respectively, reduced-spectrum artificial light sources can exceed those values up to 363 lm/W and 313 lm/W, respectively, while retaining excellent color fidelity. Experimental demonstration approaching these values is accomplished through the design and implementation of a 12-channel light engine which emits arbitrarily-tunable spectra. The color fidelity of the designed spectra is assessed through Color Rendering Maps, showing that color fidelity is preserved uniformly over a large spectral reflectance dataset, unlike other approaches to generate white light.

Cross-cultural variation of memory colors of familiar objects.

The effect of cross-regional or cross-cultural differences on color appearance ratings and memory colors of familiar objects was investigated in seven different countries/regions - Belgium, Hungary, Brazil, Colombia, Taiwan, China and Iran. In each region the familiar objects were presented on a calibrated monitor in over 100 different colors to a test panel of observers that were asked to rate the similarity of the presented object color with respect to what they thought the object looks like in reality (memory color). For each object and region the mean observer ratings were modeled by a bivariate Gaussian function. A statistical analysis showed significant (p < 0.001) differences between the region average observers and the global average observer obtained by pooling the data from all regions. However, the effect size of geographical region or culture was found to be small. In fact, the differences between the region average observers and the global average observer were found to of the same magnitude or smaller than the typical within region inter-observer variability. Thus, although statistical differences in color appearance ratings and memory between regions were found, regional impact is not likely to be of practical importance.

Indocyanine green plasma disappearance rate: a new tool for the classification of paediatric patients with acute liver failure.

BACKGROUND & AIMS: Pediatric acute liver failure is a rare disorder which results in death or the need for liver transplantation in 25-50% of cases. The adults scores are unable to predict survival without liver transplantation of pediatric patients. The present study assessed the use the of indocyanine green plasma disappearance rate as a tool to predict the evolution of pediatric patients with acute liver failure. PATIENTS AND METHODS: All patients met the criteria of acute liver failure according to the Pediatric Acute Liver Failure Study Group. King's College, Clichy's criteria and ICG-PDR were obtained on admission or when acute liver failure was diagnosed and repeated every 12-24 hours, respectively. RESULTS: Thirteen out of 48 patients suffered an irreversible liver damage. Seven of them underwent a liver transplantation and 6 died on the waiting. A total of 154 ICG-PDR measurements were taken during the study (Median 12.4 %/min, r:6.2 - 26.3). The ICG-PDR was significantly lower in patients who suffered irreversible liver damage compared with those who survived without liver transplantation (median ICG-PDR 4.1 %/min; r:4.0 - 5.7 vs median ICG-PDR 20.3 %/min; r: 9.1 - 30.1; respectively. P < 0.001). Using a ROC curve the cutoff of ICG-PDR for assessing the need for liver transplantation was set at 5.9 %/min (sensitivity 92.3%, specificity 97.1%). Sensitivity, specificity, PPV, NPV and DA for ICG-PDR were higher than the King's College and Clichy's criteria. CONCLUSIONS: ICG-PDR is a powerful tool that would improve the categorization of patients with pediatric acute liver failure.

Low plasma levels of antithrombin III in the early post-operative period following pediatric liver transplantation: should they be replaced? A single-center pilot study.

eHAT after LT remains a life-threatening complication. In the majority of anticoagulation protocols, heparin is used to prevent thromboses. Our study aimed to monitor AT-III levels in the early post-LT period to assess the need for the administration of AT-III concentrate to ensure the effectiveness of heparin. We monitored coagulation daily by measuring INR, APTT, fibrinogen, platelets, and AT-III. Anticoagulation therapy consisted of LMWH, AT-III, and dipyridamole. AT-III concentrate was administered when AT-III activity was ≤60%. DUS was performed daily for the first five post-operative days or whenever vascular thrombosis was suspected. Between October 2007 and October 2011, 39 LT were performed in our center. The median age was 26 months (6-196) with a median weight of 9 kg (5.5-49). AT-III activity was ≤60% in 27 patients. Lower levels were particularly observed in partial grafts and recipients weighing less than 10 kg. Patent arterial flow was present in all 39 LT during the first five post-operative days. AT-III levels were low in 70% of pediatric patients following LT, thereby risking heparin ineffectiveness. These results may implicate low AT-III levels in the etiology of eHAT post-LT. However, this is a small single-center pilot study and further larger prospective trials are required to confirm these results.

Stress and coping strategies of families of pediatric solid organ transplant recipients in times of pandemic.

Objective: Pediatric solid organ transplantation (SOT) is a chronic condition that impacts the whole family system. The objective of this study is to evaluate psychopathology, family stress, and coping strategies in families of SOT recipients compared to families of healthy children and adolescents. Moreover, it analyzes if the stress related to the COVID-19 pandemic has had an additional impact on these families. Methods: The sample was recruited between May and July 2021, during the fourth and fifth wave of the pandemic in Spain. It consisted of 102 families, 51 with a pediatric recipient who had undergone a SOT (liver, kidney, heart, or lung) and 51 healthy controls, matched by child age and gender. A primary caregiver from each family answered an online sociodemographic questionnaire and different tests to evaluate family stress, depression, anxiety, coping strategies, and effects of the pandemic on the family. Results: Caregivers were mostly mothers (89.2%). Families of SOT recipients showed greater anxiety (U = 863.5, p = 0.003) and more total stress, stress related to childcare (t = -2.043; p = 0.045), and parent-child interaction stress (U = 355.5, p = 0.015). SOT families used more avoidance strategies, specifically denial (U = 889.5; p = 0.010) and abandonment of coping efforts (U = 1,013; p = 0.047), more religious strategies (U = 792.5; p = 0.031), and fewer social support coping strategies (t = 2.098; p = 0.038). No differences were found between groups in terms of exposure, impact, and distress more than 1 year after the start of the pandemic. Conclusion: SOT families showed clinical levels of anxiety, more parent-child interaction stress, more difficulties in taking care of their child, more avoidance and religious strategies, and less use of social support strategies, even 4 years after transplantation. The pandemic did not have an additional differential effect on SOT families. Caregivers of SOT patients can benefit from psychological interventions focused on parents' mental health, parent-child connectedness, skill building, and social support aid groups, with attention to multiculturalism and promoting a better balance between caregivers. There is a need for family interventions that are maintained over time. Strategies that offer this support to families through digital resources can facilitate adjustment to chronic illness, especially in pandemic times.

Color rendering map: a graphical metric for assessment of illumination.

The method of evaluating color rendering using a visual, graphical metric is presented. A two-dimensional Color Rendering Map (CRM) of a light source's color-rendering capabilities is explained and demonstrated. Extension of this technique to three-dimensional CRMs of objects under illumination is explained, including the method of introducing numerical indices in order to evaluate standards for specific applications in lighting. Three diverse applications, having a range from subtle to significant color variation, are shown with their respective CRMs. These three applications are also used to demonstrate how three differing light sources produce different maps. The results show a flexible, simple method to obtain a clear, visual determination of color rendering performance from differing sources used in differing illumination applications. The use of numeric indices in these applications shows how specific standards can be imposed in assessing the applicability of a light source.

De-entangling colorfulness and fidelity for a complete statistical description of color quality.

In this Letter, the main attributes known to affect color quality are treated statistically over a set of 118 spectra representing the current mainstream lighting technology. The color rendering index (CRI) is used to assess color fidelity while colorfulness is used to complement CRI-R(a), supported by the growing evidence that assessment of light spectra cannot overlook color preference inputs. Colorfulness is evaluated by our optimal color (O(c)) index, through a code that computes the (MacAdam) theoretical maximum volumetric gamut of objects under a given illuminant for all the spectra in our database. Pearson correlation coefficients for CRI-R(a), the (Y. Ohno's) color quality scale (CQS) and O(c) show a high correlation (0.950) between CRI-R(a) and CQS-Q(a), while O(c) shows the lowest correlation (0.577) with CRI-R(a), meaning that O(c) represents the best complement to CRI-R(a) and Q(a) for an in-depth study of color quality.

Infectious complications of non-surgical biliary tract manipulation in paediatric patients. Role of antibiotic prophylaxis.

BACKGROUND: Infections related to non-surgical manipulation of the biliary tract (NSMBT) are common events despite periprocedural antibiotic prophylaxis (PAP). Since June 2017, our local protocol has indicated a 24-h regimen of intravenous piperacillin-tazobactam for this purpose. OBJECTIVE: We aimed to describe the incidence and characteristics of NSMBT-related paediatric infections, define risk factors for their development, and analyse adherence to our PAP protocol. MATERIALS AND METHODS: Epidemiological, clinical, and microbiological data were collected in consecutive NSMBT procedures performed in paediatric patients (<18 years) in our centre (2010-2019). RESULTS: 113 procedures in 37 patients, median age 4 years (IQR 1-8), were included. Main underlying diseases were biliary atresia (32%) and cancer (14%). Sixty-eight percent had undergone liver transplant and 70% hepaticojejunostomy. In 44 procedures (39%), the intervention was performed during the course of infection and previously prescribed antibiotic treatment was maintained. In the other 69, PAP was specifically indicated for NSMBT; antibiotic adequacy increased from 35% to 100% after June 2017. In total, 32 NSMBT-related infections (28%) occurred, mainly in the first 24h post-procedure (72%); no deaths happened. Causative pathogens were Gram-negative rods (64%), Gram-positive cocci (28%), and Candida spp. (8%). Main related risk factors were hepaticojejunostomy, biliary obstruction, and liver transplant. CONCLUSIONS: NSMBT in children entails a significant infection risk, even under antibiotic prophylaxis, being hepaticojejunostomy the main risk factor. Infectious complications mainly occurred immediately after the procedure. After establishing a PAP protocol, 100% of interventions received appropriate prophylaxis, decreasing antibiotic exposure time and potentially, the length of hospital stay.

Nonhepatic Cancer in the Pediatric Liver Transplant Population: Guidelines From the ILTS-SETH Consensus Conference.

The incidence and geographical distribution of cancers in children are dramatically different from the adult population. Consequent to improvements in postcancer survival, there is a progressive increase in the number of patients requiring liver transplantation (LT) who are in remission from pretransplant malignancy (PTM). Conventionally, however, PTM has been considered a relative contraindication to LT. Furthermore, with improving post-LT survival now extending beyond decades, the cumulative effect of immunosuppression and the increasing risk of de novo cancers need to be acknowledged. A working group was formed to evaluate, discuss, and retrieve all the evidence and provide guidelines with regards to best practices surrounding nonhepatic cancer in the pediatric LT (PLT) population. Further subsections of research included (a) extrahepatic solid tumors, leukemia, lymphoma, and other hematological disturbances before PLT and (b) malignancies following PLT (including posttransplant lymphoproliferative disorders). This guidance provides a collection of evidence-based expert opinions, consensus, and best practices on nonhepatic cancers in PLT.

Long-term outcome of hepatitis C virus infections acquired after pediatric liver transplantation.

The outcomes and characterization of hepatitis C virus (HCV) infections after pediatric liver transplantation (LT) have rarely been reported. We describe our experience with HCV infections after pediatric LT. Ten of 207 children (4.8%) who underwent LT at our institution (1985-2010) developed previously undiagnosed HCV disease. Eight received a liver graft before blood product and donor screening for HCV became available. The mean age at transplantation was 8.9 ± 4.3 years, and the median time from transplantation to the diagnosis of HCV was 15.1 years (range = 0.2-19.7 years). The genotypes were 1 (n = 8), 3 (n = 1), and undetermined (n = 1). At the time of this writing, all the patients were still alive with a mean follow-up of 7.3 ± 5.5 years after the diagnosis of HCV. Five patients did not receive treatment; 2 of these patients achieved spontaneous viral clearance (SVC). Four of the 5 treated patients achieved a sustained virological response, and 3 had an early virological response (EVR). Two of these 4 patients developed chronic rejection while they were on treatment, but this was resolved with a conversion from cyclosporine A to tacrolimus. The remaining patient was continuing treatment and had achieved EVR. In conclusion, despite the limitations of our series, de novo HCV infections after pediatric LT seem to have a slow histological progression. Even with genotype 1, the patients have a good long-term prognosis and respond well to treatment. Nevertheless, chronic rejection during antiviral therapy may develop. In addition, SVC may occur in this population.

[Use of warfarin and low range INR in the prevention of recurrent venous thrombosis]. / Uso de warfarina y bajo rango de INR en la prevención de trombosis venosa recurrente.

The object of this work was to determine the efficacy of a low range International Normalized Ratio (INR) between 1.5 and 1.9, in preventing recurrent venous thrombosis and the hemorrhagic manifestations that can complicate anticoagulation with warfarin. Thirty nine patients, 10 to 78 years of age were studied between January 2006 and November 2009. All of them had been treated with warfarin, for at least 6 months, due to deep venous thrombosis or pulmonary embolism. The subjects were separated, at random, into two groups. In group A (20 patients), the doses of warfarin were adjusted until the INR was stabilized between 1.5 and 1.9; in group B, the INR was maintained between 2 and 3. The coagulant activities of plasma factors II, VII, IX and X were determined in a week and between the fourth and fifth weeks, after stabilization of the INR. Plasma activities of the coagulation factors assayed were abnormally low in both groups, in the two opportunities they were determined, although significantly lower in group B (p<0.05). No thromboembolic episodes occurred during the study, in any of the patients. One of the patients from group A and four from group B, presented minor hemorrhagic manifestations (p N.S.) The above results suggest that a range on INR lower that 2, could be sufficient to prevent recurrent thrombotic episodes while diminishing the frequency of hemorrhagic complications associated with the use of warfarin. However, it is necessary to continue incorporating more individuals in the study to obtain greater certainty in the analysis of these results.

Infectious complications of non-surgical biliary tract manipulation in paediatric patients. Role of antibiotic prophylaxis.

BACKGROUND: Infections related to non-surgical manipulation of the biliary tract (NSMBT) are common events despite periprocedural antibiotic prophylaxis (PAP). Since June 2017, our local protocol has indicated a 24-h regimen of intravenous piperacillin-tazobactam for this purpose. OBJECTIVE: We aimed to describe the incidence and characteristics of NSMBT-related paediatric infections, define risk factors for their development, and analyse adherence to our PAP protocol. MATERIALS AND METHODS: Epidemiological, clinical, and microbiological data were collected in consecutive NSMBT procedures performed in paediatric patients (<18 years) in our centre (2010-2019). RESULTS: 113 procedures in 37 patients, median age 4 years (IQR 1-8), were included. Main underlying diseases were biliary atresia (32%) and cancer (14%). Sixty-eight percent had undergone liver transplant and 70% hepaticojejunostomy. In 44 procedures (39%), the intervention was performed during the course of infection and previously prescribed antibiotic treatment was maintained. In the other 69, PAP was specifically indicated for NSMBT; antibiotic adequacy increased from 35% to 100% after June 2017. In total, 32 NSMBT-related infections (28%) occurred, mainly in the first 24h post-procedure (72%); no deaths happened. Causative pathogens were Gram-negative rods (64%), Gram-positive cocci (28%), and Candida spp. (8%). Main related risk factors were hepaticojejunostomy, biliary obstruction, and liver transplant. CONCLUSIONS: NSMBT in children entails a significant infection risk, even under antibiotic prophylaxis, being hepaticojejunostomy the main risk factor. Infectious complications mainly occurred immediately after the procedure. After establishing a PAP protocol, 100% of interventions received appropriate prophylaxis, decreasing antibiotic exposure time and potentially, the length of hospital stay.