Risk for Recurrence in Long-Term Follow-Up of Children after Liver Transplantation for Hepatoblastoma or Hepatocellular Carcinoma.

The aim of this study was to assess the long-term results of liver transplantation (LT) in pediatric patients with unresectable hepatoblastoma (HB) or hepatocellular carcinoma (HCC) with special reference to the risk of tumor recurrence. We retrospectively analyzed data from 46 HB and 26 HCC patients who underwent LT between 1990 and 2022. In HCC patients, we compared outcomes depending on donor type. We evaluated the impact of a number of risk factors on recurrence-free survival after LT. Estimated patient survival after 5, 10, and 15 years was 82%, 73%, and 73% in the HB group and 79%, 75%, and 75% in the HCC group, respectively (p = 0.76). In the HCC group, living donor LT (LDLT) and deceased donor LT (DDLT) provided similar patient survival (p = 0.09). Estimated recurrence-free survival in patients who had three or fewer risk factors was significantly better than in patients with more than three risk factors (p = 0.0001). Adequate patient selection is necessary when considering LT for primary liver tumors in children. The presence of more than three risk factors is associated with a very high risk of recurrence and indicates poor prognosis, whereas extrahepatic disease may be considered a contraindication for transplantation.

Restoration of soils contaminated with PAHs by the mixture of zeolite composites mixed with exogenous organic matter and mineral salts.

The major cause of soil degradation (contamination, erosion, compaction) is closely linked to agriculture, i.e., unsustainable agriculture practices, which are reflected in the depletion of the soil organic carbon pool, loss in soil biodiversity, and reduction of C sink capacity in soils. Therefore, the agricultural practice of applying carbon-rich materials into the soil is an attractive solution for climate change mitigation and soil ecosystem sustainability. The paper aimed to evaluate the effectiveness of the addition of organic-mineral mixtures to the mineral salts (NPK), including the exogenous organic matter (lignite) mixed with zeolite-carbon (NaX-C) or zeolite-vermiculite (NaX-Ver) composites in the restoration of soils contaminated with PAHs. The addition of zeolite composites to fertilizer resulted in a significant reduction in soil PAH levels and a corresponding reduction in plant tissue content, without compromising yields, compared to the control and separate application of NPK. A Significant correlation between PAHs and pHH2O, pHKCl, EC and dehydrogenase activity (DhA) was found in soils. The addition of zeolite composites with lignite significantly reduced the content of PAHs in straws, especially following the application of NaX-C. However, in the case of grains, the highest percentage reduction in comparison to NPK was observed for the highest dose of NaX-Ver.

Is M30 staining a reliable marker predicting graft rejection and fibrosis in protocolar liver biopsies in post-liver transplant pediatric patients?

BACKGROUND: Liver transplantation is currently a treatment of choice in patients with end-stage liver disease. Acute cellular rejection (ACR), antibody-mediated rejection (AMR), and chronic rejection (ChR) are major causes of graft injury. Therefore, new markers predicting graft rejection are investigating. Apoptosis has been recently proposed as one of the mechanisms contributing to liver fibrosis in liver grafts. Coarse needle liver biopsy is still a gold standard in monitoring post-transplant pathologies. The aim of this study was to assess the utility of immunohistochemical (IHC) staining for M30 (cytokeratin 18), as a prognostic marker of rejection in pediatric recipients of liver transplant and predicting marker of liver fibrosis and worse follow-up. METHODS: The study enrolled 55 biopsies from 55 patients aged 2.37 to 18.9 years (median 13.87 years) who underwent protocolar liver biopsies taken 1-17 years after liver transplantation (median 8.36 years). The control group (positive control group) consisted of 26 biopsies from 16 patients in whom acute ACR was diagnosed. IHC staining for M30 (cytokeratin 18) and histochemical Azan staining were performed in all liver specimens. The following changes were re-evaluated in each specimen: features of ACR (the severity was assessed using RAI/Rejection Activity Index/Scale, which ranges from 3-9 points and include 3 histopathological changes suggestive of rejection), AMR or ChR; severity of fibrosis (Ishak Scale); presence of cholestasis and steatosis. Clinical parameters including laboratory tests of liver function (AST, ALT, GGTP, bilirubin) were also evaluated. RESULTS: M30 expression correlated with presence of acute cellular rejection. However, no relationship was found between M30 expression and severity of fibrosis. CONCLUSIONS: M30 staining, marker of apoptosis, seems to be a promising marker predicting acute cellular rejection.

The Impact of Hepatic Artery Thrombosis on the Outcome of Pediatric Living Donor Liver Transplantations.

The aim of our study was to assess risk factors for hepatic artery thrombosis (HAT) and to evaluate the impact of HAT management on long-term outcomes after pediatric living donor liver transplantation (LDLT). We retrospectively analyzed 400 patients who underwent primary LDLT between 1999 and 2020. We compared preoperative data, surgical factors, complications, and patient and graft survivals in patients with HAT (HAT Group) and without HAT (non-HAT Group). A total of 27 patients (6.75%) developed HAT. Acute liver failure, a hepatic artery (HA) anastomosis diameter below 2 mm, and intraoperative HA flow dysfunction were significantly more common in the HAT Group (p < 0.05, p = 0.02026, and p = 0.0019, respectively). In the HAT Group, 21 patients (77.8%) underwent urgent surgical revision. The incidence of biliary stenosis and retransplantation was significantly higher in the HAT Group (p = 0.00002 and p < 0.0001, respectively). Patient and graft survivals were significantly worse in the HAT Group (p < 0.05). The close monitoring of HA flow with Doppler ultrasound during the critical period of 2 to 3 weeks after LDLT and the immediate attempt of surgical revascularization may attenuate the elevated risk of biliary stenosis, graft loss, and the need for retransplantation due to HAT.

Choledochal Cyst Excision in Infants-A Retrospective Study.

A choledochal cyst is a rare malformation primarily diagnosed in children. The only effective therapy remains surgical cyst resection followed by Roux-en-Y hepaticojejunostomy. Treating asymptomatic neonates remains a point of discussion. Between 1984 and 2021, we performed choledochal cyst (CC) excision in 256 children at our center. Out of this group, we retrospectively reviewed the medical records of 59 patients who were operated on under one year of age. Follow-up ranged from 0.3 to 18 years (median 3.9 years). The preoperative course was asymptomatic in 22 (38%), while 37 patients (62%) had symptoms before surgery. The late postoperative course was uneventful in 45 patients (76%). In symptomatic patients, 16% had late complications, while in asymptomatic patients, only 4%. Late complications were observed in the laparotomy group in seven patients (17%). We did not observe late complications in the laparoscopy group. Early surgical intervention is not followed by a high risk of complications and may prevent the onset of preoperative complications, giving excellent early and long-term results, especially after minimally invasive laparoscopic surgery.

Effective screening of Coulomb repulsions in water accelerates reactions of like-charged compounds by orders of magnitude.

The reaction kinetics between like-charged compounds in water is extremely slow due to Coulomb repulsions. Here, we demonstrate that by screening these interactions and, in consequence, increasing the local concentration of reactants, we boost the reactions by many orders of magnitude. The reaction between negatively charged Coenzyme A molecules accelerates ~5 million-fold using cationic micelles. That is ~104 faster kinetics than in 0.5 M NaCl, although the salt is ~106 more concentrated. Rate enhancements are not limited to micelles, as evidenced by significant catalytic effects (104-105-fold) of other highly charged species such as oligomers and polymers. We generalize the observed phenomenon by analogously speeding up a non-covalent complex formation-DNA hybridization. A theoretical analysis shows that the acceleration is correlated to the catalysts' surface charge density in both experimental systems and enables predicting and controlling reaction rates of like-charged compounds with counter-charged species.

Investigating the Feasibility of Processing Activated Carbon/UHMWPE Polymer Composite Using Laser Powder Bed Fusion.

Activated Carbon (AC) is widely available at a relatively low cost, has a high porosity and is commonly used as a filter material for a range of applications. However, it is a brittle and friable material. Ultra-High Molecular Weight Polyethylene (UHMWPE) polymer is a tough engineering plastic that has been used as a binder. The traditional method used in manufacturing AC/UHMWPE filters involves compressing AC/UHMWPE composite powder during heating in a mould. This process compresses the particles together and the materials undergo sintering. This process results in a low pore interconnectivity, which has a considerable impact on the filter's efficiency. Selective Laser Sintering is a laser powder bed fusion additive manufacturing technique for polymers. This has a number of advantages compared to the conventional technique and produces a porous structure with improved filtration efficiency. We propose that this is due to the greater pore interconnectivity. In this work, AC/UHMWPE powdered composites were prepared with different AC and UHMWPE ratios. The structure and properties of the AC/UHMWPE composite were investigated and characterised to assess their suitability for selective laser sintering. Particle size and morphology analysis were conducted, as well as density measurements, powder flow, thermal analysis, and crystallinity measurements. The results reveal that the addition of AC improves the UHMWPE flow. The thermal analysis results show that the intrinsic thermal properties of UHMWPE powder are not significantly affected by the introduction of activated carbon. However, thermal gravimetric analysis revealed that the onset of mass loss is considerably shifted (20 °C) to higher temperatures for the AC/UHMWPE composites, which is favourable for laser sintering. Additionally, the change in the composition ratio of untreated composite does not have a significant effect on the degree of crystallinity. Laser-sintered AC/UHMWPE parts were successfully manufactured using a commercial laser-sintering machine.

Case Report: Sequential Liver After Kidney Transplantation in a Patient With Sensenbrenner Syndrome (Cranioectodermal Dysplasia).

Sensenbrenner syndrome, also known as cranioectodermal dysplasia (CED), is a rare ciliopathy clinically characterized by congenital craniofacial, skeletal, and ectodermal defects. Chronic kidney and liver insufficiency are also present in this disorder. Cranioectodermal dysplasia is an autosomal recessive and heterogeneous genetic disease. Six genes (IFT122, WDR35, IFT140, IFT43, IFT52, and WDR19) are known to be associated with this syndrome. Until 2021 more than 70 patients have been reported with CED, however, an orthotopic liver transplantation has been reported only in one case. Here, we present a case report of sequential liver-after-kidney transplantation in a male patient affected by CED. The kidney and liver transplantation was performed at the age of 7 and 12 years, respectively. Patients with Sensenbrenner syndrome require a multidisciplinary medical management and should regularly be followed-up by hepatologists and nephrologists, as the liver and kidney diseases are the major cause of morbidity and mortality.

Ion Complexation Explains Orders of Magnitude Changes in the Equilibrium Constant of Biochemical Reactions in Buffers Crowded by Nonionic Compounds.

The equilibrium constant (K) of biochemical complex formation in aqueous buffers with high concentration (>20 wt %) of nonionic compounds can vary by orders of magnitude in comparison with the K in a pure buffer. The precise molecular mechanisms of these profound changes are not known. Herein, we show up to a 1000-fold decrease of the K value of DNA hybridization (at nM concentration) in standard molecular crowder systems such as PEG, dextrans, Ficoll, and glycerol. The effect responsible for the decrease of K is the complexation of positively charged ions from a buffer by nonionic polymers/small molecules. We determined the average equilibrium constant for the complexation of ions per monomer (∼0.49 M-1). We retrieve K's original value for a pure buffer if we properly increase the ionic strength of the buffer crowded by the polymers, compensating for the loss of complexed ions.

Structural properties of cationic surfactant-fatty alcohol bilayers: insights from dissipative particle dynamics.

Bilayers, self-assembled by cationic surfactants and fatty alcohols in water, are the basic units of lamellar gel networks - creamy formulations extensively used in cosmetics and pharmaceutics. Mesoscopic modelling and study of the bilayers formed by single- or double-tail cationic surfactants (CTAC or DHDAC), and fatty alcohols (FAs) in the lamellar fluid and gel phases were employed. Fatty alcohols with alkyl tail equal to or greater than the surfactant alkyl tail, i.e., C16FA or C18FA and C22FA, were considered. A model formulation was explored with the FA concentration greater than that of the surfactant and the structure of the fluid and gel bilayers in tensionless state characterised via the density profiles across the bilayers, orientational order parameters of the surfactant and FA chains, intrinsic analysis of the bilayer interfaces, and bending rigidity. The intrinsic analysis allows identification and quantification of the coexistence of the interdigitated and non-interdigitated phases present within the gel bilayers. The FA chains were found to conform the primary scaffolding of the bilayers while the surfactant chains tessellate bilayer monolayers from their water-hydrophobic interface. Further, the overlap of the FA chains from the apposed monolayers of the fluid bilayers rises with increasing FA length. Finally, the prevalence of the non-interdigitated phase over the interdigitated phase within the gel bilayers becomes enhanced upon the FA length increase with a preference of the surfactant chains to reside in the non-interdigitated phase rather than the interdigitated phase.

Successful Liver Transplantation in Two Polish Brothers with Transaldolase Deficiency.

Transaldolase deficiency (TALDO; OMIM 606003) is a rare inborn autosomal-recessive error of the pentose phosphate pathway. It is an early-onset multisystem disease with dysmorphic features, anaemia, coagulopathy, thrombocytopenia, tubulopathy, hepatosplenomegaly and end-stage liver disease. We present a case of two Polish brothers, born to consanguineous parents, with early-onset TALDO. The dominant feature of disease was an early severe liver injury, with subsequent renal tubulopathy. Nodular liver fibrosis developed in the course of the underlying disease. The older brother presented stable liver function, however, he was qualified for deceased donor liver transplantation (DDLT) because of a liver tumour and suspicion of hepatocarcinoma. The boy was transplanted at the age of 14. The younger brother was qualified for DDLT due to end-stage liver disease and transplanted at the age of 11. Currently, both our patients are alive and in a good condition with normal graft function 23 and 20 months after DDLT respectively. Liver transplantation can be a therapeutic option in TALDO and should be considered in patients with coexisting severe chronic and end-stage liver disease. Long term follow-up is necessary to assess the impact of liver transplantation for quality of life, survival time and the course of the disease.

Achalasia in Children-Clinical Presentation, Diagnosis, Long-Term Treatment Outcomes, and Quality of Life.

BACKGROUND: In spite of the introduction of peroral endoscopic myotomy (POEM), Heller myotomy (HM) remains the mainstay of treatment and the role of pneumatic dilatation (PD) is being debated. The aim of this study was to present a single-center experience in the diagnostic approach and treatment of esophageal achalasia (EA), including the long-term assessment of the QoL. METHODS: Data collection was based on the retrospective analysis of clinical notes and prospective interviews with patients and their parents. RESULTS: The study group consisted of 60 patients with EA (F: 26, M: 34), with a median age of 12.0 (1-17) years at diagnosis. The time from the first symptoms until the diagnosis was 1.0 year (0.5-2.0) and the most common were: regurgitation (91.3%), dysphagia (84.8%), and chest pain (47.8%). The diagnostic approach showed a high sensitivity for barium X-ray follow through, esophageal manometry, and endoscopy. Overall, a long-term good outcome of HM was achieved in 27 out of 37 patients (73%) and it was negatively affected by the time between the first symptoms and the diagnosis. Out of the 16 patients who underwent PD before HM, a good outcome was achieved in 14 patients (87.5%), compared to 13 out of 21 patients (62%) who only underwent HM (p = 0.22). Concomitant fundoplication was routinely performed, and 18% required post-operative endoscopic dilatation. At the end of the 12.1 (0.7-26.6)-year follow up, most patients had a good QoL, which significantly corresponded with the treatment outcomes. CONCLUSIONS: Patients suspected of EA should undergo a thorough clinical evaluation including a manometry, a barium X-ray, and an endoscopy. HM is a safe and effective treatment for achalasia and the outcome is not worsened by a preceding endoscopic PD. In most patients, HM alleviates symptoms, although an impaired QoL is common in long-term follow ups.

Impact of Graft Size Matching on the Early Post-Transplant Complications and Patients Survival in Children after Living Donor Liver Transplantations.

We aimed to assess the impact of the graft-recipient weight ratio (GRWR) on early post-transplant complications and patient survival rates in children after living donor liver transplantation (LDLT). We retrospectively analyzed 321 patients who underwent LDLT from 2004 to 2019. The recipients were categorized into four groups: 37 patients had a GRWR ≤ 1.5% (Group A), 196 patients had a GRWR > 1.5% and ≤3.5% (Group B), 73 patients had a GRWR > 3.5% and <5% (Group C) and 15 patients had a GRWR ≥ 5% (Group D). Incidence of early surgical complications including vascular complications, biliary complications, postoperative bleedings, gastrointestinal perforations and graft loss were comparable among groups with a different GRWR. Delayed abdominal wound closure was more common in patients with a GRWR > 3.5%. Recipients with a GRWR < 5% had a significantly better prognosis concerning patients and graft survival. Using grafts with a GRWR < 5% allows us to expand the donor pool and decrease the risk of mortality while on the waiting list, when patients at the time of transplantation have less advanced liver disease. LDLT with a GRWR ≥ 5% is related to a higher risk of poor outcome, and thus should be an option for treating selected patients when the risk of a delayed transplantation is high and access to deceased donors is limited.

Liver Histopathology in Late Protocol Biopsies after Pediatric Liver Transplantation.

Liver transplantation has become a routine treatment for children with end stage liver failure. Recently, the long term survival of pediatric patients after liver transplantation has improved, with a life expectancy much longer than that of adult recipients, but also with longer exposition of the graft to various injuries, including immunological, inflammatory and others. Biochemical tests, although important, do not always reflect graft injury. The aim of our study was to analyze the histopathology of the graft in late protocol biopsies and correlate it with the clinical and biochemical status of these patients. We analyzed 61 protocol liver biopsies taken from 61 patients. Biopsies were taken 9.03-17.09 years (mean 12.68, median 11.74 years) after transplantation. Liver specimens were examined particularly for the presence and stage of liver fibrosis, inflammation, steatosis, and acute or chronic cellular and humoral rejection. We did not find any abnormalities in 26 (42.6%) liver specimens. None of the patients had signs of cellular or antibody mediated rejection or chronic rejection. In 23 liver biopsies (37.7%), we found non-specific lymphoid infiltrates. Another problem was fibrosis (equal to or more than three on the Ishak scale)-we found it in 17 patients, including seven liver specimens (11.5%) with severe fibrosis (Ishak 5-6). Conclusions: Various pathomorphological abnormalities were found in more than half of patients with a median 11.74 years post-transplant follow-up. Most of them presented normal laboratory liver tests at the same time, suggesting a slow subclinical process leading to pathomorphological abnormalities. No single factor for the development of these abnormalities was found, but our study supports the need for protocol liver biopsies even in patients with normal/almost normal biochemical liver tests.

Seasonal Affective Disorder: Common Questions and Answers.

Seasonal affective disorder is a mood disorder that is a subtype or qualifier of major depressive disorder or bipolar disorder in the Diagnostic and Statistical Manual of Mental Disorders. It is characterized by depressive symptoms that occur at a specific time of year (typically fall or winter) with full remission at other times of year (typically spring or summer). Possible risk factors include family history, female sex, living at a more northern latitude, and young adulthood (18 to 30 years of age). With the temporal nature of the mood episodes, diagnosis requires full remission when the specified season ends and two consecutive years of episodes in the same season. First-line therapy for seasonal affective disorder includes light therapy, antidepressants, and cognitive behavior therapy, alone or in combination. Commercial devices are available for administering light therapy or dawn simulation. The light intensity and duration of treatment depend on the device and the patient's initial response, but 2,500 to 10,000 lux for 30 to 60 minutes at the same time every day is typically effective. Lifestyle interventions, such as increasing exercise and exposure to natural light, are also recommended. If seasonal affective disorder recurs, long-term treatment or preventive intervention is typically indicated, and bupropion appears to have the strongest evidence supporting long-term use. Continuing light therapy or other antidepressants is likely beneficial, although evidence is inconclusive. Evidence is also inconclusive for psychotherapy and vitamin D supplementation.

Correction to: Investigation of organic material self-heating in oxygen-depleted condition within a coal-waste dump in Upper Silesia Coal Basin, Poland.

The original publication of this paper contains a mistake.

Investigation of organic material self-heating in oxygen-depleted condition within a coal-waste dump in Upper Silesia Coal Basin, Poland.

Self-heating occurring was studied in the Bytom coal-waste dump using petrographic, mineralogical, and organic geochemical to assess the changes induced by heating on organic material and quantify-qualify the emitted gases. The distribution of geochemical markers such as n-alkanes, alkylbenzenes, alkylcyclohexanes, phenols, sulfurous compounds, and emitted gases in the waste dump is outlined. Heating of organic material there is indicated by high vitrinite random reflectance (Rr)% values that typically characterize samples with short-chain n-alkanes, alkylbenzenes, and alkylmethylbenzenes. Contents of minerals showing minor alterations are high with ~ 90% in burned-out samples. Inside the dump where temperatures can reach up to 700-1300 °C and oxygen contents are significantly reduced, conditions favor coking. This situation is confirmed by the formation of enormous quantities of phenols and alkylbenzenes or by elevated amounts of H2 formed under low-oxygen conditions (pyrolysis). Aromatization, pyrolysis (thermal cracking), and oxidation are associated with the heating in the dump. Gases such as methane, ethane, propane, and ethylene formed during self-heating can serve as fuel for the fire inside the dump, in the process generating huge amounts of CO2.

Characterisation of UHMWPE Polymer Powder for Laser Sintering.

Ultra-high molecular weight polyethylene (UHMWPE) is a thermoplastic semicrystalline polymer that has outstanding mechanical properties, low friction coefficient, excellent wear resistance, and is highly resistant to corrosive chemicals. UHMWPE is found in many applications including artificial joints and filtration. However, UHMWPE parts cannot be produced easily by traditional techniques, such as injection moulding and extrusion because of its very high melt viscosity owing to the extremely long polymer chains. Few attempts were made to process UHMWPE by additive manufacturing, particularly laser sintering. This is due to the lack of understanding of the powder properties of UHMWPE. Therefore, the aim of the powder characterisation process in this study is to gain a better understanding of the material requirements and provide a detailed insight on whether UHMWPE is a suitable material for laser sintering. The characterisation process includes powder morphological and flow characteristics, thermal behaviour and stability, and crystallinity of UHMWPE. The study reveals that the sintering behaviour of polymers is controlled by the morphology of the particles in addition to the viscous flow of UHMWPE. There are still difficulties of processing UHMWPE due to highly agglomerated structure of smaller particles with the presence of fibrils in the UHMWPE particles.

Toilet Training: Common Questions and Answers.

Toilet training is a significant developmental milestone in early childhood. Most U.S. children achieve the physiologic, cognitive, and emotional development necessary for toilet training by 18 to 30 months of age. Markers of readiness for toilet training include being able to walk, put on and remove clothing, and follow parental instruction; expressive language; awareness of a full bladder or rectum; and demonstrated dissatisfaction with a soiled diaper. Other readiness cues include imitating toileting behavior, expressing desire to toilet, and demonstrating bladder or bowel control (staying dry through a nap or through the night). Physicians should provide anticipatory guidance to parents beginning at about 18 to 24 months of age, noting the signs of toilet training readiness, and setting realistic expectations for parents. Parents should be counseled that no training method is superior to another. Parents should choose a method that is best suited to them and their child, and the method should use positive reinforcement. Complications of toilet training include stool toileting refusal, stool withholding, encopresis, hiding to defecate, and enuresis. These problems typically resolve with time, although some may require further investigation and treatment. Medical comorbidities such as Down syndrome, autism spectrum disorder, and cerebral palsy reduce the likelihood of successfully attaining full toilet training and often require early consultation with occupational therapists, developmental pediatricians, or other subspecialists to aid in toilet training.