Indications and successes of intestinal transplantation in children in the 21st century: A retrospective cohort study.

AIMS: To report the results and successes of intestinal transplantation (ITx) in the most active European centres, to emphasize that, although it is a difficult procedure, it should remain a therapeutic option for children with total, definitive and complicated intestinal failure when intestinal rehabilitation fails. METHODS: We retrospectively collected data about all patients less than 18 receiving an ITx from 2010 to 2022 in 8 centres, and outcomes in July 2022. RESULTS: ITx was performed in 155 patients, median age 6.9 years, in 45% for short bowel syndromes, 22% congenital enteropathies, 25% motility disorders, and 15% re-transplantations. Indications were multiple in most patients, intestinal failure-associated liver disease in half. The graft was in 70% liver-containing. At last follow up 64% were alive, weaned from parenteral nutrition, for 7.9 years; 27% had died and the graft was removed in 8%, mostly early after ITx. DISCUSSION: ITx, despite its difficulties, can give a future to children with complicated intestinal failure. It should be considered among the therapeutic options offered to patients with a predicted survival rate lower than that after ITx. Patients should be early discussed within multidisciplinary teams in ITx centres, to avoid severe complications impacting the results of ITx, or even to avoid ITx.

Test of the Einstein Equivalence Principle near the Galactic Center Supermassive Black Hole.

During its orbit around the four million solar mass black hole Sagittarius A* the star S2 experiences significant changes in gravitational potential. We use this change of potential to test one part of the Einstein equivalence principle: the local position invariance (LPI). We study the dependency of different atomic transitions on the gravitational potential to give an upper limit on violations of the LPI. This is done by separately measuring the redshift from hydrogen and helium absorption lines in the stellar spectrum during its closest approach to the black hole. For this measurement we use radial velocity data from 2015 to 2018 and combine it with the gravitational potential at the position of S2, which is calculated from the precisely known orbit of S2 around the black hole. This results in a limit on a violation of the LPI of |ß_{He}-ß_{H}|=(2.4±5.1)×10^{-2}. The variation in potential that we probe with this measurement is six magnitudes larger than possible for measurements on Earth, and a factor of 10 larger than in experiments using white dwarfs. We are therefore testing the LPI in a regime where it has not been tested before.

Star formation inside a galactic outflow.

Recent observations have revealed massive galactic molecular outflows that may have the physical conditions (high gas densities) required to form stars. Indeed, several recent models predict that such massive outflows may ignite star formation within the outflow itself. This star-formation mode, in which stars form with high radial velocities, could contribute to the morphological evolution of galaxies, to the evolution in size and velocity dispersion of the spheroidal component of galaxies, and would contribute to the population of high-velocity stars, which could even escape the galaxy. Such star formation could provide in situ chemical enrichment of the circumgalactic and intergalactic medium (through supernova explosions of young stars on large orbits), and some models also predict it to contribute substantially to the star-formation rate observed in distant galaxies. Although there exists observational evidence for star formation triggered by outflows or jets into their host galaxy, as a consequence of gas compression, evidence for star formation occurring within galactic outflows is still missing. Here we report spectroscopic observations that unambiguously reveal star formation occurring in a galactic outflow at a redshift of 0.0448. The inferred star-formation rate in the outflow is larger than 15 solar masses per year. Star formation may also be occurring in other galactic outflows, but may have been missed by previous observations owing to the lack of adequate diagnostics.

Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen-induced pulmonary inflammation in mice.

BACKGROUND: Accumulation of activated eosinophils in tissue is a hallmark of allergic inflammation. The endocannabinoid 2-arachidonoylglycerol (2-AG) has been proposed to elicit eosinophil migration in a CB2 receptor/Gi/o -dependent manner. However, it has been claimed recently that this process may also involve other mechanisms such as cytokine priming and the metabolism of 2-AG into eicosanoids. Here, we explored the direct contribution of specific CB2 receptor activation to human and mouse eosinophil effector function in vitro and in vivo. METHODS: In vitro studies including CB2 expression, adhesion and migratory responsiveness, respiratory burst, degranulation, and calcium mobilization were conducted in human peripheral blood eosinophils and mouse bone marrow-derived eosinophils. Allergic airway inflammation was assessed in mouse models of acute OVA-induced asthma and directed eosinophil migration. RESULTS: CB2 expression was significantly higher in eosinophils from symptomatic allergic donors. The selective CB2 receptor agonist JWH-133 induced a moderate migratory response in eosinophils. However, short-term exposure to JWH-133 potently enhanced chemoattractant-induced eosinophil shape change, chemotaxis, CD11b surface expression, and adhesion as well as production of reactive oxygen species. Receptor specificity of the observed effects was confirmed in eosinophils from CB2 knockout mice and by using the selective CB2 antagonist SR144528. Of note, systemic application of JWH-133 clearly primed eosinophil-directed migration in vivo and aggravated both AHR and eosinophil influx into the airways in a CB2 -specific manner. This effect was completely absent in eosinophil-deficient ∆dblGATA mice. CONCLUSION: Our data indicate that CB2 may directly contribute to the pathogenesis of eosinophil-driven diseases. Moreover, we provide new insights into the molecular mechanisms underlying the CB2 -mediated priming of eosinophils. Hence, antagonism of CB2 receptors may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophilic disorders.

Liver fluke-infested graft used for living-donor liver transplantation: case report and review of the literature.

Clonorchiasis is a cholangiopathy caused by foodborne trematode parasites, also known as liver flukes. Clonorchiasis is endemic in a wide geographical area extending from Eastern Europe to Southeast Asia. Infested hosts may remain asymptomatic for decades and consequently their liver can become available as a graft. To date, 20 liver transplantations with liver fluke-infested grafts have been reported in the literature. All of them occurred in Asian countries. We, here, report the first case to our knowledge in the Western world of living-donor liver transplantation (LDLT) with an Opisthorchis felineus-infested graft, and present a review of the literature. A 6-month-old girl with decompensated secondary biliary cirrhosis underwent an LDLT with a left lateral graft infested with O. felineus. After prompt diagnosis and adequate therapy, both donor and recipient had an uneventful postoperative course and long-term follow-up. Liver grafts infested with liver flukes do not pose a contraindication to liver donation from deceased or living donors, provided that a correct diagnosis and treatment are performed in a timely fashion.

Using scale characteristics and water temperature to reconstruct growth rates of juvenile steelhead Oncorhynchus mykiss.

Juvenile steelhead Oncorhynchus mykiss from a northern California Central Valley population were reared in a controlled laboratory experiment. Significantly different rates of growth were observed among fish reared under two ration treatments and three temperature treatments (8, 14 and 20°C). Wider circulus spacing and faster deposition was associated with faster growth. For the same growth rate, however, circulus spacing was two-fold wider and deposited 36% less frequently in the cold compared to the hot temperature treatment. In a multiple linear regression, median circulus spacing and water temperature accounted for 68% of the variation in observed O. mykiss growth. These results corroborate previous research on scale characteristics and growth, while providing novel evidence that highlights the importance of water temperature in these relationships. Thus, this study establishes the utility of using scale analysis as a relatively non-invasive method for inferring growth in salmonids.

Serial evaluation of hepatic function profile after Fontan operation.

Moderate persistent elevation of the γ-glutamyltransferase (γGT) level is a frequent finding during long-term follow-up of patients with total cavopulmonary connection (TCPC) for palliation of functionally univentricular hearts. Serial intraindividual data revealed a significant increase in the γGT level within a minimum 4-year interval in more than 80 % of cases. The level of γGT elevation showed a significant correlation to hemodynamic parameters such as systemic ventricular end diastolic pressure and mean pulmonary artery pressure, but did not strongly correlate with duration of follow-up or other liver function parameters, which were less frequent and less impressively deranged. None of the patients had signs of synthetic dysfunction. With increasing postoperative follow-up, abnormalities of sonographic hepatic texture including increased echogenicity, inhomogeneity, or liver surface nodularity were found. All 17 patients with liver surface nodularity had a follow-up period of over 10 years. Structural abnormalities did not correlate with biochemical or hemodynamic parameters. Doppler evaluation revealed inspiratory dependence of hepatic vein flow in more than 90 % as a relevant finding after TCPC; a decrease in portal vein flow velocity was observed in many patients. Since long-term survivors after Fontan procedure are at an increased risk of cardiac hepatopathy and cirrhosis, detailed routine investigation and monitoring of hepatic morphology are needed.

Growing experience with mTOR inhibitors in pediatric solid organ transplantation.

Controlled trials of mTOR inhibitors in children following solid organ transplantation are scarce, although evidence from prospective single-arm studies is growing. Everolimus with reduced CNI therapy has been shown to be efficacious and safe in de novo pediatric kidney transplant patients in prospective trials. Prospective and retrospective data in children converted from CNI therapy to mTOR inhibition following kidney, liver, or heart transplantation suggest preservation of immunosuppressive efficacy. Good renal function has been maintained when mTOR inhibitors are used de novo in children following kidney transplantation or after conversion to mTOR inhibition with CNI minimization. mTOR inhibition with reduced CNI exposure is associated with a low risk for developing infection in children. Growth and development do not appear to be impaired during low-dose mTOR inhibition, but more studies are required. No firm conclusions can be drawn as to whether mTOR inhibitors should be discontinued in children requiring surgical intervention or whether mTOR inhibition delays progression of hepatic fibrosis after pediatric liver transplantation. In conclusion, current evidence suggests that use of mTOR inhibitors in children undergoing solid organ transplantation is efficacious and safe, but a number of issues remain unresolved and further studies are required.

Chemical, physical and microbial properties and microbial diversity in manufactured soils produced from co-composting green waste and biosolids.

The effects of adding biosolids to a green waste feedstock (100% green waste, 25% v/v biosolids or 50% biosolids) on the properties of composted products were investigated. Following initial composting, 20% soil or 20% fly ash/river sand mix was added to the composts as would be carried out commercially to produce manufactured soil. Temperatures during composting reached 50 °C, or above, for 23 days when biosolids were included as a composting feedstock but temperatures barely reached 40 °C when green waste alone was composted. Addition of biosolids to the feedstock increased total N, EC, extractable NH(4), NO(3) and P but lowered pH, macroporosity, water holding capacity, microbial biomass C and basal respiration in composts. Additions of soil or ash/sand to the composts greatly increased the available water holding capacity of the materials. Principal component analysis (PCA) of PCR-DGGE 16S rDNA amplicons separated bacterial communities according to addition of soil to the compost. For fungal ITS-RNA amplicons, PCA separated communities based on the addition of biosolids. Bacterial species richness and Shannon's diversity index were greatest for composts where soil had been added but for fungal communities these parameters were greatest in the treatments where 50% biosolids had been included. These results were interpreted in relation to soil having an inoculation effect and biosolids having an acidifying effect thereby favouring a fungal community.

Inverse expression states of the BRN2 and MITF transcription factors in melanoma spheres and tumour xenografts regulate the NOTCH pathway.

The use of adherent monolayer cultures have produced many insights into melanoma cell growth and differentiation, but often novel therapeutics demonstrated to act on these cells are not active in vivo. It is imperative that new methods of growing melanoma cells that reflect growth in vivo are investigated. To this end, a range of human melanoma cell lines passaged as adherent cultures or induced to form melanoma spheres (melanospheres) in stem cell media have been studied to compare cellular characteristics and protein expression. Melanoma spheres and tumours grown from cell lines as mouse xenografts had increased heterogeneity when compared with adherent cells and 3D-spheroids in agar (aggregates). Furthermore, cells within the melanoma spheres and mouse xenografts each displayed a high level of reciprocal BRN2 or MITF expression, which matched more closely the pattern seen in human melanoma tumours in situ, rather than the propensity for co-expression of these important melanocytic transcription factors seen in adherent cells and 3D-spheroids. Notably, when the levels of the BRN2 and MITF proteins were each independently repressed using siRNA treatment of adherent melanoma cells, members of the NOTCH pathway responded by decreasing or increasing expression, respectively. This links BRN2 as an activator, and conversely, MITF as a repressor of the NOTCH pathway in melanoma cells. Loss of the BRN2-MITF axis in antisense-ablated cell lines decreased the melanoma sphere-forming capability, cell adhesion during 3D-spheroid formation and invasion through a collagen matrix. Combined, this evidence suggests that the melanoma sphere-culture system induces subpopulations of cells that may more accurately portray the in vivo disease, than the growth as adherent melanoma cells.

[Physical aspects of different tomosynthesis systems]. / Physikalische Aspekte der verschiedenen Tomosynthesesysteme.

Digital breast tomosynthesis (DBT) is a new image processing technique based on digital mammography technology. Image slices of the stationary compressed breast are reconstructed from multiple images taken at different angles of the X-ray tube at the same time. The main goal is to achieve a similar radiation dose exposure as common encountered in traditional digital mammography. One of the key advantages of DBT is that lesions are less likely to be hidden amongst normal tissues as they are in traditional digital mammography. This way the quality of diagnosis can be improved, especially for dense breasts. Current DBT implementations from several manufacturers differ in certain features such as scanning angle, number of projections, scanning time, pixel size, reconstruction methods and type of tube movement. A comparison and description of these different characteristics as well as a discussion on the proposed number of imaging planes and related radiation dose requirements are given.

[Perspectives of the digital mammography platform]. / Perspektiven der digitalen Mammographieplattform.

In Europe one out of every nine women suffers from breast cancer during her lifetime. Since the introduction of mammography screening programs more breast cancers are being diagnosed when they are still small and early stage cancers with a favourable prognosis. The introduction of digital mammography systems has led to a continuous reduction of breast cancer mortality especially in specific patient subgroups. Furthermore, the digital mammography platform enables the development of new, innovative breast imaging methods to increase sensitivity and decrease breast cancer mortality. This digital mammography platform includes digital breast tomosynthesis, digital contrast medium mammography and digital contrast medium breast tomosynthesis as well as fused data sets from digital mammography with ultrasound or MRI. The following article summarizes these new applications, describes the strengths of the digital platform and illustrates the potential advantages of an improved breast cancer diagnosis by digital mammography.

The basophil activation test in the diagnosis of allergy: technical issues and critical factors.

BACKGROUND: The basophil activation test (BAT) is a widely validated and reliable tool especially for the diagnosis of hymenoptera venom allergy. Nevertheless, several pitfalls have to be considered and outcomes may differ because of diverse in-house protocols and commercially available kits. We aimed to identify the factors that may influence results of the CD63-based BAT. METHODS: Basophil responses to monoclonal anti-IgE (clone E124.2.8) and bee and wasp venom were determined by BAT based on CD63. The effect of stimulating factors such as, IL-3, cytochalasin B and prewarming of the samples was investigated. Furthermore, we compared two different flow cytometer systems and evaluated the influence of storage time, different staining protocols and anti-allergic drugs on the test results. RESULTS: Interleukin-3 enhanced the reactivity of basophils at 300 pM, but not at 75 and 150 pM. Prewarming of samples and reagents did not affect basophil reactivity. CD63 expression assayed after storage time of up to 48 h showed that basophil reactivity already started to decline after 4 h. Basophils stained with HLA-DR-PC5 and CD123-PE antibodies gated as HLA-DR(neg)/CD123(pos) cells showed the highest reactivity. No effect on test outcomes was observed at therapeutic doses of dimetindene and desloratadine. Finally, slight differences in the percentage of activated basophils, depending on the cytometer system used, were found. CONCLUSION: Basophil activation test should be performed as early as possible after taking the blood sample, preferably within 4 h. In contrast to the skin test, BAT can be performed in patients undergoing treatment with antihistamines. For reasons of multiple influencing factors, BAT should be performed only at validated laboratories.

Influence of total IgE levels on the severity of sting reactions in Hymenoptera venom allergy.

BACKGROUND: Detection of specific IgE for Hymenoptera venoms and skin tests are well established diagnostic tools for the diagnosis of insect venom hypersensitivity. The aim of our study was to analyze the effect of total IgE levels on the outcome of generalized anaphylactic reactions after a Hymenoptera sting. METHODS: Two hundred and twenty patients allergic to bee, wasp, or European hornet venom were included in the study. Their specific and total IgE levels, serum tryptase levels, skin tests, and sting history were analyzed. RESULTS: In patients with mild reactions (grade I, generalized skin symptoms) we observed higher total IgE levels (248.0 kU/l) compared to patients with moderate reactions (grade II, moderate pulmonary, cardiovascular, or gastrointestinal symptoms; 75.2 kU/l) and severe reactions (grade III, bronchoconstriction, emesis, anaphylactic shock, or loss of consciousness; 56.5 kU/l; P < 0.001). Accordingly, 25% of the patients with low levels of total IgE (<50 kU/l), but no individual with total IgE levels >250 kU/l, developed loss of consciousness (P = 0.001). Additionally, specific IgE levels were related to total IgE levels: Specific IgE levels increased from 1.6 to 7.1 kU/l in patients with low (<50 kU/l) and high (>250 kU/l) total IgE levels, respectively (P < 0.001). Specific IgE levels correlated inversely to the clinical reaction grades, however, this trend was not statistically significant (P = 0.083). CONCLUSION: Patients with Hymenoptera venom allergy and high levels (>250 kU/l) of total IgE, predominantly develop grade I and grade II reactions and appear to be protected from grade III reactions. However, this hypothesis should be confirmed by extended studies with sting challenges.

[Two sisters with progressive familial intrahepatic cholestasis]. / Twee zusjes met progressieve familiaire intrahepatische cholestase.

A few months after birth two sisters aged 5 and 9 years had developed cholestasis and abnormal liver functions with symptoms including itching and jaundice. The younger sister also developed rickets and clotting disorders. On clinical, biochemical and immunohistopathological grounds the diagnosis of 'progressive familial intrahepatic cholestasis (PFIC) type 2' was made. Medical treatment was not succesfull in reducing symptoms. An ileocolonic bypass in the younger child was not effective. Subsequently, both patients underwent partial external biliary diversion (PEBD). Except for a period of intermittent itching in the younger child, both patients remained free of symptoms 2 years after PEBD. In cases where an early diagnosis is made, PEBD could delay or even prevent the necessity of liver transplantation.

Detection of ileocecal Crohn's disease using ultrasound as the primary imaging modality.

At our hospital ultrasound (US) is used as an initial screening procedure in all patients with abdominal symptoms. The purpose of this study was to assess the effect of this policy on the detection of ileocecal Crohn's disease. We retrospectively studied all patients with a new diagnosis of ileocecal Crohn's disease from our institute over the period 1990-2001. The final diagnosis was based on clinical follow-up and pathological, surgical, US, and other radiological findings. We noted who referred the patient to the radiology department, what the initial clinical presumption was, and what the first imaging study was. US diagnoses were determined from the initial US report and US findings were registered from the images. There were a total of 47 patients (20 men, 27 women) with a mean age of 30 years and a median age of 27 years (range 14-75 years). In all patients the initial imaging study was an abdominal US. Using US, a confident diagnosis of ileocecal Crohn's disease was made in 35 of the 47 patients, Crohn's disease was suggested among the differential diagnosis in 10, and an incorrect diagnosis was made in 2 patients. In 28 of 47 patients, the referring physician did not consider Crohn's disease when requesting the initial US examination. In eight patients with appendicitis-like symptoms, the US findings strongly influenced the decision to refrain from operation at that point in time. US, when used as a low-threshold diagnostic procedure, is a reliable and noninvasive means for making an early diagnosis of ileocecal Crohn's disease in patients who present with atypical symptoms. It may prevent both unnecessary therapeutic delay as well as unnecessary surgery.

Risk indicators for falls in institutionalized frail elderly.

The aim of this study was to identify individual predisposing risk indicators for falls in a sample of institutionalized frail elderly in southern Germany. The design was a prospective observational study with a 1-year follow-up (October 1998-September 1999). The study population included 472 long-term-care residents whose mean age was 84 years; 77% were female. Risk indicators for accidental falls were analyzed by using logistic regression. Residents were found to have an incidence density rate of falls of 2,558 per 1,000 resident-years. Multiple logistic regression analysis revealed short-term memory loss, transfer assistance, urinary incontinence, positive fall history, and use of trunk restraints as predictors of falls. In a further logistic regression analysis, depressive symptoms, transfer assistance, urinary incontinence, and positive fall history were associated with frequent falls. Using these risk indicators as a screening procedure to identify fallers would be easy to administer and could be accomplished by nursing staff. Study results encourage specifically addressing urinary incontinence, cognitive impairment, use of restraints, depression, and transfer difficulties as modifiable predisposing risk factors for falls. Fall history represents an important nonmodifiable marker to identify residents at high risk.

[Abilities and restrictions of nursing home residents. Evaluation with the Minimum Data Set of the Resident Assessment Instrument]. / Fähigkeiten und Einschränkungen von Heimbewohnern. Eine Querschnittserhebung mit dem Minimum Data Set des Resident Assessment Instruments.

UNLABELLED: The main objective of the study was to examine the prevalence of problems and resources of an unselected cohort of nursing home residents. The sample includes residents (n=769) of an urban area in Southern Germany. The assessment definitions were used according to the Minimum Data Set of the Resident Assessment Instruments (Version 2.0). RESULTS: The mean age was 84.2 years, 608 of the residents were female. Dementia (446) and stroke (185) were the most common main diagnosis. Syndrome prevalences are reported for depressive symptoms (323), mobility impairments (608), urinary incontinence (461), decubitus (54), use of restraints (54), disruptive behavior (185), psychopharmacy (377), severe visual impairment (123) and severe hearing impairment (123).

Elevated heels and adaptation to new shoes in frail elderly women.

Footwear is supposed to have influence on postural control and is a potential aspect to address in the prevention of falls in the elderly. This study aimed to show whether measurements of static balance and gait are different with habitual shoes compared to new special senior shoes with different heel height and whether these results change after adaptation. In a randomized controlled intervention study, 26 subjects (median age 87 years) were recruited from two nursing homes and one facility of assisted living. Measurements of static balance and gait were performed with habitual shoes and two types of new special senior shoes differing in heel height. Measurements were repeated after five weeks. There was no difference in static balance and gait with habitual shoes compared to either of the new footwear offered. Results of performance with higher heels were not different compared to lower heels. No further effect of adaptation after wearing a new shoe over five weeks could be demonstrated. With respect to static and dynamic balance, there seems to be a wide range of acceptable footwear as long as the heel height is below a critical value. A standardized shoe can be used in the assessment of balance because the effect of adaptation can be neglected.