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We investigated metabolic changes during brain death (BD) using hyperpolarized magnetic resonance (MR) spectroscopy and ex vivo graft glucose metabolism during normothermic isolated perfused kidney (IPK) machine perfusion. BD was induced in mechanically ventilated rats by inflation of an epidurally placed catheter; sham‐operated rats served as controls. Hyperpolarized [1‐13C]pyruvate MR spectroscopy was performed to quantify pyruvate metabolism in the liver and kidneys at 3 time points during BD, preceded by injecting hyperpolarized[1‐13C]pyruvate. Following BD, glucose oxidation was measured using tritium‐labeled glucose (d‐6‐3H‐glucose) during IPK reperfusion. Quantitative polymerase chain reaction and biochemistry were performed on tissue/plasma. Immediately following BD induction, lactate increased in both organs (liver: eµd0.21, 95% confidence interval [CI] [−0.27, −0.15]; kidney: eµd0.26, 95% CI [−0.40, −0.12]. After 4 hours of BD, alanine production decreased in the kidney (eµd0.14, 95% CI [0.03, 0.25], P< .05). Hepatic lactate and alanine profiles were significantly different throughout the experiment between groups (P< .01). During IPK perfusion, renal glucose oxidation was reduced following BD vs sham animals (eµd0.012, 95% CI [0.004, 0.03], P< .001). No differences in enzyme activities were found. Renal gene expression of lactate‐transporter MCT4 increased following BD (P< .01). In conclusion, metabolic processes during BD can be visualized in vivo using hyperpolarized magnetic resonance imaging and with glucose oxidation during ex vivo renal machine perfusion. These techniques can detect differences in the metabolic profiles of the liver and kidney following BD. Differences in glucose metabolism in the liver and kidney can be visualized in vivo during brain death using hyperpolarized magnetic resonance spectroscopy and ex vivo following brain death during normothermic kidney machine perfusion using glucose oxidation.

The authors investigate the impact of brain death on graft function in a rat renal transplantation model and find that slow brain death induction may increase the incidence of delayed graft function after kidney transplantation.

The evaluation of liver grafts may be enhanced by the use of normothermic perfusion after cold storage. In this study fibrinolysis is enhanced as a correlate of ischemia/reperfusion injury in discarded human liver grafts.

The authors present data in preserved human livers discarded for transplantation that oxygenated hypothermic machine perfusion restores cellular energy stores and preserves function when tested in an ex vivo system. Oxygenated end-ischemic perfusion may add a practical, new alternative to the growing field of organ restoration in deceased donor organ retrieval.

Organ procurement is the first step toward effective liver preservation and comprises a thorough washout of blood components from the microvasculature. To study the efficacy of optimal blood washout of the liver, three groups were compared including low-pressure perfusion with UW-CSS (12 mmHg, group A), which is the routine method in clinical practice, high-pressure perfusion with UW-CSS (100 mmHg, group B) and low-pressure perfusion with modified UW solution (12 mmHg, group C). After procurement all livers were preserved in original UW-CSS for 0, 24 or 48 h, followed by reperfusion in oxygenated Williams Medium E for 24 h at 37 °C. Histology results of livers procured in group A, showed good hepatocyte viability but also remaining erythrocytes. However, injury parameters were high and ATP concentrations were low. No functional differences were found. Group B, high pressure, and group C, modified UW-CSS, both showed better results. High-pressure washout is preferable since the warm ischemia time during procurement is short. We propose to use high-pressure UW-CSS perfusion for the initial blood washout of the donor liver instead of the usually used low-pressure washout.

Organ procurement is the first step toward effective liver preservation and comprises a thorough washout of blood components from the microvasculature. To study the efficacy of optimal blood washout of the liver, three groups were compared including low-pressure perfusion with UW-CSS (12 mmHg, group A), which is the routine method in clinical practice, high-pressure perfusion with UW-CSS (100 mmHg, group B) and low-pressure perfusion with modified UW solution (12 mmHg, group C). After procurement all livers were preserved in original UW-CSS for 0, 24 or 48 h, followed by reperfusion in oxygenated Williams Medium E for 24 h at 37 °C. Histology results of livers procured in group A, showed good hepatocyte viability but also remaining erythrocytes. However, injury parameters were high and ATP concentrations were low. No functional differences were found. Group B, high pressure, and group C, modified UW-CSS, both showed better results. High-pressure washout is preferable since the warm ischemia time during procurement is short. We propose to use high-pressure UW-CSS perfusion for the initial blood washout of the donor liver instead of the usually used low-pressure washout.

After kidney transplantation, decreased graft survival is seen in grafts from brain dead (BD) donors compared with living donors. This might result partly from a progressive nonspecific inflammation in the graft. In this study, we focused on the effects of BD on inflammatory response (adhesion molecules, leukocyte invasion, gene expression) and stress-related heat shock proteins in the human kidney. Research outcomes and clinical donor parameters were then linked to outcome data after transplantation.

The objective of this study was to obtain insight into bone formation and resorption in children with newly diagnosed untreated acute lymphoblastic leukemia (ALL). In 23 consecutive children with ALL, a bone biopsy was taken from the crista iliaca posterior under ketamine anesthesia, together with the diagnostic marrow aspiration, before any treatment was given. Histomorphometric assessment was done of bone volume, bone area, trabecular thickness, osteoid volume, osteoid area, osteoid width, number of osteoblasts, erosion area, and number of osteoclasts. Data were analyzed in age groups under and over 10 y and compared with biopsies from 15 children, obtained during the work-up for other malignancies (only patients without bone marrow involvement were included). In ALL patients, bone volume and trabecular thickness were decreased in children <10 y. In patients >10 y, these parameters were not significantly different from the controls; bone densitometry showed no significant loss of bone in patients >10 y as well. Numbers of osteoblasts and osteoid surface occupied with osteoblasts were reduced in both age groups, as was the number of resorbing osteoclasts. No indications of osteomalacia were found. Childhood ALL results in a reduced number of both osteoblasts and osteoclasts, with a subsequent reduced osteoid formation and reduced bone resorption. This leads to a reduced bone volume and trabecular thickness, especially in younger children. In adolescents, the disturbance of bone (re)modeling is less serious, probably because of the strong stimulus on bone formation of sex hormones. The skeletal impairment at diagnosis is potentially reversible.

The objective of this study was to obtain insight into bone formation and resorption in children with newly diagnosed untreated acute lymphoblastic leukemia (ALL). In 23 consecutive children with ALL, a bone biopsy was taken from the crista iliaca posterior under ketamine anesthesia, together with the diagnostic marrow aspiration, before any treatment was given. Histomorphometric assessment was done of bone volume, bone area, trabecular thickness, osteoid volume, osteoid area, osteoid width, number of osteoblasts, erosion area, and number of osteoclasts. Data were analyzed in age groups under and over 10 y and compared with biopsies from 15 children, obtained during the work-up for other malignancies (only patients without bone marrow involvement were included). In ALL patients, bone volume and trabecular thickness were decreased in children <10 y. In patients >10 y, these parameters were not significantly different from the controls; bone densitometry showed no significant loss of bone in patients >10 y as well. Numbers of osteoblasts and osteoid surface occupied with osteoblasts were reduced in both age groups, as was the number of resorbing osteoclasts. No indications of osteomalacia were found. Childhood ALL results in a reduced number of both osteoblasts and osteoclasts, with a subsequent reduced osteoid formation and reduced bone resorption. This leads to a reduced bone volume and trabecular thickness, especially in younger children. In adolescents, the disturbance of bone (re)modeling is less serious, probably because of the strong stimulus on bone formation of sex hormones. The skeletal impairment at diagnosis is potentially reversible.

Coronavirus disease 2019 (COVID-19) often presents asymptomatically or milder in children compared to adults. The role of young children in the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains largely unknown. In the Netherlands, the first action of loosening the partial lockdown that had been implemented to reduce SARS-CoV-2 transmission was the reopening of primary schools on 1 May 2020. We subsequently conducted a prospective cohort study among healthcare workers (HCWs) with primary school-attending children versus HCWs without children living at home. We tested each HCW three times for SARS-CoV-2 from May 20 to June 15 2020 at 1-week intervals. In total, 832 nasopharyngeal swabs were taken from 283 HCWs with primary school-attending children living at home and 864 nasopharyngeal swabs from 285 HCWs without children living at home. All nasopharyngeal swabs tested negative for SARS-CoV-2. In our region with a low population density and low SARS-CoV-2 prevalence, reopening of primary schools did not lead to an increase in infections. The results of this study may serve as an example for the implementation of regional strategies to reduce SARS-CoV-2 transmission in countries with large variations in both population density and SARS-CoV-2 prevalence.