Imaging considerations for in vivo 13C metabolic mapping using hyperpolarized 13C-pyruvate.

One of the challenges of optimizing signal-to-noise ratio (SNR) and image quality in (13)C metabolic imaging using hyperpolarized (13)C-pyruvate is associated with the different MR signal time-courses for pyruvate and its metabolic products, lactate and alanine. The impact of the acquisition time window, variation of flip angles, and order of phase encoding on SNR and image quality were evaluated in mathematical simulations and rat experiments, based on multishot fast chemical shift imaging (CSI) and three-dimensional echo-planar spectroscopic imaging (3DEPSI) sequences. The image timing was set to coincide with the peak production of lactate. The strategy of combining variable flip angles and centric phase encoding (cPE) improved image quality while retaining good SNR. In addition, two aspects of EPSI sampling strategies were explored: waveform design (flyback vs. symmetric EPSI) and spectral bandwidth (BW = 500 Hz vs. 267 Hz). Both symmetric EPSI and reduced BW trended toward increased SNR. The imaging strategies reported here can serve as guidance to other multishot spectroscopic imaging protocols for (13)C metabolic imaging applications.

[Hopeless and unbearable suffering and deliberate ending of life of newborn infants]. / Uitzichtloos en ondraaglijk lijden en actieve levensbeëindiging bij pasgeborenen.

Deliberate ending of life of newborns is an extreme measure that is usually based on hopeless and existing unbearable suffering. There are currently developments that may lead to clarification and refinement of the standards and rules surrounding deliberate ending of life of newborns. This pertains to the phase immediately following the decision to refrain from curative treatment. An important aspect here is that parents and doctors will have to reach agreement on the extent to which the suffering of the newborn can be classified as unbearable. Furthermore, in the case of deliberate ending of life of newborns, consideration must be given not only to current suffering but also the severe suffering that will develop in the near future. The points ofspecial importance that the medical profession had developed in relation to the assessment of future unbearable suffering may provide assistance here and should be implemented.

[From the poliomyelitis epidemic to the founding of artificial respiration centres, intensive care units and centres for home mechanical ventilation]. / Van de poliomyelitisepidemie naar de oprichting van beademingscentra, intensivecareafdelingen en centra voor thuisbeademing.

In 1952, Copenhagen was confronted with a poliomyelitis epidemic that involved the respiratory musculature in large numbers of patients. The anaesthetist B. Ibsen, who established carbon dioxide intoxication due to severe hypoventilation as the cause of death, proposed that the patients be treated by tracheostomy and positive pressure respiration in order to achieve better ventilation than with an iron lung. In the Netherlands, it was decided to organise the control ofthe epidemics on a nationwide basis. Various hospitals were asked to set up artificial respiration centres. In addition, the Beatrix Fund was set up in order to collect money for combating poliomyelitis. The epidemic reached the Netherlands in 1956. In Groningen University Medical Centre, 74 patients were admitted, of whom 36 had to be ventilated. In two cases, the mechanical ventilation could not be stopped and one of these was ultimately discharged home with chronic ventilation in 1960, thus becoming the first patient in the Netherlands to be given mechanical ventilation at home. The mechanical ventilation centres developed into the intensive care units as we know them today. Most of the forms of treatment now in use are based on the techniques thought up and elaborated by the pioneers working in the mechanical ventilation centres. The latest development in this series is the development of centres for home mechanical ventilation.

Outcome after resuscitation beyond 30 minutes in drowned children with cardiac arrest and hypothermia: Dutch nationwide retrospective cohort study.

OBJECTIVES: To evaluate the outcome of drowned children with cardiac arrest and hypothermia, and to determine distinct criteria for termination of cardiopulmonary resuscitation in drowned children with hypothermia and absence of spontaneous circulation. DESIGN: Nationwide retrospective cohort study. SETTING: Emergency departments and paediatric intensive care units of the eight university medical centres in the Netherlands. PARTICIPANTS: Children aged up to 16 with cardiac arrest and hypothermia after drowning, who presented at emergency departments and/or were admitted to intensive care. MAIN OUTCOME MEASURE: Survival and neurological outcome one year after the drowning incident. Poor outcome was defined as death or survival in a vegetative state or with severe neurological disability (paediatric cerebral performance category (PCPC) ≥ 4). RESULTS: From 1993 to 2012, 160 children presented with cardiac arrest and hypothermia after drowning. In 98 (61%) of these children resuscitation was performed for more than 30 minutes (98/160, median duration 60 minutes), of whom 87 (89%) died (95% confidence interval 83% to 95%; 87/98). Eleven of the 98 children survived (11%, 5% to 17%), but all had a PCPC score ≥ 4. In the 62 (39%) children who did not require prolonged resuscitation, 17 (27%, 16% to 38%) survived with a PCPC score ≤ 3 after one year: 10 (6%) had a good neurological outcome (score 1), five (3%) had mild neurological disability (score 2), and two (1%) had moderate neurological disability (score 3). From the original 160 children, only 44 were alive at one year with any outcome. CONCLUSIONS: Drowned children in whom return of spontaneous circulation is not achieved within 30 minutes of advanced life support have an extremely poor outcome. Good neurological outcome is more likely when spontaneous circulation returns within 30 minutes of advanced life support, especially when the drowning incident occurs in winter. These findings question the therapeutic value of resuscitation beyond 30 minutes in drowned children with cardiac arrest and hypothermia.

Colonization and infection by Serratia species in a paediatric surgical intensive care unit.

Serratia species are known for the infections they cause in adult and neonatal intensive care patients. Little is known about colonization and infection in paediatric intensive care patients. This study aims to describe the type of infections in critically ill newborns, infants and children, caused by Serratia spp., to compare patients colonized by Serratia spp. to patients colonized with other micro-organisms, and to assess the importance of the respiratory and digestive tracts as reservoirs. To this end, all microbiological samples taken from patients in our paediatric surgical intensive care unit between January 1986 and November 1993 were retrieved from the hospital database and patient records reviewed. Serratia spp. were isolated 1356 times from 97 patients. Eighty-five infections were diagnosed in 40 patients. Infections of the respiratory tract occurred most frequently (n= 65), followed by septicaemia (13), urinary tract infections (3), omphalitis (2), meningitis (1) and conjunctivitis (1). Colonization by Serratia spp. was associated with yearly age at admission, long ICU stay and high mortality. Both the respiratory and digestive tracts were frequently colonized. Our findings do not support the contention that the digestive tract is more important as reservoir than the respiratory tract in neonates.

Intestinal permeability in newborns with necrotizing enterocolitis and controls: Does the sugar absorption test provide guidelines for the time to (re-)introduce enteral nutrition?

BACKGROUND: In necrotizing enterocolitis (NEC), (sub)mucosal edema, hemorrhage, ulceration, or necrosis will disturb intestinal integrity, as reflected by an increased intestinal permeability. Enteral substrate is therefore withheld for a variable period up to 3 weeks (in many clinics). The authors used the sugar absorption test to measure intestinal permeability changes in surgically treated necrotizing enterocolitis patients and surgical controls to evaluate the usefulness of this test in timing the (re-)introduction of enteral feeding in NEC patients as intestinal integrity recovers. METHODS: Changes in intestinal permeability to lactulose and rhamnose were evaluated prospectively in 13 children with NEC and 10 operated control patients. The patients were given 1 mL/kg body weight lactulose/rhamnose solution at different time intervals after admission. The lactulose to rhamnose (L/R) ratio was determined by gaschromatography in 4-hour urine samples. RESULTS: The L/R ratios in NEC patients were increased for prolonged periods of time with a tendency to decrease in the third week after the start of NEC. However, in some cases, the increased L/R ratios even exceeded the 3-week period of starvation. High peaks in the L/R ratio were seen in patients suffering from bowel perforation or sepsis. Compared with necrotizing enterocolitis patients, L/R ratios of control patients were increased only in the first days after surgery and normalized more rapidly. The results of the L/R tests in this study corroborated the clinical condition of the patients. CONCLUSIONS: The sugar absorption test shows an individual variability in the recovery of intestinal permeability in a group of seriously ill newborns with advanced stages of NEC. An individual approach in restarting enteral nutrition seems to be justified; however, the optimal time-point to restart enteral nutrition cannot be determined by the sugar absorption test alone. Combining parameters of intestinal integrity and function could enable a more accurate determination of this optimal timepoint. J Pediatr Surg 36:587-592.

The incidence of septic complications in newborns on extracorporeal membrane oxygenation is not affected by feeding route.

PURPOSE: The aim of this study was to compare the effects of enteral and total parenteral feeding on septic complications in neonates on extracorporeal membrane oxygenation (ECMO). METHODS: Ninety-six neonates were on ECMO between January 1992 and February 1998. Matching for diagnosis and exclusion of neonates with sepsis before ECMO or undergoing surgery on ECMO left 16 enterally fed neonates (cases) and 35 parenterally fed neonates (controls) for analysis. Septic complications were scored using the criteria of the Society of Critical Care Medicine and the American College of Chest Physicians adapted to children. RESULTS: Both groups were comparable with respect to gestational age, sex, and age at initiation of ECMO. The frequency of septic complications did not differ between cases and controls: no complications, 75% versus 69%; systemic inflammatory response syndrome, 13% versus 6%; bacteremia, 6% versus 14%; sepsis, 6% versus 11%. There were no complications associated with enteral feeding. The ECMO run was significantly longer in the case group (median, 161 v. 111 hours; P =.01) and mortality rate was lower in the case group (0 v. 14%; P =.17). CONCLUSIONS: Enteral nutrition does not affect the risk of sepsis in neonates on ECMO when compared with total parenteral nutrition. Enteral nutrition is well tolerated and not associated with adverse effects.

Introduction of enteral feeding in neonates on extracorporeal membrane oxygenation after evaluation of intestinal permeability changes.

BACKGROUND/PURPOSE: Neonates meeting criteria for extracorporeal membrane oxygenation (ECMO) often suffer from variable periods of hypoxia. During ECMO, starvation of the gut is common practice in many centres as splanchnic ischemia results in loss of intestinal integrity, which in turn predisposes for bacterial translocation and sepsis and eventually necrotizing enterocolitis (NEC) and multiorgan failure. However, minimal enteral feeding is thought to be of benefit in the critically ill. Data on intestinal integrity in newborns on ECMO and the effects of enteral nutrition are not available. This study prospectively evaluates the changes in small intestinal integrity in 16 neonatal ECMO patients. METHODS: With 2-day intervals, excretion percentages of lactulose/L-rhamnose (nonmediated diffusion), D-xylose (passive), and 3-O-methyl-D-glucose (active carrier-mediated transport) were measured by gas-liquid chromatography in a 4-hour urine sample. After obtaining baseline data in nine patients, enteral feeding was started in the next seven patients between the third and the ninth day of ECMO. RESULTS: Thirteen patients had increased lactulose/L-rhamnose ratios (>0.05) consistent with increased intestinal permeability. In three patients the lactulose/L-rhamnose ratios were within the normal range. D-xylose excretion percentages were normal (or slightly increased) in 11 patients consistent with normal (or increased) passive carrier-mediated transport. 3-O-methyl-D-glucose excretion percentages were decreased (<10%) in all but one patient, consistent with decreased active carrier-mediated transport. After introduction of enteral nutrition no significant changes of these parameters were seen. CONCLUSIONS: The authors conclude that intestinal integrity is compromised in neonates on ECMO and that introduction of enteral nutrition does not result in further deterioration. This conclusion does not support the practice of withholding enteral nutrition in critically ill newborns supported by ECMO.

Blunt splenic trauma in children: are we too careful?

INTRODUCTION: There has been a shift from operative treatment (OT) to non-operative treatment (NOT) of splenic injury. We evaluated the outcomes of treatment of pediatric patients with blunt splenic trauma in our hospital, with special focus on the outcomes after NOT. PATIENTS AND METHODS: The data of all patients <18 years with radiologically proven blunt splenic injury admitted between 1988 and 2007 were retrospectively analyzed. Mechanism of injury, type of treatment, ICU stay, total hospital stay, morbidity and mortality were assessed. Patients suffering isolated splenic injuries were assessed separately from patients with multiple injuries. Patients were subsequently divided into those admitted before and after 2000. RESULTS: There were 64 patients: 49 males and 15 females with a mean age of 13 years (range 0-18). 3 patients died shortly after admission due to severe neurological injury and were excluded. In the remaining 61 patients concomitant injuries, present in 62%, included long bone fractures (36%), chest injuries (16%), abdominal injuries (33%) and head injuries (30%). Mechanisms of injury were: car accidents (26%), motorcycle (20%), bicycle (19%), fall from height (17%) and pedestrians struck by a moving vehicle (8%). A change in treatment strategy was evident for the pre- and post-2000 periods. Significantly more patients had NOT after 2000 in both the isolated splenic injury group and the multi-trauma group [4/11 (36%) before vs. 10/11 (91%) after (p=0.009); 15/19 (79%) before vs. 8/20 (40%) after 2000 (p=0.03)]. There was also a significant shift to spleen-preserving operations. All life-threatening complications occurred within <24 h after injury. Mortality for the entire cohort was 7%; all of these patients were treated operatively. When comparing the median ICU and hospital stay before and after 2000 it was found to be significantly higher in the isolated injury group and remained statistically the same in the multi-trauma group. CONCLUSION: Splenic injury in children is associated with substantial mortality. This is due to concomitant injuries and not to the splenic injury. Non-operative treatment is increasingly preferred to operative procedures when treating splenic injuries in hemodynamically, stable children. ICU and hospital stay have, despite the change from OT to NOT, remained the same. Complications after NOT are rare. We are still observing children in hospital for a longer period than is necessary.

In vivo 13 carbon metabolic imaging at 3T with hyperpolarized 13C-1-pyruvate.

We present for the first time dynamic spectra and spectroscopic images acquired in normal rats at 3T following the injection of (13)C-1-pyruvate that was hyperpolarized by the dynamic nuclear polarization (DNP) method. Spectroscopic sampling was optimized for signal-to-noise ratio (SNR) and for spectral resolution of (13)C-1-pyruvate and its metabolic products (13)C-1-alanine, (13)C-1-lactate, and (13)C-bicarbonate. Dynamic spectra in rats were collected with a temporal resolution of 3 s from a 90-mm axial slab using a dual (1)H-(13)C quadrature birdcage coil to observe the combined effects of metabolism, flow, and T(1) relaxation. In separate experiments, spectroscopic imaging data were obtained during a 17-s acquisition of a 20-mm axial slice centered on the rat kidney region to provide information on the spatial distribution of the metabolites. Conversion of pyruvate to lactate, alanine, and bicarbonate occurred within a minute of injection. Alanine was observed primarily in skeletal muscle and liver, while pyruvate, lactate, and bicarbonate concentrations were relatively high in the vasculature and kidneys. In contrast to earlier work at 1.5 T, bicarbonate was routinely observed in skeletal muscle as well as the kidney and vasculature.

Gastrointestinal hormone secretion after surgery in neonates with congenital intestinal anomalies during starvation and introduction of enteral nutrition.

BACKGROUND/PURPOSE: Gastrointestinal hormones modulate gut function in response to enteral nutrition. Infants with a congenital intestinal anomaly with loss of bowel length either pre-or postnatal, who are on total parenteral nutrition for prolonged periods after surgery, are especially prone to a disturbed secretion of gut hormones. The aim of this study was to determine whether circulating gut hormones were altered in these patients and to collect baseline data for future studies in short bowel patients using different enteral substrates. METHODS: Gastrin, cholecystokinin, and peptide YY were measured in 14 operated neonates who had a congenital intestinal anomaly during starvation and introduction of enteral nutrition. None of the neonates had a short bowel. Fourteen neonates who underwent surgery for other major congenital anomalies served as age-matched controls. Gut hormones were measured with radioimmunoassays. RESULTS: Postprandial gut hormone values were higher than basal gut hormone values within both groups. Compared with the controls, postprandial gastrin and cholecystokinin were significantly higher in the patients. CONCLUSIONS: Neonates with a congenital intestinal anomaly in the absence of a short bowel have a similar secretion pattern of gastrointestinal hormones as neonates with a structurally normal intestinal tract, both during starvation and enteral nutrition.

Genetic anticipation in rheumatoid arthritis in Europe. European Consortium on Rheumatoid Arthritis Families.

OBJECTIVE: To investigate whether there is evidence for genetic anticipation in rheumatoid arthritis (RA) in Europe. METHODS: Cross sectional comparison of data from all affected parent-offspring pairs identified among (1) the RA population attending our department and (2) a large cohort of families from RA probands with both parents alive recruited by the European Consortium on RA families (ECRAF) for association studies. Longitudinal comparison between probands with and without parental RA. We used prospectively collected data on disease activity, therapies, and radiological outcomes from our Dutch inception cohort of patients with early RA during the first 6 years of followup. RESULTS: From a total of 683 Dutch and 170 European patients we identified 28 Dutch and 21 European parent-offspring pairs with RA. Probands with parental RA had an earlier disease onset compared with affected parents (Dutch p < 0.002, European p < 0.0001). In Dutch patients, the prevalence of HLA-DR4, DR4 double dose, and shared epitope (SE) double dose was slightly higher in probands with parental RA than in those without [odds ratios (95% CI) 2.0 (0.7-5.8), 2.79 (0.8-9.4), and 2.12 (0.6-8.7), respectively]. The same was true for European probands concerning SE double dose [OR (95% CI) 1.76 (0.6-8.7)]. No other relevant differences in demographic or clinical indices were found between probands with affected parents and those without. Disease course (Disease Activity Score) and therapies used during the first 6 years of followup were similar in Dutch patients with and without parental RA. Radiological damage at baseline was lower in the former group and this difference persisted after 3 and 6 years. CONCLUSION: Our data suggest that genetic anticipation in RA does occur in terms of an earlier disease onset in the offspring. Despite a slightly higher prevalence of HLA alleles encoding for the SE, probands with confirmed parental RA had no worse outcome than those without.