Rescue extracorporeal cardiopulmonary resuscitation in pediatric patients: a nine-year single-center experience in Zagreb,Croatia

AimTo investigate the risk factors and the outcomes of extracorporeal membrane oxygenation (ECMO) in pediatric patients treated at the University Hospital Center Zagreb, the largest center in Croatia providing pediatric ECMO.MethodsThis retrospective study enrolled all the pediatric patients who required E-CPR from 2011 to 2019. Demographic data, cardiac anatomy, ECMO indications, ECMO complications, and neurodevelopmental status at hospital discharge were analyzed.ResultsIn the investigated period, E-CPR was used in 16 children, and the overall survival rate was 37.5%. Six patients were in the neonatal age group, 5 in the infant group, and 5 in the “older” group. There was no significant difference between the sexes. Four patients had an out-of-hospital arrest and 12 had an in-hospital arrest. Twelve out of 16 patients experienced renal failure and needed hemodialysis, with 4 out of 6 patients in the survivor group and 8 out of 10 in the non-survivor group. Survivors and non-survivors did not differ in E-CPR duration time, lactate levels before ECMO, time for lactate normalization, and pH levels before and after the start of ECMO.ConclusionThe similarity of our results to those obtained by other studies indicates that the ECMO program in our hospital should be maintained and improved.

The use of extracorporeal cardiopulmonary resuscitation (E-CPR) is increasing (1). E-CPR is defined as an initiation of extracorporeal membrane oxygenation (ECMO) during active chest compressions. Its main goal is to provide immediate cardiovascular support to patients who do not react to CPR (2) and to lead to survival and a better neurological outcome (3). After administering CPR for more than 30 minutes, survival with conventional CPR measures ranges between 0%-5% (4,5).The most recent systematic review by the International Liaison Committee on Resuscitation from 2015 recommended that E-CPR should be considered for children with underlying cardiac conditions who have an in-hospital cardiac arrest when appropriate protocols, expertise, and equipment are available (6). According to the Extracorporeal Life Support Organization (ELSO) registry from 2017 (7), more than 60 000 people received extracorporeal life support (ECLS), between 2009 and 2015, with an overall survival rate of 61% (7). Pediatric ECMO experience in Slovenia shows that ECMO programs may be incorporated in smaller hospitals in the region (8-10). The ELSO database includes data on all reported pediatric ECMO runs, including those conducted with E-CPR, and in patients with congenital heart surgery and neonates with diaphragmatic hernia or meconium aspiration syndrome, etc. During the 6-year period, 3005 E-CPR runs were reported, with an overall survival to hospital discharge of 43% (7). A survival rate of 31% was reported by Ergűn et al (11) and in E-CPR patients with severe burn injury (12). The longer the CPR duration time, the lower was the survival to discharge rate. Matos et al reported an E-CPR survival-to-discharge rate of 33% after >35 min of chest compressions (13). Other studies reported that the overall survival rate of pediatric E-CPR cases was growing, with better neurological outcomes than among the patients in the CPR group only (14). Pilar et al found that in 73 pediatric cardiac patients requiring cardiopulmonary resuscitation for >30 min (15), the survival to hospital discharge was 43.8%, with 3/4 of the patients having normal neurological function or mild neurological disability (15). Based on ELSO registry, approximately 10% of all ECMO patients meet brain death criteria (7). One of the biggest single-center studies, involving 184 pediatric ECPR patients (16), showed a successful ECMO weaning in 63% of the patients and the overall survival rate to hospital discharge of 43%. In the same study, the risk factors linked to increased mortality were presupport pH<7.1, mechanical complications, and neurological complications (16). The E-CPR use can involve many complications, not necessarily linked to factors preceding cardiac arrest, such as low cardiac output syndrome or irreversible respiratory failure (17). Furthermore, common complications of ECMO treatment are fluid overload and acute kidney injury (18). Many studies showed renal replacement therapy (RRT) to be negatively associated with survival (15,16,18,19).This study assessed the risk factors and the outcomes of ECMO in the largest Croatian center providing pediatric E-CPR experience over nine years and compared the survivor and the non-survivor group.     

Thermal contribution of compact bone to intervening tissue-like media exposed to planar ultrasound

The presence of bone in the ultrasound beam path raises concerns, both in diagnostic and therapeutic applications, because significant temperature elevations may be induced at nearby soft tissue-bone interfaces due the facts that ultrasound is (i) highly absorbed in bone and (ii) reflected at soft tissue-bone interfaces in various degrees depending on angle of incidence. Consequently, in ultrasonic thermal therapy, the presence of bone in the ultrasound beam path is considered a major disadvantage and it is usually avoided. However, based on clinical experience and previous theoretical studies, we hypothesized that the presence of bone in superficial unfocused ultrasound hyperthermia can actually be exploited to induce more uniform and enhanced (with respect to the no-bone situation) temperature distributions in superficial target volumes. In particular, we hypothesize that the presence of underlying bone in superficial target volume enhances temperature elevation not only by additional direct power deposition from acoustic reflection, but also from thermal diffusion from the underlying bone. Here we report laboratory results that corroborate previous computational studies and strengthen the above-stated hypothesis. Three different temperature measurement techniques, namely, thermometric (using fibre-optic temperature probes), thermographic (using an infrared camera) and magnetic resonance imaging (using proton resonance frequency shifts), were used in high-power short-exposure, and in low-power extended-exposure, experiments using a 19 mm diameter planar transducer operating at 1.0 and 3.3 MHz (frequencies of clinical relevance). The measurements were performed on three technique-specific phantoms (with and without bone inclusions) and experimental set-ups that resembled possible superficial ultrasound hyperthermia clinical situations. Results from all three techniques were in general agreement and clearly showed that significantly higher heating rates (greater than fourfold) were induced in soft tissue-like phantom materials adjacent (within approximately 5 mm) to a bovine bone as compared to similar experiments without bone inclusions. For low-power long-exposure experiments, where thermal conduction effects are significant, the thermal impact of bone reached at distances > 10 mm from the bone surface (upstream of the bone). Therefore, we hypothesize that underlying bone exposed to planar ultrasound hyperthermia creates a high-temperature thermal boundary at depth that compensates for beam attenuation, thus producing more uniform temperature distribution in the intervening tissue layers. With appropriate technology, this finding may lead to improved thermal doses in superficial treatment sites such as the chest wall and the head/neck.     

Metabolites of alveolarEchinococcus as determined by [31P]- and [1H]-nuclear magnetic resonance spectroscopy

[³¹P]-Nuclear magnetic resonance (NMR) in vivo spectra ofEchinococcus multilocularis cysts growing subcutaneously inMeriones unguiculatus showed prominent signals due to phosphomonoesters (PME), phosphodiesters (PDE), inorganic phosphate (Pi) and the , and phosphate groups of adenosine triphosphate (ATP). The internal pH of the parasite cysts was 6.7–6.8. The³¹P spectra of extracts of these subcutaneous cysts showed peaks identified as glucose-6-phosphate (Glu-6-P), glycerol-3-phosphate (Gly-3-P), phosphorylethanolamine (PE), adenosine-5-monophosphate (5-AMP), nicotinamide adenine dinucleotide phosphate (NADP), phosphorylcholine (PC), Pi, glycerolphosphorylethanolamine (GPE), glycerolphosphorylcholine (GPC), phosphoenolpyruvate (PEP), adenosine diphosphate (ADP), ATP and diphosphodiesters (DPDE). These metabolites were also detected at comparable concentrations in the extracts of intraperitoneally grown cysts. In addition, significantly more phosphocreatine (PCr), probably of host origin, was detected in the subcutaneous cysts than in the intraperitoneal cysts. [¹H]-NMR spectra of cyst extracts revealed that parasites grown in the abdominal cavity contained significantly less glucose but significantly more succinate, acetate, alanine and -hydroxybutyrate. Glycogen, creatine, glycine, taurine, betaine, cholines and lactate were present at similar concentrations in cyst material from both locations.     

Evaluation of RapiDEC Staph for identification of Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus saprophyticus.

RapiDEC Staph is a test for presumptive identification of the principal human staphylococcal species, Staphylococcus aureus, S. epidermidis, and S. saprophyticus. The test includes control and test cupules for fluorogenic detection of coagulase and chromogenic substrates for alkaline phosphatase and beta-galactosidase. These tests identify S. aureus, S. epidermidis, and S. saprophyticus, respectively. Positive results with both chromogenic substrates provide a presumptive identification of S. xylosus or S. intermedius (S. xylosus-S. intermedius). Test cupules are inoculated with an organism suspension, and reactions are read after a 2-h incubation. RapiDEC-Staph was evaluated with 303 clinical and stock staphylococcal strains. Identifications were compared with those obtained by the tube coagulase test, a latex slide coagulase test (StaphAUREX), another commercial identification system (Staph-TRAC), and additional conventional tests. RapiDEC-Staph correctly identified 100% of 130 S. aureus strains, 70.3% of 74 S. epidermidis strains, and 81.3% of 32 S. saprophyticus strains. Four of five S. xylosus isolates were called S. xylosus-S. intermedius. Unidentified S. epidermidis and S. saprophyticus strains were called "Staphylococcus spp." Among the 62 other coagulase-negative staphylococci, 4 were misidentified as S. epidermidis and 7 were misidentified as S. saprophyticus. While the sensitivity and specificity of the fluorogenic coagulase test for S. aureus were 100%, failure to detect alkaline phosphatase activity in several S. epidermidis isolates resulted in fewer correct identifications by the RapiDEC-Staph test for this species.     

Behavioral and hormonal effects of attachment object separation in surrogate-peer-reared and mother-reared infant rhesus monkeys

Mother-reared and surrogate-peer-reared rhesus monkeys were separated from their respective attachment objects at 6 months of age and tested for the following 9 weeks to determine their home cage behavior and their pituitary-adrenocortical responses to stress. Both groups displayed a strong immediate behavioral response to separation which was characterized by increases vocalization, increased locomotion, and decreased self-play. However, the surrogate-peer-reared infants showed a subsequent recovery in their levels of self-play whereas the mother-reared infants instead developed stereotypic behavior patterns such as repetitive pacing. The 2 groups displayed similar plasma cortisol responses to weekly sessions in an apparatus equipped with animated toy “monsters.” Mother-reared but not surrogate-peer-reared subjects, however, also manifested elevated cortisol levels when an animal in an adjacent cage was captured and removed for stress testing. Mother-reared infant monkeys thus responded in a stronger and more prolonged manner to the loss of their attachment object than surrogate-peer-reared infants. These results suggest that infant rhesus monkeys form stronger attachments to monkey mothers than to inanimate surrogate mothers, a phenomenon which has not been as clearly demonstrated using other indices of attachment strength.     

Sequestration of tau by granulovacuolar degeneration in Alzheimer''s disease.

Antibodies directed against three regions of tau have been used in a histologic study of granulovacuolar degeneration (GVD) in Alzheimer's disease (AD). Granulovascular degeneration complexes, consisting of a dense granule in a less-dense vacuole, were found in hippocampal pyramidal neurons in all patients studied. Anti-tau antibodies directed against the N-and C-termini, and the repeat region of tau, were found to immunolabel the granule of the GVD complex. Intracellular neurofibrillary tangles also were labeled by these antibodies. In particular, MAb6.423, which recognizes tau protein sequestered in paired helical filaments (PHF) in AD, but not the normal tau proteins so far described in human brain, labeled GVD granules. Contrarily, a generic tau marker (MAb7.51), which immunolabels all known isoforms of isolated and expressed tau protein, including PHF-tau, did not label the GVD granule. These findings demonstrate that the entire tau molecule is sequestered within the GVD granule, and that the tau protein found in GVD complexes is antigenically related to that found in PHFs. There is, however, a difference in the way in which the repeat region of tau is incorporated into the two structures, making the MAb7.51 epitope unavailable in the GVD complex. These findings suggest that the formation of GVD complexes in hippocampal pyramidal neurons vulnerable to neurofibrillary degeneration may represent an alternative pathway for dealing with an aberrant molecular complex, which contributes to the formation of GVD granules and neurofibrillary tangles in AD.     

Maximal oxygen consumption,pulmonary function,body composition,and anthropometry of adolescent female athletes

Three groups of girl athletes — 10 gymnasts and 8 middle-distance swimmers averaging 14 years of age, and 8 middle-distance runners averaging almost 19 — were the subjects of this study. The maximal oxygen intake was determined by graded work load on a bicycle ergometer, certain pulmonary functions by spirometry, and total body potassium by wholebody counting of naturally radioactive⁴⁰K. The total body water was obtained from measurements of deuterium oxide and application of the dilution principle, and creatinine excretion was determined from urine collections. Fat-free mass was calculated from total body water, and the amount of body fat was obtained by subtracting fat-free mass from body weight. Cell mass was calculated from total body potassium. Supporting evidence of leanness or fatness was provided by anthropometric measurements.The runners and swimmers achieved significantly higher maximal oxygen consumption per kg of body weight, fat-free mass, and cell mass; and the runners excelled the gymnasts in certain other pulmonary functions. Total body potassium in milliequivalents per kg of body weight, total body water expressed in percentage of body weight, and creatinine coefficients were similar in all three groups of subjects. These results indicated no differences in body composition. Calculations of body fat, fat-free mass, and cellular mass verified that conclusion; and supporting evidence was obtained from subcutaneous fat folds and from appraisal of leanness by corrected limb diameters or volumes, which also were similar in all three groups.     

Demineralized bone matrix as a biological scaffold for bone repair

Experimental models were created in rat fibula to represent impaired bone healing so that biological deficiencies that cause bone repair to fail or to be delayed may be investigated. These models consist of a 4-mm-long segmental defect, created in rat fibula by osteotomy, and fitted with a 7-mm-long tubular specimen of demineralized bone matrix (DBM) over the cut ends of the fibula. The experiments in this study involved various modifications of the DBM scaffold designed to reduce its osteoinductive activity: steam sterilization (sDBM), ethylene oxide sterilization (eoDBM), trypsin digestion (tDBM), and guanidine hydrochloride extraction (gDBM). Bone healing was evaluated by bending rigidity of the fibula and mineral content of the repair site at 7 weeks post-surgery. The sDBM scaffolds resorbed completely by 7 weeks and hence this model was a nonhealing negative control. Rigidities in the unmodified DBM and tDBM groups were comparable, whereas in the gDBM and eoDBM groups it was significantly reduced. Histologically, in the 4-mm defects repaired with unmodified DBM, direct and endochondral bone formation in the scaffold and the defect resulted in a neocortex consisting of woven and lamellar bone uniting the broken bone by 7 weeks post-surgery. We conclude that the eoDBM and gDBM groups represent failure or delay of the bone repair process when compared with the unmodified DBM group in which the process is analogous to normal bone healing.     

Orexin A mediation of time spent moving in rats: Neural mechanisms

The brain regulates energy balance and spontaneous physical activity, including both small- and large-motor activities. Neural mediators of spontaneous physical activity are currently undefined, although the amount of time spent in sedentary positions versus standing and ambulating may be important in the energetics of human obesity. Orexin A, a neuropeptide produced in caudal hypothalamic areas and projecting throughout the neuraxis, enhances arousal and spontaneous physical activity. To test the hypothesis that orexin A affects the amount of time spent moving, we injected orexin A (0–1000 pmol) into three orexin projection sites in male Sprague–Dawley rats: hypothalamic paraventricular nucleus, rostral lateral hypothalamic area and substantia nigra pars compacta, and measured spontaneous physical activity. Orexin A affects local GABA release and we co-injected orexin A with a GABA agonist, muscimol, in each brain site. Dopamine signaling is important to substantia nigra function and so we also co-injected a dopamine 1 receptor antagonist (SCH 23390) in the substantia nigra pars compacta. In all brain sites orexin A significantly increased time spent vertical and ambulating. Muscimol significantly and dose-dependently inhibited orexin A effects on time spent moving only when administered to the rostral lateral hypothalamic area. In the substantia nigra pars compacta, SCH 23390 completely blocked orexin A–induced ambulation. These data indicate that orexin A influences time spent moving, in three brain sites utilizing separate signaling mechanisms. That orexin A modulation of spontaneous physical activity occurs in brain areas with multiple roles indicates generalization across brain site, and may reflect a fundamental mechanism for enhancing activity levels. This potential for conferring physical activity stimulation may be useful for inducing shifts in time spent moving, which has important implications for obesity.