Renal artery flow alterations in neonates with hypoxic ischemic encephalopathy.

BACKGROUND: To compare kidney blood flow and kidney function tests in infants with hypoxic ischemic encephalopathy (HIE), and the effects of therapeutic hypothermia (TH) during the first 7 days of life. METHODS: Fifty-nine infants with HIE were prospectively evaluated. Infants with moderate-severe HIE who required TH were classified as group 1 (n = 36), infants with mild HIE were classified as group 2 (n = 23), and healthy infants were classified as group 3 (n = 60). Kidney function tests were evaluated on the sixth hour, third and seventh days of life in Group 1 and Group 2, and on the sixth hour and third day of life in group 3. Renal artery (RA) Doppler ultrasonography (dUS) was performed in all infants on the first, third, and seventh days of life. RESULTS: Systolic and end diastolic blood flow in RA tended to increase and RA resistive index (RI) tended to decrease with time in group 1 (p = 0.0001). While end diastolic blood flow rates in RA on the third day were similar in patients with severe HIE and mild HIE, it was lower in patients with mild-moderate-severe HIE than healthy newborns. On the seventh day, all three groups had similar values (p > 0.05). Serum blood urea nitrogen (BUN), creatinine, uric acid, and cystatin C levels gradually decreased and glomerular filtration rate (GFR) gradually increased during TH in group 1 (p = 0.0001). Serum creatinine levels gradually decreased while GFR gradually increased during the study period in group 2. CONCLUSIONS: Therapeutic hypothermia seems to help restore renal blood flow and kidney functions during the neonatal adaptive period with its neuroprotective properties.

Grading the level of evidence of neonatal pharmacotherapy: midazolam and phenobarbital as examples.

BACKGROUND: Many drugs are used off-label or unlicensed in neonates. This does not mean they are used without evidence or knowledge. We aimed to apply and evaluate the Grading and Assessment of Pharmacokinetic-Pharmacodynamic Studies (GAPPS) scoring system for the level of evidence of two commonly used anti-epileptic drugs. METHODS: Midazolam and phenobarbital as anti-epileptics were evaluated with a systematic literature search on neonatal pharmacokinetic (PK) and/or pharmacodynamic [PD, (amplitude-integrated) electroencephalography effect] studies. With the GAPPS system, two evaluators graded the current level of evidence. Inter-rater agreement was assessed for dosing evidence score (DES), quality of evidence (QoE), and strength of recommendation (REC). RESULTS: Seventy-two studies were included. DES scores 4 and 9 were most frequently used for PK, and scores 0 and 1 for PD. Inter-rater agreements on DES, QoE, and REC ranged from moderate to very good. A final REC was provided for all PK studies, but only for 25% (midazolam) and 33% (phenobarbital) of PD studies. CONCLUSIONS: There is a reasonable level of evidence concerning midazolam and phenobarbital PK in neonates, although using a predefined target without integrated PK/PD evaluation. Further research is needed on midazolam use in term neonates with therapeutic hypothermia, and phenobarbital treatment in preterms. IMPACT: There is a reasonable level of evidence concerning pharmacotherapy of midazolam and phenobarbital in neonates. Most evidence is however based on PK studies, using a predefined target level or concentration range without integrated, combined PK/PD evaluation. Using the GAPPS system, final strength of recommendation could be provided for all PK studies, but only for 25% (midazolam) to 33% (phenobarbital) of PD studies. Due to the limited PK observations of midazolam in term neonates with therapeutic hypothermia, and of phenobarbital in preterm neonates these subgroups can be identified for further research.

A new line method; A direct test in spinal muscular atrophy screening for DBS.

BACKGROUND: Nucleic acid-based assays provide an opportunity to screen for genetically encoded diseases like spinal muscular atrophy (SMA), before the onset of symptoms. Nowadays, such assays could be easily utilized as high-throughputs in SMA to detect a homozygous deletion of exon 7 of the survival motor neuron 1 gene (SMN1) that is responsible for >95% of SMA patients. METHODS: We developed a new line method (NLM) as a direct real time PCR test procedure without nucleic acid extraction in dried blood spots (DBS) to screen for homozygous deletion of exon 7 of the SMN1 gene. Performance of this setup was evaluated on 580 DBS newborn samples and air dried 50 DBS from whole blood including 20 samples for homozygous deletion of the SMN1 gene detected earlier with MLPA. RESULTS: We found all 580 newborn DBS samples as wild type. DBS prepared from 50 whole blood samples also including 20 affected people were correctly identified as homozygous deletions and 30 wild types of exon 7 of SMN1 as before with MLPA. When the MLPA method was taken as the gold standard, the sensitivity and specificity of the NLM test were found 100% for the detection of SMN1 exon 7 homozygous deletion. CONCLUSION: In the NLM, the total test duration has been reduced to less than 75 min without requiring any extra process such as DNA extraction step and sample plate preparation after the punching step. Thereby, newborn SMA screening with the NLM has gained an environmentally friendly feature with not requiring additional tedious steps.

Early postnatal metabolic profile in neonates with critical CHDs.

BACKGROUND: Cyanotic CHD is a life-threatening condition that presents with low oxygen saturation in the newborn period. Hypoxemia might cause alterations in the metabolic pathways. In the present study, we aimed to evaluate the early postnatal amino acid and carnitine/acylcarnitine profiles of newborn infants with cyanotic CHD. METHODS: A single centre case-control study was conducted. Twenty-seven patients with cyanotic CHD and 54 healthy newborn controls were enrolled. As part of the neonatal screening programme, results of amino acid and carnitine/acylcarnitine were recorded and compared between groups. RESULTS: Twenty-seven neonates with cyanotic CHD and 54 healthy newborns as controls were enrolled in the study. Cyanotic CHD neonates had higher levels of alanine, phenylalanine, leucine/isoleucine, citrulline, ornithine, C5, C5-OH; but lower levels of C3, C10, C12, C14, C14:1, C16, C16.1, C18, C5-DC, C6-DC, C16-OH, C16:1-OH when compared with the healthy controls. CONCLUSION: This study showed that there are differences between patients with cyanotic CHD and healthy controls in terms of postnatal amino acid and carnitine/acylcarnitine profiles.

Does a prenatal diagnosis affect mortality and morbidity for neonatal arterial switch operation.

BACKGROUND: The effect of prenatal diagnosis on prognosis in patients with transposition of the great arteries is not clear. In this study, we compared the outcomes after arterial switch operation. METHODS: Outcome of 112 patients who had arterial switch operation in the neonatal period were analysed. The patients were divided into two groups: those who had prenatal diagnosis (Group 1; n = 34) and those who did not (Group 2; n = 78). The patients were also classified based on their diagnosis: simple transposition, transposition with ventricular septal defect and/or aortic arch hypoplasia, and Taussig-Bing anomaly. RESULTS: In Group 1, the C-section delivery rate was higher (82% vs. 44%; p = 0.004), and it was observed that patients in Group 1 were more often intubated upon admission to the neonatal ICU (38% vs. 9%; p = 0.005). No differences were found between the two groups in terms of operation time, cardiopulmonary bypass time, post-operative invasive respiratory support duration, or extracorporeal membrane oxygenation support. It was observed that those who had Taussig-Bing anomaly had a higher mortality. CONCLUSIONS: Timely treatment have a positive effect on neonatal mortality and morbidity. That's why all families with prenatal diagnosis of critical CHD should be recommended to have the delivery in a tertiary care hospital. Although it could not be demonstrated in this study, prenatal diagnosis has a potential to improve surgical results especially in countries or cities, which does not have enough resources for transfer and surgical units. Further efforts are needed to improve prenatal screening programmes.

Determining T and B Cell development by TREC/KREC analysis in primary immunodeficiency patients and healthy controls.

T cell receptor excision circles (TRECs) and kappa-deleting excision circles (KRECs) are DNA fragments potentially indicative of T and B cell development, respectively. Recent thymic emigrants (RTEs) are a subset of peripheral cells that may also represent thymic function. Here, we investigated TREC/KREC copy numbers by quantitative real-time PCR in the peripheral blood of patients with primary immunodeficiencies (PIDs, n = 145) and that of healthy controls (HCs, n = 86) and assessed the correlation between RTEs and TREC copy numbers. We found that TREC copy numbers were significantly lower in children and adults with PIDs (P < .0001 and P < .002, respectively) as compared with their respective age-matched HCs. A moderate correlation was observed between TREC copies and RTE numbers among children with PID (r = .5114, P < .01), whereas no significant correlation was detected between RTE values and TREC content in the HCs (r = .0205, P = .9208). Additionally, we determined TREC and KREC copy numbers in DNA isolated from the Guthrie cards of 200 newborns and showed that this method is applicable to DNA isolated from both peripheral blood samples and dried blood spots, with the two sample types showing comparable TREC and KREC values. We further showed that RTE values are not always reliable markers of T cell output. Although additional confirmatory studies with larger cohorts are needed, our results provide thresholds for TREC/KREC copy numbers for different age groups.

Liver Abscess in a Cyanotic Newborn.

Umbilical venous catheterisation is a common bedside procedure in the neonatal intensive care unit (NICU). Complications including thrombus formation, thromboembolism, vessel perforation, haemorrhage, and central line-associated bloodstream infection can be seen after the procedure. Pyogenic liver abscess is a rare but life-threatening complication of umbilical venous catheterisation. A male infant with cyanotic congenital heart disease was admitted to NICU. An umbilical venous catheter (UVC) was inserted. Abdominal X-ray showed an improperly positioned UVC, it was removed and replaced with a newer one. On the seventh day, the infant had abdominal distension and his clinical condition deteriorated. Abdominal ultrasonography (US) revealed a hepatic abscess. US-guided percutaneous abscess drainage was performed. Empiric antibiotic treatment was initiated and culture revealed Staphylococcus. The patient was followed by serial US and the lesion was completely resolved after three weeks. In conclusion, clinical worsening associated with gastrointestinal symptoms in a cyanotic infant with UVC should raise suspicion for liver abscess. Key Words: Neonate, Hepatic abscess, Umbilical venous catheter, Cyanotic heart disease.

Neonatal Problems and Infancy Growth of Term SGA Infants: Does "SGA" Definition Need to Be Re-evaluated?

Introduction: The exact definition of small-for-gestational-age (SGA) infant is still controversial among clinicians. In this study, we aimed to understand which definition is better in terms of establishing both early postnatal problems and growth. In this way, we compared early neonatal problems and infancy growth of term infants with birth weight (BW) < -2 SDS and with BW between 10th percentile (-1.28 SDS) and -2 SDS. Methods: A single center retrospective cohort study was conducted. Preterm infants, multiple gestations and newborns with any congenital anomalies were excluded from the study. Study group was defined as Group 1 (n = 37), infants BW < -2.00 SDS; Group 2 (n = 129), between -1.28 and -2.00 SDS; and Group 3 (n = 137), randomly selected newborns with optimal-for-gestational-age (BW between -0.67 and +0.67 SDS) as a control group. Results: The incidence of severe hypoglycemia was highest in Group 1 (%10.8) and Group 2 and 3 had similar rates of severe hypoglycemia (0.8 and 0.7%, respectively). The incidence of polycythemia was 5.4% in Group 1 and was significantly higher than Group 3 (0.0%) while it was 2.3% in Group 2. Short stature (length < -2 SDS) ratio at the age of 1 and 2 years were similar in each group. Overweight/obesity ratio at the age of 1 were 9.5, 20.8 and 16.7% in each group, respectively (p = 0.509). Conclusion: This study was planned as a pilot study to determine potential differences in the problems of hypoglycemia, polycythemia, and growth according to the differences in definition. Short term disturbances such as hypoglycemia and polycythemia are found to be higher in infants with a BW SDS below -2. From this point of view, of course, it will not be possible to change the routine applications immediately, however this study will be an initiative for discussions by making long-term studies.

Early Postnatal Metabolic Profile in Neonates With Different Birth Weight Status: A Pilot Study.

Introduction: Restricted or enhanced intrauterine growth is associated with elevated risks of early and late metabolic problems in humans. Metabolomics based on amino acid and carnitine/acylcarnitine profile may have a role in fetal and early postnatal energy metabolism. In this study, the relationship between intrauterine growth status and early metabolomics profile was evaluated. Materials and Methods: A single-center retrospective cohort study was conducted. Three hundred and sixty-one newborn infants were enrolled into the study, and they were grouped according to their birth weight percentile as small for gestational age (SGA, n = 69), appropriate for gestational age (AGA, n = 168), and large for gestational age (LGA, n = 124) infants. In all infants, amino acid and carnitine/acylcarnitine profiles with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were recorded and compared between groups. Results: LGA infants had higher levels of glutamic acid and lower levels of ornithine, alanine, and glycine (p < 0.05) when compared with AGA infants. SGA infants had higher levels of alanine and glycine levels when compared with AGA and LGA infants. Total carnitine, C0, C2, C4, C5, C10:1, C18:1, C18:2, C14-OH, and C18:2-OH levels were significantly higher and C3 and C6-DC levels were lower in SGA infants (p < 0.05). LGA infants had higher C3 and C5:1 levels and lower C18:2 and C16:1-OH levels (p < 0.05). There were positive correlations between free carnitine and phenylalanine, arginine, methionine, alanine, and glycine levels (p < 0.05). Also, a positive correlation between ponderal index and C3, C5-DC, C14, and C14:1 and a negative correlation between ponderal index and ornithine, alanine, glycine, C16:1-OH, and C18:2 were shown. Conclusion: We demonstrated differences in metabolomics possibly reflecting the energy metabolism in newborn infants with intrauterine growth problems in the early postnatal period. These differences might be the footprints of metabolic disturbances in future adulthood.

The prevalence and diagnostic criteria of health-care associated infections in neonatal intensive care units in Turkey: A multicenter point- prevalence study.

BACKGROUND: Healthcare-acquired infections (HAIs) in the neonatal period cause substantial morbidity, mortality, and healthcare costs. Our purpose was to determine the prevalence of HAIs, antimicrobial susceptibility of causative agents, and the adaptivity of the Centres for Disease Control and Prevention (CDC) criteria in neonatal HAI diagnosis. METHODS: A HAI point prevalence survey was conducted in the neonatal intensive care units (NICUs) of 31 hospitals from different geographic regions in Turkey. RESULTS: The Point HAI prevalence was 7.6%. Ventilator-associated pneumonia (VAP) and central line-associated bloodstream infections (CLABSI) and late onset sepsis were predominant. The point prevalence of VAP was 2.1%, and the point prevalence of CLABSI was 1.2% in our study. The most common causative agents in HAIs were Gram-negative rods (43.0%), and the most common agent was Klebsiella spp (24.6%); 81.2% of these species were extended spectrum beta-lactamase (ESBL) (+). Blood culture positivity was seen in 33.3% of samples taken from the umbilical venous catheter, whereas 0.9% of samples of peripherally inserted central catheters (PICCs) were positive. In our study, 60% of patients who had culture positivity in endotracheal aspirate or who had purulent endotracheal secretions did not have any daily FiO2 change (p = 0.67) and also 80% did not have any increase in positive end-expiratory pressure (PEEP) (p = 0.7). On the other hand, 18.1% of patients who had clinical deterioration compatible with VAP did not have endotracheal culture positivity (p = 0.005). CONCLUSIONS: Neonatal HAIs are frequent adverse events in district and regional hospitals. This at-risk population should be prioritized for HAI surveillance and prevention programs through improved infection prevention practices, and hand hygiene compliance should be conducted. CDC diagnostic criteria are not sufficient for NICUs. Future studies are warranted for the diagnosis of HAIs in NICUs.

Evaluation of neonatal acute kidney injury after critical congenital heart disease surgery.

BACKGROUND: Acute kidney injury (AKI) is a common complication of congenital heart diseases (CHDs) after cardiac surgery. This study aimed to define the frequency and critical course, risk factors and short-term outcomes of AKI in postoperative CHD neonates. METHODS: Postoperatively followed term CHD newborn infants were enrolled in the study. Infants with congenital anomalies of the urinary tract and other major congenital anomalies were excluded. Neonatal modified KDIGO criteria were used to assess AKI. RESULTS: A total of 199 postoperatively followed newborn infants were included in the study. Acute kidney injury was detected in 71 (35.6%) patients. Of these patients, 24 (33.8%) were in stage 1, 14 (19.7%) in stage 2, and 33 (46.5%) in stage 3. Acute kidney injury occurred within the first week (median 1 day [IQR 1-2 days]) of cardiac surgery in 93% of the patients. The duration of invasive respiratory support and extracorporeal membrane oxygenation (ECMO) and mortality were significantly higher in stage 3 patients. Higher vasoactive-inotropic score (OR, 1.02; 95% CI, 1.0-1.04; p = 0.008) and receiving ECMO (OR, 7.9; 95% CI, 2.6-24.4; p = 0.001) were associated with risk for the development of AKI. The mortality rate was 52.1% in the AKI (+) patients, and having AKI (OR 7.1; 95% CI, 3.5-14.18) was significantly associated with mortality. CONCLUSION: Acute kidney injury, a common early complication after critical neonatal CHD cardiac surgery, is associated with increased morbidity and mortality. Stage 3 AKI is associated with significantly higher mortality rates.

Negative Effects of Noise on NICU Graduates' Cochlear Functions.

AIM: To evaluate the adverse effects of noise on hearing. Methods: Thirty-two infants that had been admitted to neonatal intensive care unit (NICU) and 25 healthy controls were included in this study. Noise levels were recorded continously during the hospitalization period. Results: All healthy controls passed the hearing screening tests before discharge and on the sixth-month follow up. Hospitalized infants had lower "Distortion Product Auto Acoustic Emission Signal Noise Ratio" (DPOAE SNR) amplitudes (dB) at five frequencies (1001, 1501, 3003, 4004, 6006 Hz in both ears). DPOAE fail rates at 1001 Hz and 1501 Hz were higher than in hospitalized infants (81.8% and 50.0% vs 20.0% and 4.0%). Infants who failed the test at 1001 and 1501 Hz were exposed to noise above the recommended maximum level for longer periods of time. Conclusion: Hearing tests performed at sixth-months of life were adversely affected in NICU graduates.

Complete sternal cleft treatment in a low birth weight patient.

A complete sternal cleft is a very rare congenital anomaly causing severe respiratory compromise. Surgical reconstruction options are limited, particularly in low birth weight newborns. Herein, we report a case of low birth weight premature newborn with a complete sternal cleft and its surgical treatment.

Incidence of hypoglycemia in newborns at risk and an audit of the 2011 American academy of pediatrics guideline for hypoglycemia.

BACKGROUND: Hypoglycemia is low blood glucose level that may negatively affect neurological and developmental prognosis. The American Academy of Pediatrics (AAP), Committee on Fetus and Newborn defined the safe glucose concentrations in the 2011 guideline for newborns at risk for hypoglycemia. This study aimed to investigate the incidence and associated risk factors for hypoglycemia in newborn infants having risk and to assess compliance with the AAP guideline. METHODS: According to 2011 AAP guideline for hypoglycemia, the newborns at risk for hypoglycemia included in this study were divided to four groups [infant of diabetic mother (IDM), large-for-gestational-age (LGA) infants, small-for-gestational-age (SGA) infants, and late preterm infants (LPI)]. RESULTS: Of the 207 newborn infants, there were 12 cases in IDM group (5.7%), 79 cases in LGA group (38.1%), 66 cases in SGA group (31.8%) and 50 cases in LPI group (24.1%). The incidences of hypoglycemia in these four groups were 2 (16.6%), 10 (12.7%), 8 (12.2%) and 17 (34%), respectively. Although the gender, delivery method, birth weight and 5-min Apgar score at 5-min were not found to be associated with hypoglycemia (P > 0.05), lower gestational age was determined to be associated with higher incidence of hypoglycemia (P = 0.02). Median first feeding time was 55 min and time between first nutrition and blood glucose measurement was 30 min in all cases. CONCLUSION: Highest risk for hypoglycemia in early postnatal period was present especially in LPI group. Our compliance levels with the AAP guideline was found to be satisfactory.

Relationship between serum 25-hydroxy vitamin D levels and retinopathy of prematurity.

Aim To evaluate the relationship between serum 25-hydroxy vitamin D, 25 (OH) D, levels and retinopathy of prematurity. Methods and Results Serum 25 (OH) D levels were measured in 97 very low birth weight infants, prior to vitamin D supplementation. The development of retinopathy of prematurity and its treatment requirement were evaluated. At follow-up, retinopathy of prematurity developed in 71 (73.2%) infants. Serum 25 (OH) D levels were significantly lower in infants with retinopathy of prematurity than ones without retinopathy of prematurity ( P < 0.001). The infants who required treatment had lower 25 (OH) D levels compared with the infants who did not required treatment (7.1 ± 5.2 ng/ml vs. 11.9 ± 6.5 ng/ml; P = 0.003). Multivariate analysis showed that lower serum 25 (OH) D levels may be a risk factor for retinopathy of prematurity development [OR: 1.14, 95% CI (1.02-1.27), P = 0.02]. Conclusion Lower 25 (OH) D levels in the first days of life may be related to retinopathy of prematurity development and treatment requirement in premature infants.

Effects of Volume Guaranteed Ventilation Combined with Two Different Modes in Preterm Infants.

BACKGROUND: Volume-controlled ventilation modes have been shown to reduce duration of mechanical ventilation, incidence of chronic lung disease, failure of primary mode of ventilation, hypocarbia, severe intraventricular hemorrhage, pneumothorax, and periventricular leukomalacia in preterm infants when compared with pressure limited ventilation modes. Volume-guarantee (VG) ventilation is the most commonly used mode for volume-controlled ventilation. Assist control, pressure-support ventilation (PSV), and synchronized intermittent mandatory ventilation (SIMV) can be combined with VG; however, there is a lack of knowledge on the superiority of each regarding clinical outcomes. Therefore, we investigated the effects of SIMV+VG and PSV+VG on ventilatory parameters, pulmonary inflammation, morbidity, and mortality in preterm infants. METHODS: Preterm infants who were born in our hospital between 24-32 weeks gestation and needed mechanical ventilation for respiratory distress syndrome were considered eligible. Patients requiring high-frequency oscillatory ventilation for primary treatment were excluded. Subjects were randomized to either SIMV+VG or PSV+VG. Continuously recorded ventilatory parameters, clinical data, blood gas values, and tracheal aspirate cytokine levels were analyzed. RESULTS: The study enrolled 42 subjects. Clinical data were similar between groups. PSV+VG delivered closer tidal volumes to set tidal volumes (60% vs 49%, P = .02). Clinical data, including days on ventilation, morbidity, and mortality, were similar between groups. Chronic lung disease occurred less often and heart rate was lower in subjects who were ventilated with PSV+VG. The incidence of hypocarbia and hypercarbia were similar. Interleukin-1ß in the tracheal aspirates increased during both modes. CONCLUSION: PSV+VG provided closer tidal volumes to the set value in ventilated preterm infants with respiratory distress syndrome and was not associated with overventilation or a difference in mortality or morbidity when compared to SIMV+VG. Therefore, PSV+VG is a safe mode of mechanical ventilation to be used for respiratory distress syndrome.

Efecto aditivo de las células madre mesenquimales y del defibrótido en un modelo de trombosis arterial en ratas / Additive effect of mesenchymal stem cells and defibrotide in an arterial rat thrombosis model

Introducción. El objetivo de este estudio consistió en investigar el efecto aditivo de las células madre mesenquimales (MSC, por sus siglas en inglés) y del defibrótido (DFT) en un modelo de trombosis arterial femoral en ratas. Métodos. Se incluyeron 30 ratas Sprague Dawley. Se desarrolló un modelo de trombosis arterial mediante cloruro de hierro (FeCl3) en la arteria femoral izquierda. Las ratas se asignaron equitativamente en cinco grupos: grupo 1, intervención quirúrgica simulada (sin lesión arterial); grupo 2, inyección de solución salina tamponada con fosfato (PBS); grupo 3, MSC; grupo 4, DFT; grupo 5, MSC + DFT. Todas las ratas recibieron dos inyecciones intraperitoneales de 0,5 ml: la primera se administró 4 horas después del procedimiento y la segunda 48 horas después de la primera. Se sacrificó a las ratas siete días después de la segunda inyección. Resultados. Aunque el uso por separado de MSC derivadas de médula ósea humana (hBM-MSC) o de DFT permitió una resolución parcial del trombo, la combinación de ambos tuvo como resultado la resolución casi completa. La neovascularización fue doblemente mejor en las ratas tratadas con hBM-MSC + DFT (11,6 ± 2,4 canales) en comparación con los grupos asignados por separado a hBM-MSC (3,8 ± 2,7 canales) y DFT (5,5 ± 1,8 canales) (P < 0,0001 y P= 0,002, respectivamente). Conclusión. El uso combinado de hBM-MSC y DFT en un modelo de trombosis arterial en ratas mostró que el efecto aditivo tuvo como resultado la resolución casi completa del trombo.

Background/aim. In this study, we aimed to investigate the additive effect of mesenchymal stem cells (MSC) and defibrotide (DFT) in a rat model of femoral arterial thrombosis. Methods. Thirty Sprague Dawley rats were included. An arterial thrombosis model by ferric chloride (FeCl3) was developed in the left femoral artery. The rats were equally assigned to 5 groups: Group 1-Sham-operated (without arterial injury); Group 2-Phosphate buffered saline (PBS) injected; Group 3-MSC; Group 4-DFT; Group 5-MSC + DFT. All had two intraperitoneal injections of 0.5 ml: the 1st injection was 4 h after the procedure and the 2nd one 48 h after the 1st injection. The rats were sacrificed 7 days after the 2nd injection. Results. Although the use of human bone marrow-derived (hBM) hBM-MSC or DFT alone enabled partial resolution of the thrombus, combining them resulted in near-complete resolution. Neovascularization was two-fold better in hBM-MSC + DFT treated rats (11.6 ± 2.4 channels) compared with the hBM-MSC (3.8 ± 2.7 channels) and DFT groups (5.5 ± 1.8 channels) (P < 0.0001 and P= 0.002, respectively). Conclusion. The combined use of hBM-MSC and DFT in a rat model of arterial thrombosis showed additive effect resulting in near-complete resolution of the thrombus.