RAM Cannula Versus Bi-Nasal Prongs as Respiratory Device Interfaces in Neonates of Thirty-Two or More Weeks of Gestation With Respiratory Distress: The First "ProRAM" Randomized Trial Report.

Background: Using bilateral short nasal prongs as an interface for noninvasive respiratory support is challenging, and it is associated with nasal injury. We aimed to compare RAM cannula with nasal prongs in delivering noninvasive ventilation to newborn infants. Methods: This is a single-center randomized trial (trial registry: ISRCTN10561691). The setting involves a tertiary neonatal unit with a capacity of 30 beds and more than 13 years of experience in neonatal noninvasive ventilation. We included 50 infants born at ≥ 32 weeks of gestation, who had respiratory distress at birth. We excluded those with major congenital anomalies and those who required intubation in the delivery room. Primary outcomes were intubation rate and use of noninvasive positive-pressure ventilation (NIPPV); other outcomes included air leak and nasal injury rate. The infants were assigned using randomly generated numbers into bi-nasal prong and RAM canula groups in a 1:1 ratio. Results: Two and four babies in the RAM and prong groups, respectively, were upgraded to NIPPV (P = 0.600). One versus no baby in the RAM vs. prong groups was intubated (P = 1.000). Newborns in the prong group required oxygen support for a longer period (mean duration: 154.6 ± 255.2 h) than those in the RAM group (40.7 ± 72.6 h, P = 0.030). None of the patients in the RAM group had traumatic nasal injury compared to five babies in the prong group (P = 0.050). Four babies in our study developed air leaks, with two in each group. Conclusions: The use of RAM cannula in delivering noninvasive ventilation to newborns ≥ 32 weeks of age did not affect the noninvasive ventilation failure rate or incidence of air leak. The use was associated with a shorter duration of respiratory support and a reduced risk of nasal septal injury.

Congenital Diaphragmatic Hernia at a Non-ECMO Center in Jordan.

OBJECTIVES: We studied the clinical characteristics and outcomes of neonates with congenital diaphragmatic hernia (CDH) admitted to a non-extracorporeal membrane oxygenation (ECMO) center. METHODS: A retrospective chart review of neonates with CDH admitted to a University Hospital, in Amman, Jordan, between 2005 and 2019. Demographic characteristics and their management details were extracted and factors associated with survival were analyzed. RESULTS: A total of 28 neonates born with CDH were included; their survival rate was 39.3%. Onset of respiratory distress, pre-operative ventilation, and length of hospitalization were significantly associated with mortality. Survival after surgery was significantly associated with a higher gestational age and a longer hospital stay. CONCLUSION: Our study showed a high mortality rate for CDH patients. Decreasing the health inequity and improved clinical interventions could improve outcomes.

All-cause mortality in a pediatric intensive care unit at a teaching hospital in Amman, Jordan.

BACKGROUND: The aim of this study was to describe the main causes of admission to a general pediatric intensive care unit (PICU), and examine the main causes of mortality in this patient population. In addition, we describe the percentage of patients who died following a failed cardiopulmonary resuscitation (CPR) versus do not resuscitate (DNR) orders. METHODS: This was a retrospective, cohort study with a chart review of admissions and mortality cases that occurred in the PICU. Mortality rates in pediatric admissions are reported with a description of demographics, diagnosis, length of stay, use of mechanical ventilation, use of vasoactive agents, preexisting comorbidities, the presence of a DNR order, and final cause of mortality. Modes of mortality were described as failed CPR or a DNR order. RESULTS: During the study period there were 1,523 admissions to the PICU. Of those, 102 patients died with an overall mortality rate of 6.7%. Patients who died tended to be younger, and the majority (85%) had a preexisting comorbidity, with neuromuscular disease being the most common. The majority of the patients who died (69%) required invasive ventilation. The most common immediate cause of mortality was respiratory disease and the highest case fatality was among those with cardiac disease. Of those patients who died, 90% had failed CPR and 10% had a DNR order. Care was not withdrawn from any patient. CONCLUSION: This study describes the diagnostic categories of children admitted to the PICU, with respiratory disease being the most common cause of admission and mortality. The majority of children who died had an existing comorbidity and did not have a DNR order at the time of their death.

Gene Expression Profiling of Apoptotic Proteins in Circulating Peripheral Blood Mononuclear Cells in Type II Diabetes Mellitus and Modulation by Metformin.

INTRODUCTION: Insulin resistance in obesity and type 2 diabetes mellitus (T2DM) is associated with cardiovascular complications such as atherosclerosis. On the other hand, the reduction of apoptosis in macrophages has been linked with accelerated atherosclerosis. Apoptosis is controlled by a different family of proteins including Bcl-2 and caspases. METHODS: To examine apoptosis in insulin resistance, we assessed the mRNA expression by qRT-PCR of several Bcl-2 family members, as well as caspase-3, -7, -8, and -9 in peripheral blood mononuclear cells (PBMCs) isolated from lean, obese, diabetic, and diabetic on metformin individuals. RESULTS: PBMCs of diabetic individuals exhibited reduced expression of caspase-7 and increased expression of Bcl-10, Bad, Bax, Bid, and caspase-3. T2DM on metformin group had significantly higher Bad, Bax, and caspase-7 expression. DISCUSSION: The moderate up-regulation of pro-apoptotic Bcl-10, Bax, Bad, Bid, and the effector caspase-3 coupled with inhibition of caspase-7 in circulating PBMCs of T2DM could be the result of increased inflammation in T2DM. Metformin treatment significantly inhibited the expression of Bcl-10, Bid, and caspase-3 and upregulated Bad/Bax/caspase-7 pathway suggesting the activation of Bad/Bax/caspase-7 apoptotic pathway. Further studies are warranted to elicit the underlying apoptotic pathways of PBMCs in T2DM and following metformin treatment.

Distinctive Metabolomics Patterns Associated With Insulin Resistance and Type 2 Diabetes Mellitus.

Obesity is associated with an increased risk of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) which is a multi-factorial disease associated with a dysregulated metabolism and can be prevented in pre-diabetic individuals with impaired glucose tolerance. A metabolomic approach emphasizing metabolic pathways is critical to our understanding of this heterogeneous disease. This study aimed to characterize the serum metabolomic fingerprint and multi-metabolite signatures associated with IR and T2DM. Here, we have used untargeted high-performance chemical isotope labeling (CIL) liquid chromatography-mass spectrometry (LC-MS) to identify candidate biomarkers of IR and T2DM in sera from 30 adults of normal weight, 26 obese adults, and 16 adults newly diagnosed with T2DM. Among the 3633 peak pairs detected, 62% were either identified or matched. A group of 78 metabolites were up-regulated and 111 metabolites were down-regulated comparing obese to lean group while 459 metabolites were up-regulated and 166 metabolites were down-regulated comparing T2DM to obese groups. Several metabolites were identified as IR potential biomarkers, including amino acids (Asn, Gln, and His), methionine (Met) sulfoxide, 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate, serotonin, L-2-amino-3-oxobutanoic acid, and 4,6-dihydroxyquinoline. T2DM was associated with dysregulation of 42 metabolites, including amino acids, amino acids metabolites, and dipeptides. In conclusion, these pilot data have identified IR and T2DM metabolomics panels as potential novel biomarkers of IR and identified metabolites associated with T2DM, with possible diagnostic and therapeutic applications. Further studies to confirm these associations in prospective cohorts are warranted.

A Case Report of Takayasu's Arteritis and Ulcerative Colitis in a Pediatric Patient with Chronic Recurrent Multifocal Osteomyelitis Successfully Treated with Infliximab: Diagnostic Clues in Disease Associations and Immune Dysregulation.

BACKGROUND: Takayasu's arteritis with comorbid chronic recurrent multifocal osteomyelitis and ulcerative colitis is rare in the pediatric population. Treatment with anti-TNF alpha agents such as infliximab has been a successful treatment strategy in adults and can be used effectively in the pediatric population. CASE PRESENTATION: We present the case of a 15-year-old Caucasian girl with a history of chronic recurrent multifocal osteomyelitis and ulcerative colitis presenting with hypertensive emergency secondary to Takayasu's arteritis with middle aortic syndrome. She was treated with corticosteroids and methotrexate and ultimately required infliximab infusions of 15 mg/kg every 4 weeks to successfully control her symptoms and normalize her inflammatory markers. CONCLUSIONS: In this case, we discuss the use of infliximab in an adolescent patient with chronic recurrent multifocal osteomyelitis, ulcerative colitis, and Takayasu's arteritis. The significance of this case is determined by the unique occurrence of all three conditions in a pediatric patient, the important consideration of vasculitis in the differential of a pediatric patient presenting with hypertensive emergency, the need for vigilance for detecting diagnostic clues, signs, and symptoms, knowledge of disease associations when evaluating a patient with a predisposition for autoinflammatory conditions, and the use of increasing doses of infliximab to control symptoms.

Effect of Permissive Underfeeding with Intensive Insulin Therapy on MCP-1, sICAM-1, and TF in Critically Ill Patients.

PURPOSE: This study examined the effect of permissive underfeeding compared to target feeding and intensive insulin therapy (IIT) compared to conventional insulin therapy (CIT) on the inflammatory mediators monocyte chemoattractant protein 1 (MCP-1), soluble intercellular adhesion molecule 1 (sICAM-1), and tissue factor (TF) in critically ill patients. METHODOLOGY: This was a substudy of a 2 × 2 factorial design randomized controlled trial in which intensive care unit (ICU) patients were randomized into permissive underfeeding compared to target feeding groups and into IIT compared to CIT groups (ISRCTN96294863). In this substudy, we included 91 patients with almost equal numbers across randomization groups. Blood samples were collected at baseline and at days 3, 5, and 7 of an ICU stay. Linear mixed models were used to assess the differences in MCP-1, sICAM-1, and TF across randomization groups over time. RESULTS: Baseline characteristics were balanced across randomization groups. Daily caloric intake was significantly higher in the target feeding than in the permissive underfeeding groups (P-value < 0.01), and the daily insulin dose was significantly higher in the IIT than in the CIT groups (P-value < 0.01). MCP-1, sICAM-1, and TF did not show any significant difference between the randomization groups, while there was a time effect for MCP-1. Baseline sequential organ failure assessment (SOFA) score and platelets had a significant effect on sICAM-1 (P-value < 0.01). For TF, there was a significant association with age (P-value < 0.01). CONCLUSIONS: Although it has been previously demonstrated that insulin inhibits MCP-1, sICAM-1 in critically ill patients, and TF in non-critically ill patients, our study demonstrated that IIT in critically ill patients did not affect these inflammatory mediators. Similarly, caloric intake had a negligible effect on the inflammatory mediators studied.

Differential Expression of Human N-Alpha-Acetyltransferase 40 (hNAA40), Nicotinamide Phosphoribosyltransferase (NAMPT) and Sirtuin-1 (SIRT-1) Pathway in Obesity and T2DM: Modulation by Metformin and Macronutrient Intake.

BACKGROUND: Interactions between environmental factors, such as diet and lifestyle, and metabolic pathways are pivotal in understanding aging mechanisms. hNAA40, Nicotinamide phosphoribosyltransferase (NAMPT), and NAD-dependent protein deacetylase sirtuin-1 (SIRT-1) have been shown to exert important biological processes, including stress response and aging. METHODS: hNAA40, NAMPT, and SIRT-1 mRNA expression in peripheral blood mononuclear cells (PBMC) were quantitated in 30 lean adult volunteers of normal weight, 30 obese, 20 drug-naïve obese Type 2 diabetes mellitus (T2DM), and 30 obese T2DM on Metformin. Similarly, hNAA40, NAMPT, and SIRT-1 expression in PBMC were quantitated in 36 normal healthy adults randomly assigned to three different groups (Glucose or Whey proteins or lipids; 300 kcal). Blood samples were obtained at 1, 2, and 3 hrs after the macronutrient intake. RESULTS: There was an increase in hNAA40 and a decrease in NAMPT and SIRT-1 expression in PBMC from T2DM. Metformin treatment reverted hNAA40, NAMPT, and SIRT-1 expression levels to normal levels. Glucose intake resulted in a significant increase in expression of hNAA40 at 1 hr and decreased significantly at 3 hrs post intake. Lipid intake resulted in an increase in expression of hNAA40 at 2 hr post intake and returned to normal levels at 3 hrs. Neither glucose nor lipid intake resulted in a significant change in NAMPT or SIRT-1 expression. Whey proteins resulted in significantly lower expression of NAMPT at 3 hrs and did not alter the expression levels of SIRT-1 significantly. CONCLUSION: hNAA40, NAMPT, and SIRT-1 pathway could play a role in the determination of the healthy life-span. Metformin modulates this pathway.

Differential Expression of Human Peripheral Mononuclear Cells Phenotype Markers in Type 2 Diabetic Patients and Type 2 Diabetic Patients on Metformin.

Background: Although peripheral blood mononuclear cells (PBMC) have been demonstrated to be in a pro-inflammatory state in obesity and type 2 Diabetes Mellitus (T2DM), characterization of circulating PBMC phenotypes in the obese and T2DM and the effect of Metformin on these phenotypes in humans is still ill-defined and remains to be determined. Methods: Thirty normal healthy adult volunteers of normal weight, 30 obese subjects, 20 obese newly diagnosed diabetics and 30 obese diabetics on Metformin were recruited for the study. Fasting blood samples were collected and PBMC were isolated from whole blood. Polarization markers (CD86, IL-6, TNFα, iNOS, CD36, CD11c, CD169, CD206, CD163, CD68, CD11b, CD16, and CD14) were measured by RT-qPCR. Gene expression fold changes were calculated using the 2-ΔΔCT method for RT-qPCR. Results: Obesity and T2DM are associated an increased CD68 marker in PBMC. mRNA expression of CD11b, CD11c, CD169, and CD163 were significantly reduced in PBMC from T2DM subjects whereas CD11c was significantly inhibited in PBMC from obese subjects. On the other hand, macrophage M1-like phenotype was observed in T2DM circulation as demonstrated by increased mRNA expression of CD16, IL-6, iNOS, TNFα, and CD36. There were no significant changes in CD14 and CD86 in the obese and T2DM when compared to the lean subjects. Metformin treatment in T2DM reverted CD11c, CD169, IL-6, iNOS, TNFα, and CD36 to levels comparable to lean subjects. CD206 mRNA expression was significantly upregulated in PBMC of T2DM while Metformin treatment inhibited CD206 expression levels. Conclusions: These data support the notion that PBMC in circulation in T2DM express different pattern of phenotypic markers than the patterns typically present in M1 and M2 like cells. These phenotypic markers could be representative of metabolically activated macrophages (MMe)-like cells. Metformin, on the other hand, reduces MMe-like cells in circulation.

Phenotypic Characterization of Human Monocytes following Macronutrient Intake in Healthy Humans.

BACKGROUND: Three subsets of human monocytes in circulation have been identified and their characterization is still ill-defined. Although glucose and lipid intakes have been demonstrated to exert pro-inflammatory effects on mononuclear cells (MNCs) of healthy subjects, characterization of monocytes phenotypes following macronutrient (glucose, protein, and lipid) intake in humans remains to be determined. METHODS: Thirty-six healthy, normal weight volunteers were recruited in the study. Subjects were randomly assigned into three groups, each group consisting of 12 participants. Each group drank equal calories (300 kcal) of either glucose or lipids or whey proteins. Each subject served as his own control by drinking 300 mL of water 1 week before or after the caloric intake. Baseline blood samples were drawn at 0, 1, 2, and 3-h intervals post caloric or water intakes. MNCs were isolated, and the expression levels of different cluster of differentiation (CD) markers (CD86, CD11c, CD169, CD206, CD163, CD36, CD68, CD11b, CD16, and CD14) and IL-6 were measured by RT-qPCR. RESULTS: Equicaloric intake of either glucose or lipids or whey proteins resulted in different monocyte phenotypes as demonstrated by changes in the expression levels of CD and polarization markers. Whey proteins intake resulted in significant mRNA upregulation in MNCs of CD68 and CD11b at 1, 2, and 3 h post intake while mRNA of IL-6 was significantly inhibited at 1 h. Lipids intake, on the other hand, resulted in mRNA upregulation of CD11b at 2 and 3 h and CD206 at 1, 2, and 3 h. There were no significant changes in the other CD markers measured (CD86, CD163, CD169, CD36, CD16, and CD14) following either whey proteins or lipids intakes. Glucose intake did not alter mRNA expression of any marker tested except CD206 at 3 h. CONCLUSION: Macronutrient intake alters the expression levels of polarization markers in MNCs of human subjects. A distinct population of different monocytes phenotypes may result in human circulation following the intake of different macronutrients. Further studies are required to characterize the immunomodulatory effects of macronutrients intake on monocytes phenotypes and their characteristics in humans.

IVC filter retrieval in adolescents: experience in a tertiary pediatric center.

BACKGROUND: Inferior vena cava (IVC) filters are commonly implanted with the intent to prevent life-threatening pulmonary embolism in at-risk patients with contraindications to anticoagulation. Various studies have reported increases in the rate of venous thromboembolism within the pediatric population. The utility and safety of IVC filters in children has not yet been fully defined. OBJECTIVE: To describe the technique and adjunctive maneuvers of IVC filter removal in children, demonstrate its technical success and identify complications. MATERIALS AND METHODS: A retrospective 10-year review was performed of 20 children (13 male, 7 female), mean age: 15.1 years (range: 12-19 years), who underwent IVC filter retrieval. Eleven of 20 (55%) were placed in our institution. Electronic medical records were reviewed for filter characteristics, retrieval technique, technical success and complications. RESULTS: The technical success rate was 100%. Placement indications included: deep venous thrombosis with a contraindication to anticoagulation (10/20, 50%), free-floating thrombus (4/20, 20%), post-trauma pulmonary embolism prophylaxis (3/20, 15%) and pre-thrombolysis pulmonary patient (1/20, 5%). The mean implantation period was 63 days (range: 20-270 days). Standard retrieval was performed in 17/20 patients (85%). Adjunctive techniques were performed in 3/20 patients (15%) and included the double-snare technique, balloon assistance and endobronchial forceps retrieval. Median procedure time was 60 min (range: 45-240 min). Pre-retrieval cavogram demonstrated filter tilt in 5/20 patients (25%) with a mean angle of 17° (range: 8-40). Pre-retrieval CT demonstrated strut wall penetration and tip embedment in one patient each. There were two procedure-related complications: IVC mural dissection noted on venography in one patient and snare catheter fracture requiring retrieval in one patient. There were no early or late complications. CONCLUSION: In children, IVC filter retrieval can be performed safely but may be challenging, especially in cases of filter tilt or embedding. Adjunctive techniques may increase filter retrieval rates.