Publications by authors named "Jagdish Desai"

Background: Neonatal resuscitation is guided by Neonatal Resuscitation Program (NRP) algorithms; however, human factors affect resuscitation. Video recordings demonstrate that deviations are common. Additionally, code documentation is prone to inaccuracies.

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Background: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has significant health implications. Anemia is usually an unseen comorbidity, which could significantly affect outcomes in AECOPD patients, and there is limited data to support this. We conducted this study to assess the effect of anemia on this patient population.

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Introduction: Retinopathy of prematurity (ROP) and infantile hemangiomas (IHs) both have similar proposed pathophysiological mechanisms. IH is more common in preterm than term infants. Hypoxia-induced mediators like vascular endothelial growth factor have been found elevated in children with hemangiomas.

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Background: The available data regarding morbidity and mortality associated with multiple gestation births is conflicting and contradicting.

Objective: To compare morbidity, mortality, and length of stay (LOS) outcomes between multiple gestation (twin, triplet and higher-order) and singleton births.

Methods: Data from the national multicenter Kids' Inpatient Database of the Healthcare Cost and Utilization Project from the years 2000, 2003, 2006, 2009, 2012, and 2016 were analyzed using a complex survey design using Statistical Analysis System (SAS) 9.

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We sought to determine whether there are sex-based differences in the requirements for calories or protein for optimal growth during the transition phase (TP) when an extremely low birth weight (ELBW) infant, defined as a preterm infant with a birth weight of < 1000 g, is progressing from parenteral to enteral feeds. A retrospective review of ELBW infants born from 2014 to 2016 was performed at a tertiary NICU. Infants with necrotizing enterocolitis, short bowel syndrome, or chromosomal anomalies were excluded.

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An extremely premature infant born at a gestational age 24 5/7 and birth weight of 637 g was found to have retained a distal segment of an umbilical venous catheter (UVC) on chest radiograph after removal of the UVC. The catheter was retrieved by interventional radiology on day 10 of life when the baby weighed 660 g. To our knowledge, this is the smallest baby reported to have successfully retrieved catheter percutaneously via femoral access.

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Anti-E alloimmunization is the third most common cause of neonatal hemolytic disease, typically causing mild to moderate hemolytic anemia. We report an unusual case of severe hydrops fetalis and persistent pulmonary hypertension (PPHN) in a neonate with anti-E alloimmunization. Our case emphasizes the importance of close surveillance for development of severe fetal hemolytic anemia and possible need for antenatal intervention.

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Objective: To determine in-hospital outcomes of neonates with hypoxic ischemic encephalopathy (HIE) requiring extracorporeal membrane oxygenation (ECMO).

Study Design: Single-center retrospective study from 2005 to 2016 of neonates ≥35 weeks gestation with moderate/severe HIE, requiring ECMO for persistent pulmonary hypertension of newborn (PPHN).

Results: Our cohort (n = 20) received therapeutic hypothermia for moderate (n = 12), severe (n = 5), or undocumented severity (n = 3) of HIE.

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Harlequin ichthyosis (HI) is associated with high mortality. Early systemic retinoids are widely used, although their use remains debatable. We reported two neonates with homozygous mutations in ABCA12 consistent with harlequin ichthyosis who survived to discharge home with intensive care and without use of systemic retinoids.

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The emergence and evolution of new immunological cancer therapies has sparked a rapidly growing interest in discovering novel pathways to treat cancer. Toward this aim, a novel series of pyrrolidine derivatives (compound ) were identified as potent inhibitors of ERK1/2 with excellent kinase selectivity and dual mechanism of action but suffered from poor pharmacokinetics (PK). The challenge of PK was overcome by the discovery of a novel 3()-thiomethyl pyrrolidine analog .

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Compound 5 (SCH772984) was identified as a potent inhibitor of ERK1/2 with excellent selectivity against a panel of kinases (0/231 kinases tested @ 100 nM) and good cell proliferation activity, but suffered from poor PK (rat AUC PK @10 mpk = 0 μM h; F% = 0) which precluded further development. In an effort to identify novel ERK inhibitors with improved PK properties with respect to 5, a systematic exploration of sterics and composition at the 3-position of the pyrrolidine led to the discovery of a novel 3(S)-thiomethyl pyrrolidine analog 28 with vastly improved PK (rat AUC PK @10 mpk = 26 μM h; F% = 70).

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Objective: To evaluate short-term outcomes in infants born preterm with congenital heart defects (CHDs) and the factors associated with surgery, survival, and length of hospitalization in this population.

Study Design: We analyzed data from infants born preterm (gestational age <37 weeks) enrolled in the multicenter Kids' Inpatient Database of the Healthcare Cost and Utilization Project who were admitted to the hospital within 30 days after birth. Infants with atrial septal defects were excluded.

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8-Amino-imidazo[1,5-a]pyrazine-based Bruton's tyrosine kinase (BTK) inhibitors, such as 6, exhibited potent inhibition of BTK but required improvements in both kinase and hERG selectivity (Liu et al., 2016; Gao et al., 2017).

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Objective This study aims to evaluate the correlation of changes in serum insulin-like growth factor-1 (IGF-1) levels with the clinical staging of hypoxic-ischemic encephalopathy (HIE) in term newborns. Study Design A prospective study of 29 newborns with HIE (stage I = 15, stage II + III = 14) and 28 healthy term newborns as the control group was performed in the neonatal intensive care unit. IGF-1 levels were obtained within 6 hours after birth from HIE and control groups and again on day 3 from HIE group.

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Introduction Prediction of mortality and morbidity in newborns with congenital diaphragmatic hernia (CDH) is too complex for practical use and may not be accurate. The main objective of this study was to evaluate the usefulness of the CDH Study Group equation and Score of Neonatal Acute Physiology Perinatal Extension (SNAPPE) II score to predict short-term outcomes of newborns with CDH. Materials and Methods Fifty-two neonates were admitted with CDH at Children's Hospital of Michigan from November 2001 to July 2009.

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Starting from weak μM hits identified through affinity based Automated Ligand Identification System (ALIS) screenings, double digit nM hydroxyaniline amide Erk inhibitors were discovered. This class of compounds had the unique dual mechanism of inhibiting activated and non-activated forms of Erk. They generally had high degree of selectivity in kinase panel tested.

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Tertiary hydroxyl class of C-imidazole bridgehead azaheptapyridine FPT inhibitors were prepared in an attempt to block in vivo oxidation of secondary hydroxyl series. One representative compound 5a exhibited potent enzyme (IC50=1.4 nM) and cellular activities (soft agar IC50=1.

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The high frequency of activating RAS or BRAF mutations in cancer provides strong rationale for targeting the mitogen-activated protein kinase (MAPK) pathway. Selective BRAF and MAP-ERK kinase (MEK) inhibitors have shown clinical efficacy in patients with melanoma. However, the majority of responses are transient, and resistance is often associated with pathway reactivation of the extracellular signal-regulated kinase (ERK) signaling pathway.

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The discovery of C-linked imidazole azaheptapyridine bridgehead FPT inhibitors is described. This novel class of compounds are sub nM FPT enzyme inhibitors with potent cellular inhibitory activities. This series also has reduced hERG activity versus previous N-linked imidazole series.

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A series of novel N-cyanoguanidine tricyclic farnesyl protein transferase (FPT) inhibitors was prepared. Replacement of a piperidine amide-group with a N-cyanoguanidine functionality increased FPT activity. X-ray crystal structure determination of 42 complexed with FPT revealed differences in the interactions of the amide and N-cyanoguanidine groups with the protein.

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