A Description of IVIG Use in Term Neonates with ABO Incompatibility.

OBJECTIVE: This study aimed to determine if treatment with IVIG of neonates with ABO incompatibility (without Rh incompatibility) results in decreased number of packed red blood cell (pRBC) transfusions and phototherapy use. STUDY DESIGN: An Institutional Review Board (IRB)-approved, single-institution retrospective study was conducted. Neonates ≥38 weeks' gestational age born between January 1, 2007, and December 31, 2016, with ABO incompatibility were included. The comparison among groups was performed using chi-square and Fisher's exact tests for categorical variables; continuous variables were assessed by Kruskal-Wallis test. RESULTS: Six hundred and sixty-eight neonates with ABO incompatibility met inclusion criteria, 579 were included in the analyses. From these, 431 (74%) neonates had positive Direct Antiglobulin Test (DAT); 98 (17%) received IVIG and 352 (61%) received phototherapy. Thirty-six (6%) neonates received pRBC and 6 (1%) required exchange transfusions. Only 3 (0.5%) infants received pRBC transfusions postdischarge, by 3 months of age. Neonates requiring IVIG had lower initial hemoglobin (13.6 vs. 16.0 g/dL, p ≤ 0.0001) and higher bilirubin at start of phototherapy (9.1 vs. 8.1 mg/dL, p = 0.0064). From the 42 (7%) neonates who received simple and exchange transfusions, IVIG use was not associated with decreased use or number of transfusions (p = 0.5148 and 0.3333, respectively). Newborns with A+ and B+ blood types had comparable initial hemoglobin, DAT positivity, APGAR, and bilirubin. However, infants with B+ blood group were more likely (than A + ) to require phototherapy (p < 0.001), receive IVIG (p = 0.003), and need phototherapy for a longer duration (p = 0.001). CONCLUSION: The results of this large retrospective study reveal that giving IVIG to neonates with ABO incompatibility was associated with increased simple or exchange transfusions. Newborns with B+ blood type required more phototherapy and IVIG. Further studies are needed to better stratify neonates who would benefit from IVIG use in order to optimize treatment strategies and avoid unnecessary risks and adverse events. KEY POINTS: · IVIG use not associated with decreased use of pRBC or exchanges.. · Phototherapy duration associated with increased IVIG and pRBC use.. · Newborns with B+ blood type had worse hemolytic anemia..

Structure-based Design of JOC-x, a Conjugatable Tumor Tight Junction Opener to Enhance Cancer Therapy.

Disorganized intercellular junctions are critical for maintaining the integrity of solid epithelial tumors and prevent the infiltration of oncological therapies into the bulk of the malignancy. We have developed small, recombinant proteins which bind a critical junction protein, desmoglein 2, triggering the transient and specific opening of tumor tight junctions allowing for infiltration of the tumor with immune cells, oncolytic viruses, drugs, and other therapeutics. Our new molecule, JOC-x, is a promising candidate for a new class of tumor-targeting agents that accumulate both around and within tumors and remodel the tumor microenvironment. Native cysteines were removed from the parental protein, JO-4, followed by addition of a single cysteine to allow for convenient attachment of various payloads that can be targeted directly to the tumor. Our tumor-targeting protein exhibits high avidity, minimal aggregation, and is easily purified at good yields from E. coli. For proof of concept, we demonstrate effective conjugation to biotin as a model for flexible co-targeting, addition of metal ion chelators as models for imaging and radiotherapy, and linkage of the TLR3 agonist poly(I:C) as a model immune-oncologic agent. This second-generation cancer co-therapeutic protein is optimized for activity and primed for cGMP manufacture in preparation for upcoming clinical studies.

Inhibition of the multidrug efflux pump LmrS from Staphylococcus aureus by cumin spice Cuminum cyminum.

Staphylococcus aureus is a serious causative agent of infectious disease. Multidrug-resistant strains like methicillin-resistant S. aureus compromise treatment efficacy, causing significant morbidity and mortality. Active efflux represents a major antimicrobial resistance mechanism. The proton-driven multidrug efflux pump, LmrS, actively exports structurally distinct antimicrobials. To circumvent resistance and restore clinical efficacy of antibiotics, efflux pump inhibitors are necessary, and natural edible spices like cumin are potential candidates. The mode of cumin antibacterial action and underlying mechanisms behind drug resistance inhibition, however, are unclear. We tested the hypothesis that cumin inhibits LmrS drug transport. We found that cumin inhibited bacterial growth and LmrS ethidium transport in a dosage-dependent manner. We demonstrate that cumin is antibacterial toward a multidrug-resistant host and that resistance modulation involves multidrug efflux inhibition.