Management of nonpurulent wound drainage following spinal surgery: is empiric oral antibiotic treatment appropriate?

BACKGROUND CONTEXT: Postoperative incisional concerns including nonpurulent drainage are relatively common following spine surgery. Evidence-based management protocols are lacking. PURPOSE: The purpose of this study is to determine if prescribing empiric oral antibiotics for nonpurulent wound drainage is beneficial for the prevention of chronic infection or reoperation. STUDY DESIGN: Retrospective chart review. PATIENT SAMPLE: Patients calling the office with postsurgical wound concerns. OUTCOME MEASURES: Not applicable. METHODS: In a large, multisurgeon, spine surgery practice, a review of the communications log showed that 298 patients called or messaged the office with a concern regarding postoperative nonpurulent wound drainage. Patients were prescribed empiric oral antibiotics based on surgeon preference. Patients who received empiric oral antibiotic treatment (AbxTx) were propensity matched to patients who did not (No AbxTx) based on sex, age, BMI, ASA grade, smoking status, prior spine surgery, anatomic location, and number of surgical levels. The number of patients requiring surgical intervention (debridement) and/or developing a chronic infection was determined. RESULTS: Oral antibiotics were prescribed for 112 of the 298 (38%) patients with reports of nonpurulent drainage. Demographic and surgical characteristics of the two matched cohorts were similar. Although there were more patients in the AbxTx group who required surgical intervention (n=17, 17%) compared to the No AbxTx group (n=9, 9%), this difference was not statistically significant (p=.139). The intra-operative culture results showed no growth in 94% (16/17) of the AbxTx group vs 67% (6/9) of the No AbxTx group (p=.103). One patient in each group required a return to the operating room within the year after the initial surgical debridement for management of chronic infection. CONCLUSION: In this large series (n=298) of patients with nonpurulent wound drainage following spine surgery, 87% resolved without the need for surgical intervention. Empiric oral antibiotics did not reduce the need for surgical intervention or the development of a chronic infection. In addition to the added cost, potential adverse reactions, development of resistant organisms, and inaccurate labeling of surgical site infection; empiric oral antibiotics may lead to a negative intraoperative culture for those requiring surgical intervention impacting the ability to prescribe a specific antibiotic regimen.

Transphyseal Distal Humeral Fractures: A 13-Times-Greater Risk of Non-Accidental Trauma Compared with Supracondylar Humeral Fractures in Children Less Than 3 Years of Age.

BACKGROUND: The transphyseal distal humeral fracture has been well described as a concerning fracture pattern for non-accidental trauma (NAT) in young pediatric patients. Because of the infrequent presentation of this fracture, the association historically has been anecdotal. The purpose of this study was to determine and compare the incidence of NAT among displaced transphyseal distal humeral fractures and displaced supracondylar humeral fractures in children <3 years of age. METHODS: All displaced transphyseal distal humeral fractures and displaced supracondylar humeral fractures in patients <3 years of age admitted because of injury during an 18-year period were reviewed retrospectively for inclusion. Patient demographics, mechanisms of injury, results of child protective services investigations, and medical records were reviewed. A chi-square test was utilized to analyze significance for categorical data; p values of <0.05 were defined as significant. RESULTS: The charts of 23 transphyseal distal humeral and 205 supracondylar humeral fracture cases were reviewed. NAT was the cause for 6 (26%) of the displaced transphyseal distal humeral fractures and 4 (2%) of the displaced supracondylar fractures. The associated risk of NAT was 13 times greater (95% confidence interval [CI], 4.05 to 43.7; p < 0.001) for children admitted for operative management of displaced transphyseal distal humeral fractures compared with those admitted for operative management of displaced supracondylar humeral fractures. CONCLUSIONS: The classic 1980 paper by DeLee et al. sensitized the orthopaedic community to the relationship between transphyseal distal humeral fractures and child abuse. Our study is the first, to our knowledge, to bring statistical weight to this association. We found a 13-times-greater risk of NAT for children <3 years of age who sustain a displaced transphyseal distal humeral fracture compared with a displaced supracondylar fracture. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

PD-1 Inhibition Enhances Blinatumomab Response in a UCB/PDX Model of Relapsed Pediatric B-Cell Acute Lymphoblastic Leukemia.

Immune therapies such as blinatumomab, CD19-directed bispecific CD3 T-cell Engager (BiTE), have resulted in significant improvements in outcomes for relapsed B-cell acute lymphoblastic leukemia (B-ALL). However, up to half of blinatumomab treated patients do not respond completely or relapse after therapy. As a result, there is a need to identify potential strategies to improve the efficacy of BiTE therapy. The anti-PD-1 antibody pembrolizumab has been shown to successfully activate T cells against a wide range of cancer types. Here, we tested the ability of umbilical cord blood (UCB) reconstituted mice to respond to blinatumomab therapy with or without concurrent pembrolizumab treatment. Humanized mice were engrafted with patient-derived xenograft (PDX) cells derived from pediatric and adolescent/young adult (AYA) B-ALL patients who had either failed to achieve remission with negative minimum residual disease (MRD negative) or experienced a relapse. Mock-treated humanized mice engrafted with PDX cells efficiently developed overt disease within 30 days of engraftment of B-ALL. However, single agent therapy with either blinatumomab or pembrolizumab reduced disease burden in engrafted mice, with some mice observed to be MRD negative after the 28-day treatment course. Combination therapy significantly improved the percentage of MRD negative mice and improved long-term survival and cure rates as compared to mice that were given blinatumomab alone. Importantly, no benefits were observed in treated mice that lacked human immune cell reconstitution. These results indicate that UCB-humanized NRGS mice develop activatable immune function, and UCB-humanized PDX leukemia models can be used in preclinical studies to evaluate specificity, efficacy, and cooperativity of immune therapies in B-ALL.

Improved chemotherapy modeling with RAG-based immune deficient mice.

We have previously characterized an acute myeloid leukemia (AML) chemotherapy model for SCID-based immune deficient mice (NSG and NSGS), consisting of 5 days of cytarabine (AraC) and 3 days of anthracycline (doxorubicin), to simulate the standard 7+3 chemotherapy regimen many AML patients receive. While this model remains tractable, there are several limitations, presumably due to the constitutional Pkrdcscid (SCID, severe combined immune deficiency) mutation which affects DNA repair in all tissues of the mouse. These include the inability to combine preconditioning with subsequent chemotherapy, the inability to repeat chemotherapy cycles, and the increased sensitivity of the host hematopoietic cells to genotoxic stress. Here we attempt to address these drawbacks through the use of alternative strains with RAG-based immune deficiency (NRG and NRGS). We find that RAG-based mice tolerate a busulfan preconditioning regimen in combination with either AML or 4-drug acute lymphoid leukemia (ALL) chemotherapy, expanding the number of samples that can be studied. RAG-based mice also tolerate multiple cycles of therapy, thereby allowing for more aggressive, realistic modeling. Furthermore, standard AML therapy in RAG mice was 3.8-fold more specific for AML cells, relative to SCID mice, demonstrating an improved therapeutic window for genotoxic agents. We conclude that RAG-based mice should be the new standard for preclinical evaluation of therapeutic strategies involving genotoxic agents.

YAP/TAZ-CDC42 signaling regulates vascular tip cell migration.

Angiogenesis and vascular remodeling are essential for the establishment of vascular networks during organogenesis. Here we show that the Hippo signaling pathway effectors YAP and TAZ are required, in a gene dosage-dependent manner, for the proliferation and migration of vascular endothelial cells (ECs) during retinal angiogenesis. Intriguingly, nuclear translocation of YAP and TAZ induced by Lats1/2-deletion blocked endothelial migration and phenocopied Yap/Taz-deficient mutants. Furthermore, overexpression of a cytoplasmic form of YAP (YAPS127D) partially rescued the migration defects caused by loss of YAP and TAZ function. Finally, we found that cytoplasmic YAP positively regulated the activity of the small GTPase CDC42, deletion of which caused severe defects in endothelial migration. These findings uncover a previously unrecognized role of cytoplasmic YAP/TAZ in promoting cell migration by activating CDC42 and provide insight into how Hippo signaling in ECs regulates angiogenesis.

Desialylation of Neisseria gonorrhoeae Lipooligosaccharide by Cervicovaginal Microbiome Sialidases: The Potential for Enhancing Infectivity in Men.

Previous studies have demonstrated that Neisseria gonorrhoeae sialylates the terminal N-acetyllactosamine present on its lipooligosaccharide (LOS) by acquiring CMP-N-acetyl-5-neuraminic acid upon entering human cells during infection. This renders the organism resistant to killing by complement in normal human serum. N-acetyllactosamine residues on LOS must be free of N-acetyl-5-neuraminc acid (Neu5Ac; also known as "sialic acid") in order for organisms to bind to and enter urethral epithelial cells during infection in men. This raises the question of how the gonococcus infects men if N-acetyllactosamine residues are substituted by Neu5Ac during infection in women. Here, we demonstrate that women with gonococcal infections have levels of sialidases present in cervicovaginal secretions that can result in desialylation of (sialylated) gonococcal LOS. The principle sialidases responsible for this desialylation appear to be bacterial in origin. These studies suggest that members of the cervicovaginal microbiome can modify N. gonorrhoeae, which will enhance successful transmission to men.

Seminal Plasma Promotes Neisseria gonorrhoeae Aggregation and Biofilm Formation.

UNLABELLED: Neisseria gonorrhoeae causes the human-specific disease gonorrhea and is transmitted from person to person primarily via sexual contact. During transmission, N. gonorrhoeae is often exposed to seminal fluid and must adapt to this change in environment. Previous work demonstrated that seminal fluid facilitates N. gonorrhoeae motility and alters epithelial cell interactions. In this study, exposure to seminal fluid was found to decrease surface adherence of gonococci in a manner that was independent of Opa adhesin proteins or type IV pilus retraction. Semen was also shown to cause dispersal of bacteria that had previously established surface adherence. Although surface adherence decreased, interbacterial interactions were increased by seminal plasma both in long-term static culture and on a cell-to-cell basis over shorter time periods. The result of increased bacterium-bacterium interactions resulted in the formation of microcolonies, an important step in the N. gonorrhoeae infectious process. Seminal fluid also facilitated increased bacterial aggregation in the form of shear-resistant three-dimensional biofilms. These results emphasize the importance of the gonococcal response to the influx of seminal fluid within the genital niche. Further characterization of the N. gonorrhoeae response to semen will advance our understanding of the mechanisms behind the establishment of infection in naive hosts and the process of transmission. IMPORTANCE: N. gonorrhoeae is the causative agent of the globally prevalent sexually transmitted infection gonorrhea. An understudied aspect of this human-adapted pathogen is the change in bacterial physiology that occurs during sexual transmission. N. gonorrhoeae encounters semen when transmitted from host to host, and it is known that, when N. gonorrhoeae is exposed to seminal fluid, alterations in bacterial motility and type IV pilus arrangement occur. This work extends our previous observations on this modulation of gonococcal physiology by seminal fluid and demonstrates that seminal plasma decreases surface adherence, promotes interbacterial interactions, and enhances biofilm formation.