The effectiveness of operating room headgear in preventing airborne contamination has been called into question. We hypothesized that bouffant style hats would be as effective in preventing bacterial ...and particulate contamination in the operating room compared with disposable or cloth skull caps, and bouffant style hats would have similar permeability, particle penetration, and porosity compared with skull caps.
Disposable bouffant and skull cap hats and newly laundered cloth skull caps were tested. A mock surgical procedure was used in a dynamic operating room environment. Airborne particulate and microbial contaminants were sampled. Hat fabric was tested for permeability, particle transmission, and pore sizes.
No significant differences were observed between disposable bouffant and disposable skull caps with regard to particle or actively sampled microbial contamination. However, when compared with disposable skull caps, disposable bouffant hats did have significantly higher microbial shed at the sterile field, as measured by passive settle plate analysis (p < 0.05). When compared with cloth skull caps, disposable bouffants yielded higher levels of 0.5 μm and 1.0 μm particles and significantly higher microbial shed detected with passive analysis. Fabric assessment determined that disposable bouffant hats had larger average and maximum pore sizes compared with cloth skull caps, and were significantly more permeable than either disposable or cloth skull caps.
Disposable bouffant hats had greater permeability, penetration, and greater microbial shed, as assessed by passive microbial analysis compared with disposable skull caps. When compared with cloth skull caps, disposable bouffants yielded greater permeability, greater particulate contamination, and greater passive microbial shed. Disposable style bouffant hats should not be considered superior to skull caps in preventing airborne contamination in the operating room.
•VEGF is a critical component of wound healing.•VEGF therapy may aid ischemic tissues following injury.•Balance is needed to avoid VEGF overexpression and tumor progression.
Vascular endothelial ...growth factor (VEGF) is a notable chemokine that plays critical roles in angiogenesis and vasculogenesis. The contemporary body of literature contains a substantial amount of information regarding its chemical properties as well as its fundamental role in vascular development. Studies strongly indicate its potential use as a therapeutic agent, especially in the vascular restoration of injured and ischemic tissues. VEGF therapy could be most beneficial for diseases whose pathologies revolve around tissue inflammation and necrosis, such as myocardial infarction and stroke, as well as ischemic bowel diseases such as acute mesenteric ischemia and necrotizing enterocolitis. However, a delicate balance exists between the therapeutic benefits of VEGF and the hazards of tumor growth and neo-angiogenesis. Effective future research surrounding VEGF may allow for the development of effective therapies for ischemia which simultaneously limit its more deleterious side effects. This review will: (1) summarize the current understanding of the molecular aspects and function of VEGF, (2) review potential benefits of its use in medical therapy, (3) denote its role in tumorigenesis and inflammation when overexpressed, and (4) elucidate the qualities which make it a viable compound of study for diagnostic and therapeutic applications.
RATIONALE:There is incomplete knowledge of the impact of bone marrow cells on the gut microbiome and gut barrier function.
OBJECTIVE:We postulated that diabetes mellitus and systemic ACE2 ...(angiotensin-converting enzyme 2) deficiency would synergize to adversely impact both the microbiome and gut barrier function.
METHODS AND RESULTS:Bacterial 16S rRNA sequencing and metatranscriptomic analysis were performed on fecal samples from wild-type, ACE2, Akita (type 1 diabetes mellitus), and ACE2-Akita mice. Gut barrier integrity was assessed by immunofluorescence, and bone marrow cell extravasation into the small intestine was evaluated by flow cytometry. In the ACE2-Akita or Akita mice, the disrupted barrier was associated with reduced levels of myeloid angiogenic cells, but no increase in inflammatory monocytes was observed within the gut parenchyma. Genomic and metatranscriptomic analysis of the microbiome of ACE2-Akita mice demonstrated a marked increase in peptidoglycan-producing bacteria. When compared with control cohorts treated with saline, intraperitoneal administration of myeloid angiogenic cells significantly decreased the microbiome gene expression associated with peptidoglycan biosynthesis and restored epithelial and endothelial gut barrier integrity. Also indicative of diabetic gut barrier dysfunction, increased levels of peptidoglycan and FABP-2 (intestinal fatty acid-binding protein 2) were observed in plasma of human subjects with type 1 diabetes mellitus (n=21) and type 2 diabetes mellitus (n=23) compared with nondiabetic controls (n=23). Using human retinal endothelial cells, we determined that peptidoglycan activates a noncanonical TLR-2 (Toll-like receptor 2) associated MyD88 (myeloid differentiation primary response protein 88)-ARNO (ADP-ribosylation factor nucleotide-binding site opener)-ARF6 (ADP-ribosylation factor 6) signaling cascade, resulting in destabilization of p120-catenin and internalization of VE-cadherin as a mechanism of deleterious impact of peptidoglycan on the endothelium.
CONCLUSIONS:We demonstrate for the first time that the defect in gut barrier function and dysbiosis in ACE2-Akita mice can be favorably impacted by exogenous administration of myeloid angiogenic cells.
Understanding the mechanisms by which adult stem cells produce growth factors may represent an important way to optimize their beneficial paracrine and autocrine effects. Components of the wound ...milieu may stimulate growth factor production to promote stem cell-mediated repair. We hypothesized that tumor necrosis factor-alpha (TNF-alpha), endotoxin (LPS), or hypoxia may activate human mesenchymal stem cells (MSCs) to increase release of vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), insulin-like growth factor 1 (IGF-1), or hepatocyte growth factor (HGF) and that nuclear factor-kappa B (NF kappa B), c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) mediates growth factor production from human MSCs. To study this, human MSCs were harvested, passaged, divided into four groups (100,000 cells, triplicates) and treated as follows: 1) with vehicle; 2) with stimulant alone 24 h LPS (200 ng/ml), 24 h TNF-alpha (50 ng/ml), or 24 h hypoxia (1% O2); 3) with inhibitor alone NF kappa B (PDTC, 1 mM), JNK (TI-JIP, 10 microM), or ERK (ERK Inhibitor II, 25 microM); and 4) with stimulant and the various inhibitors. After 24 h incubation, MSC activation was determined by measuring supernatants for VEGF, FGF2, IGF-1, or HGF (ELISA). TNF-alpha, LPS, and hypoxia significantly increased human MSC VEGF, FGF2, HGF, and IGF-1 production versus controls. Stem cells exposed to injury demonstrated increased activation of NF kappa B, ERK, and JNK. VEGF, FGF2, and HGF expression was significantly reduced by NF kappa B inhibition (50% decrease) but not ERK or JNK inhibition. Moreover, ERK, JNK, and NF kappa B inhibitor alone did not activate MSC VEGF expression over controls. Various stressors activate human MSCs to increase VEGF, FGF2, HGF, and IGF-1 expression, which depends on an NFkB mechanism.
Necrotizing enterocolitis (NEC) is a devastating condition where inflammatory changes and necrosis in the gut results in activation of brain microglia and subsequent neurodevelopmental impairment. ...Chondroitin sulfate (CS) is a glycosaminoglycan in human breast milk that is absent in conventional formulas. We hypothesized that oral formula supplementation with CS during a murine model of experimental NEC would not only attenuate intestinal injury, but also brain injury.
NEC was induced in mouse pups on postnatal days (PNDs) 5 to 8. Three conditions were studied: (1) breastfed controls, (2) NEC, and (3) NEC+enteral CS (formula+200 mg/kg/d of CS). Pups were euthanized on PND 9 or reunited with dams by the evening of PND 8. Intestinal segments were H&E stained, and immunohistochemistry was performed on brain tissue for Iba-1 to assess for microglial morphology and cortical changes. Neurodevelopmental assays were performed on mice reunited with foster dams on PND 9. Single-cell RNA-sequencing analysis was performed on human intestinal epithelial cells exposed to (1) nothing, (2) hydrogen peroxide (H 2 O 2 ) alone, or (3) H 2 O 2 + CS to look at the differential gene expression between groups. Groups were compared with ANOVA or Kruskal-Wallis tests as appropriate with p < 0.05 considered significant.
Compared with NEC, mice treated with oral CS showed improved clinical outcomes, decreased intestinal injury, and attenuated microglial activation and deleterious cortical change. Mice with CS performed better on early neurodevelopmental assays when compared with NEC alone. Single-cell analysis of HIEC-6 cells demonstrated that CS treatment down regulated several inflammatory pathways including nuclear factor κB-suggesting an explanation for the improved Th17 intestinal cytokine profile.
Oral CS supplementation improved both physiological, clinical, and developmental outcomes. These data suggest that CS is a safe compound for formula supplementation for the prevention of NEC.
Necrotizing enterocolitis (NEC) continues to be a morbid surgical condition among preterm infants. Novel therapies for this condition are desperately needed. Hydrogen sulfide (H2S) is an endogenous ...gasotransmitter that has been found to have beneficial properties. We therefore hypothesized that intraperitoneal injection of various H2S donors would improve clinical outcomes, increase intestinal perfusion, and reduce intestinal injury in an experimental mouse model of necrotizing enterocolitis.
NEC was induced in five-day-old mouse C57BL/6 mouse pups through maternal separation, formula feeding, and intermittent hypoxic and hypothermic stress. The control group (n=10) remained with their mother and breastfed ad lib. Experimental groups (n=10/group) received intraperitoneal injections of phosphate buffered saline (PBS) vehicle or one of the following H2S donors: (1) GYY4137, 50mg/kg daily; (2) Sodium sulfide (Na2S), 20mg/kg three times daily; (3) AP39, 0.16mg/kg daily. Pups were monitored for weight gain, clinical status, and intestinal perfusion via transcutaneous Laser Doppler Imaging (LDI). After sacrifice on day nine, intestinal appearance and histology were scored and cytokines were measured in tissue homogenates of intestine, liver, and lung. Data were compared with Mann–Whitney and p<0.05 was considered significant.
Clinical score and weight gain were significantly improved in all three H2S-treated groups as compared to vehicle (p<0.05 for all groups). Intestinal perfusion of the vehicle group was 22% of baseline while the GYY4137 group was 38.7% (p=0.0103), Na2S was 47.0% (p=0.0040), and AP39 was 43.0% (p=0.0018). The vehicle group had a median histology score of 2.5, while the GYY4137 group's was 1 (p=0.0013), Na2S was 0.5 (p=0.0004), and AP39 was 0.5 (p=0.0001). Cytokine analysis of the intestine of the H2S-treated groups revealed levels closer to breastfed pups as compared to vehicle (p<0.05 for all groups).
Intraperitoneal administration of H2S protects against development of NEC by improving mesenteric perfusion, and by limiting mucosal injury and altering the tissue inflammatory response. Further experimentation is necessary to elucidate downstream mechanisms prior to clinical implementation.
Background
The aim of this study was to elucidate the outcomes of percutaneous internal ring suture (PIRS) technique for inguinal hernia repair augmented with thermal peritoneal injury compared to ...open inguinal hernia repair (OHR) in a large population of contemporary pediatric patients. Thermal injury with PIRS has been shown to reduce recurrence in animal models and is increasingly being incorporated into clinical practice.
Methods
Retrospective review of all PIRS procedures and OHR between Jan-2017 to Sept-2018 was performed. Data regarding patient characteristics, characteristics of the hernia, operative details, postoperative complications, and recurrence were collected. Non-parametric tests were used and
p
< 0.05 was regarded as statistically significant. 1:1 Propensity score matching was performed using “nearest-score” technique. Matching was done based on age, sex, follow-up time, side of hernia, repair of contralateral hernia, and number of additional procedures.
Results
90 modified PIRS patients were matched to 90 OHRs. Patient demographics, hernia characteristics, and follow-up time were similar between the two groups after matching. There were no differences in recurrence rates (1 vs. 3 in OHR and PIRS, respectively,
p
= 0.6), complication rates (1 vs. 4 in OHR and PIRS, respectively,
p
= 0.4), and OR time 44.5 vs. 43 min in OHR and PIRS, respectively,
p
= 0.8. There were no intraoperative complications for either technique. For OHR, laparoscopic look was performed in 23%. When successful, it revealed a contralateral PPV (patent processus vaginalis-PPV) in 41% of cases (9.4% of all OHR), all of which were repaired. For the PIRS procedures, a contralateral PPV was found in 25.6%, all of which were repaired. In the unmatched population, OHR had a metachronous hernia rate of 1.8%, none of whom had the contralateral PPV repaired at the original procedure.
Conclusions
PIRS with peritoneal injury has comparable efficacy and good safety compared to OHR. Recurrence and complication rates should further improve with increasing experience. Future studies should elucidate long term outcomes.
•Data used to support many practices in the operating room environment are supported by anecdotal data.•Certain regulatory agencies have suggested that nonscrubbed operating room personnel wear long ...sleeves while in the room.•Wearing long sleeves and gloves while prepping a mock patient led to decreased large-particle and microbial shedding compared with prepping with bare arms.•Wearing of long sleeves and gloves should be considered when applying the skin prep to patients before surgery.
The use of long sleeves by nonscrubbed personnel in the operating room has been called into question. We hypothesized that wearing long sleeves and gloves, compared with having bare arms without gloves, while applying the skin preparation solution would decrease particulate and microbial contamination.
A mock patient skin prep was performed in 3 different operating rooms. A long-sleeved gown and gloves, or bare arms, were used to perform the procedure. Particle counters were used to assess airborne particulate contamination, and active and passive microbial assessment was achieved through air samplers and settle plate analysis. Data were compared with Student's t-test or Mann-Whitney U, and P < .05 was considered to be significant.
Operating room B demonstrated decreased 5.0- µm particle sizes with the use of sleeves, while operating rooms A and C showed decreased total microbes only with the use of sleeves. Despite there being no difference in the average number of total microbes for all operating rooms assessed, the use of sleeves specifically appeared to decrease the shed of Micrococcus.
The use of long sleeves and gloves while applying the skin preparation solution decreased particulate and microbial shedding in several of the operating rooms tested. Although long sleeves may not be necessary for all operating room personnel, they may decrease airborne contamination while the skin prep is applied, which may lead to decreased surgical site infections.
The 2019 Necrotizing Enterocolitis (NEC) Symposium expanded upon the NEC Society's goals of bringing stakeholders together to discuss cutting-edge science, potential therapeutics and preventative ...measures, as well as the patient-family perspectives of NEC. The Symposium facilitated discussions and shared knowledge with the overarching goal of creating "A World Without NEC." To accomplish this goal, new research to advance the state of the science is necessary. Over the last decade, several established investigators have significantly improved our understanding of the pathophysiology of NEC and they have paved the way for the next generation of clinician-scientists funded to perform NEC research. This article will serve to highlight the contributions of these young clinician-scientists that seek to elucidate how immune, microbial and nervous system dysregulation contributes to the pathophysiology of NEC.
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