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  • 1
    In: JAMA Network Open, American Medical Association (AMA), Vol. 6, No. 4 ( 2023-04-28), p. e2310800-
    Abstract: There is some data to suggest that racial and ethnic minority infants with congenital diaphragmatic hernia (CDH) have poorer clinical outcomes. Objective To determine what patient- and institutional-level factors are associated with racial and ethnic differences in CDH mortality. Design, Setting, and Participants Multicenter cohort study of 49 US children’s hospitals using the Pediatric Health Information System database from January 1, 2015, to December 31, 2020. Participants were patients with CDH admitted on day of life 0 who underwent surgical repair. Patient race and ethnicity were guardian-reported vs hospital assigned as Black, Hispanic (White or Black), or White. Data were analyzed from August 2021 to March 2022. Exposures Patient race and ethnicity: (1) White vs Black and (2) White vs Hispanic; and institutional-level diversity (as defined by the percentage of Black and Hispanic patients with CDH at each hospital): (1) 30% or less, (2) 31% to 40%, and (3) more than 40%. Main Outcomes and Measures The primary outcomes were in-hospital and 60-day mortality. The study hypothesized that hospitals managing a more racially and ethnically diverse population of patients with CDH would be associated with lower mortality among Black and Hispanic infants. Results Among 1565 infants, 188 (12%), 306 (20%), and 1071 (68%) were Black, Hispanic, and White, respectively. Compared with White infants, Black infants had significantly lower gestational ages (mean [SD], White: 37.6 [2] weeks vs Black: 36.6 [3] weeks; difference, 1 week; 95% CI for difference, 0.6-1.4; P   & amp;lt; .001), lower birthweights (White: 3.0 [1.0] kg vs Black: 2.7 [1.0] kg; difference, 0.3 kg; 95% CI for difference, 0.2-0.4; P   & amp;lt; .001), and higher extracorporeal life support use (White: 316 patients [30%] vs Black: 69 patients [37%] ; χ 2 1  = 3.9; P  = .05). Black infants had higher 60-day (White: 99 patients [9%] vs Black: 29 patients [15%] ; χ 2 1  = 6.7; P  = .01) and in-hospital (White: 133 patients [12%] vs Black: 40 patients [21%] ; χ 2 1  = 10.6; P  = .001) mortality . There were no mortality differences in Hispanic patients compared with White patients. On regression analyses, institutional diversity of 31% to 40% in Black patients (hazard ratio [HR], 0.17; 95% CI, 0.04-0.78; P  = .02) and diversity greater than 40% in Hispanic patients (HR, 0.37; 95% CI, 0.15-0.89; P  = .03) were associated with lower mortality without altering outcomes in White patients. Conclusions and Relevance In this cohort study of 1565 who underwent surgical repair patients with CDH, Black infants had higher 60-day and in-hospital mortality after adjusting for disease severity. Hospitals treating a more racially and ethnically diverse patient population were associated with lower mortality in Black and Hispanic patients.
    Type of Medium: Online Resource
    ISSN: 2574-3805
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2931249-8
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  • 2
    In: Surgery, Elsevier BV, Vol. 173, No. 6 ( 2023-06), p. 1447-1451
    Type of Medium: Online Resource
    ISSN: 0039-6060
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2018278-8
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  • 3
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Journal of the American College of Surgeons Vol. 236, No. 6 ( 2023-06), p. 1139-1146
    In: Journal of the American College of Surgeons, Ovid Technologies (Wolters Kluwer Health), Vol. 236, No. 6 ( 2023-06), p. 1139-1146
    Abstract: Neonatal resection is the mainstay treatment of children presenting with symptomatic congenital lung malformation (CLM) at birth. The objective of this study was to evaluate risk factors for increased morbidity and mortality after neonatal CLM resection using a large multicenter database. STUDY DESIGN: Retrospective review of the Pediatric Health Information System database was performed. Children with a symptomatic CLM managed by lung resection before 30 days of age were included (2016 to 2021). Primary outcomes measures were postoperative respiratory complication and any complication, including death. RESULTS: Of 1,791 CLM patients identified, 256 (14%) underwent neonatal resection for symptomatic disease. Pathology included 123 (48%) congenital pulmonary airway malformation, 24 (10%) bronchopulmonary sequestration, 5 (2%) congenital lobar emphysema, 16 (6%) hybrid, and 88 (34%) unclassified lesion. Preoperative mechanical ventilation and extracorporeal membrane oxygenation (ECMO) were employed in 149 (58.2%) and 17 (6.7%) of cases, respectively. The median age at resection was 6.5 days (interquartile range 2 to 23). Postoperatively, 25 (10%) required mechanical ventilation for 48 hours or more, 3 (1%) continued ECMO, and 3 (1%) required ECMO rescue. The overall respiratory complication rate was 34% (87), rate of any complication was 51% (130), median postoperative length of stay was 20 days (interquartile range 9 to 52), and mortality rate was 14.5% (37). Birthweight was inversely correlated with complication risk (incidence rate ratio 0.55, 95% CI 0.36 to 0.83, p = 0.006). Cardiac structural anomaly was associated with a 21-day longer postoperative length of stay (95% CI 6 to 35, p = 0.006) and 2.2 times increased risk of any complication (95% CI 1.18 to 4.02, p = 0.014). CONCLUSIONS: In this large multicenter study, ECMO use and mortality are relatively uncommon among neonates undergoing lung resection for a symptomatic CLM. However, postoperative morbidity remains high, particularly in those with cardiac structural disease.
    Type of Medium: Online Resource
    ISSN: 1072-7515
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 4
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  Cells Vol. 10, No. 7 ( 2021-07-14), p. 1775-
    In: Cells, MDPI AG, Vol. 10, No. 7 ( 2021-07-14), p. 1775-
    Abstract: The microbial metabolite butyrate serves as a link between the intestinal microbiome and epithelium. The monocarboxylate transporters MCT1 and SMCT1 are the predominant means of butyrate transport from the intestinal lumen to epithelial cytoplasm, where the molecule undergoes rapid β-oxidation to generate cellular fuel. However, not all epithelial cells metabolize butyrate equally. Undifferentiated colonocytes, including neoplastic cells and intestinal stem cells at the epithelial crypt base preferentially utilize glucose over butyrate for cellular fuel. This divergent metabolic conditioning is central to the phenomenon known as “butyrate paradox”, in which butyrate induces contradictory effects on epithelial proliferation in undifferentiated and differentiated colonocytes. There is evidence that accumulation of butyrate in epithelial cells results in histone modification and altered transcriptional activation that halts cell cycle progression. This manifests in the apparent protective effect of butyrate against colonic neoplasia. A corollary to this process is butyrate-induced inhibition of intestinal stem cells. Yet, emerging research has illustrated that the evolution of the crypt, along with butyrate-producing bacteria in the intestine, serve to protect crypt base stem cells from butyrate’s anti-proliferative effects. Butyrate also regulates epithelial inflammation and tolerance to antigens, through production of anti-inflammatory cytokines and induction of tolerogenic dendritic cells. The role of butyrate in the pathogenesis and treatment of intestinal neoplasia, inflammatory bowel disease and malabsorptive states is evolving, and holds promise for the potential translation of butyrate’s cellular function into clinical therapies.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661518-6
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  • 5
    In: Surgery, Elsevier BV, Vol. 172, No. 2 ( 2022-08), p. 729-733
    Type of Medium: Online Resource
    ISSN: 0039-6060
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2018278-8
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  • 6
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Journal of the American College of Surgeons Vol. 235, No. 3 ( 2022-09), p. 530-538
    In: Journal of the American College of Surgeons, Ovid Technologies (Wolters Kluwer Health), Vol. 235, No. 3 ( 2022-09), p. 530-538
    Abstract: Current guidelines recommending preoperative transfusion to a hemoglobin level of 9 to 10 g/dL for patients with sickle cell disease (SCD) are based on imperfect evidence. The benefit of preoperative transfusion in children specifically is not known. This study aimed to evaluate whether preoperative RBC transfusion is associated with different rates of sickle cell crisis and surgical complications, compared with no preoperative transfusion, among children with SCD undergoing common abdominal operations. STUDY DESIGN: The NSQIP-Pediatrics database (2013 to 2019) was queried. Patients who underwent cholecystectomy, splenectomy, or appendectomy with a preoperative Hct level of less than 30% were included. The primary outcome was 30-day readmission for sickle cell crisis. Secondary outcomes were 30-day surgical complications and hospital length of stay. Propensity score matching methods were used to obtain two statistically similar cohorts of patients comprised of those who were preoperatively transfused and those who were not. RESULTS: Among 357 SCD patients, 200 (56%) received preoperative transfusion. In the matched cohort of 278 patients (139 per group), there was no statistically significant difference in 30-day readmission for sickle cell crisis in the transfused and non-transfused groups (5.8% vs 7.2%, p = 0.80). The rate of 30-day surgical complications did not differ between matched groups (10.8% vs 9.4%, p = 0.84). Subgroups defined by presenting Hct levels of 27.3% or greater or less than 27.3%, American Society of Anesthesiologists classification, wound class, and index operation were not associated with an altered risk of sickle cell crisis or surgical complications after preoperative transfusion compared with no transfusion. CONCLUSIONS: Preoperative transfusion for children with SCD undergoing semi-elective abdominal operations was not associated with improved outcomes. Prospective investigation is warranted to strengthen guidelines and minimize unnecessary perioperative transfusions in this population.
    Type of Medium: Online Resource
    ISSN: 1072-7515
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 7
    Online Resource
    Online Resource
    Elsevier BV ; 2023
    In:  Journal of Pediatric Surgery ( 2023-6)
    In: Journal of Pediatric Surgery, Elsevier BV, ( 2023-6)
    Type of Medium: Online Resource
    ISSN: 0022-3468
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2039299-0
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  • 8
    Online Resource
    Online Resource
    Public Library of Science (PLoS) ; 2022
    In:  PLOS ONE Vol. 17, No. 3 ( 2022-3-29), p. e0266251-
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 3 ( 2022-3-29), p. e0266251-
    Abstract: Previous work demonstrated enhanced enterocyte proliferation and mucosal growth in gnotobiotic mice, suggesting that intestinal flora participate in mucosal homeostasis. Furthermore, broad-spectrum enteral antibiotics are known to induce near germ-free (GF) conditions in mice with conventional flora (CONV). We hypothesized that inducing near GF conditions with broad-spectrum enteral antibiotics would cause ordered small intestinal mucosal growth in CONV mice but would have no effect in GF mice with no inherent microbiome. C57BL/6J CONV and GF mice received either an antibiotic solution (Ampicillin, Ciprofloxacin, Metronidazole, Vancomycin, Meropenem) or a vehicle alone. After treatment, small intestinal villus height (VH), crypt depth (CD), mucosal surface area (MSA), crypt proliferation index (CPI), apoptosis, and villus and crypt cell types were assessed. Antibiotic-treated CONV (Abx-CONV) mice had taller villi, deeper crypts, increased CPI, increased apoptosis, and greater MSA compared to vehicle-treated CONV mice. Minor differences were noted in enterocyte and enterochromaffin cell proportions between groups, but goblet and Paneth cell proportions were unchanged in Abx-CONV mice compared to vehicle-treated CONV mice (p 〉 0.05). Antibiotics caused no significant changes in VH or MSA in GF mice when compared to vehicle-treated GF mice (p 〉 0.05). Enteral administration of broad-spectrum antibiotics to mice with a conventional microbiome stimulates ordered small intestinal mucosal growth. Mucosal growth was not seen in germ-free mice treated with antibiotics, implying that intestinal mucosal growth is associated with change in the microbiome in this model.
    Type of Medium: Online Resource
    ISSN: 1932-6203
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2022
    detail.hit.zdb_id: 2267670-3
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  • 9
    In: International Journal of Drug Policy, Elsevier BV, Vol. 110 ( 2022-12), p. 103888-
    Type of Medium: Online Resource
    ISSN: 0955-3959
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2010000-0
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  • 10
    Online Resource
    Online Resource
    American Physiological Society ; 2023
    In:  American Journal of Physiology-Gastrointestinal and Liver Physiology Vol. 325, No. 1 ( 2023-07-01), p. G80-G91
    In: American Journal of Physiology-Gastrointestinal and Liver Physiology, American Physiological Society, Vol. 325, No. 1 ( 2023-07-01), p. G80-G91
    Abstract: Regulation of small intestinal epithelial growth by endogenous and environmental factors is critical for intestinal homeostasis and recovery from insults. Depletion of the intestinal microbiome increases epithelial proliferation in small intestinal crypts, similar to the effects observed in animal models of serotonin potentiation. Based on prior evidence that the microbiome modulates serotonin activity, we hypothesized that microbial depletion-induced epithelial proliferation is dependent on host serotonin activity. A mouse model of antibiotic-induced microbial depletion (AIMD) was employed. Serotonin potentiation was achieved through either genetic knockout of the serotonin transporter (SERT) or pharmacological SERT inhibition, and inhibition of serotonin synthesis was achieved with para-chlorophenylalanine. AIMD and serotonin potentiation increased intestinal villus height and crypt proliferation in an additive manner, but the epithelial proliferation observed after AIMD was blocked in the absence of endogenous serotonin. Using Lgr5-EGFP-reporter mice, we evaluated intestinal stem cell (ISC) quantity and proliferation. AIMD increased the number of ISCs per crypt and ISC proliferation compared with controls, and changes in ISC number and proliferation were dependent on the presence of host serotonin. Furthermore, Western blotting demonstrated that AIMD reduced epithelial SERT protein expression compared with controls. In conclusion, host serotonin activity is necessary for microbial depletion-associated changes in villus height and ISC proliferation in crypts, and microbial depletion produces a functional serotonin-potentiated state through reduced SERT protein expression. These findings provide an understanding of how changes to the microbiome contribute to intestinal pathology and can be applied therapeutically. NEW & NOTEWORTHY Antibiotic-induced microbial depletion of the murine small intestine results in a state of potentiated serotonin activity through reduced epithelial expression of the serotonin transporter. Specifically, serotonin-dependent mechanisms lead to increased intestinal surface area and intestinal stem cell proliferation. Furthermore, the absence of endogenous serotonin leads to blunting of small intestinal villi, suggesting that serotonin signaling is required for epithelial homeostasis.
    Type of Medium: Online Resource
    ISSN: 0193-1857 , 1522-1547
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2023
    detail.hit.zdb_id: 1477329-6
    SSG: 12
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