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Necrotizing enterocolitis (NEC) is a serious gastrointestinal condition that primarily affects premature infants, although it can also occur in full-term infants. It is characterized by inflammation and injury of the intestinal tissue, which can progress to necrosis and perforation of the bowel. NEC is a leading cause of morbidity and mortality in neonatal intensive care units (NICUs), particularly among very low birth weight infants. Diagnosis of NEC is based on clinical signs and symptoms, radiographic findings, and laboratory tests. Management of NEC involves a multidisciplinary approach, including supportive care, medical therapy, and surgical intervention when necessary. Supportive care includes bowel rest, intravenous fluids, and nutritional support. Medical therapy may include antibiotics, gastric decompression, and parenteral nutrition. Surgical intervention may be required for infants with intestinal perforation, severe NEC, or complications such as intestinal stricture or short bowel syndrome. This condition and its complications may carry consequences for life and especially sport performance in the child’s future. Strategies for preventing NEC include promoting breastfeeding, avoiding unnecessary antibiotic exposure, minimizing enteral feeding interruptions, practicing strict infection control measures, and implementing protocols for gradual feeding advancement in premature infants. Overall, NEC is a complex and multifactorial disease that poses significant challenges in neonatal care. Early recognition, prompt intervention, and comprehensive management are essential for optimizing outcomes for affected infants. Further research is needed to better understand the pathophysiology of NEC and to develop more effective prevention and treatment strategies.

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease primarily affecting premature neonates, marked by poorly understood pro-inflammatory signaling cascades. Recent advancements have shed light on a subset of endogenous molecular patterns, termed chromatin-associated molecular patterns (CAMPs), which belong to the broader category of damage-associated molecular patterns (DAMPs). CAMPs play a crucial role in recognizing pattern recognition receptors and orchestrating inflammatory responses. This review focuses into the realm of CAMPs, highlighting key players such as extracellular cold-inducible RNA-binding protein (eCIRP), high mobility group box 1 (HMGB1), cell-free DNA, neutrophil extracellular traps (NETs), histones, and extracellular RNA. These intrinsic molecules, often perceived as foreign, have the potential to trigger immune signaling pathways, thus contributing to NEC pathogenesis. In this review, we unravel the current understanding of the involvement of CAMPs in both preclinical and clinical NEC scenarios. We also focus on elucidating the downstream signaling pathways activated by these molecular patterns, providing insights into the mechanisms that drive inflammation in NEC. Moreover, we scrutinize the landscape of targeted therapeutic approaches, aiming to mitigate the impact of tissue damage in NEC. This in-depth exploration offers a comprehensive overview of the role of CAMPs in NEC, bridging the gap between preclinical and clinical insights.

ObjectiveThe purpose of this study is to develop a multimodal model based on artificial intelligence to assist clinical doctors in the early diagnosis of necrotizing enterocolitis in newborns.MethodsThis study is a retrospective study that collected the initial laboratory test results and abdominal x-ray image data of newborns (non-NEC, NEC) admitted to our hospital from January 2022 to January 2024.A multimodal model was developed to differentiate multimodal data, trained on the training dataset, and evaluated on the validation dataset. The interpretability was enhanced by incorporating the Gradient-weighted Class Activation Mapping (GradCAM) analysis to analyze the attention mechanism of the multimodal model, and finally compared and evaluated with clinical doctors on external datasets.ResultsThe dataset constructed in this study included 11,016 laboratory examination data from 408 children and 408 image data. When applied to the validation dataset, the area under the curve was 0.91, and the accuracy was 0.94. The GradCAM analysis shows that the model's attention is focused on the fixed dilatation of the intestinal folds, intestinal wall edema, interintestinal gas, and portal venous gas. External validation demonstrated that the multimodal model had comparable accuracy to pediatric doctors with ten years of clinical experience in identification.ConclusionThe multimodal model we developed can assist doctors in early and accurate diagnosis of NEC, providing a new approach for assisting diagnosis in underdeveloped medical areas.

Necrotizing enterocolitis (NEC) is a devastating disease of the neonatal intestine, causing widespread intestinal necrosis as well systemic illness that frequently results in death. Because the clinical onset of NEC is sudden and difficult to predict, NEC is considered an acute event. However, NEC does not occur in utero, meaning that postnatal exposures are required, and it does not typically occur right after birth, suggesting that longitudinal changes may be occurring before NEC can develop. In this perspective, the author considers whether NEC should be re-considered as a problem of disordered intestinal epithelial development, with required maladaptation over time prior to the onset of the necrotic event. This framework is similar to how bronchopulmonary dysplasia is currently conceptualized. They also advocate that NEC researchers incorporate this possibility into future studies on NEC susceptibility and pathogenesis.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in neonates, particularly preterm infants. Many factors can lead to NEC, but microbial dysbiosis is one of the most important risk factors that can induce this disease. Given the major role of the gut virome in shaping bacterial homeostasis, virome research is a fledgling but rapidly evolving area in the field of microbiome that is increasingly connected to human diseases, including NEC. This review provides an overview of the development of the gut virome in newborns, discusses its emerging role in NEC, and explores promising therapeutic applications, including phage therapy and fecal virome transplantation.

ABSTRACT Objective: To describe the long-term health outcomes of neonates affected by necrotizing enterocolitis (NEC) and its implications for quality of life. Data source: This is an integrative review, conducted by searching the literature in the following databases: Virtual Health Library (BVS), Latin American and Caribbean Health Sciences Literature (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE), and PubMed, using Health Sciences Descriptors (DeCS): “necrotizing enterocolitis,” “quality of life,” and “prognosis” combined with the Boolean operators AND and OR: “quality of life” OR “prognosis.” Inclusion criteria were: publication period between 2012 and 2022. Data synthesis: A total of 1,010 studies were located, of which ten were selected to comprise the bibliographic sample of this review. Children with NEC are prone to exhibit cognitive neurological impairment, especially those who undergo surgical procedures due to more severe conditions. Motor development was considered below average when compared to healthy children, with more noticeable delays in fine and gross motor function development. The search for the relationship between NEC and quality of life revealed that this condition has a negative impact on the well-being of affected individuals. Conclusions: NEC has proven to be a serious condition contributing to high rates of morbidity and mortality in newborns, potentially leading to a reduction in the quality of life of affected patients.

Abstract Human milk contains extracellular vesicles (HMEVs). Pre‐clinical models suggest that HMEVs may enhance intestinal function and limit inflammation; however, it is unknown if HMEVs or their cargo survive neonatal human digestion. This limits the ability to leverage HMEV cargo as additives to infant nutrition or as therapeutics. This study aimed to develop an EV isolation pipeline from small volumes of human milk and neonatal intestinal contents after milk feeding (digesta) to address the hypothesis that HMEVs survive in vivo neonatal digestion to be taken up intestinal epithelial cells (IECs). Digesta was collected from nasoduodenal sampling tubes or ostomies. EVs were isolated from raw and pasteurized human milk and digesta by density‐gradient ultracentrifugation following two‐step skimming, acid precipitation of caseins, and multi‐step filtration. EVs were validated by electron microscopy, western blotting, nanoparticle tracking analysis, resistive pulse sensing, and super‐resolution microscopy. EV uptake was tested in human neonatal enteroids. HMEVs and digesta EVs (dEVs) show typical EV morphology and are enriched in CD81 and CD9, but depleted of β‐casein and lactalbumin. HMEV and some dEV fractions contain mammary gland‐derived protein BTN1A1. Neonatal human enteroids rapidly take up dEVs in part via clathrin‐mediated endocytosis. Our data suggest that EVs can be isolated from digestive fluid and that these dEVs can be absorbed by IECs.

BackgroundPrematurity and congenital heart disease (CHD) are the leading causes of neonatal mortality and morbidity. Limited data are available about the outcomes of premature infants with severe CHD.MethodsWe queried The National Inpatient Database using ICD-10 codes for premature patients (

Neuroendocrine carcinomas (NECs) of the gallbladder are very rare and aggressive tumors with poor prognosis. Most of them are poorly differentiated and belong to the small cell type. We report a case of a 59-year-old woman who presented with abdominal pain and distension. Contrast-enhanced computed tomography revealed a large heterogeneous mass in the liver, adjacent to the gallbladder, and omental nodules. CA 19-9 level was elevated and ascitic fluid cytology was suspicious for malignancy. Percutaneous biopsy of the liver mass confirmed the diagnosis of small cell NEC of the gallbladder. The patient was considered inoperable and planned for chemotherapy, but she died 20 days after admission. This case illustrates the diagnostic challenges and the dismal outcome of small cell NEC of the gallbladder. Early detection and multimodal treatment are essential for improving the survival of these patients. [ABSTRACT FROM AUTHOR]

Abstract Background The status of anastomotic blood perfusion is associated with the occurrence of anastomotic leakage after intestinal anastomosis. Fluorescence angiography (FA) with indocyanine green (ICG) can objectively assess intestinal blood perfusion. This study aims to investigate whether anastomotic perfusion assessment with ICG influences surgical decision-making during laparoscopic intestinal resection and primary anastomosis for colonic stricture after necrotizing enterocolitis. Methods Patients who underwent laparoscopic intestinal resection and primary anastomosis between January 2022 and December 2022 were retrospectively analyzed. Before intestinal anastomosis, the ICG fluorescence technology was used to evaluate the blood perfusion of intestinal tubes on both sides of the anastomosis. After the completion of primary anastomosis, the anastomotic blood perfusion was assessed again. Results Of the 13 cases, laparoscopy was used to determine the extent of the diseased bowel to be excised, and the normal bowel was preserved for anastomosis. The anastomosis was established under the guidance of ICG fluorescence technology, and FA was performed after anastomosis to confirm good blood flow in the proximal bowel. The anastomotic intestinal tube was changed in one case because FA showed a difference between the normal range of intestinal blood flow and the macroscopic prediction. There was no evidence of ICG allergy, anastomotic leakage, anastomotic stricture, or other complications. The median follow-up was 6 months, and all patients recovered well. Conclusions The ICG fluorescence technology is helpful in precisely and efficiently determining the anastomotic intestinal blood flow during stricture resection and in avoiding anastomotic leakage caused by poor anastomotic intestinal blood flow to some extent, with satisfactory short-term efficacy.

Introduction Necrotizing enterocolitis (NEC) poses a significant threat to preterm infants, with nonspecific early manifestations complicating timely diagnosis. Therefore, this study aimed to develop a novel scoring system for early diagnosis of NEC, incorporating clinical and laboratory data with urinary caveolin-1 levels. Material and methods A single-center prospective cohort study was conducted at a tertiary hospital in East Java, Indonesia. NEC diagnosis was established by Bell’s criteria and proven gut dysbiosis. Urinary levels of claudin-2, caveolin-1, and epidermal growth factor (EGF) were assessed as potential indicators of tight junction disruption. The selected urine biomarker cutoff value was determined using symbolic classification analysis and combined with clinical and laboratory parameters from Bell’s criteria to create an NEC scoring system, validated with the Aiken index. Sensitivity and specificity analyses were performed. Results Thirty-four neonates, comprising NEC, preterm non-NEC, and term infants, were included. qPCR analysis highlighted elevated Klebsiella, Lactobacillus, Clostridium, and Bacteroides levels in NEC patients, indicating a gut dysbiosis trend. Among 3 biomarkers, caveolin-1 ≥ 17.81 ng/dl on day 3 demonstrated 72.86% negative predictive value and 87.50% positive predictive value. The combined scoring system which comprised abdominal cellulitis, distension, radiology, advanced resuscitation at birth, prematurity or low birthweight, platelet count, sepsis, orogastric retention, metabolic acidosis and caveolin-1 findings exhibited an AUC of 0.922 (95% CI: 0.81–1.00, p < 0.001), with ≥ 1.81 as the cutoff, offering 93% sensitivity and 94% specificity. Conclusions Urine caveolin-1 on day 3 signifies enterocyte tight junction damage and the acute phase of NEC in premature infants. The proposed scoring system demonstrates good performance in predicting NEC incidence in preterm infants.

Reduction–oxidation (redox) chemistry plays a vital role in human homeostasis. These reactions play critical roles in energy generation, as part of innate immunity, and in the generation of secondary messengers with various functions such as cell cycle progression or the release of neurotransmitters. Despite this cornerstone role, if left unchecked, the body can overproduce reactive oxygen species (ROS) or reactive nitrogen species (RNS). When these overwhelm endogenous antioxidant systems, oxidative stress (OS) occurs. In neonates, OS has been associated with retinopathy of prematurity (ROP), leukomalacia, and bronchopulmonary dysplasia (BPD). Given its broad spectrum of effects, research has started to examine whether OS plays a role in necrotizing enterocolitis (NEC). In this paper, we will discuss the basics of redox chemistry and how the human body keeps these in check. We will then discuss what happens when these go awry, focusing mostly on NEC in neonates.

Background: Strategies to stabilize and support overall infant health by increasing the number of Bifidobacterium longum in the infant gut are of interest, but few studies have systematically addressed this issue. We aimed to evaluate the efficacy and safety of Bifidobacterium longum use in infants using meta-analysis. Methods: We searched PubMed, EMBASE, Cochrane Library of Systematic Reviews, and SinoMed for publications until 27 July 2022. The main outcomes of interest were weight gain, risk of necrotizing enterocolitis (NEC), and adverse events. Two authors independently performed study screening, risk of bias assessment, and data extraction. Outcome data were extracted from each included study and combined using mean difference (MD) or risk ratio (RR) and finally combined using a fixed-effect model or random-effect model. Results: A total of 4481 relevant studies were identified, of which 15 were found to be eligible for randomized controlled trials and were included in the meta-analysis. The combined extracted data showed that the intervention group containing Bifidobacterium longum had a significantly lower risk of NEC (RR = 0.539, 95% CI: 0.333, 0.874) compared to the control group. There was no statistical difference between the intervention and control groups regarding weight gain (MD = 0.029, 95% CI: −0.032, 0.090), the occurrence of adverse events (RR = 0.986, 95% CI: 0.843, 1.153), and serious adverse events (RR = 0.881, 95% CI: 0.493, 1.573). Conclusions: Bifidobacterium longum may significantly reduce the risk of NEC in infants as well as being safe; thus, further research evidence is needed on whether there is a benefit on weight gain. [ABSTRACT FROM AUTHOR]

Background: The status of anastomotic blood perfusion is associated with the occurrence of anastomotic leakage after intestinal anastomosis. Fluorescence angiography (FA) with indocyanine green (ICG) can objectively assess intestinal blood perfusion. This study aims to investigate whether anastomotic perfusion assessment with ICG influences surgical decision-making during laparoscopic intestinal resection and primary anastomosis for colonic stricture after necrotizing enterocolitis. Methods: Patients who underwent laparoscopic intestinal resection and primary anastomosis between January 2022 and December 2022 were retrospectively analyzed. Before intestinal anastomosis, the ICG fluorescence technology was used to evaluate the blood perfusion of intestinal tubes on both sides of the anastomosis. After the completion of primary anastomosis, the anastomotic blood perfusion was assessed again. Results: Of the 13 cases, laparoscopy was used to determine the extent of the diseased bowel to be excised, and the normal bowel was preserved for anastomosis. The anastomosis was established under the guidance of ICG fluorescence technology, and FA was performed after anastomosis to confirm good blood flow in the proximal bowel. The anastomotic intestinal tube was changed in one case because FA showed a difference between the normal range of intestinal blood flow and the macroscopic prediction. There was no evidence of ICG allergy, anastomotic leakage, anastomotic stricture, or other complications. The median follow-up was 6 months, and all patients recovered well. Conclusions: The ICG fluorescence technology is helpful in precisely and efficiently determining the anastomotic intestinal blood flow during stricture resection and in avoiding anastomotic leakage caused by poor anastomotic intestinal blood flow to some extent, with satisfactory short-term efficacy. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H 2 S) has been shown to improve outcomes in a murine model of necrotizing enterocolitis (NEC). There is evidence in humans that H 2 S relies on endothelial nitric oxide synthase (eNOS) to exert its protective effects, potentially through the persulfidation of eNOS at the Cysteine 443 residue. We obtained a novel mouse strain with a mutation at this residue (eNOSC440G) and hypothesized that this locus would be critical for GYY4137 (an H 2 S donor) to exert its protective effects. Necrotizing enterocolitis was induced in 5-day old wild type (WT) and eNOSC440G mice using intermittent exposure to hypoxia and hypothermia in addition to gavage formula feeds. On postnatal day 9, mice were humanely euthanized. Data collected included daily weights, clinical sickness scores, histologic lung injury, intestinal injury (macroscopically and histologically), and intestinal perfusion. During the NEC model, pups received daily intraperitoneal injections of either GYY4137 (50 mg/kg) or PBS (vehicle). Data were tested for normality and compared using t-test or Mann–Whitney, and a p-value <0.05 was considered significant. In WT mice, the administration of GYY4137 significantly improved clinical sickness scores, attenuated intestinal and lung injury, and improved mesenteric perfusion compared to vehicle (p < 0.05). In eNOSC440G mice, the treatment and vehicle groups had similar clinical sickness scores, intestinal and lung injury scores, and intestinal perfusion. GYY4137 administration improves clinical outcomes, attenuates intestinal and lung injury, and improves perfusion in a murine model of necrotizing enterocolitis. The beneficial effects of GYY4137 are dependent on the Cys440 residue of eNOS. • Necrotizing enterocolitis is a highly morbid disease that occurs in premature infants. No specific treatment option is available. Hydrogen sulfide treatment has shown promising results in animal models but the exact mechanism of action is not known. • In this article, we show that hydrogen sulfide is protective against experimental necrotizing enterocolitis in mice. Additionally, this protection is dependent on a specific cysteine residue of eNOS. [ABSTRACT FROM AUTHOR]

The effectiveness of probiotics in reducing the incidence of necrotizing enterocolitis has been supported by a very large number of studies. However, the utilization of probiotics in preterm infants remains a topic of debate. This study aims to assess the rate of probiotic use in European neonatal intensive care units (NICUs), compare administration protocols, and identify barriers and concerns associated with probiotic use. An online questionnaire was distributed via email to European NICUs between October 2020 and June 2021. Different questions related to the frequency of probiotic use were proposed. Data on probiotic administration protocols and reasons for non-utilization were collected. The majority of responses were from France and Switzerland, with response rates of 85% and 89%, respectively. A total of 21% of French NICUs and 100% of Swiss NICUs reported routine probiotic use. There was significant heterogeneity in probiotic administration protocols, including variations in probiotic strains, administration, and treatment duration. The main obstacles to routine probiotic use were the absence of recommendations, lack of consensus on strain selection, insufficient scientific evidence, and concerns regarding potential adverse effects. The rate of routine probiotic administration remains low in European NICUs, with heterogeneity among protocols. Further trials are necessary to elucidate optimal treatment modalities and ensure safety of administration. [ABSTRACT FROM AUTHOR]

Abstract Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality among neonates and low birth weight children in the United States. Current treatment options, such as antibiotics and intestinal resections, often result in complications related to pediatric nutrition and development. This systematic review aimed to identify alternative dietary bioactive compounds that have shown promising outcomes in ameliorating NEC in vivo studies conducted within the past six years. Following PRISMA guidelines and registering in PROSPERO (CRD42023330617), we conducted a comprehensive search of PubMed, Scopus, and Web of Science. Our analysis included 19 studies, predominantly involving in vivo models of rats (Rattus norvegicus) and mice (Mus musculus). The findings revealed that various types of compounds have demonstrated successful amelioration of NEC symptoms. Specifically, six studies employed plant phenolics, seven utilized plant metabolites/cytotoxic chemicals, three explored the efficacy of vitamins, and three investigated the potential of whole food extracts. Importantly, all administered compounds exhibited positive effects in mitigating the disease. These results highlight the potential of natural cytotoxic chemicals derived from medicinal plants in identifying and implementing powerful alternative drugs and therapies for NEC. Such approaches have the capacity to impact multiple pathways involved in the development and progression of NEC symptoms. [ABSTRACT FROM AUTHOR]

OBJECTIVE Limited data exist comparing indomethacin and ibuprofen for the treatment of patent ductus arteriosus (PDA). The objective was to compare the safety and efficacy of indomethacin and ibuprofen for treatment of PDA closure. METHODS This single-center, pre-test/post-test quasi-experiment included preterm infants admitted to the neonatal intensive care unit who received indomethacin (July 1, 2013-September 30, 2015) or ibuprofen (December 1, 2015-July 31, 2019) for PDA. Patients were excluded if they were thrombocytopenic, had existing kidney injury, unresolved intraventricular hemorrhage (IVH) or necrotizing enterocolitis (NEC) at treatment initiation. Data were obtained from the electronic health record. Study outcomes were complete PDA closure, degree of PDA closure, resolution of symptoms, and new-onset acute kidney injury (AKI), IVH, or NEC. RESULTS A total of 114 patients were included: 44 (39%) received indomethacin and 70 (61%) received ibuprofen. Twenty-one (21%) patients experienced successful PDA closure within 1 week: 13 (32%) indomethacin patients and 8 (13%) ibuprofen patients (p = 0.023). PDA size reduction occurred in 43 (46%) patients with 29 (25%) experiencing complete symptom resolution. Significantly more indomethacin patients compared with ibuprofen patients experienced new-onset AKI (48% vs 17%; p < 0.001) and received concomitant nephrotoxins (68% vs 39%; p = 0.002). There were no significant differences in new-onset IVH or NEC. CONCLUSIONS Indomethacin administration successfully closed the PDA in more neonates than ibuprofen but resulted in higher rates of AKI. However, this was confounded by more frequent administration of concomitant nephrotoxins. Larger trials are needed to help elucidate the optimal drug for closure of the PDA in neonates. [ABSTRACT FROM AUTHOR]

We aimed to assess whether autoantibodies can be used as biomarkers for necrotizing enterocolitis (NEC) and applied for its early diagnosis. A prospective observational study was conducted in neonates with suspected NEC abdominal distension (the developmental study), which consisted of 50 neonates finally divided into NEC (n = 24) and non-NEC (n = 26) cohorts based on follow-up results. Serum samples were collected within 48 h of illness onset and used for screening NEC-associated plasma autoantibodies by autoantigen microarray. Additionally, we validated anti-myosin autoantibodies by enzyme-linked immunosorbent assay (ELISA) in an independent validation study, for which we selected plasma samples within 48 h of onset of NEC (n = 38) and samples of gestational age- and weight-matched controls (n = 13). Autoantigen microarray revealed that both IgG and IgM anti-myosin autoantibodies in plasma from neonates with NEC were significantly higher than those in neonates with other diagnoses. ELISA showed that plasma anti-myosin autoantibodies increased in the NEC cohort, with 1.5-fold higher levels than in the non-NEC cohort. Anti-myosin autoantibodies were able to distinguish NEC from non-NEC, achieving an area under the curve (AUC) of 0.8856 (95% confidence interval (CI): 0.7918–0.9795), with sensitivity of 81.58% and specificity of 76.93%. Plasma anti-myosin autoantibodies were significantly higher in all three subtypes of NEC (P < 0.0001 for NEC I; P = 0.0018 for NEC II; P = 0.0011 for NEC III), especially in NEC stage I than that in the non-NEC controls. Conclusion: Anti-myosin autoantibodies may be applied as a promising diagnostic marker for NEC, especially for NEC stage I. What is Known: • Intestinal damage and self-antigen exposure may lead to increased autoantibodies, and they are widely used as biomarkers for diagnosing inflammatory bowel disease. • Necrotizing enterocolitis (NEC) is a devastating disease with overwhelming inflammation and immune dysregulation. What is New: • Increased autoantibodies were present in patients with NEC, even before typical X-ray manifestations. • Anti-myosin autoantibodies may be applied as a promising diagnostic marker for NEC. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) is the most common surgical disease in the neonatal period with a high mortality rate. To date, there is no consensus on the indications for surgery in the absence of pneumoperitoneum. This study aimed to determine the indications for surgery in pre-term infants with NEC and their mortality. Methods: We conducted a descriptive, observational, cross-sectional, and retrospective study including pre-term infants with NEC from two perinatal hospitals in Toluca, Mexico, between 2017 and 2022. Descriptive and inferential statistics and group comparisons were performed using Fisher and Kruskal-Wallis tests. Results: Of 236 patients with NEC, 52 (22%) required surgery; we analyzed 42 cases with complete clinical records. The indications for surgery were divided into (a) clinical deterioration (33.3%); (b) radiographic findings (31%); (c) laboratory alterations (19%); and (d) positive paracentesis (16.7%). The group of radiographic findings underwent surgery later, up to 2 days after the other groups. The mortality rate of surgical NEC was 42.9%. Conclusions: The most common indication for surgery in pre-term infants with NEC was clinical worsening despite optimal medical management; radiographic findings were the indication associated with the highest mortality. Laboratory abnormalities and positive paracentesis were the indications with the best outcomes but the least used. [ABSTRACT FROM AUTHOR]

Despite an increasing necrotizing enterocolitis (NEC) incidence, treatment strategies have failed to make major advancements towards improved NEC outcomes. Heterogeneity in outcome reporting and a lack of treatment efficacy studies potentially hamper these advancements. We aimed to analyze outcome reporting in recent interventional NEC studies. We performed a systematic review identifying interventional studies on NEC between 1st of January 2016 and 1st of June 2023 in MEDLINE, Embase, CENTRAL and Cochrane reviews. Systematic reviews, clinical trials and change-in-practice cohort studies reporting any therapeutic intervention for NEC patients (Bell's stage ≥ IIa) were eligible. We excluded studies on NEC diagnostics or prevention and non-English publications. Outcomes were categorized into five core areas and presented descriptively. The review was registered with PROSPERO (CRD42022302712). Out of 1.642 screened records, 65 were eligible for full-text review and 15 were finally included for data extraction. Median number of reported outcomes per article was six (range 1–19). We identified 66 unique outcomes, which were mapped to 53 outcome terms. Thirty-four out of the 53 of the outcome terms (64%) were only reported in a single article. Mortality was the most reported outcome (11/15 articles, 73%). Core area 'Adverse outcomes' contained the most outcome terms (n = 19), whereas 'Life impact' contained the least outcome terms (n = 4) and was represented in 3 articles (20%). Considerable heterogeneity in outcome reporting and a paucity of outcomes concerning 'Life impact' exist in interventional NEC studies. Development of a NEC core outcome set may improve consistency and patient-relevance in outcome reporting. Systematic Review and Meta-Analyses. III. [Display omitted] What is currently known about this topic? • Mortality due to necrotizing enterocolitis (NEC) has remained high over the last decade, without major advancements affecting disease outcome. • Heterogeneity in outcome reporting hampers meta-analyses. What new information is contained in this article? • Outcome reporting in interventional NEC studies is heterogenous, with 66 unique outcomes extracted from 15 articles. • 'Life impact' is the least represented core area in outcome reporting, while these outcomes may be especially relevant to patients and their families. [ABSTRACT FROM AUTHOR]

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Introduction: Upon birth, a hitherto naïve immune system is confronted with a plethora of microbial antigens due to intestinal bacterial colonization. To prevent excessive inflammation and disruption of the epithelial barrier, physiological mechanisms must promote immune-anergy within the neonatal gut. As high concentrations of human lactoferrin (hLF), a transferrin glycoprotein shown to modulate macrophage function, are frequently encountered in colostrum, its direct interaction with intestinal macrophages may satisfy this physiological need. Thus, the primary objective of this study was to investigate transcriptional changes induced by human lactoferrin in neonatal monocyte-derivedmacrophages. Methods: Cord blood-derivedmonocytesweredifferentiatedwithM-CSF in presence or absence of 500 μg/mL hLF for 7 days and afterwards stimulatedwith 1 ng/mL LPS or left untreated. RNA was then isolated and subjected tomicroarray analysis. Results: Differentiation of cord blood-derived monocytes in presence of hLF induced a distinct transcriptional program defined by cell cycle arrest in the G2/M phase, induction of IL-4/IL-13-like signaling, altered extracellular matrix interaction, and enhanced propensity for cell-cell interaction. Moreover, nearcomplete abrogation of transcriptional changes induced by TLR4 engagement with LPS was observed in hLF-treated samples. Discussion: The global transition towards an M2-like homeostatic phenotype and the acquisition of quiescence elegantly demonstrate theontogenetical relevanceof hLF in attenuating pro-inflammatory signaling within the developing neonatal intestine. The marked anergy towards proinflammatory stimuli such as LPS further underlines the glycoprotein's potential therapeutic relevance. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is an inflammatory intestinal disease that profoundly affects preterm infants. Currently, the pathogenesis of NEC remains controversial, resulting in limited treatment strategies. The preterm infants are thought to be susceptible to gut inflammatory disorders because of their immature immune system. In early life, intestinal macrophages (IMjs), crucial components of innate immunity, demonstrate functional plasticity and diversity in intestinal development, resistance to pathogens, maintenance of the intestinal barrier, and regulation of gut microbiota. When the stimulations of environmental, dietary, and bacterial factors interrupt the homeostatic processes of IMjs, they will lead to intestinal disease, such as NEC. This review focuses on the IMjs related pathogenesis in NEC, discusses the multi-functional roles and relevant molecular mechanisms of IMjs in preterm infants, and explores promising therapeutic application for NEC. [ABSTRACT FROM AUTHOR]

OBJECTIVE As broader spectrum antibiotics have been associated with adverse effects, our study evaluated whether the frequency of culture-positive late-onset sepsis (LOS) and multidrug resistant (MDR) infections were increased with the use of ceftazidime as compared with cefotaxime in the neonatal intensive care unit (NICU). METHODS This was a multihospital, retrospective chart review of patients who received at least 24 hours of ceftazidime or cefotaxime in the NICU between December 1, 2012 and August 31, 2021. Patients were excluded from analysis if they expired during the admission, had an incomplete history, positive cultures for an MDR infection prior to receiving either antibiotic, or received the alternate antibiotic within the same treatment course. RESULTS A total of 334 patients were included for analysis (ceftazidime, n = 147; cefotaxime, n = 187). The average birth weight was lower in the ceftazidime cohort compared with the cefotaxime cohort [1.46 kg (95% CI, 1.29-1.63 kg) versus 1.93 kg (95% CI, 1.75-2.11 kg), p = 0.0002] with a corresponding lower gestational age [28.9 weeks (95% CI, 28.0-29.9 weeks) versus 31.7 weeks (95% CI, 30.8-32.6 weeks), p = 0.0001]. Adjusting for baseline differences showed a protective effect for ceftazidime (OR = 0.32; 95% CI, 0.16-0.62; p = 0.0009). There was no statistically significant difference in the frequency of MDR infections between the cohorts (OR = 0.25; 95% CI, 0.053-1.14; p = 0.07), however this study was underpowered to detect the difference noted. CONCLUSIONS Ceftazidime appears to be a safe and effective alternative treatment option compared with cefotaxime in the NICU with no increase in the risk of culture-positive LOS or MDR infections. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to investigate the clinical determinants of intestinal failure and death in preterm infants with surgical NEC. METHODS: Retrospective comparison of clinical information between Group A = intestinal failure (Parenteral nutrition (PN) >90 days) and death and Group B = survivors and with PN dependence < 90 days in preterm infants with surgical NEC. RESULTS: Group A (n = 99/143) had a lower mean gestational age (26.4 weeks [SD3.5] vs. 29.4 [SD 3.5]; p = 0.013), lower birth weight (873 gm [SD 427g] vs. 1425 gm [894g]; p = <0.001), later age of NEC onset (22 days [SD20] vs. 16 days [SD 17]; p = 0.128), received surgery later (276 hours [SD 544] vs. 117 hours [SD 267]; p = 0.032), had cholestasis, received dopamine (80.6% vs. 58.5%; p = 0.010) more frequently and had longer postoperative ileus time (19.8 days [SD 15.4] vs. 11.8 days [SD 6.5]; p = <0.001) and reached full feeds later (93 days [SD 45] vs. 44 [SD 22]; p = <0.001) than Group B. On multivariate logistic regression, higher birth weight was associated with lower risk (OR 0.35, 95% CI 0.15–0.82; p = 0.016) of TPN > 90 days or death. Longer length of bowel resected (OR 1.76, 95% CI 1.02–3.02; p = 0.039) and longer postoperative ileus (OR 2.87, 95% CI 1.26–6.53; p = 0.011) were also independently associated with TPN >90days or death adjusted for gestational age and antenatal steroid treatment. CONCLUSION: In preterm infants with surgical NEC, clinical factors such as lower birth weight, longer bowel loss, and postoperative ileus days were significantly and independently associated with TPN >90 days or death. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is the most common life-threatening gastrointestinal emergency in prematurity. The pathophysiology is multifactorial and remains incompletely understood. Early diagnosis and treatment could reduce the risk of mortality and morbidity. We aimed to identify factors associated with NEC in preterm newborns. This case–control study included all preterm newborns presenting with NEC and managed between January 1, 2009 and December 31, 2018 in the neonatal intensive care unit of Nancy. For each case, two controls were matched according to three criteria: gestational age (WG), date of birth, and mode of delivery. Antenatal, peripartum, and postnatal risk factors prior to NEC were analyzed. A total of 292 infants were involved in the study, 113 of whom had NEC. Mean gestational age for newborns with NEC was 29 WG, and mean birth weight, 1340 g. Only early-onset infection was identified as a significant risk factor for NEC (15% vs. 6.6% for infection p <0.04, and 28.3% vs. 16.4% p <0.02 for infection and sepsis, NEC vs. controls, respectively). Late-onset feeding and initial continuous enteral feeding were significantly associated with the occurrence of more severe NEC (p <0.02 and p = 0.03, respectively). The results of this study are consistent with intestinal dysbiosis being a risk factor for NEC. Early-onset infection was found to be a significant risk factor. Enteral feeding practice may also be associated with NEC. [ABSTRACT FROM AUTHOR]

Context Many preterm neonates often cannot be fed enterally and hence do not receive the benefits of colostrum. Oropharyngeal application of colostrum is a novel way of harnessing the immunological benefits of colostrum. Randomized controlled trials (RCTs) investigating the efficacy of this approach have shown variable results. Objective The aim of this systematic review was to synthesize available data on the effect of oropharyngeal application of colostrum or mother's own milk (CMOM) in preterm infants. Data Sources Six electronic databases (MEDLINE, Embase, CINAHL, Scopus, Web of Science, and Cochrane Library) were searched until January 13, 2022. Only RCTs comparing oral application of CMOM with placebo/routine care in preterm infants were eligible. Studies enrolling term neonates or administering enteral feeds were excluded. Data Extraction Two investigators independently extracted data using a structured proforma. Data Analysis The Cochrane Risk of Bias 2 tool was used to assess bias. Random-effects meta-analysis was undertaken using RevMan 5.4 software. From 2787 records identified, 17 RCTs enrolling 4106 preterm infants were included. There was no significant difference between groups in incidence of necrotizing enterocolitis (NEC) stage 2 or higher (RR = 0.65; 95%CI, 0.36–1.20; 1089 participants in 12 trials). Application of CMOM significantly reduced the incidence of sepsis (RR = 0.72; 95%CI, 0.56–0.92; 1511 participants in 15 studies) and any stage of NEC (RR = 0.58; 95%CI, 0.37–0.92; 1616 participants in 16 trials). The CMOM group achieved full enteral feeds 1.75 days sooner (95%CI, 0.3–3.2 days; 1580 participants in 14 studies) and had higher weight at discharge (MD = 43.9 g; 95%CI, 3–85 g; 569 participants in 3 studies). There were no statistically significant differences in other outcomes. Conclusions Evidence with low to very low certainty suggests CMOM has a beneficial effect on NEC (any stage), sepsis, and time to full enteral feeds. Given its low cost and minimal risk of harm, routine CMOM use may be considered in preterm neonates. Prospero Registration Number CRD42021262763 [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of Xuebijing combine with ulinastatin on inflammatory response and myocardial protection of neonatus with necrotizing enterocolitis (NEC). Methods: 120 neonatus with NEC who were admitted to Guangdong Women and Children Hospital from May 2019 to May 2022 were selected. According to the random number table method, they were divided into control group (intravenous infusion of physiological saline before anesthesia induction), ulinastatin group (intravenous infusion of ulinastatin injection before anesthesia induction), Xuebijing group (intravenous infusion of Xuebijing injection before anesthesia induction), and combined group (intravenous infusion of ulinastatin injection and Xuebijing injection before anesthesia induction), with 30 cases of each group. The levels of mean arterial pressure (MAP), heart rate (HR), interleukin-17 (IL-17), C-reactive protein (CRP), tumor necrosis factor -α (TNF-α), cardiac troponin (cTnI), and B-type natriuretic peptide (BNP) were compared of four groups of neonatus, and the mortality and incidence of adverse reactions of four groups were recorded. Results: There was no statistically significant difference of HR between groups before surgery(P>0.05), ulinastatin group and Xuebijing group showed that decreased compared with control group after surgery and 1 d after surgery, and combined group showed that significant decreased after surgery and 1d after surgery compared with ulinastatin group and Xuebijing group(P<0.05). There was no statistically significant difference of MAP between groups before surgery(P>0.05), ulinastatin group and Xuebijing group showed that increased compared with control group after surgery and 1 d after surgery, and combined group showed that significant increased after surgery and 1 d after surgery compared with ulinastatin group and Xuebijing group(P<0.05). The CRP, IL-17, TNF-α of ulinastatin group, Xuebijing group, and combined group after surgery and 1 d after surgery were lower than those of control group at the same time point, and combined group were lower than those of ulinastatin group and Xuebijing group at the same time point(P<0.05). The cTnI and BNP of ulinastatin group, Xuebijing group, and combined group after surgery and 1 d after surgery were lower than those of control group at the same time point, and combined group were lower than those of ulinastatin group and Xuebijing group at the same time point(P<0.05). The mortality of combined group was lower than that of control group, ulinastatin group, and Xuebijing group. There was no statistically significant difference of the incidence of adverse reactions of four groups(P>0.05). Conclusion: Perioperative use of Xuebijing combine with ulinastatin of NEC, which is beneficial for the hemodynamic stability of neonatus, can alleviate the inflammatory response of neonatus, exert myocardial protection effect, and reduce clinical mortality. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the prevalence of abnormal vaginal colonization in women with cervical incompetence and to analyze its impact on obstetric and neonatal outcomes and placental inflammation. We included 138 pregnant women diagnosed with cervical incompetence and delivered in our hospital. Patients with major fetal anomaly or multifetal pregnancy were excluded. Upper vaginal culture was performed on the day of admission. A total of 60.9% (84/138) of cervical incompetence patients had abnormal bacterial colonization, and Escherichia coli (E. coli) was the most common colonized pathogen (33.3%, 46/138). The positive vaginal E. coli group had a higher rate of prior preterm birth (p = 0.021) and an earlier gestational age at which cervical incompetence was diagnosed (p < 0.01) than the negative group. The positive vaginal E. coli group had higher rates of clinical chorioamnionitis (p = 0.008) and subchorionic microabscess of the placenta (p = 0.012). Importantly, the positive vaginal E. coli group had significantly higher rates of proven early-onset neonatal sepsis (EONS) (p = 0.046), necrotizing enterocolitis (NEC) (p = 0.001), and neonatal mortality (p = 0.023). After adjusting for confounding variables, the positive vaginal E. coli group had significantly higher risk for proven EONS (OR: 3.853, 95% CI: 1.056–14.055) and NEC (OR: 12.410, 95% CI: 1.290–119.351). In conclusion, E. coli was the most common vaginal microorganism isolated from patients with cervical incompetence. Maternal vaginal E. coli colonization was associated with adverse neonatal outcomes including proven EONS and NEC and was characterized by a higher rate of placental subchorionic microabscess. [ABSTRACT FROM AUTHOR]

Antibiotic overutilization in the neonatal intensive care unit (NICU) has many adverse effects, and necrotizing enterocolitis (NEC) is one of the most common indications for antibiotics in premature infants. Evidence for a preferred antibiotic regimen for NEC is lacking. This project aims to reduce piperacillin-tazobactam use and overall antibiotic duration in neonates with NEC through the implementation of an antibiotic stewardship pathway based on the modified Bell stage classification system. A multidisciplinary team consisting of neonatology, pharmacy, infectious disease, and surgery developed an antibiotic protocol for the management of NEC based on Bell stage. Recommendations included 48 h of ampicillin/gentamicin (AG) for stage I, 5–10 days of AG for stage II, the addition of metronidazole for stage IIIA, and 7–14 days of piperacillin-tazobactam (PT) for stage IIIB. We evaluated overall antibiotic and PT exposure, progression to surgical NEC, NEC recurrence, antibiotic resistance, bacteremia/fungemia, and mortality 1 year pre- and post-protocol implementation. 27 patients pre-intervention and 44 post-intervention were analyzed. Antibiotic exposure was reduced from a median 119.19 to 80.65 days of therapy (DOT) per 1000 patient days (p = 0.11). PT exposure decreased after protocol implementation (median 68.78 vs. 7.97 DOT per 1000 patient days, p = 0.002). There were no significant differences in morbidity or mortality outcomes. Antibiotic stewardship strategies can be implemented in the NICU without compromising outcomes in patients with NEC. Bell stage stratification appears to be an effective method for antibiotic selection. Further studies are needed in a larger population to optimize regimens and ensure safety. Retrospective comparative study. Level III. [ABSTRACT FROM AUTHOR]

Maturational changes in the gut start in utero and rapidly progress after birth, with some functions becoming fully developed several months or years post birth including the acquisition of a full gut microbiome, which is made up of trillions of bacteria of thousands of species. Many factors influence the normal development of the neonatal and infantile microbiome, resulting in dysbiosis, which is associated with various interventions used for neonatal morbidities and survival. Extremely low gestational age neonates (<28 weeks' gestation) frequently experience recurring arterial oxygen desaturations, or apneas, during the first few weeks of life. Apnea, or the cessation of breathing lasting 15–20 s or more, occurs due to immature respiratory control and is commonly associated with intermittent hypoxia (IH). Chronic IH induces oxygen radical diseases of the neonate, including necrotizing enterocolitis (NEC), the most common and devastating gastrointestinal disease in preterm infants. NEC is associated with an immature intestinal structure and function and involves dysbiosis of the gut microbiome, inflammation, and necrosis of the intestinal mucosal layer. This review describes the factors that influence the neonatal gut microbiome and dysbiosis, which predispose preterm infants to NEC. Current and future management and therapies, including the avoidance of dysbiosis, the use of a human milk diet, probiotics, prebiotics, synbiotics, restricted antibiotics, and fecal transplantation, for the prevention of NEC and the promotion of a healthy gut microbiome are also reviewed. Interventions directed at boosting endogenous and/or exogenous antioxidant supplementation may not only help with prevention, but may also lessen the severity or shorten the course of the disease. [ABSTRACT FROM AUTHOR]

Early-life gut dysbiosis has been associated with an increased risk of inflammatory, metabolic, and immune diseases later in life. Data on gut microbiota changes in infants undergoing intestinal surgery requiring enterostomy are scarce. This prospective cohort study examined the enterostomy effluent of 29 infants who underwent intestinal surgery due to congenital malformations of the gastrointestinal tract, necrotizing enterocolitis, or spontaneous intestinal perforation. Initial effluent samples were collected immediately after surgery and final effluent samples were collected three weeks later. Gut microbiota composition was analysed using real-time PCR and 16S rRNA gene sequencing. Three weeks after surgery, an increase in total bacteria number (+21%, p = 0.026), a decrease in Staphylococcus (−21%, p = 0.002) and Candida spp. (−16%, p = 0.045), and an increase in Lactobacillus (+3%, p = 0.045) and in less abundant genera belonging to the Enterobacteriales family were found. An increase in alpha diversity (Shannon's and Simpson's indexes) and significant alterations in beta diversity were observed. A correlation of necrotizing enterocolitis with higher Staphylococcus abundance and higher alpha diversity was also observed. H2-blockers and/or proton pump inhibitor therapy were positively correlated with a higher total bacteria number. In conclusion, these results suggest that positive changes occur in the gut microbiota profile of infants three weeks after intestinal surgery. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) is still one of the leading causes of neonatal death. The present study reports the data from a French case–control prospective multicenter study. Methods: A total of 146 preterm neonates (PNs) with or without NEC were included. Bacterial 16S rRNA gene sequencing was performed on stool samples (n = 103). Specific culture media were used to isolate Escherichia coli, Clostridium butyricum, and Clostridium neonatale, and strains were phenotypically characterized. Results: The gut microbiota of PNs was dominated by Firmicutes and Proteobacteria, and five enterotypes were identified. The microbiota composition was similar between NEC cases and PN controls. However, differences were observed in the relative abundance of Lactobacillus genus, which was significantly lower in the NEC group, whereas that of the Clostridium cluster III was significantly higher (p < 0.05). Within enterotypes, several phylotypes were significantly more abundant in NEC cases (p < 0.05). Regarding perinatal factors, a statistical association was found between the gut microbiota and cesarean delivery and antifungal therapy. In NEC cases and PN controls, the carriage rates and virulence genes of uropathogenic E. coli were equivalent based on culture. No correlation was found between E. coli, C. butyricum, and C. neonatale carriages, beta-lactam resistance, and antibiotic treatment. Conclusions: At disease onset, our data support a microbiota dysbiosis between NEC and control infants at the genus level. In addition, it provides valuable information on bacterial antimicrobial susceptibility. [ABSTRACT FROM AUTHOR]

Inducible nitric oxide synthase (iNOS), regulated by nuclear factor kappa B (NF-κB), is crucial for intestinal inflammation and barrier injury in the progression of necrotizing enterocolitis (NEC). The NF-κB pathway is inhibited by S-glutathionylation of inhibitory κB kinase β (IKKβ), which can be restored by glutaredoxin-1 (Grx1). Thus, we aim to explore the role of Grx1 in experimental NEC. Wild-type (WT) and Grx1-knockout (Grx1−/−) mice were treated with an NEC-inducing regimen. Primary intestinal epithelial cells (IECs) were subjected to LPS treatment. The production of iNOS, NO, and inflammation injuries were assessed. NF-κB and involved signaling pathways were also explored. The severity of NEC was attenuated in Grx1−/− mice. Grx1 ablation promoted IKKβ glutathionylation, NF-κB inactivation, and decreased iNOS, NO, and O2·– production in NEC mice. Furthermore, Grx1 ablation restrained proinflammatory cytokines and cell apoptosis, ameliorated intestinal barrier damage, and promoted proliferation in NEC mice. Grx1 ablation protected NEC through iNOS and NO inhibition, which related to S-glutathionylation of IKKβ to inhibit NF-κB signaling. Grx1-related signaling pathways provide a new therapeutic target for NEC.

Introduction: In infants undergoing bowel resection, side-to-side stapled anastomosis (SSA) may restore intestinal continuity. We describe cases of abnormal symptomatic intestinal dilation secondary to SSA in patients with short bowel syndrome (SBS). Case presentation: Case 1 is an infant who underwent SSA for meconium ileus. He developed progressive malabsorption and was found to have a dilated segment of 9 by 8 cm at the prior SSA. This was narrowed into two lumens. He continues to gain weight appropriately.Case 2 is an infant with compartment syndrome resulting in partial colectomy and small bowel resection. Continuity was restored with SSA. On abdominal exploration years later for persistent abdominal pain, the area of prior SSA measured 14 by 9 cm and was narrowed into two lumens. He has excelled postoperatively.Case 3 and Case 4 are older patients referred after initial resection and SSAs as infants. Both had adequate intestinal length excluding their dilated areas and underwent resection with redo SSA as young adults. Both continue to do well.Case 5 is an ex-premature boy with neonatal necrotizing enterocolitis and two prior SSAs. He developed chronic pain and underwent resection of dilated intestine with redo SSA. This dilation recurred at the new SSA two years later. He then underwent division back into two lumens. He is now doing well. Conclusion: In patients undergoing bowel resection, SSA can cause abnormal dilatation requiring narrowing. Based on these outcomes, we caution against SSA in patients with anticipated SBS.

BackgroundCHPS dramatically affects infant growth and development and can even cause aspiration resulting from esophageal reflux. There is potential danger. CHPS is common, while CHPS with gas in the stomach wall and portal vein is rare. Gas in the stomach wall and portal vein are often the key features of more serious disease. It can be easily mistaken as a serious disease when patients with CHPS have gas in the stomach wall and portal vein.Case presentationA 56-day-old baby was hospitalized for aspiration pneumonia after vomiting without bile for 20 days. Compared with vomiting, which is the most common symptom, pneumonia tends to attract more attention. Because of pneumonia, a chest CT scan was performed and revealed massive gas accumulation in the walls of the esophagus, stomach, and portal vein. Therefore, NEC was considered first and was treated conservatively for one week. However, the vomiting continued, and CHPS was confirmed by ultrasound. The delay in CHPS diagnosis was due to insufficient recognition of the signs of gas accumulation. Because of inexperience and lack of knowledge about CHPS with gastrointestinal pneumatosis, physicians failed to make an early accurate diagnosis. Case 2 was a 29-day-old male who was admitted to the hospital with vomiting without bile. He was examined by ultrasound, which revealed gas in the stomach wall and portal vein after admission to the hospital. No peritonitis was found after a detailed and comprehensive physical examination. Emergency life-threatening diseases such as NEC were quickly ruled out. He received surgery as soon as possible and had an uneventful recovery with no complications.ConclusionCHPS may present with gas in the gastric or esophageal wall and portal vein, which is not a contraindication to surgery.

IntroductionDisruptions of the gut microbiota of preterm infants admitted to the neonatal intensive care unit (NICU) during the first 2 weeks of life are of critical importance. These infants are prone to various complications, including necrotizing enterocolitis (NEC) and sepsis. Studying the gut microbiota will improve outcomes in preterm infants. In the present study, we examined the gut microbiota of preterm infants admitted to the NICU in the first month of life.MethodsNeonates admitted to the NICU were recruited, and stool samples were collected weekly from the seventh day of the infant’s life until the 30th day of life. DNA was extracted using a DNeasy Powersoil DNA isolation kit. 16S rRNA gene sequencing targeting the V3–V4 region was performed using the MiSeq platform. Sequenced reads were processed on DADA2 pipeline to obtain an amplicon sequence variant (ASV) table. All bioinformatic and statistical analyses were performed using different packages in the R statistical framework.ResultsFourteen preterm infants were recruited, and 48 samples were collected. Alpha diversity metrics, observed ASV count, and Shannon index were found to have no differences in any clinical variables. Permutational multivariate analysis of variance (PERMANOVA) showed discrimination of neonates by gestational age and administration of probiotics. Differential abundance analysis showed a decreased abundance of Bifidobacterium Breve in extremely preterm infants (gestational age