Research Progress on the Etiology,Diagnosis and Treatment of Neonatal Necrotizing Enterocolitis

Necrotizing enterocolitis(NEC)is a leading cause of death from gastrointestinal disease in premature and low-birth-weight infants.Early detection of severely ischemic or necrotic bowel before perforation is rather difficult.New techniques including multi-omics contribute to better understanding its underlying mechanisms and discovering differe categories of biomarkers.Combination of clinical metrics such as seven components of metabolic derangement(CMD)may provide accurate assessment of its severity.Implementation of quality improvement initiatives including breast milk feeding actually lowers its incidence.

Efficacy of peritoneal drainage in very-low-birth-weight neonates with Bell’s stage II necrotizing enterocolitis:A single-center retrospective study

BACKGROUND Currently,pediatric surgeons are challenged by a lack of consensus on the optimal management strategy(conservative or surgical)for children with Bell’s stage II necrotizing enterocolitis(NEC).AIM To evaluate the clinical efficacy of peritoneal drainage in very-low-birth-weight(VLBW)neonates with modified Bell’s stage II NEC.METHODS This was a retrospective analysis of 102 NEC(modified Bell’s stage II)neonates born with VLBW who were treated at the Fujian Children’s Hospital(Fujian Branch of Shanghai Children’s Medical Center)between January 2017 and January 2020;these included 24 cases in the peritoneal drainage group,36 cases in the exploratory laparotomy group,and 42 cases in the conservative treatment group.RESULTS The general characteristics were comparable in the three groups(P>0.05).Compared with conservative treatment,peritoneal drainage was associated with significantly shorter fasting time,abdominal distension relief time,fecal occult blood(OB)negative conversion time,and reduced hospital length of stay(HLOS)(P<0.05 for all).Despite some advantages of peritoneal drainage over conservative treatment in terms of cure,conversion to laparotomy,intestinal perforation,intestinal stenosis,and abdominal abscess rates,the differences were not statistically significant(P>0.05).Compared to exploratory laparotomy,the fecal OB negative conversion time was significantly shorter in the peritoneal drainage group(P<0.05);similarly,the exploratory laparotomy group showed longer fasting time,abdominal distension relief time,HLOS,and higher complication rate compared to peritoneal drainage group,but the between-group differences were not statistically significant(P>0.05).CONCLUSION Peritoneal drainage,an easy-to-operate procedure,can improve the clinical symptoms of VLBW neonates with Bell’s stage II NEC and help reduce the HLOS.

Prevention of necrotizing enterocolitis in premature infants——an updated review

Necrotizing enterocolitis(NEC) is among the most common and devastating diseases encountered in premature infants, yet the true etiology continues to be poorly understood despite decades of research. Recently, gut bacterial dysbiosis has been proposed as a risk factor for the development of NEC. Based on this theory, several best clinical practices designed to reduce the risk of NEC have been proposed and/or implemented. This review summarizes the results of recent clinical trials and meta-analyses that support some of the existing clinical practices for reducing the risk of NEC in premature infants. It is evident that human milk feeding can reduce the incidence of NEC. While most of the studies demonstrated that probiotic supplementation can significantly reduce the incidence of NEC in premature infants, there are still some concerns regarding the quality, safety, optimal dosage, and treatment duration of probiotic preparations. Antibiotic prophylaxis does not reduce the incidence of NEC, and prolonged initial empirical use of antibiotics might in fact increase the risk of NEC for high-risk premature infants. Lastly, standardized feeding protocols are strongly recommended, both for prevention of postnatal growth restriction and NEC.

Application of prolonging small feeding volumes early in life to prevent of necrotizing enterocolitis in very low birth weight preterm infants

Objective:To study the effects of prolonging small feeding volumes early in life on the incidence of necrotizing enterocolitis(NEC)in very low birth weight(VLBW)preterm infants.Methods:A total of 128 VLBW infants who could not be breastfed were assigned into the experimental group(63 cases)and the control group(65 cases)using a random number table.The experiment group was fed 12 mL/(kg·d)on day 1 which was increased to 24 mL/(kg·d)for the first 10 study days.The control group was fed 12 mL/(kg·d)for the first 14e48 hours.Then,the feeding volume increased by 24-36 mL/(kg·d)up to 140e160 mL/(kg·d)and maintained until the 10th day after birth.The incidence of feeding intolerance and NEC,duration of hospitalization,time to full enteral feedings,incidence of intrahepatic cholestasis,and the levels of gastrin and motilin in serum were assessed.Results:The incidence of feeding intolerance was significantly lower in the experimental group compared with the control group(15.87% vs.33.84%).There was a significant reduction in the incidence of NEC between the experimental and control groups(7.9% vs.16% in the control group).Conclusion:A protocol that prolongs small feeding volumes early in life can reduce the incidence and severity of NEC,but still warrants further study.

New Frontiers of Necrotizing Enterocolitis: From Pathophysiology to Treatment

Necrotizing enterocolitis [NEC] is an inflammatory disease of intestine largely occuring in preterm infants with a wide range of damage from minimal injury limited to mucosa to extensive necrosis of bowel wall and perforation. Despite advancements in neonatal care, mortality remains high [30% - 50%] and controversy still persists with regards to the most appropriate management of neonates with necrotizing enterocolitis. The main factors thought to be involved in the pathogenesis of NEC are: relatively hyper-reactive state of premature intestine, enteral feeding and bacterial colonization. In this review, we discuss current knowledge about the epidemiology, pathophysiology, imaging, medical and surgical management of necrotizing enterocolitis and describe novel strategies for prevention and treatment.

Mucin 1 and interleukin-11 protein expression and inflammatory reactions in the intestinal mucosa of necrotizing enterocolitis children after surgery

BACKGROUND Necrotizing enterocolitis(NEC)of the newborn is a frequently occurring clinical disease in infants.The mortality rate of NEC in premature infants is as high as 50%,and the morbidity rate is on the rise.NEC has already caused serious impacts on newborn survival and poses serious threats to both children and families.AIM To investigate the expression and significance of mucin 1(MUC1)and interleukin-11(IL-11)in the intestinal mucosa of infants with neonatal NEC after surgery.METHODS Forty-eight postoperative intestinal mucosal specimens from children with NEC(NEC group)and twenty-two intestinal mucosal specimens from children with congenital intestinal atresia(control group)were collected in our hospital.Immunohistochemical staining and Western blot analysis were used to examine the protein expression of MUC-1 and IL-11 in the two groups.The serum levels of tumor necrosis factor-α(TNF-α)and IL-1βin the two groups were measured by enzyme-linked immunosorbent assay,and the relationship between MUC-1 and IL-11 protein expression and serum TNF-αand IL-1βlevels was analyzed by the linear correlation method.RESULTS The protein expression of MUC-1 and IL-11 in the NEC group was significantly lower than that in the control group,and the difference was statistically significant(P<0.05).The levels of serum TNF-αand IL-1βin the NEC group were significantly higher than those in the control group(P<0.05).The protein expression of MUC-1 and IL-11 in the NEC group negatively correlated with serum TNF-αand IL-1βlevels(P<0.05).There was a significant negative correlation between the protein expression of MUC-1 and IL-11 and the levels of serum TNF-αand IL-1βin the NEC group.CONCLUSION The protein expression of MUC1 and IL-11 in the intestinal mucosa of children with NEC is significantly downregulated after surgery.This downregulation may be involved in the pathogenesis of this disease and has a certain correlation with inflammatory response factors in children with NEC.

Neonatal necrotizing enterocolitis caused by umbilical arterial catheter-associated abdominal aortic embolism:A case report

BACKGROUND Reports of necrotizing enterocolitis(NEC)caused by umbilical arterial catheter(UAC)-associated abdominal aortic embolism in neonates are rare.Herein,we report the case of an extremely low birth weight(ELBW)infant with NEC caused by UAC-associated abdominal aortic embolism.CASE SUMMARY A female infant,aged 21 min and weighing 830 g at 28+6 wk of gestational age,was referred to our hospital because of premature birth and shallow breathing.The patient was diagnosed with ELBW,neonatal respiratory distress syndrome,neonatal intrauterine infection,and neonatal asphyxia.Umbilical arterial and venous catheters were inserted on the day after birth and were removed 9 d later,according to the doctor’s plan.Within 48 h after extubation,the patient’s manifestations included poor responsiveness,heart rate range of 175-185/min,and currant jelly stool.Therefore,we considered a diagnosis of NEC.To determine the cause,we used B-mode ultrasound,which revealed a partial abdominal aortic embolism(2 cm×0.3 cm)and abdominal effusion.The patient was treated with nil per os,gastrointestinal decompression,anti-infective therapy,blood transfusion,and low-molecular-weight heparin sodium q12h for anticoagulant therapy(from May 20 to June 1,the dosage of low-molecular-weight heparin sodium was adjusted according to the anti-Xa activity during treatment).On the 67th day after admission,the patient fully recovered and was discharged.CONCLUSION The abdominal aortic thrombosis in this patient was considered to be catheter related,which requires immediate treatment once diagnosed.The choice of treatment should be determined according to the location of the thrombus and the patient’s condition.

Intestinal microbiome changes in an infant with right atrial isomerism and recurrent necrotizing enterocolitis:A case report and review of literature

BACKGROUND Necrotizing enterocolitis(NEC)is a multifactorial disease that predominantly affects premature neonates.Intestinal dysbiosis plays a critical role in NEC pathogenesis in premature neonates.The main risk factor for NEC in term infants is mesenteric hypoperfusion associated with ductaldependent congenital heart disease(CHD)that eventually leads to intestinal ischemia.The incidence of NEC in neonates with critical CHD is 6.8%-13%.However,the role of the intestinal microbiome in NEC pathogenesis in infants with ductal-dependent CHD remains unclear.CASE SUMMARY A male term neonate with right atrial isomerism underwent modified Blalock-Taussig shunt placement on the 14^(th)day of life and had persistent mesenteric hypoperfusion after surgery.The patient had episodes of NEC stageⅡA on the 1^(st)and 28^(th)days after cardiac surgery.Fecal microbial composition was analyzed before and after cardiac surgery by sequencing region V4 of the 16S rRNA gene.Before surgery,species belonging to genera Veillonella and Clostridia and class Gammaproteobacteria were detected,Bifidobacteriaceae showed a low abundance.The first NEC episode was associated with postoperative hemodynamic instability,intestinal ischemiareperfusion injury during cardiopulmonary bypass,and a high abundance of Clostridium paraputrificum(Clostridium sensu stricto I)(56.1%).Antibacterial therapy after the first NEC episode resulted in increased abundance of Gammaproteobacteria,decreased abundance of Firmicutes,and low alpha diversity.These changes in the microbial composition promoted the growth of Clostridium sensu strictoⅠ(72.0%)before the second NEC episode.CONCLUSION A high abundance of Clostridium sensu strictoⅠand mesenteric hypoperfusion may have contributed to NEC in the present case.

Expression of SIRT1 signaling pathway in intestinal tissues of neonatal necrotizing enterocolitis

Objective:To analyze the expression of sirtuin type 1 (SIRT1) signal pathway in intestinal tissues of neonatal necrotizing enterocolitis (NEC), and to preliminarily explore the role of SIRT1 in the occurrence of NEC.Methods: From January 2017 to June 2017, the ileal tissues of 35 neonates with NEC underwent one-stage fistula treatment were selected as NEC group, and the ileal tissues of these 35 neonates underwent two-stage fistula treatment were selected as control group. The expression levels of SIRT1, transcription factor-nuclear factor (NF-κB), and SUMO specific protease 1 (SENP1) were detected by qRT-PCR;the expressions of SIRT1, NF-κB, and SENP1 were detected by immunohistochemistry and Western blotting (WB). Results: SIRT1 mRNA, protein positive expression rate, average optical density, and relative protein expression in intestinal tissues of children in NEC group were significantly lower than those in control group (P<0.05), however, the expression of NF-κB, the SENP1 mRNA and protein positive expression rates, the average optical density, and relative protein expression were significantly increased (P<0.05).Conclusion: SIRT1 is low expressed in intestinal tissues of children with NEC, the possible reason is that SIRT1 signaling pathway is suppressed and then NEC occurs.

Induction of Necrotizing Enterocolitis in Non-Premature Sprague-Dawley Rats and the Effect of Administering Breast Milk-Isolated <i>Lactobacillus salivarius</i>LPLM-O1

Due to an increasing incidence of necrotizing enterocolitis (NEC), as well as its associated mortality and long-term complications seen in surviving patients, the main focus of research in NEC has shifted to the prevention and treatment of the disease. The hypothesis of this work is that the strain Lactobacillus salivarius LPLM-O1 can decrease the intestinal injuries in a model of induced NEC. 26 newborn Sprague-Dawley pups were used in this study and randomized in three groups: control group (n = 6), which were fed with infant formula (Similac NeosureTM, Abbott);probiotic group (n = 10), which were fed with the same infant formula but fortified with 109 colony-forming units (CFU) of Lactobacillus salivarius LPLM-O1, and the NEC-induced group (n = 10). Each group was fed with 100 μl of food formula every three hours, using a modified syringe. The probiotic and NEC groups were exposed to asphyxia- and cold-induced stress to develop experimental NEC. At the end of the experiment (96 hrs), animals were sacrificed, and their small intestines were carefully removed and evaluated for typical signs of NEC, microbiological count and histological analyses. The histological analysis of the NEC-induced group showed transmural necrosis (grade 4);in the probiotic group, the grade was comparatively lower (grade 2). Survival ratewas higher in the probiotic group (83%) than in the NEC-induced group (46%);however, the difference in not statistically significant (p = 0.14). Lactic acid bacteria counts were higher in the probiotic group than in the NEC-induced group (8.4 × 108 and 6.1 × 107 CFU/intestine tissue gram, respectively). According to these results, the model of artificial induction of NEC was effectively establishedin all pups, and the probiotic strain slightly decreases the injuries’ grade in newborn pups.

Association between Supraventricular Tachycardia and Necrotizing Enterocolitis: A Case-Control Study

Background: Necrotizing enterocolitis (NEC) is the most common and fatal gastrointestinal disease encountered in the Neonatal Intensive Care Unit. Several case reports have shown an association between supraventricular tachycardia and necrotizing enterocolitis. This study aimed to determine the association between supraventricular tachycardia and necrotizing enterocolitis. Methods: This study was conducted from April 1st, 2016 to March 31st, 2022, at the Department of Pediatrics, Zhongnan Hospital of Wuhan University, Hubei, China. The records of 74 subjects with the diagnosis of necrotizing enterocolitis (NEC) were obtained from the hospital’s medical data records. Consequently, 74 gender, gestational age, and birth weight-matched controls (babies without NEC) were recruited as controls. Results: Of the 74 cases, 47.3% of the cases were males, and 52.7% were females. Regarding the birth weight and gestational age, 77% of the cases had low birth weight (LBW) and 86.5% were premature. In terms of Apgar score, 93.2% of NEC cases had an Apgar score of >7 at five minutes. The median values of white blood cells, platelets, and hemoglobin of cases were 10.90 (8.09, 13.80), 227 (169.75, 295.50), and 155.6 (130.53, 170.95), respectively. No Association between supraventricular tachycardia and necrotizing enterocolitis (P = 1.00). Conclusion: No association between necrotizing enterocolitis and supraventricular tachycardia was found. Further multicenter-based studies examining whether there is a potential relationship exists between supraventricular tachycardia and the development of necrotizing enterocolitis are required.

NLRP3 activation in macrophages promotes acute intestinal injury in neonatal necrotizing enterocolitis

Background Macrophages are involved in various immune inflammatory disease conditions.This study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis(NEC).Methods CD68,nucleotide-binding oligomerization domain,leucine-rich repeat,and pyrin domain-containing 3(NLRP3),cysteine aspartate-specific protease-1(caspase-1),and interleukin-1β(IL-1β)in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry,immunofluorescence,and western blot.Hypertonic pet milk,hypoxia and cold stimulation were used to establish a mouse(wild type and Nlrp3^(-/-))model of NEC.The mouse macrophage(RAW 264.7)and rat intestinal epithelial cell-6 lines were also cultured followed by various treatments.Macrophages,intestinal epithelial cell injuries,and IL-1β release were determined.Results Compared to the gut“healthy”patients,the intestinal lamina propria of NEC patients had high macrophage infiltration and high NLRP3,caspase-1,and IL-1β levels.Furthermore,in vivo,the survival rate of Nlrp3^(-/-)NEC mice was dramatically improved,the proportion of intestinal macrophages was reduced,and intestinal injury was decreased compared to those of wild-type NEC mice.NLRP3,caspase-1,and IL-1β derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell injuries.Conclusions Macrophage activation may be essential for NEC development.NLRP3/caspase-1/IL-1β cellular signals derived from macrophages may be the underlying mechanism of NEC development,and all these may be therapeutic targets for developing treatments for NEC.

Necrotizing enterocolitis: A multifactorial disease with no cure

Necrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature o the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Developmen of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics.

Role of LPS/CD14/TLR4-mediated inflammation in necrotizing enterocolitis:Pathogenesis and therapeutic implications

AIM:To establish the roles of lipopolysaccharide (LPS)/CD14/toll-like receptor 4 (TLR4)-mediated inflammation in a rat model of human necrotizing enterocolitis (NEC).METHODS: Six pairs of intestinal samples from human NEC were collected before and after recovery for histological and molecular analysis of inflammatory cytokines and signaling components. In the rat NEC model, we isolated 10-cm jejunum segments and divided them into six groups (n=6) for sham operation, treatment with LPS, bowel distension, combined bowel distension and LPS stimulation, and two therapeutic groups. The potential eff icacy of a recombinant CD18 peptide and a monoclonal CD14 antibody was evaluated in the latter two groups. The serum and tissue levels of several inflammatory mediators were quantified by real-time polymerase chain reaction, ELISA and immunoblotting.RESULTS: Human acute phase NEC tissues displayed significant increases (P<0.05) in levels of TLR4, CD14, myeloid differentiation protein (MD)-2, tumor necrosis factor (TNF)-α and nuclear factor-κB when compared to those after recovery. The histological and inflammatory picture of human NEC was reproduced in rats that were treated with combined bowel distension and LPS, but not in the sham-operated and other control rats. Serum levels of interleukin-6 and TNF-α were also elevated. The NEC pathology was attenuated by treating the NEC rats with a monoclonal CD14 antibody or an LPS-neutralizing peptide.CONCLUSION:LPS and distension are required to produce the histological and inflammatory features of NEC. A potential treatment option is blocking LPS activation and leukocyte infi ltration.

Exploration of pathogenic microorganism within the small intestine of necrotizing enterocolitis

Background Necrotizing enterocolitis(NEC)is the most common severe gastrointestinal emergency in neonates.We designed this study to identify the pathogenic microorganisms of NEC in the microbiota of the small intestine of neonates.Methods Using the 16S ribosomal DNA(rDNA)sequencing method,we compared and analyzed the structure and diversity of microbiotas in the intestinal feces of different groups of neonates:patients undergoing jejunostomy to treat NEC(NP group),neonates undergoing jejunostomy to treat other conditions(NN group),and neonates with NEC undergoing conservative treatment(NC group).We took intestinal feces and saliva samples from patients at different time points.Results The beta diversities of the NP,NN,and NC groups were all similar.When comparing the beta diversities between different time points in the NP group,we found similar beta diversities at time points El to E3 but significant differences between the E2-E3 and E4 time points:the abundances of Klebsiella and Enterococcus(Proteobacteria)were higher at the E1-E3 time points;the abundance of Escherichia-Shigella(Proteobacteria)increased at the E2 time point,and the abundance of Klebsiella decreased significantly,whereas that of Streptococcus increased significantly at the E4 time point.Conclusions Our results suggest that the pathological changes of intestinal necrosis in the small intestine of infants with NEC are not directly caused by excessive proliferation of pathogenic bacteria in the small intestine.The sources of microbiota in the small intestine of neonates,especially in premature infants,may be affected by multiple factors.

Early systemic anticoagulation reduces hospital readmission in acute necrotizing pancreatitis patients:A retrospective cohort study

Background:Early systemic anticoagulation(SAC)is a common practice in acute necrotizing pancreatitis(ANP),and its impact on in-hospital clinical outcomes had been assessed.However,whether it affects long-term outcomes is unknown.This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients.Methods:During January 2013 and December 2018,ANP patients admitted within 7 days from the onset of abdominal pain were screened.The primary outcome was 90-day readmission after discharge.Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission.Results:A total of 241 ANP patients were enrolled,of whom 143 received early SAC during their hospitalization and 98 did not.Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis(SVT)[risk ratio(RR)=0.40,95%CI:0.26-0.60,P<0.01]and lower 90-day readmission with an RR of 0.61(95%CI:0.41-0.91,P=0.02)than those who did not.For the quality of life,patients who received early SAC had a significantly higher score in the subscale of vitality(P=0.03)while the other subscales were all comparable between the two groups.Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57(95%CI:0.34-0.96,P=0.04).Mediation analysis showed that SVT mediated 37.0%of the early SAC-90-day readmission causality.Conclusions:The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients,and reduced SVT incidence might be the primary contributor.

Reconstruction of cervical necrotizing fasciitis defect with the modified keystone flap technique:Two case reports

BACKGROUND Cervical necrotizing fasciitis(CNF)is a rare,aggressive form of deep neck space infection with significant morbidity and mortality rates.Serial surgical debridement acts as the cornerstone of CNF treatment;however,it often results in defects requiring complex reconstructions.CASE SUMMARY We report two cases in which the keystone flap(KF)was used for CNF defect coverage:Case 1,an 85-year-old patient with CNF in the anterior neck,and Case 2,a 54-year-old patient with CNF in the posterior neck.Both patients received empirical intravenous antibiotic therapy and underwent serial debridement,enabling adequate wound preparation and stabilization.The final defect size measured 5.5 cm×12 cm in Case 1 and 6 cm×11 cm in Case 2.For defect coverage,we employed an 8 cm×19 cm type II KF based on perforators from the superior thyroid artery in Case 1 and a 9 cm×18 cm type II KF based on perforators from the transverse cervical artery in Case 2.Both flaps showed complete survival.No postoperative complications occurred in both cases,and favorable outcomes were observed at 7-and 6-month follow-ups in case 1 and 2,respectively.CONCLUSION We effectively treated CNF-associated defects using the KF technique;KF is viable for covering CNF defects in carefully selected cases.

Umbilical cord mesenchymal stem cell exosomes alleviate necrotizing enterocolitis in neonatal mice by regulating intestinal epithelial cells autophagy

BACKGROUND Necrotizing enterocolitis(NEC)is a severe gastrointestinal disease that affects premature infants.Although mounting evidence supports the therapeutic effect of exosomes on NEC,the underlying mechanisms remain unclear.AIM To investigate the mechanisms underlying the regulation of inflammatory response and intestinal barrier function by umbilical cord mesenchymal stem cell(UCMSCs)exosomes,as well as their potential in alleviating NEC in neonatal mice.METHODS NEC was induced in 5-d-old C57BL/6 pups through hypoxia and gavage feeding of formula containing lipopolysaccharide(LPS),after which the mice received human UCMSC exosomes(hUCMSC-exos).The control mice were allowed to breastfeed with their dams.Ileal tissues were collected from the mice and analyzed by histopathology and immunoblotting.Colon tissues were collected from NEC neonates and analyzed by immunofluorescence.Molecular biology and cell culture approaches were employed to study the related mechanisms in intestinal epithelial cells.RESULTS We found that autophagy is overactivated in intestinal epithelial cells during NEC,resulting in reduced expression of tight junction proteins and an increased inflammatory response.The ability of hUCMSC-exos to ameliorate NEC in a mouse model was dependent on decreased intestinal autophagy.We also showed that hUCMSC-exos alleviate the inflammatory response and increase migration ability in intestinal epithelial cells induced by LPS.CONCLUSION These results contribute to a better understanding of the protective mechanisms of hUCMSC-exos against NEC and provide a new theoretical and experimental foundation for NEC treatment.These findings also enhance our understanding of the role of the autophagy mechanism in NEC,offering potential avenues for identifying new therapeutic targets.

Suspected coexistence of perianal necrotizing sweet syndrome in chronic myelomonocytic leukemia:A case report

BACKGROUND Chronic myelomonocytic leukemia(CMML)complicated with Sweet syndrome(SS)is a rare hematological neoplasm.However,cases of concomitant development of perianal necrotizing SS(NSS)have not been reported.CASE SUMMARY We report a case of a 49-year-old male patient who underwent sequential procedures for hemorrhoids and perianal abscess.He developed postoperative incision infection and was referred to the department where the authors work.Initially,perianal necrotizing fasciitis secondary to incision infection after perianal abscess surgery was suspected.Despite receiving antibiotic therapy and undergoing surgical debridement,deeper necrotic areas formed in the patient’s perianal wounds,accompanied by persistent high fever.Blood and fungal cultures yielded negative results.The final diagnosis was corrected to be CMML with suspected concomitant perianal NSS.CONCLUSION CMML with perianal NSS is a rare condition,often misdiagnosed as perianal abscess or perianal necrotizing fasciitis.Conventional antibiotic therapy and surgical debridement are ineffective in managing this condition.

Development of necrotizing enterocolitis after blood transfusion in very premature neonates

Background Prior studies report conflicting evidence on the association between packed red blood cell(PRBC)transfu-sions and necrotizing enterocolitis(NEC),especially in early weeks of life where transfusions are frequent and spontaneous intestinal perforation can mimic NEC.The primary objective of this study was to evaluate the association between PRBC transfusions and NEC after day of life(DOL)14 in very premature neonates.Methods A retrospective cohort analysis of very premature neonates was conducted to investigate association between PRBC transfusions and NEC after DOL 14.Primary endpoints were PRBC transfusions after DOL 14 until the date of NEC diagnosis,discharge,or death.Wilcoxon ranked-sum and Fisher's exact tests,Cox proportional hazards regression,and Kaplan-Meier curves were used to analyze data.Results Of 549 premature neonates,186(34%)received transfusions after DOL 14 and nine(2%)developed NEC(median DOL=38;interquartile range=32-46).Of the nine with NEC after DOL 14,all were previously transfused(P<0.001);therefore,hazard of NEC could not be estimated.Post hoc analysis of patients from DOL 10 onward included five additional patients who developed NEC between DOL 10 and DOL 14,and the hazard of NEC increased by a factor of nearly six after PRBC transfusion(hazard ratio=5.76,95%confidence interval=1.02-32.7;P=0.048).Conclusions Transfusions were strongly associated with NEC after DOL 14.Prospective studies are needed to determine if restrictive transfusion practices can decrease incidence of NEC after DOL 14.