Clinical Characteristics and Management of Colorectal Vascular Malformation in Children: A Retrospective Study of 23 Cases.

INTRODUCTION: The objective of this study is to summarize the clinical characteristics and management of rare diseases of colorectal vascular malformation (CRVM) in children. METHODS: We retrospectively analyzed the clinical data of CRVM patients admitted to the Children's Hospital of Fudan University from 2004 to 2019. RESULTS: A total of 23 cases (16 males, 7 females) were enrolled. The median age of symptom onset was 1.4 years. Hematochezia and anemia were cardinal symptoms. Fourteen patients (60.9%) were misdiagnosed as anal fissures (n = 4), internal hemorrhoids (n = 3), rectal polyps (n = 2), inflammatory bowel disease (n = 2), portal hypertension (n = 2), and Meckel's diverticulum (n = 1), respectively. The average time from symptom onset to diagnosis was 4.5 ± 4.4 years. Other vascular malformations were detected in eight patients (34.8%). All patients showed a positive anomalous vascular image on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI). The sensitivity of colonoscopy in the diagnosis of CRVM was 82.6% (19/23). A total of 21 patients underwent a modified Soave procedure. The lesions were mostly restricted to the colorectum and showed transmural diffuse distribution, with an average length of 20 ± 5.4 cm. Two patients (9.5%) experienced surgical complications. Bloody stools reappeared in two patients (9.5%), and colonoscopy showed abnormal angiogenesis at the anastomotic site, which were cured by sclerotherapy and/or electrocautery. The median follow-up time was 78 months. Bloody stools were absent at the last time of follow-up, and hemoglobin was in the normal range for all patients. CONCLUSION: The identification of CRVM in children often is delayed. Colonoscopy, CT, and MRI are essential in making the correct diagnosis. The modified Soave procedure is safe and feasible to treat CRVM in children. Endoscopic sclerotherapy and/or electrocautery can be used for residual lesions.

Effect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia.

To investigate the mechanism of 25 hydroxyvitamin D (25(OH)D) deficiency in children with biliary atresia (BA) and its effect on liver fibrosis. The serum vitamin D and 25(OH)D, and expression of 25 hydroxylase (CYP2R1 and CYP27A1) in the liver of BA patients were detected and compared with those in the control group. We investigated the effect of differential expression of CYP2R1 in hepatocytes on the expression of genes related to liver fibrosis in primary hepatic stellate cells (HSCs) of BA and animal models of cholestasis. The ratio of 25(OH)D/vitamin D in the BA group was significantly lower than that in the control group. The mRNA and protein expression of CYP2R1 and CYP27A1 in liver tissue of the BA group was significantly lower than that in the control group. Exogenous active vitamin D (calcitriol) inhibited the proliferation and migration of primary HSCs isolated from BA patients, and reduced the expression of fibrosis-related genes in vitro. Downregulation of expression of CYP2R1 in hepatocytes increased expression of transforming growth factor (TGF)-ß1, collagen (Col)-1α1 and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased the expression of matrix metalloproteinase (MMP)-2 in cocultured primary HSCs of BA. Upregulation of expression of CYP2R1 in mice with bile duct ligation significantly increased the level of 25(OH)D, decreased the expression of TGF-ß1, Col-1α1 and TIMP-1, and increased the expression of MMP-2. Children with BA have impaired vitamin D activation due to CYP2R1 deficiency. The dysactivation of vitamin D can promote the proliferation and activation of HSCs and participate in the development of hepatic fibrosis in BA.

Effects of an individualized analgesia protocol on the need for medical interventions after adenotonsillectomy in children: a randomized controlled trial.

BACKGROUND: It has been proposed that the dose of rescue opioids should be individually titrated to the severity of obstructive sleep apnea after adenotonsillectomy. However, a sleep study is not always available before adenotonsillectomy. This randomized, controlled and blinded trial evaluated a strategy of pain control individualized to the results of a fentanyl test, rather than the results of polysomnography, in children after adenotonsillectomy. METHODS: A total of 280 children (3-10 years old) undergoing elective adenotonsillectomy were randomized into an individualized protocol (IP) group or a conservative protocol (CP) group. All patients received a fentanyl test before extubation. Pain was assessed every 10 min in the recovery room, and rescue morphine was given when the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) score was > 6. In the IP group, the dose of rescue morphine was individualized to the results of the fentanyl test (10 µg/kg in the case of a positive result and 50 µg/kg in the case of a negative result). In the CP group, the dose was fixed (25 µg/kg). The primary outcome was the percentage of patients requiring at least one medical intervention. The secondary outcome was the median duration of CHEOPS scores > 6. RESULTS: Fewer patients in the IP group than in the CP group required medical interventions [11.9% (16/134) vs 22.3% (29/130), P = 0.025]. The median duration of CHEOPS scores > 6 was shorter in the IP group than in the CP group [20 (95% CI: 17 to 23) min vs 30 (95% CI: 28 to 32) min, P <  0.001]. CONCLUSIONS: Compared with a conservative dosing approach, this individualized protocol may improve analgesia without a significant increase in respiratory adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT02990910 , registered on 13/12/2016.

The performance of a postinduction fentanyl test in identifying severe obstructive sleep apnea syndrome.

BACKGROUND: Children with severe obstructive sleep apnea syndrome (OSAS) are more sensitive to opioids. Identifying such children and reducing or even eliminating opioids are necessary but difficult. We have previously shown that patients sensitive to intraoperative fentanyl require less opioids postoperatively. AIM: The objective of this study was to evaluate the performance of a postinduction fentanyl test in identifying severe obstructive sleep apnea syndrome. METHODS: A prospective, observational, assessor-blinded study was carried out with 104 sleep study assessed children undergoing elective adenotonsillectomy. Intravenous fentanyl (1 µg/kg) was administered as a test in nonpremedicated, spontaneously breathing, sevoflurane-induced patients before endotracheal intubation. The respiratory rates before and after fentanyl administration were studied. The primary outcome was the sensitivity and specificity of the postinduction fentanyl test in identifying severe OSAS compared with polysomnography. RESULTS: A postinduction fentanyl test had a likelihood ratio of 7.2 (95% CI: 3.6-14.6) and an area under the curve value of 0.896 (95% CI: 0.821-0.947) to identify severe obstructive sleep apnea syndrome. The pragmatic cut-off value for the postinduction fentanyl test was found to be 50%. Using a reduction in respiratory rate of >50%, the postinduction fentanyl test detected severe OSAS with a sensitivity of 87%, a specificity of 88%, a positive predictive value of 85%, and a negative predictive value of 89%. CONCLUSION: Our study showed that a postinduction fentanyl test had good predictive value in identifying severe obstructive sleep apnea syndrome and early postoperative adverse respiratory events and could provide a reference for postoperative analgesia in children undergoing adenotonsillectomy.

Associations between Vitamin D and Liver Function and Liver Fibrosis in Patients with Biliary Atresia.

OBJECTIVES: To detail the effects of vitamin D (VD) deficiency and assess the relationships between VD deficiency and liver function and liver fibrosis in patients with biliary atresia (BA). METHODS: In this study, BA patients confirmed by intraoperative cholangiography were enrolled between January 2017 and February 2019. Preoperative serum 25-(OH)D level, liver function, serum biomarker levels of liver fibrosis, and histopathologic features were recorded. Deficiency, insufficiency, and sufficiency of VD were defined as serum 25-(OH)D concentrations of <10, 10-20, and >20 ng/ml, respectively. Associations between serum 25-(OH)D level and liver function and liver fibrosis were analyzed. RESULTS: A total of 161 BA infants were included. The median (interquartile range (IQR)) serum 25-(OH)D level in all patients was 7.56 (IQR: 4.48-11.40) ng/ml. The rates of 25-(OH)D deficiency, insufficiency, and sufficiency were 67.1% (108/161), 29.2% (47/161), and 3.7% (6/161), respectively. Serum 25-(OH)D level was negatively correlated with alkaline phosphatase (r = -0.232, P = 0.003). After adjusting for age, a decrease in serum 25-(OH)D level was correlated with the increase of the Batts-Ludwig stage score (odds ratio (OR): 0.94, 95% confidence interval (CI): 0.88-0.99; P = 0.028). Serum 25-(OH)D level was also correlated with the N-terminal propeptide of type III procollagen (PIIINP) (r = -0.246, P = 0.002). Additionally, PIIINP (P = 0.038) and ALP (P = 0.031) were independently associated with serum 25-(OH)D level. CONCLUSIONS: VD deficiency was common and inversely correlated with liver fibrosis in BA patients. Furthermore, VD was not correlated with liver function except alkaline phosphatase.

Association between fentanyl test results and rescue morphine requirements in children after adenotonsillectomy.

PURPOSE: Preoperative sleep study helps to predict post-adenotonsillectomy morphine requirements. However, in some institutions, many suspected children with obstructive sleep apnoea syndrome have an adenotonsillectomy without polysomnography assessments. This study investigated the relationship between the results of a fentanyl test performed before extubation and the postoperative morphine requirements in children after adenotonsillectomy. METHODS: Intravenous fentanyl (1 µg/kg) was given as a test before extubation when spontaneous ventilation was restored in 80 children aged 3-7 years who underwent adenotonsillectomy. The result was considered positive if the patient's respiratory rate decreased >50% after the test. In the recovery room, pain was assessed every 10 min using the Children's Hospital of Eastern Ontario Pain Scale. Rescue morphine (10 µg/kg) was given when the score was ≥6. RESULTS: The median [IQR (range)] cumulative morphine consumption rates for children with a positive result (n = 25) and a negative result (n = 52) were 30 (20, 40) and 50 (40, 50) µg/kg, respectively (P = 0.002). Eighty-eight percent of the positive-result patients and 48% of the negative-result patients were light consumers of morphine (cumulative dose <50 µg/kg) (P = 0.001). CONCLUSIONS: We conclude that children with a positive result after a fentanyl test require less morphine to achieve comfort than those with a negative result. CLINICALTRIALS. GOV ID: NCT02484222.

Effect of a mixture of iprobenfos and malathion on the development of malathion resistance in the mosquito Culex pipiens pallens Coq.

A malathion-resistant (RM) strain of Culex pipiens pallens Coq was obtained by successively selecting a field population with malathion in the laboratory. The synergistic effect of iprobenfos on malathion toxicity and alpha-naphthyl acetate (alpha-NA) esterase assay revealed that malathion resistance in the RM strain was associated with increased alpha-NA esterase activity and the synergism was mainly due to the inhibition by iprobenfos of this activity. There was no difference in alpha-NA esterase activity between the larvae and female adults in the susceptible (S) strain, but the activity in the adults was 13-fold higher than in the larvae of the RM strain. To understand the effect of the application of a mixture of iprobenfos and malathion on the evolution of malathion resistance, an artificial strain (Syn) was generated by mixing the RM and S strains with 0.1 frequency of the malathion-resistant individuals. The offspring of the Syn strain were divided into two sub-strains, Rm and Rm+ibp, which were successively treated with, respectively, malathion alone and malathion + iprobenfos (1:2) at LC70. In the mixture, the fungicide iprobenfos acted as a synergist of malathion. After treatment for 10 generations, the resistance level to malathion was 317.4-fold for the Rm sub-strain, whereas for the Rm+ibp sub-strain it was only 38.9-fold, compared with the Syn strain. Similar results were obtained by measurement of alpha-NA esterase activity from both larvae and female adults. The alpha-NA esterase activities in larvae and female adults at F10 generation were 2.6- and 10.9-fold from the Rm+ibp sub-strain and 5.7- and 98.5-fold from the Rm sub-strain, respectively, compared with the Syn strain. The above results suggested that iprobenfos, although it cannot completely stop or prevent the onset of malathion resistance, could dramatically delay its evolution.

CYP6B2 Expression in Insecticide-Resistant and -Suspcitible Strains of Helicoverpa armigera.

A fragment of CYP6B2 gene was obtained from the midgut cDNA library of the fifth instar larvae of the ballworm (Helicoverpa armigera) with RT-PCR. The product of 627 bp was cloned and sequenced. The results of dot blotting analysis of mRNA proved that CYP6B2 is expressed at higher level (mRNA) in an insecticide-resistant strain than in a susceptible strain, showing that the regulation was at transcription level. The mRNA is induced by pyrethroid in susceptible, but not in the insecticide-resistant strains. We guess that mutation in the 5' upstream regulator of the insecticide-resistant strain may lead to the difference in the expression level between resistant and susceptible strains.