Clinical Predictors of Spontaneous Intestinal Perforation vs Necrotizing Enterocolitis in Extremely and Very Low Birth Weight Neonates.

PURPOSE: Spontaneous intestinal perforation (SIP) and necrotizing enterocolitis (NEC) are distinct disease processes associated with significant morbidity and mortality. Initial treatment, laparotomy (LP) versus peritoneal drainage (PD), is disease specific however it can be difficult to distinguish these diagnoses preoperatively. We investigated clinical characteristics associated with each diagnosis and constructed a scoring algorithm for accurate preoperative diagnosis. METHODS: A cohort of extreme and very low birth weight (<1500 g) neonates surgically treated for SIP or NEC between 07/2004-09/2022 were reviewed. Clinical characteristics included gestational age (GA), birth weight (BW), feeding history, physical exam, and laboratory/radiological findings. Intraoperative diagnosis was used to determine SIP vs NEC. Pre-drain diagnosis was used for patients treated with PD only. RESULTS: 338 neonates were managed for SIP (n = 269, 79.6%) vs NEC (n = 69, 20.4%). PD was definitive treatment in 146 (43.2%) patients and 75 (22.2%) patients were treated with upfront LP. Characteristics associated with SIP included younger GA, younger age at initial laparotomy or drainage (ALD), and history of trophic or no feeds. Multivariate logistic regression determined pneumatosis, abdominal wall erythema, higher ALD and history of feeds to be highly predictive of NEC. A 0-8-point scale was designed based on these characteristics with the area under the receiver operating characteristic curve of 0.819 (95% CI 0.756-0.882) for the diagnosis of NEC. A threshold score of 1.5 had a 95.2% specificity for NEC. CONCLUSION: Utilizing clinical characteristics associated with SIP & NEC we developed a scoring system designed to assist surgeons accurately distinguish SIP vs NEC in neonates. TYPE OF STUDY: Retrospective Chart Review. LEVEL OF EVIDENCE: Level III.

Comparison of preoperative and intraoperative surgeon diagnosis and pathologic findings in spontaneous intestinal perforation vs necrotizing enterocolitis.

OBJECTIVE: To investigate the accuracy of preoperative and intraoperative diagnosis via comparison to pathologic diagnosis in spontaneous intestinal perforation (SIP) vs. necrotizing enterocolitis (NEC). STUDY DESIGN: A retrospective review of neonates <1500 g treated for pneumoperitoneum between 07/2004-09/2022 was conducted. Patients treated for NEC medically prior to diagnosis and those treated with drain only were excluded. Fleiss' Kappa analysis assessed agreement between all three diagnoses: preoperative, intraoperative, and pathologic. RESULT: Overall, 125 patients were included with mean birthweight 834.2 g (SD:259.2) and mean gestational age 25.8 weeks (SD:2.2). Preoperative and intraoperative diagnoses agreed in 90.3%, intraoperative and pathologic agreed in 71.1%, and preoperative and pathologic agreed in 75.2% of patients. Fleiss' Kappa was 0.55 (95% CI:0.43,0.68), indicating moderate agreement between the three diagnoses. CONCLUSION: Our study shows moderate agreement between preoperative, intraoperative, and pathologic diagnoses. Further studies investigating the clinical characteristics of SIP and NEC are needed to improve diagnostic accuracy and management.

Incidence of Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease and Treatment with Defibrotide in Allogeneic Transplantation: A Multicenter Australasian Registry Study.

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is an established complication in patients undergoing allogeneic hemopoietic stem cell transplantation (HSCT). Defibrotide is an effective and safe pharmacologic option for treating diagnosed SOS/VOD. By exploring data provided to the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) by centers in Australia and New Zealand, this study aimed to describe the incidence of SOS/VOD and patterns of defibrotide use from 2016 to 2020. Patients who underwent allogeneic hemopoietic stem cell transplantation between 2016 and 2020 were identified from the ABMTRR. Data were extracted for a total of 3346 patients, 2692 from adult centers and 654 from pediatric centers, with a median follow-up of 21.5 months and 33.3 months, respectively. Descriptive statistics were used to describe the patient population, including the incidence of SOS/VOD and defibrotide use. Comparisons were made between patients without SOS/VOD and those with SOS/VOD, divided into defibrotide and no defibrotide cohorts. Associations with overall survival (OS) and day 100 survival with such variables as sex, age, disease at transplantation, stem cell source, conditioning agents, SOS/VOD diagnosis, and use of defibrotide, were determined. The reported incidence of SOS/VOD was 4.1% in adult centers and 11.5% in pediatric centers. Defibrotide was administered to 74.8% of adult patients and 97.3% of pediatric patients with SOS/VOD. Significant variability in the use, dosage, and duration of defibrotide was seen across the adult centers. The day 100 survival rate and median OS for patients managed with defibrotide was 51.8% and 103 days, respectively, for adult patients and 90.4% and not reached, respectively, for pediatric patients. In adults, older age at transplantation, an HLA-matched nonsibling relative donor, and a diagnosis of SOS/VOD treated with defibrotide were associated with reduced OS. In pediatric patients, the patient and transplantation characteristics associated with reduced OS were a diagnosis of SOS/VOD and a ≥2 HLA-mismatched related donor. A collaborative approach across Australasia to diagnosing and managing SOS/VOD, particularly with respect to consistent defibrotide use, is recommended.

An Analysis of the Sensitivity of the Activated Partial Thromboplastin Time (APTT) Assay, as Used in a Large Laboratory Network, to Coagulation Factor Deficiencies.

OBJECTIVES: To advance knowledge in using the ex vivo method to identify factor sensitivity of the activated partial thromboplastin time (APTT), using data from a hemophilia and reference hemostasis laboratory; to evaluate application of inclusion and exclusion criteria to eliminate data outliers; and to discuss outcomes with reference to comparable studies. METHODS: An ex vivo, retrospective analysis was performed on patient samples with conjointly ordered APTT and intrinsic pathway factors (VIII, IX, XI, XII) for application to a large network of laboratories. The relationship between factor levels and APTT, before and after application of exclusion criteria, is demonstrated. RESULTS: Curvilinear relationships were found between all factor levels and APTTs, which demonstrated both similarities and differences with available studies. Factor sensitivity data are presented. Study strengths include large sample size and use of real-world data. Limitations include inability to exclude all residual outliers and paucity of patient samples singularly deficient in factors other than FVIII. CONCLUSIONS: This ex vivo, retrospective analysis of the sensitivity of the APTT assay to intrinsic pathway factor deficiencies using real-world data from a hemophilia and reference hemostasis laboratory contains the largest sample size using this approach to date. The outcomes assist in informing practice in this area and can be used as a reference for further studies.

Effect of chronic treatment with riluzole on the nigrostriatal dopaminergic system in weaver mutant mice.

The effects of a chronic treatment with the anti-glutamate and sodium channel modulating neuroprotective agent riluzole on the degeneration of dopamine-containing neurons were studied in the brain of weaver mutant mice. In these animals, as in Parkinson's disease, dopaminergic neurons of the nigro-striatal pathway undergo spontaneous and progressive cell death. Homozygous weaver mice were orally treated twice a day with either 8 mg/kg riluzole or placebo for 2 months. Quantification of tyrosine-hydroxylase and dopamine-transporter axonal immunostaining in the striatum revealed that riluzole significantly increased the density of striatal dopaminergic nerve terminals. These results suggest that riluzole protects dopaminergic processes in the weaver mice and/or promotes their neuroplasticity.

Hepatic cytoprotection by nitric oxide and the cGMP pathway after ischaemia-reperfusion in the rat.

Many studies in diverse models suggest that nitric oxide (NO) may be protective against liver injury due to ischaemia-reperfusion (IR). We evaluated, in an experimental in vivo model of rat liver partial ischaemia, the effects of pretreatment by an NO donor (spermineNONOate, 5mg/kg), and exogenous cGMP (8Br-cGMP, 16 mg/kg) or an endogenous cGMP producer (ANP, 10 microg/kg), to assess their beneficial effects. After 6h of reperfusion, 8Br-cGMP completely prevented the adverse effect of Nomega-nitro-L-arginine (10mg/kg) and 8Br-cGMP alone showed a protective action on both hepatocytes (AST, -25%, LDH, -55%) and endothelial cells (plasma hyaluronic acid (HA), -30%). ANP caused a marked decrease in AST and LDH activities only after 1h of reperfusion (AST, -30%, LDH, -40%). Pretreatment with spermineNONOate prevented hepatocyte injury after 1 and 6h of reperfusion (AST, -22%, LDH, -27%). However, neither spermineNONOate nor ANP had any protective effect on endothelial cell damage. These results confirm the beneficial effect of an NO donor and strongly suggest the implication of a cGMP pathway that does not involve a blockade of inflammatory cytokines production (IL-6 generation was unaffected by 8Br-cGMP pre-treatment). In our model, 8Br-cGMP showed a greater protective effect than ANP or spermineNONOate and so might be used to prevent hepatic injury after IR. Finally, we propose a schematic representation of the different routes for the actions of NO in protecting the liver against IR damage.