Paediatric Adhesive Small Bowel Obstruction is Associated with a Substantial Economic Burden and High Frequency of Postoperative Complications.

BACKGROUND: Intra-abdominal adhesions can lead to adhesive small bowel obstruction (ASBO). The incidence of ASBO is higher in paediatric surgery than in adult surgery. However, ASBO related complications, economic burden and clear management guidelines in the treatment of ASBO are lacking. The aims of this study were to investigate underlying diagnoses, treatments, complications and costs in paediatric ASBO. METHOD: An observational retrospective study in children 0-15 years, hospitalised for ASBO during 2000-2020. Data were extracted from the medical records. Complications were classified based on Clavien Dindo Classification of Surgical Complications. Descriptive statistics were presented as median, continuous variables and categorical variables summarised with frequencies. Time to ASBO was presented as a Kaplan-Meier estimate. RESULTS: In total, 101 patients with 137 episodes of ASBO were included whereof 58.4% underwent first (index) surgery during the neonatal period. Median follow-up was 11.3 (0.6-19) years and median time to the first ASBO was 3.76 months (95%CI 2.23-12.02). The most common diagnoses at index surgery were necrotising enterocolitis, duodenal obstruction and primary ASBO. In 86.6% of the patients, first ASBO did not resolve with conservative treatment and a laparotomy was needed. Postoperative complications were found in 52%. Median cost for one episode of acute ASBO was 36 236 USD (1629-236 159). CONCLUSION: Neonatal surgery was the dominating cause of ASBO and surgical intervention the most common treatment with a high frequency of postoperative complications and significant healthcare costs. Future studies are needed to develop safe management guidelines for the treatment of paediatric ASBO. LEVELS OF EVIDENCE: III.

Clustering of antipsychotic-naïve patients with schizophrenia based on functional connectivity from resting-state electroencephalography.

Schizophrenia is associated with aberrations in the Default Mode Network (DMN), but the clinical implications remain unclear. We applied data-driven, unsupervised machine learning based on resting-state electroencephalography (rsEEG) functional connectivity within the DMN to cluster antipsychotic-naïve patients with first-episode schizophrenia. The identified clusters were investigated with respect to psychopathological profile and cognitive deficits. Thirty-seven antipsychotic-naïve, first-episode patients with schizophrenia (mean age 24.4 (5.4); 59.5% males) and 97 matched healthy controls (mean age 24.0 (5.1); 52.6% males) underwent assessments of rsEEG, psychopathology, and cognition. Source-localized, frequency-dependent functional connectivity was estimated using Phase Lag Index (PLI). The DMN-PLI was factorized for each frequency band using principal component analysis. Clusters of patients were identified using a Gaussian mixture model and neurocognitive and psychopathological profiles of identified clusters were explored. We identified two clusters of patients based on the theta band (4-8 Hz), and two clusters based on the beta band (12-30 Hz). Baseline psychopathology could predict theta clusters with an accuracy of 69.4% (p = 0.003), primarily driven by negative symptoms. Five a priori selected cognitive functions conjointly predicted the beta clusters with an accuracy of 63.6% (p = 0.034). The two beta clusters displayed higher and lower DMN connectivity, respectively, compared to healthy controls. In conclusion, the functional connectivity within the DMN provides a novel, data-driven means to stratify patients into clinically relevant clusters. The results support the notion of biological subgroups in schizophrenia and endorse the application of data-driven methods to recognize pathophysiological patterns at earliest stage of this syndrome.

Immuno-PET Monitoring of Lymphocytes Using the CD8-Specific Antibody REGN5054.

Assessment of immune-cell subsets within the tumor immune microenvironment is a powerful approach to better understand cancer immunotherapy responses. However, the use of biopsies to assess the tumor immune microenvironment poses challenges, including the potential for sampling error, restricted sampling over time, and inaccessibility of some tissues/organs, as well as the fact that single biopsy analyses do not reflect discordance across multiple intrapatient tumor lesions. Immuno-positron emission tomography (PET) presents a promising translational imaging approach to address the limitations and assess changes in the tumor microenvironment. We have developed 89Zr-DFO-REGN5054, a fully human CD8A-specific antibody conjugate, to assess CD8+ tumor-infiltrating lymphocytes (TIL) pre- and posttherapy. We used multiple assays, including in vitro T-cell activation, proliferation, and cytokine production, and in vivo viral clearance and CD8 receptor occupancy, to demonstrate that REGN5054 has minimal impact on T-cell activity. Preclinical immuno-PET studies demonstrated that 89Zr-DFO-REGN5054 specifically detected CD8+ T cells in lymphoid tissues of CD8-genetically humanized immunocompetent mice (VelociT mice) and discerned therapy-induced changes in CD8+ TILs in two models of response to a CD20xCD3 T-cell activating bispecific antibody (REGN1979, odronextamab). Toxicology studies in cynomolgus monkeys showed no overt toxicity, and immuno-PET imaging in cynomolgus monkeys demonstrated dose-dependent clearance and specific targeting to lymphoid tissues. This work supports the clinical investigation of 89Zr-DFO-REGN5054 to monitor T-cell responses in patients undergoing cancer immunotherapy.

Attention deficit hyperactivity disorder and educational level in adolescent and adult individuals after anesthesia and abdominal surgery during infancy.

AIM: Several studies in animal models have found that exposure to anesthetics in early life can cause cognitive dysfunction. Human studies show conflicting results and studies of cognitive function after anesthesia and neonatal surgery are scarce. The aim of this study was to investigate whether exposure to anesthesia and abdominal surgery during infancy was associated with cognitive dysfunction from the perspective of educational level, disposable income and attention deficit hyperactivity disorders (ADHD) in adolescent and adult individuals. METHODS: A cohort study with patients born 1976 to 2002 that underwent abdominal surgery during infancy at a pediatric surgical center were matched by age, sex, and gestational age to ten randomly selected individuals from the Swedish Medical Birth Register. Individuals with chromosomal aberrations were excluded. Data on highest level of education and annual disposable income were attained from Statistics Sweden and the diagnosis of ADHD were retrieved from the Swedish National Patient Register. RESULTS: 485 individuals and 4835 controls were included. Median gestational age was 38 weeks (24-44) and median age at surgery was seven days (0-365). Three hundred sixty-six individuals (70.0%) underwent surgery during the neonatal period (< 44 gestational weeks). Median operating time was 80 minutes (10-430). The mean age at follow-up was 28 years. Fisher's exact test for highest level of education for the exposed and unexposed groups were respectively: university 35% and 33%, upper secondary 44% and 47%, compulsory 21% and 20% (p = 0.6718). The median disposable income was 177.7 versus 180.9 TSEK respectively (p = 0.7532). Exposed individuals had a prevalence of ADHD of 5.2% and unexposed 4.4% (p = 0.4191). CONCLUSIONS: This study shows that exposure to anesthesia and abdominal surgery during infancy is not associated with cognitive dysfunction from the perspective of educational level, disposable income and ADHD in adolescent and adult individuals. Further studies in larger cohorts at earlier gestational ages are needed to verify these findings.

Improved Outcome of Intestinal Failure in Preterm Infants.

OBJECTIVE: The aim of the study was to evaluate the outcome and to identify predictors for survival and enteral autonomy in neonatal intestinal failure (IF). METHODS: A retrospective observational study in a Swedish tertiary centre of children born between 1995 and 2016 with neonatal IF, defined as dependency on parenteral nutrition (PN) ≥60 days, starting with PN before the age of 44 gestational weeks. Data were extracted from medical records and predictors for survival and enteral autonomy were identified by the Cox regression model. Time to death and weaning off PN analysis were performed with Kaplan-Meier curves including log rank test. RESULTS: In total, 105 children were included. Median gestational age was 28 weeks (22-42), 50% were born extremely preterm (<28 gestational weeks). PN started at a median age of 2 days (0-147) with a median duration of 196 days (60-3091). Necrotizing enterocolitis was the dominating cause of IF (61%). Overall survival was 88%, 5 children died of sepsis and 4 of intestinal failure-associated liver disease. Survival increased from 75% during 1995 to 2008 to 96% during 2009 to 2016 (P = 0.0040). Age-adjusted small bowel length of >50% and birth 2009 to 2016 were predictors for survival. Enteral autonomy was achieved in 87%, with positive prediction by small bowel length of >25% of expected for gestational age and remaining ileocecal valve. CONCLUSIONS: Preterm neonates with IF, at high risk of IF-associated morbidity, showed a high overall survival rate. Small-bowel length and being born 2009 to 2016 were predictors for survival and remaining ICV and small-bowel length were predictors for enteral autonomy.

Adhesive small bowel obstruction after appendectomy in children - Laparoscopic versus open approach.

BACKGROUND: The aims of this study were to compare the incidence of small bowel obstruction (SBO) requiring laparotomy after laparoscopic appendectomy (LA) and open appendectomy (OA) in children and to identify risk factors for SBO. METHODS: Medical records of patients who underwent appendectomy from 2000 to 2014 at our department of Pediatric Surgery were reviewed. Risk factors were analyzed using Cox proportional hazard regression. RESULTS: Totally 619 out of 840 patients were included. OA was performed in 474 (76.6%), LA in 130 patients (21%), and 15 (2.4%) were converted from LA to OA. Age, sex and proportion of perforated appendicitis were comparable in the LA and OA groups. Median follow-up time was 11.4 years (2.6-18.4). The incidence of SBO after LA was 1.5%, after OA 1.9% and in the converted group 6.7% (p = 0.3650). There were no significant differences in the incidence of postoperative intraabdominal abscess, wound infection or length of stay between LA and OA. Perforation and postoperative intra-abdominal abscess were identified as risk factors with 9.03 (p < 0.001) and 6.98 (p = 0.004) times higher risk of SBO, respectively. CONCLUSIONS: The risk for SBO after appendectomy in children was significantly related to perforated appendicitis and postoperative intra-abdominal abscess and not to the surgical approach. LEVEL OF EVIDENCE: Level III.

Polyvinylalcohol-carbazate (PVAC) reduces red blood cell hemolysis.

BACKGROUND AND OBJECTIVES: The objective of this study was to investigate whether a soluble polymer and aldehyde-scavenger, polyvinylalcohol-carbazate (PVAC), can inhibit hemolysis in the storage of red blood cells (RBC). STUDY DESIGN AND METHODS: The effect of PVAC was assessed over a wide range of concentrations, using absorption spectroscopy to evaluate the level of hemolysis. Moreover, osmotic stability and aldehyde-scavenging potential of RBC were assessed after storage in PVAC. RESULTS: After test tube storage for two weeks, red blood cell hemolysis was lower with PVAC compared to controls (mean difference 23%, 95% CI 16-29%, p < 0.001). A higher level of hemolysis led to a pronounced effect with PVAC. RBC stored in PVAC improved both the binding of free aldehydes (p <0.001) and the osmotic stability (p = 0.0036). CONCLUSION: Erythrocytes stored with PVAC showed less hemolysis, which might be explained by the ability of PVACs to stabilize the cell membrane and decrease oxidative injury.

Haemangiopericytoma presenting with acute intracerebral haemorrhage--a case report and literature review.

BACKGROUND: Intracranial haemangiopericytoma (HPC), a rare malignant tumour, should be distinguished from meningioma and solitary fibrous tumour, which have been considered as separate entities since 1993, according to histopathology and clinical characteristics. METHODS: A PUBMED search for "Intracranial Haemangiopericytoma" yielded 176 articles, where 26 were of particular interest for this review article. CASE REPORT: Our patient, a 27-year-old man with HPC of grade III according to WHO, presents with an acute intracerebral haematoma, which is extremely rare. RESULTS: Surgery (total resection) is the primary treatment. Long-term close clinical and radiological follow-up is crucial due to the high rate of recurrence and tendency for development of metastasis. DISCUSSION: The effects of postoperative radiotherapy need further investigation. Besides neurosurgery, radiotherapy should always be considered in both patients with these highly malignant tumours (WHO grade III) and in patients with partial resection or inoperable cases (WHO grade II).