Ectopic production of human chorionic gonadotrophin-like material by breast cancer

Human chorionic gonadotrophin (hCG) is a placental protein whose ectopic secretion by nontrophoblast tumors has been claimed to be of clinical relevance. Serum levels of hCG were measured in 570 patients with breast disease. A double-antibody radioimmunoassay (RIA) using antisera to hCG-beta was employed. Approximately 14% of patients with breast cancer were found to have elevated serum hCG levels. Such raised titers were not stage- or tumor-type-related, but occurred only in postmenopausal subjects. Further study showed that those patients with elevated hCG levels also had raised levels of human luteinizing hormone (hLH). Assay cross-reactivity was shown to account for the "spurious" hCG elevations. An immunocytochemical study also failed to find hCG an ectopic breast tumor constituent and/or product. It is concluded that hCG is not produced by breast tumors and has no clinical utility.     

Pediatric Multi-Organ Dysfunction Syndrome: Analysis by an Untargeted “Shotgun” Lipidomic Approach Reveals Low-Abundance Plasma Phospholipids and Dynamic Recovery over 8-Day Period,a Single-Center Observational Study

Lipids are molecules involved in metabolism and inflammation. This study investigates the plasma lipidome for markers of severity and nutritional status in critically ill children. Children with multi-organ dysfunction syndrome (MODS) (n = 24) are analyzed at three time-points and cross-referenced to sedation controls (n = 4) for a total of N = 28. Eight of the patients with MODS, needed veno-arterial extracorporeal membrane oxygenation (VA ECMO) support to survive. Blood plasma lipid profiles are quantified by nano-electrospray (nESI), direct infusion high resolution/accurate mass spectrometry (MS), and tandem mass spectrometry (MS/MS), and compared to nutritional profiles and pediatric logistic organ dysfunction (PELOD) scores. Our results show that PELOD scores were not significantly different between MODS and ECMO cases across time-points (p = 0.66). Lipid profiling provides stratification between sedation controls and all MODS patients for total lysophosphatidylserine (lysoPS) (p-value = 0.004), total phosphatidylserine (PS) (p-value = 0.015), and total ether-linked phosphatidylethanolamine (ether-PE) (p-value = 0.03) after adjusting for sex and age. Nutrition intake over time did not correlate with changes in lipid profiles, as measured by caloric and protein intake. Lipid measurement in the intensive care environment shows dynamic changes over an 8-day pediatric intensive care unit (PICU) course, suggesting novel metabolic indicators for defining critically ill children.     

Health-related quality of life,uncertainty and coping strategies in solid organ transplant recipients during shielding for the COVID-19 pandemic

Strict isolation of vulnerable individuals has been a strategy implemented by authorities to protect people from COVID-19. Our objective was to investigate health-related quality of life (HRQoL), uncertainty and coping behaviours in solid organ transplant (SOT) recipients during the COVID-19 pandemic. A cross-sectional survey of adult SOT recipients undergoing follow-up at our institution was performed. Perceived health status, uncertainty and coping strategies were assessed using the EQ-5D-5L, Short-form Mishel Uncertainty in Illness Scale (SF-MUIS) and Brief Cope, respectively. Interactions with COVID-19 risk perception, access to health care, demographic and clinical variables were assessed. The survey was completed by 826 of 3839 (21.5%) invited participants. Overall, low levels of uncertainty in illness were reported, and acceptance was the major coping strategy (92%). Coping by acceptance, feeling protected, self-perceived susceptibility to COVID-19 were associated with lower levels of uncertainty. Health status index scores were significantly lower for those with mental health illness, compromised access to health care, a perceived high risk of severe COVID-19 infection and higher levels of uncertainty. A history of mental health illness, risk perceptions, restricted healthcare access, uncertainty and coping strategies was associated with poorer HRQoL in SOT recipients during strict isolation. These findings may allow identification of strategies to improve HRQoL in SOT recipients during the pandemic.     

Variation in opioid utilization among neonates with gastroschisis

PurposeRepetitive painful stimuli and early exposure to opioids places neonates at risk for neurocognitive delays. We aimed to understand opioid utilization for neonates with gastroschisis.MethodsWe performed a retrospective review of infants with gastroschisis at a tertiary children's hospital (2017–2019). Multivariate linear regression was performed to analyze variations in opioid use.ResultsAmong 30 patients with gastroschisis, 33% were managed by primary suture-less closure, 7% by primary sutured closure, 40% by spring silo, and 20% by handsewn silo. The proportion of pain medication used was: morphine (89%), acetaminophen (8%), and fentanyl (3%). Opioids were used for a median of 6.5 days (range 0–20) per patient. Median total opioid administered across all patients was 2.2 morphine milligram equivalents (MME)/kg (IQR 0.7–3.3). Following definitive closure, median opioid use was 0.2 MME/kg (IQR 0.1–0.8). With multivariate regression, 45% of the variation in MME use was associated with the type of surgery after adjusting for weight, gestational age, and gender, p = 0.02. After definitive fascial closure, there was no significant variations in opioid use.ConclusionThere is a significant variation in the utilization of opioid, primarily prior to fascial closure. Understanding pain needs and standardization may improve opioid stewardship in infants with gastroschisis. 197/200Level of EvidenceLevel III     

Cryoanalgesia enhances recovery from minimally invasive repair of pectus excavatum resulting in reduced length of stay: A case-matched analysis of NSQIP-Pediatric patients

PurposePain control is challenging after minimally invasive repair of pectus excavatum (MIRPE). Cryoanalgesia, which temporarily ablates peripheral nerves, improves pain control and may accelerate post-operative recovery. We hypothesized that cryoanalgesia would be associated with shorter length of stay (LOS) in children undergoing MIRPE.MethodsA matched cohort study was conducted of children (<18 years) who underwent MIRPE 2016–2018, using the National Surgical Quality Improvement Program-Pediatric database. Each patient who received cryoanalgesia during MIRPE was matched to four controls (no cryoanalgesia). Univariate and multilevel regression analyses were performed.ResultsThirty-five patients who received cryoanalgesia during MIRPE were matched to 140 controls. Patients who received cryoanalgesia had a LOS reduction with similar secondary outcomes (operative time, rates of complication, reoperation, and readmission). On multilevel regression adjusted for matched groups, cryoanalgesia was associated with a 1.3-day reduction in LOS (95% CI ?1.8 to ?0.8, p < 0.001). On sensitivity analysis excluding patients with complications, cryoanalgesia remained associated with a LOS reduction.ConclusionsCryoanalgesia is a promising adjunct in the care of pediatric patients undergoing MIRPE. Utilization is associated with a shorter LOS without an increase in operative time or complications. Cryoanalgesia should be considered for inclusion in enhanced recovery strategies for patients undergoing MIRPE.     

Interactions of Haemophilus influenzae with cultured human endothelial cells

The interactions of capsulate (b+) and capsule-deficient (b-) Haemophilus influenzae type b with endothelial cells were studied in vitro using human umbilical vein endothelial cells (Huvecs). Association was determined by estimation of colony forming units (cfu) as well as the binding of 3H-thymidine-labelled bacteria. Bacteria associated with Huvecs rapidly and in a dose-dependent manner. The presence of capsule on bacteria resulted in a decrease in the rate of cell-association. Internationalisation of bacteria by Huvecs was quantitated after elimination of extracellular bacteria with gentamicin. It was found that larger numbers of b- bacteria were internalised compared to b+ bacteria. Incubation in the presence of metabolic inhibitors had little effect on the association of bacteria to Huvecs whereas internalisation was dependent on the integrity of host cellular functions. Electron microscopic studies confirmed phagocytic ingestion of both b+ and b- variants and suggested that the majority of the internalised bacteria remained viable within endothelial cell vacuoles. Haemophilus influenzae were translocated within vacuoles both from the apical to basal and the basal to apical direction.     

Human acetylator genotype: Relationship to colorectal cancer incidence and arylamine N-acetyltransferase expression in colon cytosol

Polymorphic expression of arylamine N-acetyltransferase (EC 2.3.1.5) may be a differential risk factor in metabolic activation of arylamine carcinogens and susceptibility to cancers related to arylamine exposures. Human epidemiological studies suggest that rapid acetylator phenotype may be associated with higher incidences of colorectal cancer. We used restriction fragment length polymorphism analysis to determine acetylator genotypes of 44 subjects with colorectal cancer and 28 non-cancer subjects of similar ethnic background (i.e., approximately 25% Black and 75% White). The polymorphic N-acetyltransferase gene (NAT2) was amplified by the polymerase chain reaction from DNA templates derived from human colons of colorectal and non-cancer subjects. No significant differences inNAT2 allelic frequencies (i.e., WT, M1, M2, M3 alleles) or in acetylator genotypes were found between the colorectal cancer and non-cancer groups. No significant differences inNAT2 allelic frequencies were observed between Whites and Blacks or between males and females. Cytosolic preparations from the human colons were tested for expression of arylamine N-acetyltransferase activity. Although N-acetyltransferase activity was expressed for each of the arylamines tested (i.e., p-aminobenzoic acid, 4-aminobiphenyl, 2-aminofluorene, -naphthylamine), no correlation was observed between acetylator genotype and expression of human colon arylamine N-acetyltransferase activity. Similarly, no correlation was observed between subject age and expression of human colon arylamine N-acetyltransferase activity. These results suggest that arylamine N-acetyltransferase activity expressed in human colon is catalyzed predominantly by NAT1, an arylamine N-acetyltransferase that is not regulated byNAT2 acetylator genotype. The ability to determine acetylator genotype from DNA derived from human surgical samples should facilitate further epidemiological studies to assess the role of acetylator genotype in various cancers.