Neonatal acuity tool-defined staffing ratios in a tertiary Australian neonatal intensive care unit.

AIMS: There is well-established data linking the adequacy of nurse staffing to patient outcomes. Evidence-based standards for staffing are therefore critical to drive improvements in clinical care. One such evidence-based approach is the use of patient acuity-based tools. The objective of this study is to determine the performance of a neonatal acuity tool in an Australian tertiary neonatal health-care setting, focusing on the classification of patient acuity and nursing:patient staffing ratios compared to current practice. METHODS: Acuity data were collected in a neonatal intensive care unit (NICU) and special care baby unit (SCBU) over a 10-week period in 2023. Patient data were scored in the 16 domains at two time points (prior to morning and evening nursing shift changeover) for all admitted newborns. RESULTS: For ventilated newborns nursed with a nurse:patient staffing ratio of 1:1, 78% of scores were within the L4-high acuity (score ≥ 26) band, with the remaining scores within the L3-high acuity (18-25) band. For newborns on non-invasive respiratory support in NICU staffed 1:1, the proportion scoring within the L4 acuity band was higher in the nasal high-flow group compared to the nasal continuous positive airway pressure group (P = 0.032), an effect not seen for those nursed 1:2 in NICU or for those on nasal high-flow nursed in SCBU either 1:2 or 1:3. CONCLUSION: This study of how a neonatal acuity classification system compares with current nurse:patient staffing allocations in an Australian tertiary NICU, suggests refinements in staffing ratios for specific patient groups on respiratory support are possible.

PKCζ activation promotes maturation of cord blood T cells towards a Th1 IFN-γ propensity.

A significant number of babies present transiently with low protein kinase C zeta (PKCζ) levels in cord blood T cells (CBTC), associated with reduced ability to transition from a neonatal Th2 to a mature Th1 cytokine bias, leading to a higher risk of developing allergic sensitisation, compared to neonates whose T cells have 'normal' PKCζ levels. However, the importance of PKCζ signalling in regulating their differentiation from a Th2 to a Th1 cytokine phenotype propensity remains undefined. To define the role of PKCζ signalling in the regulation of CBTC differentiation from a Th2 to a Th1cytokine phenotype we have developed a neonatal T cell maturation model which enables the cells to develop to CD45RA- /CD45RO+ T cells while maintaining the Th2 immature cytokine bias, despite having normal levels of PKCζ. The immature cells were treated with phytohaemagglutinin, but in addition with phorbol 12-myristate 13-acetate (PMA), an agonist which does not activate PKCζ. This was compared to development in CBTC in which the cells were transfected to express constitutively active PKCζ. The lack of PKCζ activation by PMA was monitored by western blot for phospho-PKCζ and translocation from cell cytosol to the membrane by confocal microscopy. The findings demonstrate that PMA fails to activate PKCζ in CBTC. The data show that CBTC matured under the influence of the PKC stimulator, PMA, maintain a Th2 cytokine bias, characterised by robust IL-4 and minimal interferon gamma production (IFN-γ), and lack of expression of transcriptional factor, T-bet. This was also reflected in the production of a range of other Th2/Th1 cytokines. Interestingly, introduction of a constitutively active PKCζ mutant into CBTC promoted development towards a Th1 profile with high IFN-γ production. The findings demonstrate that PKCζ signalling is essential for the immature neonatal T cells to transition from a Th2 to a Th1 cytokine production bias.

Red cell infusion but not saline is effective for volume expansion in preterm piglets.

BACKGROUND: A common first-line treatment for supporting cardiovascular function in preterm infants is volume expansion using saline, but this does not improve outcomes. This study aimed to determine if volume expansion with saline increases blood volume, blood pressure and cerebral oxygenation; and if volume expansion with packed red blood cells (RBC) is more effective. We hypothesized that RBC infusion is more effective than saline for increasing blood volume and maintaining cardiovascular function and cerebral oxygenation. METHODS: Five groups of preterm piglets (98/115d gestation) were infused with saline (10 or 20 mL/kg) or RBC (10 or 20 mL/kg) or no treatment. Blood volume, blood pressure, central venous pressure, heart rate, carotid flow, cerebral oxygenation, arterial pH, base excess, and lactate levels were assessed for 6 h after treatment started. RESULTS: Both RBC groups had significant increases in blood volume, and improved measures of cardiovascular function, cerebral oxygenation and metabolic acidosis. Saline infusion did not increase blood volume or measures of cardiovascular function, cerebral oxygenation or metabolic acidosis. CONCLUSIONS: The results suggest that the deteriorating cardiovascular function in the hours after birth in preterm piglets, and possibly in premature babies, may be reversed or halted by more effective support of blood volume. IMPACT: Blood volume decreases after birth in preterm piglets and this decrease is associated with deteriorating cardiovascular function and cerebral oxygenation. Infusion of saline does not increase blood volume nor prevent deterioration in cardiovascular function. Infusion of packed red blood cells results in an increase in blood volume and improvements in cardiovascular function and cerebral oxygenation. Deteriorating cardiovascular function in the hours after birth in preterm piglets, and possibly in human preterm neonates, may be reversed or halted by more effective support of blood volume.

The impact of maternal asthma on the fetal lung: Outcomes, mechanisms and interventions.

Maternal asthma affects up to 17% of pregnancies and is associated with adverse infant, childhood, and adult respiratory outcomes, including increased risks of neonatal respiratory distress syndrome, childhood wheeze and asthma. In addition to genetics, these poor outcomes are likely due to the mediating influence of maternal asthma on the in-utero environment, altering fetal lung and immune development and predisposing the offspring to later lung disease. Maternal asthma may impair glucocorticoid signalling in the fetus, a process critical for lung maturation, and increase fetal exposure to proinflammatory cytokines. Therefore, interventions to control maternal asthma, increase glucocorticoid signalling in the fetal lung, or Vitamin A, C, and D supplementation to improve alveologenesis and surfactant production may be beneficial for later lung function. This review highlights potential mechanisms underlying maternal asthma and offspring respiratory morbidities and describes how pregnancy interventions can promote optimal fetal lung development in babies of asthmatic mothers.

Intrahepatic cholestasis of pregnancy - Diagnosis and management: A consensus statement of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ): Executive summary.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy liver disease, characterised by pruritus and increased total serum bile acids (TSBA), Australian incidence 0.6-0.7%. ICP is diagnosed by non-fasting TSBA ≥19 µmol/L in a pregnant woman with pruritus without rash without a known pre-existing liver disorder. Peak TSBA ≥40 and ≥100 µmol/L identify severe and very severe disease respectively, associated with spontaneous preterm birth when severe, and with stillbirth, when very severe. Benefit-vs-risk for iatrogenic preterm birth in ICP remains uncertain. Ursodeoxycholic acid remains the best pharmacotherapy preterm, improving perinatal outcome and reducing pruritus, although it has not been shown to reduce stillbirth.

Molecular Farming of Pembrolizumab and Nivolumab.

Immune checkpoint inhibitors (ICIs) are a class of immunotherapy agents capable of alleviating the immunosuppressive effects exerted by tumorigenic cells. The programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint is one of the most ubiquitous checkpoints utilized by tumorigenic cells for immune evasion by inducing apoptosis and inhibiting the proliferation and cytokine production of T lymphocytes. Currently, the most frequently used ICIs targeting the PD-1/PD-L1 checkpoint include monoclonal antibodies (mAbs) pembrolizumab and nivolumab that bind to PD-1 on T lymphocytes and inhibit interaction with PD-L1 on tumorigenic cells. However, pembrolizumab and nivolumab are costly, and thus their accessibility is limited in low- and middle-income countries (LMICs). Therefore, it is essential to develop novel biomanufacturing platforms capable of reducing the cost of these two therapies. Molecular farming is one such platform utilizing plants for mAb production, and it has been demonstrated to be a rapid, low-cost, and scalable platform that can be potentially implemented in LMICs to diminish the exorbitant prices, ultimately leading to a significant reduction in cancer-related mortalities within these countries.

Testing the acceptability of stillbirth awareness messages in an SMS program for fathers.

ISSUE ADDRESSED: To raise expectant fathers' awareness of risk factors for stillbirth. METHODS: A set of brief text messages was developed addressing recognised risk factors for stillbirth: avoidance of maternal cigarette smoking, maternal going to sleep on side messaging, awareness of the importance of noticing and reporting changes in foetal movement and fathers' involvement in shared decision making for timing of birth. Eight messages were inserted into the SMS4dads pilot program being conducted by NSW Health. Feedback on the messages was requested. Participants rated the quality of the messages on a three-point Likert scale and provided comments. RESULTS: Overall, 2528 messages were sent to 626 fathers' mobile phones, 45% of fathers replied with 666 ratings and 115 comments evaluating the texts. The quantitative ratings indicated substantial overall approval of the messages. Within the coding category "Evaluation of Message Content," three themes described fathers' reactions and feelings about the smoking, movement, side sleeping and birth timing messages: "important-good information," "not appropriate/anxiety provoking" and "not relevant-obvious." Three themes reflecting the attributes of the messages within the "Service Quality" category were "need more information," "complements public health" and "child voice fit." CONCLUSIONS: Results indicate that the messages are an acceptable way to provide information and suggested actions addressing stillbirth risk factors to fathers-to-be. SO WHAT?: Fathers' awareness of the risk factors for stillbirth can assist mothers to take appropriate actions for a healthy birth. Information on risk factors can be provided to fathers via a father-focused text messaging service.

Parent concerns for child development following admission to neonatal intensive or special care: From birth to adolescence.

AIM: To describe the presence and nature of parent concerns regarding the development of their children admitted to Australian neonatal units (NNUs), comprising neonatal intensive care or special care. METHODS: In a cross-sectional survey, mothers and fathers provided information regarding concerns for their child's development. The self-administered survey was completed by two separate cohorts; (i) parents of child graduates from Australian NNUs (n = 381); (ii) parents of infant's inpatient in two South Australian NNUs (n = 209). Data were analysed using thematic analysis and descriptive statistics. RESULTS: Information was provided for 730 children. Developmental concern was reported for 39% of NNU graduates and 35% of inpatients. Children born very preterm (< 32 weeks' gestation) elicited greater parent concern than those born more mature (Cohort 1: 41% vs 36%; Cohort 2: 49% vs 22%), including in multiple developmental domains (Cohort 1: 17% vs 15%; Cohort 2: 28% vs 4%). Parents with inpatient infants were predominantly concerned about general development-milestones (19.1%) and the potential impact of medical or CNS issues (13.7%). Graduate parents commonly focused on specific domains, such as their child's speech-language (13.7%) and motor (12.9%) development. CONCLUSION: Neurodevelopment is a substantial source of concern for mothers and fathers during NNU admission and childhood, particularly for children born very preterm. However, in the first year of life, developmental concerns are poorly defined. This highlights the need for clinical education resources detailing infant developmental expectations and supportive strategies for parents of these high-risk infants.

Fertility preservation in female cancer sufferers: (only) a moral obligation?

PURPOSE: Advances in cancer diagnostics and therapeutics have thankfully led to high numbers of young cancer survivors, although some interventions may sometimes threaten fertility. The authors aimed to assess how evidence-based oncofertility counselling can be adequately fulfilled for the sake of female cancer patients, in light of its complexities and multidisciplinary nature, which require thorough counselling and consent pathways. MATERIALS AND METHODS: A search has been conducted in the databases PubMed/MEDLINE, Web of Science, Scopus, EMBASE and Google Scholar via search strings such as fertility preservation, reproductive counselling, oncofertility, cancer survivors, in order to identify relevant meaningful sources spanning the 2010-2021 period. RESULTS: Counselling needs to be implemented in compliance with international guidelines, so as to avoid medicolegal repercussions. Albeit fertility preservation is supported by most health care institutions, actual conditions at health care facilities often reflect several lingering difficulties in the oncofertility process. Oncofertility counselling should foster access to fertility preservation procedures. To best serve that purpose, it should be implemented in a manner consistent with ethical and legal standards, so that patients can make an informed decision based on comprehensive and relevant data. CONCLUSIONS: Counselling needs to be rooted in a close cooperation of oncologists, reproductive endocrinologists, mental health counsellors and clinical researchers. The provision of oncofertility services is grounded in the moral obligation to uphold individual autonomy, which is essential in a free society, unless the exercise thereof could pose a risk to the children conceived or to others.

A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial.

BACKGROUND: Severe early onset (less than 34 weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders. Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach. METHODS: We have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300 mg bd) with that of UDCA tablets (up to 2000 mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool. DISCUSSION: Our study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing "standard" UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial. TRIAL IDENTIFIERS: Australian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36. EudraCT number: 2018-004011-44. IRAS: 272398. NHMRC registration: APP1152418 and APP117853.

Kti12, a PSTK-like tRNA dependent ATPase essential for tRNA modification by Elongator.

Posttranscriptional RNA modifications occur in all domains of life. Modifications of anticodon bases are of particular importance for ribosomal decoding and proteome homeostasis. The Elongator complex modifies uridines in the wobble position and is highly conserved in eukaryotes. Despite recent insights into Elongator's architecture, the structure and function of its regulatory factor Kti12 have remained elusive. Here, we present the crystal structure of Kti12's nucleotide hydrolase domain trapped in a transition state of ATP hydrolysis. The structure reveals striking similarities to an O-phosphoseryl-tRNA kinase involved in the selenocysteine pathway. Both proteins employ similar mechanisms of tRNA binding and show tRNASec-dependent ATPase activity. In addition, we demonstrate that Kti12 binds directly to Elongator and that ATP hydrolysis is crucial for Elongator to maintain proper tRNA anticodon modification levels in vivo. In summary, our data reveal a hitherto uncharacterized link between two translational control pathways that regulate selenocysteine incorporation and affect ribosomal tRNA selection via specific tRNA modifications.

Feasibility and accuracy of cord blood sampling for admission laboratory investigations: A pilot trial.

AIM: Phlebotomy losses greatly contribute to anaemia following preterm birth. Therefore, the possibility of drawing initial tests from the placenta seems attractive. There is a lack of literature regarding the feasibility and accuracy of pathology tests taken from umbilical arterial and venous (UAB/UVB) compared to blood collected from the newborn. METHODS: UAB and UVB complete blood pictures were compared with the initial neonatal blood test. The relationship between UAB, UVB and neonatal complete blood picture values was determined by Spearman's Rho correlation with absolute values compared by Kruskal-Wallis. P < 0.05 was considered significant. RESULTS: Neonatal haemoglobin, white cell count, immature/total ratio and platelets were significantly correlated to the corresponding values in the UAB and UVB (all P < 0.001). While UAB and UVB haemoglobin and white cell count were similar, both were significantly lower than the neonatal values (P < 0.001 and P = 0.014, respectively). No difference was seen for immature/total ratio and platelet concentrations. UVB blood culture (BC) was feasible (90%), even with delayed cord clamping, and the UVB BC volume was significantly higher (P < 0.001), with a low rate of BC contamination (1.5%). CONCLUSIONS: Our findings support the feasibility and accuracy of umbilical blood in place of blood collected from the newborn. This reduces the phlebotomy losses and allows higher blood volume collection which may increase the sensitivity of BC collection.

An evidence-based cesarean section suggested for universal use.

OBJECTIVES: This article suggests a unified way to perform Cesarean sections. Even in the same departments, different modifications are in use. Therefore, one cannot rely on the early or late outcome of the procedure as long as all the surgical steps are not standardized. METHODS: The Misgav Ladach (Stark) Cesarean Section presented here is an evidence-based operation. Its basic principles are a modified Joel-Cohen abdominal incision, one-layer continuous suturing of the uterus using a big needle, leaving peritoneum open, closing fascia continuously and a few Donati skin sutures. RESULTS: This method has been subjected to scores of comparative studies with other methods in use, proving its advantages over them concerning duration, blood loss, febrile morbidity, need for analgesics, and costs. CONCLUSIONS: It is suggested that this method should be used as the standardized universal method which will enable comparison between obstetricians and institutions, and offer the parturient the best possible outcome.

Recurrent Instability after Arthroscopic Glenoid Labral Repair with a Minimum of Three Points of Fixation: Do the Number of Anchors or Fixation Points Correlate to Outcomes?

INTRODUCTION: The goal of this study was to evaluate the recurrence rate of instability following arthroscopic Bankart repairs in regard to the number and types of fixation utilized. A Bankart lesion is a tear in the anteroinferior capsulolabral complex within the shoulder, occurring in association with an anterior shoulder dislocation. These injuries can result in glenoid bone loss, decreased range of motion, and recurrent shoulder instability. Successful repair of these lesions has been reported in the literature with repair constructs that have three points of fixation. However, the definition of "one point of fixation" is yet to be fully elucidated. MATERIALS AND METHODS: A consecutive series of arthroscopically repaired Bankart lesions were evaluated pertaining to the points of fixation required to achieve shoulder stability. This included the number, position, and types of anchors used. Patients consented to complete a series of surveys at a minimum of two years postoperatively. The primary outcome was to determine recurrent instability via the UCLA Shoulder Score, the ROWE Shoulder Instability Score, and the Oxford Shoulder Score. A secondary outcome included pain on a Visual Analog Scale (VAS). RESULTS: There were 116 patients reviewed, 46 patients achieved three points of fixation in their surgical repair via two anchors and 70 patients achieved a similar fixation with three or more anchors. There was no significant difference in the mean age, gender, or body mass index (BMI). Patients receiving two anchors demonstrated recurrent instability 8.7% of the time (4 of 46 patients). Patients who received three or more anchors demonstrated recurrent instability 8.6% of the time (6 of 70 patients). Overall, there was no statistical significance between the number/types of anchors used. Between the two cohorts, there was no statistically significant difference found between VAS, ROWE, UCLA, and Oxford Scores. There was a significant difference in pain reported on the VAS scale with an average VAS score of 0.43 versus 2.5 in those without and with recurrent instability respectively. CONCLUSION: Contention still exists surrounding the exact definition of "a point of fixation" in arthroscopic Bankart repairs. Three-point constructs can be created through a variety of combinations including anchors and sutures, ultimately achieving the goal of a stable shoulder.

Characterization of the Transient Deficiency of PKC Isozyme Levels in Immature Cord Blood T Cells and Its Connection to Anti-Allergic Cytokine Profiles of the Matured Cells.

Cord blood T cells (CBTC) from a proportion of newborns express low/deficient levels of some protein kinase C (PKC) isozymes, with low levels of PKCζ correlating with increased risk of developing allergy and associated decrease in interferon-gamma (IFN-γ) producing T cells. Interestingly, these lower levels of PKCζ were increased/normalized by supplementing women during pregnancy with n-3 polyunsaturated fatty acids. However, at present, we have little understanding of the transient nature of the deficiency in the neonate and how PKCζ relates to other PKC isozymes and whether their levels influence maturation into IFN-γ producing T cells. There is also no information on PKCζ isozyme levels in the T cell subpopulations, CD4+ and CD8+ cells. These issues were addressed in the present study using a classical culture model of neonatal T cell maturation, initiated with phytohaemagglutinin (PHA) and recombinant human interleukin-2 (rhIL-2). Of the isozymes evaluated, PKCζ, ß2, δ, µ, ε, θ and λ/ι were low in CBTCs. The PKC isozyme deficiencies were also found in the CD4+ and CD8+ T cell subset levels of the PKC isozymes correlated between the two subpopulations. Examination of changes in the PKC isozymes in these deficient cells following addition of maturation signals showed a significant increase in expression within the first few hours for PKCζ, ß2 and µ, and 1-2 days for PKCδ, ε, θ and λ/ι. Only CBTC PKCζ isozyme levels correlated with cytokine production, with a positive correlation with IFN-γ, interleukin (IL)-2 and tumour necrosis factor-alpha (TNF), and a negative association with IL-9 and IL-10. The findings reinforce the specificity in using CBTC PKCζ levels as a biomarker for risk of allergy development and identify a period in which this can be potentially 'corrected' after birth.

Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants.

BACKGROUND: Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n-3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking. METHODS: We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen-saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first. RESULTS: A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P=0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P=0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P=0.06). CONCLUSIONS: Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk. (Funded by the Australian National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820 .).

The impact of maternal asthma during pregnancy on offspring retinal microvascular structure and its relationship to placental growth factor production in utero.

Asthma is a common chronic disease in pregnancy that affects placental function and fetal growth and associated with cardio-metabolic disorders in the offspring but the mechanisms are unknown. This study explored whether maternal asthma in pregnancy is associated with the development of offspring microvascular structure and whether it was related to biomarkers of angiogenesis in utero. Children aged 4 to 6 years, born to either asthmatic mothers (n = 38) or healthy controls (n = 25), had their retinal microvascular structure examined. Maternal plasma PlGF concentrations at 18 and 36 weeks' gestation were measured. There was a significant global difference in all retinal microvascular measures between children of asthmatic mothers relative to controls and increased retinal venular tortuosity in children born to asthmatic mothers (7.1 (95% CI 0.7-13.5); P = .031). A rise in plasma PlGF from 18 to 36 weeks' gestation was observed in the control population which was significantly lower in the asthma group by 190.9 pg/mL. PlGF concentrations were correlated with microvascular structure including arteriolar branching and venular tortuosity. These exploratory findings indicate that exposure to maternal asthma during pregnancy is associated with persistent changes in microvascular structure in childhood that may be driven by alterations to angiogenic mechanisms in utero.

Effect of repeat transfusion exposure on plasma cytokine and markers of endothelial activation in the extremely preterm neonate.

BACKGROUND: Very preterm newborns receive up to three to five red blood cell (RBC) transfusions, often early, after birth. Despite awareness of the association of transfusion with increases in cytokines and markers of endothelial activation, research has focused on single transfusions weeks after birth. With pathophysiologic processes contributing to the development of morbidities starting soon after delivery, we investigated the response to early, repeated transfusion exposure. STUDY DESIGN AND METHODS: Three consecutive transfusion exposures were studied in transfusion-naive infants less than 30 weeks' gestation (n = 46). Plasma cytokines and markers of endothelial activation were measured before and 2 to 4 hours after transfusion by multiplex enzyme-linked immunosorbent assay. RESULTS: The median (IQR) age was 3 (1-9) days at first transfusion, 7 (3-20) days at the second, and 18 (7-28) days at the third. Baseline concentrations did not differ between the three transfusions. Interleukin (IL)-17A and tumor necrosis factor (TNF)-α did not change after the first transfusion but increased after the second (P < .05) and third transfusions (P < .01). While IL-1ß, IL-6, and IL-8 concentrations did not differ after the first and second transfusions, all increased after the third (IL-1ß, P < .01; IL-6, P < .01; IL-8, P < .05). The magnitude of posttransfusion increase in IL-1ß, IL-17A, and TNF-α increased between the first and third transfusion exposure. CONCLUSION: Early, repeated transfusion results in alterations in proinflammatory cytokines and markers of endothelial activation in the very preterm newborn and suggests that the potential for transfusion-related immunomodulation is present in the initial days after birth rather than confined to later in the postnatal period.

Medicolegal Issues in Power Morcellation: Cautionary Rules for Gynecologists to Avoid Unfavorable Outcomes.

Power morcellation in laparoscopic surgery enables specialists to carry out minimally invasive procedures such as hysterectomies and myomectomies by cutting specimens into smaller pieces using a rotating blade and removing pieces through a laparoscope. Unexpected uterine sarcoma treated by surgery involving tumor disruption could be associated with poor prognosis. The current study aims to shed light on power morcellation from a medicolegal perspective: the procedure has resulted in adverse outcomes and litigation, and compensation for plaintiffs, as published in various journals cited in PubMed and MEDLINE, Cochrane Library, EMBASE, and GyneWeb. Considering the claims after the US Food and Drug Administration warnings on morcellation, the current study broadens the scope of research by including search engines, legal databases, and court filings (DeJure, Lexis Nexis, Justia, superior court of New Jersey, and US district court of Minnesota) between 1995 and 2019. Legal records show that courts determine professional responsibility regarding complications, making it essential to document adherence to safety protocols and specific guidelines, when available. Sound medical practices and clearly stated institute best practices result in better patient outcomes and are important when unfavorable clinical outcomes occur; adverse legal decisions can be avoided if there are grounds to prove professional conformity with specific guidelines and the unpredictability of an event.

Regional cluster of vanishing gastroschisis: A comparative study of antenatal and post-natal outcomes.

AIM: Vanishing gastroschisis describes the in utero spontaneous closure of the periumbilical defect. It is usually associated with intestinal loss due to ischaemia, necrosis and atresia. This comparative study aims to investigate the spectrum of pathology, antenatal ultrasound characteristics and post-natal outcomes. METHODS: Our tertiary centre provides antenatal and post-natal care of major congenital anomalies for a population of 1.6 million. Medical records were retrospectively evaluated for all cases of vanishing gastroschisis from May 2014 to May 2015. Cases of normal variant gastroschisis born during the same period were used for comparison. Maximum antenatael bowel diameter measurements were compared using the Mann-Whitney U-test. RESULTS: Six infants with vanishing gastroschisis were born during the study period, representing 50% of all live-born gastroschisis. Antenatal ultrasound showed progressively increasing intra-abdominal bowel dilatation, with antenatal intra-abdominal bowel diameter significantly greater in vanishing, than normal, variant gastroschisis (23.2 vs. 4.1 mm, P < 0.01). The classification of vanishing gastroschisis severity comprised two type I, three type II and one type III cases. Complete midgut atresia affected three infants, leading to overall mortality of 50% for the vanishing gastroschisis group versus 0% in the normal variant group (P = 0.05). CONCLUSION: Vanishing gastroschisis is a severe, often catastrophic variant of gastroschisis. Aetiological factors contributing to the recent high incidence of this rare complication in our population of newborns remain unknown, prompting secondary prevention strategies to salvage the midgut. We propose closer antenatal surveillance for fetuses with intra-abdominal bowel dilatation >10 mm to prompt consideration of earlier delivery to improve morbidity and mortality.