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Abstract Background As a result of increased life expectancy and improved care for patients suffering from chronic disease, the number of patients with multimorbidity requiring surgical intervention is increasing. For complex surgical patients, it is essential to balance the potential benefits of surgical treatment against the risk of permanent loss of functional capacity and quality of life due to complications. European and US guidelines on perioperative care recommend preoperative multidisciplinary team (MDT) discussions for high-risk noncardiac surgical patients. However, the evidence underlying benefits from preoperative MDT meetings with all relevant perioperative specialties present is limited. The current study aims to investigate the effect of implementation of preoperative MDT discussions for high-risk patients undergoing noncardiac surgery on serious adverse events. Methods/design PREPARATION is a stepped-wedge cluster randomized trial in 14 Dutch hospitals without currently established preoperative MDT meeting. The intervention, preoperative MDT meetings, will be implemented sequentially with seven blocks of 2 hospitals switching from control (preoperative screening as usual) to the intervention every 3 months. Each hospital will be randomized to one of seven blocks. We aim to include 1200 patients. The primary outcome is the incidence of serious adverse events at 6 months. Secondary outcomes include (cost)effectiveness, functional outcome, and quality of life for up to 12 months. Discussion PREPARATION is the first study to assess the effectiveness of a preoperative MDT meeting for high-risk noncardiac surgical patients in the presence of an anesthesiologist. If the results suggest that preoperative MDT discussions for high-risk patients are (cost)-effective, the current study facilitates implementation of preoperative MDT meetings in clinical practice. Trial registration ClinicalTrials.gov NCT05703230. Registered on 11/09/2022.

Background: As a result of increased life expectancy and improved care for patients suffering from chronic disease, the number of patients with multimorbidity requiring surgical intervention is increasing. For complex surgical patients, it is essential to balance the potential benefits of surgical treatment against the risk of permanent loss of functional capacity and quality of life due to complications. European and US guidelines on perioperative care recommend preoperative multidisciplinary team (MDT) discussions for high-risk noncardiac surgical patients. However, the evidence underlying benefits from preoperative MDT meetings with all relevant perioperative specialties present is limited. The current study aims to investigate the effect of implementation of preoperative MDT discussions for high-risk patients undergoing noncardiac surgery on serious adverse events. Methods/design: PREPARATION is a stepped-wedge cluster randomized trial in 14 Dutch hospitals without currently established preoperative MDT meeting. The intervention, preoperative MDT meetings, will be implemented sequentially with seven blocks of 2 hospitals switching from control (preoperative screening as usual) to the intervention every 3 months. Each hospital will be randomized to one of seven blocks. We aim to include 1200 patients. The primary outcome is the incidence of serious adverse events at 6 months. Secondary outcomes include (cost)effectiveness, functional outcome, and quality of life for up to 12 months. Discussion: PREPARATION is the first study to assess the effectiveness of a preoperative MDT meeting for high-risk noncardiac surgical patients in the presence of an anesthesiologist. If the results suggest that preoperative MDT discussions for high-risk patients are (cost)-effective, the current study facilitates implementation of preoperative MDT meetings in clinical practice. Trial registration: ClinicalTrials.gov NCT05703230. Registered on 11/09/2022. [ABSTRACT FROM AUTHOR]

Context: In adults, cortisol levels show a pronounced 24-hour rhythm with a peak in the early morning. It is unknown at what age this early-morning peak in cortisol emerges during infancy, hampering the establishment of optimal dosing regimens for hydrocortisone replacement therapy in infants with an inborn form of adrenal insufficiency., Objective: We aimed to characterize daily variation in salivary cortisol concentration across the first year of life., Methods: We conducted a systematic review followed by an individual participant data meta-analysis of studies reporting on spontaneous (ie, not stress-induced) salivary cortisol concentrations in healthy infants aged 0-1 year. A one-stage approach using linear mixed-effects modeling was used to determine the interaction between age and time of day on cortisol concentrations., Results: Through the systematic review, 54 eligible publications were identified, reporting on 29 177 cortisol observations. Individual participant data were obtained from 15 study cohorts, combining 17 079 cortisol measurements from 1904 infants. The morning/evening cortisol ratio increased significantly from 1.7 (95% CI: 1.3-2.1) at birth to 3.7 (95% CI: 3.0-4.5) at 6 to 9 months (P < .0001). Cosinor analysis using all available data revealed the gradual emergence of a 24-hour rhythm during infancy., Conclusion: The early-morning peak in cortisol secretion gradually emerges from birth onwards to form a stable morning/evening ratio from age 6 to 9 months. This might have implications for hydrocortisone replacement therapy in infants with an inborn form of adrenal insufficiency., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Semaphorin 3A (Sema3A) is an axon guidance molecule, which is also abundant in the adult central nervous system (CNS), particularly in perineuronal nets (PNNs). PNNs are extracellular matrix structures that restrict plasticity. The cellular sources of Sema3A in PNNs are unknown. Most Sema3A-bearing neurons do not express Sema3A mRNA, suggesting that Sema3A may be released from other neurons. Another potential source of Sema3A is the choroid plexus. To identify sources of PNN-associated Sema3A, we focused on the cerebellar nuclei, which contain Sema3A + PNNs. Cerebellar nuclei neurons receive prominent input from Purkinje cells (PCs), which express high levels of Sema3A mRNA. By using a non-invasive viral vector approach, we overexpressed Cre in PCs, the choroid plexus, or throughout the CNS of Sema3A fl/fl mice. Knocking out Sema3A in PCs or the choroid plexus was not sufficient to decrease the amount of PNN-associated Sema3A. Alternatively, knocking out Sema3A throughout the CNS induced a decrease in PNN-associated Sema3A. However, motor deficits, microgliosis, and neurodegeneration were observed, which were due to Cre toxicity. Our study represents the first attempt to unravel cellular sources of PNN-associated Sema3A and shows that non-invasive viral-mediated Cre expression throughout the CNS could lead to toxicity, complicating the interpretation of Cre-mediated Sema3A knock-out.

Background: Preterm infants, especially those born small for gestational age (SGA), are at risk of short-term and long-term health complications. Characterization of changes in circulating proteins postnatally in preterm infants may provide valuable fundamental insights into this population. Here, we investigated postnatal developmental patterns in preterm infants and explored protein signatures that deviate between SGA infants and appropriate for gestational age (AGA) infants using a mass spectrometry (MS)-based proteomics workflow., Methods: Longitudinal serum samples obtained at postnatal days 0, 3, 7, 14, and 28 from 67 preterm infants were analyzed using unbiased MS-based proteomics., Results: 314 out of 833 quantified serum proteins change postnatally, including previously described age-related changes in immunoglobulins, hemoglobin subunits, and new developmental patterns, e.g. apolipoproteins (APOA4) and terminal complement cascade (C9) proteins. Limited differences between SGA and AGA infants were found at birth while longitudinal monitoring revealed 69 deviating proteins, including insulin-sensitizing hormone adiponectin, platelet proteins, and 24 proteins with an annotated function in the immune response., Conclusions: This study shows the potential of MS-based serum profiling in defining circulating protein trajectories in the preterm infant population and its ability to identify longitudinal alterations in protein levels associated with SGA., Impact: Postnatal changes of circulating proteins in preterm infants have not fully been elucidated but may contribute to development of health complications. Mass spectrometry-based analysis is an attractive approach to study circulating proteins in preterm infants with limited material. Longitudinal plasma profiling reveals postnatal developmental-related patterns in preterm infants (314/833 proteins) including previously described changes, but also previously unreported proteins. Longitudinal monitoring revealed an immune response signature between SGA and AGA infants. This study highlights the importance of taking postnatal changes into account for translational studies in preterm infants., (© 2024. The Author(s).)

Objective: To investigate colony-forming unit (CFU) reduction on contaminated flexible endoscopes (FEs) without a working channel after UV-C light disinfection, compared to the current disinfection method with the endoscope washer disinfector (EWD)., Design, Setting and Participants: After pharyngolaryngoscopy, a manual pre-cleaning with tap water was performed. A culture was then collected by rolling the distal 8-10 cm of the FE over an Agar plate. The FE was disinfected using the D60 (60-s disinfection process with UV-C light) or the EWD (gold standard reprocessing process with water and chemicals). Another culture was then taken. After incubation, a CFU count was performed., Results: A total of 200 FEs without a working channel were divided equally between the two disinfection groups. After clinical use and manual pre-cleaning, 84 of the 100 (84.0%) (UV-C light group) and 79 of the 100 (79.0%) (EWD) FEs were contaminated with at least 1 CFU. FEs that showed no contamination after use were excluded from further analysis. After disinfection with UV-C light, 72 (85.7%) FEs showed no contamination (i.e., 0 CFUs) versus 66 (83.5%) FEs after reprocessing with the EWD., Conclusion: There is no difference in CFUs reduction on contaminated FEs without a working channel between UV-C light disinfection and the current gold standard, the EWD., (© 2023 The Authors. Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Background: Systemic inflammation plays a key role in the development of bronchopulmonary dysplasia (BPD). Cortisol is known to dampen inflammation. However, adrenal function following preterm birth is characterized by insufficient cortisol levels for the degree of inflammation, and a relative abundancy of cortisol precursors. We investigated whether this pattern could contribute to the development of BPD in preterm infants born <30 weeks of gestation., Methods: Cortisol, cortisone, 17-OH progesterone (17-OHP) and 11-deoxycortisol were measured in serum obtained at postnatal days 1, 3, 7, 14 and 28, using liquid-chromatography-tandem-mass-spectrometry. The presence of BPD was ascertained at 36 weeks postmenstrual age., Results: Sixty-five infants were included for analysis, of whom 32 (49%) developed BPD. Preterm infants developing BPD, as compared to those without BPD, had higher levels of 17-OHP, 11-deoxycortisol and cortisone relative to cortisol in their first week of life, but not at birth or beyond day 7., Conclusion: Preterm infants developing BPD had higher levels of cortisol precursors and cortisone relative to cortisol in their first week of life than infants without BPD. These findings suggest that BPD is preceded by an activated hypothalamus-pituitary-adrenal axis that could not meet the high cortisol demands, which may predispose to inflammation and BPD., Impact: Relative adrenal insufficiency is common in the first weeks after preterm birth, resulting in insufficient cortisol production for the degree of inflammation and a relative abundance of cortisol precursors; Whether this pattern contributes to the development of bronchopulmonary dysplasia (BPD) is not fully elucidated, since most studies focused on cortisol levels; Preterm infants developing BPD had higher levels of cortisol precursors and cortisone relative to cortisol in the first week of life, suggestive of a hypothalamus-pituitary-adrenal-axis activation during BPD development which cannot meet the high cortisol demands in tissues; This glucocorticoid pattern is likely to dispose to inflammation and BPD., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: To review systematically and assess the accuracy of prediction models for bronchopulmonary dysplasia (BPD) at 36 weeks of postmenstrual age., Study Design: Searches were conducted in MEDLINE and EMBASE. Studies published between 1990 and 2022 were included if they developed or validated a prediction model for BPD or the combined outcome death/BPD at 36 weeks in the first 14 days of life in infants born preterm. Data were extracted independently by 2 authors following the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (ie, CHARMS) and PRISMA guidelines. Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool (ie, PROBAST)., Results: Sixty-five studies were reviewed, including 158 development and 108 externally validated models. Median c-statistic of 0.84 (range 0.43-1.00) was reported at model development, and 0.77 (range 0.41-0.97) at external validation. All models were rated at high risk of bias, due to limitations in the analysis part. Meta-analysis of the validated models revealed increased c-statistics after the first week of life for both the BPD and death/BPD outcome., Conclusions: Although BPD prediction models perform satisfactorily, they were all at high risk of bias. Methodologic improvement and complete reporting are needed before they can be considered for use in clinical practice. Future research should aim to validate and update existing models., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Neurofilament light (NfL) has been identified as a biomarker for neuroaxonal damage in preterm infants, but its relation with bronchopulmonary dysplasia (BPD) has not been established. We hypothesized that BPD is associated with increased NfL levels at an early stage, indicative of early neuroaxonal damage., Methods: We included preterm infants born <30 weeks of gestation for assessment of NfL levels from cord blood and blood obtained at postnatal days 3, 7, 14, and 28. We used linear regression analysis to compare NfL levels between infants with moderate/severe BPD and infants with no/mild BPD, and linear mixed model analysis to compare the effect of time on NfL levels between groups., Results: Sixty-seven infants with a gestational age (GA) of 27 ± 1.3 weeks were included for analysis, of whom 19 (28%) developed moderate/severe BPD. Although NfL levels were higher at every time point in infants with BPD, statistical significance was lost after adjustment for GA, small for gestational age (SGA) and intraventricular hemorrhage (IVH). Groups did not differ in NfL change over time., Conclusions: The positive association between BPD and NfL in the first weeks of life could be explained by GA, SGA and IVH rather than by development of BPD., Impact: Neurofilament light chain (NfL) is a known biomarker for neuroaxonal damage. Biomarkers for brain damage during the first weeks of life in preterm infants developing BPD are lacking. NfL levels obtained during the first weeks of life did not differ between infants with and without BPD in analyses adjusted for GA, SGA, and IVH., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective(s): To investigate the predictive performances of exhaled breath volatile organic compounds (VOCs) for development of bronchopulmonary dysplasia (BPD) in infants born preterm., Methods: Exhaled breath was collected from infants born <30 weeks' gestation at days 3 and 7 of life. Ion fragments detected by gas chromatography-mass spectrometry analysis were used to derive and internally validate a VOC prediction model for moderate or severe BPD at 36 weeks of postmenstrual age. We tested the predictive performance of the National Institute of Child Health and Human Development (NICHD) clinical BPD prediction model with and without VOCs., Results: Breath samples were collected from 117 infants (mean gestation 26.8 ± 1.5 weeks). Thirty-three percent of the infants developed moderate or severe BPD. The VOC model showed a c-statistic of 0.89 (95% CI 0.80-0.97) and 0.92 (95% CI 0.84-0.99) for the prediction of BPD at days 3 and 7, respectively. Adding the VOCs to the clinical prediction model in noninvasively supported infants resulted in significant improvement in discriminative power on both days (day 3: c-statistic 0.83 vs 0.92, P value .04; day 7: c-statistic 0.82 vs 0.94, P value .03)., Conclusions: This study showed that VOC profiles in exhaled breath of preterm infants on noninvasive support in the first week of life differ between those developing and not developing BPD. Adding VOCs to a clinical prediction model significantly improved its discriminative performance., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The most abundant immunoglobulin present in the human body is IgA. It has the highest concentrations at the mucosal lining and in biofluids such as milk and is the second most abundant class of antibodies in serum. We assessed the structural diversity and clonal repertoire of IgA1-containing molecular assemblies longitudinally in human serum and milk from three donors using a mass spectrometry-based approach. IgA-containing molecules purified from serum or milk were assessed by the release and subsequent analysis of their Fab fragments. Our data revealed that serum IgA1 consists of two distinct structural populations, namely monomeric IgA1 (∼80%) and dimeric joining (J-) chain coupled IgA1 (∼20%). Also, we confirmed that IgA1 in milk is present solely as secretory (S)IgA, consisting of two (∼50%), three (∼33%) or four (∼17%) IgA1 molecules assembled with a J-chain and secretory component (SC). Interestingly, the serum and milk IgA1-Fab repertoires were distinct between monomeric, and J-chain coupled dimeric IgA1. The serum dimeric J-chain coupled IgA1 repertoire contained several abundant clones also observed in the milk IgA1 repertoire. The latter repertoire had little to no overlap with the serum monomeric IgA1 repertoire. This suggests that human IgA1s have (at least) two distinct origins; one of these produces dimeric J-chain coupled IgA1 molecules, shared in human serum and milk, and another produces monomeric IgA1 ending up exclusively in serum., (© 2022. The Author(s).)

Human milk is important for antimicrobial defense in infants and has well demonstrated antiviral activity. We evaluated the protective ability of human milk against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a human fetal intestinal cell culture model. We found that, in this model, human milk blocks SARS-CoV-2 replication, irrespective of the presence of SARS-CoV-2 spike-specific antibodies. Complete inhibition of both enveloped Middle East respiratory syndrome coronavirus and human respiratory syncytial virus infections was also observed, whereas no inhibition of non-enveloped enterovirus A71 infection was seen. Transcriptome analysis after 24 h of the intestinal monolayers treated with human milk showed large transcriptomic changes from human milk treatment, and subsequent analysis suggested that &lt;i&gt;ATP1A1&lt;/i&gt; down-regulation by milk might be of importance. Inhibition of ATP1A1 blocked SARS-CoV-2 infection in our intestinal model, whereas no effect on EV-A71 infection was seen. Our data indicate that human milk has potent antiviral activity against particular (enveloped) viruses by potentially blocking the ATP1A1-mediated endocytic process., (© 2022 Aknouch et al.)

Background: It has been demonstrated that human milk from mothers who have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains antibodies against the virus, which could play an important role in protecting the recipient infant against coronavirus disease 2019 (COVID-19). Seroconversion is measured frequently around the world, but the milk conversion rate is unknown., Research Aims: To determine (1) the prevalence and (2) the dynamics of immunoglobulin A (IgA) antibodies against SARS-CoV-2 in human milk amongst lactating mothers in the Netherlands., Methods: In this large prospective cohort study, lactating mothers ( N = 2312) were included between October 12, 2020 and February 24, 2021. Enzyme-linked immunosorbent assay was used to determine levels of IgA antibodies in human milk and immunoglobulin G (IgG) antibodies in serum against the ectodomain of the SARS-CoV-2 spike protein., Results: A total of 691 (30.6%) participants had SARS-CoV-2 specific antibodies in human milk and/or serum. Of these participants, 524 (23.1%) had IgA antibodies against SARS-CoV-2 in human milk, and 356 (15.7%) had IgG antibodies against SARS-CoV-2 in serum. A total of 199 (8.8%) participants had antibodies in both human milk and serum. SARS-CoV-2 specific IgA antibodies in human milk remain present at least 10 months after a polymerase chain reaction confirmed infection., Conclusion: The prevalence of IgA antibodies against SARS-CoV-2 in human milk was 23.1% in our cohort. This high prevalence of antibodies in human milk might lead to passive immunity in many breastfed infants and may serve as protection against COVID-19.

Studies in preterm infants have shown an association between late-onset sepsis (LOS) and the development of bronchopulmonary dysplasia (BPD). It is unknown whether clinical or biochemical characteristics during sepsis modulate the risk for BPD. This single-center retrospective cohort study included all patients with a gestational age < 30 weeks, born between 2009 and 2015, in whom empiric antimicrobial treatment was initiated > 72 h after birth and continued for at least 5 days, independent on microbiological results. The association between clinical and biochemical characteristics of LOS and the development of BPD in survivors were assessed with multivariate logistic regression analysis adjusted for early-onset sepsis, small for gestational age, and gestational age. Of the 756 admitted infants, 256 infants (mean GA: 27.0 weeks; birthweight: 924 grams) had at least one LOS episode, of whom 79 (30.9%) developed BPD. Analyses showed that only the need for and duration of mechanical ventilation during LOS were independently associated with an increased risk for BPD (adjusted OR 2.62, 95% CI 1.38, 4.96, p value 0.003, and OR 1.004, 95% CI 1.00, 1.007, p value 0.045, respectively).Conclusion: During a LOS, the need for and duration of mechanical ventilation are independently associated with the risk of developing BPD in preterm infants. What is Known: • Premature infants diagnosed with a late-onset sepsis are at higher risk of developing bronchopulmonary dysplasia • This association is mainly shown in infants with a positive blood culture What is New: • This study investigates the clinical and biochemical characteristics of late-onset sepsis and the development of bronchopulmonary dysplasia • The need for mechanical ventilation and duration of mechanical ventilation during late-onset sepsis are associated with an increased risk of developing bronchopulmonary dysplasia.

Background: Since the outbreak of coronavirus disease 2019 (COVID-19), many put their hopes in the rapid availability of effective immunizations. Human milk, containing antibodies against syndrome coronavirus 2 (SARS-CoV-2), may serve as means of protection through passive immunization. We aimed to determine the presence and pseudovirus neutralization capacity of SARS-CoV-2 specific IgA in human milk of mothers who recovered from COVID-19, and the effect of pasteurization on these antibodies., Methods: This prospective case control study included lactating mothers, recovered from (suspected) COVID-19 and healthy controls. Human milk and serum samples were collected. To assess the presence of SARS-CoV-2 antibodies we used multiple complementary assays, namely ELISA with the SARS-CoV-2 spike protein (specific for IgA and IgG), receptor binding domain (RBD) and nucleocapsid (N) protein for IgG in serum, and bridging ELISA with the SARS-CoV-2 RBD and N protein for specific Ig (IgG, IgM and IgA in human milk and serum). To assess the effect of pasteurization, human milk was exposed to Holder (HoP) and High Pressure Pasteurization (HPP)., Results: Human milk contained abundant SARS-CoV-2 antibodies in 83% of the proven cases and in 67% of the suspected cases. Unpasteurized milk with and without these antibodies was found to be capable of neutralizing a pseudovirus of SARS-CoV-2 in (97% and 85% of the samples respectively). After pasteurization, total IgA antibody levels were affected by HoP, while SARS-CoV-2 specific antibody levels were affected by HPP. Pseudovirus neutralizing capacity of the human milk samples was only retained with the HPP approach. No correlation was observed between milk antibody levels and neutralization capacity., Conclusions: Human milk from recovered COVID-19-infected mothers contains SARS-CoV-2 specific antibodies which maintained neutralization capacity after HPP. All together this may represent a safe and effective immunization strategy after HPP.

Background: Chronic stress is often accompanied by alterations in the diurnal rhythm of hypothalamus-pituitary-adrenal activity. However, there are limited data on the diurnal rhythmicity of breast milk glucocorticoids (GCs) among women with psychological distress. We compared mothers who sought consultation at an expertise center for pregnant women with an increased risk of psychological distress with control mothers for GC diurnal rhythmicity in milk and saliva obtained at the same time., Methods: We included 19 mothers who sought consultation at the psychiatry-obstetric-pediatric (POP) outpatient clinic and 44 control mothers. One month postpartum, mothers collected on average eight paired milk and saliva samples during a 24 h period. GC levels were measured using liquid chromatography-tandem mass spectrometry. GC rhythmicity parameters were determined with specialized software., Results: For both milk and saliva, no group differences regarding GC rhythms were found. Milk cortisol area under the curve with respect to the ground was lower in the POP group than in the control group ( p = 0.02). GC levels in human milk and saliva were highly correlated within each group ( p < 0.001)., Conclusion: Although there were no differences between groups in GC rhythmicity, the total amount of milk cortisol was lower in the POP group. Long-term follow-up is needed to address the impact of vertical transmission of breast milk GCs.

Background: Thyroid storm is a well-known complication of surgical procedures in the lower neck, but is rare after a blunt neck trauma. The cases described previously have mainly focussed on adults with pre-existent thyroid disease. In this case report, we describe the disease course of a previously healthy adolescent who had asymptomatic hyperthyroxinemia after a blunt trauma of the jaw and neck. Case Presentation . A 17-year-old girl presented at our emergency department after she fell on her head while roller blading. On physical examination, among other injuries, she had a swelling in the lower neck, which appeared to involve the thyroid gland. Subsequent laboratory analysis was indicative of primary hyperthyroxinemia, with a free T4 of 59 pmol/L (reference range: 12-22) and a TSH of 0.46 mU/L (reference range: 0.5-4.3), but the patient had no symptoms fitting with this. Four weeks after the initial presentation, the patient reported only complaints regarding tenderness in the jaw and neck region. She was no longer hyperthyroidic on biochemical evaluation (with a free T4 level of 15.6 pmol/L and a TSH level of 0.33 mU/L), and antibodies against thyroid peroxidase or TSH receptor were not present., Conclusions: This case might indicate that hyperthyroxinemia following a neck trauma may go unnoticed if hyperthyroid symptoms are mild or absent and thyroid function tests are not performed., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Michelle Romijn et al.)

Objective: Sex-specific differences in hypothalamic-pituitary-adrenal axis activity might explain why male preterm infants are at higher risk of neonatal mortality and morbidity than their female counterparts. We examined whether male and female preterm infants differed in cortisol production and metabolism at 10 days post-partum., Design and Methods: This prospective study included 36 preterm born infants (18 boys) with a very low birth weight (VLBW) (<1.500 g). At 10 days postnatal age, urine was collected over a 4- to 6-h period. Glucocorticoid metabolites were measured using gas chromatography-mass spectrometry. Main outcome measures were: (1) cortisol excretion rate, (2) sum of all glucocorticoid metabolites, as an index of corticosteroid excretion rate, and (3) ratio of 11-OH/11-OXO metabolites, as an estimate of 11B-hydroxysteroid dehydrogenase (11B-HSD) activity. Differences between sexes, including interaction with Score of Neonatal Acute Physiology Perinatal Extension-II (SNAPPE II), sepsis and bronchopulmonary dysplasia (BPD), were assessed., Results: No differences between sexes were found for cortisol excretion rate, corticosteroid excretion rate or 11B-HSD activity. Interaction was observed between: sex and SNAPPE II score on 11B-HSD activity (P = 0.04) and sex and BPD on cortisol excretion rate (P = 0.04)., Conclusion: This study did not provide evidence for sex-specific differences in adrenocortical function in preterm VLBW infants on a group level. However, in an interaction model, sex differences became manifest under stressful circumstances. These patterns might provide clues for the male disadvantage in neonatal mortality and morbidity following preterm birth. However, due to the small sample size, the data should be seen as hypothesis generating.

Objectives: Nocturnal haemodialysis (NHD), characterised by 8-hour sessions ≥3 times a week, is known to improve clinical parameters in the short term compared with conventional-schedule haemodialysis (HD), generally 3×3.5-4 hours a week. We studied long-term effects of NHD and used patients on conventional HD/haemodiafiltration (HDF) as controls., Design: Four-year prospective follow-up of patients who switched to NHD; we compared patients with patients on HD/HDF using propensity score matching., Setting: 28 Dutch dialysis centres., Participants: We included 159 patients starting with NHD any time since 2004, aged 56.7±12.9 years, with median dialysis vintage 2.3 (0.9-5.1) years. We propensity-score matched 100 patients on NHD to 100 on HD/HDF., Primary and Secondary Outcome Measures: Control of hypertension (predialysis blood pressure, number of antihypertensives), phosphate (phosphate, number of phosphate binders), nutritional status and inflammation (albumin, C reactive protein and postdialysis weight) and anaemia (erythropoiesis-stimulating agent (ESA) resistance)., Results: Switching to NHD was associated with a non-significant reduction of antihypertensives compared with HD/HDF (OR <2 types 2.17, 95% CI 0.86 to 5.50, P=0.11); and a prolonged lower need for phosphate binders (OR <2 types 1.83, 95% CI 1.10 to 3.03, P=0.02). NHD was not associated with significant changes in blood pressure or phosphate. NHD was associated with significantly higher albumin over time compared with HD/HDF (0.70 g/L/year, 95% CI 0.10 to 1.30, P=0.02). ESA resistance decreased significantly in NHD compared with HD/HDF, resulting in a 33% lower ESA dose in the long term., Conclusions: After switching to NHD, the lower need for antihypertensives, phosphate binders and ESA persists for at least 4 years. These sustained improvements in NHD contrast significantly with the course of these parameters during continued treatment with conventional-schedule HD and HDF. NHD provides an optimal form of dialysis, also suitable for patients expected to have a long waiting time for transplantation or those convicted to indefinite dialysis., Competing Interests: Competing interests: MPCG reports personal fees and non-financial support from Baxter Healthcare and personal fees from Fresenius Medical Care Netherlands, outside the submitted work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background and Aim: To determine the incremental diagnostic value of epicardial adipose tissue (EAT) volume in addition to the coronary artery calcium (CAC) score for detecting hemodynamic significant coronary artery disease (CAD)., Methods and Results: 122 patients (mean age 61 ± 10 years, 61% male) without a previous cardiac history underwent a non-contrast CT scan for calcium scoring and EAT volume measurements. Subsequently all patients underwent invasive coronary angiography (ICA) in conjunction with fractional flow reserve (FFR) measurements. A stenosis >90% and/or a FFR ≤0.80 were considered significant. Mean EAT volume and CACscore were 128 ± 51 cm(3) and 418 ± 704, respectively. The correlation between EAT volume and the CACscore was poor (r = 0.11, p = 0.24). Male gender (odds ratio [OR] 2.86, p = 0.01), CACscore ([cut-off value 100] OR 3.31, p = 0.003, and EAT volume ([cut-off value 92 cm(3)] OR 4.28, p = 0.01) were associated with flow-limiting disease. The multivariate model revealed that only male gender (OR 2.50, p = 0.045), CAC score (OR 3.60, p = 0.005), and EAT volume (OR 4.95, p = 0.02) were independent predictors of myocardial ischemia. Using the cut-off values of 100 (CAC score) and 92 cm(3) (EAT volume), sensitivity, specificity, negative predictive value, positive predictive value, and accuracy for detecting functionally relevant CAD as indicated by FFR were 71, 57, 77, 50 and 63% and 91, 29, 85, 44 and 52% for the CACscore and EAT volume, respectively. Adding EAT volume to the CAC score and cardiovascular risk factors did not enhance diagnostic performance for the detection of significant CAD (p = 0.57)., Conclusion: EAT volume measurements have no diagnostic value beyond calcium scoring and cardiovascular risk factors in the detection of hemodynamic significant CAD., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Bell's palsy is an acute idiopathic paralysis of the facial nerve. Antiviral drugs and corticosteroids have been suggested as treatment. Due to a lack of consistent, significant treatment effects in various studies, controversy has remained. Recently, a large randomised placebo-controlled, Scottish study concluded that corticosteroids significantly improve outcome in all patients with Bell's palsy. In our opinion the study had several considerable drawbacks. For instance, the results were not in accordance with the expected natural course. Also an analysis of the effect of treatment between patients with complete or incomplete Bell's palsy could not be made. A meta-analysis shows a significant effect of corticosteroids due to domination by the Scottish study. Therefore, we consider it inappropriate to treat all Bell's palsy patients with corticosteroids and patients with incomplete palsy should not be treated at all. More research is needed to clarify the role of corticosteroids in patients with complete Bell's palsy.

Background and Purpose: Our aim was to determine the diagnostic accuracy of multisection CT angiography combined with matched mask bone elimination (CTA-MMBE) for detection of intracranial aneurysms compared with digital subtraction angiography (DSA) and 3D rotational angiography (3DRA)., Materials and Methods: Between January 2004 and February 2006, 108 patients who presented with clinically suspected subarachnoid hemorrhage underwent both CTA-MMBE and DSA for diagnosis of an intracranial aneurysm. Two neuroradiologists, independently, evaluated 27 predefined vessel locations in the CTA-MMBE images for the presence of an aneurysm. After consensus, diagnostic accuracy of CTA was calculated per predefined location and per patient. Interobserver agreement was calculated with kappa statistics., Results: In 88 patients (81%), 117 aneurysms (82 ruptured, 35 unruptured) were present on DSA. CTA-MMBE detected all ruptured aneurysms except 1. Overall specificity, sensitivity, positive predictive value, and negative predictive value of CTA-MMBE were 0.99, 0.90, 0.98, and 0.95 per patient and 0.91, 1.00, 0.97, and 0.99 per location, respectively. Sensitivity was 0.99 for aneurysms >/=3 mm and 0.38 for aneurysms <3 mm. Interobserver agreement for aneurysm detection was excellent (kappa value of 0.92 per location and 0.80 per patient)., Conclusion: CTA-MMBE is accurate in detecting intracranial aneurysms in any projection without overprojecting bone. CTA-MMBE has limited sensitivity in detecting very small aneurysms. Our data suggest that DSA and 3DRA can be limited to the vessel harboring the ruptured aneurysm before endovascular treatment, after detection of a ruptured aneurysm with CTA.