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Summary: Background: An episode of acute ulcerative colitis (UC) represents an important watershed moment in a patient's disease course. Aims: To derive a personalised algorithm for identifying patients at high risk of corticosteroid non‐response from variables available at hospital presentation using a large prospectively collected acute UC patient database and machine learning‐based techniques. Methods: We analysed data from 682 consecutive presentations of acute UC. We used an Akaike information criterion‐based elastic net model to select variables based on the 419 earliest presentations of acute UC (1996–2017). We constructed two risk‐scoring algorithms, with and without utilising additional endoscopic variables, using logistic regression models. We validated these risk scores on separate cohorts of 181 (2018–2022) and 82 (2015–2022) acute UC presentations. Results: The partial risk of rescue (ROR) score included the admission indices of oral corticosteroid treatment, bowel frequency ≥6/24 h, albumin, CRP ≥12 mg/mL and log10CRP. The full ROR score incorporates the same variables with the addition of the Mayo endoscopic subscore and disease extent. The AUCs in the main validation cohort were 0.76 (95% CI: 0.69–0.83) and 0.78 (95% CI: 0.71–0.85) for the partial and full ROR scores, respectively. Conclusions: These pragmatic personalised risk scores (available at www.severecolitis.com) have comparably strong performance characteristics and usability enabling the identification of individuals at high risk of corticosteroid non‐response before or after endoscopic assessment. The ROR scores have the potential to challenge conventional acute UC treatment paradigms by identifying patients who may benefit from early rescue therapy or participation in relevant clinical trials. [ABSTRACT FROM AUTHOR]

Good sleep is essential for children's healthy growth. In 2005, we conducted a questionnaire survey on children's sleep habits and their background, targeting parents who attended health checkups for their 3-year-old children in Asahikawa City, Hokkaido. In 2020, we performed a secondary survey, including additional questions regarding media usage. We analyzed changes in children's sleep environment by comparing the results of both surveys. Children from 500 families (n = 420; 219 males, 201 females; mean age, 3.6 years) who underwent 3.5-year-old health checkups (per the changed schedule in 2015) in Asahikawa City from July 2020 to November 2020 and their parents who had completely answered the questionnaire were included. The proportion of children who used childcare support system such as nursery schools or kindergarten increased from 30% in the previous survey to 95% in the present survey. The mean nocturnal sleep duration of children was 9.33 h in the present survey, 0.77 h shorter than that in the previous survey; similar to the previous survey results, it was significantly short (8.71 h) in children who went to bed after 10 PM. Moreover, it was significantly short in children who watched television for more than two hours or used media within two hours before going to bed or if parents used smartphones or watched motion pictures for >30 min/day. The rate of consulting pediatricians regarding sleep problems decreased from 3% to 2.4%. Parents' lifestyles greatly influenced children's sleep habits in 2020. Pediatricians should actively participate in managing children's sleep problems. [ABSTRACT FROM AUTHOR]

Background: Wisconsin syndrome is a congenital anomaly caused by a 3q interstitial deletion. It is associated with characteristic facies and developmental delays. Only 33 cases with a deletion estimated to be in the associated region 3q25 have been reported.Case Report: We present the case of a 5-year-old Japanese girl with a 3q24q25.2 deletion. Her facial features corresponded to the Wisconsin syndrome phenotype, and she exhibited brain volume laterality, which has not been reported previously.Conclusion: The clinical features of our case may contribute to narrowing down the list of candidate genes of Wisconsin syndrome. [ABSTRACT FROM AUTHOR]

Excessive daytime sleepiness is a frequently described phenomenon in pregnant women. The Epworth Sleepiness Scale (ESS) is a self reported standardized method of assessing sleep propensity and has been used extensively within pregnant populations. An elevated score is associated with sleep disordered breathing, as well as adverse obstetric and neonatal outcomes which may be indicative of a degree of placental dysfunction. Thus the aim of this study was to prospectively assess women using the Epworth questionnaire in conjunction with an ultrasound in both the second and third trimesters to determine if there was a difference in ESS scores across gestation and if a mid or late gestation assessment was correlated with Doppler ultrasound measures of fetal well-being. Participants were prospectively recruited from a tertiary obstetric hospital and completed both an Epworth questionnaire and ultrasound examination in the second and third trimesters. A total of 302 women took part in this cohort study. There was a statistically significant (p =.02) increase in ESS score across gestation. There was however no correlation identified in either the second or third trimester between ESS score and umbilical artery pulsatility index, middle cerebral artery pulsatility index, cerebroplacental ratio, umbilical venous flow, uterine artery pulsatility index or estimated fetal weight. A higher birth weight is associated with a higher ESS score in the second trimester but not in the third trimester (p =.03). Maternal sleep disordered breathing assessed by the ESS score is only correlated with increased birth weight but not with fetal Doppler parameters in low risk pregnancies. [ABSTRACT FROM AUTHOR]

Background: Accurate prostate cancer imaging is critical for patient management. Multiple studies have demonstrated superior diagnostic accuracy of [68Ga]-PSMA-11 PET/CT over conventional imaging for disease detection, with validated clinical and biochemical predictors of disease detection. More recently [18F]PSMA-1007 offers theoretical imaging advantages, but there is limited evidence of clinical and biochemical predictors of scan findings in the staging population. This study investigates the association of clinical variables with imaging characteristics among patients who underwent [18F]PSMA-1007 PET/CT for primary staging of men with histopathologically confirmed prostate carcinoma. A retrospective review of 194 consecutive patients imaged between May 2019 to May 2020 was performed. Association between imaging variables (presence and distribution of metastatic disease, primary tumour SUVmax) and clinical variables (EAU risk criteria) were assessed using descriptive statistics, logistic regression model and ROC analysis. Results: The median age, PSA level and ISUP grade were 70 years, 10 ng/mL and ISUP grade 3, respectively. There were 36.6% of patients with intermediate-risk and 60.8% of patients with high-risk disease. ISUP grade was associated with the presence of metastasis overall (p = 0.008) as well as regional nodal (p = 0.003), non-regional nodal (p = 0.041) and bone (p = 0.006) metastases. PSA level was associated with metastatic disease overall (p = 0.001), regional (p = 0.001) and non-regional nodal metastases (p = 0.004), but not with bone metastases (p = 0.087). There were too few visceral metastases for meaningful analysis. SUVmax of the primary prostatic tumour was associated with ISUP grade (p = 0.004), PSA level (p < 0.001) and AJCC stage (p = 0.034). PSA > 20 ng/mL and ISUP grade > 3 had a specificity of 85% (95% CI 78–91%) and 60% (95% CI 50–68%) and a sensitivity of 36% (95% CI 25–49%) and 62% (95% CI 49–74%), respectively, for detection of metastatic disease. Conclusion: Metastatic disease according to [18F]PSMA-1007 PET/CT was associated with ISUP grade and PSA level. This is the largest study using [18F]PSMA-1007 PET/CT to confirm a positive correlation of PSA level, ISUP grade and stage with primary prostate tumour SUVmax. [ABSTRACT FROM AUTHOR]

Peripheral nerve blocks can provide surgical anaesthesia as well as excellent postoperative analgesia. When questioned postoperatively, however, some patients report low levels of satisfaction with their nerve block experience. At our hospital, patients undergoing regional anaesthesia have their patient characteristics, block characteristics and postoperative feedback routinely recorded in a block registry. We analysed data from 979 consecutive patients undergoing peripheral nerve block for orthopaedic surgery to identify factors associated with low levels of patient satisfaction. The primary outcome was patient satisfaction with their peripheral nerve block (scale 1-5: 4-5 is 'satisfied', 1-3 is 'not satisfied'). Eighty-nine percent (871/979) of patients reported being 'satisfied' with their block. Factors negatively associated with patient satisfaction were rebound pain (adjusted odds ratio (aOR) 0.19, 95% confidence interval (CI) 0.04 to 0.85 for moderate rebound pain; aOR 0.11, 95% CI 0.03 to 0.48 for severe rebound pain), discomfort during the block (aOR 0.37, 95% CI 0.16 to 0.82 for moderate discomfort; aOR 0.19, 95% CI 0.05 to 0.76 for severe discomfort) and pain in the post-anaesthesia care unit (aOR 0.30, 95% CI 0.17 to 0.55 for pain ≥8/10). Only 24% (26/108) of patients who reported being 'not satisfied' stated that they would be unwilling to undergo a hypothetical future nerve block. Rebound pain of at least moderate intensity, procedural discomfort of at least moderate intensity and severe pain in the post-anaesthesia care unit are all negatively associated with patient satisfaction. Of these factors, rebound pain occurs most frequently, being present in 52% (403/777) of our respondents. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the adult population globally. Since liver fibrosis is the most important predictor of liver-related complications in patients with NAFLD, identification of patients with advanced fibrosis among at-risk individuals is an important issue in clinical practice. Transient elastography is the best evaluated non-invasive method used in referral centres to assess liver fibrosis, however serum-based tests, such as the Enhanced Liver Fibrosis (ELF) score, have a practical advantage as first-line tests due to their wider availability and lower cost. We previously identified matrix metalloproteinase 7 (MMP7) as a serum biomarker of histological advanced fibrosis in a mixed-etiology patient cohort. In this study we aimed to determine the association between MMP7 and fibrosis, assessed by transient elastography, in patients with NAFLD. Serum MMP7 levels were measured in a cohort of 228 patients with NAFLD. Associations between MMP7, liver stiffness measurement (LSM), ELF score and clinical parameters were determined using logistic regression modelling. Serum MMP7 was associated with clinically significant fibrosis (LSM ≥ 8.2), independent of age, gender, BMI and diabetes. The addition of MMP7 significantly improved the diagnostic performance of the ELF test, particularly in patients over the age of 60. Combinations of serum biomarkers have the potential to improve the sensitivity and specificity of detection of advanced fibrosis in at-risk patients with NAFLD. We have demonstrated that serum MMP7 is independently associated with clinically significant fibrosis and improves the diagnostic performance of currently available tests in older patients. [ABSTRACT FROM AUTHOR]

Background: Snoring, gasping or choking during sleep are common symptoms of sleep‐disordered breathing and are associated with multiple adverse maternal and obstetric outcomes. The mechanisms responsible remain unknown; however, placental dysfunction is suspected. Aims: The aim of this study was to investigate feto‐placental and fetal cardiac function in women with pregnancies complicated by obstructive sleep apnoea symptoms. Materials and methods: This was a prospective observational cohort study at a large tertiary obstetric hospital in Australia. Women were asked to complete a questionnaire relating to the presence and severity of obstructive sleep apnoea symptoms. They also underwent an ultrasound scan where Doppler indices of various feto‐placental vessels and fetal cardiac function were measured. Regional cerebral perfusion was also assessed. Results: A total of 255 women were included in the final analysis. Of these, 36.1% (92/255) of women reported no obstructive sleep apnoea symptoms; 63.9% (163/255) reported they experienced some form of obstructive sleep apnoea symptoms that included any frequency of snoring or choking/gasping, while 42.0% (107/255) complained of severe obstructive sleep apnoea symptoms (snoring ≥ 3 times a week or choking/gasping). There were no significant differences in feto‐placental Dopplers or fetal cardiac function parameters in women with obstructive sleep apnoea symptoms. There were also no differences in regional cerebral blood flow between groups, or any correlation with severity of symptoms. Conclusions: Our data challenge the current perspective that adverse perinatal outcomes in women with obstructive sleep apnoea symptoms are related primarily to placental dysfunction and fetal compromise. [ABSTRACT FROM AUTHOR]

Background: Central venous access devices (CVAD) are commonly employed in the management of cancer patients. While having several benefits they are associated with significant risks. Aim: To review the incidence and risk factors for catheter‐related thrombosis (CRT) in cancer patients with a CVAD. Methods: We performed a prospective observational cohort study of adult patients with cancer requiring a CVAD between 1 January 2004 and 29 June 2016. The rate of, and risk factors for the development of, symptomatic CRT were evaluated. Results: A total of 4920 central lines was inserted into 3130 patients. The incidence of CRT was 3.6%. CRT developed a median of 12 days following line insertion. Peripherally inserted central catheters (PICC) were associated with the highest rates of CRT (hazards ratio (HR) 22.2, 95% confidence interval (CI) 2.9–170.6). Older age groups developed CRT at lower rates (HR 0.57; 95% CI 0.39–0.84 for age 50–61 years, and HR 0.63; 95% CI 0.45–0.89 for age >61 years) compared to age <50 years. Increased CRT was seen in patients with prior CRT (HR 1.81; 95% CI 1.19–2.77). There was a trend to more CRT events with a Khorana tumour score of 1 compared to those with a score of 0 (HR 1.37, 95% CI 1.00–1.88). Hodgkin lymphoma, germ cell and oesophagus cancers had the highest CRT rates. Side of insertion was not associated with thrombosis risk (HR 0.77; 95% CI 0.57–1.05; P = 0.10). Conclusions: Age <50 years, PICC lines and prior CRT were associated with highest CRT rate. Cancer subtype and insertion side were not predictive of thrombosis. [ABSTRACT FROM AUTHOR]

Background: Therapeutic hypothermia (TH) for 72h is the standard treatment following neonatal encephalopathy (NE). However, one-third do not benefit and adjunctive therapies are urgently needed. Xenon enhances neuroprotection with TH when administered at 50% concentration within 5hours of hypoxia in experimental studies. Delayed initiation (~10 hours of age) of 30% xenon for 24 hours during TH did not improve early adverse biomarkers in a clinical trial of Xenon+TH vs TH. After hypoxia-ischemia, excitotoxic injury via N-methyl-D-aspartate receptor overactivation lasts days. Since xenon partially inhibits this receptor, we hypothesised that giving 50% xenon throughout the entire 72h TH and rewarming periods would enhance neuroprotection. Xenon costs $30/litre, so a closed-circuit breathing system is desirable with automated fresh gas delivery. Methods: Seven mechanically ventilated newborn pigs were randomized to receive 50% inhaled xenon for 72h during hypothermia (rectal-temperature 35°C) and subsequent rewarming following a global hypoxic-ischemic insult (XeHT, N = 4) or under normothermia for 72h (rectal-temperature 38.5°C) following sham insult (XeNT, N = 3). An automated fresh gas delivery system injected oxygen/air/xenon boluses into a closed-circuit based on measured gas concentrations. Results and discussion: Median (IQR) xenon consumption was 0.31 L/h (0.18, 0.50) and 0.34L/h (0.32, 0.49) for hypothermic and normothermic groups respectively, 0.34L/h (0.25, 0.53) overall. 92% of 9626 xenon and 69% of 9635 oxygen measurements were within 20% variation from targets. For xenon concentration, the median absolute performance errors for the XeHT and XeNT groups were 6.14% and 3.84% respectively and 4.31% overall. For oxygen these values were 13.42%, 15.05% and 12.4% respectively. There were no adverse pulmonary pathophysiology findings. Clinical problems over the total period included three related to sensors, seven breathing system leaks, ten partial and one complete tracheal tube occlusion episodes. Conclusion: The automated controller functioned as intended maintaining an inhaled xenon concentration close to the 50% target for 72-78h at a xenon cost of $11.1/h. [ABSTRACT FROM AUTHOR]

COL4A1- related disorder is recognized as a systemic disease because the alpha 1 chain of type IV collagen, encoded by COL4A1, is essential for basement membrane stability. However, muscular manifestations related to this disorder are rarely reported. We report the case of a 2-year-old boy with porencephaly, who harbored a de novo COL4A1 mutation of c.1853G > A, p. (Gly618Glu) and exhibited recurrent rhabdomyolysis with viral or bacterial infections. Moreover, he developed obstructive hypertrophic cardiomyopathy which required surgical intervention. Skeletal muscle biopsy revealed findings compatible with fiber-type disproportion. Ultrastructural study demonstrated the similar findings previously reported in mice with Col4a1 mutation including collagen disarray and reduction of electron density in the basement membrane of capillary endothelial cells and muscle fibers. Dilated endoplasmic reticulum in the capillary endothelial cells is also noted. This report adds another disease spectrum of COL4A1 mutation which include porencephaly, hypertrophic cardiomyopathy, rhabdomyolysis and fiber-type disproportion. [ABSTRACT FROM AUTHOR]

Hormone-sensitive lipase (HSL) is a key enzyme regulating the acute activation of lipolysis. HSL functionality is controlled by multiple phosphorylation events, which regulate its association with the surface of lipid droplets (LDs). We determined the progression and stability of HSL phosphorylation on individual serine residues both spatially and temporally in adipocytes using phospho-specific antibodies. Within seconds of β-adrenergic receptor activation, HSL was phosphorylated on Ser-660, the phosphorylated form appearing in the peripheral cytosol prior to rapid translocation to, and stable association with, LDs. In contrast, phosphorylation of HSL on Ser-563 was delayed, the phosphorylated protein was predominantly detected on LDs, and mutation of the Ser-659/Ser-660 site to Ala significantly reduced subsequent phosphorylation on Ser-563. Phosphorylation of HSL on Ser-565 was observed in control cells; the phosphorylated protein was translocated to LDs with similar kinetics to total HSL, and the degree of phosphorylation was inversely related to phospho-HSLSer-563. These results describe the remarkably rapid, sequential phosphorylation of specific serine residues in HSL at spatially distinct intracellular locales, providing new insight into the complex regulation of lipolysis. [ABSTRACT FROM AUTHOR]

Background/Objectives: There is a lack of certainty in dietary prescription for individuals with inflammatory bowel disease (IBD) due to heterogeneity in studies to date. The aim of this study was to investigate the efficacy on disease activity of a modified anti-inflammatory dietary pattern purposely designed to reduce intake of food additives (IBD-MAID), compared to standard care, in adults with IBD. Subject/Methods: Adults with IBD were randomised to IBD-MAID (meals provided) [n = 29] or general healthy eating (GHE) [n = 29] for 8 weeks. Disease activity, faecal calprotectin (FC), C-reactive protein (CRP), symptoms, and quality of life (S&QOL) were assessed using validated tools. Results: The IBD-MAID was well tolerated and adhered to (92% adherence). At week 8, there was no statistically significant difference in change from baseline in outcome measures between groups. However, baseline to week 8 analysis indicated: (1) statistically significant improvements in S (p = 0.001) & QOL (p = 0.004), FC (p = 0.007), and Crohn's disease activity (p = 0.03) but not ulcerative colitis, in individuals following the IBD-MAID and (2) statistically significant improvement in QOL in individuals receiving GHE (p = 0.015). Correlation analysis on change from baseline to week 8 revealed a greater decrease in food additives intake was associated with statistically significant improvements in FC, S & QOL and alignment of anti-inflammatory dietary principles with improvements in QOL. Conclusion: The IBD-MAID was well tolerated. The most novel finding pertains to the correlation between reduced food additives intake and improvements in inflammatory markers, S&QOL. Further research is needed to explore the effects of food additives exposure on IBD course. Trial registration: 12619001500145 [ABSTRACT FROM AUTHOR]

Mutations in DDX3X have recently been identified as a common cause of intellectual disability and congenital anomalies. DDX3X (Xp11.4) encodes the DEAD box RNA helicase that plays an important role in gene regulation, apoptosis, and oncogenesis. Here, we report a case of 6-year-old Japanese girl with a novel variant (NM_001193416.3: c.1574A > G; p.(Tyr525Cys), who exhibited psychomotor retardation, severe constipation, and a recurrent paralytic ileus. This is the second report of severe gastrointestinal symptoms being associated with this disease. This report expands the phenotype caused by DDX3X variants and reveals an important clinical aspect for patients and medical staff. [ABSTRACT FROM AUTHOR]

The supine sleep position in late pregnancy is a major risk factor for stillbirth, with a population attributable risk of 5.8% and one in four pregnant women reportedly sleeping in a supine position. Although the mechanisms linking the supine sleep position and late stillbirth remain unclear, there is evidence that it exacerbates pre-existing maternal sleep disordered breathing, which is another known risk factor for adverse perinatal outcomes. Given that maternal sleep position is a potentially modifiable risk factor, the aim of this study was to characterize and correlate uteroplacental and fetal hemodynamics, including cardiac function, in a cohort of women with apparently uncomplicated pregnancies with their nocturnal sleep position. This was a prospective observational cohort study at an Australian tertiary obstetric hospital. Women were asked to complete a series of questions related to their sleep position in late pregnancy after 35 weeks of completed gestation. They also underwent an ultrasound assessment where Doppler indices of various fetoplacental vessels and fetal cardiac function were measured. Regional cerebral perfusion was also assessed. Pregnancy outcome data was extracted from the electronic hospital database for analysis. A total of 274 women were included in the final analysis. Of these, 78.1% (214/274) reported no supine sleep, and 21.9% (60/274) reported going to sleep in a supine position. The middle cerebral artery, anterior cerebral artery, and vertebral artery pulsatility indices were all significantly lower in the supine sleep cohort, as was the cerebroplacental ratio. There were no significant differences in the mode or indication for delivery or in serious neonatal outcomes, including 5-min Apgar score < 7, acidosis, and neonatal intensive care unit admission between cohorts. Women in the supine cohort were more likely to have an infant with a BW > 90th centile (p = 0.04). This data demonstrates fetal brain sparing in association with the maternal supine sleep position in a low-risk population. This data contributes to the growing body of literature attempting to elucidate the etiological pathways responsible for the association of late stillbirth with the maternal supine sleep position. [ABSTRACT FROM AUTHOR]

Background: Queensland introduced a colour‐coded cardiotocograph (CTG) classification system (green, blue, yellow and red) to complement the Royal Australian and New Zealand College of Obstetricians and Gynaecologists prose‐based classification system of 'low, unlikely, maybe or likely' fetal compromise. Aims: The aim of the study was to determine the clinical impact of the introduction of the colour‐coded CTG classification system compared to the prose‐based system. We hypothesised there would be no change in the rate of operative delivery for intrapartum fetal compromise (OD‐IFC). Materials and methods: This retrospective non‐inferiority study from November 2014 to May 2018 used routinely collected data from the Mater Mother's Hospital. Non‐insured women with a singleton, non‐anomalous, cephalic fetus at term, attempting a vaginal birth with continuous intrapartum CTG were included. The primary outcome was OD‐IFC. Secondary outcomes included various obstetric and perinatal outcomes. Non‐inferiority analysis was performed with a pre‐specified non‐inferiority margin of 2% risk difference. Results: Eleven thousand seven hundred and twenty‐seven participants were included. The OD‐IFC rate was similar across the study groups (prose‐based 15.1% vs colour‐coded 15.3%, adjusted odds ratio (aOR) 1.02, 95% CI 0.93–1.13) with the adjusted risk difference of 0.29% (95% CI −0.98 to 1.56), which did not exceed the inferiority margin. There were more spontaneous (aOR 1.11, 95% CI 1.04–1.19) and fewer instrumental (aOR 0.87, 95% CI 0.80–0.95) vaginal births in the colour‐coded cohort. There were no differences in neonatal outcomes. Conclusions: Reassuringly, the colour‐coded CTG classification system was non‐inferior to the prose‐based system, did not influence OD‐IFC but was associated with more spontaneous vaginal deliveries. [ABSTRACT FROM AUTHOR]

Aim: To understand the relationship between scores on two standardized measures of cognition, the Montreal Cognitive Assessment (MoCA) and the cognitive subscale of the Functional Independence Measure (FIMCog), and whether these scores can predict functional outcomes in rehabilitation. Methods: Retrospective data analysis was conducted on all inpatients admitted to a general rehabilitation unit within a 6‐month period (N = 477). The average age of patients was 74 years. The Functional Independence Measure (FIM) was completed for all patients on admission and discharge. The MoCA was administered to patients on clinical suspicion of cognitive impairment. The MoCA was completed with 116 patients. Cognitive status was assessed using FIMCog and MoCA. The motor subscale of FIM was used to assess functional status in calculating the motor Rehabilitation Functional Gain (mRFG) and motor Rehabilitation Functional Efficiency (mRFE) scores. Discharge destination was also used as an outcome measure. Results: There was a moderate correlation between FIMCog and MoCA scores on admission (r = 0.49, P < 0.001). Higher FIMCog and MoCA scores were associated with higher mRFG and mRFE scores. There was an indication that patients with higher MoCA scores were more likely to be discharged to a private residence (adjusted odds ratio 1.11; 95% confidence interval: 0.99, 1.25, P = 0.072). Cut‐off points of <25 on the MoCA (sensitivity 88.9%, specificity 48.9%), and <29 on the FIMCog (sensitivity 77.8%, specificity 53.3%) predicted those patients who were less likely to discharge to a private residence. Conclusions: FIMCog and MoCA scores on admission were moderately correlated, and strongly correlated with functional rehabilitation outcomes. The FIMCog and MoCA had moderately high utility in predicting discharge destination. Geriatr Gerontol Int 2020; 20: 336–342. [ABSTRACT FROM AUTHOR]

Objective: The 'Red Blanket' protocol fast tracks trauma patients with severe blood loss to the designated trauma operating theatre directly from the hospital helipad or Emergency Department. This study aimed to assess the impact of patient blood management (PBM) strategies on severely injured trauma patients treated under the 'Red Blanket' protocol at a quaternary referral hospital. Methods: This retrospective review was conducted on all urgent trauma cases that were treated under the 'Red Blanket' protocol in a ten-year period between January 2007 and December 2017. The use of blood products and patient outcomes was compared between the 3.5-year periods pre- and post-ROTEM® implementation on 30th June 2014 (Jan 2011-June 2014 versus July 2014-Dec 2017). Results: During the study period, 120 trauma patients were treated under the 'Red Blanket' protocol at our institution. Intention to treat analysis showed a reduction in fresh frozen plasma usage following the introduction of ROTEM®-guided transfusion. Furthermore, subgroup analysis suggested reduced blood product usage in patients who survived. Conclusions: Patient blood management is a coordinated package of systems and tools, including education, patient logistics, anaemia management, intraoperative cell salvage, rotational thromboelastometry and massive transfusion protocols that together conserve blood products and improve outcomes. The implementation of ROTEM®-guided transfusion demonstrated a reduction in fresh frozen plasma usage. [ABSTRACT FROM AUTHOR]

Introduction: mRECIST were introduced in early 2000 for radiofrequency ablation (RFA) of lung tumours. This retrospective study was performed to evaluate mRECIST in the assessment of lung tumours treated with microwave ablation (MWA). Material and Methods: All percutaneous CT–guided MWA of lung tumours performed between June 2010 and December 2016 were identified and cases with at least 10 months follow-up were included. The therapeutic response was evaluated based on mRECIST. Results: Of the 35 patients included 23 had non-small cell lung cancer (NSCLC) and 12 patients had colorectal cancer (CRC) metastases. Compared to the 24-h post-ablation scan, at 24 months the median CT mass size had reduced to 51.1% from baseline. Based on mRECIST, at 12 months 84.8% showed partial response and 15.2% had stable disease. At 24 months 90% (n = 20) showed partial response whereas 5% had stable disease and another 5% showed complete response. A large proportion of patients were alive 12 months after MWA with a partial response based on mRECIST; this partial response rate had not changed at the 24 months mark. Conclusion: This study challenges the use of mRECIST for the assessment of therapeutic response of lung tumours treated with MWA suggesting that timelines, especially regarding the baseline scan and ablation characteristics, may need to be revised. [ABSTRACT FROM AUTHOR]

Background: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can be used to treat heart diseases; however, the optimal maturity of hiPSC-CMs for effective regenerative medicine remains unclear. We aimed to investigate the benefits of long-term cultured mature hiPSC-CMs in injured rat hearts. Methods: Cardiomyocytes were differentiated from hiPSCs via monolayer culturing, and the cells were harvested on day 28 or 56 (D28-CMs or D56-CMs, respectively) after differentiation. We transplanted D28-CMs or D56-CMs into the hearts of rat myocardial infarction models and examined cell retention and engraftment via in vivo bioluminescence imaging and histological analysis. We performed transcriptomic sequencing analysis to elucidate the genetic profiles before and after hiPSC-CM transplantation. Results: Upregulated expression of mature sarcomere genes in vitro was observed in D56-CMs compared with D28-CMs. In vivo bioluminescence imaging studies revealed increased bioluminescence intensity of D56-CMs at 8 and 12 weeks post-transplantation. Histological and immunohistochemical analyses showed that D56-CMs promoted engraftment and maturation in the graft area at 12 weeks post-transplantation. Notably, D56-CMs consistently promoted microvessel formation in the graft area from 1 to 12 weeks post-transplantation. Transcriptomic sequencing analysis revealed that compared with the engrafted D28-CMs, the engrafted D56-CMs enriched genes related to blood vessel regulation at 12 weeks post-transplantation. As shown by transcriptomic and western blot analyses, the expression of a small heat shock protein, alpha-B crystallin (CRYAB), was significantly upregulated in D56-CMs compared with D28-CMs. Endothelial cell migration was inhibited by small interfering RNA-mediated knockdown of CRYAB when co-cultured with D56-CMs in vitro. Furthermore, CRYAB overexpression enhanced angiogenesis in the D28-CM grafts at 4 weeks post-transplantation. Conclusions: Long-term cultured mature hiPSC-CMs promoted engraftment, maturation and angiogenesis post-transplantation in infarcted rat hearts. CRYAB, which was highly expressed in D56-CMs, was identified as an angiogenic factor from mature hiPSC-CMs. This study revealed the benefits of long-term culture, which may enhance the therapeutic potential of hiPSC-CMs. [ABSTRACT FROM AUTHOR]

Background and Objective: Neutrophil elastase (NE), is an important host defence against lung pathogens. Maintaining a homeostatic balance between proteases such as NE and anti‐proteases such as secretory leukocyte protease inhibitor (SLPI), is important to prevent tissue damage. In the cystic fibrosis (CF) lung, elevated protease levels and impaired anti‐protease defences contribute to tissue destruction. Methods: We assessed lung function and sputum SLPI and NE levels from Pseudomonas aeruginosa infected and non‐infected CF patients (median age 20 years at recruitment) during different phases of clinical disease. Healthy, never smokers served as healthy controls (HC). Sputum total cell counts (TCC) and colony forming units of P. aeruginosa were also determined in each sputum sample. Results: Compared to HC, sputum SLPI was significantly reduced and NE increased in all CF subjects whether infected with P. aeruginosa or not, but the presence of P. aeruginosa worsened these parameters. Females with chronic P. aeruginosa infection had significantly lower sputum SLPI levels than males (p < 0.001). Higher sputum SLPI levels were associated with a significantly reduced rate of longitudinal decline in FEV1% predicted (p < 0.05). Antibiotic treatment in P. aeruginosa‐infected patients significantly decreased sputum TCC and increased SLPI levels, which positively correlated with improved lung function. Conclusion: Airway SLPI is deficient in CF, which appears more marked in P. aeruginosa‐infected female patients. Importantly, a reduced anti‐protease to protease ratio is associated with accelerated lung function decline. Treatment of an exacerbation is accompanied by partial recovery of anti‐protease defences and significant improvement in lung function, an important clinical outcome. Cystic fibrosis (CF) patients have impaired lung proteases and maintaining anti‐protease: protease ratios is crucial in preventing tissue damage. Secretory leukocyte protease inhibitor (SLPI) is significantly reduced and neutrophil elastase increased in P. aeruginosa‐infected female patients with CF; correlating with lung function decline. Antibiotic treatment restored SLPI levels and improved lung function. See relatedEditorial [ABSTRACT FROM AUTHOR]

Background: Hyperglycaemia occurs frequently in the critically ill. Dietary intake of advanced glycation end‐products (AGEs), specifically Nε‐(carboxymethyl)lysine (CML), may exacerbate hyperglycaemia through perturbation of insulin sensitivity. The present study aimed to determine whether the use of nutritional formulae, with varying AGE loads, affects the amount of insulin administered and inflammation. Methods: Exclusively tube fed patients (n = 35) were randomised to receive Nutrison Protein Plus Multifibre®, Diason® or Glucerna Select®. Insulin administration was standardised according to protocol based on blood glucose (<10 mmol L–1). Samples were obtained at randomisation and 48 h later. AGEs in nutritional formula, plasma and urine were measured using mass spectrometry. Plasma inflammatory markers were measured using an enzyme‐linked immunosorbent assay and multiplex bead‐based assays. Results: AGE concentrations of CML in nutritional formulae were greatest with delivery of Nutrison Protein Plus® (mean [SD]; 6335 pmol mol–1 [2436]) compared to Diason® (4836 pmol mol–1 [1849]) and Glucerna Select® (4493 pmol mol–1 [1829 pmol mol–1]) despite patients receiving similar amounts of energy (median [interquartile range]; 12 MJ [8.2–13.7 MJ], 11.5 MJ [8.3–14.5 MJ], 11.5 MJ [8.3–14.5 MJ]). More insulin was administered with Nutrison Protein Plus® (2.47 units h–1 [95% confidence interval (CI) = 1.57–3.37 units h–1]) compared to Diason® (1.06 units h–1 [95% CI = 0.24–1.89 units h–1]) or Glucerna Select® (1.11 units h–1 [95% CI = 0.25–1.97 units h–1]; p = 0.04). Blood glucose concentrations were similar. There were associations between greater insulin administration and reductions in circulating interleukin‐6 (r = –0.46, p < 0.01), tumour necrosis factor‐α (r = −0.44, p < 0.05), high sensitivity C‐reactive protein (r = −0.42, p < 0.05) and soluble receptor for advanced glycation end‐products (r = −0.45, p < 0.01) concentrations. Conclusions: The administration of greater AGE load in nutritional formula potentially increases the amount of insulin required to maintain blood glucose within a normal range during critical illness. There was an inverse relationship between exogenous insulin and plasma inflammatory markers. Key points: Enteral nutrition formula comprise varying amounts of advanced glycation end‐products, specifically Nε‐(carboxymethyl)lysine (CML), which has the potential to exacerbate hyperglycaemia as seen in the healthy population.Patients in the control arm, receiving the highest carbohydrate and CML quantity, had a higher exogenous insulin requirement compared to the two interventional formulae.Our findings also showed an association between increasing doses of insulin and a reduction in inflammatory markers (interleukin‐6, tumour necrosis factor‐α and high sensitivity C‐reactive protein).Further research is required to determine whether manipulation of AGEs in enteral nutrition formula impacts insulin sensitivity and inflammation. [ABSTRACT FROM AUTHOR]

Aim: Colorectal cancer (CRC) is the third most common cancer in Australia, and survival after diagnosis of metastatic disease is improving. Our aim was to assess trends in epidemiology, treatment, molecular testing and survival in patients with metastatic CRC (mCRC). Methods: Clinical data from February 2013 to December 2018 was recorded in a prospective, observational, multicenter cohort study conducted in Queensland, Australia, examining clinical and molecular biomarkers in cases of mCRC. Results: A total of 159 patients who had metastasis diagnosed after February 2013 were included in survival analysis. Median age at diagnosis was 63.9 years, but 29% had early‐onset disease (diagnosis aged <50 years). Median overall survival was 2.5 years (95% confidence interval [CI], 2.2–3.0) for the 159 patients included in survival analysis. Independent factors correlated with poor prognosis included right‐sided primary tumor, neutrophil–lymphocyte ratio >5, increased alkaline phosphatase level (ALP) and an increasing number of sites of metastatic disease. In contrast, metastasectomy was associated with improved overall survival (adjusted HR = 0.29' 95% CI, 0.16–0.54), with similar survival between patients who had liver and non‐liver metastasectomy sites. Half (10/20) of the BRAF mutant CRC were also microsatellite unstable. The proportion of detected mutations amongst tested samples increased over time for Kirsten Rat Sarcoma (KRAS; OR [per year] = 1.19; 95% CI, 1.01–1.39). Concurrently, the methods of molecular genetics testing employed in routine clinical practice changed towards the adoption of next‐generation sequencing. Conclusions: Metastasectomy in mCRC may be beneficial regardless of the anatomical site of metastasis. The adoption of next‐generation sequencing techniques for molecular genetics testing coincided with a slightly increased rate of detection of KRAS and BRAF mutations, potentially reflecting greater test sensitivity. Further translational research is required in mCRC to define novel targets for treatment. [ABSTRACT FROM AUTHOR]

Background: Placenta praevia (PP) is a rare obstetric condition associated with significant maternal and perinatal morbidity. Traditionally, the degree of PP has been classified into minor and major; however, there are very few robust studies that compare the maternal outcomes of these types of PP. Aims: To identify any significant differences in obstetric outcomes between major and minor PP, including antepartum, intraoperative and postpartum complications. Materials and Methods: A retrospective cohort study was conducted at the Royal Brisbane & Women's Hospital between 2009 and 2018; all women were diagnosed with PP. Results: Of the total of 368 women recruited, over half of the participants were diagnosed with major PP (57%), while the remaining had minor PP. Women with major PP, compared to women with minor PP, had an increased risk of antepartum haemorrhage (odds ratio (OR) 2.77, P < 0.001), delivery at an earlier gestational age (36.1 vs 37.4 weeks), general anaesthesia (OR 3.25, P < 0.001), greater proportion of emergency lower segment (51% vs 40%) and classical caesarean (7.7% vs 3.8%), increased number of uterotonics (incidence rate ratio (IRR) 1.17, P < 0.031), greater blood loss (IRR 1.32, P < 0.001) and higher frequency of blood transfusion (IRR 2.00, P < 0.027), and longer postpartum hospital stay (IRR 1.26, P < 0.001). Hysterectomy was performed for three women with major PP, compared to one with minor PP. Conclusions: The degree of PP significantly impacts obstetric outcomes, with major PP associated with worse maternal morbidity antenatally, intraoperatively and postpartum. Therefore, to optimise patient care, this study emphasises the importance of identifying and distinguishing between different types of PP. [ABSTRACT FROM AUTHOR]

Purpose: Patients with primarily ligamentous injuries of the distal tibiofibular joint comprise up to 12% of all ankle sprains. Patients frequently present late after a syndesmosis injury and delayed treatment potentially leads to pain, prolonged disability and arthritis in the long term. This study aimed to assess clinical outcomes in patients who required syndesmosis fixation in the presence of arthroscopically proven instability, the hypothesis being that a delay to treatment would be associated with worse function. Method: A retrospective cohort study was performed of patients with dynamic instability requiring fixation between the years of 2010–2016. The procedures were performed by two foot and ankle fellowship trained orthopaedic surgeons, over three hospital sites. Patients were classified into three groups based on the time since injury to surgery, acute syndesmotic injury (< 6 weeks), sub-acute (6 weeks–6 months) and chronic syndesmotic injury (> 6 months). Functional scores were retrospectively collected using the Foot and Ankle Outcome Score (FAOS). Results: Compared to patients with acute injuries, those with chronic injuries had significantly lower FAOS subscales (p < 0.001), with the greatest difference in quality of life (− 20.7, 95% CI − 31.6 to − 9.8, p = 0.012). There was a mean follow-up of 4.3 years. Although the average FAOS subscales in those with sub-acute injuries were lower than in those with acute injuries, the difference was not statistically significant. Conclusion: The results of this study suggest that delayed surgical stabilisation (> 6 months) is associated with significantly worse clinical function, and thus timely identification and early referral of those patients with potentially unstable syndesmotic injuries is recommended. Level of evidence: Level III. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Psychosocial assessment should be part of clinic visits for people with diabetes mellitus (DM). Aims: To assess the usage and acceptance of a diabetes psychosocial assessment tool (DPAT) and to profile the clinical and psychosocial characteristics of young people with diabetes. Methods: Over a 12‐month period, young adults (18–25 years) attending diabetes clinic were offered DPAT. The tool embeds validated screening tools including the Problem Areas in Diabetes 20 (PAID‐20) questionnaire, the Patient Health Questionnaire‐4 (PHQ‐4) and the World Health Organization Well‐Being Index‐5 (WHO‐5). Baseline clinical data were collected and questions regarding social support, body image, eating concerns, hypoglycaemia and finances were included. Results: Over the 12 month, the form was offered to 155 participants (64.6% of eligible attendees). The majority (96.1%) had type 1 DM with a mean duration of 10.5 (±5.3 SD) years. Average glycated haemoglobin (HbA1c) was 8.7% (±1.5 SD) (or 71.2 mmol/mol ±16.5 SD). Severe diabetes‐related distress (PAID‐20 ≥ 40) was found in 19.4%. Low WHO‐5 scores (28–50 points) were seen in 14.8%. PHQ‐4 identified 25.8% with anxiety and 16.1% with depression. Significant weight, shape and eating concerns were identified in 27.1, 26.6 and 28.4%, respectively. Serious hypoglycaemia concerns were raised by 4.5%. Conclusion: DPAT revealed a high prevalence of psychosocial stress among young adults with DM. The tool was easy to use and accepted by patients and may aid streamlining referrals to relevant members of a multidisciplinary team. [ABSTRACT FROM AUTHOR]

Background: Preterm birth is associated with significant perinatal morbidity and mortality. The fetal fibronectin test (fFN) is used to manage women presenting with threatened preterm labour (TPTL). Aim: To evaluate the use of fFN in women presenting with TPTL with regard to hospital admission, tertiary hospital transfer and use of tocolytics and steroids in our hospital, against recommended guidelines. The ability of fFN <10 ng/mL, 10–49 ng/mL, 50–199 ng/mL and >200 ng/mL to predict outcome was also examined. Material and Methods: This was a single‐centre retrospective study from January 2015 to June 2017. All women who presented to Ipswich hospital, a level two facility for births at >32 weeks of gestation, between 23 and 346 weeks of gestation with TPTL and who had fFN tests were included in the study. Results: Fetal fibronectin <50 ng/mL had a negative predictive value of 93.5% (95% CI 86.5–97.1). Despite this assurance, one in four presentations resulted in hospital admission and nearly one in ten in steroids and tocolysis administration. Birth <34 weeks was 0% for fFN <10 and 2% for women with fFN levels <200 ng/mL compared to nearly 30% for levels >200 ng/mL. Conclusion: There is noncompliance with use of fFN to its full potential. This small study also provides support for the use of a 200 ng/mL cut‐off fFN level for birth <34 weeks. This would avoid the need to transfer to a tertiary facility many women who present with TPTL. [ABSTRACT FROM AUTHOR]

Purpose: Although both anti-PD-1 antibody and treatments using anti-PD-L1 antibody are currently in clinical use, their therapeutic effects vary according to cancer type. One of the factors accounting for this variability is the expression level of the immune checkpoint molecule that differs between cancer types; thus, it is important to clarify the relationship between clinical outcomes and immune checkpoint molecules for all types of human cancer. The purpose of this study is to evaluate the clinical outcome of osteosarcoma in relation to PD-L1, PRF, GZMB, and IFNγ expression. Methods: Using 19 clinical specimens of osteosarcoma, we examined the expression of PD-L1, PRF, GZMB, and IFNγ in relation to their clinical outcomes. Results: PD-L1 expression correlated with early metastatic formation in clinical specimens of osteosarcoma, and the group with highly expressed functional markers for T cells such as PRF and GZMB resulted in a long overall survival time. Conclusion: This is the first study to elucidate the clinical outcomes of osteosarcoma in relation to PD-L1, PRF, GZMB, and IFNγ expression. This study provides valuable information regarding the clinical indication and prediction of effect for anti-PD-1 antibody in osteosarcoma. [ABSTRACT FROM AUTHOR]

The generation of caveolae involves insertion of the cholesterol- binding integral membrane protein caveolin-1 (Cav1) into the membrane, however, the precise molecular mechanisms are as yet unknown. We have speculated that insertion of the caveolin scaffolding domain (CSD), a conserved amphipathic region implicated in interactions with signaling proteins, is crucial for caveola formation. We now define the core membrane-juxtaposed region of Cav1 and show that the oligomerization domain and CSD are protected by tight association with the membrane in both mature mammalian caveolae and a model prokaryotic system for caveola biogenesis. Cryoelectron tomography reveals the core membrane-juxtaposed domain to be sufficient to maintain oligomerization as defined by polyhedral distortion of the caveolar membrane. Through mutagenesis we demonstrate the importance of the membrane association of the oligomerization domain/CSD for defined caveola biogenesis and furthermore, highlight the functional significance of the intramembrane domain and the CSD for defined caveolin-induced membrane deformation. Finally, we define the core structural domain of Cav1, constituting only 66 amino acids and of great potential to nanoengineering applications, which is required for caveolin- induced vesicle formation in a bacterial system. These results have significant implications for understanding the role of Cav1 in caveola formation and in regulating cellular signaling events. [ABSTRACT FROM AUTHOR]

Background: Basal meningoceles are rare congenital defects and often clinically occult until they result in life-threatening complications. Therefore, it is important to know the diagnostic clues to early diagnosis.Case Presentation: We describe three cases of congenital basal meningocele in a 3-year-old Japanese boy, a 1-month-old Japanese baby boy, and a 10-month-old Japanese baby girl. One of our patients died of sepsis due to traumatic rupture of the meningocele during nasal suction. His meningocele remained undiagnosed until it resulted in the fatal complication. The other patients underwent surgical repair without any complications. Their meningoceles were complicated by midfacial anomalies including cleft palate and hypertelorism, or a sign of nasal obstruction such as snoring.Conclusions: These clinical features may be a clue to the early diagnosis of congenital basal meningocele, which enables its safe preoperative management and provides an opportunity for surgical repair before the condition results in serious complications. [ABSTRACT FROM AUTHOR]

Caveolin-1 (CAV1) is an important regulator of adipose tissue homeostasis. In the present study we examined the impact of CAV1 deficiency on the properties of mouse adipose tissue both in vivo and in explant cultures during conditions of metabolic stress. In CAV1-/- mice fasting caused loss of adipose tissue mass despite a lack of hormone-sensitive lipase (HSL) phosphorylation. In addition, fasting resulted in increased macrophage infiltration, enhanced deposition of collagen, and a reduction in the level of the lipid droplet protein perilipin A (PLIN1a). Explant cultures of CAV1-/- adipose tissue also showed a loss of PLIN1a during culture, enhanced secretion of IL-6, increased release of lactate dehydrogenase, and demonstrated increased susceptibility to cell death upon collagenase treatment. Attenuated PKA-mediated signaling to HSL, loss of PLIN1a and increased secretion of IL-6 were also observed in adipose tissue explants of CAV1+/+ mice with diet- induced obesity. Together these results suggest that while alterations in adipocyte lipid droplet biology support adipose tissue metabolism in the absence of PKA-mediated pro-lipolytic signaling in CAV1-/- mice, the tissue is intrinsically unstable resulting in increased susceptibility to cell death, which we suggest underlies the development of fibrosis and inflammation during periods of metabolic stress. [ABSTRACT FROM AUTHOR]