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Introduction: End-tidal CO2 (ETCO2) detector is currently recommended for confirmation of endotracheal tube placement during neonatal resuscitation. Whether it is feasible to use ETCO2 detectors during mask ventilation to reduce risk of bradycardia and desaturations, which are associated with increased risk of death in preterm babies, is unknown., Methods: This is a pilot randomized controlled trial (NCT04287907) involving newborns 24 + 0/7 to 32 + 0/7 weeks gestation who required mask ventilation at birth. Infants were randomized into groups with or without colorimetric ETCO2 detectors. Combined duration of any bradycardia (<100 bpm) and time below prespecified target oxygen saturation (SpO2) as measured by pulse oximetry were compared., Results: Fifty participants were randomized, 47 with outcomes analysed (2 incomplete data, 1 postnatal diagnosis of trachea-oesophageal fistula). Mean gestational age and birthweight were 28.5 ± 1.9 versus 29.4 ± 1.6 weeks (p = 0.1) and 1,252.7 ± 409.7 g versus 1,334.6 ± 369.1 g (p = 0.5) in the intervention and control arm, respectively. Mean combined duration of bradycardia and desaturation was 276.7 ± 197.7 s (intervention) and 322.7 ± 277.7 s (control) (p = 0.6). Proportion of participants with any bradycardia or desaturation at 5 min were 38.1% (intervention) and 56.5% (control) (p = 0.2). No chest compressions, epinephrine administration, or death occurred in the delivery room., Conclusion: This pilot study demonstrates the feasibility of a trial to evaluate colorimetric ETCO2 detectors during mask ventilation of very preterm infants to reduce bradycardia and low SpO2. Further assessment with a larger population will be required to determine if ETCO2 detector usage at resuscitation reduces risk of adverse outcomes, including death and disability, in very preterm infants., (© 2024 S. Karger AG, Basel.)

Background: Gut dysbiosis contributes to the high risk of bloodstream infection (BSI) among premature infants. Most prior studies of the premature infant gut microbiota were conducted in Western countries and prior to development of current tools for strain-resolved analysis., Methods: We performed metagenomic sequencing of weekly fecal samples from 75 premature infants at a single hospital in Singapore. We evaluated associations between clinical factors and gut microbiota composition using PERMANOVA and mixed effects linear regression. We used inStrain to perform strain-level analyses evaluating for gut colonization by BSI-causing strains., Results: Median (interquartile range) gestation was 27 (25, 29) weeks, and 63% of infants were born via Cesarean section. Antibiotic exposures (PERMANOVA; R 2  = 0.017, p = 0.001) and postnatal age (R 2  = 0.015, p = 0.001) accounted for the largest amount of variability in gut microbiota composition. Increasing postnatal age was associated with higher relative abundances of several common pathogens (Enterococcus faecalis: p < 0.0001; Escherichia coli: p < 0.0001; Klebsiella aerogenes: p < 0.0001; Klebsiella pneumoniae: p < 0.0001). Antibiotic exposures were generally associated with lower relative abundances of both frequently beneficial bacteria (e.g., Bifidobacterium species) and common enteric pathogens (e.g., Enterobacter, Klebsiella species). We identified strains identical to the blood culture isolate in fecal samples from 12 of 16 (75%) infants who developed BSI, including all infections caused by typical enteric bacteria., Conclusions: Antibiotic exposures were the dominant modifiable factor affecting gut microbiota composition in a large cohort of premature infants from South-East Asia. Strain-resolved analyses indicate that the gut is an important reservoir for organisms causing BSI among premature infants., (© 2023. The Author(s).)

Objective: The diagnosis of axial spondyloarthritis (axSpA) is hampered by diagnostic delay. Computed tomography (CT) undertaken for nonmusculoskeletal (non-MSK) indications in patients with inflammatory bowel disease (IBD) offers an opportunity to identify sacroiliitis for prompt rheumatology referral. This study aims to identify what proportion of patients with IBD who underwent abdominopelvic CT for non-MSK indications have axSpA and to explore the role of a standardized screening tool to prospectively identify axSpA on imaging., Methods: Abdominopelvic CT scans of patients with verified IBD, aged 18 to 55 years, performed for non-MSK indications were reviewed by radiologists for the presence of CT-defined sacroiliitis (CTSI), using criteria from a validated CT screening tool. All patients identified were sent a screening questionnaire, and those with self-reported chronic back pain (CBP), CBP duration of greater than 3 months, and age of onset of less than 45 years were invited for rheumatology review., Results: CTSI was identified in 60 out of 301 (19.9%) patients. Out of these 60 patients, 32 (53%) responded to an invitation to participate, and 27 out of 32 (84.3%) were enrolled. Of these, 8 had a preexisting axSpA diagnosis and 5 did not report CBP. In total, 14 patients underwent rheumatology assessment, and 3 out of 14 (21.4%, 95% CI 4.7-50.8) had undiagnosed axSpA. In total, 11 out of 27 (40.7%, 95% CI 22.4-61.2) patients had a rheumatologist-verified diagnosis of axSpA., Conclusion: In this study, 5% (3/60) of patients with IBD undergoing abdominopelvic CT for non-MSK indications with CTSI were found to have undiagnosed axSpA and, overall, 18.3% (11/60) were found to have axSpA. This reveals a significant hidden population of axSpA and highlights the need for a streamlined pathway from sacroiliitis detection to rheumatology referral., (Copyright © 2023 by the Journal of Rheumatology.)

Objective: To elucidate the prevalence of undiagnosed rheumatology-verified diagnosis of axial spondyloarthritis (RVD-axSpA) in patients attending routine secondary care IBD clinics with chronic back pain., Methods: Screening questionnaires were sent to consecutive patients attending IBD clinics in a university teaching hospital. Patients fulling the eligibility criteria (gastroenterologist-verified diagnosis, 18-80 years old, biologic therapy naive, no previous diagnosis of axSpA); and a moderate diagnostic probability of axSpA [self-reported chronic back pain (CBP) >3 months, onset <45 years] were invited for rheumatology assessment. This included medical review, physical examination, patient reported outcome measures, human leucocyte antigen B27, C-reactive protein, pelvic radiograph and axSpA protocol magnetic resonance imaging. A diagnosis of RVD-axSpA was made by a panel of rheumatologists., Results: Of the 470 patients approached, 91 had self-reported CBP >3 months, onset <45 years, of whom 82 were eligible for clinical assessment. The prevalence of undiagnosed RVD-axSpA in patients attending IBD clinics in a secondary care setting, with self-reported CBP, onset <45 years is estimated at 5% (95% CI 1.3, 12.0) with a mean symptom duration of 12 (s.d. 12.4) years., Conclusion: There is a significant hidden disease burden of axSpA among IBD patients. Appropriate identification and referral from gastroenterology is needed to potentially shorten the delay to diagnosis and allow access to appropriate therapy., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The rich biodiversity of medicinal plants and their importance as sources of novel therapeutics and lead compounds warrant further research. Despite advances in debulking surgery and chemotherapy, the risks of recurrence of ovarian cancer and resistance to therapy are significant and the clinical outcomes of ovarian cancer remain poor or even incurable., Objective: This study aims to investigate the effects of leaf extracts from a medicinal plant Leea indica and its selected phytoconstituents on human ovarian cancer cells and in combination with oxaliplatin and natural killer (NK) cells., Methods: Fresh, healthy leaves of L. indica were harvested and extracted in 70% methanol by maceration. The crude extract was partitioned with n-hexane, dichloromethane and ethyl acetate. Selected extracts and compounds were analyzed for their effects on cell viability of human ovarian cancer cells, NK cell cytotoxicity, and stress ligands expression for NK cell receptors. They were also evaluated for their effects on TNF-α and IL-1β production by enzyme-linked immunosorbent assay in lipopolysaccharide-stimulated human U937 macrophages., Results: Leaf extracts of L. indica increased the susceptibility of human ovarian tumor cells to NK cell-mediated cytotoxicity. Treatment of cancer cells with methyl gallate but not gallic acid upregulated the expression of stress ligands. Tumor cells pretreated with combination of methyl gallate and low concentration of oxaliplatin displayed increased levels of stress ligands expression and concomitantly enhanced susceptibility to NK cell-mediated cytolysis. Further, NK cells completely abrogated the growth of methyl gallate-pretreated ovarian cancer cells. The leaf extracts suppressed TNF-α and IL-1β production in human U937 macrophages. Methyl gallate was more potent than gallic acid in down-regulating these cytokine levels., Conclusions: We demonstrated for the first time that leaf extracts of L. indica and its phytoconstituent methyl gallate enhanced the susceptibility of ovarian tumor cells to NK cell cytolysis. These results suggest that the combined effect of methyl gallate, oxaliplatin and NK cells in ovarian cancer cells warrants further investigation, for example for refractory ovarian cancer. Our work is a step towards better scientific understanding of the traditional anticancer use of L. indica., (© 2023. The Author(s).)

Objective: To determine the risk factors for mortality associated with late onset sepsis (LOS) among preterm very-low-birthweight (VLBW) infants., Study Design: We performed a retrospective cohort study of infants born <32 weeks gestation and <1,500 gm admitted to a Singaporean tertiary-level neonatal intensive care unit. We determined the clinical, microbial, and laboratory risk factors associated with mortality due to culture-positive LOS in this cohort., Results: A total of 1,740 infants were admitted, of which 169 (9.7%) developed LOS and 27 (16%) died. Compared to survivors, those who died had lower birth gestational age (median 24 vs. 25 weeks, p = 0.02) and earlier LOS occurrence (median 10 vs. 17 days, p = 0.007). There was no difference in the incidence of meningitis (11.1 vs. 16.9%, p = 0.3), NEC (18.5 vs. 14.8%, p = 0.6), or intestinal surgery (18.5 vs. 23.3%, p = 0.6) among infants who died compared to survivors. Gram-negative bacteria accounted for 21/27 (77.8%) LOS-associated deaths and almost all (13/14, 93%) fulminant episodes. The presence of multiorgan failure, as evidenced by the need for mechanical ventilation (100 vs. 79.0%, p = 0.008), elevated lactate (12.4 vs. 2.1 mmol/L, p < 0.001), and inotropic support (92.6 vs. 37.5%, p < 0.001), was significantly associated with mortality. Infants who died had significantly lower white blood cell (WBC) counts (median 4.2 × 10 9 /L vs. 9.9 × 10 9 /L, p = 0.001), lower platelet count (median 40 × 10 9 /L vs. 62 × 10 9 /L, p = 0.01), and higher immature to total neutrophil (I: T) ratio (0.2 vs. 0.1, p = 0.002). Inotrope requirement [AOR 22.4 (95%CI 2.9, 103.7)], WBC <4 × 10 9 /L [AOR 4.7 (1.7, 13.2)], and I: T ratio >0.3 [AOR 3.6 (1.3, 9.7)] were independently associated with LOS mortality., Conclusions: In a setting with predominantly Gram-negative bacterial infections, the need for inotropic support, leukopenia, and elevated I: T ratio were significantly associated with LOS mortality among preterm VLBW infants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Goh, Lim, Sultana, De La Puerta, Rajadurai and Yeo.)

Background: The utility of determining maternal-neonatal surface colonization as detected by standard microbiological cultures around the time of birth is unclear. The aim of this study is to evaluate the association between maternal and neonatal surface colonization at birth and neonatal early onset sepsis (EOS)., Objective: To investigate the association of white matter hyperintensities (WMHs) present in the brain with AD CSF biomarker levels., Methods: We conducted a case-control study of newborns admitted to the neonatal department of a referral women's and children's hospital from 2009 to 2017. Cases were infants with blood-culture-confirmed EOS (<3 days of life), and controls were infants without EOS randomly chosen based on the cases' date of birth. Maternal genitourinary and neonatal ear swab cultures were used to determine bacterial surface colonization status., Results: Fifty-one infants were diagnosed with EOS during the study period, where Escherichia coli (45%), and Group B Streptococcus (23%) accounted for 68% of infecting organisms. Compared to infants without EOS, those infected were more likely to have surface colonization of the mothers (60% vs 40%, p = 0.048) and infants (90% vs 11%, p < 0.001). In univariate analysis, chorioamnionitis [7.1 (95% CI 2.9, 16.8)], small-for-gestational-age [OR 0.08 (95% CI 0.02, 0.4)], exposure to antibiotics around time of birth [2.3 (95% CI 1.0, 5.1)], maternal surface colonization [2.2 (95% CI 1.0, 4.9)] and neonatal surface colonization [23.5 (95% CI 7.3, 76.1)] were significantly associated with EOS. Adjusting for potential confounders, neonatal colonization remained significantly associated with neonatal EOS [AOR 15.0 (95% CI 3.5, 64.2), p < 0.001]., Conclusion: In our setting with predominant Gram-negative EOS, neonatal colonization but not maternal colonization was significantly associated with EOS in the newborn.

Ethnopharmacological Relevance: The extensive biodiversity of plants in Southeast Asia and inadequate research hitherto warrant a continued investigation into medicinal plants. On the basis of a careful review of fresh medicinal plant usage to treat cancer from previous ethnobotanical interviews in Singapore and from the traditional uses of the indigenous plants, fresh leaves of seven locally grown medicinal plant species were evaluated for anti-proliferative activity., Aim of the Study: To evaluate the anti-proliferative activity of local medicinal plant species Clausena lansium Skeels, Clinacanthus nutans (Burm. f.) Lindau, Leea indica (Burm. f.) Merr., Pereskia bleo (Kunth) DC., Strobilanthes crispus (L.) Blume, Vernonia amygdalina Delile and Vitex trifolia L., Materials and Method: Fresh, healthy and mature leaves of the seven medicinal plants were harvested from various locations in Singapore and Malaysia for Soxhlet, ultrasonication and maceration extractions in three different solvents (water, ethanol and methanol). Cell proliferation assay using water soluble tetrazolium salt (WST-1) assay was performed on twelve human cancer cell lines derived from breast (MDA-MB-231, T47D), cervical (C33A), colon (HCT116), leukemia (U937), liver (HepG2, SNU-182, SNU-449), ovarian (OVCAR-5, PA-1, SK-OV-3) and uterine (MES-SA/DX5) cancer., Results: A total of 37 fresh leaf extracts from seven medicinal plants were evaluated for their anti-tumour activities in twelve human cancer cell lines. Of these, the extracts of C. lansium, L. indica, P. bleo, S. crispus, V. amygdalina and V. trifolia exhibited promising anti-proliferative activity against multiple cancer cell lines. Further investigation of selected promising leaf extracts indicated that maceration methanolic extract of L. indica was most effective overall against majority of the cancer cell lines, with best IC 50 values of 31.5 ± 11.4 µg/mL, 37.5 ± 0.7 µg/mL and 43.0 ± 6.2 µg/mL in cervical C33A, liver SNU-449, and ovarian PA-1 cancer cell lines, respectively., Conclusion: The results of this study provide new scientific evidence for the traditional use of local medicinal plant species C. lansium, L . indica, P. bleo, S. crispus, V. amygdalina and V. trifolia in cancer treatment. These results highlight the importance of the upkeep of these indigenous plants in modern society and their relevance as resources for drug discovery., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Leea indica (Vitaceae) is a Southeast Asian medicinal plant. In this study, an ethyl acetate fraction of L. indica leaves was studied for its phytoconstituents using high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-microTOF-Q-MS/MS) analysis. A total of 31 compounds of different classes, including benzoic acid derivatives, phenolics, flavonoids, catechins, dihydrochalcones, coumarins, megastigmanes, and oxylipins were identified using LC-MS/MS. Among them, six compounds including gallic acid, methyl gallate, (-)-epigallocatechin-3- O -gallate, myricetin-3- O -rhamnoside, quercetin-3- O -rhamnoside, and 4',6'-dihydroxy-4-methoxydihydrochalcone 2'- O -β-d-glucopyranoside were isolated and identified by NMR analysis. The LC-MS/MS analysis led to the tentative identification of three novel dihydrochalcones namely 4',6'-dihydroxy-4-methoxydihydrochalcone 2'- O -rutinoside, 4',6'-dihydroxy-4-methoxydihydrochalcone 2'- O -glucosylpentoside and 4',6'-dihydroxy-4-methoxydihydrochalcone 2'- O -(3″- O -galloyl)-β-d-glucopyranoside. The structural identification of novel dihydrochalcones was based on the basic skeleton of the isolated dihydrochalcone, 4',6'-dihydroxy-4-methoxydihydrochalcone 2'- O -β-d-glucopyranoside and characteristic LC-MS/MS fragmentation patterns. This is the first comprehensive analysis for the identification of compounds from L. indica using LC-MS. A total 24 compounds including three new dihydrochalcones were identified for the first time from the genus Leea .

The association between HLA-B27 and AS was first established in the early 1970s. Since then, our understanding of this disease has changed, such that we now recognize AS to be the extreme of the clinical phenotype within a disease spectrum known as axial SpA (axSpA). Recent advances in therapeutic options have driven the need for earlier diagnosis and many screening strategies have been proposed to facilitate this. In parallel, our understanding of axSpA genetics, and especially the contribution of HLA-B27, has expanded. In this article we will present and discuss the evidence supporting the use of HLA-B27 in clinical practice. We will briefly summarize the evolution of the concept of axSpA, the prevalence of HLA-B27 and axSpA and the potential role of HLA-B27 in the aetiopathogenesis of axSpA and focus on the utility of HLA-B27 in everyday clinical practice.