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This study investigated (a) differences between males and females for changes in serum, tear, and urine osmolality, hematocrit, and urine specific gravity following acute passive dehydration and (b) assessed the reliability of these biomarkers separately for each sex. Fifteen males (age: 26.3 ± 3.5 years, body mass: 76 ± 7 kg) and 15 females (age: 28.8 ± 6.4 years, body mass: 63 ± 7 kg) completed a sauna protocol twice (5–28 days apart), aiming for 4% body mass loss (BML). Urine, blood, and tear markers were collected pre- and postdehydration, and change scores were calculated. Male BML was significantly greater than that of females in Trial 1 (3.53% ± 0.55% vs. 2.53% ± 0.43%, p <.001) and Trial 2 (3.36% ± 0.66% vs. 2.53% ± 0.44%, p =.01). Despite significant differences in BML, change in hematocrit was the only change marker that displayed a significant difference in Trial 1 (males: 3% ± 1%, females: 2% ± 1%, p =.004) and Trial 2 (males: 3% ± 1%, females: 1% ± 1%, p =.008). Regression analysis showed a significant effect for sex (male) predicting change in hematocrit (β = 0.8, p =.032) and change in serum osmolality (β = −3.3, p =.005) when controlling for BML but not for urinary or tear measures. The intraclass correlation coefficients for females (ICC 2, 1) were highest for change in urine specific gravity (ICC =.62, p =.006) and lowest for change in tear osmolarity (ICC = −.14, p =.689), whereas for males, it was posthematocrit (ICC =.65, p =.003) and post tear osmolarity (ICC =.18, p =.256). Generally, biomarkers showed lower test–retest reliability in males compared with females but, overall, were classified as poor–moderate in both sexes. These findings suggest that the response and reliability of hydration biomarkers are sex specific and highlight the importance of accounting for BML differences. [ABSTRACT FROM AUTHOR]

Objective: To determine whether pediatric emergency medicine physicians are compliant with the 9-year-old simple febrile seizure guideline created by the American Academy of Pediatrics (AAP). Methods: A retrospective chart review of patients, ages 6 to 60 months, who presented to the emergency department between May 2011 and December 2019. Key variables abstracted were urine, blood, nasal viral swab, and radiographic results. Results: The retrospective cohort of 285 children met inclusion criteria. Among 285 children, 342 studies were performed with a median of 1.2 studies per patient. There were 77 urine cultures obtained with 6 bacterial pathogens. Nasal viral swabs were performed on 65 children with 9 positive results. Blood cultures were obtained for 28 children and none were positive. Chest radiographs were performed on 37 children with 4 showing pneumonia. Conclusion: The study results reflect areas of opportunity to update guidelines with a focus to consider obtaining urine studies, viral sampling, and chest x-rays. [ABSTRACT FROM AUTHOR]

Background: Currently, the treatment and prevention of migraine remain highly challenging. Mendelian randomization (MR) has been widely used to explore novel therapeutic targets. Therefore, we performed a systematic druggable genome-wide MR to explore the potential therapeutic targets for migraine. Methods: We obtained data on druggable genes and screened for genes within brain expression quantitative trait locis (eQTLs) and blood eQTLs, which were then subjected to two-sample MR analysis and colocalization analysis with migraine genome-wide association studies data to identify genes highly associated with migraine. In addition, phenome-wide research, enrichment analysis, protein network construction, drug prediction, and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic drugs. Results: We identified 21 druggable genes significantly associated with migraine (BRPF3, CBFB, CDK4, CHD4, DDIT4, EP300, EPHA5, FGFRL1, FXN, HMGCR, HVCN1, KCNK5, MRGPRE, NLGN2, NR1D1, PLXNB1, TGFB1, TGFB3, THRA, TLN1 and TP53), two of which were significant in both blood and brain (HMGCR and TGFB3). The results of phenome-wide research showed that HMGCR was highly correlated with low-density lipoprotein, and TGFB3 was primarily associated with insulin-like growth factor 1 levels. Conclusions: This study utilized MR and colocalization analysis to identify 21 potential drug targets for migraine, two of which were significant in both blood and brain. These findings provide promising leads for more effective migraine treatments, potentially reducing drug development costs. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung Cancer Screening (LCS) is an evolving field presenting variations in its implementation worldwide. This manuscript is delivered by a multidisciplinary Task Force (TF) in LCS. It aims to identify and present existing evidence regarding biomarkers in LCS and form an up-to-date overview of the current evidence. Background: Lung Cancer Screening (LCS) is an evolving field with variations in its implementation in various countries. There are only scarce data from National LCS programs. Aim: We aim to provide an up-to-date overview of the current evidence regarding the use of biomarkers in LCS. Materials and Methods: A multidisciplinary Task Force experts' panel collaborated and conducted a systematic literature search, followed by screening, review and synthesis of available evidence. Results: Biomarkers in LCS could be used to improve risk stratification in high-risk participants, improve clarification regarding indeterminate lung nodules and avoid overdiagnosis in suspicious lung findings. Currently, there seem to be promising biomarkers (blood/serum/breath) that have been studied in various trials; however, there is still a lack of solid evidence in clinical validation that would pave the way for their integration into LCS programs. Conclusions: Biomarkers are the next logical step in improving the LCS pathway and its efficiency by playing an adjuvant role in a minimally invasive way. National LCS programs and pilot studies should integrate biomarkers to validate their accuracy in real-life LCS participants. [ABSTRACT FROM AUTHOR]

Rat lungworm disease or neuroangiostrongyliasis is a cerebral parasitic infection that affects humans and animals alike. Its clinical signs and symptoms can range from mild self-resolving to serious life-threatening conditions. Studies suggest therapeutic interventions during the early stages of infection to be more effective than in later stages. However, early diagnosis of infection is usually problematic without the knowledge of exposure and/or detection of the parasite’s DNA or antibody against the parasite in the cerebrospinal fluid. This requires a lumbar puncture, which is an invasive procedure that generally requires hospitalization. This study evaluates an affordable and less invasive alternative to detect parasitic DNA by PCR from the peripheral blood of potentially infected animals. Blood samples from 58 animals (55 dogs and 3 cats) with clinical suspicion of infection were submitted to our lab between February 2019 and August 2022 by local, licensed veterinarians. DNA was extracted from whole blood, plasma, serum, and/or packed cells using the Qiagen DNeasy Blood & Tissue Kit as per the manufacturer’s protocol. All 58 animals were tested by real-time PCR using the AcanITS1 assay and 32 of these animals (31dogs; 1 cat) were also tested using the AcanR3990 assay. The PCR results for both assays were classified into strongly positive > positive > weakly positive > negative, and equivocal for ambiguous results, based on the strength of the signal. The percent infection detected using the AcanITS1 and AcanR3990 assays was 12.72% (7/55) and 20.68% (6/29), respectively. The overall percent infection detected was 34.37% (11/32), with only two animals testing positive by both assays. The three cats involved in this study tested negative by both assays. These results are promising and warrant further investigations to increase sensitivity including variables that might affect detection in the blood, such as parasite load, and laboratory methodologies. [ABSTRACT FROM AUTHOR]

Background: Age-related hearing loss (ARHL) is a general term used to describe the sensorineural type of hearing loss occurring in both ears in older adults. Neurotrophins are the most promising candidates for supporting the auditory nerve by increasing neuronal survival. This study aimed to help elucidate the pathophysiology of ARHL by determining whether any relationship exists between brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) levels in serum samples from patients diagnosed with ARHL. Materials and Method: Seventy-seven individuals, a study group of 41 patients diagnosed with ARHL, and a control group of 36 participants without hearing loss were evaluated. Serum samples were collected and used to measure serum BDNF and NT-3 levels with the new Nepenthe enzyme-linked immunosorbent assay method. Results: Median pure-tone average results in the 2000, 4000, and 6000 Hz ranges were 52.5 (44.3–67.3) dB HL in the ARHL group and 13.5 (11.1–17.1) dB HL in the control group. The difference was statistically significant (p = .001). Although NT-3 and BDNF levels were both lower in ARHL patients than in participants without hearing loss, only the BDNF levels were significantly (p = .002) lower. Mean left and right ear word recognition scores were also lower in ARHL patients than in control groups. The ARHL group was further divided into two subgroups based on word recognition scores to evaluate significant differences in BDNF and NT-3 levels. No statistically significant difference was observed in BDNF and NT-3 levels between these subgroups. However, there was a significant difference in word recognition scores. Conclusions: Low BDNF levels in the ARHL group suggest that BDNF may play a role in the pathogenesis of ARHL. Patients with low (ARHL1) and high (ARHL2) word recognition scores were compared for the first time in the literature in terms of BDNF and NT-3 levels. However, the results were not statistically significant. This article is a preliminary study and was written to provide guidance for our next comprehensive project. [ABSTRACT FROM AUTHOR]

Introduction: High mobility group box 1 protein (HMGB1) is a member of the molecular family known as damage-associated molecular patterns, which is implicated to have a role in neuroinflammation processes. In recent years, a growing number of studies have focused on the role of inflammation in Bipolar Disorder (BD). This study aimed to investigate the serum levels of HMGB1 and other inflammatory markers in patients with bipolar manic episodes compared to those in healthy controls (HC). Methods: A single-center, observational, case-control study was conducted. Thirty-five patients with BD in manic episodes and 35 HC were assessed. Young Mania Rating Scale (YMRS) was used to assess the symptom severity of the patient group. While inflammatory markers (such as HMGB1, C-reactive protein (CRP) and white blood cell count) were assessed at the first three and the last day of hospitalization in the patient group, they were evaluated once in HC. Levels of inflammatory markers were compared between (patient-HC) and within groups (before-after treatment). Results: No difference was observed in serum HMGB1 levels of bipolar patients with manic episodes compared to the HC (p>0.05). C-reactive protein levels of manic patients were higher than HC (p<0.001), and the difference persisted even after treatment (p=0.007). In addition, there was a significant positive correlation between CRP levels and antipsychotic drug dosage (r=0.382, p=0.024). Conclusion: There were no differences in HMGB1 levels between bipolar patients with acute manic episode and HC. However, higher CRP levels in bipolar patients support the low-grade inflammation hypothesis in the etiology of BD. [ABSTRACT FROM AUTHOR]

Background: The hypothalamus plays a crucial role in the health and productivity of dairy cows, yet studies on its functionality and its impact on peripheral circulation in these animals are relatively scarce, particularly regarding dietary interventions. Therefore, our study undertook a comprehensive analysis, incorporating both metabolomics and transcriptomics, to explore the effects of a grain-based diet on the functionality of the hypothalamus, as well as on blood and milk in dairy cows. Results: The hypothalamic metabolome analysis revealed a significant reduction in prostaglandin E2 (PGE2) level as a prominent response to the grain-based diet introduction. Furthermore, the hypothalamic transcriptome profiling showed a notable upregulation in amino acid metabolism due to the grain-based diet. Conversely, the grain-based diet led to the downregulation of genes involved in the metabolic pathway from lecithin to PGE2, including phospholipase A2 (PLA2G4E, PLA2G2A, and PLA2G12B), cyclooxygenase-2 (COX2), and prostaglandin E synthase (PTGES). Additionally, the plasma metabolome analysis indicated a substantial decrease in the level of PGE2, along with a decline in adrenal steroid hormones (tetrahydrocortisol and pregnenolone) following the grain-based diet introduction. Analysis of the milk metabolome showed that the grain-based diet significantly increased uric acid level while notably decreasing PGE2 level. Importantly, PGE2 was identified as a critical metabolic marker in the hypothalamus, blood, and milk in response to grain intervention. Correlation analysis demonstrated a significant correlation among metabolic alterations in the hypothalamus, blood, and milk following the grain-based diet. Conclusions: Our findings suggest a potential link between hypothalamic changes and alterations in peripheral circulation resulting from the introduction of a grain-based diet. [ABSTRACT FROM AUTHOR]

The transition from concentric primary flow to non-tangential secondary flow of blood was investigated using experimental steady shear rheometry and numerical modelling. The aims were to: assess the difference in secondary flow in a Newtonian versus shear-thinning blood analogue; and measure the secondary flow in the blood. Both experiments and numerical modelling showed that the transition from primary to secondary flow was the same in a Newtonian fluid and a shear-thinning blood analogue. Experiments showed whole blood transitioned to secondary flow at lower modified Reynolds numbers than the Newtonian fluid; and transition was haematocrit dependent with higher RBC concentrations transitioning at lower modified Reynolds numbers. These results indicate that modelling blood as a purely shear-thinning fluid does not predict the correct secondary flow fields in whole blood; non-Newtonian effects beyond shear-thinning behaviour are influential, and incorporating effects such as multiphase contributions and viscoelasticity, yield stress and thixotropy is necessary. [ABSTRACT FROM AUTHOR]

Aim: The serum creatinine/cystatin C ratio (CCR) or sarcopenia index is considered a useful marker of muscle mass. However, its usefulness in late‐stage older adults remains unclear. We aimed to determine the usefulness of CCR as an indicator of sarcopenia in community‐dwelling Japanese adults aged >75 years. Methods: Our study recruited participants aged 70, 80, and 90 ± 1 years during the baseline years, and included a 3‐year follow‐up in the Septuagenarians, Octogenarians, Nonagenarians, Investigation with Centenarians study. From 2015 to 2018, 955 participants were eligible: 367 in their 70s, 304 in their 80s, and 284 in their 90s. The diagnostic components of sarcopenia, including "low muscle mass, plus low muscle strength, and/or low physical performance," were evaluated using the bioelectrical impedance analysis‐measured skeletal muscle mass index (SMI), handgrip strength, and short physical performance battery (SPPB) score, respectively, in accordance with the Asia Working Group for Sarcopenia 2019 criteria. Separate analyses were performed between each component and CCR, adjusting for sex, body mass index, and other blood biomarkers in each group. Results: The relationship between CCR and sarcopenia components was significant for handgrip strength (β = 0.21, 0.13, 0.19, and P < 0.0001, =0.0088, <0.0001, for the 70s, 80s, and 90s age groups, respectively); however, it was limited for SMI (β = 0.14; P = 0.0022, only for the 90s) and not significant for the SPPB score. Conclusion: CCR is a limited indicator of sarcopenia in late‐stage older adults. Although its association with muscle strength was significant, its relationship with muscle mass and physical performance was less pronounced. Geriatr Gerontol Int 2024; 24: 529–536. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of motor neurons, and there is currently a lack of reliable diagnostic biomarkers. This meta-analysis aimed to evaluate CHIT1, CHI3L1, and CHI3L2 levels in the cerebrospinal fluid (CSF) or blood and their diagnostic potential in ALS patients. A systematic, comprehensive search was performed of peer-reviewed English-language articles published before April 1, 2023, in PubMed, Scopus, Embase, Cochrane Library, and Web of Science. After a thorough screening, 13 primary articles were included, and their chitinases-related data were extracted for systematic review and meta-analysis. In ALS patients, the CSF CHIT1 levels were significantly elevated compared to controls with healthy control (HC) (SMD, 1.92; 95% CI, 0.78 – 3.06; P < 0.001). CHIT1 levels were elevated in the CSF of ALS patients compared to other neurodegenerative diseases (ONDS) control (SMD, 0.74; 95% CI, 0.22 – 1.27; P < 0.001) and exhibited an even more substantial increase when compared to ALS-mimicking diseases (AMDS) (SMD, 1.15; 95% CI, 0.35 – 1.94, P < 0.001). Similarly, the CSF CHI3L1 levels were significantly higher in ALS patients compared to HC (SMD, 3.16; 95% CI, 1.26 – 5.06, P < 0.001). CHI3L1 levels were elevated in the CSF of ALS patients compared to ONDS (SMD, 0.75; 95% CI, 0.32 – 1.19; P = 0.017) and exhibited a more pronounced increase when compared to AMDS (SMD, 1.92; 95% CI, 0.41 – 3.42; P < 0.001). The levels of CSF chitinases in the ALS patients showed a significant increase, supporting the role of CSF chitinases as diagnostic biomarkers for ALS. [ABSTRACT FROM AUTHOR]

Background: The identification of biomarkers for the early diagnosis of Alzheimer's disease (AD) is a crucial goal of the current research. Blood biomarkers are less invasive, easier to obtain and achievable by a cheaper means than those on cerebrospinal fluid (CSF) and significantly more economic than functional neuroimaging investigations; thus, a great interest is focused on blood isoforms of the phosphorylated Tau protein (pTau), indicators of ongoing tau pathology (i.e. neurofibrillary tangles, NFTs, an AD neuropathological hallmark) in the central nervous system (CNS). However, current data often highlight discordant results about the ability of blood pTau to predict CSF status. Objective: We aim to synthesise the studies that compared pTau levels on CSF and blood to assess their correlation in AD continuum. Methods: We performed a narrative literature review using, first, MEDLINE (via PubMed) by means of MeSH terms, and then, we expanded the reults by means of Scopus and Web of Sciences to be as inclusive as possible. Finally, we added work following an expert opinion. Only papers presenting original data on pTau values on both blood and CSF were included. Results: The 33 included studies show an extreme heterogeneity in terms of pTau isoform (pTau181, 217 and 231), laboratory methods, diagnostic criteria and choice of comparison groups. Most studies evaluated plasma pTau181, while data on other isoforms and serum are scarcer. Discussion: Most papers identify a correlation between CSF and blood measurements. Furthermore, even when not specified, it is often possible to show an increase in blood pTau values as AD-related damage progresses in the AD continuum and higher values in AD than in other neurodegenerative diseases. Notably, plasma pTau231 seems the first biomarker to look for in the earliest and pre-clinical stages, quickly followed by pTau217 and, finally, by pTau181. Conclusions: Our results encourage the use of blood pTau for the early identification of patients with AD continuum. [ABSTRACT FROM AUTHOR]

This study investigated the effects of ghrelin on oxidative stress, working memory, inflammatory parameters, and neuron degeneration. TBI was produced with the weight-drop technique. Rats in the G+TBI and TBI+G groups received ghrelin for 7 or 2 days, respectively. The control group received saline. On the 8th day of the study, the brain and blood tissue were taken under anesthesia. A significant increase in brain GSH-PX, MDA, IL-1β, TGF-β1, and IL-8 levels and a significant decrease in CAT levels were found in the TBI group compared to the control. Serum MDA, GSH, IL-1β, and IL-8 levels were increased with TBI. Ghrelin treatment after TBI significantly increased the serum GSH, CAT, GSH-PX, and brain GSH and CAT levels, while it significantly decreased the serum MDA, IL-1β, and brain MDA, TGF-β1, and IL-8 levels. Histological evaluations revealed that ghrelin treatment led to a reduction in inflammation, while also significantly ameliorating TBI-induced neuron damage and vascular injuries. Immunohistochemistry staining showed that GFAP staining intensity was significantly increased in the cortex and hippocampus in TBI, and GFAP immunoreactivity was decreased with ghrelin treatment. The results from this study suggested that ghrelin may have curative effects on TBI. [ABSTRACT FROM AUTHOR]

Objective: Diabetes retinopathy (DR) is one of the top listed world health issues. Screening is usually advised for diabetic cases on a routine basis. However, there is only partial access to ophthalmologists in all parts of the world. Irisin is a myokine that is being investigated for this reason. Our study aims to assess the role of irisin in detecting DR. Methods and materials: In a cross-sectional study, 140 diabetes cases, including 70 patients with diabetic retinopathy and 70 patients free from diabetic retinopathy, were enrolled. Demographic and anthropometric data were gathered, and the patients underwent physical examination. Also, microalbuminuria and serum irisin levels were assessed in both groups. The results were compared between the two study groups. Results: Among the enrolled cases, 55 (39.28%) were men, and 85 (60.72%) were women. The disease duration (p = 0.016) and the serum level of HBA1c (p = 0.014) were significantly higher in the diabetic retinopathy group compared to the group free from diabetic retinopathy. Moreover, irisin was significantly higher in the patients free from diabetic retinopathy (p = 0.007). Conclusion: Irisin may have value in screening diabetic retinopathy; however, further studies are needed for this proposal. [ABSTRACT FROM AUTHOR]

Introduction: People with obesity have high circulating bile acids (BA). Although aerobic fitness favors low circulating BA, the effect of training intensity before clinically meaningful weight loss on BA is unclear. This study aimed to test the hypothesis that 2 wk of interval (INT) versus continuous (CONT) exercise would lower plasma BA in relation to insulin sensitivity. Methods: Twenty-three older adults with prediabetes (ADA criteria) were randomized to 12 work-matched bouts of INT (n = 11, 60.3 ± 2.4 yr, 32.1 ± 1.2 kg⋅m-2) at 3 min at 50% HRpeak and 3 min at 90% HRpeak or CONT (n = 12, 60.8 ± 2.4 yr, 34.0 ± 1.7 kg⋅m-2) at 70% HRpeak cycling training for 60 min⋅d-1 over 2 wk. A 180-min 75-g oral glucose tolerance test (OGTT) was performed to assess glucose tolerance (tAUC), insulin sensitivity (Siis), and metabolic flexibility (RERpostprandial-RERfast; indirect calorimetry). BA (n = 8 conjugated and 7 unconjugated) were analyzed at 0, 30, and 60 min of the OGTT. Anthropometrics and fitness (...O2peak) were also assessed. Results: INT and CONT comparably reduced body mass index (BMI; P < 0.001) and fasting RER (P < 0.001) but raised insulin sensitivity (P = 0.03). INT increased ...O2peak as compared with CONT (P = 0.01). Exercise decreased the unconjugated BA chenodeoxycholic acid iAUC60min (P < 0.001), deoxycholic acid iAUC60min (P < 0.001), lithocholic acid iAUC60min (P < 0.001), and glycodeoxycholic acid (GCDCA) iAUC60min (P < 0.001). Comparable reductions were also seen in the conjugated BA hyodeoxycholic acid iAUC60min (P = 0.01) and taurolithocholic acid iAUC60min (P = 0.007). Increased ...O2peak was associated with lowered UDCA0min (r = -0.56, P = 0.02) and cholic acid iAUC60min (r = -0.60, P = 0.005), whereas reduced BMI was related to higher GDCA0min (r = 0.60, P = 0.005) and GCDCA0min (r = 0.53, P = 0.01). Improved insulin sensitivity correlated with lower GCDCA iAUC60min (r = -0.45, P = 0.03) and GDCA iAUC60min (r = -0.48, P = 0.02), whereas increased metabolic flexibility was related to deoxycholic acid iAUC60min (r = 0.64, P = 0.004) and GCDCA iAUC60min (r = 0.43, P = 0.05). Conclusions: Short-term training lowers some BA in relation to insulin sensitivity independent of intensity. [ABSTRACT FROM AUTHOR]

• Serum concentrations of metal ions, notably titanium, were markedly higher in the spinal fusion surgery group compared to the control group. • The percentage of patients with metal concentrations exceeding normal ranges was significantly greater in the surgery cohort versus controls. • Mean chromium elevations in the surgical group were approximately 24-fold higher than levels in healthy subjects. • Future studies require standardized methodology in areas including patient age ranges, definitions of elevated metal levels, separated versus pooled data groups, and complete reporting of numerical data. Elevated blood metal levels have been reported in patients after spinal surgery using metallic implants. Although some studies have suggested an association between heightened blood metal concentrations and potential adverse effects, estimates of the incidence of abnormal metal levels after spinal surgery have been inconsistent. The aims of this systematic review and meta-analysis were to assess: (1) mean differences in blood metal ion levels between patients undergoing spinal fusion surgery and healthy controls, (2) odds of elevated blood metal ion levels after surgery compared to presurgery levels, and (3) pooled incidence of elevated blood metal ions overall and by metal type. Systematic review and meta-analysis. The patient sample included 613 patients from 11 studies who underwent spinal surgery instrumentation. Blood metal ion concentrations and the incidence of patients with elevated metal levels compared with in those the control group. A comprehensive search was conducted in PubMed, EMBASE, Scopus, and Cochrane Library to identify studies reporting blood metal ion levels after spinal fusion surgery. Mean differences (MD), odds ratios (OR), and incidence rates were pooled using random effects models. Heterogeneity was assessed using I2 statistics, and fixed-effects models were used if no heterogeneity was detected. Detailed statistical analysis was performed using the Review Manager version 5.4 software. The analysis included 11 studies, with a total of 613 patients. Mean blood metal ion levels were significantly higher after spinal fusion surgery (MD 0.56, 95% CI 0.17–0.96; I2=86%). Specifically, titanium levels were significantly elevated (MD 0.81, 95% CI 0.32–1.30; I2=47%). The odds of elevated blood metal ions were higher after surgery (OR 8.17, 95% CI 3.38–19.72; I2=41%), primarily driven by chromium (OR 23.50, 95% CI 5.56–99.31; I2=30%). The incidence of elevated chromium levels was found to be 66.98% (95% CI 42.31–91.65). In conclusion, blood metal ion levels, particularly titanium and chromium, were significantly increased after spinal fusion surgery compared to presurgery levels and healthy controls. Approximately 70% of the patients exhibited elevated blood levels of chromium and titanium. [ABSTRACT FROM AUTHOR]

2-Phenoxyethanol (PhE) is an aromatic glycol ether and is used in a variety of functions and applications, e.g., as preservative in pharmaceuticals, cosmetic and personal care products, as biocide in disinfectants (e.g. human hygiene), or as a solvent in formulations (e.g. coatings, functional fluids). Despite its widespread use, little is yet known on its biotransformation and toxicokinetics in humans. Therefore, a pilot study was conducted with oral administration of PhE (5 mg/kg body weight) to five volunteers. Blood and urine samples were collected and analyzed for PhE and three of its presumed metabolites up to 48 h post-exposure. Additionally, one volunteer was dermally exposed to PhE and monitored until 72 h post-exposure. PhE was rapidly resorbed following both oral and dermal application with tmax-levels in blood of about 1 h and 3 h, respectively. Metabolism of PhE was observed to be rather extensive with phenoxyacetic acid (PhAA) and 4-hydroxyphenoxyacetic acid (4-OH-PhAA) as the main metabolites found in blood and urine following oral and dermal exposure. PhE was excreted rapidly and efficiently via urine mostly in metabolized form: following oral exposure, on average 77% and 12% of the applied dose was excreted within 48 h as PhAA and 4-OH-PhAA, respectively. A similar metabolism pattern was observed following the single dermal exposure experiment. The obtained data on biotransformation and toxicokinetics of PhE in humans provide valuable information on this important chemical and will be highly useful for pharmacokinetic modelling and evaluation of human PhE exposure. [ABSTRACT FROM AUTHOR]

Background: Impella devices are used for mechanical circulatory support in patients with cardiogenic shock or those undergoing high-risk percutaneous coronary intervention (PCI). Anticoagulation protocols in this population are not well established and are complicated by concomitant use of purge solutions containing unfractionated heparin (UFH) and intravenous UFH continuous infusion (CI) for systemic anticoagulation. Objectives: To evaluate thrombotic and bleeding complications when using a novel UFH protocol with a reduced initial UFH CI dose of 6 units/kg/hour targeting an anti-Xa goal of 0.3 to 0.5 units/mL in patients receiving Impella support. Methods: This single-center, retrospective study included 41 patients on Impella support who received an UFH purge solution and/or an IV UFH infusion. The primary outcome was overall composite bleeding. Secondary outcomes included thrombotic events and systemic UFH exposure. An exploratory analysis was performed to identify risk factors for bleeding. Results: Anti-Xa values were in therapeutic range 46% of the time while on support (interquartile range 16.6%-75%), with a median IV UFH dose of 6 units/kg/hour. The overall bleeding rate was 29.2%, with 6 minor bleeds and 2 major bleeds with no fatal bleeding or intracranial hemorrhage. Rate of overall thrombosis was 4.9%, including 1 ischemic stroke and 1 occurrence of limb ischemia. Conclusion: Use of a modified UFH protocol to target an anti-Xa goal of 0.3 to 0.5 units/mL resulted in bleeding and thrombotic event rates similar to previous literature. This protocol utilizing an initial rate of 6 units/kg/hour may be a useful approach to achieve therapeutic anticoagulation while accounting for UFH exposure from the purge solution and minimizing need for frequent calculations. [ABSTRACT FROM AUTHOR]

Objective Cord gas values and Apgar scores, currently used as markers for newborn wellbeing and postpartum complications, provide rough estimates, and their use remains elusive. Circulating cell-free DNA (cfDNA) may better represent newborn status at birth and the effect of parturition on the fetus. This pilot study investigates the association between cord blood (CB) cfDNA and neonatal outcomes. Study Design In a prospective cohort study, cfDNA concentration was measured in immediately following delivery collected CB sera of newborns using our rapid fluorescent assay. Results During the study period, blood samples from umbilical cords of 100 newborns were collected. Vaginal delivery was associated with a higher median CB cfDNA than cesarean delivery (277 [95% confidence interval [CI] 199–377] vs. 100 [95% CI 43–265] ng/mL, p < 0.01). cfDNA levels were significantly associated with gestational age at delivery (rho = 0.308, p = 0.002) and CB base deficit (BD, r = 0.252, p = 0.017). According to maternal and fetal complications, CB cfDNA was elevated in fetuses with category II of heart rate tracing (p < 0.05), with maternal positive vaginal culture (p < 0.01), and with premature rupture of membranes (PROM, p < 0.001). Logistic regression models of CB cfDNA fourth quartiles demostrate a double odds ratio for elevated BD (>3mmol/L) and for worse heart rate tracing category. Conclusion Serum CB cfDNA concentration reflects the newborn's status and hazards with an excellent association with CB BD, fetal heart rate category, and maternal risk factors for infection (positive vaginal culture and PROM). This preliminary observation suggests that cfDNA can serve as a point of care biomarker for newborn status at the time of delivery. Key Points CB cfDNA levels correlated with newborn's BD. CB cfDNA levels reflect parturition stress and inflammation. cfDNA serve as a diagnostic and prediction tool for the identification of newborns at risk for morbidity. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The distribution and elimination of infused crystalloid fluid is known to be affected by general anesthesia, but it is unclear whether changes differ depending on whether the patient is operated in the flat recumbent position, the Trendelenburg (“legs up”) position, or the reverse Trendelenburg (“head up”) position.Retrospective data on hemodilution and urine output obtained during and after infusion of 1–2 L of Ringer's solution over 30–60 min were collected from 61 patients undergoing surgery under general anesthesia and 106 volunteers matched with respect to the infusion volume and infusion time. Parameters describing fluid distribution in the anesthetized and awake subjects were compared by population volume kinetic analysis.General anesthesia decreased the rate constant for urine output by 79% (flat recumbent), 91% (legs up) and 91% (head up), suggesting that laparoscopic surgery per se intensified the already strong anesthesia‐induced fluid retention. General anesthesia also decreased the rate constant governing the return of the distributed fluid to the plasma by 32%, 15%, and 70%, respectively. These results agree with laboratory data showing a depressive effect of anesthetic drugs on lymphatic pumping, and further suggest that the “legs up” position facilitates lymphatic flow, whereas the “head up” position slows this flow. Both Trendelenburg positions increased swelling of the “third fluid space”.General anesthesia caused retention of infused fluid with preferential distribution to the extravascular space. Both Trendelenburg positions had a modifying influence on the kinetic adaptations that agreed with the gravitational forces inflicted by tilting to body. [ABSTRACT FROM AUTHOR]

Background: Tumor recurrence remains the main barrier to survival after surgery for pleural mesothelioma (PM). Soluble mesothelin‐related protein (SMRP) and cancer antigen 125 (CA‐125) are established blood‐based biomarkers for monitoring PM. We prospectively studied the utility of these biomarkers after pleurectomy decortication (PD). Methods: Patients who underwent PD and achieved complete macroscopic resection with available preoperative SMRP levels were included. Tumor marker levels were determined within 60 days of three timepoints: (1) preoperation, (2) post‐operation, and (3) recurrence. Results: Of 356 evaluable patients, 276 (78%) had recurrence by the end of follow‐up interval. Elevated preoperative SMRP levels were associated with epithelioid histology (p < 0.013), advanced TNM (p < 0.001) stage, and clinical stage (p < 0.001). Preoperative CA‐125 levels were not significantly associated with clinical covariates. Neither biomarker was associated with survival or disease‐free survival. With respect to nonpleural and nonlymphatic recurrences, mean SMRP levels were elevated in patients with pleural (p = 0.021) and lymph node (p = 0.042) recurrences. CA‐125 levels were significantly higher in patients with abdominal (p < 0.001) and lymph node (p = 0.004) recurrences. Among patients with all three timepoints available, we observed an average decrease in SMRP levels by 1.93 nmol/L (p < 0.001) postoperatively and again an average increase at recurrence by 0.79 nmol/L (p < 0.001). There were no significant changes in levels of CA‐125 across the study timepoints (p = 0.47). Conclusions: Longitudinal changes in SMRP levels corresponded with a radiographic presence of disease in a subset of patients. SMRP surveillance could aid in detection of local recurrences, whereas CA‐125 could be helpful in recognizing abdominal recurrences. [ABSTRACT FROM AUTHOR]

High-altitude cerebral edema (HACE) is a severe neurological condition that can occur at high altitudes. It is characterized by the accumulation of fluid in the brain, leading to a range of symptoms, including severe headache, confusion, loss of coordination, and even coma and death. Exosomes play a crucial role in intercellular communication, and their contents have been found to change in various diseases. This study analyzed the metabolomic characteristics of blood exosomes from HACE patients compared to those from healthy controls (HCs) with the aim of identifying specific metabolites or metabolic pathways associated with the development of HACE conditions. A total of 21 HACE patients and 21 healthy controls were recruited for this study. Comprehensive metabolomic profiling of the serum exosome samples was conducted using ultraperformance liquid chromatography–tandem mass spectrometry (UPLC‒MS/MS). Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to identify the metabolic pathways affected in HACE patients. Twenty-six metabolites, including (+)-camphoric acid, choline, adenosine, adenosine 5′-monophosphate, deoxyguanosine 5′-monophosphate, guanosine, and hypoxanthine-9-β-D-arabinofuranoside, among others, exhibited significant changes in expression in HACE patients compared to HCs. Additionally, these differentially abundant metabolites were confirmed to be potential biomarkers for HACE. KEGG pathway enrichment analysis revealed several pathways that significantly affect energy metabolism regulation (such as purine metabolism, thermogenesis, and nucleotide metabolism), estrogen-related pathways (the estrogen signaling pathway, GnRH signaling pathway, and GnRH pathway), cyclic nucleotide signaling pathways (the cGMP-PKG signaling pathway and cAMP signaling pathway), and hormone synthesis and secretion pathways (renin secretion, parathyroid hormone synthesis, secretion and action, and aldosterone synthesis and secretion). In patients with HACE, adenosine, guanosine, and hypoxanthine-9-β-D-arabinofuranoside were negatively correlated with height. Deoxyguanosine 5′-monophosphate is negatively correlated with weight and BMI. Additionally, LPE (18:2/0:0) and pregnanetriol were positively correlated with age. This study identified potential biomarkers for HACE and provided valuable insights into the underlying metabolic mechanisms of this disease. These findings may lead to potential targets for early diagnosis and therapeutic intervention in HACE patients. [ABSTRACT FROM AUTHOR]

The use of biomarker-led clinical trial designs has been transformative for investigating amyloid-targeting therapies for Alzheimer's disease (AD). The designs have ensured the correct selection of patients on these trials, supported target engagement and have been used to support claims of disease modification and clinical efficacy. Ultimately, this has recently led to approval of disease-modifying, amyloid-targeting therapies for AD; something that should be noted for clinical trials investigating tau-targeting therapies for AD. There is a clear overlap of the purpose of biomarker use at each stage of clinical development between amyloid-targeting and tau-targeting clinical trials. However, there are differences within the potential context of use and interpretation for some biomarkers in particular measurements of amyloid and utility of soluble, phosphorylated tau biomarkers. Given the complexities of tau in health and disease, it is paramount that therapies target disease-relevant tau and, in parallel, appropriate assays of target engagement are developed. Tau positron emission tomography, fluid biomarkers reflecting tau pathology and downstream measures of neurodegeneration will be important both for participant recruitment and for monitoring disease-modification in tau-targeting clinical trials. Bespoke design of biomarker strategies and interpretations for different modalities and tau-based targets should also be considered. [ABSTRACT FROM AUTHOR]

Background: Sepsis is one of the main causes of death in newborns worldwide. Vitamin D levels during fetal and neonatal periods have a significant role in the development of the immunological system. The study aims to evaluate the association between vitamin D levels and the risk of early-onset neonatal sepsis in full-term neonates in a developing country. Methods: This case–control study was conducted at the Neonatal Intensive Care Units (NICUs) of Kasr Alainy Hospital, Cairo, Egypt. The study was composed of two groups; the sepsis group involved full-term neonates appropriate for gestational age with sepsis-related clinical signs. The control group included newborns with no signs of clinical/laboratory infection within 72 h of life. Blood samples were collected on admission during the first three days of life in both groups for the measurement of 25-hydroxyvitamin D levels, Complete Blood Count (CBC), C reactive protein (CRP), and blood culture. Results: Forty-five newborns with clinical and laboratory findings of early-onset neonatal sepsis within 72 h of life were enrolled, and the control group included forty-five newborns with no evidence of sepsis. Vitamin D levels in the sepsis group were significantly lower than in the control group. Apgar score at the first minute was significantly lower in the sepsis group. 57.8% of neonates with sepsis had positive blood cultures. There was a statistical difference between deficient, insufficient, and sufficient vitamin D levels regarding the duration of the NICU stay, which was longer in neonates with deficient vitamin D levels. CRP was significantly higher in neonates with deficient vitamin D levels. The area under the receiver operating characteristic curve for serum vitamin D in the prediction of neonatal sepsis was 0.76 at a cutoff < 19.7(ng/ml). Conclusion: In the current study, full-term newborns with EOS had considerably lower vitamin D levels than healthy controls. Through appropriate vitamin supplementation of the mothers during pregnancy, it could be possible to ensure adequate vitamin D levels for newborns. This may contribute to the reduction of the risk of EOS, together with the other well-known preventive measures (i.e. breastfeeding and intrapartum antibiotic prophylaxis). [ABSTRACT FROM AUTHOR]

Background Cell-based quadrivalent-inactivated influenza vaccine has been shown to have higher vaccine effectiveness than traditional egg-based quadrivalent-inactivated influenza vaccine. This is observed despite similar levels of serum hemagglutinin antibodies induced by each vaccine. Methods In this study, we examine peripheral immune activation after egg-based or cell-based influenza vaccination in a clinical trial in children. Peripheral blood mononuclear cells were isolated, and ribonucleic acid was sequenced from 81 study participants (41 Fluzone, egg based and 40 Flucelvax, cell based) pre- and 7 days postvaccination. Seroconversion was assessed by hemagglutinin inhibition assay. Differential gene expression was determined and pathway analysis was conducted. Results Cell-based influenza vaccine induced greater interferon-stimulated and innate immune gene activation compared with egg-based influenza vaccine. Participants who seroconverted had increased interferon-signaling activation versus those who did not seroconvert. Conclusions These data suggest that cell-based influenza vaccine stimulates immune activation differently from egg-based influenza vaccine, shedding light on reported differences in vaccine effectiveness. [ABSTRACT FROM AUTHOR]

Background Nontoxigenic Corynebacterium diphtheriae , often associated with wounds, can rarely cause infective endocarditis (IE). Five patients with C. diphtheriae IE were identified within 12 months at a Seattle-based hospital system. We reviewed prior C. diphtheriae –positive cultures to determine if detections had increased over time and evaluated epidemiologic trends. Methods We conducted a formal electronic health record search to identify all patients aged ≥18 years with C. diphtheriae detected in a clinical specimen (ie, wound, blood, sputum) between 1 September 2020 and 1 April 2023. We collected patient demographics, housing status, comorbidities, substance-use history, and level of medical care required at detection. We extracted laboratory data on susceptibilities of C. diphtheriae isolates and on other pathogens detected at the time of C. diphtheriae identification. Results Between 1 September 2020 and 1 April 2023, 44 patients (median age, 44 years) had a C. diphtheriae– positive clinical culture, with most detections occurring after March 2022. Patients were predominantly male (75%), White (66%), unstably housed (77%), and had a lifetime history of injecting drugs (75%). Most C. diphtheriae –positive cultures were polymicrobial, including wound cultures from 36 (82%) patients and blood cultures from 6 (14%) patients, not mutually exclusive. Thirty-four patients (77%), including all 5 patients with C. diphtheriae IE, required hospital admission for C. diphtheriae or a related condition. Of the 5 patients with IE, 3 died of IE and 1 from COVID-19. Conclusions Findings suggest a high-morbidity outbreak disproportionately affecting patients who use substances and are unstably housed. [ABSTRACT FROM AUTHOR]

Background: To determine the association between neurological soft signs, executive functions, and serum brain-derived neurotrophic factor (BDNF) levels in children with attention-deficit hyperactivity disorder (ADHD). Methods: Serum BDNF levels were measured in 87 drug-naive boys with ADHD, aged 7--12 years. The Revised Physical and Neurological Examination for Subtle Signs for neurological soft signs, Stroop Color-Word Test for attention functions, and Judgment of Line Orientation Test (JLOT) for visuospatial abilities were performed. Results: Age correlated negatively with dysrhythmia, total time, and total overflow in timed movements, Stroop Color-Word Time (SCWT), and serum BDNF levels. The JLOT significantly negatively correlated with Total Gaits and Stations (P1) and Total Time in Timed Movements (adjusted R2 = 0.247). In addition, SCWT maintained a significant correlation with Total Overflow in Timed Movements (adjusted R2 = 0.206). There was no correlation between serum BDNF levels and NSS. Conclusion: The association between NSS, visuospatial abilities, and selective attention may express a maturational delay in ADHD pathophysiology. Moreover, BDNF may play a role in this maturational delay. Future studies should investigate the contribution of BDNF to neuronal maturation in ADHD. [ABSTRACT FROM AUTHOR]

Background Increasing mortality and morbidity of coronary artery disease (CAD) highlight the emerging need for novel noninvasive markers such as circulating microRNAs (miRNAs). Objective To evaluate the circulating levels of miR-126-3p, miR-210-3p, let-7g-5p, and miR-326, and their associations with known contributors to CAD, in CAD subgroups. Methods We divided the cohort into 4 groups: non-CAD controls (≤30% stenosis; n = 55), and patients with stable angina pectoris (SAP; n = 48), unstable AP (UAP; n = 46), and myocardial infarction (MI; n = 36). The circulating levels of miR-126-3p, miR-210-3p, let-7g-5p, and miR-326 were determined using TaqMan Advanced miRNA Assays in serum specimens. Results Circulating miR-126-3p levels were lower in the MI and UAP groups, compared with the non-CAD group, whereas miR-210-3p circulating levels were lower in the MI group than others. The levels of circulating let-7g-5p were shown to be useful for distinguishing UAP from MI, and there were substantial differences in circulating let-7g-5p levels between the UAP and MI groups. Moreover, lipid levels and ratios were lower in individuals with high circulating miR-126-3p and miR-210-3p levels. Conclusions The study results suggest that circulating miR-126-3p, miR-210-3p, and let-7g-5p are differentiated between different clinical presentations of CAD and associated with lipid levels, which are important risk factors and determinants of CAD. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for detection of minimal residual disease (MRD), monitoring treatment response, and early detection of recurrence in cancer patients. In this study, we explored the utility of ctDNA‐based MRD detection to predict recurrence in a real‐world cohort of primarily early‐stage non‐small cell lung cancer (NSCLC) patients treated with curative intent. Methods: Longitudinal plasma samples were collected post curative‐intent treatment from 36 patients with stage I–IV NSCLC. A personalized, tumor‐informed assay was used to detect and quantify ctDNA in plasma samples. Results: Of the 24 patients with plasma samples available during the MRD window (within 6 months of curative surgery and before adjuvant therapy), ctDNA was detectable in two patients. Patients with ctDNA‐positivity during the MRD window were 15 times more likely to recur compared to ctDNA‐negative patients (HR: 15.0, 95% CI: 1.0–253.0, p = 0.010). At any time post‐curative intent treatment, ctDNA‐positivity was associated with significantly poorer recurrence‐free survival compared to persistently ctDNA‐negative patients (p < 0.0001). Conclusion: Our real‐world data indicate that longitudinal, personalized, tumor‐informed ctDNA monitoring is a valuable tool in patients with NSCLC receiving curative treatment to identify patients at high risk for recurrence. [ABSTRACT FROM AUTHOR]

Objective: To describe a multicenter outbreak of R. pickettii that occurred in a large number of critically ill patients in a city in Colombia, during the COVID-19 pandemic. Methods: In April 2021, the National Institute for Food and Drug Surveillance (INVIMA) reported an outbreak of R. pickettii infection associated with contaminated intravenous medications. The Municipal Health Department began collecting data for all cases identified by the hospitals and the results of microbiological studies. Medical records and death certificates of included cases were reviewed. Results: Between March and May 2021, 66 cases of R. pickettii bloodstream infections from nine hospitals were documented. The median age of the patients was 60 years (IQR 51–72), and most of them had comorbidities (78.8%), mainly arterial hypertension and diabetes mellitus. At the time of the R. pickettii bloodstream infection, 89.4% had COVID-19, 86.4% were on mechanical ventilation, and 98.5% were receiving corticosteroids. The overall mortality was 81.8%. Nearly 60% of the deaths were related to R. pickettii bloodstream infections. R. pickettii was identified in the cultures from intravenous medications. Conclusions: This large multicenter outbreak caused by intravenous medications contaminated with R. pickettii mainly affected critically ill COVID-19 patients. Mortality was high and largely related to R. pickettii bloodstream infection. [ABSTRACT FROM AUTHOR]

Background: Today, with wars raging in Ukraine and the Middle East, the demand for blood is high. Despite this, few companies produce the necessary equipment to draw, store, and transfuse whole blood. This study evaluated the safety and performance of a 3D printed bottle cap in conjunction with a water bottle and some available consumables to draw and store fresh whole blood. Study Design and Methods: Bags of saline, and freshly donated whole blood, was transferred to the water bottle through a 3D printed bottle cap and stored for 72 h. An identical setup, transferring saline to a Terumo blood collection bag was used as control. Performance and safety were evaluated by calculating infusion rate and observing for backflow, respectively. The blood was also tested for hemolysis and bacterial growth at four sampling points. Results: The cap‐and‐bottle setup was faster than control in terms of flow rate when transferring saline (1.53 vs. 1.81 mL/s, p <.001), and non‐inferior to saline control when transfusing blood (1.53 vs. 1.49 mL/s, p =.641). We did not observe any risks of causing the donor iatrogenic harm, and there was no evidence of increased hemolysis. However, there were traces of bacterial contamination in three of six bottles. Conclusion: This study indicates that drawing blood is both feasible and safe, utilizing a 3D printed cap and bottle setup. Flow rate was faster than control, and mechanical properties of the blood were not affected. We were unable to determine the source of bacterial contamination in the blood. [ABSTRACT FROM AUTHOR]

Introduction: The use of low titer O whole blood (LTOWB) has expanded although it remains unclear how many civilian trauma centers are using LTOWB. Methods: We analyzed data on civilian LTOWB recipients in the American College of Surgeons Trauma Quality Improvement Program (TQIP) database 2020–2021. Unique facility keys were used to determine the number of centers that used LTOWB in that period. Results: A total of 16,603 patients received LTOWB in the TQIP database between 2020 and 2021; 6600 in 2020, and 10,003 in 2021. The total number of facilities that reported LTOWB use went from 287/779 (37%) in 2020 to 302/795 (38%) in 2021. Between 2020 and 2021, among all level 1–3 designated trauma facilities that report to TQIP LTOWB use increased at level‐1 centers (118 to 129), and level‐2 centers (81 to 86), but decreased in level‐3 facilities (9 to 4). Among pediatric and dual pediatric‐adult designated hospitals there was a decrease in the number of pediatric level‐1 centers (29 to 28) capable of administering LTOWB. Among centers with either single or dual level‐1 trauma center designation with adult centers, the number that administered LTOWB to injured pediatric patients also decreased from 17 to 10, respectively. Conclusions: There was an increase in the number of facilities transfusing LTOWB between 2020 and 2021. The use of LTOWB is underutilized in children at centers that have it available. These findings inform the expansion of LTOWB use in trauma. [ABSTRACT FROM AUTHOR]

Background: The Role 2 setting represents the most far‐forward military treatment facility with limited surgical and holding capabilities. There are limited data to guide recommendations on blood product utilization at the Role 2. We describe the consumption of blood products in this setting. Study Design and Methods: We analyzed data from 2007 to 2023 from the Department of Defense Trauma Registry (DODTR) that received care at a Role 2. We used descriptive and inferential statistics to characterize the volumes of blood products consumed in this setting. We also performed a secondary analysis of US military, Coalition, and US contractor personnel. Results: Within our initial cohort analysis of 15,581 encounters, 17% (2636) received at least one unit of PRBCs or whole blood, of which 11% received a submassive transfusion, 4% received a massive transfusion, and 1% received a supermassive transfusion. There were 6402 encounters that met inclusion for our secondary analysis. With this group, 5% received a submassive transfusion, 2% received a massive transfusion, and 1% received a supermassive transfusion. Conclusions: We described volumes of blood products consumed at the Role 2 during recent conflicts. The maximum number of units consumed among survivors exceeds currently recommended available blood supply. Our findings suggest that rapid resupply and cold‐stored chain demands may be higher than anticipated in future conflicts. [ABSTRACT FROM AUTHOR]

• Rare genetic diseases are an important global public health problem. • This study aims to present prevalence of hematopoietic rare genetic diseases. • Diagnosed female population (53.04%) were higher than male (46.96%) • The prevalence increased gradually from 2018 to 2022. Rare genetic diseases are an important global public health problem. At present there are defined approximately 8120 genetic diseases in 15,465 epidemiological datasets and 70% of them start in childhood. Hematopoiesis is the production of all cellular components of blood and continues throughout life. This study aims to present prevalence of hematopoietic rare genetic diseases recorden in Turkey. The population of study consist of 84.680.273 people who received healthcare from the Turkish National Health Service (49.9% female, 50.1% male). TNHS collects and records electronic data which relates with illness or health information of Turkish population since 2018. All healthcare facilities utilize the Personal Electronic Health Record System (PHR), aligning with standards outlined in the Turkish National Health Data Dictionary and the Health Coding Reference Server (HCRS) established by the Ministry of Health in 2007. The data dictionary comprises essential packages such as patient application and examination records. Diagnosed female population (53.04%) were higher than male (46.96%). Data shows that most of the people with rare genetic diseases were diagnosed in Marmara Region. The overall prevalence of Hematopoietic Rare Genetic Diseases higher in the years of 2021 and 2022. The prevalence increased gradually from 2018 to 2022. The consanguinity marriage seems to be the main problem which resulted higher rate of rare genetic diseases in Türkiye. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess whether circulating histone‐specific T cells represent tools for precision medicine in systemic lupus erythematosus (SLE). Methods: Seroprevalence of autoantibodies and HLA‐DR beta (DRB) 1 profile were assessed among 185 patients with SLE and combined with bioinformatics and literature evidence to identify HLA–peptide autoepitope couples for ex vivo detection of antigen‐specific T cells through flow cytometry. T cell differentiation and polarization was investigated in patients with SLE, patients with Takayasu arteritis, and healthy controls carrying HLA‐DRB1*03:01 and/or HLA‐DRB1*11:01. SLE Disease Activity Index 2000 and Lupus Low Disease Activity State were used to estimate disease activity and remission. Results: Histone‐specific CD4+ T cells were selectively detected in patients with SLE. Among patients with a history of anti‐DNA antibodies, 77% had detectable histone‐specific T cells, whereas 50% had lymphocytes releasing cytokines or upregulating activation markers after in vitro challenge with histone peptide antigens. Histone‐specific regulatory and effector T helper (Th) 1‐, Th2‐, and atypical Th1/Th17 (Th1*)‐polarized cells were significantly more abundant in patients with SLE with quiescent disease. In contrast, total Th1‐, Th2‐, and Th1*‐polarized and regulatory T cells were similarly represented between patients and controls or patients with SLE with active versus quiescent disease. Histone‐specific effector memory T cells accumulated in the blood of patients with quiescent SLE, whereas total effector memory T cell counts did not change. Immunosuppressants were associated with expanded CD4+ histone‐specific naive T (TN) and terminally differentiated T cells. Conclusion: Histone‐specific T cells are selectively detected in patients with SLE, and their concentration in the blood varies with disease activity, suggesting that they represent innovative tools for patient stratification and therapy. [ABSTRACT FROM AUTHOR]

Purpose: Exercise-induced cell-free DNA (ei-cfDNA) has been studied in response to various types of exercise. Its correlation with exercise intensity and duration has been observed consistently. However, comprehensive measurements and exploration of the tissue of origin are lacking. The aim of this study is to establish precise connections between exercise variables and the distribution of tissue of origin, aiming to provide further evidence supporting its use as a biomarker for exercise. Methods: Twelve self-identified active adults (six men and six women) performed a crossover study starting with either endurance testing or resistance testing under different intensities and protocols. We obtained blood before and after each exercise session and measured the levels of cfDNA and determined its tissue of origin utilizing cell type-specific DNA methylation patterns in plasma. Results: We found that when duration and intensity are fixed, ei-cfDNA fold change correlates with energy expenditure (P = 0.001) in endurance testing and years trained (P = 0.001) in resistance testing. Most of the ei-cfDNA comes from increases in white blood cells (~95%) where neutrophils make up the majority (~74%) and the distribution is different between exercise modalities and protocols. Conclusions: This study highlights the potential of exercise-induced cfDNA as a biomarker for exercise, showing correlations with energy expenditure and a consistent pattern of tissue origin. Additional research is needed to investigate potential sex differences in the response of cfDNA to exercise, further exploring its clinical implications. [ABSTRACT FROM AUTHOR]

There are two FDA‐approved bisphosphonate products, clodronate (Osphos®) and tiludronate (Tildren®), for use in horses. It is hypothesized that bisphosphonates can produce analgesic effects and prevent proper healing of microcracks in bone. Therefore, bisphosphonate use is banned in racehorses. However, bisphosphonates have a short detection window in the blood before sequestration in the skeleton, making the reliability of current drug tests questionable. Seven exercising Thoroughbred horses were administered clodronate (1.8 mg/kg i.m.), and four were administered saline. RNA was isolated from peripheral blood mononuclear cells (PBMCs) collected immediately before a single dose of clodronate or saline and then on Days 1, 6, 28, 56 and 182 post‐dose. mRNA was sequenced and analysed for differentially expressed transcripts. While no single transcripts were differentially expressed, pathway analysis revealed that p38 MAPK (p =.04) and Ras (p =.04) pathways were upregulated, and cadherin signalling (p =.02) was downregulated on Day 1. Previously investigated biomarkers, cathepsin K (CTSK) and type 5 acid phosphatase (ACP5), were analysed with RT‐qPCR in a targeted gene approach, with no significant difference observed. A significant effect of time on gene expression for ACP5 (p =.03) and CTSK (p <.0001) was observed. Thus, these genes warrant further investigation for detecting clodronate use over time. [ABSTRACT FROM AUTHOR]

This study aims to show the relation between biomarkers in maternal and cord-blood samples and fetal heart rate variability (fHRV) metrics through a non-invasive fetal magnetocardiography (fMCG) technique. Twenty-three women were enrolled for collection of maternal serum and fMCG tracings immediately prior to their scheduled cesarean delivery. The umbilical cord blood was collected for measurement of biomarker levels. The fMCG metrics were then correlated to the biomarker levels from the maternal serum and cord blood. Brain-derived neurotrophic factor (BDNF) had a moderate correlation with fetal parasympathetic activity (0.416) and fetal sympathovagal ratios (−0.309; −0.356). Interleukin (IL)-6 also had moderate-sized correlations but with an inverse relationship as compared to BDNF. These correlations were primarily in cord-blood samples and not in the maternal blood. In this small sample-sized exploratory study, we observed a moderate correlation between fHRV and cord-blood BDNF and IL-6 immediately preceding scheduled cesarean delivery at term. These findings need to be validated in a larger population. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), a primary cause of dementia globally, is traditionally diagnosed via cerebrospinal fluid (CSF) measures and positron emission tomography (PET). The invasiveness, cost, and limited accessibility of these methods have led to exploring blood-based biomarkers as a promising alternative for AD diagnosis and monitoring. Recent advancements in sensitive immunoassays have identified potential blood-based biomarkers, such as Aβ42/Aβ40 ratios and phosphorylated tau (p-tau) species. This paper briefly evaluates the clinical utility and reliability of these biomarkers across various AD stages, highlighting challenges like refining plasma Aβ42/Aβ40 assays and enhancing the precision of p-tau, particularly p-tau181, p-tau217, and p-tau231. The discussion also covers other plasma biomarkers like neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and synaptic biomarkers, assessing their significance in AD diagnostics. The need for ongoing research and development of robust assays to match the performance of CSF and PET biomarkers is underscored. In summary, blood-based biomarkers are increasingly crucial in AD diagnosis, follow-up, prognostication, treatment response evaluation, and population screening, particularly in primary care settings. These developments are set to revolutionize AD diagnostics, offering earlier and more accessible detection and management options. [ABSTRACT FROM AUTHOR]

• Twenty-one PFASs levels in human serum, blood and urine of patients with liver diseases were analyzed. • Higher total PFAS concentrations were detected in hepatocellular carcinoma (HCC) patients than in non-HCC patients. • Significant correlation between PFAS concentrations in patients and their demographic characteristics (including gender, age, and BMI) were found. • Serum PFNA and PFBS concentrations were associated with elevated liver function biomarkers ALP and GGT. Studies have shown that per- and polyfluoroalkyl substances (PFASs) may be hepatotoxic in animals or humans. However, data on clinical epidemiology are very limited. In this study, 21 PFASs were determined in patients with liver diseases, with the highest median concentrations detected in the serum sample (26.7 ng/mL), followed by blood (10.7 ng/mL) and urine (5.02 ng/mL). Higher total PFAS concentrations were found in hepatocellular carcinoma (HCC) patients compared to non-HCC patients, with significant discrepancies in serum and blood samples. Besides, significant correlations were also found among PFAS concentrations and age, gender, body mass index (BMI), and liver function biomarkers levels. For example, PFAS concentrations are significantly higher in males than in females; Several serum PFASs concentrations increase with age and BMI, while the serum perfluorohexane sulfonic acid (PFHxS) concentrations are negatively correlated with age. In addition, multiple regression models adjusted for age, gender and BMI found that increased serum perfluorobutane sulfonic acid (PFBS), perfluoroheptane sulfonic acid (PFHpS) and perfluorohexylphosphonic acid (PFHxPA) conentrations are correlated with elevated alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alpha-fetoprotein (AFP) (p < 0.05). Our results provide epidemiological support for the future study on the potential clinical hepatotoxicity of PFAS. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Critical adolescent neural refinement is controlled by the DCC (deleted in colorectal cancer) protein, a receptor for the netrin-1 guidance cue. We sought to describe the effects of reduced DCC on neuroanatomy in the adolescent and adult mouse brain. Methods: We examined neuronal connectivity, structural covariance, and molecular processes in a DCC -haploinsufficient mouse model, compared with wild-type mice, using new, custom analytical tools designed to leverage publicly available databases from the Allen Institute. Results: We included 11 DCC -haploinsufficient mice and 16 wild-type littermates. Neuroanatomical effects of DCC haploinsufficiency were more severe in adolescence than adulthood and were largely restricted to the mesocorticolimbic dopamine system. The latter finding was consistent whether we identified the regions of the mesocorticolimbic dopamine system a priori or used connectivity data from the Allen Brain Atlas to determine de novo where these dopamine axons terminated. Covariance analyses found that DCC haploinsufficiency disrupted the coordinated development of the brain regions that make up the mesocorticolimbic dopamine system. Gene expression maps pointed to molecular processes involving the expression of DCC , UNC5C (encoding DCC's co-receptor), and NTN1 (encoding its ligand, netrin-1) as underlying our structural findings. Limitations: Our study involved a single sex (males) at only 2 ages. Conclusion: The neuroanatomical phenotype of DCC haploinsufficiency described in mice parallels that observed in DCC -haploinsufficient humans. It is critical to understand the DCC- haploinsufficient mouse as a clinically relevant model system. [ABSTRACT FROM AUTHOR]

Background: This work aimed to analyze serum S100B levels and brain-derived neurotrophic factor (BDNF) in patients with lumbar disc prolapse to test their predictive values concerning the therapeutic efficacy of pulsed radiofrequency. Methods: This prospective interventional study was carried out on 50 patients candidates for radiofrequency for treating symptomatic lumbar disc prolapse. Pain severity and functional disability were assessed using the Numeric Rating Scale (NRS) and Functional rating index (FRI) before as well as two weeks, 1, 3, and 6 months after the radiofrequency. Quantitative assessment of serum S100B level and BDNF was done for all the included patients one day before radiofrequency. Results: The scores of NRS and FRI were significantly improved at two weeks, 1, 3, and 6 months following radiofrequency (P-value < 0.001 in all comparisons). Statistically significant positive correlations were found between duration of pain, NRS, and S100B serum level before radiofrequency, and both NRS (P-value = 0.001, 0.035, < 0.001 respectively) and FRI (P-value = < 0.001, 0.009, 0.001 respectively) 6 months following radiofrequency. Whereas there were statistically significant negative correlations between BDNF serum level before radiofrequency and both NRS and FRI 6 months following radiofrequency (P-value = 0.022, 0.041 respectively). NRS and S100B serum levels before radiofrequency were found to be independent predictors of NRS 6 months following radiofrequency (P-value = 0.040. <0.001, respectively). Conclusion: Serum level of S100B is a promising biomarker that can predict functional outcomes after pulsed radiofrequency in patients with lumbar disc prolapse. [ABSTRACT FROM AUTHOR]

We assessed human immunodeficiency virus (HIV) load in plasma and semen during primary HIV infection using serial samples of semen and plasma during the first 24 weeks after diagnosis in untreated participants and those who started antiretroviral therapy (ART) immediately at diagnosis. In the absence of treatment, semen viral load was >1000 copies/mL in almost all specimens (83%) collected 2–10 weeks after the estimated date of HIV acquisition and remained >1000 copies/mL in 35% of untreated participants at the last observed time point. Thus, in the absence of ART, semen viral load remained at a level consistent with transmissibility throughout primary infection. [ABSTRACT FROM AUTHOR]

Objective A heart rate characteristics index (HeRO score), incorporating low variability and superimposed decelerations, was developed as a sepsis risk indicator for preterm infants in the neonatal intensive care unit (NICU). A rise in the risk score should prompt consideration of other clinical changes that may be signs of sepsis to decide whether a workup and antibiotics are needed. We aimed to develop a framework to systematically consider signs potentially indicating sepsis in very low birth weight (VLBW) infants. Study Design We developed easy-recall acronyms for 10 signs of sepsis in VLBW infants. Over 12 months in a level IV NICU, neonatology fellows completed a brief survey after each shift to document changes prompting sepsis workups. We analyzed associations between survey data, hourly heart rate characteristic data, and the diagnosis of the workup, grouped as culture-positive sepsis (CXSEP, positive blood or urine culture), clinical sepsis (CLINSEP, negative cultures treated with antibiotics ≥5 days), or sepsis ruled out (SRO, negative cultures and <3 days antibiotics). Results We analyzed 93 sepsis workups in 48 VLBW infants (35 CXSEP, 20 CLINSEP, and 38 SRO). The most frequently cited changes prompting the workups were heart rate patterns and respiratory deterioration, which were common in all three categories. Low blood pressure and poor perfusion were uncommonly cited but were more likely to be associated with CXSEP than the other signs. A rise in the HeRO score ≥1 from 0 to 12 hours before compared with 12to 72 hours prior the blood culture occurred in 31% of workups diagnosed as CXSEP, 16% CLINSEP, and 31% SRO. Conclusion The HeRO score can alert clinicians to VLBW infants at high or increasing risk of a sepsis-like illness, but heart rate characteristic patterns are highly variable in individual babies. The easy-recall NeoSEP-10 framework can assist clinicians in considering other clinical changes when making decisions about sepsis workups and the duration of antibiotics. Key Points Abnormal heart rate characteristics can indicate sepsis or other pathologies in preterm infants. We developed a simple bedside tool to consider clinical signs potentially associated with sepsis. Considering vital sign trends together with clinical changes is a key to right-timing antibiotics. [ABSTRACT FROM AUTHOR]

Simple Summary: In cancer, including head and neck cancer (HNC), certain key players in the body's inflammatory process, such as the interleukin (IL)-6 and IL-1 systems, are associated with outcomes. We studied some of these key players in a subgroup of HNC patients. From one blood sample measured at diagnosis, we determined high levels of molecules from members of the IL-6 and IL-1 families with their associated soluble cytokine receptors. High values indicated a lower survival rate. This prediction was to some extent better than the standard clinical predictors used. The results highlight potential new targets for immune treatment development. Additionally, these findings could contribute to the refinement of cancer treatment strategies, particularly in the context of emerging immune therapies. Activation of the acute-phase cascade (APC) has been correlated with outcomes in various cancers, including head and neck squamous cell carcinoma (HNSCC). Primary drivers of the APC are the cytokines within the interleukin-6 (IL-6) and IL-1 families. Plasma levels of IL-6 family cytokines/soluble receptors (IL-6, IL-27, IL-31, OSM, CNTF, soluble (s-)gp130, s-IL-6Rα) and IL-1 family members (IL-1RA, s-IL-33Rα) were determined at diagnosis for 87 human papillomavirus (HPV)-negative (−) HNSCC patients. We then studied the 5-year Disease-Specific Survival (DSS) and Overall Survival (OS). Increased plasma levels of IL-6 (p < 0.001/p < 0.001) (DSS/OS), IL-31 (p = 0.044/p = 0.07), IL-1RA (p = 0.004/p = 0.035), soluble (s)-IL-6Rα p = 0.022/p = 0.035), and s-gp130 (p = 0.007/p = 0.003) at diagnosis were predictors of both OS and DSS from HPV(−) HNSCC patients. The cytokine DSS/OS predictions were associated with TNM stage and smoking history, whereas the soluble receptors IL-6Rα, gp130, and IL33Rα more uniquely predicted DSS/OS. Clinically, IL-6 levels above 2.5 pg/mL yielded 75% specificity and 70% sensitivity for DSS. In conclusion, high plasma levels of IL-6, IL-31, and IL-1RA, as well as the soluble receptors IL-6Rα, gp130, and IL33Rα, predicted clinical outcome. This shows their potential as candidates for both general therapy and immune therapy stratification, as well as being future platforms for the development of new immunotherapy. [ABSTRACT FROM AUTHOR]

Background The 2023 Duke-ISCVID (International Society of Cardiovascular Infectious Diseases) classification is a new diagnostic tool for infective endocarditis, updating the 2000 modified Duke and the 2015 European Society for Cardiology (ESC) classifications. In comparison, its sensitivity is higher; however, its specificity remains to be evaluated and compared to that of the 2 other classifications in endocarditis suspected patients. Methods We retrospectively collected the characteristics of patients hospitalized in Bichat University's Hospital, Paris, in 2021, who had been evaluated for clinical suspicion of endocarditis, have had at least a transthoracic echocardiography, 2 pairs of blood cultures, 3-month follow-up and in whom endocarditis diagnosis was finally rejected. All patients were classified by 2000 modified Duke, 2015 ESC and 2023 Duke-ISCVID, as though the endocarditis diagnosis had not been rejected. Results In total, 130 patients' charts were analyzed. Mean age was 62 years, 84 (64.6%) were male, 39 (30.0%) had prosthetic cardiac valve or valve repair, 21 (16.2%) cardiac implanted electronic device, and 30 (23.1%) other cardiac conditions. Overall, 5, 2, and 5 patients were falsely classified as definite endocarditis with the 2000 modified Duke, 2015 ESC, and 2023 Duke-ISCVID classifications, respectively. The corresponding specificities were 96.2% (95% confidence interval [CI] [90.8%, 98.6%]), 98.5% (95% CI [93.9%, 99.7%]), and 96.2% (95% CI [90.8%, 98.6%]). The rates of possible endocarditis were of 38%, 35%, and 35% in the 3 classifications, respectively. Conclusions The 2023 Duke-ISCVID classification is highly specific for ruling out the diagnosis of definite infective endocarditis in patients who had been evaluated for IE. [ABSTRACT FROM AUTHOR]

Background The development of chatbot artificial intelligence (AI) has raised major questions about their use in healthcare. We assessed the quality and safety of the management suggested by Chat Generative Pre-training Transformer 4 (ChatGPT-4) in real-life practice for patients with positive blood cultures. Methods Over a 4-week period in a tertiary care hospital, data from consecutive infectious diseases (ID) consultations for a first positive blood culture were prospectively provided to ChatGPT-4. Data were requested to propose a comprehensive management plan (suspected/confirmed diagnosis, workup, antibiotic therapy, source control, follow-up). We compared the management plan suggested by ChatGPT-4 with the plan suggested by ID consultants based on literature and guidelines. Comparisons were performed by 2 ID physicians not involved in patient management. Results Forty-four cases with a first episode of positive blood culture were included. ChatGPT-4 provided detailed and well-written responses in all cases. AI's diagnoses were identical to those of the consultant in 26 (59%) cases. Suggested diagnostic workups were satisfactory (ie, no missing important diagnostic tests) in 35 (80%) cases; empirical antimicrobial therapies were adequate in 28 (64%) cases and harmful in 1 (2%). Source control plans were inadequate in 4 (9%) cases. Definitive antibiotic therapies were optimal in 16 (36%) patients and harmful in 2 (5%). Overall, management plans were considered optimal in only 1 patient, as satisfactory in 17 (39%), and as harmful in 7 (16%). Conclusions The use of ChatGPT-4 without consultant input remains hazardous when seeking expert medical advice in 2023, especially for severe IDs. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To define the utility of the Triage Revised Trauma Score (TRTS), GCS/Age/arterial Pressure (GAP) score, and shock index (SI) in predicting the need for in‐flight blood product administration in civilian trauma patients transported by an aeromedical platform.A retrospective chart review of 3582 aeromedical trauma cases was conducted. An initial TRTS, GAP score and SI were calculated for each patient, and the administration of in‐flight blood products was also recorded. Receiver operating characteristic (ROC) curves were used to quantify the predictive discrimination of the TRTS, GAP score and SI on the need for in‐flight blood product administration.The SI showed a superior predictive value compared to the TRTS and GAP score. The SI showed an area under the curve on the ROC curve of 0.85 in both primary and inter‐hospital transfer cases, indicating reasonable predictive value.The SI demonstrates favourable test characteristics for predicting the need for in‐flight blood product administration. Prospective validation of these results is warranted. [ABSTRACT FROM AUTHOR]

Objective: Calprotectin (CLP), S100A6, and high mobility group nucleosome-binding protein 1 (HMGN1), known as alarmins, are involved in the pathogenesis of many tumors. In this study, we aimed to investigate the relationships of serum CLP, S100A6, and HMGN1 levels with the clinical and laboratory findings of patients with multiple myeloma (MM) and their roles in the pathogenesis of MM. Materials and Methods: We measured the serum CLP, S100A6, and HMGN1 levels of 55 newly diagnosed patients and 32 healthy controls using the sandwich enzyme-linked immunosorbent assay method. The medical records of the patients were also reviewed. Results: Serum CLP, S100A6, and HMGN1 levels were significantly decreased in MM patients compared to the control group (p=0.012, p=0.001, and p=0.030, respectively). Receiver operating characteristic analysis was used to determine diagnostic cut-off values for serum CLP, S100A6, and HMGN1 of <98 ng/mL (area under the curve [AUC]: 0.663, 95% confidence interval [CI]: 0.554-0.761, p=0.009), <1174.5 pg/mL (AUC: 0.706, 95% CI: 0.598-0.799, p=0.001), and <440.18 pg/mL (AUC: 0.640, 95% CI: 0.530-0.740, p=0.03), respectively. CLP levels were found to be statistically significantly higher in patients with light chain MM (91.58±22.57 ng/mL) compared to heavy chain MM (79.42±15.83 ng/mL) (p=0.03). A negative correlation was observed between CLP and M protein, immunoglobulin G, globulin, and beta-2 microglobulin (correlation coefficients: -0.361, -0.370, -0.279, -0.300, respectively; p=0.024, p=0.06, p=0.04, p=0.0033). Conclusion: In this study, we found that serum CLP, S100A6, and HMGN1 levels were statistically lower in patients with newly diagnosed MM compared to the control group. These results suggest that CLP may bind to the paraprotein produced by heavy chain MM in the blood, causing its blood levels to be low. Additionally, low levels of HMGN1, which is involved in DNA repair, suggest that HMGN1 may contribute to the complex genetic abnormalities found in cases of MM. [ABSTRACT FROM AUTHOR]