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This study aimed to determine whether caffeine gum influenced perceptual-cognitive and physical performance during the extra-time period of simulated soccer match-play. Semiprofessional male soccer players (n = 12, age: 22 ± 3 years, stature: 1.78 ± 0.06 m, mass: 75 ± 9 kg) performed 120-min soccer-specific exercise on two occasions. In a triple-blind, randomized, crossover design, players chewed caffeinated (200 mg; caffeine) or control (0 mg; placebo) gum for 5 min following 90 min of soccer-specific exercise. Perceptual-cognitive skills (i.e., passing accuracy, reaction time, composure, and adaptability) were assessed using a soccer-specific virtual reality simulator, collected pre- and posttrial. Neuromuscular performance (reactive-strength index, vertical jump height, absolute and relative peak power output, and negative vertical displacement) and sprint performance (15 and 30 m) were measured at pretrial, half-time, 90 min, and posttrial. Caffeine gum attenuated declines in reaction time (pre: 90.8 ± 0.8 AU to post: 90.7 ± 0.8 AU) by a further 4.2% than placebo (pre: 92.1 ± 0.8 AU to post: 88.2 ± 0.8 AU; p <.01). Caffeine gum reduced composure by 4.7% (pre: 69.1 ± 0.8 AU to post: 65.9 ± 0.8 AU) versus placebo (pre: 68.8 ± 0.8 AU to post: 68.3 ± 0.8 AU; p <.01). Caffeine gum did not influence any other variables (p >.05). Where caffeine gum is consumed by players prior to extra-time, reaction time increases but composure may be compromised, and neuromuscular and sprint performance remain unchanged. Future work should assess caffeine gum mixes with substances like L-theanine that promote a relaxed state under stressful conditions. [ABSTRACT FROM AUTHOR]

Optimal omega-3 status, influenced by increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is vital for physiological health. This study investigated the impact of ad libitum fish oil supplementation on the omega-3 status of female athletes in a professional rugby league team during a competitive season. Twenty-four (n = 24) athletes participated, and their omega-3 status was assessed using the Omega-3 Index (O3I) and arachidonic acid (AA) to EPA ratio through finger-prick blood samples taken at the start and end of the season. They were given access to a fish oil supplement (PILLAR Performance, Australia) with a recommended daily dose of four capsules per day (2,160 mg EPA and 1,440 mg docosahexaenoic acid). At the beginning of the season, the group mean O3I was 4.77% (95% confidence interval [CI: 4.50, 5.04]) and the AA to EPA ratio was 14.89 (95% CI [13.22, 16.55]). None of the athletes had an O3I exceeding 8%. By the season's end, the O3I was a significantly increased to 7.28% (95% CI [6.64, 7.93], p <.0001) and AA to EPA ratio significantly decreased to a mean of 6.67 (95% CI [5.02, 8.31], p <.0001), driven primarily by the significant increase in EPA of +1.14% (95% CI [0.77, 1.51], p <.0001). However, these changes were varied between the athletes and most likely due to compliance. This study has demonstrated that using the objective O3I feedback scale is possible with elite female rugby athletes, but individual strategies will be required to achieve daily intake targets of EPA + DHA. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated within- and between-matches blood lactate (La−) responses across an international Rugby Sevens tournament (5 matches over 2 d) in male and female players. Methods: Earlobe blood samples were taken from 25 professional players around matches: before warm-up (PRE), immediately upon finishing match participation (POST), and 30 minutes postmatch (30 min). Results: POST [La−] (mean [SD], range) for males was 10.3 (3.2; 2.9–20.2) mmol·L−1 and for females was 9.1 (2.3; 3.4–14.6) mmol·L−1. Linear mixed-effects models revealed a decrease in POST [La−] after match 5, compared to match 1. Increased PRE [La−] was found before match 2 (+0.8 [0.6–1.1] mmol·L−1), match 3 (+0.8 [0.5–1.1] mmol·L−1), and match 5 (+0.6 [0.4–0.9] mmol·L−1) compared to match 1 (all P <.001). The [La−] remained elevated at 30 min, compared to PRE (+1.7 [1.4–2.0] mmol·L−1, P <.001), with ∼20% of values persisting >4 mmol·L−1. Higher POST was observed in males compared to females (+1.6 [0.1–3.2] mmol·L−1, P =.042); however, no differences between sexes were found across 30 min or PRE [La−]. No [La−] differences between positions (backs and forwards) were identified. Conclusions: Lactate concentrations above 10 mmol·L−1 are required to effectively simulate the anaerobic demands of international Rugby Sevens matches. Practitioners are advised to individualize anaerobic training prescription due to the substantial variability observed within positional groups. Additionally, improving athletes' metabolic recovery capacity through training, nutrition, and recovery interventions may enhance physical preparation for subsequent matches within a day, where incomplete lactate clearance was observed. [ABSTRACT FROM AUTHOR]

Sample preparation presents a major challenge in point-of-care (POC) diagnostic assays, including ones requiring whole blood as the starting specimen. This study presents an integrated sample preparation device -- which we call PRECISE -- that performs both plasma separation and nucleic acid extraction, enabling streamlined sample preparation from whole blood requiring only a commercially available blood collection tool and a syringe, and no other external equipment or electricity. Plasma separation is performed using a dual-membrane filter (which filters out blood components while limiting membrane clogging) integrated into the cartridge, and nucleic acid extraction is performed by users moving magnets (to mix the samples, and along a guided track). The plasma filtration demonstrated recovery on par with lab-based centrifugation, and the extraction module showed performance similar to benchtop-based magnetic bead extraction. A sample-to-result demonstration on 50 μL of whole blood spiked with virions of hepatitis C virus (HCV), operating the PRECISE cartridge in 16 minutes followed by benchtop PCR, showed a limit of detection (~6770 IU mL-1) on the order of the minimal requirements of target product profile for POC HCV detection. Future work on the PRECISE cartridge, building on POC accessibility and fast sample preparation demonstrated in this work, may enable detection of bloodborne pathogens from whole-blood specimens collected at the POC. [ABSTRACT FROM AUTHOR]

Background and Objectives Materials and Methods Results Conclusion Wrong blood in tube (WBIT) continues to be a preventable cause of unintended harm to the patient. The literature describing extent of the problem, its consequences and factors leading to WBIT from the perspective of lower middle‐income countries (LMICs) is limited. The present study describes WBIT and its outcome in a hospital‐based blood centre from an LMIC.WBIT events occurring during the study period were analysed to identify the root cause. In addition, they were analysed according to discipline, department and time of sample draw. Root causes were divided and compared with standard operating procedure (SOP) for sample collection for blood requests. All WBIT events were followed and their outcomes analysed.WBIT events occurred at a rate of 4.8/10,000 blood requests, with a higher rate in urgent requests (5.2/10,000 requests). The average rate of WBIT was higher in surgical disciplines compared to medical and acute care services (6.58 vs. 4.43 vs. 3/10,000 requests). The highest rate of WBIT was observed when requests were received during 8:00 PM–2:00 AM (p = 0.02). Deviations from SOP with contribution from human and organizational elements were identified as the root cause. The consequences ranged from delay in providing blood to acute haemolytic transfusion reactions.We found that WBITs occurred at a rate comparable to that reported from developed countries. Use of software and automation may reduce the rate of WBIT but not eliminate it completely. Strict adherence to SOPs and continuous training of phlebotomy staff would help reduce it to a minimum. Blood centres need to develop specific strategies with respect to their root causes. [ABSTRACT FROM AUTHOR]

A crucial measure of diabetes management is to monitor blood glucose, which often requires continuous blood collection, leading to economic burden and discomfort. Blood glucose and glycated hemoglobin A1c serve as traditional indicators of glucose monitoring. But now glycated albumin, fructosamine, and 1,5-anhydroglucitol (1,5-AG) have been gaining more attention. 1,5-AG is a chemically stable monosaccharide that exists in the human body. Its serum concentration remains stable when blood glucose levels are normal. However, it decreases when blood glucose exceeds the renal glucose threshold. Studies have shown that 1.5-AG reflects blood glucose changes in 1 to 2 weeks; therefore, decreased levels of serum 1,5-AG can serve as a clinical indicator of short-term blood glucose disturbances. Recent studies have shown that 1,5-AG can be used not only for the screening and managing of diabetes but also for predicting diabetes-related adverse events and islet β cell function in prediabetic patients. In addition, saliva 1,5-AG demonstrates potential value in the screening and diagnosis of diabetes. This review focuses on the biological characteristics, detection methods, and clinical application of 1,5-AG to promote understanding and applicable research of 1,5-AG in the future. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMethodsResultsConclusionsA chronic subdural haematoma (cSDH) is an encapsulated collection of fluid and blood degradation products in the subdural space. It is increasingly common, affecting older people and those living with frailty. Currently, no guidance exists to define optimal care from onset of symptoms through to recovery. This paper presents the first consensus-built recommendations for best practice in the care of cSDH, co-designed to support each stage of the patient pathway.Guideline development was led by a multidisciplinary Steering Committee with representation from diverse clinical groups, professional associations, patients, and carers. Literature searching to identify relevant evidence was guided by core clinical questions formulated through facilitated discussion with specially convened working groups. A modified Delphi exercise was undertaken to build consensus on draft statements for inclusion in the guideline using survey methodology and an in-person meeting. The proposed guideline was subsequently endorsed by the Society for British Neurological Surgeons, Neuroanaesthesia and Critical Care Society, Association of Anaesthetists, British Association of Neuroscience Nurses, British Geriatric Society, and Centre for Perioperative Care.We identified that high quality evidence was generally lacking in the literature, although randomised controlled trial (RCT) data were available to inform specific recommendations on aspects of surgical technique and use of corticosteroids. The final guideline represents the outcome of synthesising available evidence, consensus-built expert opinion and patient involvement. The guideline comprises 67 recommendations across eight major themes, covering: presentation and diagnosis, neurosurgical triage and shared decision-making, non-operative management, perioperative management (including anticoagulation), timing of surgery, intraoperative and postoperative care, rehabilitation and recovery.We present the first multidisciplinary guideline for the care of patients with cSDH. The recommendations reflect a paradigm shift in the care of cSDH, recognising and formalising the need for multidisciplinary and collaborative clinical management, communication and decision-making delivered effectively across secondary and tertiary care. [ABSTRACT FROM AUTHOR]

Background: Thiol-disulfide homeostasis (TDH) plays a pivotal role in various physiological mechanisms, including antioxidant defence, detoxification, apoptosis, regulation of enzyme activities and cellular signal transduction. TDH can be used as a biomarker to detect oxidative stress (OS) levels and ischemia status in the tissues. Coronary artery bypass grafting (CABG) surgery is a procedure associated with high oxidative stress. Dexmedetomidine, an alpha-2 agonist anaesthetic agent, has antioxidant effects. In this study, the effects of dexmedetomidine on oxidative stress in CABG surgery were investigated. Methods: Patients who underwent on-pump CABG surgery were divided into two groups: those receiving dexmedetomidine (Group D) and those not receiving dexmedetomidine (Group C). From anesthesia induction to the end of surgery, patients in Group D received intravenous infusions of 0.05–0.2 mcg/kg/min remifentanil and 0.2–0.7 mcg/kg/h dexmedetomidine. Patients in Group C received intravenous infusion of 0.05–0.2 mcg/kg/min remifentanil. Blood samples were collected from the patients 30 min before induction of anesthesia (T1), 30 min after removal of the aortic cross-clamp (T2), and at the end of the surgery (T3). Thiol-disulfide homeostasis (TDH) was assessed using a novel method. A novel automated method enables the determination of native thiols, total thiols and disulfides levels in plasma, allowing the calculation of their respective ratios. Results: In patients receiving dexmedetomidine, lower postoperative levels of disulfide, disulfide/native thiol, and disulfide/total thiol, along with higher native thiol/total thiol, were observed compared to the control group. (p < 0.05) Postoperative native thiol and total thiol levels were similar for both groups. (p > 0.05) Conclusions: In our study, through dynamic thiol-disulfide measurements, we found that levels of oxidative stress (OS) were lower in patients who received dexmedetomidine. We believe that the positive effects of dexmedetomidine on OS could be beneficial in CABG surgery. Furthermore, we anticipate that with further studies conducted in larger patient cohorts, the clinical utilization of dexmedetomidine will become more widespread. Trial registration number: NCT05895331 / 06.07.2023. [ABSTRACT FROM AUTHOR]

Blood-based tests for multi-cancer early detection (MCED) are being developed to facilitate the detection of various cancer types. The Detecting cancers Earlier Through Elective mutation-based blood Collection and Testing study (DETECT-A) study evaluated an MCED test in 9,911 women, age 65-75, without personal history of cancer. In a post-hoc analysis, we report on the detection of precancerous neoplasms consequent to MCED testing and follow-up. Participants with positive baseline and confirmatory MCED testing underwent 2-deoxy-2[fluorine-18] fluoro-D-glucose positron emission tomography-computed tomography (PET-CT) and diagnostic evaluation as indicated by PET-CT results. We reviewed the electronic health records of participants with a precancerous neoplasm and summarized their clinical course. MCED results were positive in 134 participants. Clinically significant pre-malignant conditions were identified in three of these participants: A 71-year-old with an ovarian mucinous cystadenoma, a 67-year-old with an appendiceal mucinous neoplasm, and a 70-year-old with colon adenomas displaying high-grade dysplasia. All three participants underwent surgical treatment and remain alive and cancer-free as of last follow up. The diagnostic evaluation of a positive MCED test may occasionally reveal clinically significant pre-cancerous conditions amenable to interventions. The frequency of such findings and their clinical impact warrants further study. [ABSTRACT FROM AUTHOR]

Background: Feline blood transfusion is required for the treatment of various illnesses in cats, and the safety of donor cats is vital. Donor adverse reactions can include cardiorespiratory, venepuncture‐related, and behavioral abnormalities. Hypothesis/Objectives: To describe a large number of feline blood donation events and document use of sedation and anxiolysis, record volume of blood collected and describe the frequency, type, and risk factors for, adverse reactions. Animals: The study included 7812 individual cats and 29 201 donation events at a blood banking center over 5 years. Methods: Retrospective analysis of donation event records with signalment, donation volume, sedation status, donation number, and adverse reactions (acute and caregiver reported) recorded. Risk factors for adverse reactions were examined by stratifying data according to groups exposed to relevant predictors and calculating odds ratios with 95% and 99% confidence intervals (CIs). Results: Adverse reactions were uncommon (0.29%, 2.88/1000 donor events) and most commonly were cardiorespiratory (0.08%, 0.75/1000 donor events) or behavioral (0.06%, 0.62/1000 donor events). The only risk factor significantly associated with adverse reactions was conscious donation, with conscious donors 4.4 times more likely to have an adverse reaction (95% CI, 2.5‐7.9, P ≤.0001). Conclusions and Clinical Importance: Feline blood donation is associated with a low rate of adverse reactions. Sedation should be considered to reduce adverse reactions, and the environment and interactions optimized to reduce donor stress. Caregiver education on care postdonation could reduce behavioral adverse reactions. [ABSTRACT FROM AUTHOR]

Background: The Dog Aging Project (DAP) is a longitudinal study examining aging in US companion dogs, where missing data pose a challenge to result validity and statistical power. Early recognition and procedural adjustments are vital to address missing samples. Objectives: This research assesses missing biospecimen samples within the PRECISION cohort of the DAP, aiming to identify contributing factors and propose mitigation strategies. Methods: Ninety sample kits collected between August 2021 and October 2021 were evaluated for the missingness of individual kit components. A primary assessment reviewed the missingness of each sample type with hypothesized associated factors. A secondary assessment addressed the missingness of plasma and serum aliquots made after check‐in. Results: EDTA samples for flow cytometry, peripheral blood mononuclear cells (PBMCs), DNA and biobanking were missing at rates of 18.9%, 13.3%, 6.7% and 5.6%, respectively. Faecal samples were missing at 5.6%. Urine and plasma were each missing at 2.2%. Serum, hair and dried blood spot cards were each missing at 1.1%. No statistically significant difference in missingness was seen across regions, ease of blood collection, or cooperativeness of dog during sample collection. Higher time‐to‐receipt was associated with a higher missingness proportion. Increasing missingness proportions were seen across plasma and serum aliquots that were created in sequential order. Conclusion: The study suggests reevaluating sample collection instructions to address frequently missing sample types and prevent further loss. Investigation into collection procedures for these types is recommended to identify potential causes of sample yield loss. [ABSTRACT FROM AUTHOR]

The Asia‐Pacific Plasma Leaders' Network (APPLN) plays a crucial role in addressing the regional shortage of plasma‐derived medicinal products (PDMPs), particularly in low‐ and middle‐income countries (LMICs). It provides a platform for experts to share their expertise and drive multi‐stakeholder collaborations. While several PDMPs are acknowledged by the World Health Organization (WHO) as life‐saving therapeutics on the Model List of Essential Medicine for treating various chronic and acute life‐threatening diseases, there are still many inadequacies in the availability and affordability of PDMPs. These challenges arise from insufficient domestic supplies of plasma suitable for fractionation, as well as a lack of technical and financial capabilities to implement contract or domestic plasma fractionation programmes. At two separate dialogue forums organized by the APPLN in 2023, experts discussed the unmet needs of PDMPs for individuals living with haemophilia and immunodeficiencies in the region. They also highlighted the limited access to early diagnosis and patient‐centred care in several LMICs. To address these issues, there is an urgent need to increase the availability of high‐quality domestic plasma for fractionation. Adopting a stepwise approach to utilize unused recovered plasma and establishing contract fractionation programmes could be viable strategies to potentially enhance PDMP availability in LMICs. However, achieving this goal requires improving existing domestic infrastructures for blood collection, implementing adequate policy reforms and fostering competent local leadership. Ultimately, there is no 'one‐size‐fits‐all' strategy for securing safe plasma proteins for all patients in need. Collaborative efforts are essential for achieving progressive self‐sufficiency in PDMPs. [ABSTRACT FROM AUTHOR]

Objective The aim of this work was to resolve the uncertainty of whether transfusion of fresher red blood cells (RBCs) is better or not with regard to the safety and efficacy. Methods This systematic review was performed in accordance with our protocol registered on PROSPERO (https://www.crd.york.ac.uk/prospero/display%5frecord.php?ID=CRD42022379183). Results After a literature search, 13,247 records were identified, and 26 randomized controlled trials (RCTs) involving 53,859 participants were eligible and included in this review. The results in our review suggested that there was no significant effect of fresher vs older RBCs on mortality (relative risk [RR] = 1.04; 95% CI, 0.99-1.09; P =.39; I 2 = 0%), transfusion reactions (RR = 0.87; 95% CI, 0.57-1.33; P =.64; I 2 = 0%). However, the transfusion of fresher RBCs might increase the risk of nosocomial infection (RR = 1.11; 95% CI, 1.02-1.20; P =.02; I 2 = 0%), whereas there was no significant difference in the fresh vs old subgroup (RR = 0.87; 95% CI, 0.68 to 1.12; P =.28; I 2 = 0%). Conclusion Our study updated and reinforced the evidence of previously published systematic reviews that support the safety and efficiency of current practice of issuing the oldest available RBCs in the blood bank inventory. [ABSTRACT FROM AUTHOR]

Background Type 2 diabetes mellitus (T2DM) intricately involves disrupted lipid metabolism. Exosomes emerge as carriers of biomarkers for early diagnosis and monitoring. This study aims to identify lipid metabolites in serum exosomes for T2DM diagnosis. Methods Serum samples were collected from newly diagnosed T2DM patients and age and body mass index−matched healthy controls. Exosomes were isolated using exosome isolation reagent, and untargeted/targeted liquid chromatography−tandem mass spectrometry (LC-MS/MS) was used to identify and validate altered lipid metabolites. Receiver operating characteristic curve analysis was used to evaluate the diagnostic value of candidate lipid metabolites. Results Serum exosomes were successfully isolated from both groups, with untargeted LC-MS/MS revealing distinct lipid metabolite alterations. Notably, phosphatidylethanolamine (PE) (22:2(13Z,16Z)/14:0) showed stable elevation in T2DM-serum exosomes. Targeted LC-MS/MS confirmed significant increase of PE (22:2(13Z,16Z)/14:0) in T2DM exosomes but not in serum. PE (22:2(13Z,16Z)/14:0) levels not only positively correlated with hemoglobin A1C levels and blood glucose levels, but also effectively distinguished T2DM patients from healthy individuals (area under the curve = 0.9141). Conclusion Our research sheds light on the importance of serum exosome lipid metabolites in diagnosing T2DM, providing valuable insights into the complex lipid metabolism of diabetes. [ABSTRACT FROM AUTHOR]

Objective This study aimed to investigate the diagnostic value of stress-induced phosphoprotein 1 (STIP1) in serum for hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP)–negative HCC (ANHC). Methods In this study, serum samples were collected from 158 HCC patients and 63 non-HCC patients. Logistic regression analysis was performed to identify independent risk factors associated with HCC and ANHC. The diagnostic values of each index for HCC and ANHC were analyzed using receiver operating characteristic (ROC) curve analysis. Results The STIP1, des-γ-carboxy prothrombin (DCP), and AFP levels were higher in the HCC groups than in the non-HCC groups (P <.05). Age, DCP, STIP1, and hepatitis B virus infection were independent predictors of HCC (P <.05). The diagnostic value of STIP1 for HCC was higher than that of DCP. Additionally, age, STIP1, and hepatitis B virus infection were independent predictors for ANHC patients. The ROC curve exhibited an area under the curve value of 0.919 for STIP1, with a diagnostic cutoff value of 68.5 U/mL. Moreover, 36 ANHC patients and 19 AFP-negative non-HCC patients were included to validate the diagnostic model. A total of 20 patients had STIP1 levels greater than 68.5 U/mL, resulting in diagnostic accuracy of 67.3%, sensitivity of 55.6%, and specificity of 89.5%. Conclusion STIP1 demonstrates excellent diagnostic value for HCC and ANHC. [ABSTRACT FROM AUTHOR]

The article discusses the importance of developing a standardized set of circuit diagrams for continuous renal replacement therapy (CRRT) to aid in understanding the various CRRT modalities and machine components. The diagrams aim to simplify complex CRRT techniques and facilitate teaching, training, and academic communication. The authors have created a set of atlases with icons and symbols representing different CRRT components, which have been incorporated into the SMART CRRT information system in China. The diagrams are designed to be user-friendly, even for those without drawing skills, and are intended to reduce learning costs and enhance academic communication in the field of CRRT. [Extracted from the article]

Background/Objectives: This study investigated intraocular pressure (IOP) changes after a blood draw in older adults considering sex, age, and baseline IOP. Methods: Fifty-three subjects (54.7% females; age: 68.50 ± 4.46 years; Visual Function Index [VF14]: 94.50 ± 7.50 points; mean contrast sensitivity function (CSF) for both eyes in each spatial frequency [cdp]: 1.5 cdp [1.41 ± 0.20 log], 3 cdp [1.57 ± 0.29 log], 6 cdp [1.45 ± 0.39 log], 12 cdp [1.04 ± 0.40 log], 18 cdp [0.63 ± 0.31 log]) voluntarily participated. Subjects fasted for at least 8 h before attending the laboratory. First, IOP was measured in a seated position using a portable rebound tonometer. Ten minutes after the initial measurement, two 10 mL tubes of blood were drawn. Five minutes after the blood draw IOP was measured again following the same procedure as the initial measurement. We evaluated the differences using an analysis of variance. Results: Significant, but not clinically relevant, decreases were found in the right eye, with small effect sizes (p = 0.013–0.079, d = 0.35). Only males and subjects older than 68 years showed trends toward IOP reduction in the right eye. Subjects with baseline IOP ≥ 14 mmHg experienced significant IOP reductions in both eyes, with moderate effect sizes (p = 0.001–0.002, d = 0.56–0.69). Conclusions: Our findings suggest that a blood draw of 20 mL is safe for the IOP levels of older adults with baseline IOP between 11 and 21 mmHg. Variations in IOP were observed based on baseline IOP, sex, and age, suggesting the importance of personalized clinical assessments. The primary factor influencing IOP changes appears to be the baseline IOP level. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chemical and carcinogenic risk in workplace are linked to an increase of the incidence of cancer in exposed workers. The aim of this observational study was to identify an association between exposure to chemical risk and changes in hematochemical parameters of workers exposed. Methods: The study examined blood count parameters performed on 4523 employees of Sapienza University of Rome from September 2019 to February 2020. A total of 1402 workers in research laboratories, exposed to chemical risk and carcinogens, was compared with a cohort of 3121 blood donors, in apparently good health, matched for age, sex, and period of blood collection. Results: Multivariate analysis demonstrated acrylamide is the most frequently associated chemical with significant changes between the groups. It is related to an increase in monocytes and MPV, a reduction of lymphocytes, platelets, and red series values, while MCH remained unchanged. Formaldehyde reveals the same changes as acrylamide, with the exception of the percentage of lymphocytes, red blood cells, and HB, which remain unchanged. Other chemicals and carcinogens show variations for few blood count parameters. Conclusions: The present study found out a significant change in blood count values in workers exposed to acrylamide and formaldehyde. It also showed an increase in the mean monocyte value in employees exposed to carcinogenic risk, compared to non-exposed, with the exception of Trypan Blue. The implementation of efficient health surveillance remains of critical importance. These data should be compared with those from follow-up studies. [ABSTRACT FROM AUTHOR]

Simple Summary: This study focuses on extracellular vesicles (EVs) as potential novel biomarkers predicting the outcome of immunotherapy with atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma. Firstly, we detected significantly smaller EVs in treatment responders in terms of overall survival. Secondly, a decrease in vesicle size during immunotherapy was related to a longer progression-free survival. Lastly, higher vesicle concentrations and lower zeta potentials were identified as a positive prognostic factor throughout treatment. Our data highlight the potential promising role of EVs as novel biomarkers, potentially helping to identify optimal candidates for checkpoint inhibitor-based treatments for patients with advanced HCC. Background and Aims: Treatment with atezolizumab and bevacizumab has been approved as one of the standards of care for patients with advanced hepatocellular carcinoma (HCC). The median overall survival (OS) upon available treatments still remains below 2 years, urgently suggesting better stratification tools to identify ideal candidates for this treatment and potentially allowing personalized approaches. In this study, we evaluated the potential role of extracellular vesicles (EVs) as a novel biomarker in patients receiving atezolizumab and bevacizumab for HCC. Methods: We characterized EVs in 212 longitudinal serum samples from an observational cohort of 53 individuals with advanced HCC, who started therapy with atezolizumab plus bevacizumab at our center between January 2020 and March 2022. Results: In our cohort, the overall efficacy of atezolizumab and bevacizumab was comparable to previously published phase III data. We detected significantly smaller EVs in treatment responders, while enlarged EVs were associated with significantly decreased efficacy of atezolizumab and bevacizumab in terms of OS. A decrease in vesicle size during immunotherapy was related to a longer progression-free survival (PFS). A univariate Cox regression analysis including various clinicopathological parameters (e.g., tumor stage, markers of inflammation, organ dysfunction, or tumor markers) revealed vesicle size as an independent prognostic marker in HCC patients receiving atezolizumab and bevacizumab. Moreover, higher vesicle concentrations and lower zeta potentials were identified as a positive prognostic factor throughout treatment. Conclusions: Distinct EV characteristics such as vesicle size, concentration, and zeta potential represent promising novel biomarkers in patients with advanced HCC receiving atezolizumab and bevacizumab, potentially helping to identify optimal candidates for checkpoint inhibitor-based treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the relationship between systemic inflammatory reaction (SIR) indices and endometrial thickness in postmenopausal women with abnormal uterine bleeding. A new biomarker, SIR-En, combining SII (Systemic Inflammatory Index) and endometrial thickness, was developed. This study compared 192 patients with endometrial cancer and 50 with endometrial hyperplasia. The results showed that patients with cancer had significantly higher SIR-En values than those with hyperplasia (8710 vs. 6420; p = 0.003). The SIR-En index demonstrated moderate diagnostic ability for endometrial cancer, with an area under the ROC curve (AUC) of 0.6351 and a cut-off of 13,806, yielding high specificity (94%) and positive predictive value (96%). This suggests that SIR-En could aid in discriminating the endometrial carcinoma from atypical hyperplasia, improving diagnosis and treatment strategies. Objective: This study aimed to evaluate the efficacy of a new biomarker, termed SIR-En, in identifying patients at risk of endometrial carcinoma among those presenting with abnormal uterine bleeding during menopause. Material and Methods: A retrospective case–control analysis was conducted on 242 women with menopausal abnormal uterine bleeding and endometrial thickness ≥ 4 mm. Peripheral blood samples were collected within 7 days before histological diagnosis. systemic inflammatory reaction (SIR) indices were calculated, including NLR, MLR, PLR, and SII. SIR-En was derived by multiplying SII and endometrial thickness. Statistical analyses, including multivariate linear regression and ROC curve analysis, were performed to assess the diagnostic capability of SIR-En. Results: Patients were categorized into endometrial hyperplasia (50 patients) and endometrial cancer (192 patients) groups. The SIR-En index was significantly higher in the carcinoma group (8710 vs. 6420; p = 0.003). The ROC curve for SIR-En had an AUC of 0.6351 (95% CI: 0.5579–0.7121). Using Youden's method, the optimal SIR-En cutoff was 13,806, showing a specificity of 0.940 and a positive predictive value of 0.957. Conclusions: Combining systemic inflammatory indices with endometrial thickness, the SIR-En index can effectively distinguish between endometrial hyperplasia and carcinoma in menopausal women with abnormal uterine bleeding. Despite the retrospective design, the identified cutoff's high specificity and positive predictive value support its potential utility in clinical practice. Further prospective studies are required to validate these findings and optimize clinical application. [ABSTRACT FROM AUTHOR]

The objective of this randomized controlled trial was to determine if providing a rest stop including provision of feed and water between periods of continuous transportation mitigates the effect of long-distance transportation on markers of energy status and hydration in calves transported by road for 16 h. This study was conducted between September 2022 to January 2023 and included male and female Holstein and crossbred dairy calves ≥7 d old from 2 commercial dairy farms in Ontario, Canada (n = 96). On the day before transportation, calves were enrolled and randomly assigned to one of 2 treatment groups: (1) continuous transportation by road for 16 h or (2) 8 h of transport, 8 h of rest, and a further 8 h of transport to a single calf-raising facility. Calves that received a rest stop were fed 2 L of milk replacer at the time of unloading for the rest period and again immediately before reloading for the second leg of the journey. Blood samples were collected before and after transportation as well as daily for 3 d following arrival to the calf-raising facility. Serum was analyzed for concentrations of BHB, nonesterified fatty acids (NEFA), haptoglobin, and creatine kinase, and acid-base disturbances were evaluated within 1 h of collection of whole blood to assess glucose, sodium, potassium, ionized calcium, hematocrit, hemoglobin, pH, base excess, partial pressure of oxygen, total carbon dioxide, bicarbonate, partial pressure of carbon dioxide, and oxygen saturation. Mixed linear regression models with repeated measures were built to assess the effect of treatment group, age at transportation, breed, and sex on these parameters. Immediately after transportation, calves that received the rest period had lower BHB (−68.04 μmol/L, 95% CI: −99.59 to −36.49), NEFA (−0.14 mmol/L, 95% CI −0.22 to −0.07), and sodium (−1.10 mmol/L, 95% CI = −2.18 to −0.02), and higher glucose (0.48 mmol/L, 95% CI = 0.21 to 0.74), potassium (0.27 mmol/L, 95% CI = 0.11 to 0.43), ionized calcium (0.06 mmol/L, 95% CI = 0.03 to 0.08), and oxygen saturation (8.76%, 95% CI = 1.61 to 15.91) compared with calves that were continuously transported for 16 h. Additionally, calves transported between 11 and 12 d old had lower hematocrit (−1.22%, 95% CI = −2.19 to −0.25), hemoglobin (−3.07 g/L, 95% CI = −5.70 to −0.43), haptoglobin (−0.13 g/L, 95% CI = −0.23 to −0.02), and potassium (−0.13 mmol/L, 95% CI = −0.22 to −0.04) and higher sodium (0.83 mmol/L, 95% CI = 0.03 to 1.63) than 7 to 8 d old calves. Furthermore, calves that were 13 to 24 d old at transport had lower haptoglobin (−0.16 g/L, 95% CI = −0.27 to −0.06) and potassium (−0.14 mmol/L, 95% CI = −0.23 to −0.05), and higher sodium (1.02 mmol/L, 95% CI = 0.22 to 1.82) and ionized calcium (0.02 mmol/L, 95% CI = 0.002 to 0.035) compared with calves transported at 7 to 8 d old. The results of this trial demonstrate that a rest period improves energy status upon arrival to a calf-raising facility, suggesting that the benefit of a rest period may be mostly related to the provision of mid-journey milk meals. The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. [ABSTRACT FROM AUTHOR]

Purpose: Bloodstream infections (BSIs) are associated with significant morbidity, mortality and costs, while prolonged blood culture (BC) diagnosis may delay the initiation of targeted therapy. This study evaluates the impact of an optimized microbiology laboratory process on turnaround times, antibiotic use, clinical outcomes and economics for hospitalized BSI patients. Methods: A pre-post study was conducted in a Chinese hospital in which BSI derived BC results before (Oct. 2020- Sep. 2021) and after (Oct. 2021- Sep. 2022) newly implemented microbiology diagnostics and workflow changes were analyzed. Turnaround times, antibiotic initiation, length of stay and in-hospital costs were compared. Results: From 213 included patients, 134 were pre-optimization (pre-op) and 79 were post-optimization (post-op) cases. The median time from blood sample collection (BSC) to pathogen identification (ID) decreased from 70.12 to 47.43 h post-op (P < 0.001). The median time from BSC to the first ID report related initiation of pathogen-directed antibiotic use decreased from 88.48 to 47.85 h post-op (P < 0.001). The average hospital stay decreased from 19.54 to 16.79 days and 30-day readmissions declined from 18.7 to 13.9%, while the mean total antimicrobial drug usage costs decreased by 3,889 CNY per patient (P = 0.022) after optimization. Conclusions: Implementing new diagnostics technologies and optimizing laboratory workflows significantly reduced antimicrobial drug usage costs, shortened the time to ID results and improved the timeliness of appropriate antibiotic choices to treat BSIs. Investments in faster testing and process improvements were clearly beneficial for patient outcomes and healthcare economics. [ABSTRACT FROM AUTHOR]

Background: Blood draws for laboratory investigations are essential for patient management in neonatal intensive care units (NICU). When blood samples clot before analysis, they are rejected, which delays treatment decisions and necessitates repeated sampling. Aim: To decrease the incidence of rejected blood samples taken for laboratory investigation as a result of clotted sample. Study Design: This retrospective observational study used routine data on blood draws from preterm infants collected between January 2017 and June 2019 in a 112‐cot NICU in Qatar. Quality improvement interventions to reduce the rate of clotted blood samples included: awareness raising and safe sampling workshops with NICU staff, involvement of the neonatal vascular access team, development of a complete blood count (CBC) sample collection pathway, review of sample collection equipment, introducing the Tenderfoot® heel lance, establishment of benchmarks and provision of dedicated blood extraction equipment. Results: First attempt blood draw occurred in 10 706 cases, representing a 96.2% success rate. In 427 (3.8%) cases, the samples were clotted requiring repeat collection. The overall rate of clotted specimens decreased from 4.8% in 2017 and 2018 to 2.4% in 2019, with odds ratios of 1.42 (95% confidence interval [CI] 1.13–1.78, p =.002), 1.46 (95% CI 1.17–1.81, p <.001) and 0.49 (95% CI 0.39–0.63, p <.001), respectively. The majority (87%–95%) of blood samples were by venepuncture using an intravenous (IV) catheter or the NeoSafe™ blood sampling device. Heel prick sampling was the second (2%–9%) most common method. Clotted samples were most frequently associated with needle use, 228 of 427 (53%), and IV cannula, 162 of 427 (38%), with odds ratios of 4.14 (95% CI 3.34–5.13, p <.001) and 3.11 (95% CI 2.51–3.86, p <.001), respectively. Conclusions: Our interventions over 3 years were associated with reduced rates of sample rejection due to clotting, and this led to improved patient experience through fewer repeated samplings. Relevance to Clinical Practice: The insights gained from this project can help to improve patient care. Interventions that reduce the rate of blood sample rejection by clinical laboratories can lead to economic savings, timelier diagnostic and treatment decisions, and contribute to an improved quality care experience for all critical care patients, irrespective of age, by reducing the need for repeated phlebotomy and the risk of related complications. [ABSTRACT FROM AUTHOR]

• We screened the expression profiles of miRNAs in the late stage of RBC preservation. • We identified miRNAs that changed during different storage times as well as potential target genes. • We predicted the potential regulatory effects of these differential miRNAs through bioinformatics. To detect the differentially expressed regulatory miRNAs in the late stage of red blood cell (RBC) preservation and predict their roles. Suspended RBCs with different storage periods of 35 day, 42 day, and 50 day were collected for routine blood tests, RNA extraction, and preparation of small RNA sequencing libraries. The constructed libraries were sequenced and the biological functions of differential miRNAs in RBCs in the late storage were analyzed by bioinformatics. Routine indicators of RBCs in the late stage were not significantly affected by preservation time. The Pearson correlation analysis performing on RBC miRNAs with different storage days revealed that RBC miRNAs changed with the increase of storage days. RBC miRNAs from day 35 (D35), day 42 (D42) and day 50 (D50) showed significant differences (P < 0.05). Compared RBC miRNAs from D42 with these from D35, there were 690 up-regulated miRNAs and 82 down-regulated miRNAs; compared RBC miRNAs from D50 with these from D35, there were 638 up-regulated miRNAs and 123 down-regulated miRNAs; compared RBC miRNAs from D42 with these from D50, there were 271 up-regulated miRNAs and 515 down-regulated miRNAs. GO enrichment analysis of target genes of differential miRNAs were mainly involved in cell metabolism, biosynthesis, protein modification, gene expression and transcriptional regulation of biological processes. KEGG pathway enrichment analysis of miRNA target genes showed that differential miRNA target genes were closely related to pathways in cancer. MiRNAs were differentially expressed in the late stage of RBC preservation, and may be involved in various biological processes, especially cancer. [ABSTRACT FROM AUTHOR]

Objective: Autoantibodies are a hallmark of lupus nephritis (LN), but their association with LN classes and treatment response are not adequately known. In this study, we quantified circulating autoantibodies in the Accelerating Medicines Partnership LN longitudinal cohort to identify serological biomarkers of LN histologic classification and treatment response and how these biomarkers change over time based on treatment response. Methods: Peripheral blood samples were collected from 279 patients with systemic lupus erythematosus undergoing diagnostic kidney biopsy based on proteinuria. Of these, 268 were diagnosed with LN. Thirteen autoantibody specificities were measured by bead‐based assays (Bio‐Rad Bioplex 2200) and anti‐C1q by enzyme‐linked immunosorbent assay at the time of biopsy (baseline) and at 3, 6, and 12 months after biopsy. Clinical response was determined at 12 months. Results: Proliferative LN (International Society of Nephrology/Renal Pathology Society class III/IV±V, n = 160) was associated with higher concentrations of anti‐C1q, anti‐chromatin, anti–double‐stranded DNA (dsDNA), and anti–ribosomal P autoantibodies compared to nonproliferative LN (classes I/II/V/VI, n = 108). Anti‐C1q and‐dsDNA were independently associated with proliferative LN. In proliferative LN, higher baseline anti‐C1q levels predicted complete response (area under the curve [AUC] 0.72; P = 0.002) better than baseline proteinuria (AUC 0.59; P = 0.21). Furthermore, all autoantibody levels except for anti‐La/SSB decreased over 12 months in patients with proliferative, but not membranous, LN with a complete response. Conclusion: Baseline levels of anti‐C1q and anti‐dsDNA may serve as noninvasive biomarkers of proliferative LN, and anti‐C1q may predict complete response at the time of kidney biopsy. In addition, tracking autoantibodies over time may provide further insights into treatment response and pathogenic mechanisms in patients with proliferative LN. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the influence of sodium bicarbonate (SB) supplementation on physical performance, neuromuscular and metabolic responses during CrossFit® exercise. Seventeen Advanced CrossFit®-trained athletes completed the randomized, double-blind, placebo-controlled crossover protocol consisting of four visits, including two familiarization sessions and two experimental trials separated by a 7-day washout period. Participants supplemented 0.3 g/kg body mass (BM) of SB or placebo 120-min prior to performing the CrossFit® benchmark Fran followed by 500 m of rowing. SB improved time to complete Fran compared to PLA (291.2 ± 71.1 vs. 303.3 ± 77.8 s, p = 0.047), but not 500 m rowing (112.1 s ± 7.9 vs. 113.2 s ± 8.9 s, p = 0.26). No substantial side-effects were reported during the trials. This study showed that SB improved CrossFit® benchmark Fran performance, but not subsequent 500-m rowing. These data suggest that SB might be an interesting supplementation strategy for CrossFit® athletes. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the effects of a 16-wk combined exercise training on body composition, and metabolic and inflammatory markers in sedentary middle-aged workers. We also assessed whether alterations in metabolic markers were associated with changes in health-related outcomes. Methods: This randomized controlled trial involved 46 participants randomly allocated into control and exercise groups. The exercise group performed 16-wk combined aerobic and resistance training for 75 min per session, 3 times a week. Fasting blood samples were collected at baseline and after 16-wk intervention to determine lipid profile, and metabolic and inflammatory markers as primary outcomes. Results: A total of 36 participants completed the intervention (53.70 ± 6.92 yr old; n = 18 in each group). Waist circumference (interaction effect: F = 7.423, P = 0.002), fat mass (interaction effect: F = 5.070, P = 0.011), and muscle mass (interaction effect: F = 5.420, P = 0.007) were improved in the exercise group compared with the control group. Fasting glucose increased after the 16-wk follow-up (time effect: F = 73.253, P < 0.001), without an intergroup difference. Insulin levels were greater in the control compared with exercise group (group effect: F = 6.509, P = 0.015). The control group tended to increase the homeostatic model assessment of insulin resistance index (interaction effect: F = 3.493, P = 0.070) and to decrease the QUICKI index (interaction effect: F = 3.364, P = 0.075) to a greater extent compared with the exercise group. Exercise group reduced leptin (interaction effect: F = 11.175, P = 0.002) and adiponectin (interaction effect: F = 4.437, P = 0.043) concentrations in a greater magnitude than the control group. Interleukin (IL)-6 (time effect: F = 17.767, P < 0.001) and tumor necrosis factor α (time effect: F = 9.781, P = 0.004) concentrations decreased after the intervention, without an intergroup difference. IL-17A levels increased in the control compared with exercise group (interaction effect: F = 5.010, P = 0.033). Effects on adiponectin, IL-6, and IL-17A levels seem to depend on baseline body mass index, age, and sex. Percentage changes in leptin correlated positively with changes in homeostatic model assessment of insulin resistance index in the exercise (r = 0.565, P = 0.015) and control (r = 0.670, P = 0.002) groups. Conclusions: A combined training program can be an effective strategy to improve body composition and inflammatory markers and prevent marked reductions in insulin sensitivity among middle-aged workers. [ABSTRACT FROM AUTHOR]

Background: This Intensive Care Medicine Rapid Practice Guideline (ICM‐RPG) provides an evidence‐based recommendation to address the question: in adult patients in intensive care units (ICUs), should we use small‐volume or conventional blood collection tubes? Methods: We included 23 panelists in 8 countries and assessed and managed financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. We conducted a systematic review, including evidence from observational and randomized studies. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, we evaluated the certainty of evidence and developed recommendations using the Evidence‐to‐Decision framework. Results: We identified 8 studies (1 cluster and 2 patient‐level randomized trials; 5 observational studies) comparing small‐volume to conventional tubes. We had high certainty evidence that small‐volume tubes reduce daily and cumulative blood sampling volume; and moderate certainty evidence that they reduce the risk of transfusion and mean number of red blood cell units transfused, but these estimates were limited by imprecision. We had high certainty that small‐volume tubes have a similar rate of specimens with insufficient quantity. The panel considered that the desirable effects of small‐volume tubes outweigh the undesirable effects, are less wasteful of resources, and are feasible, as demonstrated by successful implementation across multiple countries, although there are upfront implementation costs to validate small‐volume tubes on laboratory instrumentation. Conclusion: This ICM‐RPG panel made a strong recommendation for the use of small‐volume sample collection tubes in adult ICUs based on overall moderate certainty evidence. [ABSTRACT FROM AUTHOR]

Biological variation is a relevant component of diagnostic uncertainty. In addition to within-subject and between-subject variation, preanalytical variation also includes components that contribute to biological variability. Among these, daily recurring, i.e., diurnal physiological variation is of particular importance, as it contains both a random and a non-random component if the exact time of blood collection is not known. We introduce four time-dependent characteristics (TDC) of diurnal variations for measurands to assess the relevance and extent of time dependence on the evaluation of laboratory results. TDC address (i) a threshold for considering diurnality, (ii) the expected relative changes per time unit, (iii) the permissible time interval between two blood collections at different daytimes within which the expected time dependence does not exceed a defined analytical uncertainty, and (iv) a rhythm-expanded reference change value. TDC and their importance will be exemplified by the measurands aspartate aminotransferase, creatine kinase, glucose, thyroid stimulating hormone, and total bilirubin. TDCs are calculated for four time slots that reflect known blood collection schedules, i.e., 07:00–09:00, 08:00–12:00, 06:00–18:00, and 00:00–24:00. The amplitude and the temporal location of the acrophase are major determinates impacting the diagnostic uncertainty and thus the medical interpretation, especially within the typical blood collection time from 07:00 to 09:00. We propose to check measurands for the existence of diurnal variations and, if applicable, to specify their time-dependent characteristics as outlined in our concept. [ABSTRACT FROM AUTHOR]

BACKGROUND: Discussion of the benefits of moderate alcohol consumption is ongoing. Broadly, research focusing on ethanol consumption tends to report no benefits. However, studies that distinguish between different types of alcoholic beverages, particularly beers, often reveal positive effects. The present study evaluated the genotoxic and mutagenic effects of moderate chronic consumption of India Pale Ale (IPA) craft beer. Sixty‐four adult male Swiss mice were used and divided into control and treatment groups receiving water, IPA beer with 55.23 g of ethanol per liter of beer, aqueous solution with 55.23 g of ethanol per liter, and hop infusion ad libitum for 30 days. After this period, the animals were genetically evaluated with a comet assay. For the ex vivo comet assay, blood was collected and exposed to hydrogen peroxide (H2O2). For the in vivo assay, the alkylating agent cyclophosphamide (CP) was administered to the groups after blood collection and sacrificed after 24 h. Brain, liver, and heart tissues were analyzed. Bone marrow was collected and submitted to the micronucleus test. RESULTS: The groups treated with IPA beer, ethanol, and hops did not show genotoxic and mutagenic action in the blood, brain, heart, or liver. The antigenotoxic action of IPA beer and hops was observed in both in vivo and ex vivo models, showing a similar reduction in DNA damage caused by CP. There was no significant difference between the groups with regard to the formation of micronuclei by CP. CONCLUSION: Moderate chronic consumption of IPA beer and hops infusion showed antigenotoxic effects in mice but no antimutagenic action. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Family caregivers are at a high risk for lowquality of life due to caregiving-related stress. Caregivers' stress is commonly assessed using self-reported measures, which reflect relatively subjective and long-term stress related to caregiving, but objective biologicalmarkers of stress are rarely used for caregivers. The purposes of this studywere (1) to determine whether caregiver characteristics were associated with stress assessed using a stress biomarker (serum cortisol) and a self-reported caregiving distress measure (Caregiver Burden Inventory) and (2) to determine the predictability of both stress measures for quality of life in caregivers of patients with heart failure. Methods: Taiwanese family caregivers (N = 113; mean age, 54.5 years; 70.8% female) of patients with heart failure completed surveys including caregiving distress and quality of life measured by the Caregiver Burden Inventory and the Short Form-36 (physical and psychological well-being subscales), respectively, and provided blood samples for serum cortisol. Independent t tests, correlation, and hierarchical regression were conducted. Results: Single caregivers had higher serum cortisol levels than married caregivers (P = .002). Men had significantly higher serum cortisol levels than women (P = .010), but men reported lower caregiving distress thanwomen (P = .049). Both serumcortisol (β = -0.32, P = .012) and caregiving distress (β = -0.29, P = .018) were significant predictors of quality of life in the physical well-being scale while controlling for caregivers' characteristics and depressive symptoms. Serum cortisol (β = -0.28, P = .026) and caregiving distress (β = -0.25, P = .027) also predicted quality of life in the psychological well-being scale. Conclusions: Serum cortisol and self-reported caregiving distress have similar predictability for quality of life in family caregivers of patientswith heart failure. Reducing stress and caregiving distress is critical to improving quality of life in this population. [ABSTRACT FROM AUTHOR]

The need of the hour is to incorporate a rapid assay that could efficiently detect neonatal sepsis. We evaluated the diagnostic utility of 16SrRNA broad-range polymerase chain reaction (PCR) in neonatal sepsis. The demographic and clinical details of 100 neonates clinically suspected to have sepsis were collected adopting pretested clinical proforma, followed by baseline laboratory investigations, including blood culture, complete blood counts, and C-reactive protein (CRP). Around, 0.2–0.3 ml of the EDTA blood was subjected to enrichment followed by DNA isolation using the modified spin column method. Based on the blood culture report, neonates were further divided into the suspected sepsis group (n = 50) and the confirmed sepsis group (n = 50). We performed 16SrRNA broad-range PCR to identify the presence of bacteria, and the results were analyzed statistically using SPSS software. Neonates in both groups were found to have clinical parameters comparable to each other except for birth weight, length, and head circumference, which was found to be lower in the culture-positive group than in culture-negative group (p < 0.05). The diagnosis of neonatal sepsis by 16SrRNA broad-range PCR compared to blood culture revealed 100% sensitivity, 64% specificity, and 73.5% positive and 100% negative predictive value. The 18 cases detected positive by PCR had clinical and other diagnostic findings consistent with sepsis. The 16SrRNA broad-range PCR effectively ruled out sepsis in 32 neonates within 8 h of sample collection compared to blood culture, which took 24 h. The method may not replace blood culture but can be used to complement it. [ABSTRACT FROM AUTHOR]

The hormone ghrelin serves a protective role in cancer-related anorexia-cachexia syndrome (CACS)—a condition in which plasma levels of ghrelin rise, its administration lessens CACS severity, and experimentally reduced signaling by its receptor (GHSR) worsens fat loss and anorexia and accelerates death. Yet, actions for the related hormone liver-expressed antimicrobial peptide-2 (LEAP2), which is an endogenous GHSR antagonist, are unexplored in CACS. Here, we found that plasma LEAP2 and LEAP2/ghrelin ratio were lower in Lewis lung carcinoma (LLC) and RM-9 prostate cancer CACS mouse models. Ghrelin deletion exaggerated losses of tumor-free body weight and fat mass, reduced food intake, reduced soleus muscle weight, and/or lowered grip strength in LLC or RM-9 tumor-bearing mice. LEAP2 deletion lessened reductions in tumor-free body weight and fat mass and increased food intake in LLC or RM-9 tumor-bearing mice. In a 55-subject cohort of patients with CACS or weight-stable cancer, the plasma LEAP2/total ghrelin ratio was negatively correlated with 6-month weight change preceding blood collection. These data demonstrate that ghrelin deletion exacerbates CACS in the LLC and RM-9 tumor-bearing mouse models while contrastingly, LEAP2 deletion reduces measures of CACS in these tumor-bearing mouse models. Further, they suggest that lower plasma LEAP2/ghrelin ratio protects against worsened CACS. [ABSTRACT FROM AUTHOR]

Background: Autologous blood donation for placental malposition is common in Japan, but no studies have scientifically evaluated its usefulness. The purpose of this study was to evaluate the necessity for autologous blood donation for placental malposition. Methods: A retrospective study was conducted of patients who underwent autologous blood donation for placental malposition at Kindai University Hospital from 2012 to 2022. The primary outcome was the proportion of patients who were able to avoid allogeneic blood transfusion by autologous blood transfusion; secondary outcomes were autologous blood disposal rate, allogeneic blood transfusion rate, and complications of autologous blood donation and allogeneic blood transfusion. A systematic review of studies on autologous blood transfusion for placental malposition was conducted on PubMed. Results: Fifty-two patients (total placenta previa 16; marginal placenta previa 20; low-lying placenta 16) were included. Eight (15%) had complications at the time of autologous blood donation, including non-reassuring fetal heart rate, but no sequelae. Allogeneic blood transfusion was avoided by autologous blood transfusion in only five cases (9.6%). Autologous blood was discarded in nine cases (17%), seven of which had a low-lying placenta positioned normally at delivery. Allogeneic blood transfusion was performed in eight cases (15%) with no complications. In the systematic review, seven articles that met the inclusion criteria were selected for further evaluation. The results showed that there were no publications that scientifically demonstrated the benefit of autologous blood transfusion. Conclusions: The results of this study indicate that autologous blood donation for placental malposition has little benefit. [ABSTRACT FROM AUTHOR]

Background/Objectives: The aim of this study is to assess the knowledge, attitudes, and practices of pregnant women and hospital staff regarding umbilical cord blood (UCB) donation and storage to understand its limitations in clinical practice. Methods: MEDLINE, Scopus, LILACS, EMBASE, Scielo.br, and PROSPERO were searched from inception to 30 November 2023 with no geographic or language restrictions. The study eligibility criteria included cross-sectional studies that interviewed pregnant women and/or hospital staff about their knowledge, attitudes, and practices regarding private or public storage. A random-effects restricted maximum-likelihood model with Freeman–Tukey Double arcsine transformation meta-analysis was carried out to calculate the pooled estimates. MOOSE guidelines were followed. STATA 14.1 was used for statistical analysis. The Newcastle–Ottawa Scale and ROBINS-I tool were used for quality and risk of bias assessments. Results: In total, 19 studies providing data for 19,904 pregnant women and 1245 hospital staff members were included. Pooled pregnant women awareness was 61% ((95% CI 0.60 to 0.62), I2 = 0%, τ2 = 0.00, Q = 11.0 (p = 0.950)), and 61% for hospital staff (95% CI 0.58 to 0.64), I2 = 0%, τ2 = 0.00, Q = 4.00 (p = 0.310)). In total, 57% ((95% CI 0.56 to 0.58), I2 = 0, τ2 = 0.00, Q = 4.00 (p = 0.320)) of pregnant women had a positive attitude about UCB, while 34% ((95% CI 0.32 to 0.36), I2 = 0%, τ2 = 0.00, Q = 4.00 (p = 0.310)) were in favor of donating UCB for research and 65% ((95% CI 0.63 to 0.66), I2 = 0%, τ2 = 0.00, Q = 4.0 (p = 0.350)) were planning UCB storage. A significant (p < 0.001) preference for public relative to private banking (51% ([95% CI 0.49 to 0.54], I2 = 0%, τ2 = 0.00, Q = 4.0 (p = 0.310)) vs. 12% ([95% CI 0.10 to 0.13], I2 = 0%, τ2 = 0.00, Q = 4.0 (p = 0.300))) was noted for pregnant women. The same was retrievable for professionals (84% ([95% CI 0.79 to 0.88], I2 = 0%, τ2 = 0.00, Q = 2.0 (p = 0.110)) vs. 6% ([95% CI 0.03 to 0.09], I2 = 0%, τ2 = 0.00, Q = 1.0 (p = 0.070); p < 0.001)). Conclusions: Despite these efforts, lack of knowledge and positive attitudes about UCB banking remain, emphasizing the need for increasing educational programs on the subject. [ABSTRACT FROM AUTHOR]

Sexually minoritized men (SMM) with HIV who use stimulants experience difficulties achieving and maintaining an undetectable viral load (VL). Home-based VL monitoring could augment HIV care by supporting interim, early identification of detectable VL. We describe implementation challenges associated with a home-collection device for laboratory-based VL testing among SMM with HIV who use stimulants. From March-May 2022, cisgender SMM with HIV reporting moderate-to-severe stimulant use disorder and suboptimal (< 90%) past-month antiretroviral therapy (ART) adherence were recruited via a consent-to-contact participant registry. Eligible men completed teleconference-based informed consent and were mailed a HemaSpot-HD blood collection device (volume capacity 160 µL; lower limit of detection 839 copies/mL) with detailed instructions for home blood self-collection and return shipment. Implementation process measures included estimated blood volume and VL quantification. Among 24 participants, 21 (88%) returned specimens with a median duration of 23 days (range: 10–71 days) between sending devices to participants and receiving specimens. Of these, 13/21 (62%) included enough blood (≥ 40 µL) for confidence in detectable/undetectable results; 10/13 (77%) had detectable VL, with 4/10 (40%) were quantifiable at ≥ 839 copies/mL. The remaining 8/21 had low blood volume (< 40 µL), but 3/8 (38%) still had detectable VL, with 1/3 (33%) quantifiable at ≥ 839 copies/mL. Home blood collection of ≥ 40 µL using HemaSpot-HD was feasible among this high-priority population, with > 50% having a VL detected. However, interim VL monitoring using HemaSpot-HD among those experiencing difficulties with ART adherence may be strengthened by building rapport via teleconferencing and providing detailed instructions to achieve adequate sample volume. [ABSTRACT FROM AUTHOR]

Background: EDTA-induced pseudothrombocytopenia (PTCP) during whole blood collection requires significant laboratory resources to obtain accurate results. We evaluated platelet-deaggregation function in EDTA-induced PTCP and platelet-clump flagging by the BC-6800Plus hematology analyzer using integrated digital image analysis. Methods: We prospectively collected 132 whole blood samples suspected of platelet clumping (102 in EDTA and 30 in sodium citrate) from 88 individuals. We compared platelet counts determined using the platelet count by impedance (PLT-I) function of the DxH 900 hematology analyzer and the PLT-I or optical platelet count (PLT-O) function of the BC6800Plus. Platelet clumping was verified through manual inspection and the MC-80 digital image analyzer. Results: Among the 132 whole blood samples, 43 EDTA samples showed platelet clumping. The DxH 900 PLT-I and BC-6800Plus PLT-I results demonstrated a strong correlation (r=0.711) for the EDTA samples but only a moderate correlation with the BC-6800Plus PLT-O results (r=0.506 and 0.545, respectively). The BC-6800Plus PLT-O results were consistent with the sodium citrate platelet counts, with a median dissociation rate of 102.5% (range, 74.9%–123.1%). The DxH 900 and BC-6800Plus analyzers had sensitivity values of 0.79 and 0.72, respectively, for platelet-clump flagging. When integrating the MC-80 digital image analysis results, the sensitivity of BC-6800Plus improved to 0.89 (standard mode) or 1.0 (PLT-Pro mode). Conclusions: BC-6800Plus PLT-O measurement results are close to the actual values obtained by platelet deaggregation with PTCP samples. Integrating the BC-6800Plus with a digital imaging analyzer effectively improved the diagnosis of PTCP and reduced the requirement for additional laboratory procedures. [ABSTRACT FROM AUTHOR]

Introduction: The basophil activation test (BAT) has shown evidence of high sensitivity and high specificity to support the diagnosis of IgE-mediated allergy. It is a functional test that uses live cells analyzed by flow cytometry and thus needs to be performed within 24h of blood collection. BAT has shown to be reproducible and reliable when tested in a clinical diagnostic laboratory with standardized protocols and flow cytometry settings. Areas covered: In this review, we summarize the evidence to support clinical use of BAT and the next steps required for clinical implementation for an improve clinical care for patients with suspected IgE-mediated food allergy. Expert opinion: BAT has recently been included in Clinical Guidelines of Food Allergy Diagnosis and its implementation in clinical practice depends largely on availability. Proposed clinical applications of the BAT include: distinction between food allergy and asymptomatic IgE sensitization; determination of food allergic status to peanut, tree nuts and seeds in polysensitized children; evaluation of tolerance to baked egg and baked milk in egg and milk allergic children; identification of patients at high-risk of severe allergic reactions; monitoring for spontaneous resolution of food allergy; confirmation of eligibility for specific treatments of food allergy; prediction and monitoring of response to immunomodulatory treatments. [ABSTRACT FROM AUTHOR]

The rising burden of dementia calls for high‐quality data on cognitive decline and dementia onset. The second wave of the Harmonized Diagnostic Assessment for the Longitudinal Aging Study in India (LASI‐DAD) was designed to provide longitudinal assessments of cognition and dementia in India. All Wave 1 participants were recruited for a follow‐up interview, and a refresher sample was drawn from the Longitudinal Aging Study in India, a nationally representative cohort of Indians aged 45 and older. Respondents underwent a battery of cognitive tests, geriatric assessments, and venous blood collection. Their health and cognitive status were also assessed through an interview with a close family member or friend. Clinical consensus diagnosis was made based on the Clinical Dementia Rating®, and comprehensive data on risk factors of dementia were collected, including neurodegenerative biomarkers, sensory function, and environmental exposures. A total of 4635 participants were recruited between 2022 and 2024 from 22 states and union territories of India, accounting for 97.9% of the population in India. The response rate was 84.0%, and 71.5% of the participants provided venous blood specimen. LASI‐DAD provides rich new data to study cognition, dementia, and their risk factors longitudinally in a nationally representative sample of older adults in India. Longitudinal cognitive data, together with longitudinally assessed biomarker data and novel data on sensory function and environmental exposures, provide a unique opportunity to establish associations between risk factors and biologically defined cognitive aging phenotypes. [ABSTRACT FROM AUTHOR]

Background: Non-communicable diseases (NCDs) are the leading cause of death around the world. The Dietary Quality Index-International (DQI-I) is one of the indicators that shows changes in diet and its association with NCDs. The aim of this study is to measure the association between the DQI-I and major metabolic risk factors. Methods: This study is a cross-sectional study based on data collected in the first phase of the prospective cohort study on Ravansar non-communicable diseases (RaNCD). To perform clinical and biochemical tests such as lipid profile, blood glucose and liver enzymes, blood samples were collected using standard vacutainer blood collection techniques. Information from the food frequency questionnaire containing 118 food items was used to score each person's DQI-I. Binary logistic regression was used to determine the association between the DQI-I tertile and the metabolic risk factors. Linear regression was also used for the association between subgroups of DQI-I score and the metabolic risk factors. Results: The total number of subjects in this study was 7,115, with a mean age of 47.14 ± 8.29 years. Dietary quality was generally poor, with 37.03% in the lowest tertile. Men had better dietary quality than women. Anthropometric measures, blood pressure, triglycerides and blood glucose were lower in the lowest tertile of dietary quality. A one-unit increase in the total DQI-I resulted in a 0.19 decrease in total cholesterol. Higher dietary quality was associated with a 22% increased risk of high triglycerides, a 19% increased risk of low high-density density lipoprotein, a 5% decreased risk of elevated low-density lipoprotein, a 42% increased risk of high blood pressure, and a 99% increased risk of high fasting blood glucose. Higher dietary quality was also associated with a 33% increased risk of overweight/obesity. Conclusion: The study found that participants had poor dietary quality, with some favorable metabolic outcomes in the lowest tertile, but concerning associations in the highest tertile, including increased risk for high triglycerides, blood pressure, and obesity. The complex associations suggest that balanced, multifaceted interventions are needed. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Therapeutic drug monitoring for astronauts faces limitations in conventional blood sampling and sample management onboard the international space station. Here, we explore the feasibility of dried blood spot (DBS) collection during parabolic flights (PF) to overcome these constraints.We assessed the feasibility of blood deposition on blotting paper for preanalytical aspects in a PF using synthetic blood. Subsequently, DBS sampling validation was carried out in another PF campaign. Twenty volunteers participated in a pharmacokinetic study on caffeine and its metabolite, paraxanthine, conducted during parabolic flights. After >18 h caffeine washout, coffee (115 mg), tea (30 mg) or dark chocolate (11 mg) were ingested by the participants. DBS samples were collected at baseline, during weightlessness and post‐flight. Caffeine and paraxanthine were analysed using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Genotyping for cytochrome P450‐1A2 (CYP1A2) was performed and a metabolic ratio by area under the curve for caffeine and paraxanthine (AUCPAX/AUCCAF) for CYP1A2 was determined. A user experience survey was also conducted.Full in‐flight pharmacokinetic study was feasible in seventeen volunteers with three unable to perform the sampling due to motion sickness. Nineteen participants (twelve males and seven females) completed pharmacokinetic profiles, with repeated pharmacokinetic studies for six participants. CYP1A2 genotyping resulted in eight ultrarapid, eleven intermediate, and one poor metabolizer. Among the women, four were on oestrogen contraceptives, a known inhibitor of CYP1A2, and were considered as poor metabolizers. Expected differences in kinetic profiles, consistent with consumption habits, the ingested dose and the genotypic/phenotypic information, were observed. The mean caffeine AUC for coffee, tea and chocolate were 9419 ng.h.mL−1 (95% confidence interval [CI]: 6222–12 616, n = 10), 6917 ng.h.mL−1 (95% CI: 2729–11 105), n = 7) and 3039 ng.h.mL−1 (95% CI: 1614–4142, n = 12), respectively. The mean paraxanthine AUC were 10 566 ng.h.mL−1 (95% CI: 6242–14 890, n = 10), 4011 ng.h.mL−1 (95% CI: 2305–5716, n = 7) and 3638 ng.h.mL−1 (95% CI: 1589–40 859, n = 12), respectively. The mean metabolic ratio in oestrogen‐treated women was 0.53 (95% CI: 0.35–0.71) compared to 1.19 (95% CI: 0.99–1.33) in others. The mean metabolic ratio was 1.02 (95% CI: 0.81–1.23, n = 15) on the ground and 1.10 (95% CI: 0.70–1.41, n = 13) during the parabolic flights, with no significant difference observed between the two conditions. Overall participants were satisfied with the usability of the method.DBS collection was safe, stable, feasible and well accepted in weightlessness. This method would offer valuable insights into human metabolism adaptation during long‐term spaceflight, addressing space pharmacology challenges. [ABSTRACT FROM AUTHOR]

Background: Obesity and frailty are prevalent geriatric conditions that share some pathophysiological mechanisms and are associated with adverse clinical outcomes. The relationship between frailty, obesity, and polymorphism remains inadequately explored. Single nucleotide polymorphisms (SNPs) offer insights into genetic predispositions that may influence the development of both frailty and obesity. Methods: We aimed at investigating whether SNPs associated with frailty also play a role in obesity. Data were collected from the FRASNET cross-sectional study, which included community-dwelling older individuals residing in Milan and nearby areas. Participants were recruited through random sampling. They underwent multidimensional geriatric assessments, which included the collection of blood samples for SNP analysis. Frailty was assessed using the frailty index, and body composition was evaluated using bioelectrical impedance analysis and anthropometric measures. Results: SNPs related to frailty and linked to the renin-angiotensin system (CYP11B2 rs1799998, AGT rs5051, and AGTR1 rs2131127), apoptosis pathways (CASP8 rs6747918), growth hormone signaling (GHR rs6180), inflammation (TLR4 rs5030717, CD33 rs3865444, and FN1 rs7567647), adducin (ADD3 rs3731566), and the 9p21-23 region (rs518054) were found to be associated with various measures of obesity in community-dwelling older adults. Conclusions: Frailty-related SNPs contribute to obesity in community-dwelling older adults. We identified a novel association between adducin SNPs and visceral fat, which has not been previously reported. Detecting genetic predispositions to obesity and frailty early could aid in identifying individuals at risk, facilitating the adoption of preventive interventions. This represents an initial step toward promoting early intervention strategies. [ABSTRACT FROM AUTHOR]

Background: A hospital-based cross-sectional case-control study was conducted to investigate the association between exposure through various pesticide residues detected in the plasma and serum 8-OHdG levels among farmers and non-farmers diagnosed with leukaemia, lymphoma and breast cancers and compare the same with healthy controls with no cancer and no exposure. Methodology: The present study was conducted among the farmers and non-farmers visiting a regional tertiary cancer care hospital in Hyderabad, Telangana State, India. Data were collected by administering a pre-tested questionnaire through an interview followed by the collection of blood samples which were analyzed for pesticide residues using LC-MS/MS while the serum levels of 8-OHdG were measured using ELISA. Data were analyzed using SPSS 24. Results: The pesticide residues detected were chlorpyrifos, dimethoate, malathion, phosalone, and quinalphos which were approved and recommended for their use on the crops that were cultivated by the farmers in their plasma samples along with banned pesticide residues like monocrotophos, diazinon, and dichlorvos among farmers diagnosed with all three types of cancers while the non-farmers and healthy controls were not detected with any such residues. In addition, farmers diagnosed with leukemia had higher levels of all the pesticide residues in their plasma than those diagnosed with lymphoma and breast cancers. Further, a significant difference was also observed between profenofos residues in plasma and serum 8-OHdG levels. Conclusion: In the present study, though the farmers diagnosed with three types of cancers were detected with various types of pesticide residues analysed, only residues of profenofos showed a significant difference with serum levels of 8-OHdG suggesting the need for an in-depth follow up molecular studies in a larger cohort to assess the possible association between 8-OHdG levels with the pesticide residues among the exposed. [ABSTRACT FROM AUTHOR]

Background and Objectives Materials and Methods Results Conclusion Sickle cell trait (SCT) persons are significant donors, and discarding these blood units reduces their supplies, mainly in the third‐world countries. This work focused on 12 metabolites associated with the red blood cell (RBC) storage lesion and 23 amino acids in the supernatants of packed RBC units from SCT and reference (non‐SCT) donors stored in the same conditions.All samples of RBC concentrates were collected and separated from the storage of Colsan (Beneficient Association of Blood Collection), where they were routinely processed and separated as packed RBC units and stored in the refrigerator (2°–6°C). The supernatant samples of each packed RBC bag were separated by centrifugation at days 1, 7, 14, 21, 28 and 35 of storage and kept at −80°C till the metabolite analysis together.The quantitation of metabolites and amino acids examined in the supernatant of SCT and reference donors showed no statistical differences along the cold storage. Lactic acid and malic acid releases occur in three phases during RBC storage. Basic and acid amino acids and corresponding amides have low and stable values during the first 14 days of storage, followed by a steep increase.Our metabolomic results give elements that seem not to contraindicate the transfusion of RBC with SCT, besides its more structural fragility. [ABSTRACT FROM AUTHOR]

Introduction: Patients with chronic HBV infection (CHI) exhibit defective antiviral immune-response whose underlying causes still remain unclear. Monocytes act as immune sentinels for pathogens and can regulate immunity via interaction with other immune-cells, apart from differentiating into macrophages. Immunecheckpoint molecules (ICMs) expressed by immune-cells, including monocytes are known to negatively regulate immune-responses. Here, we evaluated the expression of ICMs, namely, Gal-9, PD-L1, and CTLA-4 on monocytes in different phases of CHI, identified the viral and the host factors causing their aberrant expression and investigated their impact during interaction of monocytes with Tcells, B-cells and NK-cells and also on monocyte to macrophage differentiation. Influence of Tenofovir therapy on the expression of monocytic ICMs was also studied. Methods: Collection of blood and liver-tissue samples from HBV infected patients and controls, flow-cytometry, cell sorting, cell culture and immunefluorescence were performed for this study. Results: Gal-9+ and PD-L1+-monocytes were significantly increased in HBeAgpositive as well as HBeAg-negative chronic hepatitis B (CHB) patients than healthy controls (HC). In immune-tolerant (IT) subjects, only Gal-9+- monocytes and in inactive carriers (IC), PD-L1+-monocytes were higher than HC while CTLA-4+-monocytes remained comparable among groups. High serum Hepatitis B surface antigen (HBsAg) concentration in CHB as well as IT and TNF-α in CHB triggered monocytic Gal-9-expression whereas, PD-L1 was induced by elevated TNF-α and IL-4 in CHB and IL-1β in CHB and IC. Purified monocytes from CHB and IT having high Gal-9 expression led to expansion of CD4+CD25+FOXP3+-Tregs, CD19+IL-10+-Bregs and CD19+CD27-CD21- atypical memory B-cells and these monocytes also preferentially differentiated into M2-macrophages. These phenomena were reversed by anti-Gal-9- antibody. Parallelly, PD-L1+-monocytes in CHB and IC reduced IL-2/IFN-γ and IL-6 production by HBV-specific T- and B-cells respectively, which were restored by anti-PD-L1-antibody. Both Gal-9+- and PD-L1+ -monocytes caused decline in IFN-γ+-NK-cells but enhanced IL-10-expressing HBVspecific-T-cells and NK-cells. Increased intrahepatic CD14+Gal-9+ and CD14+PD-L1+-monocytes were noted in CHB patients than HC. One-year tenofovir therapy failed to reduce monocytic Gal-9 and PD-L1 along with the levels of HBsAg, TNF-α, IL-1β and IL-4. Conclusions: Monocytic Gal-9 and PD-L1, expressed heterogeneously in different phases of CHI, exert diverse inhibitory effects on immune-responses and their therapeutic targeting could boost anti-HBV immunity. [ABSTRACT FROM AUTHOR]

Background: Hypothermia and acidosis individually inhibit haemostasis. We designed this study with the aim to investigate whether rivaroxaban combined with hypothermia or acidosis exhibit synergistic inhibitory effects on haemostasis using ROTEM®. Methods: Patients with a clinical indication to start rivaroxaban treatment were prospectively included. Blood samples were collected before initiation of treatment and the day after. All blood samples were in vitro modified with respect to temperature (incubated and analysed at 28, 33, 37 and 40 degrees Celsius (°C)) and pH (6.8, 7.0, 7.2 and 7.4). The temperature and acidosis effects on the ROTEM EXTEM variables clotting time (CT), clot formation time (CFT) and alpha-angle (AA) were measured along with the individual effect of rivaroxaban on the same variables. The additive effect was calculated. The observed (potential synergistic) effects for the temperature and pH modified rivaroxaban samples on the same ROTEM variables, were registered. Differences between the additive and observed (potential synergistic) effects were analysed using matched non-parametric hypothesis testing. Results: In total, 13 patients were included. Hypothermia and rivaroxaban exhibited a synergistic effect on CT at 28 °C (p = 0.0002) and at 33 °C (p = 0.0007). The same applied for acidosis at pH 6.8 (p = 0.003) and pH 7.0 (p = 0.003). There were no signs of synergistic effects of rivaroxaban and temperature or acidosis on CFT. In AA there were signs of synergism at 28 °C (p = 0,001), but not at other tested temperatures or pH levels. Conclusions: The combination rivaroxaban together with hypothermia or acidosis demonstrated inhibitory synergistic effects on haemostasis. Trial registration: The study was retrospectively registered 2023-03-01 at ClinTrials.gov with NCT05669313. [ABSTRACT FROM AUTHOR]

Background: Hyperuricaemia is common among obese children and adolescents, and is closely related to insulin resistance. The aim of this study was to explore the relationships between youth insulin resistance and hyperuricaemia, as well as their relationships with lifestyle factors in youths, to provide early guidance on the risk factors for hyperuricaemia in adolescents. Methods: This study included 233 adolescents aged 10 to 20 years. Insulin resistance was evaluated via the homeostasis model assessment-insulin resistance (HOMA-IR) method. Binary logistic regression analysis was used to assess the associations of HOMA-IR with hyperuricaemia status and serum uric acid (UA) levels. The participants were subsequently divided into two groups, the noninsulin resistant group (HOMA-IR ≤ 3.2) and the insulin resistant group (HOMA-IR > 3.2), to further explore the factors that may affect the serum UA level. Finally, the predictive ability of different indicators of hyperuricaemia was evaluated via the ROC curve. Results: Binary logistic regression analysis revealed a significant increase in the risk of developing hyperuricaemia for individuals with elevated HOMA-IR (p < 0.001) and insulin resistance (p < 0.01). Spearman's correlation analysis revealed a significant positive linear correlation between HOMA-IR and serum UA levels (r = 0.4652, p < 0.001). Among insulin-resistant adolescents, UA levels were positively correlated with weight ratings, frequency of staying up late, and sugary beverages intake. Notably, individuals who engaged in 1–3 h of weekly exercise had the lowest UA levels. The area under the ROC curve for HOMA-IR was 0.847 (cut-off value = 2.165, p < 0.001), and the optimal prediction model included HOMA-IR, BMI z-score, and other lifestyle factors (AUC: 0.870, p < 0.001)). Conclusion: HOMA-IR was identified as an independent risk factor for the development of hyperuricaemia and could be used as a sensitive indicator for the prediction its development in adolescents. In insulin-resistant adolescents with hyperuricaemia, maintaining normal weight, engaging in physical exercise for 1–3 h per week, avoiding staying up late and limiting sugary beverages intake are recommended to reduce the prevalence of hyperuricaemia among adolescents. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) has a rising incidence and poor prognosis due to late diagnosis and limited treatments. Currently, treatment is based solely on TNM staging, without considering molecular tumor characterization. In the present study, we validated a combined amplification refractory mutation system (ARMS) and high-resolution melting analysis (HRMA) technique for detecting mutations in codon 12 of KRAS in PDAC tumor and plasma samples and assessed its prognostic value. We included 88 newly diagnosed PDAC patients, treated with either surgery, chemotherapy, or best supportive treatment only. Both tumor and plasma samples were analyzed, and the most frequent mutations were G12D (36%) and G12V (25%). KRAS mutations G12D and/or G12C in tumors and plasma were associated with lower progression-free survival (PFS) and overall survival (OS) independently of disease stage or treatment performed. ARMS–HRMA offers a rapid, cost-effective method for detecting KRAS mutations and can aid in prognosis and treatment decisions. Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) incidence is rising, and prognosis remains poor due to late diagnosis and limited effective therapies. Currently, patients are treated based on TNM staging, without molecular tumor characterization. This study aimed to validate a technique that combines the amplification refractory mutation system (ARMS) with high-resolution melting analysis (HRMA) for detecting mutations in codon 12 of KRAS in tumor and plasma, and to assess its prognostic value. Methods: Prospective study including patients with newly diagnosed PDAC with tumor and plasma samples collected before treatment. Mutations in codon 12 of KRAS (G12D, G12V, G12C, and G12R) were detected using ARMS–HRMA and compared to Sanger sequencing (SS). Univariate and multivariate analyses were used to evaluate the prognostic significance of these mutations. Results: A total of 88 patients, 93% with ECOG-PS 0–1, 57% with resectable disease. ARMS–HRMA technique showed a higher sensitivity than SS, both in tumor and plasma (77% vs. 51%; 25 vs. 0%, respectively). The most frequent mutation was G12D (n = 32, 36%), followed by G12V (n = 22, 25%). On multivariate analysis, patients with G12D and/or G12C mutations, either in tumor or plasma, had lower PFS (HR 1.792, 95% CI 1.061–3.028, p = 0.029; HR 2.081, 95% CI 1.014–4.272, p = 0.046, respectively) and lower OS (HR 1.757, 95% CI 1.013–3.049, p = 0.045; HR 2.229, 95% CI 1.082–4.594, p = 0.030, respectively). Conclusions: ARMS–HRMA is a rapid and cost-effective method for detecting KRAS mutations in PDAC patients, offering the potential for stratifying prognosis and guiding treatment decisions. The presence of G12D and G12C mutations in both tumor and plasma is associated with a poorer prognosis. [ABSTRACT FROM AUTHOR]

The study published in the International Journal of Laboratory Hematology explores the impact of preanalytical conditions on fibrin monomers (FMs) and D-dimer biomarkers. The research involved 20 healthy volunteers and compared nine simulated conditions to a reference condition. The study found that certain preanalytical conditions significantly affected FMs levels, while D-dimer levels remained consistent across all conditions. The findings suggest that FMs assays are sensitive to preanalytical artifacts, highlighting the importance of stringent guidelines for accurate measurements. [Extracted from the article]

Background The treatment of carbapenem-resistant Acinetobacter baumannii / calcoaceticus complex (CRAB) presents significant treatment challenges. Methods We report the case of a 42-year-old woman with CRAB meningitis who experienced persistently positive cerebrospinal fluid (CSF) cultures for 13 days despite treatment with high-dose ampicillin-sulbactam and cefiderocol. On day 13, she was transitioned to sulbactam-durlobactam and meropenem; 4 subsequent CSF cultures remained negative. After 14 days of sulbactam-durlobactam, she was cured of infection. Whole genome sequencing investigations identified putative mechanisms that contributed to the reduced cefiderocol susceptibility observed during cefiderocol therapy. Blood and CSF samples were collected pre-dose and 3-hours post initiation of a sulbactam-durlobactam infusion. Results The CRAB isolate belonged to sequence type 2. An acquired bla OXA-23 and an intrinsic bla OXA-51-like (ie, bla OXA-66) carbapenemase gene were identified. The paradoxical effect (ie, no growth at lower cefiderocol dilutions but growth at higher dilutions) was observed by broth microdilution after 8 days of cefiderocol exposure but not by disk diffusion. Potential markers of resistance to cefiderocol included mutations in the start codon of piuA and piuC iron transport genes and an A515V substitution in PBP3, the primary target of cefiderocol. Sulbactam and durlobactam were detected in CSF at both timepoints, indicating CSF penetration. Conclusions This case describes successful treatment of refractory CRAB meningitis with the administration of sulbactam-durlobactam and meropenem and highlights the need to be cognizant of the paradoxical effect that can be observed with broth microdilution testing of CRAB isolates with cefiderocol. [ABSTRACT FROM AUTHOR]