Time Points Research Articles

Advancing our ability to quantify an individual’s habitual motion path and deviation when running

The habitual motion path theory states that exhibiting kinematic differences between running and habitual movement tasks may increase the risk of running-related injury. Staying near one’s habitual motion path when running has been shown to reduce compression of the knee joint cartilage, a proxy for decreased soft tissue loading. Previous efforts to quantify one’s habitual motion path and deviation when running have utilised just one habitual movement and one time point during the stance phase of running. The methodology advancement described in this manuscript focused on advancing habitual motion path theory research by (1) increasing the number of movements for quantifying an individual’s habitual motion path; and (2) utilising the entire stance phase when running to quantify deviations as opposed to one time point. We liken the advancements in the method described in this manuscript as with the first method we were using a ruler to assess one’s habitual motion path and deviations, and now we are using calipers; providing a more accurate understanding of an individual’s unique habitual movement and deviation when running. We also discuss future potential research avenues related to understanding running biomechanics and footwear effects that this tool will allow us to explore.

Effects of prednisolone on 1,2-O-dilauryl-rac-glycero glutaric acid-(60-methylresorufin) ester-lipase activity and pancreatic lipase immunoreactivity in healthy cats.

Corticosteroids are among the most commonly used drugs in cats and are increasingly discussed as a treatment for feline pancreatitis. However, its effects on serum lipase in healthy cats remain unknown. To evaluate the effects of prednisolone on serum lipase activity and pancreatic lipase immunoreactivity (PLI) in cats. Seven clinically healthy colony cats, aged 4 to 7 years, with unremarkable CBC/biochemistry panel were studied. Prospective study: Prednisolone (1.1-1.5 mg/kg, median 1.28 mg/kg PO) was given daily for 7 consecutive days. Lipase activity (LIPC Roche; RI, 8-26 U/L) and PLI (Spec fPL; RI, 0-3.5 μg/L) were determined at day 1 before first treatment and at days 2, 3, 8, 10, and 14. Cats were examined daily. An a priori power analysis indicated that 6 cats were needed to find a biological relevant effect at 1-β = 0.8. Statistical analyses comprised the Friedman test, random intercept regression, and repeated-measures linear regression. Median (range) day 1 lipase activities and PLI were 22 U/L (14-52 U/L) and 3.2 μg/L (2.3-15.7 μg/L). One cat with abnormally high lipase activity (52 U/L) and PLI (15.7 μg/L) at day 1 continued having elevated lipase activities and PLI throughout the study. Lipase activities and PLI concentrations did not differ significantly among time points regardless of whether the cat with elevated values was included or not. All cats remained healthy throughout the study. Administration of prednisolone in anti-inflammatory doses does not significantly increase serum lipase activity and PLI concentration.

Characteristics of Users of a Digital Hypnotherapy Intervention for Hot Flashes: Retrospective Study.

Hot flashes are associated with a lower quality of life and sleep disturbances. Given the many consequences of hot flashes, it is important to find treatments to reduce them. Hypnotherapy, the use of hypnosis for a medical disorder or concern, has been shown in clinical trials to be effective in reducing hot flashes, but it is not routinely used in clinical practice. One solution to close this implementation gap is to administer hypnotherapy for hot flashes via a smartphone app. Evia is a smartphone app that delivers hypnotherapy for hot flashes. Evia has made hypnotherapy more widely accessible for women who are experiencing hot flashes; however, the app has yet to undergo empirical testing. Additionally, research on user characteristics is lacking. This study aims to (1) determine the average age, stage of menopause, and length of menopause symptoms for users of the Evia app; (2) determine the characteristics of hot flashes and night sweats for users of the Evia app; (3) determine the self-reported sleep quality of users of the Evia app; (4) determine the self-reported mental health of users of the Evia app; and (5) determine the relationship between hot flash frequency and anxiety and depression for users of the Evia app. This study analyzed data collected from participants who have downloaded the Evia app. Data were collected at 1 time point from a self-report questionnaire that assessed the demographic and clinical characteristics of users. The questionnaire was given to users when they downloaded the Evia app. Users of the Evia app fill out a questionnaire upon enrolling in the program and prior to beginning the intervention. This included 9764 users. Results showed that the mean age of users was 49.31 years. A total of 41.6% (1942/4665) of users reported experiencing 5 or more hot flashes per day, while 51.2% (1473/2877) of users reported having difficulty falling asleep each night and 47.7% (1253/2626) of users reported their sleep quality to be terrible. In addition, 38.4% (1104/2877) of users reported that they often feel anxious or depressed. There was a small, significant, and negative correlation between hot flash frequency and self-report frequency of anxiety and depression (r=-0.09). This study showed that the average age of app users is in line with the median age of natural menopause. A large percentage of users reported experiencing 5 or more hot flashes per day, reported difficulties with sleep, and reported experiencing depression and anxiety. These findings are in line with previous studies that assessed hot flash frequency and the consequences of hot flashes. This was the first study to report on the characteristics of users of the Evia app. Results will be used to optimize the hypnotherapy program delivered via the Evia app.

I help, therefore, I am? - A registered report on longitudinal inter-relations of the three-dimensional moral self-concept and prosocial behaviours in preschool children.

Children's moral self-concept (MSC) has been proposed to relate to prosocial behaviour. However, systematic assessments of their inter-relations are scarce. Therefore, this longitudinal study investigated the development, structure and inter-relation of prosocial behaviours and the MSC in childhood, using three measurement points at ages 4, 5 and 6 years. We assessed children's MSC and helping, sharing and comforting behaviours in a laboratory setting. Confirmatory factor analyses revealed a three-dimensional MSC structure at 5 and 6 years, but not at 4 years. There was inconsistent stability across time points regarding prosocial behaviour and MSC. For the comforting domain, but not the other domains, cross-lagged relations between self-concept and behaviour were present. Moreover, helping behaviour and self-concept were inter-related at 6 years. Results provide support for reciprocal associations between MSC and prosocial behaviour, albeit only in the comforting domain. They highlight the importance of distinguishing between types of prosocial behaviour and corresponding dimensions of the self-concept, as different developmental trajectories and associations emerge.

Associations of Kidney Tubular Biomarkers With Incident Macroalbuminuria and Sustained Low eGFR in DCCT/EDIC.

Tubulointerstitial injury contributes to diabetic kidney disease (DKD) progression. We tested tubular biomarker associations with DKD development in type 1 diabetes (T1D). We performed a case-cohort study examining associations of tubular biomarkers, measured across seven time points spanning ∼30 years, with incident macroalbuminuria ("severely elevated albuminuria," urinary albumin excretion rate (AER) ≥300 mg/day) and sustained low estimated glomerular filtration rate (eGFR) (persistent eGFR <60 mL/min/1.73 m2) in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. Biomarkers included KIM-1 and sTNFR1 in serum/plasma, MCP-1 and EGF in urine, and a composite tubular secretion score reflecting secreted solute clearance. We assessed biomarkers using single values, as mean values from consecutive time points, and as change over consecutive time points, each as time-updated exposures. At baseline, mean diabetes duration was 5.9 years, with mean HbA1c 8.9%, eGFR 125 mL/min/1.73 m2, and AER 16 mg/day. There were 4.8 and 3.5 cases per 1,000 person-years of macroalbuminuria and low eGFR, respectively. Assessed according to single biomarker values, KIM-1 was associated with risk of subsequent macroalbuminuria and low eGFR (hazard ratio [HR] per 20% higher biomarker 1.11 [95% CI 1.06, 1.16] and 1.12 [1.04, 1.21], respectively) and sTNFR1 was associated with subsequent macroalbuminuria (1.14 [1.03, 1.25]). Mean KIM-1 and EGF-to-MCP-1 ratio were associated with subsequent low eGFR. In slope analyses, increases in KIM-1 and sTNFR1 were associated with subsequent macroalbuminuria (per 20% biomarker increase, HR 1.81 [1.40, 2.34] and 1.95 [1.18, 3.21]) and low eGFR (2.26 [1.65, 3.09] and 2.94 [1.39, 6.23]). Serial KIM-1 and sTNFR1 are associated with incident macroalbuminuria and sustained low eGFR in T1D.

Monitoring Educational Intervention Programs for Children and Young People with Disabilities through a Web Application

Early care professionals have to use instruments for assessing functional skills in children susceptible to early intervention that apply records and produce developmental profiles and personalized intervention proposals. The aims of the study were (1) to analyze the development of functional skills in users with an age range of 48–252 months attending school in a therapeutic intervention center for people with motor impairments; and (2) to analyze the development of functional skills in users with different impairments and ages ranging from 7 to 162 months participating in an early outpatient care program. Study 1 applied a sample of 50 users aged between 48 and 252 months all with motor disabilities and Study 2 included a sample of 71 users aged between 7 and 162 months with different disabilities. Factorial and descriptive–correlational designs were applied in both studies. The Student’s t-test for dependent samples, supervised machine learning techniques (linear regression analysis and logarithmic regression analysis), unsupervised machine learning techniques (k-means), ANOVA, and cross-tabulations were used as contrast tests. In Study 1, no significant changes were found in the development of users’ functional skills, except for a decrease in maladaptive behaviors. Likewise, the chronological age variable did not seem to be a determining factor in the results. In Study 2, significant differences were found in the development of all functional skills between the three measurement time points (initial–intermediate–final). In this group, the type of impairment explained 29% and chronological age 40% of the variance in functional development at the final measurement. This study found that intervention before four years old in outpatient mode produced better results in the acquisition of functional skills, with better results in users affected by rare diseases or communication and language delay at ages 49–60 months.

Impact effects of COVID-19 pandemic on chronic disease patients: A longitudinal prospective study.

To assess the effects of COVID-19 pandemic on clinical variables as part of the routine clinical monitoring of patients with chronic diseases in primary care. A prospective longitudinal study was conducted in primary care centres of the Andalusian Health Service. Data were recorded before the pandemic (T1), during the declaration of the state of emergency (T2) and in the transition phase (T3). The Barthel index and the Short Portable Mental Status Questionnaire (SPMSQ) were used to analyse functional and cognitive changes at the three time points. HbA1c, systolic and diastolic blood pressure, heart rate, BMI and lipid levels were assessed as clinical variables. Descriptive statistics and non-parametric chi-square test were used for analysis. STROBE checklist was used for the preparation of this paper. A total fo148 patients with chronic conditions were included in the analysis. Data analysis revealed in T2 only significant reductions in BMI, total levels of cholesterol and HDL during the onset of the pandemic. Barthel Index, SPMSQ, blood pressure and triglycerides and LDL levels worsened in T2, and the negative effects were maintained in T3. Compared to pre-pandemic values, HbA1c levels improved in T3, but HDL levels worsened. COVID-19 has drastically disrupted several functional, cognitive and biological variables. These results may be useful in identifying clinical parameters that deserve closer attention in the case of a new health crisis. Further studies are needed to assess the potential impacts of each specific chronic condition. Cognitive and functional status, blood pressure and triglycerides and LDL levels worsen in short term, maintaining the negative effects in medium-term.

Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating.

Comparative analysis of infections by SARS-CoV-2 ancestral virus and variants of concern, including Alpha, Beta, Delta, and Omicron, indicated that variants were selected for efficiency in replication. In infections of patient-derived primary nasal cultures grown at air-liquid interface to model upper respiratory infection, Omicron reached the highest titers at early time points, a finding that was confirmed by parallel population sampling studies. While all infections overcame dsRNA-mediated host responses, infections with Omicron induced the strongest interferon and interferon-stimulated gene response. In both primary nasal cultures and lower respiratory cell line, infections by Delta were most damaging to the cells as indicated by syncytia formation, loss of cell barrier integrity, and nasal ciliary function.

Longitudinal Free-Water Changes in Dementia with Lewy Bodies.

Diffusion-weighted magnetic resonance imaging (dMRI) examines tissue microstructure integrity in vivo. Prior dementia with Lewy bodies (DLB) diffusion tensor imaging studies yielded mixed results. We employed free-water (FW) imaging to assess DLB progression and correlate with clinical decline in DLB. Baseline and follow-up MRIs were obtained at 12 and/or 24 months for 27 individuals with DLB or mild cognitive impairment with Lewy bodies (MCI-LB). FW was analyzed using the Mayo Clinic Adult Lifespan Template. Primary outcomes were FW differences between baseline and 12 or 24 months. To compare FW change longitudinally, we included 20 cognitively unimpaired individuals from the Alzheimer's Disease Neuroimaging Initiative. We followed 23 participants to 12 months and 16 participants to 24 months. Both groups had worsening in Montreal Cognitive Assessment (MoCA) and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores. We found significant FW increases at both time points compared to baseline in the insula, amygdala, posterior cingulum, parahippocampal, entorhinal, supramarginal, fusiform, retrosplenial, and Rolandic operculum regions. At 24 months, we found more widespread microstructural changes in regions implicated in visuospatial processing, motor, and cholinergic functions. Between-group analyses (DLB vs. controls) confirmed significant FW changes over 24 months in most of these regions. FW changes were associated with longitudinal worsening of MDS-UPDRS and MoCA scores. FW increased in gray and white matter regions in DLB, likely due to neurodegenerative pathology associated with disease progression. FW change was associated with clinical decline. The findings support dMRI as a promising tool to track disease progression in DLB. © 2024 International Parkinson and Movement Disorder Society.

Biodistribution of Drug/ADA Complexes: The Impact of Immune Complex Formation on Antibody Distribution

The clinical use of therapeutic monoclonal antibodies (mAbs) for the treatment of cancer, inflammation, and other indications has been successfully established. A critical aspect of drug-antibody pharmacokinetics is immunogenicity, which triggers an immune response via an anti-drug antibody (ADA) and forms drug/ADA immune complexes (ICs). As a consequence, there may be a reduced efficacy upon neutralization by ADA or an accelerated drug clearance. It is therefore important to understand immunogenicity in biological therapies. A drug-like immunoglobulin G (IgG) was radiolabeled with tritium, and ICs were formed using polyclonal ADA, directed against the complementary-determining region of the drug-IgG, to investigate in vivo biodistribution in rodents. It was demonstrated that 65% of the radioactive IC dose was excreted within the first 24 h, compared with only 6% in the control group who received non-complexed 3H-drug. Autoradiographic imaging at the early time point indicated a deposition of immune complexes in the liver, lung, and spleen indicated by an increased radioactivity signal. A biodistribution study confirmed the results and revealed further insights regarding excretion and plasma profiles. It is assumed that the immune complexes are readily taken up by the reticuloendothelial system. The ICs are degraded proteolytically, and the released radioactively labeled amino acids are redistributed throughout the body. These are mainly renally excreted as indicated by urine measurements or incorporated into protein synthesis. These biodistribution studies using tritium-labeled immune complexes described in this article underline the importance of understanding the immunogenicity induced by therapeutic proteins and the resulting influence on biological behavior.Graphical Created with BioRender.com

Ten-year results from the UK National Ligament Registry: Patient characteristics and factors predicting nonresponders for completion of outcome scores.

The aim of this study was to report the demographic and mechanism of injury data in the UK National Ligament Registry (NLR) at 10 years and determine factors leading to poor compliance with completion of Patient-Reported Outcome Scores (PROMs). A retrospective review was performed for prospectively collected data on the NLR between January 2013 and December 2022. All patients who underwent primary anterior cruciate ligament reconstruction (ACLR) were included. Patient demographics, mechanism of injury and patient compliance with completing PROMs were analysed. Patient characteristics were further analysed in relation to compliance with completing the different PROMs at the predefined time points. Patients were identified as nonresponders if they had not completed either 1- or 2-year postoperative Knee injury and Osteoarthritis Outcome Score (KOOS). A total of 17,492 patients were included in this study. The average age for patients undergoing ACLR between 2013 and 2022 was 29.4 (SD, 10.3). Seventy percent were men and 30% women. Football was the most common activity associated with an ACL injury. Patient compliance with recording PROMs was 55% preoperatively and 37%, 32% and 24% at 1-, 2- and 5-year postoperative follow-up, respectively. Nonresponders represented 54% of eligible patients. Multivariate analyses showed that sex, age, smoking, time interval between injury and surgery and low socioeconomic status were associated with low compliance with postoperative PROM completion (p < 0.001). This study reports the demographic characteristics for patients on the NLR since 2013. Male sex, young age, increased waiting time between injury and surgery, smoking and lower socioeconomic class were predictors of low compliance with completion of postoperative PROMs on the UK NLR. Understanding the factors that affect patient compliance with PROMs improves our ability to provide targeted interventions and information to specific patient populations with the aim of enhancing inclusiveness and representation of population in the registry. Level III.

Precursors to infant sensorimotor synchronization to speech and non-speech rhythms: A longitudinal study.

Impaired sensorimotor synchronization (SMS) to acoustic rhythm may be a marker of atypical language development. Here, Motion Capture was used to assess gross motor rhythmic movement at six time points between 5- and 11 months of age. Infants were recorded drumming to acoustic stimuli of varying linguistic and temporal complexity: drumbeats, repeated syllables and nursery rhymes. Here we show, for the first time, developmental change in infants' movement timing in response to auditory stimuli over the first year of life. Longitudinal analyses revealed that whilst infants could not yet reliably synchronize their movement to auditory rhythms, infant spontaneous motor tempo became faster with age, and by 11 months, a subset of infants decelerate from their spontaneous motor tempo, which better accords with the incoming tempo. Further, infants became more regular drummers with age, with marked decreases in the variability of spontaneous motor tempo and variability in response to drumbeats. This latter effect was subdued in response to linguistic stimuli. The current work lays the foundation for using individual differences in precursors of SMS in infancy to predict later language outcomes. RESEARCH HIGHLIGHT: We present the first longitudinal investigation of infant rhythmic movement over the first year of life Whilst infants generally move more quickly and with higher regularity over their first year, by 11 months infants begin to counter this pattern when hearing slower infant-directed song Infant movement is more variable to speech than non-speech stimuli In the context of the larger Cambridge UK BabyRhythm Project, we lay the foundation for rhythmic movement in infancy to predict later language outcomes.

Body fluids should be identified before estimating the time since deposition (TsD) in microbiome-based stain analyses for forensics.

Identification and the time since deposition (TsD) estimation of body fluid stains from a crime scene could provide valuable information for solving the cases and are always difficult for forensics. Microbial characteristics were considered as a promising biomarker to address the issues. However, changes in the microbiota may damage the specific characteristics of body fluids. Correspondingly, incorrect body fluid identification may result in inaccurate TsD estimation. The mutual influence is not well understood and limited the codetection. In the current study, saliva, semen, vaginal secretion, and menstrual blood samples were exposed to indoor conditions and collected at eight time points (from fresh to 30 days). High-throughput sequencing based on the 16S rRNA gene was performed to characterize the microbial communities. The results showed that a longer TsD could decrease the discrimination of different body fluid stains. However, the accuracies of identification still reached a quite high value even without knowing the TsD. Correspondingly, the mean absolute error (MAE) of TsD estimation significantly increased without distinguishing the types of body fluids. The predictive TsD of menstrual blood reached a quite low MAE (1.54 ± 0.39 d). In comparison, those of saliva (6.57 ± 1.17 d), semen (6.48 ± 1.33 d), and vaginal secretion (5.35 ± 1.11 d) needed to be further improved. The great effect of individual differences on these stains limited the TsD estimation accuracy. Overall, microbial characteristics allow for codetection of body fluid identification and TsD estimation, and body fluids should be identified before estimating TsD in microbiome-based stain analyses.IMPORTANCEEmerged evidences suggest microbial characteristics could be considered a promising tool for identification and time since deposition (TsD) estimation of body fluid stains. However, the two issues should be studied together due to a potential mutual influence. The current study provides the first evidence to understand the mutual influence and determines an optimal process for codetection of identification and TsD estimation for unknown stains for forensics. In addition, we involved aged stains into our study for identification of body fluid stains, rather than only using fresh stains like previous studies. This increased the predictive accuracy. We have preliminary verified that individual differences in microbiotas limited the predictive accuracy of TsD estimation for saliva, semen, and vaginal secretion. Microbial characteristics could provide an accurate TsD estimation for menstrual blood. Our study benefits the comprehensive understanding of microbiome-based stain analyses as an essential addition to previous studies.

Development of an Engineered Single-Domain Antibody for Targeting MET in Non-Small Cell Lung Cancer.

The Mesenchymal Epithelial Transition (MET) receptor tyrosine kinase is upregulated or mutated in 5% of non-small-cell lung cancer (NSCLC) patients and overexpressed in multiple other cancers. We sought to develop a novel single-domain camelid antibody with high affinity for MET that could be used to deliver conjugated payloads to MET expressing cancers. From a naïve camelid variable-heavy-heavy (VHH) domain phage display library, we identified a VHH clone termed 1E7 that displayed high affinity for human MET and was cross-reactive with MET across multiple species. When expressed as a bivalent human Fc fusion protein, 1E7-Fc was found to selectively bind to EBC-1 (MET amplified) and UW-Lung 21 (MET exon 14 mutated) cell lines by flow cytometry and immunofluorescence imaging. Next, we investigated the ability of [89Zr]Zr-1E7-Fc to detect MET expression in vivo by PET/CT imaging. [89Zr]Zr-1E7-Fc demonstrated rapid localization and high tumor uptake in both xenografts with a %ID/g of 6.4 and 5.8 for EBC-1 and UW-Lung 21 at 24 h, respectively. At the 24 h time point, clearance from secondary and nontarget tissues was also observed. Altogether, our data suggest that 1E7-Fc represents a platform technology that can be employed to potentially both image and treat MET-altered NSCLC.

Parotid glands have a dysregulated immune response following radiation therapy.

Head and neck cancer treatment often consists of surgical resection of the tumor followed by ionizing radiation (IR), which can damage surrounding tissues and cause adverse side effects. The underlying mechanisms of radiation-induced salivary gland dysfunction are not fully understood, and treatment options are scarce and ineffective. The wound healing process is a necessary response to tissue injury, and broadly consists of inflammatory, proliferative, and redifferentiation phases with immune cells playing key roles in all three phases. In this study, select immune cells were phenotyped and quantified, and certain cytokine and chemokine concentrations were measured in mouse parotid glands after IR. Further, we used a model where glandular function is restored to assess the immune phenotype in a regenerative response. These data suggest that irradiated parotid tissue does not progress through a typical inflammatory response observed in wounds that heal. Specifically, total immune cells (CD45+) decrease at days 2 and 5 following IR, macrophages (F4/80+CD11b+) decrease at day 2 and 5 and increase at day 30, while neutrophils (Ly6G+CD11b+) significantly increase at day 30 following IR. Additionally, radiation treatment reduces CD3- cells at all time points, significantly increases CD3+/CD4+CD8+ double positive cells, and significantly reduces CD3+/CD4-CD8- double negative cells at day 30 after IR. Previous data indicate that post-IR treatment with IGF-1 restores salivary gland function at day 30, and IGF-1 injections attenuate the increase in macrophages, neutrophils, and CD4+CD8+ T cells observed at day 30 following IR. Taken together, these data indicate that parotid salivary tissue exhibits a dysregulated immune response following radiation treatment which may contribute to chronic loss of function phenotype in head and neck cancer survivors.

Advancing randomized controlled trial methodologies: The place of innovative trial design in eating disorders research.

Randomized controlled trials can be used to generate evidence on the efficacy and safety of new treatments in eating disorders research. Many of the trials previously conducted in this area have been deemed to be of low quality, in part due to a number of practical constraints. This article provides an overview of established and more innovative clinical trial designs, accompanied by pertinent examples, to highlight how design choices can enhance flexibility and improve efficiency of both resource allocation and participant involvement. Trial designs include individually randomized, cluster randomized, and designs with randomizations at multiple time points and/or addressing several research questions (master protocol studies). Design features include the use of adaptations and considerations for pragmatic or registry-based trials. The appropriate choice of trial design, together with rigorous trial conduct, reporting and analysis, can establish high-quality evidence to advance knowledge in the field. It is anticipated that this article will provide a broad and contemporary introduction to trial designs and will help researchers make informed trial design choices for improved testing of new interventions in eating disorders. PUBLIC SIGNIFICANCE: There is a paucity of high quality randomized controlled trials that have been conducted in eating disorders, highlighting the need to identify where efficiency gains in trial design may be possible to advance the eating disorder research field. We provide an overview of some key trial designs and features which may offer solutions to practical constraints and increase trial efficiency.

Left ventricular global longitudinal strain and acute myocardial injury in patients with sickle cell disease admitted to the intensive care unit for vaso-occlusive crisis.

In patients with sickle cell disease (SCD), SCD-related cardiomyopathy may be partly due to repeated ischaemic events related to sickling during vaso-occlusive crises, but few clinical studies support this hypothesis. We evaluated the incidence of acute myocardial ischaemia during vaso-occlusive crises as assessed by the left ventricular global longitudinal strain (LVGLS) and high-sensitive cardiac troponin T (hs-cTnT). We included adult patients with SCD admitted to the intensive care unit (ICU) for vaso-occlusive crisis. We collected hs-cTnT and measured LVGLS with echocardiography at admission (day 1), day 2, day 3 and ICU discharge. Among 55 patients included, considering only the first hospitalization of patients admitted several times, 3 (5%) had elevated hs-cTnT at ≥1 time point of the ICU stay. It was ≤2 times the upper limit of normal in two of these patients. LVGLS was altered at ≥1 time point of the ICU stay in 13 (24%) patients. Both hs-cTnT and LVGLS were abnormal at ≥1 time point of the hospital stay in 2 (4%) patients. Acute myocardial injury as assessed by troponin elevation and LVGLS impairment was a rare event during vaso-occlusive crises.

Superficial skin temperature recovery of distal limbs of thoroughbred racehorses after training in a racetrack in different seasons.

In the present study we aimed to investigate superficial skin temperature of racehorses' distal limbs after training in a racetrack. Male and female Thoroughbred racehorses were investigated in summer, after light training, and in the winter, after light and intense training. Horses were exercised (Exercise group, EG) under trainers' protocol while others were maintained inside their stalls (Control group, CG). Thermographic images were obtained from the front (fetlock, cannon, and carpus) and hindlimbs (fetlock, cannon, and tarsus), before exercise and 45, 60, 120 and 180min after exercising. Images were analyzed using the Flir Tools® program. Temperatures of different moments of each group were compared using Anova for repeated measures and each moment of EG versus CG using Student t test. Horses of the CG maintained steady temperature in the winter, but in summer temperature increased at M45 until M180 (P < 0,01). EG increased temperatures after exercises that remained higher than M0 even at 180min post-exercise (P < 0,0001), for most of the regions in winter and summer. EG temperatures were higher than CG at most of the time points after exercise. There was positive correlation between all regions' temperature and the atmospheric temperature for the CG during the summer (P = 0,003, r2 = 0,9622), observed for the front fetlock and carpal regions for the EG (P = 0.035, r2 = 0,8166). This pilot study demonstrates that, after race exercising under natural conditions skin temperature might take more than 180min to return to basal values.

18F]FDG PET/CT for prognosis and toxicity prediction of diffuse large B-cell lymphoma patients with chimeric antigen receptor T-cell therapy.

Chimeric antigen receptor (CAR) T-cell therapy has been confirmed to benefit patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL). It is important to provide precise and timely predictions of the efficacy and toxicity of CAR T-cell therapy. In this study, we evaluated the value of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) combining with clinical indices and laboratory indicators in predicting outcomes and toxicity of anti-CD19 CAR T-cell therapy for DLBCL patients. Thirty-eight DLBCL patients who received CAR T-cell therapy and underwent [18F]FDG PET/CT within 3 months before (pre-infusion) and 1 month after CAR T-cell infusion (M1) were retrospectively reviewed and regularly followed up. Maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), metabolic tumor volume (MTV), clinical indices, and laboratory indicators were recorded at pre-infusion and M1 time points, and changes in these indices were calculated. Progression-free survival (PFS) and overall survival (OS) were as endpoints. Based on the multivariate Cox regression analysis, two predictive models for PFS and OS were developed and evaluated the efficiency. Pre-infusion indices were subjected to predict the grade of cytokine release syndrome (CRS) resulting from toxic reactions. For survival analysis at a median follow-up time of 18.2 months, patients with values of international prognostic index (IPI), SUVmax at M1, and TLG at M1 above their optimal thresholds had a shorter PFS (median PFS: 8.1 months [IPI ≥ 2] vs. 26.2 months [IPI < 2], P = 0.025; 3.1 months [SUVmax ≥ 5.69] vs. 26.8 months [SUVmax < 5.69], P < 0.001; and 3.1 months [TLG ≥ 23.79] vs. 26.8 months [TLG < 23.79], P < 0.001). In addition, patients with values of SUVmax at M1 and ∆SUVmax% above their optimal thresholds had a shorter OS (median OS: 12.6 months [SUVmax ≥ 15.93] vs. 'not reached' [SUVmax < 15.93], P < 0.001; 32.5 months [∆SUVmax% ≥ -46.76] vs. 'not reached' [∆SUVmax% < -46.76], P = 0.012). Two novel predictive models for PFS and OS were visualized using nomogram. The calibration analysis and the decision curves demonstrated good performance of the models. Spearman's rank correlation (rs) analysis revealed that the CRS grade correlated strongly with the pre-infusion SUVmax (rs = 0.806, P < 0.001) and moderately with the pre-infusion TLG (rs = 0.534, P < 0.001). Multinomial logistic regression analysis revealed that the pre-infusion value of SUVmax correlated with the risk of developing a higher grade of CRS (P < 0.001). In this group of DLBCL patients who underwent CAR T-cell therapy, SUVmax at M1, TLG at M1, and IPI were independent risk factors for PFS, and SUVmax at M1 and ∆SUVmax% for OS. Based on these indicators, two novel predictive models were established and verified the efficiency for evaluating PFS and OS. Moreover, pre-infusion SUVmax correlated with the severity of any subsequent CRS. We conclude that metabolic parameters measured using [18F]FDG PET/CT can identify DLBCL patients who will benefit most from CAR T-cell therapy, and the value before CAR T-cell infusion may predict its toxicity in advance.

Changes in OCTA-related parameters and their impact on retinal sensitivity after ILM flap inversion surgery in patients with IMH

Objective: To analyze the changes in optical coherence tomography angiography(OCTA)-related parameters before and after idiopathic macular hole (IMH) internal limiting membrane (ILM) flap inversion surgery and assess their impact on retinal sensitivity. Methods: A retrospective case series study was conducted, collecting clinical data of 30 patients (30 eyes) diagnosed with IMH who underwent vitrectomy combined with ILM flap inversion surgery at Shanxi Eye Hospital, affiliated with Shanxi Medical University, between January 2020 and December 2021. Visual acuity and best-corrected visual acuity were examined preoperatively and at 1, 3, and 6 months postoperatively. Microperimetry measured retinal sensitivity (RS), and OCTA measured retinal thickness (RT) as well as vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Statistical analysis was performed using t-tests, repeated measures analysis of variance, and Pearson correlation analysis. Results: Thirty patients with IMH (30 eyes) were included, with 3 males (3 eyes) and 27 females (27 eyes). The mean age was (62.5±3.0) years, and the follow-up time was (96.3±1.3) days, with a 100% closure rate of macular holes postoperatively. RT in the macular was significantly lower at 1, 3, and 6 months postoperatively compared to preoperative values (F=46.21, P<0.001). The RT in the upper macular region showed statistically significant differences at different time points (P<0.001). VD in the SCP layer showed no significant differences between the upper and lower macular regions at various time points (F=3.21, P=0.601). VD in the upper region of the DCP layer increased at 1, 3, and 6 months postoperatively (P<0.001). RS in the macular was higher at 1, 3, and 6 months postoperatively compared to preoperative values (F=52.01, P<0.001). RS in the lower macular region increased at 3 and 6 months postoperatively (P<0.001), while in the upper region, it increased only at 6 months postoperatively (P<0.001). There was a positive correlation between RS and RT at 1 and 3 months postoperatively, but not at 6 months postoperatively in the upper macular region (r=0.40, P=0.071). In the lower macular region, there was a positive correlation between RS and RT at 1 and 3 months postoperatively (P<0.001). There was no correlation between RS in the upper macular region at 6 months postoperatively and preoperative RT (r=0.43, P=0.072), but there was a positive correlation with RT at 3 months postoperatively (r=0.58, P=0.041). Conclusions: After idiopathic macular hole internal limiting membrane flap inversion surgery, the OCTA-related parameters have changed. There are transient changes in deep vascular parameters and thinning of the retinal layers at the ILM inversion site, leading to decreased sensitivity.