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For prostate cancer patients who experience biochemical progression during androgen deprivation therapy (ADT), prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has not been prospectively compared to planar bone scan plus CT. This was a single-arm, head-to-head, prospective phase II trial (NCT04928820) designed to enroll 102 men with prostate cancer who experienced biochemical progression (rising prostate-specific antigen [PSA] ≥ 1 ng/mL) during ADT. All patients received 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scans. Each scan was interpreted by three central independent readers. The primary endpoint was the per-patient bone metastasis detection rate of PSMA PET/CT versus planar bone scan and CT. Secondary endpoints compared the number of bone metastases detected per patient and the inter-reader agreement of each imaging modality. Twenty-two men were enrolled between July 2021 and June 2022. Due to slow accrual following approval of PSMA PET radiotracers in the U.S. and a lack of a statistical signal between the two imaging modalities on interim analysis, this trial was closed early on October 2022. Median PSA was 8.5 ng/mL (interquartile range: 1.6-77.6). There was 100% agreement between the two scans. Six patients (27%) had negative findings and 16 patients (73%) had positive findings on both scans. PSMA PET/CT and bone scan plus CT detected an equal number of bone lesions for 14 patients (64%), PSMA PET/CT detected more bone lesions for six patients (27%), and bone scan plus CT detected more bone lesions for two patients (9.1%) (p = 0.092). The inter-reader agreement rates of PSMA PET/CT and bone scan plus CT were 96% and 82%, respectively (p = 0.25). In men with biochemical progression during ADT, 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scan plus CT had identical bone metastasis detection rates. Bone scan plus CT can continue to serve as a cost-effective and readily accessible restaging modality in patients with biochemical progression. ClinicalTrials.gov NCT04928820. Registered 16/06/2021.

The Brazilian Amazon is a vast area with limited health care resources. To assess the epidemiology of critically ill acute kidney injury (AKI) patients in this area, a prospective cohort study of 1029 adult patients of the three intensive care units (ICUs) of Rio Branco city, the capital of Acre state, were evaluated from February 2014 to February 2016. The incidence of AKI was 53.3%. Risk factors for AKI included higher age, nonsurgical patients, admission to the ICU from the ward, higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores at ICU admission, and positive fluid balance > 1500 ml/24 hours in the days before AKI development in the ICU, with aOR of 1.3 (95% CI 1.03-1.23), 1.47 (95% CI 1.07-2.03), 1.96 (95% CI 1.40-2.74), 1.05 (95% CI 1.03-1.08) for each unit increase, and 1.62 (95% CI 1.16-2.26), respectively. AKI was associated with higher ICU mortality (aOR 2.03, 95% CI 1.29-3.18). AKI mortality was independently associated with higher age, nonsurgical patients, sepsis at ICU admission, presence of shock or use of vasoactive drugs, mechanical ventilation and mean positive fluid balance in the ICU > 1500 ml/24 hours, both during ICU follow-up, with aOR 1.27 (95% CI 1.14-1.43) for each 10-year increase, 1.64 (95% CI 1.07-2.52), 2.35 (95% CI 1.14-4.83), 1.88 (95% CI 1.03-3.44), 6.73 (95% CI 4.08-11.09), 2.31 (95% CI 1.52-3.53), respectively. Adjusted hazard ratios for AKI mortality 30 and 31-180 days after ICU discharge were 3.13 (95% CI 1.84-5.31) and 1.69 (95% CI 0.99-2.90), respectively. AKI incidence was strikingly high among critically ill patients in the Brazilian Amazon. The AKI etiology, risk factors and outcomes were similar to those described in high-income countries, but mortality rates were higher.

In a prospective cohort of subjects who subsequently developed preeclampsia (PE, n = 14) versus remaining healthy (NORM, n = 12), early gestation circulating extracellular vesicles (EVs) containing a panel of microRNA signatures were characterized and their biological networks of targets deciphered. Multiple microRNAs of which some arose from the placenta (19MC and 14MC) demonstrated changes in association with advancing gestation, while others expressed were pathognomonic of the subsequent development of characteristic clinical features of PE which set in as a late-onset subtype. This panel of miRNAs demonstrated a predictability with an area under the curve of 0.96 using leave-one-out cross-validation training in a logistic regression model with elastic-net regularization and precautions against overfitting. In addition, this panel of miRNAs, some of which were previously detected in either placental tissue or as maternal cell-free non-coding transcripts, lent further validation to our EV studies and the observed association with PE. Further, the identified biological networks of targets of these detected miRNAs revealed biological functions related to vascular remodeling, cellular proliferation, growth, VEGF, EGF and the PIP3/Akt signaling pathways, all mediating key cellular functions. We conclude that we have demonstrated a proof-of-principle by detecting a panel of EV packaged miRNAs in the maternal circulation early in gestation with possibilities of biological function in the placenta and other maternal tissues, along with the probability of predicting the subsequent clinical appearance of PE, particularly the late-onset subtype.

Recent clinical trials have found that the serotonergic psychedelic psilocybin effectively alleviates anxiodepressive symptoms in patients with life-threatening illnesses when given in a supportive environment. These outcomes prompted Canada to establish legal pathways for therapeutic access to psilocybin, coupled with psychological support. Despite over one-hundred Canadians receiving compassionate access since 2020, there has been little examination of these real-world patients. We conducted a prospective longitudinal survey which focused on Canadians who were granted Section 56 exemptions for legal psilocybin-assisted psychotherapy. Surveys assessing various symptom dimensions were conducted at baseline, two weeks following the session (endpoint), and optionally one day post-session. Participant characteristics were examined using descriptive statistics, and paired sample t-tests were used to quantify changes from baseline to the two-week post-treatment endpoint. Eight participants with Section 56 exemptions (four females, Mage = 52.3 years), all with cancer diagnoses, fully completed baseline and endpoint surveys. Significant improvements in anxiety and depression symptoms, pain, fear of COVID-19, quality of life, and spiritual well-being were observed. Attitudes towards death, medical assistance in dying, and desire for hastened death remained unchanged. While most participants found the psilocybin sessions highly meaningful, if challenging, one reported a substantial decrease in well-being due to the experience. These preliminary data are amongst the first to suggest that psilocybin-assisted psychotherapy can produce psychiatric benefits in real-world patients akin to those observed in clinical trials. Limited enrollment and individual reports of negative experiences indicate the need for formal real-world evaluation programs to surveil the ongoing expansion of legal access to psychedelics.

Acute kidney injury (AKI) following hyperthermic intraperitoneal chemotherapy (HIPEC) is common. Identifying patients at risk could have implications for surgical and anesthetic management. We aimed to develop a predictive model that could predict AKI based on patients preoperative characteristics and intraperitoneal chemotherapy regimen. We retrospectively gathered data of adult patients undergoing HIPEC at our health system between November 2013 and April 2022. Next, we developed a model predicting postoperative AKI using multivariable logistic regression and calculated the performance of the model (area under the receiver operating characteristics curve [AUC]) via tenfold cross-validation. A total of 412 patients were included, of which 36 (8.7%) developed postoperative AKI. Based on our multivariable logistic regression model, multiple preoperative and intraoperative characteristics were associated with AKI. We included the total intraoperative cisplatin dose, body mass index, male sex, and preoperative hemoglobin level in the final model. The mean area under the receiver operating characteristics curve value was 0.82 (95% confidence interval 0.71-0.93). Our risk model predicted AKI with high accuracy in patients undergoing HIPEC in our institution. The external validity of our model should now be tested in independent and prospective patient cohorts.

Both body mass index (BMI) and family history of cancer are established risk factors for female breast cancer. However, few studies explored the potential interaction between both factors. We assessed the association of BMI and its interaction with family cancer history on the risk of female breast cancer in Shanghai, China. Based on a population-based prospective cohort study started from 2008 to 2012 with 15,055 Chinese female participants in Minhang district, Shanghai. Cox regression models were used to estimate the association of BMI and its interaction with a family history of cancer on breast cancer risk. The additive interaction was evaluated by the relative excess risk due to interaction (RERI) and the attributable proportion due to interaction (AP), and the multiplicative interaction was assessed by the product term (BMI* family history of cancer) in the Cox regression model. Compared with BMI of

Psilocybin, a serotonergic psychedelic, is being increasingly researched in clinical studies for the treatment of psychiatric disorders. The relatively lengthy duration of oral psilocybins acute effects (4-6 h) may have pragmatic and cost-effectiveness limitations. Here, we explored the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT), a closely related, but faster-acting psychedelic intervention, on mental health outcomes in healthy volunteers. Data is reported from two separate analyses: (1) A comparison of mental health-related variables 1 week after 7, 14, 18, and 20 mg of IV DMT versus IV saline placebo (n = 13) and, (2) A prospective dataset assessing effects before versus 2 weeks after 20 mg of IV DMT (n = 17). Mental health outcomes included measures of depression severity (QIDS-SR16), trait anxiety (STAI-T), Neuroticism (NEO-FFI), wellbeing (WHO-5), meaning in life (MLQ), optimism (LOT-R), and gratitude (GQ-6). In both the prospective and placebo-controlled datasets, significant improvements in scores of depression were found 1-2 weeks after DMT administration. Significant reductions in trait Neuroticism were only found for the placebo-controlled sample. Finally, changes in depression and trait anxiety correlated with acute peak experiences (assessed via Oceanic Boundlessness). While the use of two separate cohorts in pooled analysis limits the generalizability of these correlational findings, these results suggest that DMT may reduce depressive symptomatology by inducing peak experiences. The short half-life of IV DMT and its potential for flexible dosing via controlled infusions makes it an appealing candidate for psychedelic medicine. Further research in clinical samples is needed to corroborate the therapeutic potential of DMT.

Floodlight Open was a global, open-access, digital-only study designed to understand the drivers and barriers in deployment and use of a smartphone app in a naturalistic setting and broad study population of people with and without multiple sclerosis (MS). The study utilised the Floodlight Open app: a bring-your-own-device solution that remotely measures a users mood, cognition, hand motor function, and gait and postural stability via smartphone sensor-based tests requiring active user input (active tests). Levels of mobility of study participants (life-space measurement) were passively measured. Study data from these tests were made available via an open-access platform. Data from 1350 participants with self-declared MS and 1133 participants with self-declared non-MS from 17 countries across four continents were included in this report. Overall, MS participants provided active test data for a mean duration of 5.6 weeks or a mean duration of 19 non-consecutive days. This duration increased among MS participants who persisted beyond the first week to a mean of 10.3 weeks or 36.5 non-consecutive days. Passively collected life-space measurement data were generated by MS participants for a mean duration of 9.8 weeks or 50.6 non-consecutive days. This duration increased to 16.3 weeks/85.1 non-consecutive days among MS participants who persisted beyond the first week. Older age, self-declared MS disease status, and clinical supervision as part of concomitant clinical research were all significantly associated with higher persistence of the use of the Floodlight Open app. MS participants performed significantly worse than non-MS participants on four out of seven active tests. The findings from this multinational study inform future research to improve the dynamics of persistence of use of digital monitoring tools and further highlight challenges and opportunities in applying them to support MS clinical care.

We present an ensemble transfer learning method to predict suicide from Veterans Affairs (VA) electronic medical records (EMR). A diverse set of base models was trained to predict a binary outcome constructed from reported suicide, suicide attempt, and overdose diagnoses with varying choices of study design and prediction methodology. Each model used twenty cross-sectional and 190 longitudinal variables observed in eight time intervals covering 7.5 years prior to the time of prediction. Ensembles of seven base models were created and fine-tuned with ten variables expected to change with study design and outcome definition in order to predict suicide and combined outcome in a prospective cohort. The ensemble models achieved c-statistics of 0.73 on 2-year suicide risk and 0.83 on the combined outcome when predicting on a prospective cohort of [Formula: see text] 4.2 M veterans. The ensembles rely on nonlinear base models trained using a matched retrospective nested case-control (Rcc) study cohort and show good calibration across a diversity of subgroups, including risk strata, age, sex, race, and level of healthcare utilization. In addition, a linear Rcc base model provided a rich set of biological predictors, including indicators of suicide, substance use disorder, mental health diagnoses and treatments, hypoxia and vascular damage, and demographics.

This study evaluated the tolerability and efficacy of the topical rho-kinase inhibitor netarsudil for canine primary corneal endothelial degeneration (PCED). Twenty-six eyes of 21 client-owned dogs with PCED were enrolled in a prospective, randomized, vehicle control clinical trial and received topical netarsudil 0.02% (Rhopressa®) or vehicle control twice daily (BID) for the first 4 months. Then, all patients received netarsudil for the next 4 or 8 months. Complete ophthalmic examination, ultrasonic pachymetry, Fourier-domain optical coherence tomography, and in vivo confocal microscopy were performed at baseline and 1, 2, 4, 6, 8 and 12 months. Effect of netarsudil on central corneal thickness (CCT), percentage of cornea with edema, and endothelial cell density (ECD) were evaluated by repeated measures ANOVA. Kaplan-Meier curves and log-rank test were used to compare corneal edema and clinical progression of eyes in netarsudil versus vehicle control groups. All dogs developed conjunctival hyperemia in at least one eye while receiving netarsudil. Unilateral transient reticulated intraepithelial bullae and stromal hemorrhage were observed respectively in 2 dogs in the netarsudil group. Two dogs showed persistently decreased tear production while receiving netarsudil, requiring topical immunomodulatory treatment. No significant differences in CCT, ECD, corneal edema or clinical progression were observed between netarsudil or vehicle treated eyes. When comparing efficacy of topical netarsudil BID and topical ripasudil 0.4% administered four times daily from our previous study, dogs receiving ripasudil had significantly less progression than those receiving netarsudil.

The relationship between depression and severe non-alcoholic fatty liver disease (NAFLD) has not been clearly defined. We conducted a longitudinal cohort study and a two-sample Mendelian randomization (MR) analysis to assess the association of depression with severe NAFLD risk. We used individual data from the UK Biobank study with 481,181 participants, and summary data from published genome-wide association studies. The association between depression and severe NAFLD was assessed using Cox proportional hazards regression analysis. Two-sample MR for depression with NAFLD was conducted, the principal analysis employed the inverse variance weighted (IVW) approach. In the observational study, after a median follow-up of 13.46 years, 4,563 participants had severe NAFLD. In multivariable-adjusted model, participants with depression had an increased risk of severe NAFLD (hazards ratio:1.21, 95% confidence interval (CI):1.09–1.34), as compared to those without depression. In subgroup analyses, the association between depression and severe NAFLD risk was generally observed across different subgroups. For the MR, result also showed that genetically predicted depression was causally associated with a higher risk of NAFLD (odds ratio:1.55, 95%CI:1.10–2.19) in IVW. Our study revealed a prospective association of depression with severe NAFLD, thus potentially necessitating clinical monitoring of individuals with depression for severe NAFLD. [ABSTRACT FROM AUTHOR]

Abstract The relationship between depression and severe non-alcoholic fatty liver disease (NAFLD) has not been clearly defined. We conducted a longitudinal cohort study and a two-sample Mendelian randomization (MR) analysis to assess the association of depression with severe NAFLD risk. We used individual data from the UK Biobank study with 481,181 participants, and summary data from published genome-wide association studies. The association between depression and severe NAFLD was assessed using Cox proportional hazards regression analysis. Two-sample MR for depression with NAFLD was conducted, the principal analysis employed the inverse variance weighted (IVW) approach. In the observational study, after a median follow-up of 13.46 years, 4,563 participants had severe NAFLD. In multivariable-adjusted model, participants with depression had an increased risk of severe NAFLD (hazards ratio:1.21, 95% confidence interval (CI):1.09–1.34), as compared to those without depression. In subgroup analyses, the association between depression and severe NAFLD risk was generally observed across different subgroups. For the MR, result also showed that genetically predicted depression was causally associated with a higher risk of NAFLD (odds ratio:1.55, 95%CI:1.10–2.19) in IVW. Our study revealed a prospective association of depression with severe NAFLD, thus potentially necessitating clinical monitoring of individuals with depression for severe NAFLD.

Muscle force production is influenced by muscle fiber and aponeurosis architecture. This prospective cohort study utilizes special MR imaging sequences to examine the structure-function in-vivo in the Medial Gastrocnemius (MG) at three-ankle angles (dorsiflexion, plantar flexion-low and high) and two sub-maximal levels of maximum voluntary contraction (25% and 50%MVC). The study was performed on 6 young male participants. Muscle fiber and aponeurosis strain, fiber strain normalized to force, fiber length and pennation angle (at rest and peak contraction) were analyzed for statistical differences between ankle positions and %MVC. A two-way repeated measures ANOVA and post hoc Bonferroni-adjusted tests were conducted for normal data. A related samples test with Friedmans 2-way ANOVA by ranks with corrections for multiple comparisons was conducted for non-normal data. The dorsiflexed ankle position generated significantly higher force with lower fiber strain than the plantarflexed positions. Sarcomere length extracted from muscle fiber length at each ankle angle was used to track the location on the Force-Length curve and showed the MG operates on the curves ascending limb. Muscle force changes predicted from the F-L curve going from dorsi- to plantarflexion was less than that experimentally observed suggesting other determinants of force changes with ankle position.

Psilocybin and lysergic acid diethylamide (LSD) experiences can range from very positive to highly challenging (e.g., fear, grief, and paranoia). These challenging experiences contribute to hesitancy toward psychedelic-assisted psychotherapy among health care providers and patients. Co-use of 3,4-Methylenedioxy methamphetamine (MDMA) with psilocybin/LSD anecdotally reduces challenging experiences and enhances positive experiences associated with psilocybin/LSD. However, limited research has investigated the acute effects of co-use of MDMA and psilocybin/LSD. In a prospective convenience sample (N = 698) of individuals with plans to use psilocybin/LSD, we examined whether co-use of MDMA with psilocybin/LSD (n = 27) is associated with differences in challenging or positive experiences. Challenging experiences were measured using the Challenging Experiences Questionnaire and positive experiences were measured using the Mystical Experience Questionnaire and single-item measures of self-compassion, compassion, love, and gratitude. Potentially confounding variables were identified and included as covariates. Relative to psilocybin/LSD alone, co-use of psilocybin/LSD with a self-reported low (but not medium-high) dose of MDMA was associated with significantly less intense total challenging experiences, grief, and fear, as well as increased self-compassion, love and gratitude. Co-use of psilocybin/LSD and MDMA was not associated with differences in mystical-type experiences or compassion. Findings suggest co-use of MDMA with psilocybin/LSD may buffer against some aspects of challenging experiences and enhance certain positive experiences. Limitations include use of a convenience sample, small sample size, and non-experimental design. Additional studies (including controlled dose-response studies) that examine the effects and safety of co-administering MDMA with psilocybin/LSD (in healthy controls and clinical samples) are warranted and may assist the development of personalized treatments.

This prospective, observer-masked, randomized clinical trial was conducted between December 2018 and June 2021 at Eye Hospital, China Academy of Chinese Medical Sciences. A total of 45 glaucoma patients from Beijing, China, were enrolled in this clinical trial to compare the short-term efficacy of primary single-selective laser trabeculoplasty (SLT) to 0.005% latanoprost eye drops for the treatment of 24-h intraocular pressure (IOP) in patients with newly diagnosed primary open angle glaucoma (POAG) and ocular hypertension (OHT). Both SLT and latanoprost significantly decreased mean 24-h IOP and peak IOP, although the latanoprost group effect was more potent when compared to the SLT group (both Ps

Exposure to traumatic events during pregnancy may influence pregnancy and birth outcomes. Growing evidence suggests that exposure to traumatic events well before pregnancy, such as childhood maltreatment (CM), also may influence the course of pregnancy and risk of adverse birth outcomes. We aimed to estimate associations between maternal CM exposure and small-for-gestational-age birth (SGA) and preterm birth (PTB) in a diverse US sample, and to examine whether common CM-associated health and behavioral sequelae either moderate or mediate these associations. The Measurement of Maternal Stress (MOMS) Study was a prospective cohort study that enrolled 744 healthy English-speaking participants ≥ 18 years with a singleton pregnancy, who were

Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease in humans and cats and lacks efficacious pharmacologic interventions in the preclinical phase of disease. LV outflow tract obstruction (LVOTO) is commonly observed in HCM-affected patients and is a primary driver of heart failure symptoms and reduced quality of life. Novel small-molecule cardiac myosin inhibitors target actin-myosin interactions to alleviate overactive protein interactions. A prospective, randomized, controlled cross-over study was performed to evaluate pharmacodynamic effects of two doses (0.3 and 1 mg/kg) of a next-in-class cardiac myosin inhibitor, aficamten (CK-3773274, CK-274), on cardiac function in cats with the A31P MYBPC3 mutation and oHCM. Dose-dependent reductions in LV systolic function, LVOT pressure gradient, and isovolumetric relaxation times compared to baseline were observed. Promising beneficial effects of reduced systolic function warrant further studies of this next-in-class therapeutic to evaluate the benefit of long-term administration in this patient population.

Autoantibodies to desmoglein-2 have been associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) in people. ARVC is a common disease in the Boxer dog. The role of anti-desmoglein-2 antibodies in Boxers with ARVC and correlation with disease status or severity is unknown. This prospective study is the first to evaluate dogs of various breeds and cardiac disease state for anti-desmoglein-2 antibodies. The sera of 46 dogs (10 ARVC Boxers, 9 healthy Boxers, 10 Doberman Pinschers with dilated cardiomyopathy, 10 dogs with myxomatous mitral valve disease, and 7 healthy non-Boxer dogs) were assessed for antibody presence and concentration via Western blotting and densitometry. Anti-desmoglein-2 antibodies were detected in all dogs. Autoantibody expression did not differ between study groups and there was no correlation with age or body weight. In dogs with cardiac disease, there was weak correlation with left ventricular dilation (r = 0.423, p = 0.020) but not left atrial size (r = 0.160, p = 0.407). In ARVC Boxers there was strong correlation with the complexity of ventricular arrhythmias (r = 0.841, p = 0.007) but not total number of ectopic beats (r = 0.383, p = 0.313). Anti-desmoglein-2 antibodies were not disease specific in the studied population of dogs. Correlation with some measures of disease severity requires further study with larger populations.

It is critical for hospitals to accurately predict patient length of stay (LOS) and mortality in real-time. We evaluate temporal convolutional networks (TCNs) and data rebalancing methods to predict LOS and mortality. This is a retrospective cohort study utilizing the MIMIC-III database. The MIMIC-Extract pipeline processes 24 hour time-series clinical objective data for 23,944 unique patient records. TCN performance is compared to both baseline and state-of-the-art machine learning models including logistic regression, random forest, gated recurrent unit with decay (GRU-D). Models are evaluated for binary classification tasks (LOS > 3 days, LOS > 7 days, mortality in-hospital, and mortality in-ICU) with and without data rebalancing and analyzed for clinical runtime feasibility. Data is split temporally, and evaluations utilize tenfold cross-validation (stratified splits) followed by simulated prospective hold-out validation. In mortality tasks, TCN outperforms baselines in 6 of 8 metrics (area under receiver operating characteristic, area under precision-recall curve (AUPRC), and F-1 measure for in-hospital mortality; AUPRC, accuracy, and F-1 for in-ICU mortality). In LOS tasks, TCN performs competitively to the GRU-D (best in 6 of 8) and the random forest model (best in 2 of 8). Rebalancing improves predictive power across multiple methods and outcome ratios. The TCN offers strong performance in mortality classification and offers improved computational efficiency on GPU-enabled systems over popular RNN architectures. Dataset rebalancing can improve model predictive power in imbalanced learning. We conclude that temporal convolutional networks should be included in model searches for critical care outcome prediction systems.

Although universal biometrics have been broadly called for, and there are many validated technologies to recognize adults, these technologies have been ineffective in newborns and young children. The present work describes the development and clinical testing of a fingerprint capture system for longitudinal biometric recognition of newborns and young children to support vaccination and clinical follow-up. The reader consists of a high-resolution monochromatic imaging system with an ergonomic industrial design to comfortably support and align infant fingers for imaging without a platen. This imaging approach without a platen, also called free-space imaging, reduces fingerprint distortion and ensures a more consistent finger placement. This system was tested in a newborn ward and immunization clinic at an urban hospital in Baja, California, Mexico, from 2017 to 2019. Nearly five hundred children were enrolled and followed for up to 24 months. With a protocol of imaging all ten fingers, the failure to enroll (FTE) rate was

Preterm infants are at a greater risk for the development of asthma and atopic disease, which can lead to lifelong negative health consequences. This may be due, in part, to alterations that occur in the gut microbiome and metabolome during their stay in the Neonatal Intensive Care Unit (NICU). To explore the differential roles of family history (i.e., predisposition due to maternal asthma diagnosis) and hospital-related environmental and clinical factors that alter microbial exposures early in life, we considered a unique cohort of preterm infants born ≤ 34 weeks gestational age from two local level III NICUs, as part of the MAP (Microbiome, Atopic disease, and Prematurity) Study. From MAP participants, we chose a sub-cohort of infants whose mothers had a history of asthma and matched gestational age and sex to infants of mothers without a history of asthma diagnosis (control). We performed a prospective, paired metagenomic and metabolomic analysis of stool and milk feed samples collected at birth, 2 weeks, and 6 weeks postnatal age. Although there were clinical factors associated with shifts in the diversity and composition of stool-associated bacterial communities, maternal asthma diagnosis did not play an observable role in shaping the infant gut microbiome during the study period. There were significant differences, however, in the metabolite profile between the maternal asthma and control groups at 6 weeks postnatal age. The most notable changes occurred in the linoleic acid spectral network, which plays a role in inflammatory and immune pathways, suggesting early metabolomic changes in the gut of preterm infants born to mothers with a history of asthma. Our pilot study suggests that a history of maternal asthma alters a preterm infants' metabolomic pathways in the gut, as early as the first 6 weeks of life.

The purpose of this study is to develop and validate an optimal timing protocol for a low-radiation-dose CT pulmonary perfusion technique using only two volume scans. A total of 24 swine (48.5 ± 14.3 kg) underwent contrast-enhanced dynamic CT. Multiple contrast injections were made under different pulmonary perfusion conditions, resulting in a total of 141 complete pulmonary arterial input functions (AIFs). Using all the AIF curves, an optimal contrast timing protocol was developed for a first-pass, two-volume dynamic CT perfusion technique (one at the base and the other at the peak of AIF curve). A subset of swine was used to validate the prospective two-volume pulmonary perfusion technique. The prospective two-volume perfusion measurements were quantitatively compared to the previously validated retrospective perfusion measurements with t-test, linear regression, and Bland-Altman analysis. As a result, the pulmonary artery time-to-peak ([Formula: see text]) was related to one-half of the contrast injection duration ([Formula: see text]) by [Formula: see text] (r = 0.95). The prospective two-volume perfusion measurements (PPRO) were related to the retrospective measurements (PRETRO) by PPRO = 0.87PRETRO + 0.56 (r = 0.88). The CT dose index and size-specific dose estimate of the two-volume CT technique were estimated to be 28.4 and 47.0 mGy, respectively. The optimal timing protocol can enable an accurate, low-radiation-dose two-volume dynamic CT perfusion technique.

Diffusion-weighted magnetic resonance imaging (DWI) of the musculoskeletal system has various applications, including visualization of bone tumors. However, DWI acquired with echo-planar imaging is susceptible to distortions due to static magnetic field inhomogeneities. This study aimed to estimate spatial displacements of bone and to examine whether distortion corrected DWI images more accurately reflect underlying anatomy. Whole-body MRI data from 127 prostate cancer patients were analyzed. The reverse polarity gradient (RPG) technique was applied to DWI data to estimate voxel-level distortions and to produce a distortion corrected DWI dataset. First, an anatomic landmark analysis was conducted, in which corresponding vertebral landmarks on DWI and anatomic T2-weighted images were annotated. Changes in distance between DWI- and T2-defined landmarks (i.e., changes in error) after distortion correction were calculated. In secondary analyses, distortion estimates from RPG were used to assess spatial displacements of bone metastases. Lastly, changes in mutual information between DWI and T2-weighted images of bone metastases after distortion correction were calculated. Distortion correction reduced anatomic error of vertebral DWI up to 29 mm. Error reductions were consistent across subjects (Wilcoxon signed-rank p

The aim of this study was to assess whether adolescents following anorectal malformation repair have a decreased cardiorespiratory performance capacity and impaired motor skills. All eligible children treated for ARMs between 2000 and 2014 were invited to participate in a prospective study consisting of a clinical examination, evaluation of Bowel function and Quality of Life, spirometry, spiroergometry and assessment of the motor activity. The results were compared to a healthy age- and sex-matched control group. There was no statistically significant difference in height, weight, BMI, muscle mass or body fat percentage between the study and the control group. Nine out of 18 patients (50%) had an excellent functional outcome with a normal Bowel Function Score. Spirometry revealed no significant differences between ARM patients and controls, four patients showed a ventilation disorder. Spiroergometry revealed a significantly lower relative performance capacity and the overall rating of the motor activity test showed significantly decreased grades in ARM patients. ARM patients were affected by an impaired cardiopulmonary function and decreased motor abilities. Long-term examinations consisting of routine locomotor function evaluation and spiroergometry are advisable to detect impaired cardiopulmonary function and to prevent a progression of associated complications and related impaired quality of life.

The role of ST2 in stable coronary artery disease (CAD) has not yet been well defined. This study was performed to investigate baseline serum soluble ST2 (sST2) level can predict clinical outcomes in patients with stable CAD. A total of 388 consecutive patients with suspected CAD (65 years and 63.7% male) in stable condition referred for elective invasive coronary angiography (ICA) was prospectively recruited. Major adverse cardiovascular event (MACE), including cardiac death, non-fatal myocardial infarction, coronary revascularization (90 days after ICA), and ischemic stroke during clinical follow-up was assessed. Most of the patients (88.0%) had significant CAD (stenosis ≥ 50%). During median follow-up of 834 days, there was 29 case of MACE (7.5%). The serum sST2 level was significantly higher in patients with MACE than those without (47.3 versus 30.6 ng/ml, P

The chronological age of a person is a key determinant of etiology and prognosis in the setting of ischemic stroke. Telomere length, an indicator of biological aging, progressively shortens with every cell cycle. Herein, we determined telomere length from peripheral blood leukocytes by Southern blot analyses in a prospective cohort of ischemic stroke patients (n = 163) and equal number of non-stroke controls and evaluated its association with various ischemic stroke features including etiology, severity, and outcome. A shorter telomere length (i.e. lowest quartile; ≤ 5.5 kb) was significantly associated with ischemic stroke (OR 2.95, 95% CI 1.70-5.13). This significant relationship persisted for all stroke etiologies, except for other rare causes of stroke. No significant association was present between admission lesion volume and telomere length; however, patients with shorter telomeres had higher admission National Institutes of Health Stroke Scale scores when adjusted for chronological age, risk factors, etiology, and infarct volume (p = 0.046). On the other hand, chronological age, but not telomere length, was associated with unfavorable outcome (modified Rankin scale > 2) and mortality at 90 days follow-up. The association between shorter telomere length and more severe clinical phenotype at the time of admission, might reflect reduced resilience of cerebral tissue to ischemia as part of biological aging.

Lexical retrieval requires selecting and retrieving the most appropriate word from the lexicon to express a desired concept. Few studies have probed lexical retrieval with tasks other than picture naming, and when non-picture naming lexical retrieval tasks have been applied, both convergent and divergent results emerged. The presence of a single construct for auditory and visual processes of lexical retrieval would influence cognitive rehabilitation strategies for patients with aphasia. In this study, we perform support vector regression lesion-symptom mapping using a brain tumor model to test the hypothesis that brain regions specifically involved in lexical retrieval from visual and auditory stimuli represent overlapping neural systems. We find that principal components analysis of language tasks revealed multicollinearity between picture naming, auditory naming, and a validated measure of word finding, implying the existence of redundant cognitive constructs. Nonparametric, multivariate lesion-symptom mapping across participants was used to model accuracies on each of the four language tasks. Lesions within overlapping clusters of 8,333 voxels and 21,512 voxels in the left lateral prefrontal cortex (PFC) were predictive of impaired picture naming and auditory naming, respectively. These data indicate a convergence of heteromodal lexical retrieval within the PFC.

Fluid resuscitation following severe inflammation-induced hypoperfusion is critical for the restoration of hemodynamics and the prevention of multiorgan dysfunction syndrome during septic shock. Fluid resuscitation with commercially available crystalloid and colloid solutions only provides transient benefits, followed by fluid extravasation and tissue edema through the inflamed endothelium. The increased molecular weight (M.W.) of polymerized human serum albumin (PolyHSA) can limit fluid extravasation, leading to restoration of hemodynamics. In this prospective study, we evaluated how fluid resuscitation with PolyHSA impacts the hemodynamic and immune response in a lipopolysaccharide (LPS) induced endotoxemia mouse model. Additionally, we evaluated fluid resuscitation with PolyHSA in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Resuscitation with PolyHSA attenuated the immune response and improved the maintenance of systemic hemodynamics and restoration of microcirculatory hemodynamics. This decrease in inflammatory immune response and maintenance of vascular wall shear stress likely contributes to the maintenance of vascular integrity following fluid resuscitation with PolyHSA. The sustained restoration of perfusion, decrease in pro-inflammatory immune response, and improved vascular integrity that results from the high M.W. of PolyHSA indicates that a PolyHSA based solution is a potential resuscitation fluid for endotoxic and septic shock.

People with obstructive sleep apnea (OSA) often have psychological symptoms including depression and anxiety, which are commonly treated with anti-depression or anti-anxiety interventions. Psychological stress is a related symptom with different intervention targets that may also improve mental state, but this symptom is not well characterized in OSA. We therefore aimed to describe stress in relation to other psychological symptoms. We performed a prospective cross-sectional study of 103 people, 44 untreated OSA (mean ± s.d. age: 51.2 ± 13.9 years, female/male 13/31) and 57 healthy control participants (age: 46.3 ± 13.8 years, female/male 34/23). We measured stress (Perceived Stress Scale; PSS), excessive daytime sleepiness (Epworth Sleepiness Scale; ESS), depressive symptoms (Patient Health Questionnaire; PHQ-9), and anxiety symptoms (General Anxiety Disorder; GAD-7). We compared group means with independent samples t-tests and calculated correlations between variables. Mean symptom levels were higher in OSA than control, including PSS (mean ± s.d.: OSA = 15.3 ± 6.9, control = 11.4 ± 5.5; P = 0.002), GAD-7 (OSA = 4.8 ± 5.0, control = 2.1 ± 3.9; P = 0.02), PHQ-9 (OSA = 6.9 ± 6.1, control = 2.6 ± 3.8; P = 0.003) and ESS (OSA = 8.1 ± 5.3, control = 5.0 ± 3.3; P = 0.03). Similar OSA-vs-control differences appeared in males, but females only showed significant differences in PHQ-9 and ESS, not PSS or GAD-7. PSS correlated strongly with GAD-7 and PHQ-9 across groups (R = 0.62-0.89), and moderately with ESS. Perceived stress is high in OSA, and closely related to anxiety and depressive symptoms. The findings support testing stress reduction in OSA.

Circulating concentrations of brain-derived neurotrophic factor (BDNF) have been linked to cancer, neuropsychiatric, diabetes, and gynecological disorders. However, factors influencing plasma storage and subsequent BDNF quantification are incompletely understood. Therefore, the anticoagulant used in plasma separator tubes, storage-time, storage-temperature, and repeated freeze-thaw cycles on circulating BDNF concentrations was evaluated. Peripheral blood samples were collected from healthy women (n = 14) and men (n = 10) recruited prospectively from McMaster University (August 2014). Blood was collected from the cubital vein into plasma separator tubes containing five different anticoagulant systems [K2EDTA, Li-Hep, Li-Hep (gel), Na-Hep, Na-Hep (glass)], and placed on ice for transport to the lab for centrifugation. Plasma samples (n = 16) collected in K2EDTA tubes from women recruited to a previous study (April 2011 to December 2012) were used to determine the effect of multiple freeze-thaw cycles. Plasma BDNF was quantified using a commercially available ELISA kit. Plasma concentrations of BDNF were significantly affected by the type of plasma separator tube, storage-time, and number of freeze-thaw cycles. Storage temperature (- 20 vs. - 80 °C) did not significantly affect the quantity of BDNF measured as mean BDNF concentrations generally fell within our calculated acceptable change limit up to 6 months in the freezer. Our results suggest that for quantification of circulating BDNF blood collected in K2EDTA tubes and plasma stored up to 6 months at either - 20 or - 80 °C produces reproducible results that fall within an acceptable range. However, plasma samples stored beyond 6 months and repeated freeze-thaw cycles should be avoided.

Recent studies revealed culturable periodontal keystone pathogens are associated with preterm low birth weight (PLBW). However, the oral microbiome is also comprised of hundreds of 'culture-difficult' or 'not-yet-culturable' bacterial species. To explore the potential role of unculturable and culturable periodontitis-related bacteria in preterm low birth weight (PLBW) delivery, we recruited 90 pregnant women in this prospective study. Periodontal parameters, including pocket probing depth, bleeding on probing, and clinical attachment level were recorded during the second trimester and following interviews on oral hygiene and lifestyle habits. Saliva and serum samples were also collected. After delivery, birth results were recorded. Real-time PCR analyses were performed to quantify the levels of periodontitis-related unculturable bacteria (Eubacterium saphenum, Fretibacterium sp. human oral taxon(HOT) 360, TM7 sp. HOT 356, and Rothia dentocariosa), and cultivable bacteria (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum and Prevotella intermedia) in saliva samples. In addition, ELISA analyses were used to determine the IgG titres against periodontal pathogens in serum samples. Subjects were categorized into a Healthy group (H, n = 20) and periodontitis/gingivitis group (PG, n = 70) according to their periodontal status. The brushing duration was significantly lower in the PG group compared to the H group. Twenty-two of 90 subjects delivered PLBW infants. There was no significant difference in periodontal parameters and serum IgG levels for periodontal pathogens between PLBW and healthy delivery (HD) groups. However, ordinal logistic regression analysis revealed that a higher abundance of Treponema denticola, Prevotella intermedia, Fretibacterium sp. HOT360 and lower levels of Rothia dentocariosa were significantly associated with the presence of periodontal disease during pregnancy. Moreover, the amount of Eubacterium saphenum in saliva and serum IgG against Aggregatibacter actinomycetemcomitans were negatively correlated with PLBW. Taken together, unculturable periodontitis-associated bacteria may play an important role both in the presence of periodontal inflammation during pregnancy and subsequent PLBW.

Knee Osteoarthritis (OA) is a common musculoskeletal disorder in the United States. When diagnosed at early stages, lifestyle interventions such as exercise and weight loss can slow OA progression, but at later stages, only an invasive option is available: total knee replacement (TKR). Though a generally successful procedure, only 2/3 of patients who undergo the procedure report their knees feeling "normal" post-operation, and complications can arise that require revision. This necessitates a model to identify a population at higher risk of TKR, particularly at less advanced stages of OA, such that appropriate treatments can be implemented that slow OA progression and delay TKR. Here, we present a deep learning pipeline that leverages MRI images and clinical and demographic information to predict TKR with AUC 0.834 ± 0.036 (p

Feline chronic enteropathy (CE) is a common gastrointestinal disorder in cats and mainly comprises inflammatory bowel disease (IBD) and small cell lymphoma (SCL). Both IBD and SCL in cats share features with chronic enteropathies such as IBD and monomorphic epitheliotropic intestinal T-cell lymphoma in humans. The aim of this study was to characterize the fecal microbiome of 38 healthy cats and 27 cats with CE (13 cats with IBD and 14 cats with SCL). Alpha diversity indices were significantly decreased in cats with CE (OTU p = 0.003, Shannon Index p = 0.008, Phylogenetic Diversity p = 0.019). ANOSIM showed a significant difference in bacterial communities, albeit with a small effect size (P = 0.023, R = 0.073). Univariate analysis and LEfSE showed a lower abundance of facultative anaerobic taxa of the phyla Firmicutes (families Ruminococcaceae and Turicibacteraceae), Actinobacteria (genus Bifidobacterium) and Bacteroidetes (i.a. Bacteroides plebeius) in cats with CE. The facultative anaerobic taxa Enterobacteriaceae and Streptococcaceae were increased in cats with CE. No significant difference between the microbiome of cats with IBD and those with SCL was found. Cats with CE showed patterns of dysbiosis similar to those in found people with IBD.

Lower extremity peripheral artery disease (PAD) burden differs by race/ethnicity. Although familial aggregation and heritability studies suggest a genetic basis, little is known about the genetic susceptibility to PAD, especially in non-European descent populations. Genome-wide association studies (GWAS) of the ankle brachial index (ABI) and PAD (defined as an ABI 45 years from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We also performed GWAS for ABI stratified by Hispanic/Latino ethnic subgroups: Central American, Mexican, and South American (Mainland group), and Cuban, Dominican, and Puerto Rican (Caribbean group). We detected two genome-wide significant associations for the ABI in COMMD10 in Puerto Ricans, and at SYBU in the Caribbean group. The lead SNP rs4466200 in the COMMD10 gene had a replication p = 0.02 for the ABI in Multi-Ethnic Study of Atherosclerosis (MESA) African Americans, but it did not replicate in African Americans from the Cardiovascular Health Study (CHS). In a regional look-up, a nearby SNP rs12520838 had Bonferroni adjusted p = 0.05 (unadjusted p = 7.5 × 10-5) for PAD in MESA Hispanics. Among three suggestive associations (p

Impaired insulin sensitivity (IS) and β-cell dysfunction result in hyperglycaemia in patients of acromegaly. However, alterations in incretins and their impact on glucose-insulin homeostasis in these patients still remain elusive. Twenty patients of active acromegaly (10 each, with and without diabetes) underwent hyperinsulinemic euglycaemic clamp and mixed meal test, before and after surgery, to measure indices of IS, β-cell function, GIP, GLP-1 and glucagon response. Immunohistochemistry (IHC) for GIP and GLP-1 was also done on intestinal biopsies of all acromegalics and healthy controls. Patients of acromegaly, irrespective of presence or absence of hyperglycaemia, had similar degree of insulin resistance, however patients with diabetes exhibited hyperglucagonemia, and compromised β-cell function despite significantly higher GIP levels. After surgery, indices of IS improved, GIP and glucagon levels decreased significantly in both the groups, while there was no significant change in indices of β-cell function in those with hyperglycaemia. IHC positivity for GIP, but not GLP-1, staining cells in duodenum and colon was significantly lower in acromegalics with diabetes as compared to healthy controls possibly because of high K-cell turnover. Chronic GH excess induces an equipoise insulin resistance in patients of acromegaly irrespective of their glycaemic status. Dysglycaemia in these patients is an outcome of β-cell dysfunction consequent to GIP resistance and hyperglucagonemia.

Strong evidence suggests that genetic variations in DNA methyltransferases (DNMTs) may alter the downstream expression and DNA methylation patterns of neuronal genes and influence cognition. This study investigates the association between a DNMT1 polymorphism, rs2162560, and chemotherapy-associated cognitive impairment (CACI) in a cohort of breast cancer patients. This is a prospective, longitudinal cohort study. From 2011 to 2017, 351 early-stage breast cancer patients receiving chemotherapy were assessed at baseline, the midpoint, and the end of chemotherapy. DNA was extracted from whole blood, and genotyping was performed using Sanger sequencing. Patients' self-perceived cognitive function and cognitive performance were assessed at three different time points using FACT-Cog (v.3) and a neuropsychological battery, respectively. The association between DNMT1 rs2162560 and cognitive function was evaluated using logistic regression analyses. Overall, 33.3% of the patients reported impairment relative to baseline in one or more cognitive domains. Cognitive impairment was observed in various objective cognitive domains, with incidences ranging from 7.2% to 36.9%. The DNMT1 rs2162560 A allele was observed in 21.8% of patients and this was associated with lower odds of self-reported cognitive decline in the concentration (OR = 0.45, 95% CI: 0.25-0.82, P = 0.01) and functional interference (OR = 0.48, 95% CI: 0.24-0.95, P = 0.03) domains. No significant association was observed between DNMT1 rs2162560 and objective cognitive impairment. This is the first study to show a significant association between the DNMT1 rs2162560 polymorphism and CACI. Our data suggest that epigenetic processes could contribute to CACI, and further studies are needed to validate these findings.

Kawasaki Disease (KD) is the most common cause of pediatric acquired heart disease, but its etiology remains unknown. We examined 1164 cases of KD treated at a regional children's hospital in San Diego over a period of 15 years and uncovered novel structure to disease incidence. KD cases showed a well-defined seasonal variability, but also clustered temporally at much shorter time scales (days to weeks), and spatiotemporally on time scales of up to 10 days and spatial scales of 10-100 km. Temporal clusters of KD cases were associated with strongly significant regional-scale air temperature anomalies and consistent larger-scale atmospheric circulation patterns. Gene expression analysis further revealed a natural partitioning of KD patients into distinct groups based on their gene expression pattern, and that the different groups were associated with certain clinical characteristics that also exhibit temporal autocorrelation. Our data suggest that one or more environmental triggers exist, and that episodic exposures are modulated at least in part by regional weather conditions. We propose that characterization of the environmental factors that trigger KD in genetically susceptible children should focus on aerosols inhaled by patients who share common disease characteristics.

Although early diagnosis and treatment reduce the risk of blindness from glaucoma, the decision on whether or not to begin treatment in patients with suspected glaucoma is often a dilemma because the majority of patients never develop definite glaucoma. A growing body of evidences suggests that posterior bowing of the lamina cribrosa (LC) is the earliest structural change preceding the retinal nerve fiber layer (RNFL) loss in glaucomatous optic neuropathy. Based on this notion, we conducted a prospective study enrolling 87 eyes suspected of having glaucoma to investigate whether the future rate of RNFL loss is associated with the baseline LC curve evaluated by measuring the LC curve index (LCCI) using enhanced depth imaging optical coherence tomography. A faster rate of RNFL loss was significantly associated with greater LCCI (P

Artificial intelligence (AI), particularly large language models like GPT-4o, holds promise for enhancing diagnostic accuracy in healthcare. This study evaluates the diagnostic performance of GPT-4o compared to human ophthalmologists in glaucoma cases. A prospective, observational study was conducted at a tertiary care ophthalmology center. Twenty-six glaucoma cases, including both primary and secondary types, were selected from publicly available databases and institutional records. The cases were analyzed by GPT-4o and three ophthalmologists with varying levels of experience. The accuracy and completeness of primary and differential diagnoses were assessed using 10-point and 6-point Likert scales, respectively. Statistical analyses were performed using nonparametric methods, including the Kruskal-Wallis and Mann-Whitney U tests. GPT-4o was significantly less accurate in primary diagnosis compared to human ophthalmologists. Specifically, GPT-4o achieved a mean score of 5.500 (p < 0.001) compared to Doctor C, who had the highest score of 8.038 (p < 0.001). Completeness scores for GPT-4o 3.077 (p < 0.001) were also lower than Doctor B, who had the lowest score of 3.615 (p < 0.001) among human ophthalmologists. However, for differential diagnosis, GPT-4o (7.577) showed comparable accuracy to Doctor A (7.615) and Doctor C (7.673) (p < 0.0001) while achieving the highest completeness score (4.096), outperforming Doctor C (3.846), Doctor A (2.923), and Doctor B (2.808) (p < 0.0001). AI, including GPT-4o, is currently not an acceptable standalone method for diagnosing glaucoma due to its lower accuracy compared to human clinicians. These findings suggest that GPT-4o could serve as a valuable adjunct in clinical practice, particularly in complex cases, but should not replace human expertise, especially for initial diagnoses. Future improvements in AI models could enhance their utility in ophthalmology., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: At least 20% of the future liver remnant must function properly after liver tumor resection to avoid post-hepatectomy liver failure (PHLF). [ 99m Tc]Tc-mebrofenin scintigraphy and SPECT are unique noninvasive, quantitative methods for evaluating liver function via hepatocellular bilirubin clearance., Aim: To evaluate the value of dynamic [ 99m Tc]Tc-mebrofenin SPECT/CT parameters for predicting clinically relevant PHLF according to the ISGLS criteria., Methods: Thirty-five patients underwent dynamic [ 99m Tc]Tc-mebrofenin SPECT/CT imaging to determine the FLR volumetric rate, functional volume rate, total liver filtration and FLR filtration. On the same day, two-dimensional ultrasound shear wave elastography (2D-SWE) was used to assess parenchymal fibrosis in the FLR. The quantitative dynamic SPECT parameters were compared with the relevant clinical scores and ICG., Results: The total liver filtration was inversely correlated with the ICG-R15 and MELD-Na score. Twenty-four patients underwent major liver resection due to an adequate FLR rate and did not die within 90 days after the procedure. ROC analysis revealed that the FLR filtration was a significant predictor of PHLF. The best cutoff value for FLR filtration was 2.72%/min/m 2 ., Conclusion: Dynamic [ 99m Tc]Tc-mebrofenin SPECT/CT is an essential tool for selecting patients at risk of clinically relevant PHLF after liver resection., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Local Ethical Committee for Clinical Research at our university (reference no. 123/2022-SZTE RKEB). The study protocol adheres to the ethical guidelines outlined in the 1975 Declaration of Helsinki, as confirmed in prior approval by the institution’s human research committee. Informed consent was obtained from all participating patients. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

To investigate the safety, efficacy and risk factors for complications of stenting with optional coiling versus coiling alone for acutely ruptured cerebral aneurysms (ARCAs) using different antiplatelet schemes, 2021 patients were prospectively enrolled into the stenting group (n = 967) and the coiling group (n = 1054). Four different antiplatelet regimens were used. The clinical and treatment data were analyzed and compared. In the stenting group, the common antiplatelet regimen was applied in 259 patients (26.8%), loading regimen in 210 (21.7%), intravenous tirofiban regimen in 240 (24.8%), and premedication free regimen in 258 (26.7%). The aneurysm occlusion degrees in the coiling vs. stenting group were not significantly (P > 0.05) different after treatment. Complications occurred in 168 (15.94%) and 171 (17.68%) patients in the coiling and the stenting group, respectively. Fifteen (1.55%) patients experienced stent-related ischemic complications. The only significant (P < 0.05) independent protective factor for complete occlusion was stent-assisted coiling in the stenting group but aneurysm daughter sac in the coiling group. Significant (P < 0.05) independent risk factors for poor mRS (3-6) were posterior circulation aneurysms and neurological bleeding complications in the stenting group and neurological complications in the coiling group. In the stenting group, the only independent risk factor was parent artery stenosis for neurological complications, Raymond grade III for neurological ischemic complications, and the ice cream technique for total complications in the stenting group. In conclusion, different antiplatelet schemes can be safely and efficiently used for intracranial stenting with optional coiling as compared with coiling alone for ARCAs., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: numerous epidemiological studies demonstrate the correlation between obesity and urolithiasis. Bariatric surgery is effective in significant weight loss, reducing mortality rates, and lowering the incidence of obesity-related comorbidities. However, it may be associated with long-term complications such as urolithiasis, with an estimated increase of 7.6% in bariatric patients. This study investigates the impact of various bariatric surgical techniques and personal and nutritional habits on post-operative urolithiasis., Material and Method: 185 patients were prospectively enrolled in the study. All patients underwent nutritional assessment two years after surgery, and urinary stone disease was evaluated through urinalysis. Patients with urinary crystals were subsequently sent to the division of Urology to evaluate the possible presence of urinary stones through an abdominal CT scan., Results: kidney stone disease was present in 12 female patients (12/ 185 - 6.49%) out of the 25 (12/25-48%) with urinary crystals. Among the various surgical techniques, 8 patients underwent SG, 2 patients each for OAGB and RYGB, without a proven significant correlation. Hypertension, Dyslipidemia, and OSAS were significantly correlated with the incidence of urolithiasis (p-value < 0.05). BMI > 30 kg/m2 was significantly correlated with urinary stone formation (p-value < 0.05)., Conclusion: patients undergoing bariatric surgery should receive counseling about the risk of developing urolithiasis (6.49%) independently from the surgical treatment, highlighting the necessity of adhering to nutritional guidelines. Evaluation for urinary stones could be recommended during follow-up, especially for patients with a BMI > 30 kg/m 2 ., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Sentinel lymph node biopsy (SLNB) is an important technique in the staging of pediatric melanomas, sarcomas, and potentially useful for other solid tumors. Precise visual localization of the sentinel lymph node (SLN) during the operation is a key challenge of this procedure. Presently, the gold standard method employing Technetium 99 (99mTc) for localization carries a notable false-negative rate. In this context, we propose evaluating the use of Indocyanine Green near-infrared (ICG-NIR) as a supplementary tool to enhance the identification of SLN. A prospective observational study focused on pediatric and adolescent patients undergoing SLNB using ICG-NIR at a single institution from 2019 to 2022. Lymphoscintigraphy with 99mTc was performed before surgery and 99mTc was detected intraoperatively using a handheld gamma probe. ICG was administered intraoperatively and assessed using transcutaneous NIR. The study collected demographic data, intra-operative findings (Technetium 99 m, ICG fluorescence), and histopathological data. Eight patients with a median age of 16 years (range: 8-19 years) underwent fluorescence-guided sentinel lymph node harvesting with 100% sensitivity. Sentinel lymph node fluorescence was verified with a positive radiosignal in all patients. No adverse events were recorded. Fluorescence-guided assessment of the lymphatic system is both feasible and effective for sentinel lymph node identification. Nevertheless, larger-scale studies are essential to establish indocyanine green as a viable alternative rather than a complementary technique alongside the gold-standard radioisotope-guided method for sentinel lymph node assessment in children., Competing Interests: Declarations. Competing interests: All the authors have nothing to disclose, including non-financial competing interests., (© 2024. The Author(s).)

The insulin tolerance test (ITT) is the gold standard for the diagnosis of cortisol and growth hormone (GH) deficiencies. Once hypoglycemia is detected whether patients should receive carbohydrates to recover faster from hypoglycemia is controversial. The aim of our study was to assess the impact of shortening the duration of hypoglycemia by providing a sugar drink on patient comfort and hormonal responses. This prospective, single-center, crossover, single-blind study enrolled 15 healthy participants. Each subject performed two ITT: one with normal Cola and the other with Cola Zero. Glucose and hormone levels were measured at baseline and after the induction of insulin-induced hypoglycemia. Patient tolerance to ITT was evaluated using reported hypoglycemia side effects, visual analog scale scores, and quality-of-life questionnaire. Normal Cola shortened the period of hypoglycemia (plasma glucose < 40 mg/dl) from 30 to 15 min (p = 0.005), allowing a higher proportion of participants to recover from potentially dangerous values after 45 min (12 vs. 5; p = 0.008). Cola also improved patient comfort, as evaluated using a visual analog scale (VAS score 2.6 vs 3.7, p = 0.016). Sugar did not significantly change the median cortisol and GH peaks. Body mass index was the only factor determining the cortisol peak, independent of the injected insulin dose. The time to reach hormone peaks was similar between the two protocols. Cortisol and GH values were significantly higher at 120 min in the Cola Zero group, suggesting the prolongation of hypothalamic-pituitary stress in the absence of sugar. Our study confirmed that rapid correction of hypoglycemia during ITT improves subject comfort, reduces the duration of hypoglycemia and associated symptoms, while guaranteeing unchanged cortisol and GH peaks., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Postoperative delirium (POD) is a significant complication of surgery that most severely affects older adults and patients with cognitive impairment. This study investigated the relationship between POD and oxidative stress, hypothesizing that increased oxidative stress, measured using diacron-reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) tests, is associated with the incidence of POD. This prospective cohort study, involving female patients who underwent unilateral or bilateral joint replacement, was conducted at the Osaka University Graduate School of Medicine from June 2022 to July 2023. Blood samples were collected preoperatively and postoperatively to measure oxidative stress markers using the REDOXLIBRA system. The primary endpoint was the association between changes in oxidative stress markers and the occurrence of POD as diagnosed using the Confusion Assessment Method for the Intensive Care Unit and Richmond Agitation-Sedation Scale. Of the 144 patients screened, 60 were eligible, of which 5 developed POD (8.3%). Analysis of oxidative stress markers revealed no significant changes between preoperative and postoperative values of d-ROMs (mean increase + 6.3 ± 54.2 U CARR) and BAP (mean decrease - 37.4 ± 322.9 µM) tests, or BAP/d-ROMs ratio (mean decrease - 0.4 ± 1.7). Further, no significant differences were observed in oxidative stress markers between patients who underwent unilateral and bilateral procedures. However, patients with POD exhibited a significantly higher increase in d-ROMs than those without complications (p = 0.015), whereas changes in BAP and BAP/d-ROM ratios were not statistically significant. Although general oxidative stress markers do not significantly change postoperatively, increased d-ROM levels are associated with POD occurrence, indicating that oxidative stress could be a contributing factor to its development. This study underscores the need for further research into specific oxidative markers that may predict POD and guide the development of targeted interventions to prevent this debilitating condition.Trial registration Name of the registry Association Between Changes in Blood Oxidative Stress and Postoperative Delirium Following Joint Replacement Surgery: A Retrospective Study. Trial registration number 22021. Date of registration 6/29/2022. URL of trial registry record https://bvits.dmi.med.osaka-u.ac.jp/esct/Apply/project.aspx?PROJECT&#95;ID=6987 ., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study was approved by the Ethical Review Committee of Osaka University Hospital (Approval No. 22021). Informed consent was obtained from all participants. This study adhered to national ethical guidelines and the Declaration of Helsinki., (© 2024. The Author(s).)

Lung cancer, the leading cause of cancer deaths globally, has better survival rates with early detection. Annual low-dose CT (LDCT) screenings are recommended for high-risk individuals due to age and smoking. These individuals are also at risk for other cancers. Our study explores gastrointestinal (GI) cancer mortality in lung cancer screening participants and the potential of LDCT screenings to detect pancreatic cancer. We utilized data from a prospective multi-institutional cohort study, the International Early Lung Cancer Action Project (I-ELCAP). We analyzed GI cancer deaths among participants in New York State (1992-2010), exploring demographics and GI cancer distribution. Radiologists retrospectively reviewed pancreatic cancer cases within 24 months post-LDCT, comparing findings with original reports. Among 10,150 participants, 189 died from GI cancers; mean age 75, mostly male smokers. Pancreatic cancer (41.8%) led, followed by esophageal (17.5%) and colon cancer (16.9%). Median time between baseline LDCT and death was 116 months (9.7 years). 82/189 (43.4%) participants died within 5 years of their last LDCT screening, with pancreatic cancer again prominent (45.1%). In 79 pancreatic cancer deaths, 17.7% occurred within 24 months post-LDCT. A re-review identified previously undetected pancreatic findings, with 4 out of 14 participants (28.6%) showing abnormalities. This underscores the potential of lung cancer screening programs to provide insights beyond lung health. This study of over 10,000 participants in a lung cancer screening program reveals that they are at risk for GI cancer deaths, particularly pancreatic cancer. Re-reviews of LDCT scans revealed previously undocumented pancreatic findings in a third of participants who died from pancreatic cancer, underscoring the need to identify, document, and follow up on these findings., Competing Interests: Declarations. Competing interests: Dr. Yankelevitz is a named inventor on a number of patents and patent applications related to the evaluation of chest diseases including measurements of chest nodules. Dr. Yankelevitz has received financial compensation for the licensing of these patents. In addition, he is a consultant and co-owner of Accumetra, a private company developing tools to improve the quality of CT imaging. He is on the advisory board and owns equity in HeartLung, a company that develops software related to CT scans of the chest. He is on the medical advisory board of Median Technology that is developing technology related to analyzing pulmonary nodules and is on the medical advisory board of Carestream, a company that develops radiography equipment. He is also on the advisory board for LungLife AI.• Dr. Claudia Henschke is also an inventor of the patents and pending patents owned by Cornell Research Foundation (CRF). As of April 2009, she has divested herself of all royalties and other interests arising from these. She is on the medical advisory board for LungLife AI. • The other authors have no competing interests., (© 2024. The Author(s).)

Serum leucine-rich alpha-2 glycoprotein (LRG) can monitor disease activities during biologics treatment in patients with inflammatory bowel disease (IBD). It is unclear whether the pretreatment serum LRG level can predict clinical effectiveness including serum trough levels of ustekinumab in patients with IBD. This multicenter prospective cohort study included 184 patients (Crohn's disease, 104; ulcerative colitis, 80) who received ustekinumab (n = 119) or anti-tumor necrosis factor (n = 65) between January 2019 and March 2023. Multivariate logistic regression analysis revealed serum LRG level at week 0 (0w-LRG, odds ratio 0.12, 95% confidence interval 0.02-0.68) as one of significant factors for clinical remission at week 8. We divided patients into the low- and the high-LRG groups by the median 0w-LRG (18.2 µg/mL) and compared the effectiveness. In patients who received ustekinumab, the proportion of clinical remission at week 8 was significantly different between in the low- (76.9%) and in the high-LRG group (59.3%, P = 0.038), and median serum trough level at week 8 was significantly different between in the low- (10.9 µg/mL, interquartile range 6.7-13.4) and the high-LRG group (5.3 µg/mL, interquartile range 2.4-8.3, P < 0.001). The 0w-LRG can predict the effectiveness including serum trough levels of ustekinumab during induction treatment for patients with IBD., Competing Interests: Declarations. Competing interests: S. Shinzaki received lecture fees from Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, and lecture fees and grants from AbbVie GK, Sekisui Medical Co., Ltd.; A. Yonezawa: grants from Shimadzu Corporation and Ayumi Pharma Corporation.; H. Iijima: lecture fees from AbbVie GK and Mitsubishi-Tanabe Pharma Corporation; T. Takehara: grants from Mitsubishi-Tanabe Pharma Corporation, and lecture fees and grants from AbbVie GK. None of the aforementioned are related to this study. The remaining authors do not have any conflicts of interest to disclosure. Ethnics approval and consent to participate: This study was carried out in accordance with the Declaration of Helsinki, and approved by the ethics committee of Osaka University Hospital, the ethics committee of National Hospital Organization Osaka National Hospital, the ethics committee of Osaka Rosai Hospital, the ethics committee of Toyonaka Municipal Hospital, the ethics committee of Japan Community Healthcare Organization Osaka Hospital, the ethics committee of Itami City Hospital, the ethics committee of Suita Municipal Hospital, the ethics committee of Ikeda Municipal Hospital, the ethics committee of Otemae Hospital, the ethics committee of Kansai Rosai Hospital, the ethics committee of Higashiosaka City Medical Center, the ethics committee of Osaka General Medical Center, the ethics committee of Osaka Police Hospital, the ethics committee of Yao Municipal Hospital and the ethics committee of Hyogo Prefectural Nishinomiya Hospital. Written informed consent was obtained from all patients., (© 2024. The Author(s).)

Early mortality after hemodialysis (HD) initiation significantly impacts the longevity of HD patients. This study aimed to quantify the effect sizes of risk factors on mortality using various machine learning approaches. A cohort of 3284 HD patients from the CRC-ESRD (2008-2014) was analyzed. Mortality risk models were validated using logistic regression, ridge regression, lasso regression, and decision trees, as well as ensemble methods like bagging and random forest. To better handle missing data and time-series variables, a recurrent neural network (RNN) with an autoencoder was also developed. Additionally, survival models predicting hazard ratios were employed using survival analysis techniques. The analysis included 1750 prevalent and 1534 incident HD patients (mean age 58.4 ± 13.6 years, 59.3% male). Over a median follow-up of 66.2 months, the overall mortality rate was 19.3%. Random forest models achieved an AUC of 0.8321 for first-year mortality prediction, which was further improved by the RNN with autoencoder (AUC 0.8357). The survival bagging model had the highest hazard ratio predictability (C-index 0.7756). A shorter dialysis duration (< 14.9 months) and high modified Charlson comorbidity index scores (7-9) were associated with hazard ratios up to 7.76 (C-index 0.7693). Comorbidities were more influential than age in predicting early mortality. Monitoring dialysis adequacy (KT/V), RAAS inhibitor use, and urine output is crucial for assessing early prognosis., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Recent research in patients with functionally univentricular hearts (UVH) is focusing on pathologies of the lymphatic vessels. Morphology of the abdominal lymphatic vessels was analyzed by MRI in patients with UVH following total cavopulmonary connection (TCPC) and it was examined, if clinical and laboratory parameters correlate with changes after TCPC. We prospectively examined 33 patients at the age of 19.8 (14.6;30.2) years [median (Q1;Q3)] after TCPC (follow-up 14.3 years (9.7;24.9) with a heavily T2-weighted MRI sequence on a 3.0 T scanner. Examinations in coronal orientation were performed with respiratory gating, slice thickness 0.6 mm, TR 2400 ms, TE 692 ms, FoV 460 mm (covering thoracic and abdominal regions), scan time 14:41 min (13:18;16:30) after a solid meal and a cup of pineapple juice. The findings were classified according to delineation of abdominal lymphatic vessels. Type 1: <3 abdominal vessels (av) definable; type 2: 4-6 av definable; type 3: >6 av and/or oedematous changes or ascites. The results were correlated with parameters obtained at the annual routine check-up. Statistical analysis was performed using U-test and Chi-square test. Fifteen patients (group 1) showed type 3 lymphatic morphologies, two of which had ascites. Eighteen patients (group 2) showed lower grade morphologies (type 1-2). Image quality was rated considering the delineation of the common hepatic duct and did not differ between groups (p = 0.134). "Lymphatic burden" was automatically examined and was indexed to the number of delineated abdominal vessels and showed quantification according to the chosen categories type 1-3. Patients in group 1 were younger at MRI examination (17.4;14.3/18.9 vs. 26.2;18.2/32.3 years, p = 0.03). Superior cavopulmonary connection (SCPC) had been performed earlier in group 1 (9.9;7.9/25.5 vs. 29.2;13.7/66.6 months, p = 0.018). Laboratory examinations in group 1 showed lower levels for Immunoglobulin G (IgG), Lipase, α-Antitrypsin, Cystatin C and TSH. There were no significant differences for total protein, NTproBNP, lymphocytes or platelets. A history of chylothorax was present in 7/15 versus 2/18 p = 0.022. Protein-losing enteropathy (PLE) occurred in 4/15 versus 1/18 (p = 0.092). T2 weighted MRI is feasible for noninvasive delineation of abdominal lymphatic vessel in patients following TCPC. In the long-term follow-up, patients with more pronounced changes of the abdominal lymphatic vessels were younger at SCPC and were more likely to show a history of chylothorax and lower IgG values., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Consent for publication: Written informed consent was obtained from the patient for publication and any accompanying pictures. A copy of the written consent is available for review by the Editor of this journal., (© 2024. The Author(s).)

Sensitization to Staphylococcus aureus (S. aureus) enterotoxins (SEs) A (SEA) and B (SEB) is associated with the pathogenesis of several chronic airway diseases, including asthma and chronic rhinosinusitis, but its role in chronic obstructive pulmonary disease (COPD) remains unclear. This cohort study aimed to investigate the impact of sensitization to SEs on total IgE levels, and capsaicin cough reflex sensitivity (C-CS) in COPD. This study prospectively enrolled 68 patients with COPD from the outpatient department at Nagoya City University Hospital and Shizuoka General Hospital, Japan, from June 2018 to January 2020 for posthoc analysis. Patient characteristics and biomarkers, including total IgE, and C-CS, were collected. We additionally measured and serum SEA-IgE and SEB-IgE levels for this analysis. Total IgE and SEs-IgE levels in individuals with COPD were compared to those of 20 healthy individuals. The correlation between C-CS and IgE levels was evaluated using Pearson's correlation coefficient. Multivariate analyses were used to adjust the impact on SE sensitization in total IgE levels and C-CS. The prevalence of SEs sensitization was higher in patients with COPD (23.5%, N = 16) than in healthy individuals (0%, N = 0) at a cut-off value of 0.35 UA/mL or more (p = 0.018). There was a negative correlation between total serum SEB-IgE levels and declined C-CS values. Multivariate analysis showed that SEs sensitization was associated with increased total IgE levels, and declined C-CS values. This study indicated that SEs sensitization was associated with increased IgE levels and decreased C-CS in COPD. This study was approved by the ethics committee of Nagoya City University (60-18-0012) and registered in the UMIN Clinical Trials Registry (Registry ID UMIN000032497)., Competing Interests: Declarations. Competing interests: There is no conflict of interest in the submitted work.　The authors have competing interests outside the submitted work. Y.K. received research grants from MSD life foundation and personal fees from GSK, Novartis Pharma, AstraZeneca, Sanofi, and Kyorin. K.F. received research grants from Novartis Pharma and GSK. S.F. received personal fees from AstraZeneca and Eli Lilly. H.O. received a research grant from Boehringer Ingelheim. A.N. reports personal fees from Astellas, AstraZeneca, Kyorin, GSK, MSD, Shionogi, Bayer, Sanofi, Taiho, and Boehringer Ingelheim, and research grants from Astellas, Kyorin, Boehringer Ingelheim, Novartis, MSD, Daiichi Sankyo, Taiho, Teijin, Ono, Takeda, and Sanofi Pharmaceutical. R.K., T. A., Y.I., Y. A., T. S., K.I., Y. M., T. U., T.T., or T.S. did not receive any grants or personal fees. Ethics approval and consent to participate: This study was approved by the ethics committee of Nagoya City University (60-18-0012) and registered in the UMIN Clinical Trials Registry (Registry ID UMIN000032497). Written informed consent was obtained from all participants. All methods were performed in accordance with the Declaration of Helsinki., (© 2024. The Author(s).)