Differential Item Functioning and Clinical Utility of the Subjective Memory Complaints Questionnaire in a Multi-Ethnic Cohort.

INTRODUCTION: This study evaluated psychometric properties of the Subjective Memory Complaints Questionnaire (SMCQ) in a non-Hispanic White (NHW) and Mexican American (MA) sample from Texas in the United States. METHODS: Data were obtained from the Health and Aging Brain Study - Health Disparities (HABS-HD; N=1691, age=66.5±8.7, education=12.4±4.8, 60.6% female, 33.2% MA Spanish-speaking). Unidimensionality of the SMCQ was evaluated with confirmatory factor analysis. Differential item functioning (DIF) of the SMCQ was assessed across age, sex, education, and ethnicity/language using item response theory (IRT) / logistic ordinal regression. Associations of the SMCQ in relation to cognitive status, Alzheimer's disease (AD) blood-based biomarkers, and psychological distress were examined. RESULTS: The SMCQ showed excellent fit in a single-factor model (CFI=0.97, TLI=0.97, RMSEA [95% CI] = 0.05 [0.04, 0.05], SRMR=0.07). Significant item-level DIF was detected by education level and ethnicity/language, but not by age or sex; when detected, DIF was not salient (i.e., adverse). The SMCQ was associated with greater psychological distress, worse Clinical Dementia Rating scores, and greater disease burden as measured by total tau and neurofilament light. CONCLUSIONS: Practically negligible item-level bias was identified across education and ethnicity/language. Detected DIF can be described as benign, indicating that some items manifested differently between groups but had minimal impact on measurement properties. These results demonstrate that the SMCQ performs appropriately across demographic variables. Our findings also provide support for the associations of SMCQ scores with self-reported mood, cognitive status, and AD blood-based biomarkers.

Adipocyte derived exosomes promote cell invasion and challenge paclitaxel efficacy in ovarian cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is the deadliest gynaecological cancer with high mortality rates driven by the common development of resistance to chemotherapy. EOC frequently invades the omentum, an adipocyte-rich organ of the peritoneum and omental adipocytes have been implicated in promoting disease progression, metastasis and chemoresistance. The signalling mechanisms underpinning EOC omentum tropism have yet to be elucidated. METHODS: Three-dimensional co-culture models were used to explore adipocyte-EOC interactions. The impact of adipocytes on EOC proliferation, response to therapy and invasive capacity was assessed. Primary adipocytes and omental tissue were isolated from patients with ovarian malignancies and benign ovarian neoplasms. Exosomes were isolated from omentum tissue conditioned media and the effect of omentum-derived exosomes on EOC evaluated. Exosomal microRNA (miRNA) sequencing was used to identify miRNAs abundant in omental exosomes and EOC cells were transfected with highly abundant miRNAs miR-21, let-7b, miR-16 and miR-92a. RESULTS: We demonstrate the capacity of adipocytes to induce an invasive phenotype in EOC populations through driving epithelial-to-mesenchymal transition (EMT). Exosomes secreted by omental tissue of ovarian cancer patients, as well as patients without malignancies, induced proliferation, upregulated EMT markers and reduced response to paclitaxel therapy in EOC cell lines and HGSOC patient samples. Analysis of the omentum-derived exosomes from cancer patients revealed highly abundant miRNAs that included miR-21, let-7b, miR-16 and miR-92a that promoted cancer cell proliferation and protection from chemotherapy when transfected in ovarian cancer cells. CONCLUSIONS: These observations highlight the capacity of omental adipocytes to generate a pro-tumorigenic and chemoprotective microenvironment in ovarian cancer and other adipose-related malignancies.

Development of Subcutaneous Panniculitis-Like T-cell Lymphoma After Immune Checkpoint Inhibitor Treatment.

Program death 1 (PD-1) inhibitors such as nivolumab are immune checkpoint inhibitors that have revolutionized the treatment of metastatic melanoma. Despite its success in treating melanoma, immune activation can lead to immune-related adverse effects, which are experienced by half of melanoma patients treated with PD-1 inhibitors. Despite the common frequency of immune-mediated adverse events, the development of a secondary lymphoma is exceedingly rare. We present the case of a 53-year-old woman diagnosed with stage IV metastatic melanoma, treated with nivolumab, who subsequently developed fatal subcutaneous panniculitis-like T-cell lymphoma (SPTCL).

A Directed Content Analysis for Greatest Problems Among People With and Without Traumatic Brain Injury.

OBJECTIVE: To characterize the greatest problem or need among individuals with a history of traumatic brain injury (TBI), as compared with individuals with a history of other neurologic conditions, mental health conditions, and no history of neurologic or mental health conditions. DESIGN: A directed content analysis of open-text responses to a single online survey question using a framework guided by the Mayo-Portland Adaptability Inventory-4. SETTING: Community. PARTICIPANTS: A total of 2861 community-dwelling adults (n=274 with TBI; n=289 with other neurologic conditions besides TBI; n=454 with mental health conditions but no neurologic conditions; and n=1844 controls). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Open-text responses to the survey prompt: "What was your greatest problem or need over the past 2 weeks?" RESULTS: The Participation index comprised the greatest proportion of responses across all 4 participant groups. A quarter (25.4%) of controls reported None (no problem/need), whereas only 7.9%-10.7% of participants in all other groups reported None. Among all groups, individuals with TBI reported the greatest proportion of problems in the Adjustment and Ability indices. Among people with TBI, Money Management (19.7%), None (10.6%), and Anxiety (7.7%) were the 3 most frequently reported problems. Compared with individuals with mild TBI (mTBI), individuals with moderate-to-severe TBI (msTBI) reported a higher proportion of problems in the Ability and Adjustment indices. Among individuals with msTBI, the Adjustment index accounted for the greatest proportion of problems. CONCLUSIONS: This study employed a person-centered approach to understanding the greatest needs among individuals with TBI. Qualitative differences were observed between individuals with and without TBI, between people with mTBI and msTBI, and across genders among people with TBI. These findings can help guide research and policy toward addressing challenges perceived as highly important by people living in the community with TBI.

Off-target effects of statins: molecular mechanisms, side effects and the emerging role of kinases.

Statins are one of the most important classes of drugs. In this analytical review, we elucidate the intricate molecular mechanisms and toxicological rationale regarding both the on- (targeting 3-hydroxy-3-methylglutaryl-coenzyme A reductase [HMGCR]) and off-target effects of statins. Statins interact with a number of membrane kinases, such as epidermal growth factor receptor (EGFR), erb-b2 receptor tyrosine kinase 2 (HER2) and MET proto-oncogene, receptor tyrosine kinase (MET), as well as cytosolic kinases, such as SRC proto-oncogene, non-receptor tyrosine kinase (Src) and show inhibitory activity at nanomolar concentrations. In addition, they interact with calcium ATPases and peroxisome proliferator-activated receptor α (PPARα/NR1C1) at higher concentrations. Statins interact with mitochondrial complexes III and IV, and their inhibition of coenzyme Q10 synthesis also impairs the functioning of complexes I and II. Statins act as inhibitors of kinases, calcium ATPases and mitochondrial complexes, while activating PPARα. These off-target effects likely contribute to the side effects observed in patients undergoing statin therapy, including musculoskeletal symptoms and hepatic effects. Interestingly, some off-target effects of statins could also be the cause of favourable outcomes, relating to repurposing statins in conditions such as inflammatory disorders and cancer.

Systematic review and meta-analysis of two decades of reported outcomes for robotic coronary artery bypass grafting.

Background: Despite the well-documented safety and feasibility of robotic coronary artery bypass grafting (CABG), widespread adoption of this approach remains limited by its steep learning curve, high procedural costs and paucity of data on longer-term efficacy. This current meta-analysis aims to provide a systematic overview of the outcomes of robot-assisted CABG, with a focus on long term graft patency and freedom from major adverse cardiac and cerebrovascular events (MACCE). Methods: A systematic literature search of three electronic databases was conducted for studies reporting outcomes of robotic-assisted CABG, and were grouped based on whether patients underwent robot-assisted minimally invasive direct coronary artery bypass (RA-MIDCAB), totally endoscopic coronary artery bypass (TECAB) or were mixed. Perioperative and mid-to-long term results from included studies were pooled using meta-analysis of proportion or means in a random effects model. Results: In the quantitative analysis, thirty-nine eligible studies included 6,152 patients who underwent RA-MIDCAB, 1,729 patients who underwent TECAB and 21,642 patients who underwent either form of robot-assisted CABG. A high level of heterogeneity was observed amongst baseline characteristics. Perioperative mortality and complication rates were low. Conversion rate to full sternotomy overall was less than 3.2% [95% confidence interval (CI): 2.1-5.2%, I2=39%]. At a mean follow-up duration of 5.2 years, overall graft patency was 96% for both RA-MIDCAB and TECAB, and freedom from major adverse cardiac events (MACE) or MACCE was 83.2% (95% CI: 72.0-90.4%; I2=90%) for RA-MIDCAB and 91.6% (95% CI: 86.6-94.9%; I2=76%) for TECAB. Conclusions: Robot-assisted CABG is observed to have acceptable perioperative and mid-to-long term outcomes with promising overall graft patency.

Cholangiocarcinoma.

Cholangiocarcinoma (CC) is a heterogeneous group of malignancies that originates at any point along the biliary tree. CC is an uncommon malignancy as it represents approximately 3% of all gastrointestinal malignancies, though its global incidence is rising. CC can often be asymptomatic in its early stages and as a result, it is frequently diagnosed in later stages, leading to challenges in clinical management.

Comparative Life Cycle Assessment of alternative winter salad value chains supplying the United Kingdom.

Lettuce is an established food commodity in the UK increasingly facing supply challenges in winter due to adverse weather events and rising energy costs. We investigate whether an agroecologically grown salad mix of lettuce and underutilised leafy greens produced in the Azores, Portugal, could be part of a sustainable solution. We performed a Life Cycle Assessment to compare the environmental impacts of this salad mix with four other value chains for winter salad supply to the UK: conventional open-field lettuce production chains in Spain using (1) current irrigation practices; (2) 100 % desalinated irrigation water; or hydroponic controlled environment agriculture within the UK powered by (3) the national electricity mix; (4) 100 % wind-generated electricity. Results indicated that the leafy-greens agroecological value chain incurred the smallest environmental burdens across 7 to 11 of 16 impact categories studied. Substituting Spanish winter salad supply with agroecological leafy green production in the Azores, if well managed, could reduce many environmental burdens whilst diversifying leafy greens intake. Nevertheless, all winter value chains were associated with larger environmental burdens than conventional open-field production of lettuce in the UK summer, pointing to the importance of seasonal consumption and wider adoption of agroecological techniques to effectively reduce environmental impact.

Concomitant tricuspid valve surgery in patients with significant tricuspid regurgitation undergoing left ventricular assist device implantation: A systematic review and meta-analysis.

BACKGROUND: Significant tricuspid regurgitation (TR) is a predictor of right heart failure (RHF) and increased mortality following left ventricular assist device (LVAD) implantation, however the benefit of tricuspid valve surgery (TVS) at the time of LVAD implantation remains unclear. This study compares early and late mortality and RHF outcomes in patients with significant TR undergoing LVAD implantation with and without concomitant TVS. METHODS: A systematic search of four electronic databases was conducted for studies comparing patients with moderate or severe TR undergoing LVAD implantation with or without concomitant TVS. Meta-analysis was performed for primary outcomes of early and late mortality and RHF. Secondary outcomes included rate of stroke, renal failure, hospital and ICU length of stay. An overall survival curve was constructed using aggregated, reconstructed individual patient data from Kaplan-Meier (KM) curves. RESULTS: Nine studies included 575 patients that underwent isolated LVAD and 308 patients whom received concomitant TVS. Both groups had similar rates of severe TR (46.5% vs. 45.6%). There was no significant difference seen in risk of early mortality (RR 0.90; 95% CI, 0.57-1.42; p = 0.64; I2 = 0%) or early RHF (RR 0.82; 95% CI, 0.66-1.19; p = 0.41; I2 = 57) and late outcomes remained comparable between both groups. The aggregated KM curve showed isolated LVAD to be associated with overall increased survival (HR 1.42; 95% CI, 1.05-1.93; p = 0.023). CONCLUSIONS: Undergoing concomitant TVS did not display increased benefit in terms of early or late mortality and RHF in patients with preoperative significant TR. Further data to evaluate the benefit of concomitant TVS stratified by TR severity or by other predictors of RHF will be beneficial.

Central Nervous System Prophylaxis Utilization in Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Within a Large Community Health System.

Purpose: The impact of central nervous system (CNS) prophylaxis in diffuse large B-cell lymphoma (DLBCL) is contentious. The CNS International Prognostic Index (IPI) calculator offers prognostic guidance in identifying those patients who may be at highest risk of disease progression or relapse to the CNS. However, it is unclear whether this tool has guided clinician decision-making in a real-world setting. Studies have suggested that CNS prophylaxis may not offer clinically significant benefit in terms of preventing CNS disease progression. Given this, we investigated the utilization of CNS prophylaxis within our own population and documentation of the CNS-IPI score. Methods: We retrospectively evaluated patients with newly diagnosed DLBCL between January 1, 2014, and December 31, 2017. Patients were assessed for receipt of CNS prophylaxis in the form of intrathecal (IT) chemotherapy and/or high-dose intravenous (IV) methotrexate. CNS-IPI scores were calculated for all patients who received CNS prophylaxis or those who experienced CNS disease. Long-term outcomes at five years from diagnosis included CNS progression/relapse and survival. Results: Of 234 patients who met criteria, 20 (8.6%) received either IV methotrexate or IT chemotherapy; most received IT methotrexate. No patients in the IT prophylaxis group developed CNS disease, while two of eight IV methotrexate patients experienced CNS disease involvement. The incidence of CNS progression was 3.7% in the no prophylaxis group and 10% in those who received prophylaxis. Conclusions: This study revealed low utilization of CNS prophylaxis and CNS-IPI documentation in a community hospital system. Given large differences between groups, claims of CNS prophylaxis efficacy are unable to be made. CNS relapse rates were consistent with existing literature and promote continued evaluation of the utility of current CNS prophylaxis approaches in DLBCL. New unambiguously effective therapeutic approaches are needed and may encourage a higher rate of standardized use.

A stress-induced source of phonon bursts and quasiparticle poisoning.

The performance of superconducting qubits is degraded by a poorly characterized set of energy sources breaking the Cooper pairs responsible for superconductivity, creating a condition often called "quasiparticle poisoning". Both superconducting qubits and low threshold dark matter calorimeters have observed excess bursts of quasiparticles or phonons that decrease in rate with time. Here, we show that a silicon crystal glued to its holder exhibits a rate of low-energy phonon events that is more than two orders of magnitude larger than in a functionally identical crystal suspended from its holder in a low-stress state. The excess phonon event rate in the glued crystal decreases with time since cooldown, consistent with a source of phonon bursts which contributes to quasiparticle poisoning in quantum circuits and the low-energy events observed in cryogenic calorimeters. We argue that relaxation of thermally induced stress between the glue and crystal is the source of these events.

Factors Associated With Tobacco Cessation Advice Recall and Quit Rates in Vascular Surgery Patients. A Single Center Study.

OBJECTIVES: Smoking is an important modifiable risk factor in all vascular diseases and verbal advice from providers has been shown to increase rates of tobacco cessation. We sought to identify factors that will improve tobacco cessation and recall of receiving verbal cessation advice in vascular surgery patients at a single institution. METHODS: The study is a retrospective cohort study. Patients seen in outpatient vascular surgery clinic who triggered a tobacco Best Practice Advisory (BPA) during their office visits over a 10-month period were contacted post-clinic and administered surveys detailing smoking status, cessation advice recall, and validated scales for nicotine dependence and willingness to quit smoking. This BPA is a "hard stop" that requires providers to document actions taken. Charts were reviewed for tobacco cessation documentation. Nine-digit zip-codes identified the area deprivation index, a measure of socioeconomic status. Univariate analysis was used to identify factors associated with cessation and advice recall. RESULTS: One hundred out of 318 (31.4%) patients responded to the survey. Epic Slicer Dicer found 97 BPA responses. To dismiss the BPA, 89 providers (91.8%) selected "advised tobacco cessation" and "Unable to Advise" otherwise. Of the 318 patients, 115 (36.1%) had cessation intervention documented in their provider notes and 151 (47.5%) received written tobacco cessation advice. Of survey respondents, 70 recalled receiving verbal advice, 27 recalled receiving written advice, 28 reported receiving offers of medication/therapy for cessation. 55 patients reported having tobacco cessation plans, and among those 17 reported having quit tobacco. Recall of receiving written advice (P < .001) and recall of receiving medication/therapy (P = .008) were associated with recall of receiving verbal cessation advice. CONCLUSIONS: Providing patients with tobacco cessation medication/therapy and written tobacco cessation education during office visits is associated with increased patients' recall of tobacco cessation advice. Vascular surgeons should continue to provide directed tobacco cessation advice.

Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial.

PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.

Long-term effects of Preweaning environmental impoverishment on neurobehavioral and neurocognitive outcomes in Sprague Dawley rats: An early environmental stress model.

Developmental stress, including low socioeconomic status (SES), can induce dysregulation of the hypothalamic-pituitary-adrenal axis and result in long-term changes in stress reactivity. Children in lower SES conditions often experience more stress than those in other SES groups. There are multiple model systems of early environmental stress (EES), one of which is reduced cage bedding. Here we tested the effects of both prenatal and lactational EES in rats on a range of long-term behavioral and cognitive outcomes. There were persistent reductions in body weight in the EES rats in both sexes. The behavioral results showed no effects on learning and memory using tests of spatial learning or cognitive flexibility in the Morris water maze, egocentric learning in the Cincinnati water maze, or working memory in the radial-arm maze. There were no effects on basic open-field activity, elevated zero-maze, or forced swim test, but EES rats had reduced time in the dark side of the light/dark test. When rats were drug challenged in the open-field with d-amphetamine or MK-801, there were no differential responses to d-amphetamine, but the EES group under responded compared with the drug-induced hyperactivity in the control group in both males and females. The objective was to establish a developmental stress model that induced cognitive deficits and to the extent that this method did not cause such effects it was not the model we sought. However, the data showed several long-term effects of EES, including the reduced response to the irreversible NMDA antagonist MK-801. This effect merits further investigation.

Genomic and morphological characterization of Knufia obscura isolated from the Mars 2020 spacecraft assembly facility.

Members of the family Trichomeriaceae, belonging to the Chaetothyriales order and the Ascomycota phylum, are known for their capability to inhabit hostile environments characterized by extreme temperatures, oligotrophic conditions, drought, or presence of toxic compounds. The genus Knufia encompasses many polyextremophilic species. In this report, the genomic and morphological features of the strain FJI-L2-BK-P2 presented, which was isolated from the Mars 2020 mission spacecraft assembly facility located at the Jet Propulsion Laboratory in Pasadena, California. The identification is based on sequence alignment for marker genes, multi-locus sequence analysis, and whole genome sequence phylogeny. The morphological features were studied using a diverse range of microscopic techniques (bright field, phase contrast, differential interference contrast and scanning electron microscopy). The phylogenetic marker genes of the strain FJI-L2-BK-P2 exhibited highest similarities with type strain of Knufia obscura (CBS 148926T) that was isolated from the gas tank of a car in Italy. To validate the species identity, whole genomes of both strains (FJI-L2-BK-P2 and CBS 148926T) were sequenced, annotated, and strain FJI-L2-BK-P2 was confirmed as K. obscura. The morphological analysis and description of the genomic characteristics of K. obscura FJI-L2-BK-P2 may contribute to refining the taxonomy of Knufia species. Key morphological features are reported in this K. obscura strain, resembling microsclerotia and chlamydospore-like propagules. These features known to be characteristic features in black fungi which could potentially facilitate their adaptation to harsh environments.

Effect of recipient age on prioritisation for liver transplantation in the UK: a population-based modelling study.

BACKGROUND: Following the introduction of an algorithm aiming to maximise life-years gained from liver transplantation in the UK (the transplant benefit score [TBS]), donor livers were redirected from younger to older patients, mortality rate equalised across the age range and short-term waiting list mortality reduced. Understanding age-related prioritisation has been challenging, especially for younger patients and clinicians allocating non-TBS-directed livers. We aimed to assess age-related prioritisation within the TBS algorithm by modelling liver transplantation prioritisation based on data from a UK transplant unit and comparing these data with other regions. METHODS: In this population-based modelling study, serum parameters and age at liver transplantation assessment of patients attending the Scottish Liver Transplant Unit, Edinburgh, UK, between December, 2002, and November, 2023, were combined with representative synthetic data to model TBS survival predictions, which were compared according to age group (25-49 years vs ≥60 years), chronic liver disease severity, and disease cause. Models for end-stage liver disease (UKELD [UK], MELD [Eurotransplant region], and MELD 3.0 [USA]) were used as validated comparators of liver disease severity. FINDINGS: Of 2093 patients with chronic liver disease, 1808 (86%) had complete datasets and liver disease parameters consistent with eligibility for the liver transplant waiting list in the UK (UKELD ≥49). Disease severity as assessed by UKELD, MELD, and MELD 3.0 did not differ by age (median UKELD scores of 56 for patients aged ≥60 years vs 56 for patients aged 25-49 years; MELD scores of 16 vs 16; and MELD 3.0 scores of 18 vs 18). TBS increased with advancing age (R=0·45, p<0·0001). TBS predicted that transplantation in patients aged 60 years or older would provide a two-fold greater net benefit at 5 years than in patients aged 25-49 years (median TBS 1317 [IQR 1116-1436] in older patients vs 706 [411-1095] in younger patients; p<0·0001). Older patients were predicted to have shorter survival without transplantation than younger patients (263 days [IQR 144-473] in older patients vs 861 days [448-1164] in younger patients; p<0·0001) but similar survival after transplantation (1599 days [1563-1628] vs 1573 days [1525-1614]; p<0·0001). Older patients could reach a TBS for which a liver offer was likely below minimum criteria for transplantation (UKELD <49), whereas many younger patients were required to have high-urgent disease (UKELD >60). US and Eurotransplant programmes did not prioritise according to age. INTERPRETATION: The UK liver allocation algorithm prioritises older patients for transplantation by predicting that advancing age increases the benefit from liver transplantation. Restricted follow-up and biases in waiting list data might limit the accuracy of these benefit predictions. Measures beyond overall waiting list mortality are required to fully capture the benefits of liver transplantation. FUNDING: None.

Comparison of intermittent intravenous tacrolimus to continuous tacrolimus in adult allogeneic stem cell transplant recipients.

Introduction: Initial continuous intravenous (CIV) tacrolimus (0.03 mg/kg/day based on ideal body weight [IBW]) has been favored for graft versus host disease (GVHD) prevention in allogeneic stem cell transplant patients due to the consistent, steady-state degree of immunosuppression; however, this method poses many logistical challenges. We implemented intermittent (IIV) tacrolimus at a starting dose of 0.015 mg/kg IBW twice daily over 4 h. To our knowledge this is the first retrospective comparison of CIV to IIV tacrolimus. Objectives: The primary objective was to evaluate the safety of IIV tacrolimus in comparison to CIV with respect to nephrotoxicity and neurotoxicity. The secondary objectives were to compare the incidence of grade II-IV acute GVHD (aGVHD) and chronic GVHD (cGVHD) at day +180, outcomes including relapse and overall survival, cell engraftment, and reactivation of cytomegalovirus and Epstein-Barr virus. Methods: This retrospective, single-center review evaluated adults who received an allogeneic stem cell transplant patients between January 1, 2020, and December 31, 2022. Results: Fifty-one unique patients were eligible for evaluation - 28 in the IIV cohort and 23 in the CIV group. The number of patients who developed nephrotoxicity and neurotoxicity were comparable between groups with no significant differences noted. No severe neurotoxicity was identified in either population. Secondary objectives revealed no significant difference in GVHD incidence or survival outcomes. Conclusion: IIV tacrolimus is comparable to CIV in terms of safety while also maintaining similar outcomes at day +180. IIV is a safe and feasible alternative to CIV in adult allogeneic stem cell transplant recipients.

Neurobehavioral Symptom Profiles for the Behavioral Assessment Screening Tool in Chronic Traumatic Brain Injury.

OBJECTIVE: To identify neurobehavioral symptom profiles among persons with chronic traumatic brain injury (TBI) using the Behavioral Assessment Screening Tool (BAST) and to consider participant characteristics that differ between profile groups. SETTING: Community. PARTICIPANTS: Participants (n = 615) were English-speaking adults (≥18) and had a self-reported history of at least one TBI of any severity. DESIGN: Secondary analysis of cross-sectional data. MAIN MEASURES: The BAST measures neurobehavioral symptoms in the domains of Negative Affect, Fatigue, Executive Dysfunction, Impulsivity, and Substance Misuse. RESULTS: Using latent profile analysis (LPA), we identified 3 different neurobehavioral profiles. Overall symptom frequency and differences in the pattern of symptom frequency across domains differentiated the profile groups. Average domain scores differed significantly across the profiles ( P < .001) for all domains except Fatigue ( P = .076). Those in profile 3 (High-Risk group) reported the most frequent symptoms across all domains (similar Negative Affect frequency as profile 1). Substance Misuse was especially high in this group. Compared to profile 2 (High Negative Affect group), participants in profile 1 (Moderate-Risk group) endorsed significantly more frequent (and more variable) symptoms across all BAST domains, particularly Impulsivity and Substance Misuse. Participants in profile 2 endorsed the least frequent symptoms across all domains. Demographic comparison showed that groups differed based on gender, age, and injury severity (mild vs moderate-severe), with profile 3 composed of the most men and the most persons in early adulthood, and profile 2 composed of the most women and those with mild TBI. CONCLUSIONS: We differentiated 3 neurobehavioral symptom profiles among persons with chronic TBI and determined differences in sociodemographic factors between the groups. Future research should focus on validating these profiles in another sample of individuals with chronic TBI. Characterizing persons according to multidimensional symptom profiles could allow for more tailored approaches to predict and prevent long-term negative outcomes.

The outcomes of concomitant catheter ablation in non-mitral valve cardiac surgery-a systematic review and meta-analysis of the literature.

Background: Atrial fibrillation (AF) is the most common form of cardiac arrythmia, with a key importance in the perioperative setting of cardiac surgery. In recent years, the question as to whether pre-existent AF should be treated concomitantly when undergoing cardiac surgery has been heatedly debated. This systematic review and meta-analysis sought to delineate the outcomes of patients undergoing concomitant AF ablation procedures alongside cardiac surgery. Methods: The methods for this systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Four databases were searched, ultimately yielding 22 papers for inclusion, using appropriate search terminology. Meta-analysis using proportions or means, as appropriate, were applied. Kaplan-Meier curves were digitized and aggregated using previously reported and validated techniques. Results: A total of 9,428 patients (67% male) were identified across the study period as having received non-mitral cardiac surgery and concomitant AF ablation procedures. On actuarial assessment, freedom from AF was found to be 93%, 88%, 85%, 82%, and 79% at 1 through to 5 years, respectively. Freedom from mortality was found to be 94%, 93%, 91%, 90%, and 87% at 1 through to 5 years, respectively. Conclusions: This review demonstrated excellent freedom from AF out to a long-term follow-up of 5 years. Freedom from mortality was also encouraging. Emerging data are increasingly illustrating that in this patient cohort, concurrent treatment of pre-existent AF with cardiac and/or valvular disease at the point of operation should be the standard of care. Robust data in the form of randomized control trials will hopefully solidify this assertion.