Distinct Mindfulness States Produce Dissociable Effects on Neural Markers of Emotion Processing: Evidence From the Late Positive Potential.

Background: Mindfulness has long been theorized to benefit emotion regulation, but despite the ubiquity of the claim, there is little empirical evidence demonstrating how mindfulness modulates the neurophysiology of emotion processing. The current study aimed to fill this gap in knowledge by leveraging a novel research approach capable of discretizing mindfulness into distinct states of open monitoring (OM) and focused attention (FA) to distinguish their influence on multimodal subjective and objective measures of emotion processing. Methods: Utilizing a fully within-participant picture viewing state induction protocol (N = 30), we compared the effects of OM and FA, rigorously contrasted against an active control, on the visually evoked late positive potential (LPP), a neural index of motivated attention. Bayesian mixed modeling was used to distinguish OM versus FA effects on the early and late sustained LPP while evaluating the influence of subjective arousal ratings as a within-participant moderator of the state inductions. Results: When negative picture trials were retrospectively rated as more subjectively arousing, the OM induction reduced the late sustained LPP response, whereas the FA induction enhanced the LPP. Conclusions: Acute manipulation of OM and FA states may reduce and enhance motivated attention to aversive stimuli during conditions of high subjective arousal, respectively. Functional distinctions between different mindfulness states on emotion processing may be most dissociable after accounting for within-participant variability in how stimuli are appraised. These results support the future potential of the state induction protocol for parsing the neural affective mechanisms that underlie mindfulness training programs and interventions.

Mindfulness, defined as a nonjudgmental awareness of present moment experience, is widely thought to benefit emotional well-being. Despite substantial research in this area, it remains unclear how mindfulness influences emotion-related processes at the level of brain functioning. The current study utilized an EEG picture viewing task to examine how open monitoring (OM) and focused attention (FA), 2 distinct mindfulness states, influence the late positive potential (LPP), a neural marker of motivated attention. The results show that when participants rated negatively valenced pictures as more subjectively arousing, the OM state decreased the LPP response, whereas the FA state increased the LPP. These findings suggest that OM and FA states may reduce and enhance motivated attention to unpleasant high arousing stimuli, respectively. At a broader level, the study shows that the effects of experientially distinct mindfulness states are distinguishable and provides a methodological foundation for future studies to disentangle the neural mechanisms of mindfulness programs and interventions.

The design of a sample rapid magnetic resonance imaging (MRI) acquisition protocol supporting assessment of multiple articular tissues and pathologies in knee osteoarthritis.

Objective: This expert opinion paper proposes a design for a state-of-the-art magnetic resonance image (MRI) acquisition protocol for knee osteoarthritis clinical trials in early and advanced disease. Semi-quantitative and quantitative imaging endpoints are supported, partly amendable to automated analysis. Several (peri-) articular tissues and pathologies are covered, including synovitis. Method: A PubMed literature search was conducted, with focus on the past 5 years. Further, osteoarthritis imaging experts provided input. Specific MRI sequences, orientations, spatial resolutions and parameter settings were identified to align with study goals. We strived for implementation on standard clinical scanner hardware, with a net acquisition time ≤30 â€‹min. Results: Short- and long-term longitudinal MRIs should be obtained at ≥1.5T, if possible without hardware changes during the study. We suggest a series of gradient- and spin-echo-sequences, supporting MOAKS, quantitative analysis of cartilage morphology and T2, and non-contrast-enhanced depiction of synovitis. These sequences should be properly aligned and positioned using localizer images. One of the sequences may be repeated in each participant (re-test), optimally at baseline and follow-up, to estimate within-study precision. All images should be checked for quality and protocol-adherence as soon as possible after acquisition. Alternative approaches are suggested that expand on the structural endpoints presented. Conclusions: We aim to bridge the gap between technical MRI acquisition guides and the wealth of imaging literature, proposing a balance between image acquisition efficiency (time), safety, and technical/methodological diversity. This approach may entertain scientific innovation on tissue structure and composition assessment in clinical trials on disease modification of knee osteoarthritis.

Low-dose abiraterone plus Olaparib as a late-line treatment for mCRPC patients without BRCA1/2 mutations: a multicenter retrospective pilot study.

Although overall survival data are still premature, the PROpel study found radiological progression-free survival (PFS) benefits of abiraterone and olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC). However, for patients who have not been genetically tested or lack BRCA1/2 mutations (BRCAm), this combination therapy has been questioned as a first-line conventional treatment for mCRPC, mainly due to significant health economics and side effects. In our retrospective study, we found that treatment with low-dose abiraterone plus olaparib as a late-line treatment for mCRPC could lead to prostate-specific antigen (PSA) and symptom PFS in selective cases even without BRCAm. The median PSA-PFS was 8 months (IQR: 6.5-11.5), with a median follow-up duration of 39.0 months (IQR: 27.5-64.5). Gene tests were conducted in all patients, identifying non-BRCA mutations through ctDNA testing (24%), tumor tissue testing (12%), or both (64%). Adverse events occurred in 72% of patients, with 16% experiencing Grade ≥ 3 events. Common adverse events included anemia (64%), decreased appetite (48%), and fatigue (25%). Our findings support low-dose abiraterone plus olaparib as a potential option for mCRPC patients without BRCAm, offering manageable safety and efficacy profiles.

Abnormal late postprandial glucagon response in type 1 diabetes is a function of differences in stimulated C-peptide concentrations.

Background: The functional changes in alpha cells in patients with type 1 diabetes (T1D) with different residual beta cell functions remain poorly elucidated. The study aimed to investigate the relationship between glucagon secretion and C-peptide levels and to explore the relationship between glucagon response and glucose increment in respond to a secretagogue in a steamed bread meal tolerance test (BMTT) in T1D. Methods: The study enrolled 43 adult patients with T1D and 24 healthy control subjects. Patients with T1D who underwent BMTT were divided into two groups based on peak C-peptide levels: C peptide low (CPL; C-peptide < 200 pmol/L; n=14) and high (CPH; C peptide ≥ 200 pmol/L; n=29). Plasma glucose, C-peptide, glucagon levels at 0, 30, 60, 120, and 180 min were measured. The glucagon response to the BMTT was defined by areas under the curve (AUC) as early (AUC0-30), late (AUC30-180), or total (AUC0-180) glucagon. Results: Compared to healthy individuals, fasting plasma glucagon was lower and postprandial plasma glucagon level was increased in patients with T1D. Glucagon levels after BMTT between the CPL and CPH group showed significant group by time interaction. Peak glucagon and glucagon at 60-180 min, total and late glucagon response were higher in CPL than CPH group, while fasting glucagon and early glucagon response adjusted for glucose were comparable between CPL and CPH group. The higher late glucagon response and late glucagon response adjusted for glucose were associated with lower peak C-peptide in T1D. The higher late glucagon response and lower peak C-peptide were associated with the higher value of ▵glucose at 180 min. Conclusion: Stimulated C-peptide levels affect the paradoxical increase in postprandial glucagon secretion in patients with T1D, especially late glucagon response. The exaggerated postprandial glucagon secretion further stimulates the elevation of postprandial glucose in patients with T1D.

Generalized root agenesis in permanent dentition of a young adolescent patient with rhabdomyosarcoma: a case report.

BACKGROUND: Parameningeal rhabdomyosarcoma (PM-RMS) is a rare and aggressive soft tissue malignancy that primarily occurs in the head and neck region. The standard treatment approach for RMS involves a multimodal therapy regimen, which includes surgery, chemotherapy, and radiotherapy. However, the routine use of radiotherapy and chemotherapy in young patients with RMS in the head and neck region can lead to adverse effects on dental development and thereby, pose a challenge in planning dental intervention. CASE PRESENTATION: This case report outlines the dental and facial developmental consequences in a 13-year-old child, who received chemo-radiotherapeutic intervention at the age of 7 years for the management of PM-RMS. Following treatment, the child exhibited significant dental complications, including arrested root growth and restricted mouth opening. CONCLUSIONS: This case highlights the necessity for interdisciplinary collaboration between oncologists, dentists, and other healthcare professionals to mitigate the adverse effects on dental health and overall quality of life in patients undergoing chemo-radiotherapy for rhabdomyosarcoma.

Characteristics, management and outcome of patients with late-arrival STEMI in the Acute Coronary Syndrome Israeli Surveys (ACSIS).

Introduction: Patients with ST-elevation myocardial infarction (STEMI) and late arrival (>12 h) after symptom onset, are at high risk for mortality and heart failure and represent a challenge for management. We aimed to define patient characteristics, management, and outcome of late-arrival STEMI in Israel over the last 20 years. Methods: We analyzed data of late-arrival STEMI (12-48 h and > 48 h) from the biennial acute coronary syndrome Israeli Surveys (ACSIS), as well as time-dependent changes [early (2000-2010) Vs. late (2013-2021) period]. Results: Data regarding time from symptom onset to hospital arrival was available in 6,466 STEMI patients. Of these, 9.6 % arrived 12-48 h and 3 % >48 h from symptom onset. Late-arrival patients were more likely to be older women with diabetes and high GRACE score and less likely to have prior myocardial infarction.In recent years, 95 % of patients arriving 12-48 h and 96 % of those arriving > 48 h had coronary angiography, as opposed to 75 % and 77 % in the early years (p = 0.007). Percutaneous coronary intervention (PCI) increased from 60 % and 55 % respectively to 85 % (p ≤ 0.001).TIMI-3 flow after primary PCI was 89-92 %, irrespective of arrival time. Late arrival patients (12-48 h but not > 48 h) who had PCI had better adjusted 1-year survival, HR 0.49 (95 %CI 0.29-0.82), p = 0.01. Conclusions: Late-arrival STEMI patients have higher risk characteristics. Most late-arrival patients undergo coronary angiography and PCI and have TIMI-3 flow after primary PCI. In patients arriving 12-48 h after symptom onset PCI is associated with better survival.

A Systematic Review of Palliative Care Needs in Young-Onset Dementia.

BACKGROUND: The distinctive differences in clinical needs and disease trajectory between persons with young-onset (YOD) and late-onset dementia (LOD) make dementia palliative care unique. Limited studies have reported on the differences in palliative care needs between YOD and LOD, and the optimal time point to introduce palliative care in YOD remains controversial. We performed a systematic review to summarize key issues surrounding palliative care in YOD and highlight unmet needs in this pertinent area. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed database for all studies published between January 2000 and July 2022 that reported on palliative care in YOD. RESULTS: Of 32 records identified, 8 articles were eligible for inclusion. The top 3 themes extracted centered around (1) clinical differences between YOD and LOD, (2) symptoms and causes of death in end-stage YOD, and (3) the importance of early advanced care planning (ACP). YOD diagnosis is often delayed and persons with YOD have fewer somatic comorbidities but more neuropsychiatric symptoms, longer survival times, and a more malignant disease course. Persons with YOD and their families face unique psychosocial challenges when symptoms start at a younger age. End-stage YOD is not dissimilar to LOD where patients suffer from a broad spectrum of physical and psychological symptoms requiring palliation. Early initiation of ACP discussion is crucial in YOD given the more rapid progression of disease affecting cognition and decision-making capacity; however, rates of ACP completion in YOD remain low. CONCLUSIONS: Given the complex care needs and more rapid disease trajectory in YOD, palliative care in YOD should be considered from the time of diagnosis, and to be incorporated into routine dementia care.

Adult Pompe disease: Analysis of 13 patients. / Enfermedad de Pompe del adulto: análisis de 13 pacientes.

INTRODUCTION: Pompe Disease (PD) is a lysosomal disorder caused by a deficiency of the enzyme acid alpha-glucosidase (GAA), primarily manifesting as a progressive myopathy with early respiratory involvement. Enzyme replacement therapy (ERT) is available since 2006. MATERIALS AND METHODS: We describe 13 patients with partial GAA deficiency, followed at Hospital 12 de Octubre, 8 of whom were receiving treatment. RESULTS: 8 patients exhibit symptoms, all with late onset. They display axial and proximal weakness predominantly in the lower limbs but maintain autonomous gait. Five patients require non-invasive mechanical ventilation due to respiratory insufficiency. All symptomatic patients receive ERT, and in 7/8 (87.5%), there is a decline in motor and pulmonary function after an average of 8.25 years of treatment (baseline and post-treatment FVC and 6MWT mean 86.6% vs 70.8% and 498 vs 430 meters, respectively). CONCLUSION: Not all patients with partial GAA deficiency experience symptoms of PD, and symptomatic patients, despite ERT with recombinant alpha-glucosidase, mostly experience a gradual decline in motor and respiratory function.

Early, typical, and late talkers: an exploratory study on predictors of language development in the first two years of life.

Background: The consensus in scientific literature is that each child undergoes a unique linguistic development path, albeit with shared developmental stages. Some children excel or lag behind their peers in language skills. Consequently, a key challenge in language acquisition research is pinpointing factors influencing individual differences in language development. Methods: We observed children longitudinally from 3 to 24 months of life to explore early predictors of vocabulary size. Based on the productive vocabulary size of children at 24 months, 30 children met our sample selection criteria: 10 late talkers and 10 early talkers, and we compared them with 10 typical talkers. We evaluated interactive behaviors at 3, 6, 9 and 12 months, considering vocal production, gaze at mother's face, and gestural production during mother-child interactions, and we considered mothers' report of children's actions and gestures and receptive-vocabulary size at 15 and 18 months. Results: Results indicated early precursors of language outcome at 24 months identifiable as early as 3 months in vocal productions, 6 months for gaze at mother's face and 12 months for gestural productions. Conclusions: Our research highlights both theoretical and practical implications. Theoretically, identifying the early indicators of belonging to the group of late or early talkers underscores the significant role of this developmental period for future studies. On a practical note, our findings emphasize the crucial need for early investigations to identify predictors of vocabulary development before the typical age at which lexical delay is identified.

Cardiac sarcoidosis treated with nonsteroidal immunosuppressive therapy.

Background: Nonsteroidal immunosuppressive therapy is a potential therapeutic strategy for cardiac sarcoidosis. However, it is not recommended as an established treatment option. This study aimed to demonstrate the clinical outcomes of patients with cardiac sarcoidosis using nonsteroidal immunosuppressants through the ILLUstration of the Management and PrognosIs of JapaNese PATiEnts with Cardiac Sarcoidosis multicenter retrospective registry. Methods: From a cohort of 512 patients, 426 who received corticosteroid therapy and 26 who received other immunosuppressive therapy were included for analysis. Clinical outcomes included all-cause death, fatal ventricular arrhythmic events (FVAE), and worsening heart failure with hospitalization. Results: Nonsteroidal immunosuppressants were used for retained fluorodeoxyglucose uptake in the heart (n = 14), corticosteroid side effects (n = 7), ventricular arrhythmia (n = 4), complete atrioventricular block (n = 2), worsened extracardiac sarcoidosis (n = 2), and other reasons (n = 2). They comprised of methotrexate (n = 20), cyclosporine (n = 2), cyclophosphamide (n = 2), and azathioprine (n = 3). After the addition of a nonsteroidal immunosuppressant, corticosteroids were reduced in 14 of 26 patients (5 [5-17] mg), although no patient discontinued corticosteroids. Of the 14 patients, decreased fluorodeoxyglucose uptake was observed in seven at follow-up. Clinical outcomes were observed in 11 patients (42.3 %). Detected events included all-cause death in five patients (19.2 %), FVAE in four (15.4 %), and worsening heart failure with hospitalization in five (19.2 %), with some overlap. Conclusions: Nonsteroidal immunosuppressive therapy may be a possible treatment option for patients who are not stabilized with corticosteroids alone or develop corticosteroid side effects.

Novel de novo SPAST mutation in a Han Chinese SPG4 patient: a case report.

Spastic paraplegia type 4 (SPG4), the predominant form of Autosomal Dominant Hereditary spastic paraplegia (AD-HSP), is characterized by variants in the SPAST gene. This study reports a unique case of a late-onset SPG4 in a Han Chinese male, manifesting primarily as gait disturbances from lower extremity spasticity. Uncovered through whole-genome sequencing, a previously undocumented frameshift variant, c.1545dupA in exon 14 of the SPAST gene, was identified. Notably, this variant was absent in asymptomatic parents with confirmed paternity and maternity status, suggesting a de novo variant occurrence. This discovery emphasizes the potential of de novo variants to exhibit a late-onset pure pattern, extending the SPG4 variant spectrum, and consideration of such variants should be given in HSP patients with a negative family history.

Blunted sensitivity to expected value during risky decision making in individuals with problematic pornography use.

Background and aims: Neurobiological models of addiction posit that addiction manifests through an amplified salience towards addiction-associated stimuli and a diminished responsiveness to non-addiction-related incentives. However, existing research on reward processing in individuals with problematic pornography use (PPU) has primarily been limited to sexual cue reactivity. Methods: In this event-related potential (ERP) study, we employed a risky decision-making task involving 30 individuals with PPU and 33 healthy controls (HCs) to examine the effects of PPU on non-pornographic (money) reward valuation. Results: Compared to HCs, individuals with PPU exhibited compromised sensitivity to monetary rewards. Specifically, while the HC group demonstrated a differential response in late positive potential (LPP) amplitude to various expected value (EV) levels, this pattern was absent in the PPU group. This impairment was associated with poorer adaptive decision-making, as evidenced by PPU participants' inability to adjust risk choices based on changes in EV, leading to a propensity for riskier decisions in disadvantageous situations. Discussion and conclusions: The findings of impaired monetary evaluation in individuals with PPU may potentially explain why they continually pursue pornographic rewards while showing insensitivity to other rewards in daily life. Consequently, treatment development strategies may prioritize improving sensitivity to non-pornographic rewards within this population.

Spatial analysis and characteristics of persistent late potentials after ablation of scar-related VT substrate- implications for late potential elimination as a procedural endpoint with high-resolution mapping.

BACKGROUND: Late potential elimination has been proposed as a surrogate endpoint for scar-related VT ablation procedures. The characteristics, distribution, and predictors of persistent LPs (pLP) after ablation have not been studied. OBJECTIVE: We sought to characterize the spatial distribution and features of pLP after catheter ablation of VT substrate with high-resolution mapping. METHODS: Cases of scar-related VT ablation with adequate pre- and post-ablation electroanatomical maps (EAM) acquired exclusively using a high-density grid (HDG) catheter were reviewed from 2021-2023. RESULTS: A total of 62 EAM (pre- and post-ablation) from 31 cases using HDG were reviewed. Persistent late potentials (pLP) were observed in 19 cases after ablation (61%). New LP, spatially distinct from pre-ablation LP, at the periphery of the ablation area comprised the majority of pLP (16/19, 84%). Isolated pLP were more prevalent than fractionated pLP with a median amplitude of 0.26mV (0.09-0.59mV). The presence of pLP was associated with a significantly lower LVEF and septal ablation but not low voltage, late potential, or ablation area as compared to absence of pLP (22.8±7.8% vs 31.5±8.0% [p =0.008] for LVEF, and 83% vs 44% [p = 0.033] for septal ablation). CONCLUSIONS: Formation of spatially distinct new LP after targeted VT ablation is common especially in patients with lower LVEF and septal substrate independent of ablation burden. This finding highlights the limitations of complete LP elimination as an endpoint to VT ablation procedures.

Long-term observation of patients with advanced late-onset Pompe disease undergoing enzyme replacement therapy: A 15-year observation in a single center.

BACKGROUND: There have been few descriptions in the literature on long-term enzyme replacement therapy (ERT) in patients with advanced late-onset Pompe disease (LOPD). OBJECTIVES: This study aimed to assess the efficacy and limitations of ERT in advanced LOPD patients. METHODS: We retrospectively reviewed the clinical courses of patients with advanced LOPD (two juvenile-onset and five adult-onset patients) who were treated with recombinant human alglucosidase alfa to examine improvements achieved with and limitations of ERT until their death or when switching to avalglucosidase alfa occurred. RESULTS: All patients were non-ambulant and ventilator dependent. The duration of follow-up ranged from 3.7 to 15.0 years (median 9.0 years). All patients reported improvements in their lives during the first two or three years of ERT. Vital capacity was clearly improved in patients with relatively spared respiratory function, although it deteriorated after respiratory complications such as pneumothorax. Pinch and grip power tended to be preserved during the treatment period. Muscle CT revealed progression of atrophy and fatty replacement predominantly in the proximal limb muscles without improvement after ERT. Four patients died due to aspergillosis, respiratory failure, ileus, and sudden death of unknown cause. CONCLUSIONS: Our findings demonstrate that patients undergoing ERT show certain improvements, even in the advanced stage of Pompe disease. Respiratory complications are lethal even during ERT, and early diagnosis and induction of therapy are critical. Muscle wasting progressed more severely in the proximal limbs, even after ERT.

Baicalin ameliorates heat stress-induced hepatic injury and intestinal microecology dysbiosis in late gestational mice.

Heat stress (HS) disrupts intestinal microbiota, glycolipid metabolism, and hepatic mitochondrial function in late gestational mice. Baicalin (BAI), a Chinese herbal medicine known for its heat-clearing and anti-inflammatory properties, has shown promise in modulating intestinal microecology and mitigating inflammation in various organs. This study investigates whether baicalin attenuates HS-induced intestinal microbial dysbiosis and liver damage in pregnant mice during late gestation. Twenty-four pregnant mice were randomly assigned to four groups, including thermoneutral (TN) (24 ± 1 ℃), HS (35 ± 1 ℃), HS+BAI200 (oral gavaged with 200 mg/kg BW of BAI), and HS+BAI400 (oral gavaged with 400 mg/kg BW of BAI). 400 mg/kg BAI treatment markedly decreased the rectal temperature and increased fetal weight in HS pregnant mice. Furthermore, 400 mg/kg BAI administration effectively ameliorated HS-induced hepatic damage and lipid disorders, reducing HSP70, AST, and ALT levels while increasing TG concentration. Notably, it activated a network of genes involved in lipid synthesis, including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and oxidation, such as peroxisome proliferator-activated receptor alpha (PPARα), carnitine palmityl transferase 1 beta (CPT1ß). Moreover, BAI intervention restored the intestinal morphology and barrier function, evidenced by increased intestinal villus height, the ratio of villus height to crypt depth, and colonic goblet cells numbers. 400 mg/kg of BAI treatment up-regulated the expression of tight junction proteins, such as claudin-1 and Zonula Occludens-1 (ZO-1), in the jejunum and ileum, counteracting HS-induced downregulation. High-throughput sequencing showed that BAI treatment altered cecal microbial composition, increasing the relative abundance of beneficial Bacteroidota and decreasing Deferribacterota, Turicibacter, and Akkermansia. Spearman's correlation analysis highlighted significant correlations between differential cecal microbiota and physiological indexes. In conclusion, BAI administration alleviated adverse impacts in heat-exposed mice during late gestation, improving maternal physiological parameters, and ameliorating hepatic damage with altered cecal microbial composition. The findings suggest that BAI may regulate the gut-liver axis by modulating intestinal morphology, microecology, and hepatic function.

Drug Survival on First Biologic Therapy Among Late-Onset Rheumatoid Arthritis Patients Compared to Early-Onset Patients: A Population-Based Cohort Study.

INTRODUCTION: Rheumatoid arthritis (RA) patients can be divided according to the age of disease onset and classified as late-onset RA ≥ 60 years old or early-onset RA < 60 years old. Current treatment guidelines do not stipulate any preference regarding the biologic that should be used first in the late-onset group. This study aims to compare the drug survival times on first biological treatment between late and early-onset RA patients. METHODS: This is a population based cohort study using the medical records of Leumit healthcare services. We included all eligible RA patients between 2000 and 2017. RA patients were divided into late- and early-onset RA groups and compared according to drug survival time on the first biological therapy. RESULTS: The final cohort included 3814 RA patients, 2807 (73.6%) of whom had early-onset RA. Overall, biologic disease-modifying anti-rheumatic drugs (bDMARDs) were used more often among early-onset compared to late-onset patients (16.9% vs. 7.8%, p < 0.001). Among early-onset patients, etanercept was associated with the longest drug survival time on the first biologic, and adalimumab and infliximab were associated with the longest drug survival times among late-onset patients. No differences were observed in drug survival times between late and early-onset patients on the first bDMARD, except for abatacept and golimumab with longer drug survival time among early-onset patients. CONCLUSION: Late-onset RA patients were treated with biologics to a lesser extent than early-onset patients, but no differences were observed in drug survival times at the first bDMARD between the two groups.

Late-onset relapsing neurotoxicity after Brexucabtagene autoleucel associated with high chimeric antigen receptor T cells in cerebrospinal fluid.

BACKGROUND AIMS: Mounting evidence suggests that persistent cell expansion is the main driver for both efficacy and toxicity of chimeric antigen receptor (CAR) T-cell therapy. Hereby, we describe a case of delayed recurrent neurotoxicity associated with late CAR T-cells re-expansion. CASE DESCRIPTION: A 44-year-old man suffering from mantle cell lymphoma received brexu-cel. After infusion, he developed grade 2 cytokine release syndrome. On day +11, grade 3 neurotoxicity was reported and high-dose methylprednisolone was started with a complete resolution of neurological manifestations. On day +30, he experienced a late-onset CAR T-cell toxicity associated with CAR T-cell re-expansion. The patient was treated with tocilizumab and dexamethasone, with resolution of symptoms. On day +58, he was readmitted for new onset of neurotoxicity. Notably, a new CAR T-cell expansion was observed, with an unexpectedly elevated cerebrospinal fluid/blood ratio. The patient was promptly treated with dexamethasone and then escalated to high-dose methylprednisolone and anakinra, with resolution of his neurologic condition noted. CONCLUSIONS: CAR T-cell-related neurotoxicity usually has an early monophasic course. To our knowledge, this is the first case of late-onset, recurrent neurotoxicity. Moreover, an elevated level of cerebrospinal fluid CAR T cells was observed, which may suggest that the delayed neurotoxicity was primarily caused by the brain infiltration of CAR T cells rather than driven by cytokine-mediated neuroinflammation.

Automated cardiovascular MR myocardial scar quantification with unsupervised domain adaptation.

Quantification of myocardial scar from late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) images can be facilitated by automated artificial intelligence (AI)-based analysis. However, AI models are susceptible to domain shifts in which the model performance is degraded when applied to data with different characteristics than the original training data. In this study, CycleGAN models were trained to translate local hospital data to the appearance of a public LGE CMR dataset. After domain adaptation, an AI scar quantification pipeline including myocardium segmentation, scar segmentation, and computation of scar burden, previously developed on the public dataset, was evaluated on an external test set including 44 patients clinically assessed for ischemic scar. The mean ± standard deviation Dice similarity coefficients between the manual and AI-predicted segmentations in all patients were similar to those previously reported: 0.76 ± 0.05 for myocardium and 0.75 ± 0.32 for scar, 0.41 ± 0.12 for scar in scans with pathological findings. Bland-Altman analysis showed a mean bias in scar burden percentage of -0.62% with limits of agreement from -8.4% to 7.17%. These results show the feasibility of deploying AI models, trained with public data, for LGE CMR quantification on local clinical data using unsupervised CycleGAN-based domain adaptation. RELEVANCE STATEMENT: Our study demonstrated the possibility of using AI models trained from public databases to be applied to patient data acquired at a specific institution with different acquisition settings, without additional manual labor to obtain further training labels.

Late-onset capsular bag distension syndrome 33 years after cataract surgery.

Purpose: Describe the clinical features and management of this uncommon case of late-onset Capsular bag distension syndrome that occurred 33 years after cataract surgery. Observation: An 87-year-old male was referred to our clinic complaining of blurred and gradual, painless reduction in vision in his left eye over the past year. A complete ophthalmological examination, Ultrasound biomicroscopy (UBM), anterior segment optical coherence tomography (AS-OCT), and optical biometry were performed to confirm the diagnosis. A 25-gauge pars plana vitrectomy combined with posterior capsulotomy was performed. The aspirated fluid was sent for microbiological analyses. After surgery, the patient's visual acuity returned to previous values, and anterior chamber depth slightly deepened. Samples taken were negative for bacteria. Conclusions and Importance: Late-onset Capsular bag distension syndrome may occur up to 33 years following cataract surgery. A surgical approach offers the advantage of complete clearance of the turbid fluid, also removing the residual cortical material and enabling microbial and pathological testing.

Better performance of the APPLE score for the prediction of very early atrial fibrillation recurrence post-ablation.

BACKGROUND: The benefits of rhythm control in the early atrial fibrillation (AF) are increasingly recognized. This study aimed to investigate whether early AF ablation contributes to long-term sinus rhythm maintenance and to identify a suitable predictive score. METHODS: According to the diagnosis-to-ablation time, this study prospectively enrolled 245 very early AF patients, 262 early AF patients, and 588 late AF patients for radiofrequency ablation from June 2017 to December 2022. Clinical data, risk scores and follow-up results were collected and analyzed. RESULTS: Baseline characteristics were similar among the three cohorts. During a median follow-up period of 26 months, AF recurrence was observed in 61 (24.9%), 66 (25.2%), and 216 (36.7%) patients in the very early, early, and late AF cohorts, respectively. In the multivariable-adjusted model, very early and early AF were associated with a reduced risk of AF recurrence, with hazard ratios of 0.72 (95% confidence interval [CI]: 0.52-0.99) and 0.57 (95% CI: 0.41-0.78), respectively. The APPLE score demonstrated the highest predictive power for very early AF, with an area under the curve (AUC) of 0.74. However, its predictive power decreased with time from diagnosis, and a low predictive power for late AF (AUC=0.58). In addition, the time-dependent concordance index showed consistent results. For very early AF, the Akaike information criterion and decision curve analysis showed that APPLE had the highest predictive value. CONCLUSION: Very early AF ablation was associated with a lower recurrence rate, and the APPLE score can provide a higher predictive value for them. (URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR-OIN-17013021).