Citations

AimsKikuchi‐Fujimoto disease (KFD) is a rare disease that typically manifests with fever and cervical lymphadenopathy. Little is known about the risk factors associated with recurrence and their correlation with clinicopathologic features.Methods and ResultsWe analysed 112 patients with KFD, predominantly female (61/112, 54.5%), with an average age of 29.4 years. The incidence was higher in males up to the age of 20 and higher in females from their 30s onwards. Of the 70 patients with follow‐up data, 23% experienced recurrence. Recurrence was associated with lower C4 levels (P = 0.038) and higher antinuclear antibody (ANA) rates (P = 0.007) compared to transient disease. The mean duration of symptoms was 71.5 days. Lymph node histology in 98 cases (excluding 14 needle biopsy specimens) was classified into three patterns: proliferative (n = 75, 77%), necrotizing (n = 22, 22%), and xanthomatous (n = 1, 1%). The necrotizing pattern associated with significantly enlarged lymph nodes (P = 0.047) and a longer symptom duration (P = 0.009) than the proliferating pattern. The number of CD4‐positive lymphocytes was significantly lower in the necrotizing type than in the proliferative type (P < 0.001).ConclusionThese results indicated that low C4 levels and positive ANA were associated with KFD recurrence. Although the aetiology of KFD remains elusive, given that some cases develop autoimmune disease, the results suggest that patients with recurrent KFD represent an intermediate status between those with transient KFD and those with overt autoimmune disease. The comprehensive clinicopathological findings of this study may be useful for elucidating its pathogenesis and predicting the clinical course.

Abstract Background Percutaneous endoscopic gastrostomy (PEG) and percutaneous radiologic gastrostomy (PRG) are used for gastric drainage, decompression, and feeding. Recent innovations enable bumper and balloon‐type tube placement via transabdominal approach under guidance of fluoroscopy or sonography. Method This is a single‐center retrospective cohort study to evaluate the outcomes of balloon and bumper gastrostomy tube placement under guide of fluoroscopy and ultrasound. The total sample size was 470 consecutive patients. The eligibility criteria included all patients aged ≥18 years who underwent a balloon or bumper‐type gastrostomy tube insertion for nutrition support in both the interventional radiology unit and at the bedside between 2017 and 2022. Result This study revealed no significant differences between the two types of tubes in terms of time to tube replacement or requiring a gastrostomy tube. There was a positive correlation between the time that a patient has a gastrostomy tube and major complications ( P = 0.005) and a positive correlation between number of tubes replaced and minor complications ( P < 0.001). Both types of tubes were associated with low rates of complications. However, patients with a balloon tube were more likely to experience gastric‐tube–related hospitalization/ED visits and require a >24‐h hospital stay postoperation. Conclusion These findings can help healthcare providers make informed decisions when selecting the appropriate type of tube for their patients to have more durability with less complication.

Abstract Despite recent approval of monoclonal antibodies that reduce amyloid (Aβ) accumulation, the development of disease-modifying strategies targeting the underlying mechanisms of Alzheimer’s disease (AD) is urgently needed. We demonstrate that mitochondrial complex I (mtCI) represents a druggable target, where its weak inhibition activates neuroprotective signaling, benefiting AD mouse models with Aβ and p-Tau pathologies. Rational design and structure‒activity relationship studies yielded novel mtCI inhibitors profiled in a drug discovery funnel designed to address their safety, selectivity, and efficacy. The new lead compound C458 is highly protective against Aβ toxicity, has favorable pharmacokinetics, and has minimal off-target effects. C458 exhibited excellent brain penetrance, activating neuroprotective pathways with a single dose. Preclinical studies in APP/PS1 mice were conducted via functional tests, metabolic assessment, in vivo 31 P- NMR spectroscopy, blood cytokine panels, ex vivo electrophysiology, and Western blotting. Chronic oral administration improved long-term potentiation, reduced oxidative stress and inflammation, and enhanced mitochondrial biogenesis, antioxidant signaling, and cellular energetics. These studies provide further evidence that the restoration of mitochondrial function and brain energetics in response to mild energetic stress represents a promising disease- modifying strategy for AD.

ABSTRACT Atraumatic and precise drug delivery to arteries and veins remains an unmet need in interventional medicine, with significant implications for managing vascular diseases and long-term patient outcomes. Conventional endovascular methods, such as drug-coated balloons and drug-eluting stents, often damage vessel endothelium and compromise wall integrity, leading to reduced therapeutic efficacy and severe complications including restenosis and thrombosis. To address these limitations, we introduce EndoBot, an untethered soft millirobot designed for atraumatic vessel navigation and localized drug delivery under physiological blood flow. EndoBot achieves this through magnetically actuated corkscrew propulsion and mechanically adaptive surface crawling, exerting low radial pressure (< 1 kPa) to preserve endothelial integrity. We validated its performance in phantom vessels, ex vivo human umbilical veins under normothermic perfusion, and in vivo rat inferior vena cava under fluoroscopic guidance using a human-scale magnetic manipulation platform. Despite dynamic vessel contractions and compressions along non-uniform cross-sections, mechanically adaptive locomotion strategy ensures safe navigation and protects the inner endothelial lining. EndoBot is deployable and retrievable via clinical vascular sheaths and remains stable even under supra-physiological blood flow conditions (> 155 cm/s). Extensive blood compatibility tests demonstrated minimal hemolysis (<0.01%), low platelet activation on the robot surface, and no increased coagulation tendency. For drug delivery, a hydrophobic transfer coating enables EndoBot to gently deposit a stable, flow-resistant drug layer onto the vessel wall without fragmentation. This novel platform enables safer and more effective targeted endovascular drug delivery, paving the way for transformative approaches to address early-stage vascular pathologies and deliver more effective preventive interventions.

This cohort study examines changes in oxygen consumption among patients with multiple morbidities undergoing cardiac rehabilitation.

ImportanceMyeloperoxidase is one of the most abundant peroxidase enzymes in activated myeloid cells. Myeloperoxidase inhibitors may have a clinical benefit in amyotrophic lateral sclerosis (ALS) by slowing neurodegeneration via reduced neuroinflammation and oxidative stress.ObjectiveTo determine the safety, tolerability, and efficacy of verdiperstat, a selective myeloperoxidase inhibitor, in ALS.Design, Settings, and ParticipantsVerdiperstat was tested as a regimen of the HEALEY ALS Platform Trial, a multicenter, double-blind, perpetual platform design, randomized clinical trial, with sharing of trial infrastructure and placebo data across multiple regimens. The study was conducted at 54 ALS referral centers across the US from July 2020 to April 2022. Adult participants with a diagnosis of clinically possible, probable, laboratory-supported probable, or definite ALS defined by the revised El Escorial criteria were randomized to verdiperstat or regimen-specific placebo. An additional group of participants concurrently randomized to placebo from other regimens was included in the analyses.InterventionsEligible participants were randomized in a 3:1 ratio to receive oral verdiperstat, 600 mg, twice daily or matching placebo for a planned placebo-controlled duration of 24 weeks.Main Outcomes and MeasuresThe primary efficacy outcome was change from baseline through week 24 in disease severity, as measured by a joint model of ALS Functional Rating Scale–Revised and survival, with the treatment effect quantified by the disease rate ratio (DRR), with DRR less than 1 indicating a slowing in disease progression of verdiperstat relative to placebo.ResultsA total of 167 participants (mean [SD] age, 58.5 [11.4] years; 59 [35.3%] female; 108 [64.6%] male) were randomized to either verdiperstat (126 [75.4%]) or to placebo (41 [25.6%]). Among the participants randomized to the verdiperstat regimen, 130 (78%) completed the trial. The estimated DRR was 0.98 (95% credible interval, 0.77-1.24; posterior probability = 0.57 for slowing of disease progression [DRR &amp;lt;1]). Verdiperstat was estimated to slow progression by 2% vs placebo (95% credible interval, −23% to 24%; posterior probability 0.57). Verdiperstat was overall safe and well tolerated. Common adverse events in the verdiperstat group were nausea, insomnia, and elevated thyrotropin levels.Conclusions and RelevanceResults demonstrate that treatment with verdiperstat was unlikely to alter disease progression in ALS.Trial RegistrationClinical Trial Identifiers: NCT04297683 and NCT04436510

ImportanceAmyotrophic lateral sclerosis (ALS) is a fatal disease. The sigma-1 (σ1) receptor emerged as a target for intervention.ObjectiveTo determine the effects of pridopidine, a σ1-receptor agonist, in ALS.Design, Settings, and ParticipantsPridopidine was tested as a regimen of the HEALEY ALS Platform Trial, a phase 2/3, multicenter, randomized, double-blind, platform trial. The study was conducted at 54 sites in the US from January 2021 to July 2022 (final follow-up, July 14, 2022). A total of 163 participants with ALS were randomized to receive pridopidine or placebo. An additional 122 concurrently randomized participants were assigned to receive placebo in other regimens and included in the analyses.InterventionsEligible participants were randomized 3:1 to receive oral pridopidine 45 mg twice daily (n = 121) or matching oral placebo (n = 42) for a planned duration of 24 weeks.Main Outcomes and MeasuresThe primary efficacy outcome was change from baseline through week 24 in ALS disease severity, analyzed using a bayesian shared parameter model, which has components for function (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS-R]) and survival that were linked through an integrated estimate of treatment-dependent disease slowing across these 2 components. This was denoted as the disease rate ratio (DRR), with DRR less than 1 indicating a slowing in disease progression on pridopidine relative to placebo. There were 5 key secondary end points: time to 2-point or greater reduction in ALSFRS-R total score among participants with bulbar dysfunction at baseline, rate of decline in slow vital capacity among participants with bulbar dysfunction at baseline, percentage of participants with no worsening in the ALSFRS-R bulbar domain score, time to 1-point or greater change in the ALSFRS-R bulbar domain score, and time to death or permanent assisted ventilation.ResultsAmong 162 patients (mean age, 57.5 years; 35% female) who were randomized to receive the pridopidine regimen and included in the primary efficacy analysis, 136 (84%) completed the trial. In the primary analysis comparing pridopidine vs the combined placebo groups, there was no significant difference between pridopidine and placebo in the primary end point (DRR, 0.99 [95% credible interval, 0.80-1.21]; probability of DRR &amp;lt;1, 0.55) and no differences were seen in the components of ALSFRS-R or survival. There was no benefit of pridopidine on the secondary end points. In the safety dataset (pridopidine, n = 121; placebo, n = 163), the most common adverse events were falls (28.1% vs 29.3%, respectively) and muscular weakness (24.0% vs 31.7%, respectively).Conclusions and RelevanceIn this 24-week study, pridopidine did not impact the progression of ALS.Trial RegistrationClinicalTrials.gov Identifiers: NCT04297683, NCT04615923

Background: Unmet social needs may hinder health care providers’ ability to deliver suitable care. Telehealth has emerged as a mechanism to broaden care reach; however, limited studies have examined the relationships between telehealth services and social need outcomes. This study explores the impact of telehealth services, encompassing (1) telestroke, (2) telepsychiatry and addiction treatment, (3) teleconsultation and office visits,(4) tele-intensive care units, (5) telemonitoring postdischarge, (6) ongoing chronic care management, and (7) other remote monitoring, on social need performance outcomes. Methods: The 2022 American Hospital Association annual survey and the Area Health Resource Files, which include comprehensive hospital and community indicators, were utilized. A mixed-effects logistic regression was applied, analyzing 1,005 acute care general hospitals. Results: The results revealed that patients who received telemonitoring services after discharge were 1.72 (95% confidence interval [CI]: 1.03-2.88) times more likely to achieve better health outcomes compared with those who did not receive such services. These patients also experienced a significant decrease in the likelihood of requiring additional hospital or system services, with an odds ratio of 2.39 (95% CI: 1.32-4.00). Additionally, patients utilizing telepsychiatry and addiction treatment services had 1.66 times higher odds of reporting improved community health status (95% CI: 1.22-2.27). Lastly, patients who used teleconsultation and office visit services had 38% lower odds of experiencing poor community health status (95% CI: 0.40-0.95). Discussion: The findings highlight the potential of targeted telehealth services to positively impact health outcomes, reduce health care costs, and improve community health status.

ABSTRACTBackgroundContrast‐enhanced magnetic resonance neurography (ceMRN) can enhance brachial plexus visualization and quality of imaging. However, the interval between contrast injection and scanning that provides the highest‐quality images is not known.MethodsFifteen patients underwent brachial plexus imaging using the 3D T2‐NerveView sequence with a scanning duration of 5 min. A consecutive six‐phase scan was initiated immediately at the start of contrast agent injection. Subsequently, all patients' images were classified into six groups according to the phases: group A (phase 1, delay 0 min), group B (phase 2, delay 5 min), group C (phase 3, delay 10 min), group D (phase 4, delay 15 min), group E (phase 5, delay 20 min), and group F (phase 6, delay 25 min). The image quality in each group was assessed based on nerve signal (signalnerve), muscle signal (signalmuscle), lymph node signal (signallymph node), background noise (BN), signal‐to‐noise ratio (SNR), contrast‐to‐noise ratio (CNR), and subjective score.ResultsSignalnerve, signalmuscle, BN, and SNR did not significantly differ among the six groups (p > 0.05). However, significant differences (p < 0.05) were observed in signallymph node (F = 16.067), CNR (F = 9.495), and subjective score (χ2 = 23.586). As the scanning delay increased, signallymph node intensity gradually increased whereas the CNR gradually decreased. The subjective score was significantly higher in groups B (4.83 ± 0.24), C (4.90 ± 0.21), D (4.87 ± 0.30), E (4.83 ± 0.31), and F (4.83 ± 0.31) than in group A (4.47 ± 0.30).ConclusionWe recommend performing brachial plexus ceMRN 5 min after contrast injection. With this delay, the brachial plexus can be visualized optimally with minimal interference from background signals.

Importance The etiology of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is unknown. However, neuroinflammation and complement activation may play a role in disease progression. Objective To determine the effects of zilucoplan, an inhibitor of complement C5, in individuals with ALS. Design, Setting, and Participants Zilucoplan was tested as regimen A of the HEALEY ALS Platform Trial, a phase 2 to 3 multicenter, randomized, double-blind, placebo-controlled perpetual platform clinical trial with sharing of trial infrastructure and placebo data across multiple regimens. Regimen A was conducted from August 17, 2020, to May 4, 2022. A total of 162 participants were randomized to receive zilucoplan (122 [75.3%]) or regimen-specific placebo (40 [24.7%]). An additional 124 concurrently randomized participants were randomized to receive placebo in other regimens. Interventions Eligible participants were randomized in a 3:1 ratio to receive zilucoplan or matching placebo within strata of edaravone and/or riluzole use for a planned duration of 24 weeks. Active drug (zilucoplan, 0.3 mg/kg) and placebo were provided for daily subcutaneous dosing. Main Outcomes and Measures The primary end point was change in disease severity from baseline through 24 weeks as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) total score and survival, analyzed using a bayesian shared-parameter model and reported as disease rate ratio (DRR; &amp;lt;1 indicating treatment benefit). The study included prespecified rules for early stopping for futility. Outcome analyses were performed in the full analysis set comparing the zilucoplan group with the total shared placebo group (n = 164). Results Among the 162 participants who were randomized (mean [SD] age, 59.6 [11.3]; 99 [61.1%] male), 115 (71.0%) completed the trial. The estimated DRR common to ALSFRS-R and survival was 1.08 (95% credible interval, 0.87-1.31; posterior probability of superiority, 0.24). The trial was stopped early for futility. No unexpected treatment-related risks were identified. Conclusions and Relevance In this randomized clinical trial of zilucoplan in ALS, treatment did not alter disease progression. The adaptive platform design of the HEALEY ALS Platform Trial made it possible to test a new investigational product with efficient use of time and resources. Trial Registration ClinicalTrials.gov Identifier: NCT04297683