Tardive dyskinesia (TD) is characterized by involuntary movements that develop in association with chronic use of antipsychotic medications. While second-generation antipsychotics are associated with lower risk of TD compared with first-generation antipsychotics, their widespread use across a range of chronic mental health conditions (such as psychotic disorders, autism, and mood disorders) has resulted in substantial public health burden of TD. The therapeutic landscape of managing TD has been transformed by the U.S. Food and Drug Administration (FDA) approval of two selective vesicular monoamine transporter 2 (VMAT2) inhibitors in 2017. This report reviews efficacy and safety considerations for the two FDA-approved VMAT2 inhibitors, deutetrabenazine and valbenazine, which are recommended as first-line treatment for troublesome TD in current practice guidelines. Overall, these VMAT2 inhibitors offer significant benefit to patients experiencing TD through improved health and quality of life.

To evaluate the efficacy, safety, and tolerability of esketamine nasal spray vs psychoactive placebo (oral midazolam) in rapidly reducing depressive symptoms in adolescents with major depressive disorder at imminent risk for suicide.

This double-blind, double-dummy, phase 2b study randomized (1:1:1:2) 147 adolescents (12 to <18 years old) to esketamine (28, 56, or 84 mg) or midazolam twice weekly for 4 weeks. Participants concomitantly received comprehensive standard of care, including initial hospitalization, oral antidepressant, and evidenced-based psychotherapy. The primary efficacy end point-change in Children's Depression Rating Scale-Revised (CDRS-R) total score from baseline to 24 hours post first dose-was analyzed using analysis of covariance, according to a pooled sequential multiple testing procedure.

All participants were moderately to severely depressed at enrollment; approximately 95% were moderately to extremely suicidal. Pooled esketamine doses (56 and 84 mg) showed superiority over midazolam in reducing CDRS-R total score at 24 hours post first dose (between-group difference of least squares means [95% CI]:-5.8 [-11.19,-0.35], p =.037). The between-group differences for individual esketamine 84 mg and 56 mg doses vs midazolam were -5.7 ([-12.91, 1.55], p =.123) and 5.9 ([12.25, 0.53], p =.072), respectively. Severity of suicidality, per Clinical Global Impression of Severity of Suicidality-revised (CGI-SS-R), improved in all 4 groups (between-group difference of least squares means [95% CI]:-0.2 [-0.90, 0.41], -0.3 [-0.93, 0.31], 0.0 [-0.69, 0.72] for esketamine 28, 56, and 84 mg, respectively, at 24 hours post first dose). Common adverse events (incidence ≥20%) reported for esketamine were dizziness, nausea, dissociation, headache, dysgeusia, somnolence, vomiting, hypoesthsesia, and intentional self-injury.

The primary efficacy end point of the study was met for the pooled esketamine doses (56 and 84 mg). Esketamine in conjunction with comprehensive standard of care rapidly improved depressive symptoms among adolescents at imminent risk for suicide.

This double-blind randomized controlled clinical trial compared the effects of esketamine nasal spray (28, 56, or 84 mg) to a psychoactive placebo (midazolam) in 147 adolescents with major depressive disorder who were at imminent risk for suicide. All participants also received standard-of-care treatment, including initial hospitalization, oral antidepressant treatment, and evidenced-based psychotherapy. Combined 56- and 84-mg doses of esketamine were superior to midazolam in reducing depressive symptoms at 24 hours following the first dose; all 4 treatment groups showed continued improvement in depressive symptoms and severity of suicidality after 4 weeks of treatment. The most common side effects reported for esketamine-treated participants were dizziness, nausea, dissociation, headache, bitter taste, and sleepiness.Appeared originally in J Am Acad Child Adolesc Psychiatry 2026; 65:42-55.

Hypoxemia is a common and serious complication during sedated gastrointestinal endoscopy for out- and in-patients. Though diagnostic and severity scoring systems of obstructive sleep apnea (OSA) and difficult airway assessment (DAA) are widely used to assess hypoxemia risk, there is no exclusively designed prediction model and convenient tool in real-world practice. We aimed to develop and validate a robust and accurate hypoxemia risk prediction model for pre-operative use in this context.

Using data from out-patients undergoing gastrointestinal endoscopy between May 2020 and November 2023 across seven hospitals in China with diverse regional and ethnic backgrounds, we developed and independently validated a hypoxemia risk prediction model for sedated gastrointestinal endoscopy (HAPPY-12K). The model was developed to pre-operatively predict occurrence of hypoxemia during sedated gastrointestinal endoscopy, defined as SpO₂ falling below 95% for a duration exceeding 10 s. HAPPY-12K was a logistic regression model incorporating eight predictors: body mass index, Mallampati grade, limited jaw protrusion, short thyromental distance, large tongue, history of snoring, short neck with large circumference and pre-operative mean arterial pressure. The model was constructed by a well-established 3-D modeling strategy composed of Double types of effects, Double steps of screening, and Double steps of modeling. The discriminative ability was evaluated using the area under the receiver operating characteristic curve (AUC). The model calibration was examined through calibration slope, expected-to-observed (E:O) ratio and Brier score. For clinical utility, decision curve analysis was performed to assess net benefit (NB) and net reduction (NR). Furthermore, we systematically compared HAPPY-12K with other newly developed models using scores or raw variables from questionaries of OSA and DAA using DeLong's test. This study is registered in the Chinese Clinical Trial Registry (ChiCTR2300074128).

We included 11,957 patients, divided into a Training Set (n = 2,518, hypoxemia rate 10.37%), and five validation sets (n = 9,439, hypoxemia rate raining from 8.40% to 28.45%). HAPPY-12K was developed in a Han Chinese population and exhibited satisfactory discrimination ability with AUCs ranging from 0.818 to 0.895 in external populations of the same ethnicity, and an acceptable AUC of 0.771 in a Uygur Chinese population. Although its Brier scores were satisfactory across all ethnic populations, HAPPY-12K displayed acceptable calibration (calibration slope < 1.2) in external Han Chinese populations, and good calibration (E:O ratio = 0.962) in independent homogenous populations comparable to the training set. The average NB and NR were 45.2‰ and 59.5%, respectively. It was estimated that HAPPY-12K would identify over half a million patients with truly developing hypoxemia during sedated gastrointestinal endoscopy and could help avoid over six million unnecessary interventions annually in China. Meanwhile, a head-to-head comparison revealed that HAPPY-12K outperformed other models. HAPPY-12K has been implemented as an interactive online tool available at http://bigdata.njmu.edu.cn/HAPPY-12K/.

HAPPY-12K could enable efficient and precise hypoxemia risk assessment before sedated gastrointestinal endoscopy, providing timely alerts for high-risk outpatients.

National Natural Science Foundation of China; Noncommunicable Chronic Diseases-National Science and Technology Major Project; Science and Technology Project of Jiangsu Disease Control and Prevention Administration; Science and Technology Development Project of Nanjing Medical University; Priority Academic Program Development of Jiangsu Higher Education Institutions; and Outstanding Young Level Academic Leadership Training Program of Nanjing Medical University.

Glycemic control is a critical component in the management of diabetes mellitus among children and adolescents. This narrative review synthesizes existing evidence on the status of glycemic control-both good and poor-and its associated factors among Ethiopian children and adolescents living with diabetes. The objective of the review was to assess the pattern of glycemic control and identify factors associated with both good and poor glycemic outcomes among children and adolescents with diabetes in Ethiopia. Relevant studies reporting on glycemic control and associated factors were identified through searches conducted in Google Scholar, PubMed/MEDLINE, African Journals Online, and the Ethiopian Medical Journal. Additional grey literature sources were also reviewed. Eligible studies were screened and narratively synthesized. The prevalence of poor glycemic control among Ethiopian children and adolescents ranged from 39.3% to 89.3%. Conversely, good glycemic control was reported in 16.4% to 60.7% of participants. Factors associated with glycemic control included socio-demographic characteristics, treatment-related variables, health system constraints, and dietary habits. Poor glycemic control is widespread among Ethiopian children and adolescents with diabetes, underscoring the urgent need for improved management strategies and targeted interventions. Strengthening diabetes education, promoting self-monitoring of blood glucose, and improving access to essential medical supplies and insulin may help enhance glycemic outcomes.

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β-cells, necessitating lifelong insulin therapy. While islet transplantation has demonstrated efficacy in restoring glycemic control, donor scarcity and the requirement for chronic immunosuppression limit its widespread application. Recent advances in stem cell biology, bioengineering, and immunomodulation have catalyzed a paradigm shift toward stem cell-derived β-cell replacement therapies. This narrative review presents recent clinical trials and technological innovations in cell-based therapies for T1D, with particular emphasis on stem cell-derived islet generation, encapsulation strategies for immunoprotection, and emerging clinical evidence. Landmark clinical trials and pioneering work with chemically induced pluripotent stem cells have demonstrated proof-of-concept for insulin independence and glucose-responsive C-peptide secretion. Encapsulation technologies, ranging from macroencapsulation devices to microencapsulation with bioactive materials, aim to eliminate the need for systemic immunosuppression while protecting grafts from immune rejection. Despite promising early results, challenges including fibrosis, vascularization, long-term graft survival, and scalable manufacturing remain. This review provides a comprehensive overview of the current state of cell-based therapies for T1D and outlines future directions for translating these innovations into routine clinical practice.

Parkinson's disease (PD) and type 2 diabetes mellitus (T2DM) are increasingly recognized as comorbid conditions. Epidemiological evidence suggests that T2DM is associated with faster PD progression, but the biological processes that may connect these disorders remain incompletely understood. Oxidative stress is a shared pathological feature of both diseases, and the DJ-1/Nrf2/HO-1 pathway is an important antioxidant defence system.

To determine whether T2DM is associated with more severe PD-like neurodegeneration and whether these changes are accompanied by reduced DJ-1/Nrf2/HO-1 antioxidant signalling in a mouse model of PD-T2DM comorbidity.

Male C57BL/6 mice were assigned to control, T2DM, PD, or PD + T2DM groups. T2DM was induced by high-fat diet feeding combined with streptozotocin injection; PD was induced by unilateral intrastriatal 6-hydroxydopamine injection. Behavioural performance was assessed using rotarod and apomorphine-induced rotation tests. Nigrostriatal pathology was examined by haematoxylin-eosin, Nissl, and tyrosine hydroxylase immunohistochemistry. Oxidative stress markers (SOD, MDA, GSH) and DJ-1/Nrf2/HO-1 protein expression were measured in substantia nigra-striatum and serum. Final analyses included 10 control, 9 T2DM, 9 PD, and 9 PD + T2DM mice, with assay-specific sample sizes indicated in the Methods and figure legends.

Compared with PD mice, PD + T2DM mice exhibited shorter rotarod latency, greater dopaminergic neuron loss, and stronger nigrostriatal oxidative stress (P < 0.05). DJ-1, Nrf2, and HO-1 expression was reduced in the substantia nigra-striatum of disease groups relative to controls, with Nrf2 and HO-1 significantly lower in PD + T2DM than in PD mice. Protein expression correlated positively with rotarod latency and antioxidant indices, and negatively with MDA content and fasting glucose. Serum oxidative stress markers showed similar directional trends, but most between-group differences were not statistically significant.

In this combined toxin- and metabolism-based mouse model, T2DM was associated with more severe PD-like motor impairment and dopaminergic neuron loss, accompanied by reduced DJ-1/Nrf2/HO-1 antioxidant signalling and increased nigrostriatal oxidative stress. These findings are consistent with the possibility that impaired antioxidant defence contributes to PD-T2DM comorbidity, while causal pathway involvement requires confirmation by future gain- or loss-of-function studies.

This study aims to evaluate the demographic characteristics, anatomical distribution, diagnostic and treatment patterns, postoperative complications, recurrence rates, and recurrence-associated factors in patients diagnosed with tenosynovial giant cell tumors (TGCTs).

A total of 246 patients diagnosed with TGCT and treated between January 2010 and March 2021, were retrospectively analyzed. Pre- and postoperative data of the patients were recorded. Histopathological diagnosis was reviewed, and tumors were classified as localized TGCT and diffuse-type TGCT. Recurrence was defined as the reappearance of a lesion at the same location following an initially complete surgical excision. Survival time was defined as the time elapsed since surgery. Recurrence-free survival was calculated from the date of the surgical procedure to the date of recurrence or the last follow-up.

Of a total of 246 patients included in the study, 87 were male and 159 were female with a mean age of 44.3 ± 16.3 (range, 18 to 75) years. The lesions were most commonly located in the hand (62.6%), predominantly at the phalangeal level (89.6%). Foot involvement was mainly at the ankle region (40.8%), while the knee was the third most frequently affected site (15%), with 64.8% of knee lesions being intra-articular. Multiple lesions were observed in 3.3% of patients. Small joints were involved in 63% of cases. Excisional biopsy was the most common diagnostic approach (63.8%), followed by Tru-Cut biopsy (23.2%) and incisional biopsy (8.5%), while macroscopically complete marginal resection was performed in 4.5% of cases. Postoperative complications occurred in 15.4% of patients, including infection, sensory deficits, hematoma, motion restriction, and vascular complications. The median follow-up was 43 months, and recurrence occurred in 15.4% of patients, of whom 76.3% required reoperation.

Our study results suggest that TGCT is associated with a notable recurrence rate and postoperative morbidity. Accurate diagnosis, complete surgical excision, and long-term follow-up are essential for optimal management. Recurrence may be associated with factors such as pain at presentation, presence of multiple lesions, delayed treatment, and postoperative infection. Adequate surgical excision with sufficient margins is of utmost importance in reducing the risk of recurrence.

Cancer remains a leading cause of mortality worldwide, highlighting the need for therapeutic strategies that reduce systemic toxicity and drug resistance. Resveratrol (RES), a natural polyphenolic stilbenoid, possesses antioxidant, anti-inflammatory, pro-apoptotic, anti-metastatic, and chemosensitizing activities. However, its clinical translation is limited by poor aqueous solubility, chemical instability, rapid metabolic clearance, and consequently low systemic bioavailability. Nanotechnology-based drug delivery systems provide a promising strategy to address these limitations. This review summarizes recent advances in RES-loaded nanoformulations, including polymeric nanoparticles, liposomes, solid lipid nanoparticles, micelles, inorganic nanocarriers, protein-based systems, and biomimetic vesicles. Their therapeutic performance is evaluated across prostate, lung, colorectal, breast, and other cancers, with attention to tumor targeting, controlled release, combination therapy, multidrug-resistance reversal, and modulation of cancer-relevant pathways such as NF-κB, p53, and PI3K/Akt/mTOR. Current oncology-related clinical evidence for RES is still largely based on conventional oral or micronized formulations. Translation of engineered RES nanocarriers therefore requires stronger evidence on scalable manufacturing, carrier-specific safety, heterogeneous tumor delivery, and biomarker-guided trial design. This review also introduces a semi-quantitative prioritization framework based on model-readiness, translational priority, and safety-alert scoring for future PBPK, PK-PD, nano-QSAR, and machine-learning analyses.

Antimicrobial resistance is an important clinical challenge in patients with hematologic malignancies, who are highly susceptible to severe infections due to prolonged neutropenia, disrupted mucosal barriers, intensive chemotherapy, and hematopoietic stem-cell transplantation. This systematic review synthesizes available international evidence on pathogen distribution, antimicrobial resistance patterns, and clinical outcomes in hemato-oncology settings. This systematic review searched PubMed, Scopus, and Google Scholar for English-language studies published from January 2014 to 15 November 2025. Studies reporting microbiologically confirmed infections in patients with hematologic malignancies, with extractable antimicrobial susceptibility or resistance data, were included. Due to substantial clinical, microbiological, methodological, and epidemiological heterogeneity, findings were synthesized qualitatively. Seventeen studies met the inclusion criteria. Gram-negative bacteria predominated across most settings, although pathogen distribution varied by region, age group, infection type, and denominator unit. Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, carbapenem-resistant Gram-negative bacteria, multidrug-resistant Gram-negative organisms, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus were reported across included studies. Where extractable study-level data were available, ESBL-related estimates ranged from 40% to 78%, while carbapenem-resistance estimates varied widely by organism group and study setting, from low carbapenem resistance among Enterobacteriaceae in one pediatric oncology cohort to 38.2% carbapenem-resistant Gram-negative bacteria in an Indian adult febrile neutropenia cohort. Mortality outcomes were heterogeneously reported and were not pooled. In comparative studies, resistant or multidrug-resistant bloodstream infections were associated with worse outcomes, including increased mortality and ICU admission, although causality cannot be inferred from the predominantly observational evidence. Antimicrobial resistance is a clinically important problem in patients with hematologic malignancies, particularly due to resistant Gram-negative pathogens. The findings support strengthened hemato-oncology-specific surveillance, local antibiogram-guided empirical therapy, antimicrobial stewardship, and standardized reporting of resistance phenotypes and clinical outcomes.

Intravascular large B-cell lymphoma (IVLBCL) is a rare extranodal neoplasm in which malignant B cells proliferate predominantly within small blood vessels. Because lymphadenopathy, mass lesions, circulating malignant cells, and specific radiological findings may be absent, IVLBCL can closely mimic other medical conditions, resulting in delayed diagnosis. This case is notable for a prolonged culture-negative sepsis-like presentation with persistent unexplained hypoxemia due to predominant pulmonary microvascular involvement, further obscured by lupus-like autoimmune features and subsequent COVID-19 infection. An older woman in her early 70s presented with fever, lethargy, weight loss, back pain, hypotension, raised inflammatory markers, cytopenia, markedly elevated lactate dehydrogenase (LDH), and progressive hypoxemia. She was initially treated for presumed sepsis, but repeated microbiological investigations and serial imaging did not identify an infectious source, and clinical improvement was not sustained. A transient malar rash and a positive antinuclear antibody raised concern for a lupus-like autoimmune disease; however, testing for anti-double-stranded DNA and extractable nuclear antigen was negative, and the broader autoimmune workup did not support systemic lupus erythematosus as the unifying diagnosis. Subsequent severe acute respiratory syndrome coronavirus 2 infection further complicated the interpretation of hypoxemia and deterioration. Despite antimicrobial therapy, corticosteroids, antiviral treatment, and supportive care, she developed progressive multiorgan failure and died approximately six weeks after admission. Postmortem examination revealed widespread multiorgan IVLBCL involving the lungs, heart, kidneys, liver, spleen, and multiple additional extranodal sites. Pulmonary capillary involvement provided a clinicopathological explanation for persistent unexplained hypoxemia. This case demonstrates how IVLBCL may remain concealed when several plausible diagnoses coexist. Persistent culture-negative fever, constitutional decline, cytopenia, high LDH, nondiagnostic imaging, treatment nonresponse, and unexplained hypoxemia should prompt consideration of IVLBCL and early tissue-based investigation.