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Epigenetics and In Silico Transcriptome Analysis of Pediatric Acute Myeloid Leukemia.

Pediatric acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy that accounts for about 15%-20% of childhood leukemias. Despite therapeutic advances, relapses remain common, and survival for high-risk patients is below 60%. Unlike adult AML, pediatric AML displays distinct genetic mutations, including FLT3-ITD, NPM1, KMT2A rearrangements, and core-binding factors (CBF) fusions, as well as extensive epigenetic dysregulation. Aberrant DNA methylation, histone modifications, and altered non-coding RNA expressions disrupt hematopoietic differentiation and activate oncogenic transcriptional networks. Recent advances in silico transcriptomic analysis have transformed the study of pediatric AML by integrating gene expression and epigenetic data to identify molecular drivers and regulatory networks. Computational RNA-seq pipelines and pathway analyses have highlighted key epigenetic regulators, including DNMT3A, TET2, and HDACs, as potential therapeutic targets. Multi-omics approaches combining transcriptomic, methylomic, and chromatin accessibility data are increasingly used to define biomarkers for diagnosis, prognosis, and therapeutic response. This review provides a comprehensive overview of the molecular and epigenetic landscape of pediatric AML, emphasizing the power of in silico transcriptome analysis to uncover disease mechanisms, refine patient stratification, and guide the development of precision-based epigenetic therapies aimed at improving long-term outcomes in children with AML.

Humans

Complicated urinary tract infections: evolving definitions, clinical burden, and treatment landscape amid antimicrobial resistance.

INTRODUCTION: Complicated urinary tract infection (cUTI) is a common and heterogeneous infection associated with substantial morbidity, high healthcare utilization, and increasing antimicrobial resistance. Evolving definitions, increasing device use, and changing patient populations have altered its epidemiology and management. Marked variability in diagnostic criteria, clinical trial endpoints within and outside registrational settings, and treatment strategies complicates clinical decision-making and interpretation of therapeutic advances. AREAS COVERED: This review examines contemporary cUTI epidemiology, classification frameworks, and drivers of disease burden. It evaluates resistance trends and their therapeutic implications, alongside stewardship-based management strategies, including empiric antibiotic selection, intravenous-to-oral transition, treatment duration, and source control. Challenges in catheter-associated infection, recurrence, and regulatory endpoint design are discussed, together with the emerging role of novel agents targeting resistant Gram-negative pathogens. EXPERT OPINION: Rising multidrug resistance and limited oral options are reshaping cUTI management, necessitating individualized, stewardship-aligned therapy guided by illness severity and local epidemiology. Current regulatory endpoints inadequately reflect patient-centered outcomes, particularly in the context of asymptomatic bacteriuria. Expanding availability of effective oral agents may enable earlier discharge and outpatient care. Integration of rapid diagnostics and risk stratification will be essential to optimize therapy, limit resistance, and improve outcomes.

Humans

Artificial Intelligence Technologies in Nursing Clinical Decision-Making: An Umbrella Review.

AIM: To describe contemporary peer-reviewed literature on artificial intelligence in nurses' clinical decision-making. METHODS: An umbrella review of literature reviews. DATA SOURCES: Four major databases were searched for reviews published between 2019 and 2024. RESULTS: Sixteen literature reviews reported on 965 nursing artificial intelligence primary studies. The studies focused on technology development and emerging performance evaluations, whilst real-world testing or implementation in nursing clinical settings was rare. Rigorous comparative analyses were lacking. While artificial intelligence demonstrates promise in decision-making, challenges such as a lack of controlled studies, algorithmic bias, limited reproducibility and insufficient clinical trials hinder its practical impact. Ethical concerns, transparency and patient data privacy issues pose barriers to AI integration in nursing practice. Ethical and legal guidelines for patient privacy are needed and should be taught along with AI literacy training for nurses. CONCLUSIONS: Artificial intelligence has the potential to enhance clinical nursing decision-making, although evidence is limited by too few examples of nurse participation during development. Underutilisation in administrative nursing functions hinders implementation. Nurses should assume a central role in the design and development of AI applications to ensure that these technologies address the realities of nursing practice. With such improvements, artificial intelligence can transform nursing practice, improve nurses' clinical decision-making and ultimately enhance consumer healthcare outcomes. PATIENT OR PUBLIC INVOLVEMENT: No Patient or Public Involvement. REPORTING METHOD: While there is no reporting checklist for umbrella reviews, the PRISMA guide for systematic reviews was followed.

Artificial Intelligence

Forensic taphonomy in fluvial water: A systematic review.

Human remains are frequently recovered from fluvial (lotic) water environments. Rivers, streams, canals and other flowing water bodies pose distinct challenges in forensic practice, particularly due to their current. Compared to other aquatic contexts, fluviatile taphonomy is underrepresented in the forensic literature and the last comprehensive summary was written over a decade ago. Therefore, a systematic review was performed to collect and summarise the current knowledge in forensics about fluvial taphonomy, including decomposition of remains, transport characteristics, search, postmortem submersion interval (PMSI) estimation, taphonomic alterations, and differences to other water bodies. 92 reports met the inclusion criteria for this review, most of them showed a moderate risk of bias. Their main findings were summarised and two major challenges identified. First, predictions about fluvial transport of human bodies pose a tremendous issue in forensic practice, leading to later detection and lower recovery rate of remains, complicating various subsequent analyses. Second, PMSI estimations are difficult particularly due to variable environmental conditions in fluviatile systems. Recommendations for future research in the area of fluvial forensic taphonomy include that case-related data such as the detailed decomposition state and river characteristics need to be made available. More standardised research protocols are required for a facilitated comparison between studies, environments and regions. This review provides forensic practitioners with a comprehensive, updated resource for the investigation of fluvial remains. It also guides future research towards a more efficient practice to build the basis for a broader, more robust and comprehensive synthesis, subsequently supporting analyses in forensic casework.

Humans

A profile of suspected female homicide cases at the Johannesburg and Diepkloof Forensic Pathology Service Medico-legal Mortuaries for 2020-2022.

This study profiles suspected female homicide victims in Johannesburg, South Africa, during the COVID-19 period marked by socio-environmental changes from lockdown restrictions. Guided by the Socio-Ecological Model, a retrospective case series of 369 victims was reviewed using medico-legal mortuary records from Johannesburg and Diepkloof Forensic Pathology Service facilities. Descriptive analyses were conducted, supplemented by a chi-square test to assess whether distributions of causes of death among women differed between COVID-19 and non-COVID-19 periods. No statistically significant association was found, χ2 (6, N = 339) = 6.68, p = 0.35. Key findings highlight that Black, unemployed, unmarried women aged 21-40 were at greatest risk. Cause of death was established in 97.0% (358/369) of cases, with firearm injuries predominating (43.9%), followed by sharp‑force (24.5%) and blunt‑force trauma (13.1%). Approximately 90% of victims were suspected to have been killed by males, with half of deaths attributed to intimate partner violence. Homicide frequency decreased during strict lockdowns but rose as restrictions eased, suggesting that movement and alcohol controls may reduce risk. Despite temporary disturbance caused by COVID‑19 restrictions, the underlying risk profile of female homicide victims remained unchanged. These findings inform multi-level prevention and intervention strategies in South Africa.

Humans

Socket motility assessment of anophthalmic sockets: a systematic review.

PURPOSE: Systematically review and categorize the methods used to assess socket and prosthetic motility in anophthalmic patients following enucleation or evisceration. METHODS: A systematic review was conducted in accordance with PRISMA guidelines. PubMed, Embase, Web of Science, and Scopus were searched from inception through September 2024. Studies reporting qualitative or quantitative assessments of motility in anophthalmic sockets or ocular prostheses were included. Motility assessment methods were categorized as qualitative (descriptive or graded clinical evaluation) or quantitative (numerical measurements in millimeters, degrees, or objective tracking systems). RESULTS: Thirty-five studies encompassing 1,819 patients met inclusion criteria. Nineteen studies used qualitative assessment methods, including subjective observation, graded scales based on cardinal gaze positions, or comparison with the contralateral eye. Sixteen studies employed quantitative techniques, such as the Kestenbaum limbus test, Lister perimeter measurements, conjunctival or limbal markings, photographic image analysis, infrared eye-tracking systems, and magnetic search-coil technology. Considerable heterogeneity was observed in measurement techniques, reporting standards, timing of assessment, and distinction between socket and prosthetic motility. CONCLUSIONS: Substantial variability exists in the methods used to assess motility in anophthalmic sockets, limiting comparability across studies. Establishing standardized, feasible, and reproducible assessment approaches may improve outcome reporting and facilitate meaningful comparisons in future oculoplastic research.

Humans

CNNM2 in schizophrenia: multilevel evidence of genetic susceptibility, magnesium homeostasis, neurodevelopment and cognitive dysfunction.

Schizophrenia (SCZ) is a common psychiatric disorder with a complex, genetically and environmentally influenced etiology, but the specific pathogenesis remains unclear. In recent years, the SCZ susceptibility gene CNNM2 (encoding cyclin M2) located at the 10q24.32-33 locus has received widespread attention. The well-validated SCZ risk interval 10q24.32-33 harbors two independent risk variants: rs11191580 in NT5C2 (significantly associated with CNNM2 mRNA and protein levels) and rs7914558 in CNNM2. Results from functional genomic analyses indicate that lower CNNM2 expression is significantly associated with SCZ. Imaging genetics studies have demonstrated that carriers of risk alleles of CNNM2 SNPs exhibit alterations in brain structure. Animal model studies have revealed that Cnnm2 downregulation in mice leads to impairments in sensorimotor gating and cognitive function. As an Mg2+ transporter, CNNM2 primarily maintains systemic Mg2+ homeostasis. According to clinical studies, a proportion of patients with SCZ exhibit reduced Mg2+ concentrations in plasma and cerebrospinal fluid. CNNM2 dysfunction may contribute to the pathology of SCZ by disrupting Mg2+ homeostasis, thereby affecting neurodevelopment and synaptic plasticity. A systematic consolidation of current evidence supporting the involvement of CNNM2 in SCZ pathogenesis provides a direction for further investigation of the pathological mechanisms underlying this disease, and for identification of novel targets for clinical intervention..

Schizophrenia

Tracking GAD-specific T-cell expansions in Type 1 diabetes by intradermal GAD-Alum challenge.

Identifying and monitoring autoreactive T cells that drive beta cell destruction remains a major obstacle to developing effective immunotherapies for type 1 diabetes (T1D). These cells are extremely rare in peripheral blood and cannot be accessed directly from the pancreas. We used intradermal injection of Glutamic Acid Decarboxylase (GAD)-Alum to recruit GAD-specific T cells to accessible sites in the skin and skin-draining lymph nodes (LNs), sampled by skin suction blisters and ultrasound-guided LN aspiration. Peripheral blood samples obtained before GAD injection were restimulated with GAD in vitro to detect reactive CD4+ T cells. Single-cell RNA sequencing (scRNAseq) followed by re-expression of selected T cell receptors (TCRs) confirmed antigen specificity. Up to 70% of T cells at the skin injection site were clonally-expanded and 4 of 14 (28%) re-expressed TCRs were GAD-reactive. In LNs 1 of 14 (4%) clonally-expanded TCRs was GAD-reactive, representing ~0.08% of all T-cells. GAD-reactive cells across compartments displayed Th1 and Th17-associated transcription signatures. These results demonstrate the intradermal autoantigen challenge and scRNAseq, enable direct identification and molecular profiling of autoreactive T cells in vivo. This minimally invasive approach provides a powerful platform for tracking antigen-specific T cells to monitor disease activity and evaluate immune interventions in T1D.

Autoimmunity

An Update on Inborn Errors of V(D)J Recombination.

V(D)J recombination is the fundamental process by which developing T and B lymphocytes generate diverse antigen receptors, enabling adaptive immunity. This tightly regulated program operates exclusively in lymphoid precursors during G1 phase and depends on the lymphocyte-specific RAG1-RAG2 recombinase to introduce programmed DNA double-strand breaks at recombination signal sequences, followed by repair through the classical nonhomologous end joining (c-NHEJ) pathway. Disruption of any step in this molecular choreography compromises antigen receptor diversity and underlies a spectrum of inborn errors of immunity (IEIs), ranging from severe combined immunodeficiency (SCID) to immune dysregulation with autoimmunity and granulomatous disease. In this review, we place disorders of V(D)J recombination within the broader framework of T-cell development, detailing the temporal waves of recombinase activity, chromatin accessibility, and DNA damage responses that guide thymocyte differentiation. We discuss pathogenic variants affecting the cleavage phase [RAG1, RAG2, and the recently identified RAG cochaperone NudC domain-containing 3 (NUDCD3)], end processing (ARTEMIS), ligation and repair (LIG4, XLF, XRCC4, PRKDC), and genome surveillance pathways (ATM, MRN complex, RNF168), highlighting genotype-phenotype correlations and mechanisms driving immune deficiency and dysregulation. We briefly review recent diagnostic advances, including newborn screening using T-cell receptor excision circles, repertoire sequencing, and functional assays, alongside current therapeutic strategies. Finally, we outline key unanswered questions and argue that continued integration of clinical observation with molecular discovery is essential to improve outcomes and deepen understanding of adaptive immune development.

Humans

Effect of Motor-Control Exercises on Scapulohumeral and Scapulothoracic Muscle Activations in Athletes With Secondary Subacromial Impingement Syndrome.

CONTEXT: Unbalanced or uncoordinated activity across either the scapulohumeral or the scapulothoracic muscle may impair scapulohumeral rhythm during arm elevation. OBJECTIVE: To compare the effects of progressive resistance exercises (PREs), integrated with and without facilitatory motor-control exercises (MCEs), on scapulohumeral and scapulothoracic myoelectric activities in overhead athletes diagnosed with secondary subacromial impingement syndrome (SAIS). DESIGN: Randomized controlled clinical trial. SETTING: Neuromuscular Rehabilitation Research Center. PATIENTS OR OTHER PARTICIPANTS: Overhead athletes diagnosed with secondary SAIS were assigned randomly to 3 parallel groups: 2 intervention groups and 1 control group. INTERVENTIONS: All groups received contemporary physical therapy modalities every other day for 8 weeks. Intervention groups I and II also completed scapulohumeral and scapulothoracic PREs, integrated, respectively, with and without facilitatory MCEs targeting infraspinatus and lower trapezius muscles. MAIN OUTCOME MEASURES: Scapulohumeral and scapulothoracic myoelectric activities were recorded during scapular arm abduction between 80° and 110° before and after the prescribed treatment protocols. RESULTS: Scapulohumeral and scapulothoracic PREs reduced the corresponding myoelectric activities during scapular arm abduction within the groups (P ≤ .02, partial η2 ≥ 0.127). Facilitatory biofeedback-guided exercises integrated into PREs preserved scapulohumeral and scapulothoracic myoelectric activities (P ≤ .03), excluding teres minor myoelectric activity (P > .99). CONCLUSIONS: Scapulohumeral and scapulothoracic PREs reduced the corresponding muscle activations during scapular arm abduction in overhead athletes with secondary SAIS. Facilitatory MCEs targeting infraspinatus and lower trapezius muscles, integrated into PREs, preserved scapulohumeral and scapulothoracic muscle activations.

Humans

All-inside repair is an effective treatment for medial meniscus posterior root tears: a systematic review and meta-analysis of biomechanical and clinical evidence.

BACKGROUND: Medial meniscus posterior root tears (MMPRTs) reproduce the biomechanics of subtotal meniscectomy. Repair is favored, but the role of all-inside repair (AR) remains unclear relative to transtibial pull-out (TP). This study aimed to review the biomechanical and clinical evidence on AR for MMPRTs. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO). MEDLINE, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Outcomes included patient-reported outcome measures (PROMs), magnetic resonance imaging (MRI), and biomechanical performance. When available, random-effects meta-analysis was performed. RESULTS: Thirteen studies were included. AR restored contact mechanics and showed load to failure comparable to TP, with lower stiffness. Meta-analysis showed lower conversion to total knee arthroplasty with AR versus non-repair (RR 0.18, 95% CI 0.05-0.58), and no significant PROM differences between AR and TP. CONCLUSIONS: AR showed favorable biomechanical properties and improved outcomes versus non-repair. Compared with TP, no significant clinical differences were observed. AR may represent a reasonable option in selected scenarios.

Humans

Clinical pharmacokinetics of afatinib: A systematic review.

BACKGROUND: Afatinib is commonly used in the treatment of non-small cell lung cancer (NSCLC). This systematic review summarizes clinical pharmacokinetics (PK) evidence focusing on the effect of disease state and drug interactions on afatinib exposure. METHODS: Google Scholar, Science Direct, PubMed, and the Cochrane library were searched for human studies reporting the clinical PK of afatinib. The search yielded 24 articles that met the predefined inclusion criteria. RESULTS: Afatinib exposure increased slightly more than dose proportionally, with higher doses producing greater AUC0-24 and Cmax values. The apparent oral clearance reported after administration of the oral solution was lower than that observed following tablet administration. The Cmax of afatinib increases by 38.5% after coadministration with ritonavir and exposure decreases 34.3% with rifampicin. The Cmax decreases 31.45% when given with pemetrexed. Both the AUC0-24 and Cmax increase in NSCLC and tumor state. The AUC0-24 of afatinib is 2.61 folds higher following multiple oral doses among patients with solid tumors. Afatinib exposure is 22.1 % higher in renal impaired patients than in healthy controls. In grade 2 diarrhea, the AUC0-24 of afatinib is 83.93% higher as than in grade 0-1 diarrhea in solid tumor patients. CONCLUSION: This systematic review provides an updated synthesis of clinical PK evidence on afatinib. Afatinib exposure is influenced by dose, repeated administration, renal impairment, diarrhea associated toxicity, and P-glycoprotein mediated drug interactions. These findings may support individualized dosing, toxicity-guided dose adjustment, and future development of PK models for afatinib.

Humans

Real-time intraoperative perfusion assessment using indocianine green in pediatric extrinsic ureteropelvic junction obstruction with crossing vessel.

INTRODUCTION: In vascular hitch (VH) particular attention must be paid to preserving lower pole perfusion. Hypoperfusion is normally excluded by macroscopic visual assessment of parenchyma appearance. Our aim is to explore the possible role of indocyanine green (ICG) in highlighting focal hypoperfusion. MATERIALS AND METHODS: This prospective study included pediatric patients with UPJO caused by crossing vessels, treated with robot-assisted VH. Intraoperative evaluation assessed UPJ appearance, reduction of hydronephrosis after vessel mobilization, and the adequacy of pelvic drainage during diuretic testing. ICG was used to assess renal perfusion via NIRF imaging. A 25 mg ICG solution was prepared in 10 mL and administered in 1 mL doses. Fluorescence distribution, operative time, and complications were recorded. Follow-up at 3, 6, and 12 months included clinical evaluations, blood pressure measurements, and Doppler ultrasound. RESULTS: Eight patients (median age 8years) were enrolled between October 2023 and February 2025. ICG assessed renal perfusion post-procedure; one case of focal hypoperfusion due to vessel tension was resolved with intraoperative revision. At a median follow-up of 18 months, no hypertension, pain, or UTIs were observed. Ultrasound demonstrated improved hydronephrosis and normal Doppler flow. CONCLUSION: ICG angiography is a safe and effective tool for the real-time assessment of renal perfusion during pediatric VH procedures.

Humans

Long-term mortality in pediatric sepsis: a systematic review and meta-analysis.

BACKGROUND: Pediatric sepsis represents a significant factor in the mortality rates among children, with survivors remaining highly fragile during the period following discharge. While in-hospital and short-term mortality have been widely studied, the long-term mortality of pediatric sepsis is not adequately synthesized or appreciated. This study aims to estimate the long-term mortality associated with pediatric sepsis, providing a basis for optimizing post-discharge surveillance and care protocols. METHODS: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251137504). Exhaustive searches were conducted in PubMed, Embase, the Cochrane Library, and Web of Science for studies published from the inception of each database to June 30, 2025. Studies reporting long-term mortality in pediatric sepsis patients diagnosed using international consensus criteria were included. After literature screening, long-term mortality was pooled using a random effects meta-analysis in R statistical software. RESULTS: A total of 72,065 records were identified through database searching. After removing duplicates and screening, six studies comprising 11,318 pediatric sepsis patients were included. The pooled long-term mortality in pediatric sepsis was 11% (95% CI: 7-16%), though significant heterogeneity was observed (I2 = 98.2%, p&#x2009;<&#x2009;0.001). Sensitivity analyses yielded similar results, and evidence of publication bias was limited. CONCLUSION: Long-term mortality after pediatric sepsis was 11%, highlighting the persistent risk of mortality after hospital discharge. Further high-quality longitudinal studies are required to identify modifiable risk factors and guide evidence-based follow-up and personalized care.

Humans

Dynamic evolution of chaperone-mediated autophagy is associated with tumor microenvironment remodeling and prognostic stratification in lung adenocarcinoma: insights from single-cell transcriptomics, ensemble machine learning, and experimental validation.

BACKGROUND: Lung adenocarcinoma (LUAD) shows prognostic heterogeneity, and tumor-node-metastasis (TNM) staging is limited for individualized management. Chaperone-mediated autophagy (CMA) maintains proteostasis, but its role during adenocarcinoma in situ (AIS)-minimally invasive adenocarcinoma (MIA)-invasive adenocarcinoma (IAC) progression remains unclear. METHODS: Single-cell RNA sequencing (scRNA-seq) data from GSE189357 and bulk transcriptomes from The Cancer Genome Atlas (TCGA)-LUAD and Gene Expression Omnibus (GEO) cohorts were integrated. CMA activity, cell-cell communication, weighted gene co-expression network analysis (WGCNA), tumor-normal differential expression, machine-learning survival modeling, tumor microenvironment (TME) features, drug sensitivity, and EPC1 function were analyzed. RESULTS: CMA-high tumor epithelial cells increased from AIS (58.1%) to MIA (65.7%) but declined in IAC (44.4%; p < 0.001). CMA-low cells preferentially received fibroblast-derived extracellular matrix cues. A CMA-negatively correlated module identified 69 core genes. Random survival forest (RSF) performed best among 117 machine-learning combinations (mean concordance index > 0.873). High-risk patients had worse survival across cohorts, and the risk score was independently associated with overall survival (hazard ratio = 16.013, 95% confidence interval: 9.579-26.768, p < 0.001). High-risk tumors showed proliferative activation and M0 macrophage enrichment, whereas low-risk tumors showed stronger immune-related signaling. EPC1 overexpression suppressed malignant phenotypes in A549 cells. CONCLUSION: CMA dynamics are associated with stromal and immune remodeling during LUAD progression. A CMA-based model provides robust prognostic stratification and may offer a basis for future TME-guided studies.

Chaperone-mediated autophagy

The Natural History of Residual and Recurrent Disease in Advanced Juvenile Nasopharyngeal Angiofibroma: A Systematic Review.

OBJECTIVE: This systematic review explores the natural history of residual and recurrent juvenile nasopharyngeal angiofibromas (JNAs) to inform clinical decision-making. DATA SOURCES: PubMed, Embase, Scopus, and Web of Science. REVIEW METHODS: A systematic literature review was conducted according to PRISMA guidelines across PubMed, Embase, Scopus, and Web of Science from inception to February 20, 2025 and was re-run on September 21, 2025. Studies included patients with advanced JNA and documented follow-up of residual or recurrent disease. Descriptive statistics, chi-squared analysis, and analysis of variance were used to evaluate treatment outcomes across different modalities including surgery, radiotherapy, gamma knife surgery, and medical therapies. RESULTS: Twenty-one studies encompassing 131 male patients (mean age 16.3&#x2009;years) were included. Residual or recurrent disease demonstrated complete involution in 41%, stable disease in 29%, and reduction in size in 25% of cases. Only 2% of patients had progressive disease. A statistically significant association was observed between treatment modality and outcome (p&#x2009;=&#x2009;0.015), with radiotherapy, either alone, or as part of a multimodal approach, showing the highest rates of spontaneous involution. CONCLUSION: Residual and recurrent JNAs often remain stable or regress without further intervention. Close surveillance with imaging is a safe and effective strategy for asymptomatic patients, minimizing the risks of additional treatment in a young patient population with disease near critical anatomical structures.

Humans

Evaluation of the intraoperative analgesic effects of perioperative electroacupuncture: a randomised, blinded clinical trial in dogs.

OBJECTIVE: To evaluate the effect of perioperative electroacupuncture (EA) on intraoperative analgesic requirements in dogs undergoing tibial tuberosity advancement (TTA) surgery. STUDY DESIGN: Prospective, randomised, blinded, controlled clinical study. ANIMALS: A group of 29 client-owned dogs diagnosed with cranial cruciate ligament rupture that underwent TTA surgery. METHODS: Dogs were treated with EA at predefined acupuncture points (LI-4, ST-36, LIV-3, SP-6 and GB-34) perioperatively as additional analgesia (group EA, n = 14) or were allocated to the control group (group C, n = 15). All dogs were anaesthetised with a standardised protocol including methadone, dexmedetomidine, propofol and ketamine. The intraoperative delivery of sevoflurane and fentanyl was guided in response to signs of nociception by a purpose-designed flowchart, by the same anaesthetist who was blinded to treatment group. A Wilcoxon rank sum test was applied for the fentanyl consumption analysis. Heart rate, mean arterial blood pressure and end-tidal sevoflurane were descriptively analysed between groups for specific time points. A p value < 0.05 was considered significant. RESULTS: The EA group needed significantly less fentanyl with 0.7 (0-2.7) &#x3bc;g kg-1 hour-1 administered versus 2.0 (1.2-5.5) &#x3bc;g kg-1 hour-1 in group C (p = 0.031). Fifty percent of the EA group was not administered a fentanyl bolus, whereas all dogs in group C required at least one bolus. CONCLUSIONS AND CLINICAL RELEVANCE: Perioperative EA reduced mean fentanyl consumption by more than 60% in dogs undergoing TTA surgery.

Animals

A Novel Moisturizer Formulated With Micronized Centella asiatica and Mandelic Acid Improves Mature, Crepey Skin.

BACKGROUND: Dermatoporosis is a condition of fragile, aging skin that manifests as altered pH, wrinkles, laxity, easy bruising, and hyperpigmentation. This study evaluated efficacy, safety, and subject perception after the use of a novel cream, GC (Galderma Laboratories, LP, Fort Worth, TX), on subjects with mature, aging skin. METHODS: A 12-week multicenter, randomized, blinded, in-use study enrolled female and male subjects aged 40 to 60 years of all races, ethnicities, and Fitzpatrick skin types. Subjects were required to have a history of fragile skin and dry, crepey skin on the knees and thighs. GC cream was applied to knee and upper thigh skin twice daily. Assessments included clinical grading, digital photography, bioinstrumentation (skin texture, pH, and heatmap hydration), standard safety assessments, and satisfaction. RESULTS: Use of GC cream for 12 weeks resulted in significant improvements in skin crepiness, photodamage, and firmness, as well as decreased skin pH and early improvements in skin roughness and smoothness from baseline. Corneometer heatmapping documented improved skin hydration over baseline. No adverse events were reported; the GC cream was well tolerated, and subjects reported high satisfaction. CONCLUSION: Twice-daily application of the novel GC skin cream significantly improved the overall skin quality of mature, aging skin, including crepiness, photodamage, firmness, texture, pH, and hydration. GC cream was well tolerated with high subject satisfaction. These data are intended to help guide healthcare providers and patients in choosing an effective moisturizer that was specifically designed for patients with fragile, mature skin.

Humans