Psychiatric manifestations of primary mitochondrial diseases are increasingly recognized, and optimal strategies for managing these represent a significant unmet clinical need for this group of patients with complex multisystem symptomatology and high mortality and morbidity. Secondary mitochondrial dysfunction and oxidative stress have also been implicated in the pathophysiology of various psychiatric diseases. It has been well documented that medications used to treat neuropsychiatric disorders could directly modulate mitochondrial functions. The objective of this book chapter is to review antidepressant drugs and other psychiatric medications that are available for the treatment of psychiatric disorders and the evidence that exists in relation to the mitochondria using these drugs.
LBA5500 Background: Optimal timing of cytoreduction in non-frail patients (pts) with seemingly resectable stage IIIB-IVB ovarian, tubal, and peritoneal carcinoma (OC) remains controversial. Methods: TRUST is an international randomized multicenter phase III trial in pts with stage IIIB-IVB OC and good performance status (ECOG 0/1) comparing primary cytoreductive surgery (PCS) followed by 6 cycles of intravenous (iv) chemotherapy to 3 cycles of neoadjuvant iv chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) and 3 further iv cycles. Maintenance treatment with bevacizumab and/or PARP inhibitors was allowed if selection criteria was similar for both arms. Pts were eligible for the study if preoperative clinical and radiologic assessment identified them as potential candidates for PCS. To ensure surgical quality, participating centers complied with an onsite surgery quality assurance audit, had adequate infrastructure, surgical proficiency (complete resection rates ≥50% in PCS) and sufficient volume (≥36 PCS/year). The intent to treat analysis population included all eligible pts with confirmed stage IIIB-IVB disease. The primary endpoint was overall survival (OS). Superiority was tested using a two-sided stratified log-rank test with significance level 0.05. Secondary endpoints were progression-free survival (PFS) and surgical complications. Results: A total of 688 eligible pts (median age: 63y; range: 32-83) underwent randomization: 345 were assigned to PCS and 343 to NACT/ICS. 91% had high-grade serous histology. Complete resection was achieved in 61.7%/62.9% of all randomized/all operated pts in the PCS group and 72%/76.6% in the ICS group. Median PFS was 22.2 months in the PCS group, and 19.7 months in the ICS group (HR 0.80 95%CI: 0.66-0.96; p=0.02). Median OS was 54.3 months in the PCS group and 48.3 months in the ICS group (HR 0.89 95%CI: 0.74-1.08; p=0.24). Pts with complete cytoreduction after PCS had the most favorable outcome, with a median PFS and OS of 27.9 and 67.0 months, respectively. A long-term benefit from PCS was seen in all analyzed subgroups. The benefit of PCS was most prominent in stage III pts (n=468): median PFS for PCS vs ICS, 26.3 vs 21.4 mos; median OS for PCS vs ICS, 63.7 vs 53.2 months. Major postoperative complication rates were acceptable, with a 30-day postoperative mortality rate of < 1% in both groups. Conclusions: In expert centers with proven surgical quality, PCS followed by iv chemotherapy resulted in a significantly longer median PFS and a numerically longer OS compared to NACT/ICS in non-frail OC pts. Although statistical significance in the primary endpoint was not reached, this is the first randomized trial to show a benefit of PCS over ICS. This benefit is likely to be associated with the high complete resection rate, reinforcing PCS as a standard of care in non-frail pts with seemingly resectable advanced OC. Clinical trial information: NCT02828618 .
The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). The resource comprised 906,359 women and men (66.9
Background Longevity is increasing worldwide due to improvements in healthcare and living standards. Aging is often associated with disability and multiple health concerns. To address these challenges, effective interventions are essential. This study investigated potential age-related declines in gait, balance, and strength. We also sought to assess any relationships between these three parameters and explore potential differences between women and men. Methods Healthy individuals over 50 years of age were recruited for this cross-sectional study. Upper extremity (grip) strength and lower extremity (knee) strength of the dominant side were measured. Static balance was performed on the force plate in different situations each for 30 seconds: bilateral stance with eyes open, bilateral stance with eyes closed, as well as dominant leg and non-dominant leg unilateral stance with eyes open. Gait was measured during level walking using an optical motion capture system. Additionally, the dynamic stability margin (DSM) was calculated for the level walking trials. Results The study results indicated that gait parameters were not significantly affected by age (p≥0.12), while knee and grip strength, along with several balance parameters, showed a significant decline with age. All individuals were able to maintain their bipedal balance, but their center of pressure movement increased significantly by age (p≤0.028). Z-scores were calculated to compare significant age parameters. Unipedal stance time was found to be the most affected by age compared to other contributing factors (p≤0.001). The duration of unipedal balance showed the most significant change per decade (non-dominant: -0.62 SDs; dominant: -0.53 SDs), while strength measures exhibited the lowest amount of change per decade (grip strength: -0.34 SDs; knee strength: -0.26 SDs). Sex differences were observed exclusively in strength parameters, with no discernible impact on the decline in balance parameters. Conclusions These findings suggest that the duration of unipedal stance can serve as a reliable and gender-independent measure of neuromuscular aging for both elderly male and female subjects.
BACKGROUND:Acupuncture, a key modality in traditional Chinese medicine, is gaining global recognition as a complementary therapy and a subject of increasing scientific interest. However, fragmented and unstructured acupuncture knowledge spread across diverse sources poses challenges for semantic retrieval, reasoning, and in-depth analysis. To address this gap, we developed AcuKG, a comprehensive knowledge graph that systematically organizes acupuncture-related knowledge to support sharing, discovery, and artificial intelligence-driven innovation in the field. METHODS:AcuKG integrates data from multiple sources, including online resources, guidelines, PubMed literature, ClinicalTrials.gov, and multiple ontologies (SNOMED CT, UBERON, and MeSH). We employed entity recognition, relation extraction, and ontology mapping to establish AcuKG, with human-in-the-loop to ensure data quality. Two cases evaluated AcuKG's usability: (1) how AcuKG advances acupuncture research for obesity and (2) how AcuKG enhances large language model (LLM) application on acupuncture question-answering. RESULTS:AcuKG comprises 1839 entities and 11 527 relations, mapped to 1836 standard concepts in 3 ontologies. Two use cases demonstrated AcuKG's effectiveness and potential in advancing acupuncture research and supporting LLM applications. In the obesity use case, AcuKG identified highly relevant acupoints (eg, ST25, ST36) and uncovered novel research insights based on evidence from clinical trials and literature. When applied to LLMs in answering acupuncture-related questions, integrating AcuKG with GPT-4o and LLaMA 3 significantly improved accuracy (GPT-4o: 46% → 54%, P = .03; LLaMA 3: 17% → 28%, P = .01). CONCLUSION:AcuKG is an open dataset that provides a structured and computational framework for acupuncture applications, bridging traditional practices with acupuncture research and cutting-edge LLM technologies.
