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Abstract Background and objective Retinal vein occlusion (RVO) and acute myocardial infarction (MI) are significant vascular events that impact patient health and mortality. Both conditions share common risk factors, such as hypertension, diabetes, and atherosclerosis. This study investigated the potential connection between RVO and MI, particularly among younger individuals, to improve preventive measures and management protocols. Method A systematic review and meta-analysis were conducted, adhering to the PRISMA and MOOSE guidelines. Multiple databases, including PubMed, Scopus, MEDLINE, ScienceDirect, and ClinicalTrials.gov, were exhaustively searched until August 24, 2024. Studies were selected based on their reports of the association between RVO and MI risk. Quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale, and data were pooled using a random-effects model with hazard ratios and 95% confidence intervals. Result Twelve studies comprising 371,817 participants were included. Meta-analysis revealed a pooled hazard ratio of 1.324 (95% CI, 1.238–1.415), indicating a significant association between RVO and increased MI risk (p = 0.0001). Subgroup analysis for central retinal vein occlusion (CRVO) showed a hazard ratio of 1.691 (95% confidence interval [CI] 1.142, 2.502, p = 0.009) with moderate heterogeneity (I2 = 36%), whereas branch retinal vein occlusion (BRVO) yielded a non-significant hazard ratio of 1.167 (95% CI 0.843, 2.106, p = 0.444; I2 = 33%). Publication bias was identified (Egger’s test, p = 0.036) and addressed through trim-and-fill adjustment, maintaining statistical significance. Conclusion Our meta-analysis shows a strong association between CRVO and a 69.1% increased risk of MI, while BRVO shows no significant correlation. Overall, RVO is linked to a 32.4% elevated risk of MI. Despite slight publication bias, adjusted analyses confirm reliability, indicating that improved cardiovascular monitoring for RVO patients, especially those with CRVO, is essential to mitigate MI risk. Clinical trial number Not applicable.

Background: Sodium–glucose co-transporter-2 (SGLT2) inhibitors have emerged as vital medications for the management of type 2 diabetes mellitus (T2DM). Numerous studies have highlighted the cardioprotective and renal protective benefits of SGLT2 inhibitors. Consequently, it is essential to assess their efficacy and safety in patients with chronic diseases. Method: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the effects of SGLT2 inhibitors on major cardiovascular and safety outcomes in patients with T2DM, heart failure (HF), and chronic kidney disease (CKD). We searched the PubMed, Cochrane, and Embase databases for trials published between 30 September 2021 and 17 May 2023. The primary outcomes of interest included nonfatal myocardial infarction (MI), hospitalization for heart failure (HHF), cardiovascular death, and nonfatal stroke. The safety outcomes assessed were hypoglycemia, urinary tract infections (UTIs), and acute kidney injury (AKI). Result: We identified 13 RCTs involving 90,413 participants. In patients with T2DM, SGLT2 inhibitors significantly reduced the risk of nonfatal MI by 12% (hazard ratio [HR] = 0.88, 95% confidence interval [CI]: 0.78–0.98), HHF by 33% (HR = 0.67, 95% CI: 0.62–0.74), and cardiac death by 15% (HR = 0.95, 95% CI: 0.80–1.13). However, they did not significantly reduce the risk of nonfatal stroke (HR = 0.85, 95% CI: 0.75–0.95). In patients with HF, SGLT2 inhibitors reduced the risk of HHF by 28% (HR = 0.72, 95% CI: 0.66–0.77) and cardiac death by 12% (HR = 0.88, 95% CI: 0.80–0.96). For patients with CKD, SGLT2 inhibitors reduced the risk of HHF by 35% (HR = 0.65, 95% CI: 0.55–0.76) and cardiac death by 16% (HR = 0.84, 95% CI: 0.73–0.96). Regarding safety outcomes, SGLT2 inhibitors did not significantly increase the risk of hypoglycemia in patients with T2DM, HF, or CKD, nor did they increase the risk of urinary tract infections (UTIs) in patients with HF or CKD, or the risk of acute kidney injury (AKI) in patients with HF. However, they did increase the risk of UTIs by 8% (risk ratio [RR] = 1.08, 95% CI: 1.01–1.16) in patients with T2DM and reduced the risk of AKI by 22% (RR = 0.78, 95% CI: 0.67–0.89) and 19% (RR = 0.81, 95% CI: 0.69–0.97) in patients with T2DM and CKD, respectively. Conclusions: SGLT2 inhibitors have demonstrated a significant improvement in cardiovascular outcomes for patients with T2DM, HF, and CKD while also maintaining a favorable safety profile. These findings advocate for the broader application of SGLT2 inhibitors in the management of chronic diseases, particularly in reducing the incidence of nonfatal MI, HHF, and cardiac death. Further research is essential to optimize their use across diverse patient populations and stages of disease.

Background: Diabetic retinopathy is the most common retinal vascular disease, affecting the retina’s blood vessels and causing chronic inflammation, oxidative stress, and, ultimately, vision loss. Diabetes-induced elevated glucose levels increase glycolysis, the main methylglyoxal (MGO) formation pathway. MGO is a highly reactive dicarbonyl and the most rapid glycation compound to form endogenous advanced glycation end products (AGEs). MGO can act both intra- and extracellularly by glycating molecules and activating the receptor for AGEs (RAGE) pathway. Conclusions: This review summarizes the sources of MGO formation and its actions on various cell pathways in retinal cells such as oxidative stress, glycation, autophagy, ER stress, and mitochondrial dysfunction. Finally, the detoxification of MGO by glyoxalases is discussed.

Abstract Background Although stimulating autophagy caused by UV has been widely demonstrated in skin cells to exert cell protection, it remains unknown the cellular events in UVA-treated retinal pigment epithelial (RPE) cells. Methods Human ARPE-19 cells were used to measure cell viability, mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondrial mass and lysosomal mass by flow cytometry. Mitochondrial oxygen consumption rate (OCR) was recorded using Seahorse XF flux analyzer. Confocal microscopic images were performed to indicate the mitochondrial dynamics, LC3 level, and AMPK translocation after UVA irradiation. Results We confirmed mitochondrial ROS production and DNA damage are two major features caused by UVA. We found the cell death is prevented by autophagy inhibitor 3-methyladenine and gene silencing of ATG5, and UVA induces ROS-dependent LC3II expression, LC3 punctate and TFEB expression, suggesting the autophagic death in the UVA-stressed RPE cells. Although PARP-1 inhibitor olaparib increases DNA damage, ROS production, and cell death, it also blocks AMPK activation caused by UVA. Interestingly we found a dramatic nuclear export of AMPK upon UVA irradiation which is blocked by N-acetylcysteine and olaparib. In addition, UVA exposure gradually decreases lysosomal mass and inhibits cathepsin B activity at late phase due to lysosomal dysfunction. Nevertheless, cathepsin B inhibitor, CA-074Me, reverses the death extent, suggesting the contribution of cathepsin B in the death pathway. When examining the role of EGFR in cellular events caused by UVA, we found that UVA can rapidly transactivate EGFR, and treatment with EGFR TKIs (gefitinib and afatinib) enhances the cell death accompanied by the increased LC3II formation, ROS production, loss of MMP and mass of mitochondria and lysosomes. Although AMPK activation by ROS-PARP-1 mediates autophagic cell death, we surprisingly found that pretreatment of cells with AMPK activators (A769662 and metformin) reverses cell death. Concomitantly, both agents block UVA-induced mitochondrial ROS production, autophagic flux, and mitochondrial fission without changing the inhibition of cathepsin B. Conclusion UVA exposure rapidly induces ROS-PARP-1-AMPK-autophagic flux and late lysosomal dysfunction. Pre-inducing AMPK activation can prevent cellular events caused by UVA and provide a new protective strategy in photo-oxidative stress and photo-retinopathy.

The activation of microglia and the production of cytokines are key factors contributing to progressive neurodegeneration. Despite the well-recognized neuronal programmed cell death regulated by microglial activation, the death of microglia themselves is less investigated. Nucleotide-binding oligomerization domain, leucine-rich repeat-containing X1 (NLRX1) functions as a scaffolding protein and is involved in various central nervous system diseases. In this study, we used the SM826 microglial cells to understand the role of NLRX1 in lipopolysaccharide (LPS)-induced cell death. We found LPS-induced cell death is blocked by necrostatin-1 and zVAD. Meanwhile, LPS can activate poly (ADP-ribose) polymerase-1 (PARP-1) to reduce DNA damage and induce heme oxygenase (HO)-1 expression to counteract cell death. NLRX1 silencing and PARP-1 inhibition by olaparib enhance LPS-induced SM826 microglial cell death in an additive manner. Less PARylation and higher DNA damage are observed in NLRX1-silencing cells. Moreover, LPS-induced HO-1 gene and protein expression through the p62-Keap1-Nrf2 axis are attenuated by NLRX1 silencing. In addition, the Nrf2-mediated positive feedback regulation of p62 is accordingly reduced by NLRX1 silencing. Of note, NLRX1 silencing does not affect LPS-induced cellular reactive oxygen species (ROS) production but increases mixed lineage kinase domain-like pseudokinase (MLKL) activation and cell necroptosis. In addition, NLRX1 silencing blocks bafilomycin A1-induced PARP-1 activation. Taken together, for the first time, we demonstrate the role of NLRX1 in protecting microglia from LPS-induced cell death. The underlying protective mechanisms of NLRX1 include upregulating LPS-induced HO-1 expression via Nrf2-dependent p62 expression and downstream Keap1-Nrf2 axis, mediating PARP-1 activation for DNA repair via ROS- and autophagy-independent pathway, and reducing MLKL activation.

Diabetic retinopathy (DR) is a major cause of blindness in adult, and the accumulation of advanced glycation end products (AGEs) is a major pathologic event in DR. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is a precursor of AGEs. Although the therapeutic potential of metformin for retinopathy disorders has recently been elucidated, possibly through AMPK activation, it remains unknown how metformin directly affects the MGO-induced stress response in retinal pigment epithelial cells. Therefore, in this study, we compared the effects of metformin and the AMPK activator A769662 on MGO-induced DR in mice, as well as evaluated cytotoxicity, mitochondrial dynamic changes and dysfunction in ARPE-19 cells. We found MGO can induce mitochondrial ROS production and mitochondrial membrane potential loss, but reduce cytosolic ROS level in ARPE-19 cells. Although these effects of MGO can be reversed by both metformin and A769662, we demonstrated that reduction of mitochondrial ROS production rather than restoration of cytosolic ROS level contributes to cell protective effects of metformin and A769662. Moreover, MGO inhibits AMPK activity, reduces LC3II accumulation, and suppresses protein and gene expressions of MFN1, PGC-1α and TFAM, leading to mitochondrial fission, inhibition of mitochondrial biogenesis and autophagy. In contrast, these events of MGO were reversed by metformin in an AMPK-dependent manner as evidenced by the effects of compound C and AMPK silencing. In addition, we observed an AMPK-dependent upregulation of glyoxalase 1, a ubiquitous cellular enzyme that participates in the detoxification of MGO. In intravitreal drug-treated mice, we found that AMPK activators can reverse the MGO-induced cotton wool spots, macular edema and retinal damage. Functional, histological and optical coherence tomography analysis support the protective actions of both agents against MGO-elicited retinal damage. Metformin and A769662 via AMPK activation exert a strong protection against MGO-induced retinal pigment epithelial cell death and retinopathy. Therefore, metformin and AMPK activator can be therapeutic agents for DR.

Calcium/calmodulin-dependent serine protein kinase (CASK) is a scaffold protein and plays critical roles in neuronal synaptic formation and brain development. Previously, CASK was shown to associate with EGFR to maintain the vulval cell differentiation in C. elegans. In this study, we explored the role of CASK in CHME3 microglial cells. We found that CASK silencing protects cells from H2O2-induced cell death by attenuating PARP-1 activation, mitochondrial membrane potential loss, reactive oxygen species production, and mitochondrial fission, but it increases oxidative phosphorylation. The PARP-1 inhibitor olaparib blocks H2O2-induced cell death, suggesting the death mode of parthanatos. CASK silencing also increases AKT activation but decreases AMPK activation under H2O2 treatment. Pharmacological data further indicate that both signaling changes contribute to cell protection. Different from the canonical parthanatos pathway, we did not observe the AIF translocation from mitochondria into the nucleus, suggesting a non-canonical AIF-independent parthanatos in H2O2-treated CHME3 cells. Moreover, we found that CASK silencing upregulates the EGFR gene and protein expression and increases H2O2-induced EGFR phosphorylation in CHME3 microglia. However, EGFR activation does not contribute to cell protection caused by CASK silencing. In conclusion, CASK plays a crucial role in microglial parthanatos upon H2O2 treatment via stimulation of PARP-1 and AMPK but the inhibition of AKT. These findings suggest that CASK might be an ideal therapeutic target for CNS disorders.

Background/Purpose Fragility hip fracture (FHF) is the most prevalent fragility fracture, causing deterioration in ambulatory ability and disability. Early detection of patients who are at risk of prolonged hospitalization and functional decline after FHF is crucial as this facilitates post-operative management and healthcare resources allocation. Handgrip strength (HGS) is an easily-administered and cost-effective tool to assess whole body strength. The objectives of this study were to examine the relationship between pre-operative HGS, length of stay (LOS) and functional outcomes at 1-year follow up in patients with FHF in Hong Kong. Methods Patients aged 65 years old or above who were admitted to a local acute hospital from April 2017 to March 2020 due to FHF that were treated operatively, and subsequently attended the multidisciplinary fragility fracture clinic at 1-year follow up were evaluated. HGS measured at pre-operative physiotherapy initial assessment, post-fracture total LOS, Modified Functional Ambulation Classification (MFAC) and Elderly Mobility Scale (EMS) at 1-year follow up were retrieved for analysis. Correlation between HGS and LOS was analyzed using Pearson's correlation coefficient. Correlations between HGS and MFAC, and HGS and EMS were analyzed using Spearman's rank correlation coefficient. Results One hundred and nineteen patients (mean age = 80.8 ± 7.3 years) (33 males, 86 females) were evaluated. Statistical significant negative correlation between HGS and LOS was found ( r = -0.245, p = 0.007), implying that the lower the HGS, the longer the period of hospitalization. HGS also showed statistical significant positive correlation with MFAC ( r = 0.358, p

Adenosine triphosphate (ATP) released from dying cells with high concentrations is sensed as a danger signal by the P2X7 receptor. Sodium iodate (NaIO3) is an oxidative toxic agent, and its retinal toxicity has been used as the model of dry age-related macular degeneration (AMD). In this study, we used NaIO3-treated mice and cultured retinal cells, including BV-2 microglia, 661W photoreceptors, rMC1 Müller cells and ARPE-19 retinal epithelial cells, to understand the pathological action of P2X7 in retinal degeneration. We found that NaIO3 can significantly decrease the photoreceptor function by reducing a-wave and b-wave amplitudes in electroretinogram (ERG) analysis. Optical coherence tomography (OCT) analysis revealed the degeneration of retinal epithelium and ganglion cell layers. Interestingly, P2X7−/− mice were protected from the NaIO3-induced retinopathy and inflammatory NLRP3, IL-1β and IL-6 gene expression in the retina. Hematoxylin and eosin staining indicated that the retinal epithelium was less deteriorated in P2X7−/− mice compared to the WT group. Although P2X7 was barely detected in 661W, rMC1 and ARPE-19 cells, its gene and protein levels can be increased after NaIO3 treatment, leading to a synergistic cytotoxicity of BzATP [2′(3′)-O-(4-benzoylbenzoyl)adenosine-5′-triphosphate tri(triethyleneammonium)salt] and NaIO3 administration in ARPE-19 cells. In conclusion, the paracrine action of the ATP/P2X7 axis via cell–cell communication is involved in NaIO3-induced retinal injury. Our results show that P2X7 antagonist might be a potential therapy in inflammation-related retinal degeneration.

After the publication of this article [1], the authors would like to clarify that some immunoblotting data in Figs. 2f, 3a and 4b were obtained from the same samples but individual SDS-PAGE gels.

Abstract Background Oxidative stress is a major factor in retinal pigment epithelium (RPE) cells injury that contributes to age-related macular degeneration (AMD). NaIO3 is an oxidative toxic agent and its selective RPE cell damage makes it as a reproducible model of AMD. Although NaIO3 is an oxidative stress inducer, the roles of ROS in NaIO3-elicited signaling pathways and cell viability have not been elucidated, and the effect of NaIO3 on autophagy in RPE cells remains elusive. Methods In human ARPE-19 cells, we used Annexin V/PI staining to determine cell viability, immunoblotting to determine protein expression and signaling cascades, confocal microscopy to determine mitochondrial dynamics and mitophagy, and Seahorse analysis to determine mitochondrial oxidative phosphorylation. Results We found that NaIO3 can dramatically induce cytosolic but not mitochondrial ROS production. NaIO3 can also activate ERK, p38, JNK and Akt, increase LC3II expression, induce Drp-1 phosphorylation and mitochondrial fission, but inhibit mitochondrial respiration. Confocal microscopic data indicated a synergism of NaIO3 and bafilomycin A1 on LC3 punctate formation, indicating the induction of autophagy. Using cytosolic ROS antioxidant NAC, we found that p38 and JNK are downstream signals of ROS and involve in NaIO3-induced cytotoxicity but not in mitochondrial dynamics, while ROS is also involved in LC3II expression. Unexpectedly NAC treatment upon NaIO3 stimulation leads to an enhancement of mitochondrial fragmentation and cell death. Moreover, inhibition of autophagy and Akt further enhances cell susceptibility to NaIO3. Conclusions We conclude that NaIO3-induced oxidative stress and cytosolic ROS production exert multiple signaling pathways that coordinate to control cell death in RPE cells. ROS-dependent p38 and JNK activation lead to cytotoxicity, while ROS-mediated autophagy and mitochondrial dynamic balance counteract the cell death mechanisms induced by NaIO3 in RPE cells.

Background/purpose: Sarcopenia is a predictor of fall, which is a leading cause of fragility hip fractures (FHF). Dual energy X-ray absorptiometry (DXA) is a costly measurement method for sarcopenia. Rehabilitation and prognosis can be determined by early functional outcomes. Meanwhile, 1-year mortality of FHF patients is high. Aims: (i) To report the prevalence of sarcopenia. (ii) To investigate the relationships of sarcopenia, premorbid factors, early functional outcomes and 1-year mortality in Hong Kong Chinese FHF patients. Methods: FHF patients admitted to Queen Elizabeth Hospital in Hong Kong from April 2016 to March 2017 were reviewed, including outcomes of relative appendicular skeletal muscle mass index (RASM), handgrip strength (HGS), New Mobility Score (NMS), Modified Functional Ambulation Classification (MFAC), Modified Barthel Index (MBI), Cumulated Ambulation Score (CAS), Elderly Mobility Scale (EMS) and 1-year mortality. Results: One hundred sixty nine FHF patients, aged 82.68 ± 7.32 years, were reviewed. Prevalence of sarcopenia in male and female were 71.4% and 37.7%, respectively. RASM was correlated with HGS of both dominant ( r = 0.366, p < 0.001) and non-dominant side ( r = 0.383, p < 0.001), NMS ( r s = 0.239, p < 0.001), MFAC ( r s = 0.192, p = 0.013), MBI ( r s = 0.182, p = 0.018) and CAS ( r s = 0.183, p = 0.019). RASM was not significantly correlated with EMS-1 ( r s = 0.050, p = 0.525) and EMS-DC ( r s = 0.092, p = 0.249). There was significant correlation between Sarcopenia and EMS-DC ( r rb = −0.226, p = 0.004). Sarcopenia was marginally not associated with 1-year mortality ( χ 2 = 3.745, p = 0.053). One-year mortality of FHF patients with Sarcopenia and without Sarcopenia were 16.5% and 7.1%, respectively. FHF patients with Sarcopenia were not statistically significant to be more likely to face mortality within 1 year ( R 2 = 0.030, OR = 2.638, p = 0.060). Conclusions: Prevalence of sarcopenia was high in FHF patients and RASM was correlated with HGS and NMS, which can be easily administered as screening tools. Sarcopenia was correlated with early functional outcome but not with 1-year mortality. Early detection of Sarcopenia is crucial for early implementation of rehabilitation and treatment.

Oxidative stress-associated retinal pigment epithelium (RPE) cell death is critically implicated in the pathogenesis of visual dysfunction and blindness of retinal degenerative diseases. Sodium iodate (NaIO3) is an oxidative retinotoxin and causes RPE damage. Previously, we found that NaIO3 can induce human ARPE-19 cell death via inducing mitochondrial fission and mitochondrial dysfunction. Although metformin has been demonstrated to benefit several diseases possibly via AMP-activated protein kinase (AMPK) activation, it remains unknown how AMPK affects retinopathy in NaIO3 model. Therefore, in this study, we compared the effects of metformin and AMPK activator A769662 on NaIO3-induced cellular stress and toxicity. We found that A769662 can protect cells against NaIO3-induced cytotoxicity, while metformin exerts an enhancement in cell death. The mitochondrial reactive oxygen species (ROS) production as well as mitochondrial membrane potential loss induced by NaIO3 were not altered by both agents. In addition, NaIO3-induced cytosolic ROS production, possibly from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and counteracting cell death, was not altered by A769662 and metformin. Notably, NaIO3-induced mitochondrial fission and inhibition of mitochondrial respiration for ATP turnover were reversed by A769662 but not by metformin. In agreement with the changes on mitochondrial morphology, the ERK-Akt signal axis dependent Drp-1 phosphorylation at S616 (an index of mitochondrial fission) under NaIO3 treatment was blocked by A769662, but not by metformin. In summary, NaIO3-induced cell death in ARPE cells primarily comes from mitochondrial dysfunction due to dramatic fission and inhibition of mitochondrial respiration. AMPK activation can exert a protection by restoring mitochondrial respiration and inhibition of ERK/Akt/Drp-1 phosphorylation, leading to a reduction in mitochondrial fission. However, inhibition of respiratory complex I by metformin might deteriorate mitochondrial dysfunction and cell death under NaIO3 stress.

In diseases such as proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy, and age-related macular degeneration, retinal pigment epithelial (RPE) cells proliferate and migrate. Moreover, platelet-derived growth factor (PDGF) has been shown to enhance proliferation and migration of RPE cells in PVR. Even resveratrol can suppress the migration and adhesion of many cell types, its effects on RPE cell migration and adhesion remain unknown. In this study, we investigated the inhibitory effects of resveratrol on RPE cell migration induced by PDGF-BB, an isoform of PDGF, and adhesion to fibronectin, a major ECM component of PVR tissue.The migration of RPE cells was assessed by an electric cell-substrate impedance sensing migration assay and a Transwell migration assay. A cell viability assay was used to determine the viability of resveratrol treated-cells. The cell adhesion to fibronectin was examined by an adhesion assay. The interactions of resveratrol with PDGF-BB were analyzed by a dot binding assay. The PDGF-BB-induced signaling pathways were determined by western blotting and scratch wound healing assay.Resveratrol inhibited PDGF-BB-induced RPE cell migration in a dose-dependent manner, but showed no effects on ARPE19 cell adhesion to fibronectin. The cell viability assay showed no cytotoxicity of resveratrol on RPE cells and the dot binding assay revealed no direct interactions of resveratrol with PDGF-BB. Inhibitory effects of resveratrol on PDGF-BB-induced platelet-derived growth factor receptor β (PDGFRβ) and tyrosine phosphorylation and the underlying pathways of PI3K/Akt, ERK and p38 activation were found; however, resveratrol and PDGF-BB showed no effects on PDGFRα and JNK activation. Scratch wound healing assay demonstrated resveratrol and the specific inhibitors of PDGFR, PI3K, MEK or p38 suppressed PDGF-BB-induced cell migration.These results indicate that resveratrol is an effective inhibitor of PDGF-BB-induced RPE cell migration via PDGFRβ, PI3K/Akt and MAPK pathways, but has no effects on the RPE cell adhesion to fibronectin.

Background/Purpose: Fragility hip fracture (FHF) is the most prevalent fragility fracture, causing deterioration in ambulatory ability and disability. Early detection of patients who are at risk of prolonged hospitalization and functional decline after FHF is crucial as this facilitates post-operative management and healthcare resources allocation. Handgrip strength (HGS) is an easily-administered and cost-effective tool to assess whole body strength. The objectives of this study were to examine the relationship between pre-operative HGS, length of stay (LOS) and functional outcomes at 1-year follow up in patients with FHF in Hong Kong. Methods: Patients aged 65 years old or above who were admitted to alocalacute hospital from April 2017 toMarch 2020 due to FHF that were treated operatively, and subsequently attended the multidisciplinary fragility fracture clinic at 1-year followupwere evaluated.HGSmeasured at pre-operative physiotherapy initial assessment, post-fracture total LOS, Modified Functional Ambulation Classification (MFAC) and Elderly Mobility Scale (EMS) at 1-year follow up were retrieved for analysis. Correlation between HGS and LOS was analyzed using Pearson's correlation coefficient. Correlations between HGS and MFAC, and HGS and EMS were analyzed using Spearman's rank correlation coefficient. Results:One hundred and nineteen patients (mean age=80.8±7.3 years) (33 males, 86 females) were evaluated. Statistical significant negative correlation between HGS and LOS was found (r=-0.245, p=0.007), implying that the lower the HGS, the longer the period of hospitalization. HGS also showed statistical significant positive correlation with MFAC (r=0.358, p < 0.001) and EMS (r=0.507, p < 0.001), suggesting that the greater the HGS, the better the functional outcomes after 1 year. In short, pre-operative HGS measured by physiotherapists was shown to be associated with LOS and functional outcomes at 1-year follow up. Conclusion: HGS is significantly associated with patient's LOS, MFAC and EMS after FHF. HGS is an easily-administered and cost-effective tool to facilitate frontline practitioners to determine and stratify patients' rehabilitation potential and subsequently establish customized rehabilitation and discharge plan, such as intensive training, caregiver education and potential prediction of discharge destination. Key Messages: HGS is significantly associated with patient's LOS, MFAC and EMS after FHF. HGS is an easily-administered and cost-effective tool to facilitate frontline practitioners to determine and stratify patients' rehabilitation potential and subsequently establish customized rehabilitation and discharge plan. [ABSTRACT FROM AUTHOR]