The structural landscape of Microprocessor-mediated processing of pri-let-7 miRNAs.

MicroRNA (miRNA) biogenesis is initiated upon cleavage of a primary miRNA (pri-miRNA) hairpin by the Microprocessor (MP), composed of the Drosha RNase III enzyme and its partner DGCR8. Multiple pri-miRNA sequence motifs affect MP recognition, fidelity, and efficiency. Here, we performed cryoelectron microscopy (cryo-EM) and biochemical studies of several let-7 family pri-miRNAs in complex with human MP. We show that MP has the structural plasticity to accommodate a range of pri-miRNAs. These structures revealed key features of the 5' UG sequence motif, more comprehensively represented as the "flipped U with paired N" (fUN) motif. Our analysis explains how cleavage of class-II pri-let-7 members harboring a bulged nucleotide generates a non-canonical precursor with a 1-nt 3' overhang. Finally, the MP-SRSF3-pri-let-7f1 structure reveals how SRSF3 contributes to MP fidelity by interacting with the CNNC motif and Drosha's Piwi/Argonaute/Zwille (PAZ)-like domain. Overall, this study sheds light on the mechanisms for flexible recognition, accurate cleavage, and regulated processing of different pri-miRNAs by MP.

Intraoperative Complications as Predictors of Flap Failure in Autologous Breast Reconstruction.

BACKGROUND: Intraoperative microvascular complications in autologous breast reconstruction significantly increase the risk of post-operative complications. No study has identified which specific intraoperative complications contribute to partial or total flap loss. METHODS: A retrospective chart review of microsurgical breast reconstructions by five surgeons between 2009-2020 analyzed operative variables and patient outcomes, with complications determined from the operative report. Flap loss rates were compared between cases with and without intraoperative complications. Statistical analysis was performed using Fischer exact and t-tests for discrete and continuous variables, respectively. RESULTS: Intraoperative complications were analyzed for 1465 autologous breast flaps performed in 916 patients. Early partial flap loss was predicted by arterial anastomosis revision (2.90% vs 0.44%, p=.03) and alternate venous outflow (14.29% vs 0.41%, p=.002), with no association with intraoperative thrombosis, venous revision, or difficult recipient or flap dissection. In comparison, early total flap loss was predicted by intraoperative arterial revision (5.80% vs 0.51%, p=.001), venous revision (5.45% vs 0.57%, p=.007), intraoperative thrombosis (12.12% vs 0.49%, p<.001), and difficult flap dissection (2.91% vs 0.59%, p=.04). Difficult flap dissection was the only intraoperative variable associated with late partial flap loss (6.80% vs 1.69%, p=.004). Late total flap loss only occurred in 6/1465 flaps, the sole association being difficult recipient vessel dissection (2.78% vs 0.29%, p=.03). Post-operative arterial and venous compromise occurred in 1.10% (13/1187) and 2.53% (30/1187) of cases with no intraoperative complications, respectively, compared to 3.2% (9/278, p=0.02) and 6.12% (17/278, p=0.002) in cases with an intraoperative complication. CONCLUSIONS: Alternate venous outflow predicts early partial flap loss, while intraoperative thrombosis, and arterial and venous revision predict early total loss. Difficult flap dissection was associated with early total and late partial flap loss, while difficult recipient vessel dissection was associated with late total flap loss.

Genetic regulation of microRNAs in the older adult brain and their contribution to neuropsychiatric conditions.

MicroRNAs are essential post-transcriptional regulators of gene expression and involved in many biological processes; however, our understanding of their genetic regulation and role in brain illnesses is limited. Here, we mapped brain microRNA expression quantitative trait loci (miR-QTLs) using genome-wide small RNA sequencing profiles from dorsolateral prefrontal cortex (dlPFC) samples of 604 older adult donors of European ancestry. miR-QTLs were identified for 224 miRNAs (48% of 470 tested miRNAs) at false discovery rate < 1%. We found that miR-QTLs were enriched in brain promoters and enhancers, and that intragenic miRNAs often did not share QTLs with their host gene. Additionally, we integrated the brain miR-QTLs with results from 16 GWAS of psychiatric and neurodegenerative diseases using multiple independent integration approaches and identified four miRNAs that contribute to the pathogenesis of bipolar disorder, major depression, post-traumatic stress disorder, schizophrenia, and Parkinson's disease. This study provides novel insights into the contribution of miRNAs to the complex biological networks that link genetic variation to disease.

Propensity Score-matched Analysis Comparing Robotic Versus Laparoscopic Minor Liver Resections of the Anterolateral Segments: an International Multi-center Study of 10,517 Cases.

OBJECTIVE: To compare the outcomes of robotic minor liver resections (RMLR) versus laparoscopic (L) MLR of the anterolateral segments. BACKGROUND: Robotic liver surgery has been gaining prominence over the years with increasing usage for a myriad of hepatic resections. Robotic liver resections(RLR) has demonstrated non-inferiority to laparoscopic(L)LR while illustrating advantages over conventional laparoscopy especially for technically difficult and major LR. However, the advantage of RMLR for the anterolateral(AL) (segments II, III, IVb, V and VI) segments, has not been clearly demonstrated. METHODS: Between 2008 to 2022, 15,356 of 29,861 patients from 68 international centres underwent robotic(R) or laparoscopic minor liver resections (LMLR) for the AL segments Propensity score matching (PSM) analysis was performed for matched analysis. RESULTS: 10,517 patients met the study criteria of which 1,481 underwent RMLR and 9,036 underwent LMLR. A PSM cohort of 1,401 patients in each group were identified for analysis. Compared to the LMLR cohort, the RMLR cohort demonstrated significantly lower median blood loss (75ml vs. 100ml, P<0.001), decreased blood transfusion (3.1% vs. 5.4%, P=0.003), lower incidence of major morbidity (2.5% vs. 4.6%, P=0.004), lower proportion of open conversion (1.2% vs. 4.5%, P<0.001), shorter post operative stay (4 days vs. 5 days, P<0.001), but higher rate of 30-day readmission (3.5% vs. 2.1%, P=0.042). These results were then validated by a 1:2 PSM analysis. In the subset analysis for 3,614 patients with cirrhosis, RMLR showed lower median blood loss, decreased blood transfusion, lower open conversion and shorter post operative stay than LMLR. CONCLUSION: RMLR demonstrated statistically significant advantages over LMLR even for resections in the AL segments although most of the observed clinical differences were minimal.

Implementing a Photodocumentation Program.

The widespread availability of smart devices has facilitated the use of medical photography, yet photodocumentation workflows are seldom implemented in healthcare organizations due to integration challenges with electronic health records (EHR) and standard clinical workflows. This manuscript details the implementation of a comprehensive photodocumentation workflow across all phases of care at a large healthcare organization, emphasizing efficiency and patient safety. From November 2018 to December 2023, healthcare workers at our institution uploaded nearly 32,000 photodocuments spanning 54 medical specialties. The photodocumentation process requires as few as 11 mouse clicks and keystrokes within the EHR and on smart devices. Automation played a crucial role in driving workflow efficiency and patient safety. For example, body part rules were used to automate the application of a sensitive label to photos of the face, chest, external genitalia, and buttocks. This automation was successful, with over 50% of the uploaded photodocuments being labeled as sensitive. Our implementation highlights the potential for standardizing photodocumentation workflows, thereby enhancing clinical documentation, improving patient care, and ensuring the secure handling of sensitive images.

The impact of social isolation on functional disability in older people: A multi-cohort study.

OBJECTIVES: We assessed the relationship between social isolation and functional disability in older people. DESIGN: Comparison of longitudinal cohort studies. SETTING AND PARTICIPANTS: Harmonised longitudinal datasets from the United States, England, European countries, Japan, Korea, China and Hong Kong. METHODS: Social isolation was operationalised as a composite score with five domains, such as marital status, living alone, and social contact with others. Functional disability was defined as whether the cohort participant had any difficulty in activities of daily living (ADL). In each dataset, we used robust Poisson regression models to obtain the relative risks (RRs) and the corresponding 95 % confidence intervals (CI). We combined the RRs to synthesize a pooled estimate using meta-analysis with random-effects models. RESULTS: Overall, the social isolation composite score was not associated with ADL disability (pooled RR = 1.05, 95 % CI [0.97-1.14], n = 40,119). Subgroup analysis suggested social isolation composite score was associated with ADL disability in Asian regions (pooled RR = 1.09, 95 % CI [1.02, 1.16], but not in Western regions (pooled RR = 1.01, 95 % CI [0.96, 1.07]). The relationships between different domains of social isolation and ADL disability were heterogeneous, except that no participation in any social clubs or religious groups was consistently associated with ADL disability (pooled RR = 1.12, 95 % CI [1.04, 1.21]). CONCLUSION: Targeting social isolation may prevent decline in functional abilities in older adults, providing an avenue to active and healthy ageing. Nonetheless, interventions tackling social isolation should tailor to the unique cultural and social underpinnings. A limitation of the study is that reverse causality could not be ruled out definitively.

Underserved groups could be better considered within population-based eye health surveys: a methodological study.

OBJECTIVES: In pursuit of health equity, the World Health Organization has recently called for more extensive monitoring of inequalities in eye health. Population-based eye health surveys can provide this information, but whether underserved groups are considered in the design, implementation, and reporting of surveys is unknown. We conducted a systematic methodological review of surveys published since 2000 to examine how many population-based eye health surveys have considered underserved groups in their design, implementation, or reporting. STUDY DESIGN AND SETTING: We identified all population-based cross-sectional surveys reporting the prevalence of objectively measured vision impairment or blindness. Using the PROGRESS + framework to identify underserved groups, we assessed whether each study considered underserved groups within 15 items across the rationale, sampling or recruitment methods, or the reporting of participation and prevalence rates. RESULTS: 388 eye health surveys were included in this review. Few studies prospectively considered underserved groups during study planning or implementation, for example within their sample size calculations (n = 5, ∼1%) or recruitment strategies (n = 70, 18%). The most common way that studies considered underserved groups was in the reporting of prevalence estimates (n = 374, 96%). We observed a modest increase in the number of distinct PROGRESS + factors considered by a publication over the study period. Gender/sex was considered within at least one item by 95% (n = 367) of studies. Forty-three percent (n = 166) of included studies were conducted primarily on underserved population groups, particularly for subnational studies of people living in rural areas, and we identified examples of robust population-based studies in socially excluded groups. CONCLUSION: More effort is needed to improve the design, implementation, and reporting of surveys to monitor inequality and promote equity in eye health. Ideally, national-level monitoring of vision impairment and service coverage would be supplemented with smaller-scale studies to understand the disparities experienced by the most underserved groups.

Protocol for the creation and characterization of SARS-CoV-2 variant testing panels using remnant clinical samples for diagnostic assay testing.

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Alpha variant in 2020 demonstrated the need for reanalysis of diagnostic tests to ensure detection of emerging variants. Here, we present a protocol for creating and characterizing SARS-CoV-2 variant testing panels using remnant clinical samples for diagnostic assay testing. We describe steps for characterizing SARS-CoV-2 remnant clinical samples and preparing them into pools and their use in preparing varying quantities of virus. We then detail procedures for verifying variant detection using the resulting sample panel. For complete details on the use and execution of this protocol, please refer to Rao et al.1,2.

Defining Global Benchmarks for Laparoscopic Right Posterior Sectionectomy/H67: An International Multicenter Study.

OBJECTIVE: We aimed to establish global benchmark outcomes indicators for L-RPS/H67. BACKGROUND: Minimally invasive liver resections has seen an increase in uptake in recent years. Over time, challenging procedures as laparoscopic right posterior sectionectomies (L-RPS)/H67 are also increasingly adopted. METHODS: This is a post hoc analysis of a multicenter database of 854 patients undergoing minimally invasive RPS (MI-RPS) in 57 international centers in 4 continents between 2015 and 2021. There were 651 pure L-RPS and 160 robotic RPS (R-RPS). Sixteen outcome indicators of low-risk L-RPS cases were selected to establish benchmark cutoffs. The 75th percentile of individual center medians for a given outcome indicator was set as the benchmark cutoff. RESULTS: There were 573 L-RPS/H67 performed in 43 expert centers, of which 254 L-RPS/H67 (44.3%) cases qualified as low risk benchmark cases. The benchmark outcomes established for operation time, open conversion rate, blood loss ≥500 mL, blood transfusion rate, postoperative morbidity, major morbidity, 90-day mortality and textbook outcome after L-RPS were 350.8 minutes, 12.5%, 53.8%, 22.9%, 23.8%, 2.8%, 0% and 4% respectively. CONCLUSIONS: The present study established the first global benchmark values for L-RPS/H6/7. The benchmark provided an up-to-date reference of best achievable outcomes for surgical auditing and benchmarking.

The structural landscape of Microprocessor mediated pri-let-7 miRNA processing.

miRNA biogenesis is initiated upon cleavage of a primary miRNA (pri-miRNA) hairpin by the Microprocessor (MP), composed of the Drosha RNase III enzyme and its partner DGCR8. Multiple pri-miRNA sequence motifs affect MP recognition, fidelity, and efficiency. Here, we performed cryo-EM and biochemical studies of several let-7 family pri-miRNAs in complex with human MP. We show that MP has the structural plasticity to accommodate a range of pri-miRNAs. These structures revealed key features of the 5' UG sequence motif, more comprehensively represented as the "fUN" motif. Our analysis explains how cleavage of class-II pri-let-7 members harboring a bulged nucleotide generates a noncanonical precursor with a 1-nt 3' overhang. Finally, the MP-SRSF3-pri-let-7f1 structure reveals how SRSF3 contributes to MP fidelity by interacting with the CNNC-motif and Drosha's PAZ-like domain. Overall, this study sheds light on the mechanisms for flexible recognition, accurate cleavage, and regulated processing of different pri-miRNAs by MP.

Update on management of pancreatic cancer: a literature review.

BACKGROUND AND OBJECTIVE: Pancreatic cancer is an aggressive malignancy with high mortality. At the time of diagnosis, majority of patients (80-90%) present with either locally advanced unresectable disease or metastatic disease. Even after curative resection, the recurrence rate remains quite high. This article aimed at reviewing the updated management of pancreatic cancer. METHODS: We identified literature by searching Medline and PubMed from January 2010 to June 2023 using the keywords. KEY CONTENT AND FINDINGS: A multidisciplinary approach is essential to optimize the outcomes for both curable and advanced diseases. Management of pancreatic cancer divided into resectable, borderline resectable, locally advanced, and metastatic diseases. Surgery and adjuvant chemotherapy is a standard treatment approach for resectable pancreatic cancer. The recommended adjuvant chemotherapy regimen for patients with good functional status is modified FOLFIRINOX (5-fluorouracil, folinic acid, irinotecan, and oxaliplatin). The recommended adjuvant chemotherapy regimen for patients with suboptimal functional status is gemcitabine plus capecitabine or monotherapy gemcitabine. The optimal treatment strategy for borderline resectable pancreatic cancer is still uncertain. Traditionally, upfront surgery is the choice of treatment. There is increasing evidence showing benefits of neoadjuvant therapy in borderline resectable pancreatic cancer. However, the optimal neoadjuvant treatment regimen was not certain yet. Advancement of chemotherapy has a positive impact for the survival of advanced disease. For patients with good functional status, the recommended first-line systemic chemotherapy for unresectable locally advanced disease or metastatic disease is combination chemotherapy regimens such as FOLFIRINOX, gemcitabine plus nab-paclitaxel. For patients with suboptimal functional status, the recommended first-line systemic chemotherapy for unresectable locally advanced disease or metastatic disease is gemcitabine plus capecitabine or monotherapy gemcitabine. Recently, more researches showed promising results in the use of nanoliposomal irinotecan, targeted agents such as a poly [adenosine diphosphate (ADB)-ribose] polymerase inhibitor, tyrosine receptor kinase (TRK) inhibitors, and immune checkpoint-inhibitors. CONCLUSIONS: Pancreatic cancer is a challenging disease for management. Radical surgery itself is not enough for prolong survival. The improvement of chemotherapy, target agents and immunotherapy with multidisciplinary approach will be the only solution for improvement of survival outcome and quality of life for patients with pancreatic cancer.

The rapidly evolving X-linked MIR-506 family fine-tunes spermatogenesis to enhance sperm competition.

Despite rapid evolution across eutherian mammals, the X-linked MIR-506 family miRNAs are located in a region flanked by two highly conserved protein-coding genes (SLITRK2 and FMR1) on the X chromosome. Intriguingly, these miRNAs are predominantly expressed in the testis, suggesting a potential role in spermatogenesis and male fertility. Here, we report that the X-linked MIR-506 family miRNAs were derived from the MER91C DNA transposons. Selective inactivation of individual miRNAs or clusters caused no discernible defects, but simultaneous ablation of five clusters containing 19 members of the MIR-506 family led to reduced male fertility in mice. Despite normal sperm counts, motility, and morphology, the KO sperm were less competitive than wild-type sperm when subjected to a polyandrous mating scheme. Transcriptomic and bioinformatic analyses revealed that these X-linked MIR-506 family miRNAs, in addition to targeting a set of conserved genes, have more targets that are critical for spermatogenesis and embryonic development during evolution. Our data suggest that the MIR-506 family miRNAs function to enhance sperm competitiveness and reproductive fitness of the male by finetuning gene expression during spermatogenesis.

Social determinants of intrinsic capacity: A systematic review of observational studies.

BACKGROUND: The World Health Organization defined healthy ageing as the maintenance of functional ability with ageing. Intrinsic capacity is a measurement of healthy ageing, and can be shaped by social determinants. However, an overall understanding of how multiple social determinants contribute to intrinsic capacity remains unclear. We aim to summarize observational studies investigating the relationships between social determinants and intrinsic capacity among community-dwelling adults. METHODS: A systematic search was conducted through Medline, Embase, PsycInfo, Web of Science, and CINAHL until August 14, 2023. RESULTS: After reviewing 813 articles, we included 21 studies from nine countries in Asia, Europe, and America. Seventeen studies used a cross-sectional design and the others were longitudinal studies. Social determinants related to intrinsic capacity can be classified into five domains, containing socioeconomic status (16, 76.2% of studies), lifestyles (14, 66.7%), psychosocial factors (9, 42.9%), material circumstances (4, 19.0%), and healthcare systems (1, 4.8%). Strong evidence supported that better intrinsic capacity was associated with higher education, higher wealth, more physical activities, no smoking, more social engagement, and being married or partnered. The relationships of intrinsic capacity with dietary patterns and alcohol drinking were contradictory across studies. Research on the associations of working status, housing environments, and healthcare accessibility with intrinsic capacity was insufficient to draw conclusions. CONCLUSION: These findings highlight roles of socioeconomic status, lifestyles, and psychosocial factors in improving intrinsic capacity thus promoting healthy ageing. Future research is needed to investigate causal relationships between social determinants and intrinsic capacity, especially material circumstances and healthcare systems.

A tailed mirtron promotes longevity in Drosophila.

Thousands of atypical microRNAs (miRNAs) have been described in the genomes of animals; however, it is unclear if many of these non-canonical miRNAs can measurably influence phenotypes. Mirtrons are the largest class of non-canonical miRNAs that are produced from hairpins excised by splicing, which after debranching become substrates for Dicer and load into RISC. Most mirtrons require additional processing after splicing to remove 'tail' residues interposed between one of the host intron splice sites and base of the hairpin precursor structure. Despite most mirtrons requiring tail removal no function has been elucidated for a tailed species, indeed for all mirtrons identified function has only been assigned to a single species. Here we study miR-1017, a mirtron with a 3' tail, which is well expressed and conserved in Drosophila species. We found that miR-1017 can extend lifespan when ectopically expressed in the neurons, which seems partly due to this miRNA targeting its host transcript, acetylcholine receptor Dα2. Unexpectedly we found that not only did miR-1017 function in trans but also in cis by affecting splicing of Dα2. This suggests a mechanism for mirtron evolution where initial roles of structural elements in splicing lead to secondary acquisition of trans-regulatory function.

Impact of liver cirrhosis, severity of cirrhosis and portal hypertension on the difficulty of laparoscopic and robotic minor liver resections for primary liver malignancies in the anterolateral segments.

INTRODUCTION: We performed this study in order to investigate the impact of liver cirrhosis (LC) on the difficulty of minimally invasive liver resection (MILR), focusing on minor resections in anterolateral (AL) segments for primary liver malignancies. METHODS: This was an international multicenter retrospective study of 3675 patients who underwent MILR across 60 centers from 2004 to 2021. RESULTS: 1312 (35.7%) patients had no cirrhosis, 2118 (57.9%) had Child A cirrhosis and 245 (6.7%) had Child B cirrhosis. After propensity score matching (PSM), patients in Child A cirrhosis group had higher rates of open conversion (p = 0.024), blood loss >500 mls (p = 0.001), blood transfusion (p < 0.001), postoperative morbidity (p = 0.004), and in-hospital mortality (p = 0.041). After coarsened exact matching (CEM), Child A cirrhotic patients had higher open conversion rate (p = 0.05), greater median blood loss (p = 0.014) and increased postoperative morbidity (p = 0.001). Compared to Child A cirrhosis, Child B cirrhosis group had longer postoperative stay (p = 0.001) and greater major morbidity (p = 0.012) after PSM, and higher blood transfusion rates (p = 0.002), longer postoperative stay (p < 0.001), and greater major morbidity (p = 0.006) after CEM. After PSM, patients with portal hypertension experienced higher rates of blood loss >500 mls (p = 0.003) and intraoperative blood transfusion (p = 0.025). CONCLUSION: The presence and severity of LC affect and compound the difficulty of MILR for minor resections in the AL segments. These factors should be considered for inclusion into future difficulty scoring systems for MILR.

The Rapidly Evolving X-linked miR-506 Family Finetunes Spermatogenesis to Enhance Sperm Competition.

Despite rapid evolution across eutherian mammals, the X-linked miR-506 family miRNAs are located in a region flanked by two highly conserved protein-coding genes (Slitrk2 and Fmr1) on the X chromosome. Intriguingly, these miRNAs are predominantly expressed in the testis, suggesting a potential role in spermatogenesis and male fertility. Here, we report that the X-linked miR-506 family miRNAs were derived from the MER91C DNA transposons. Selective inactivation of individual miRNAs or clusters caused no discernable defects, but simultaneous ablation of five clusters containing nineteen members of the miR-506 family led to reduced male fertility in mice. Despite normal sperm counts, motility and morphology, the KO sperm were less competitive than wild-type sperm when subjected to a polyandrous mating scheme. Transcriptomic and bioinformatic analyses revealed that these X-linked miR-506 family miRNAs, in addition to targeting a set of conserved genes, have more targets that are critical for spermatogenesis and embryonic development during evolution. Our data suggest that the miR-506 family miRNAs function to enhance sperm competitiveness and reproductive fitness of the male by finetuning gene expression during spermatogenesis.

Autologous Breast Reconstruction Success Rates in Hypercoagulable Patients.

BACKGROUND: Hypercoagulable disorders may adversely affect microsurgical outcomes, including increased flap failure and complication rates. Outcomes specific to autologous breast reconstruction are not well described. METHODS: A retrospective review was performed of autologous breast reconstructions between 2009 and 2020. Patients with either a thrombophilic disorder (TD) diagnosis or a previous thrombotic event (TE) were identified. The analysis compared perioperative complications and flap success rates. RESULTS: In this series, 23 patients with a TD underwent 39 flaps, and 78 patients who had experienced a TE underwent 126 flaps, compared with 815 control patients, who underwent 1300 flaps. In logistic regression models, a TD diagnosis was an independent predictor of early total flap loss [OR, 8.42 (95% CI, 1.59 to 44.47); P = 0.01], late partial flap loss [OR, 3.9 (95% CI, 1.0 to 15.22); P = 0.05], and delayed healing [OR, 2.26 (95% CI, 1.02 to 5.04); P = 0.04]. TE history trended toward an association only with late partial flap loss ( P = 0.057). Flap salvage rates (25%) and flap success rates (92.3%) were statistically lower in patients with a TD but normal in patients who had experienced a TE. CONCLUSIONS: Microsurgical breast reconstruction is a reasonable option for patients with hypercoagulation disorders. No increased risk of flap complications was associated with a previous TE; however, TDs carried increased risk. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

The role of older adult-focused social vulnerability on the relationship between temperature and emergency department attendance in a subtropical Asian city.

PURPOSE: Older adults exhibit a wide range of capabilities and vulnerabilities that affect their capacity to respond to heat. This study analysed the associations between hot temperatures and Accident & Emergency (A&E) attendance taking into account older adult-focused social vulnerability. METHODS: Daily A&E attendance data of Young-old (65-74) and Old-old (75+) was obtained for Hong Kong 2010-2019 hot seasons and stratified into three Social Vulnerability Index (SVI) groups (Low, Moderate, High). Mean temperature (lag 0-2) was analysed on A&E attendance at each SVI using Generalized Additive Models and Distributed Lag Non-linear Models. RESULTS: High temperatures were associated with increased same-day (lag 0) relative risk (RR) of A&E attendance for Young-old and Old-old in High SVI districts, with RR being 1.024 (95 % CI: 1.011, 1.037) and 1.036 (95 % CI: 1.018, 1.053), respectively. The Old-old living in Moderate and Low SVI districts also demonstrated increased RR of 1.037 (95 % CI: 1.028, 1.047) and 1.022 (95 % CI: 1.009, 1.036), respectively. Fewer emergency visits were found on the subsequent day (lag 1) of hot temperatures. CONCLUSIONS: Older adults, both young-old and old-old, living in districts with higher social vulnerability tended to have increased risk of A&E attendance associated with same-day high temperature. With climate change and rapidly aging population, cities should prepare to meet needs of more vulnerable older adults in extreme heat.