SF-CORNER (splenic flexure colorectal cancer): an international survey of operative approaches and outcomes for cancers of the splenic flexure.

AIM: The optimum surgical approach to splenic flexure cancers (SFCs) remains uncertain. The aim of this survey was to explore the opinions of an international surgical community on the management and outcomes of SFC. METHOD: A questionnaire was constructed comprising five sections (information about respondents; definition and prognosis of SFC; operative approach; approach in specific scenarios; outcomes) and circulated through an international dissemination committee and social media. RESULTS: The survey received 576 responses over 4 weeks across 50 countries. There was no consensus regarding the definition of the splenic flexure, whilst the proportion of respondents who did and did not think that patients with SFC had a worse outcome was equal. The overall preferred operative approach was left hemicolectomy [203 (35.2%)], followed by segmental resection [167 (29%)], extended right hemicolectomy [126 (21.9%)] and subtotal colectomy [7 (12%)]. The stated pedicles for ligation varied between resection types and also within the same resection. One hundred and sixty-six (28.8%) respondents thought a segmental resection was associated with the worst survival and 190 (33%) thought it was associated with the best quality of life. CONCLUSION: This survey confirms a lack of consensus across all aspects SFC treatment. The differing approaches described are likely to represent different beliefs around the variable anatomy of this region and the associated lymphatic drainage. Future studies are required to address such inconsistencies and identify the optimum surgical strategy, whilst also incorporating quality-of-life metrics and patient-reported outcomes. A one-size-fits-all approach is probably not appropriate with SFC, and a more bespoke approach is required.

Vitamin D status and clinical implications in the adult population of Malaysia: a position paper by the Malaysian Vitamin D Special Interest Group.

PURPOSE: Vitamin D deficiency and insufficiency is common among populations globally, and in Asia and Malaysia. The purpose of this Position Paper is to propose recommendations for both clinicians and non-clinicians to promote vitamin D sufficiency in Malaysian adults. Formation of a national multisector, multidisciplinary alliance is also proposed to progress initiatives relating to safe sun exposure, adequate vitamin D intake through food fortification, and vitamin D supplementation for high-risk groups. METHODS: Literature reviews were undertaken to inform summaries of the following: vitamin D status globally and in Asian and Malaysian populations, vitamin D status among individuals with common medical conditions, and current recommendations to achieve vitamin D sufficiency through sun exposure, food intake and supplementation. Recommendations were based on the findings of the literature reviews, recent European guidance on vitamin D supplementation, the 2018 road map for action on vitamin D in low- and middle-income countries, and research recommendations proposed by the Malaysian Ministry of Health in 2017. RESULTS: Recommendations on assessment of vitamin D in the adult Malaysian population include using serum or plasma 25-hydroxyvitamin D concentration as a biomarker, widespread participation by Malaysian laboratories in the Vitamin D Standardization Program, adoption of the US Endocrine Society definitions of vitamin D deficiency and insufficiency, and development of a comprehensive nationwide vitamin D status study. Specific high-risk groups are identified for vitamin D assessment and recommendations relating to loading doses and ongoing management are also made. CONCLUSION: This Position Paper provides individual clinicians and national stakeholder organisations with clear recommendations to achieve vitamin D sufficiency in the adult population of Malaysia.

Development of the Asia Pacific Consortium on Osteoporosis (APCO) Framework: clinical standards of care for the screening, diagnosis, and management of osteoporosis in the Asia-Pacific region.

Guidelines for doctors managing osteoporosis in the Asia-Pacific region vary widely. We compared 18 guidelines for similarities and differences in five key areas. We then used a structured consensus process to develop clinical standards of care for the diagnosis and management of osteoporosis and for improving the quality of care. PURPOSE: Minimum clinical standards for assessment and management of osteoporosis are needed in the Asia-Pacific (AP) region to inform clinical practice guidelines (CPGs) and to improve osteoporosis care. We present the framework of these clinical standards and describe its development. METHODS: We conducted a structured comparative analysis of existing CPGs in the AP region using a "5IQ" model (identification, investigation, information, intervention, integration, and quality). One-hundred data elements were extracted from each guideline. We then employed a four-round Delphi consensus process to structure the framework, identify key components of guidance, and develop clinical care standards. RESULTS: Eighteen guidelines were included. The 5IQ analysis demonstrated marked heterogeneity, notably in guidance on risk factors, the use of biochemical markers, self-care information for patients, indications for osteoporosis treatment, use of fracture risk assessment tools, and protocols for monitoring treatment. There was minimal guidance on long-term management plans or on strategies and systems for clinical quality improvement. Twenty-nine APCO members participated in the Delphi process, resulting in consensus on 16 clinical standards, with levels of attainment defined for those on identification and investigation of fragility fractures, vertebral fracture assessment, and inclusion of quality metrics in guidelines. CONCLUSION: The 5IQ analysis confirmed previous anecdotal observations of marked heterogeneity of osteoporosis clinical guidelines in the AP region. The Framework provides practical, clear, and feasible recommendations for osteoporosis care and can be adapted for use in other such vastly diverse regions. Implementation of the standards is expected to significantly lessen the global burden of osteoporosis.

Effect of atrial fibrillation on endovascular thrombectomy for acute ischemic stroke. A meta-analysis of individual patient data from six randomised trials: Results from the HERMES collaboration.

BACKGROUND: Atrial fibrillation is an important risk factor for ischemic stroke, and is associated with an increased risk of poor outcome after ischemic stroke. Endovascular thrombectomy is safe and effective in acute ischemic stroke patients with large vessel occlusion of the anterior circulation. This meta-analysis aims to investigate whether there is an interaction between atrial fibrillation and treatment effect of endovascular thrombectomy, and secondarily whether atrial fibrillation is associated with worse outcome in patients with ischemic stroke due to large vessel occlusion. METHODS: Individual patient data were from six of the recent randomised clinical trials (MR CLEAN, EXTEND-IA, REVASCAT, SWIFT PRIME, ESCAPE, PISTE) in which endovascular thrombectomy plus standard care was compared to standard care alone. Primary outcome measure was the shift on the modified Rankin scale (mRS) at 90 days. Secondary outcomes were functional independence (mRS 0-2) at 90 days, National Institutes of Health Stroke Scale score at 24 h, symptomatic intracranial hemorrhage and mortality at 90 days. The primary effect parameter was the adjusted common odds ratio, estimated with ordinal logistic regression (shift analysis); treatment effect modification of atrial fibrillation was assessed with a multiplicative interaction term. RESULTS: Among 1351 patients, 447 patients had atrial fibrillation, 224 of whom were treated with endovascular thrombectomy. We found no interaction of atrial fibrillation with treatment effect of endovascular thrombectomy for both primary (p-value for interaction: 0.58) and secondary outcomes. Regardless of treatment allocation, we found no difference in primary outcome (mRS at 90 days: aOR 1.11 (95% CI 0.89-1.38) and secondary outcomes between patients with and without atrial fibrillation. CONCLUSION: We found no interaction of atrial fibrillation on treatment effect of endovascular thrombectomy, and no difference in outcome between large vessel occlusion stroke patients with and without atrial fibrillation.

IQ driving QI: the Asia Pacific Consortium on Osteoporosis (APCO): an innovative and collaborative initiative to improve osteoporosis care in the Asia Pacific.

Asia Pacific Consortium on Osteoporosis (APCO) comprises of clinical experts from across the Asia Pacific region, uniting to develop solutions to problems facing osteoporosis management and care. The vision of APCO is to reduce the burden of osteoporosis and fragility fractures in the Asia Pacific region. INTRODUCTION: The Asia Pacific (AP) region comprises 71 countries with vastly different healthcare systems. It is predicted that by 2050, more than half the world's hip fractures will occur in this region. The Asia Pacific Consortium on Osteoporosis (APCO) was set up in May 2019 with the vision of reducing the burden of osteoporosis and fragility fractures in the AP region. METHODS: APCO has so far brought together 39 clinical experts from countries and regions across the AP to develop solutions to challenges facing osteoporosis management and fracture prevention in this highly populous region of the world. APCO aims to achieve its vision by engaging with relevant stakeholders including healthcare providers, policy makers and the public. The initial APCO project is to develop and implement a Framework of pan-AP minimum clinical standards for the screening, diagnosis and management of osteoporosis. RESULTS AND CONCLUSIONS: The Framework will serve as a platform upon which new national clinical guidelines can be developed or existing guidelines be revised, in a standardised fashion. The Framework will also facilitate benchmarking for provision of quality of care. It is hoped that the principles underlying the formation and functioning of APCO can be adopted by other regions and that every health care facility and progressively every country in the world can follow our aspirational path and progress towards best practice.

Survival after non-resection of colorectal cancer: the argument for including non-operatives in consultant outcome reporting in the UK.

INTRODUCTION: Although the mainstay of colorectal cancer treatment remains operative, a significant proportion of patients end up without surgery. This is because they are either deemed to have no oncological benefit from the resection (too much disease) or to be unfit for major surgery (too frail). The aim of this study was to assess the proportion and survival of these two groups among the totality of practice in a tertiary unit and to discuss the implications on the conceptual understanding of outcome measures. METHODS: Data was collected over two study periods with the total duration of four years. Patient demographics, comorbidities, cancer staging and management pathways were all recorded. The primary endpoint was all-cause mortality. RESULTS: The total of 909 patients were examined. In the 29% who did not undergo resectional surgery, 6.5% had too little disease, 13.8% had too much disease, while 8.7% were deemed too frail. The highest two-year mortality was observed in the too much (83.2%) and too frail (75.9%) groups, whereas in patients with too little cancer the rate was 5.1%, and in those undergoing a resection it was 19.2% (P < 0.001). CONCLUSIONS: The study has expectedly shown poor survival in the too much and too frail groups. We believe that understanding the prognosis in these subgroups is vital, as it informs complex decisions on whether to operate. Moreover, an overall reporting taking into account the proportion of these groups in an multidisciplinary team practice (the non-surgical index) is proposed to render individual surgeon's mortality results meaningful as a comparative measure.

A global call to action to improve the care of people with fragility fractures.

The ageing of society is driving an enormous increase in fragility fracture incidence and imposing a massive burden on patients, their families, health systems and societies globally. Disrupting the status quo has therefore become an obligation and a necessity. Initiated by the Fragility Fracture Network (FFN) at a "Presidents' Roundtable" during the 5th FFN Global Congress in 2016 several leading organisations agreed that a global multidisciplinary and multiprofessional collaboration, resulting in a Global Call to Action (CtA), would be the right step forward to improve the care of people presenting with fragility fractures. So far global and regional organisations in geriatrics/internal medicine, orthopaedics, osteoporosis/metabolic bone disease, rehabilitation and rheumatology were contacted as well as national organisations in five highly populated countries (Brazil, China, India, Japan and the United States), resulting in 81societies endorsing the CtA. We call for implementation of a systematic approach to fragility fracture care with the goal of restoring function and preventing subsequent fractures without further delay. There is an urgent need to improve: To address this fragility fracture crisis, the undersigned organisations pledge to intensify their efforts to improve the current management of all fragility fractures, prevent subsequent fractures, and strive to restore functional abilities and quality of life.

Mind the (treatment) gap: a global perspective on current and future strategies for prevention of fragility fractures.

This narrative review considers the key challenges facing healthcare professionals and policymakers responsible for providing care to populations in relation to bone health. These challenges broadly fall into four distinct themes: (1) case finding and management of individuals at high risk of fracture, (2) public awareness of osteoporosis and fragility fractures, (3) reimbursement and health system policy and (4) epidemiology of fracture in the developing world. Findings from cohort studies, randomised controlled trials, systematic reviews and meta-analyses, in addition to current clinical guidelines, position papers and national and international audits, are summarised, with the intention of providing a prioritised approach to delivery of optimal bone health for all. Systematic approaches to case-finding individuals who are at high risk of sustaining fragility fractures are described. These include strategies and models of care intended to improve case finding for individuals who have sustained fragility fractures, those undergoing treatment with medicines which have an adverse effect on bone health and people who have diseases, whereby bone loss and, consequently, fragility fractures are a common comorbidity. Approaches to deliver primary fracture prevention in a clinically effective and cost-effective manner are also explored. Public awareness of osteoporosis is low worldwide. If older people are to be more pro-active in the management of their bone health, that needs to change. Effective disease awareness campaigns have been implemented in some countries but need to be undertaken in many more. A major need exists to improve awareness of the risk that osteoporosis poses to individuals who have initiated treatment, with the intention of improving adherence in the long term. A multisector effort is also required to support patients and their clinicians to have meaningful discussions concerning the risk-benefit ratio of osteoporosis treatment. With regard to prioritisation of fragility fracture prevention in national policy, there is much to be done. In the developing world, robust epidemiological estimates of fracture incidence are required to inform policy development. As the aging of the baby boomer generation is upon us, this review provides a comprehensive analysis of how bone health can be improved worldwide for all.

Association between CYP2C19 Polymorphisms and Outcomes in Cerebral Endovascular Therapy.

BACKGROUND AND PURPOSE: Differing responses to clopidogrel following endovascular treatment of cerebrovascular diseases may increase the risk of vascular complications. CYP2C19 gene polymorphisms influence clopidogrel activity. We aimed to study the clinical impact of CYP2C19 gene polymorphisms in patients undergoing endovascular treatment. MATERIALS AND METHODS: This was a prospective, longitudinal, observational study. Information on demographics and cerebrovascular status was collected as baseline. Clopidogrel response was tested by the VerifyNow P2Y12 assay. CYP2C19 genotyping was undertaken by polymerase chain reaction-restriction fragment length polymorphism. Three-month follow-up data included vascular complications, mortality, and modified Rankin Scale score. Associations were investigated among CYP2C19 genotypes, clopidogrel responsiveness, and clinical outcomes. RESULTS: One hundred and eight participants were included. Median age was 56 years (interquartile range, 48.8-65.0 years), and 35 (32.4%) were male. Forty-four participants were classified into group 1 (homozygous CYP2C19*1/*1); 31, into group 2 (25 with CYP2C19*1/*2, two with CYP2C19*1/*3, three with CYP2C19*3/*3, one with CYP2C19*2/*3); 28, into group 3 (24 with CYP2C19*1/*17, four with CYP2C19*17/*17); and 5, into group 4 (CYP2C19*2/*17). A significantly higher proportion of participants in group 3 experienced ischemic events (9 of 28, 32.1%) compared with group 1 (5 of 44, 11.4%; P = .04; odds ratio, 3.7; 95% confidence interval, 1.1-12.6). There was no significant difference in clopidogrel response among the 4 genotype groups. CONCLUSIONS: Individuals with CYP2C19*17 may have increased risk of ischemic events following endovascular treatment, independent of clopidogrel responsiveness. Larger studies are required to confirm the influence of CYP2C19*17 on clinical outcomes and to understand the mechanisms for increased ischemic events.

The detection of periapical pathoses using digital periapical radiography and cone beam computed tomography in endodontically retreated teeth - part 2: a 1 year post-treatment follow-up.

AIM: Part 2 of this prospective clinical study aimed to compare the 1-year outcome of root canal retreatments, when individual roots and teeth were assessed by periapical radiographs and cone beam computed tomography (CBCT). METHODOLOGY: Subjects participating in this study had been referred for management of an endodontic problem associated with one or more root filled teeth. Root canal retreatment was performed by Specialists or postgraduate students under the direct supervision of Specialist endodontic staff. A total of 98 teeth (84 patients) were reassessed clinically and radiographically 1 year after completion of root canal retreatment. The postoperative periapical radiographs and CBCT scans were compared with their respective pre-treatment (diagnostic) periapical radiographs and CBCT scans. The increase or decrease in size of existing periapical radiolucencies and development of new radiolucencies were assessed by a consensus panel consisting of two calibrated examiners. They also determined an appropriate management plan for each case based on the radiographical findings. Comparison of the outcome diagnosis of individual roots and teeth and case management, when assessed by periapical radiographs and CBCT scans, was performed using chi-squared and McNemar's tests. RESULTS: An overall favourable result of 93% success for teeth (96% roots) was recorded when the assessment was undertaken by periapicals compared with 77% success for teeth (87% roots) when assessed by CBCT. A significant difference in outcome diagnosis of single paired roots (P < 0.0001) and teeth (P = 0.0001) was observed when comparing periapicals to CBCT for the cohort of teeth as a whole. When comparing the future management plan on the basis of radiographic information alone, there was a significant difference between periapicals and CBCT-based management (P = 0.01). CONCLUSION: Diagnosis using CBCT revealed a significantly lower number of favourable outcomes than periapicals in root canal retreatment. This significantly affected the future management of cases attending for a review.

Life-course approach to nutrition.

This narrative review summarizes the role that nutrition plays in the development and maintenance of a healthy skeleton throughout the life-course. Nutrition has a significant influence on bone health throughout the life cycle. This narrative review summarizes current knowledge and guidance pertaining to the development and maintenance of a healthy skeleton. The primary objectives proposed for good bone health at the various stages of life are the following: Children and adolescents: achieve genetic potential for peak bone mass Adults: avoid premature bone loss and maintain a healthy skeleton Seniors: prevention and treatment of osteoporosis Findings from cohort studies, randomized controlled trials, systematic reviews and meta-analyses, in addition to current dietary guidelines, are summarized with the intention of providing clear nutritional guidance for these populations and pregnant women.

Effective secondary fracture prevention: implementation of a global benchmarking of clinical quality using the IOF Capture the Fracture® Best Practice Framework tool.

UNLABELLED: Fracture Liaison Services are the best model to prevent secondary fractures. The International Osteoporosis Foundation developed a Best Practice Framework to provide a quality benchmark. After a year of implementation, we confirmed that a single framework with set criteria is able to benchmark services across healthcare systems worldwide. INTRODUCTION: Despite evidence for the clinical effectiveness of secondary fracture prevention, translation in the real-world setting remains disappointing. Where implemented, a wide variety of service models are used to deliver effective secondary fracture prevention. To support use of effective models of care across the globe, the International Osteoporosis Foundation's Capture the Fracture® programme developed a Best Practice Framework (BPF) tool of criteria and standards to provide a quality benchmark. We now report findings after the first 12 months of implementation. METHODS: A questionnaire for the BPF was created and made available to institutions on the Capture the Fracture website. Responses from institutions were used to assign gold, silver, bronze or black (insufficient) level of achievements mapped across five domains. Through an interactive process with the institution, a final score was determined and published on the Capture the Fracture website Fracture Liaison Service (FLS) map. RESULTS: Sixty hospitals across six continents submitted their questionnaires. The hospitals served populations from 20,000 to 15 million and were a mix of private and publicly funded. Each FLS managed 146 to 6200 fragility fracture patients per year with a total of 55,160 patients across all sites. Overall, 27 hospitals scored gold, 23 silver and 10 bronze. The pathway for the hip fracture patients had the highest proportion of gold grading while vertebral fracture the lowest. CONCLUSION: In the first 12 months, we have successfully tested the BPF tool in a range of health settings across the globe. Initial findings confirm a significant heterogeneity in service provision and highlight the importance of a global approach to ensure high quality secondary fracture prevention services.

Transdisciplinary synthesis for ecosystem science, policy and management: The Australian experience.

Mitigating the environmental effects of global population growth, climatic change and increasing socio-ecological complexity is a daunting challenge. To tackle this requires synthesis: the integration of disparate information to generate novel insights from heterogeneous, complex situations where there are diverse perspectives. Since 1995, a structured approach to inter-, multi- and trans-disciplinary(1) collaboration around big science questions has been supported through synthesis centres around the world. These centres are finding an expanding role due to ever-accumulating data and the need for more and better opportunities to develop transdisciplinary and holistic approaches to solve real-world problems. The Australian Centre for Ecological Analysis and Synthesis (ACEAS ) has been the pioneering ecosystem science synthesis centre in the Southern Hemisphere. Such centres provide analysis and synthesis opportunities for time-pressed scientists, policy-makers and managers. They provide the scientific and organisational environs for virtual and face-to-face engagement, impetus for integration, data and methodological support, and innovative ways to deliver synthesis products. We detail the contribution, role and value of synthesis using ACEAS to exemplify the capacity for synthesis centres to facilitate trans-organisational, transdisciplinary synthesis. We compare ACEAS to other international synthesis centres, and describe how it facilitated project teams and its objective of linking natural resource science to policy to management. Scientists and managers were brought together to actively collaborate in multi-institutional, cross-sectoral and transdisciplinary research on contemporary ecological problems. The teams analysed, integrated and synthesised existing data to co-develop solution-oriented publications and management recommendations that might otherwise not have been produced. We identify key outcomes of some ACEAS working groups which used synthesis to tackle important ecosystem challenges. We also examine the barriers and enablers to synthesis, so that risks can be minimised and successful outcomes maximised. We argue that synthesis centres have a crucial role in developing, communicating and using synthetic transdisciplinary research.

Picture-to-puncture time in acute stroke endovascular intervention: are we getting faster?

BACKGROUND: In acute stroke management, time efficiency in the continuum of patient management is critical. We aimed to determine if implementation of system improvements at our institution translated to reduced picture-to-puncture (P2P) times over a 6-year period. METHODS: We conducted a single-center retrospective analysis using a prospective acute stroke database of patients treated with intra-arterial therapy from October 2007 to October 2013. Patient demographics, stroke severity, neuroimaging and treatment time points were collected. Annual P2P times, defined as the interval between pretreatment neuroimaging (picture) and commencement of intra-arterial therapy (puncture), were assessed and compared. RESULTS: From 2007 to 2013 a total of 189 patients were identified, of which 181 met the study criteria. At initial presentation, median baseline NIH Stroke Severity score was 17.00 (IQR 11.00-22.00). Annual median P2P times decreased from 171 to 123.5 min, showing a median decrease of 11.5 min per annum (95% CI -23.9 to 0.9) and trending towards statistical significance (p=0.069). Plotted data revealed longer P2P times in instances where stroke onset or CT acquisition times were out-of-hours. Using median regression modeling, the annual decrease in P2P median time reached statistical significance when independently adjusting for CT acquisition time (13.5 min P2P median time reduction, 95% CI -27.0 to -0.1, p=0.048) and for stroke onset time (14.5 min annual P2P median time reduction, 95% CI -26.1 to -2.8, p=0.015). CONCLUSIONS: As a consequence of systems improvement at our institution, we were able to demonstrate improved annual median P2P times from 2007 to 2013.

Anal acoustic reflectometry predicts the outcome of percutaneous nerve evaluation for faecal incontinence.

BACKGROUND: Sacral nerve stimulation (SNS) is effective for some patients with faecal incontinence. Before insertion of a costly implant, percutaneous nerve evaluation (PNE) is undertaken to identify patients likely to report success from SNS. The aim of this study was to determine whether variables of anal sphincter function measured by anal acoustic reflectometry (AAR) could predict the outcome of PNE for faecal incontinence. METHODS: Women with faecal incontinence undergoing PNE were recruited. AAR, followed by anal manometry, was performed on the day of surgery, immediately before PNE. The outcome of PNE was determined by bowel diary results and incontinence severity score. Patients with a successful PNE outcome were compared with those with an unsuccessful outcome; logistic regression analysis was used to identify any independent predictors of success. RESULTS: Fifty-two patients were recruited, of whom 32 (62 per cent) had a successful PNE outcome and 20 (38 per cent) an unsuccessful outcome. The AAR variable opening pressure was significantly greater in patients who subsequently had a successful PNE result compared with the pressure in patients who did not (28 versus 17 cmH2 O; P = 0·008). No difference was seen in the manometric equivalent, maximum resting pressure. Opening pressure was an independent predictor of success with an odds ratio of 1·08 (95 per cent confidence interval 1·01 to 1·16; P = 0·018). CONCLUSION: AAR is a sensitive test of sphincter function and can identify differences between patients who respond to PNE and those who do not. Opening pressure is an independent predictor of success in PNE, and may be of value in the selection of patients for this expensive treatment option.

Co-ordination of growth, gas exchange and hydraulics define the carbon safety margin in tree species with contrasting drought strategies.

Gas exchange, growth, water transport and carbon (C) metabolism diminish during drought according to their respective sensitivities to declining water status. The timing of this sequence of declining physiological functions may determine how water and C relations compromise plant survival. In this paper, we test the hypothesis that the degree of asynchrony between declining C supply (photosynthesis) and C demand (growth and respiration) determines the rate and magnitude of changes in whole-plant non-structural carbohydrates (NSC) during drought. Two complementary experiments using two tree species (Eucalyptus globulus Labill. and Pinus radiata D. Don) with contrasting drought response strategies were performed to (i) assess changes in radial stem growth, transpiration, leaf water potential and gas exchange in response to chronic drought, and (ii) evaluate the concomitant impacts of these drought responses on the temporal patterns of NSC during terminal drought. The three distinct phases of water stress were delineated by thresholds of growth cessation and stomatal closure that defined the 'carbon safety margin' (i.e., the difference between leaf water potential when growth is zero and leaf water potential when net photosynthesis is zero). A wider C safety margin in E. globulus was defined by an earlier cessation of growth relative to photosynthesis that reduced the demand for NSC while maintaining C acquisition. By contrast, the narrower C safety margin in P. radiata was characterized by a synchronous decline in growth and photosynthesis, whereby growth continued under a declining supply of NSC from photosynthesis. The narrower C safety margin in P. radiata was associated with declines in starch concentrations after ∼ 90 days of chronic drought and significant depletion of starch in all organs at mortality. The observed divergence in the sensitivity of drought responses is indicative of a potential trade-off between maintaining hydraulic safety and adequate C availability.