Diagnosis, management and outcome of splenic torsion; a systematic review of published studies.

INTRODUCTION: Splenic torsion is a rare condition but one that many surgeons will encounter once in their career. Management options are varied but due to the rarity of the condition there are no contemporary evidence-based summaries to inform a treating clinician. We aim to describe patterns of presentation and provide an evidence-based guide to the management. METHODS: A PRISMA structured meta-analysis was conducted of all published cases of splenic torsion and a recent case added from our institution. RESULTS: 408 cases were identified between 1888 and 2021 and a single case added from our institution, 312 cases were sourced from case reports and 96 from 40 case series. 8% of patients had a co-existing congenital anomaly and 28% an identified risk factor for splenic torsion. 82% required emergency surgery. A preoperative diagnosis is becoming more common, reaching 80% in 2020's. While spleen conserving surgery is feasible using a variety of techniques. splenectomy was the definitive management for the majority (82%). On histopatholy no occult disease was identified and a significant number of resected spleens were potentially viable; 32% were reported to be normal or congested and 14% demonstrated only partial or focal necrosis. DISCUSSION: Despite the significant publication bias implied by the methodology this is a large dataset in a rare condition. Splenic torsion frequently occurs in a premorbid population. The presence of a palpable mass in the context of abdominal pain should increase suspicion and trigger cross sectional imaging. Conservation of the spleen, using the techniques discussed, should be seriously considered.

Primary hyperparathyroidism in adults-(Part II) surgical management and postoperative follow-up: Position statement of the Endocrine Society of Australia, The Australian & New Zealand Endocrine Surgeons, and The Australian & New Zealand Bone and Mineral Society.

OBJECTIVE: To develop evidence-based recommendations to guide the surgical management and postoperative follow-up of adults with primary hyperparathyroidism. METHODS: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing eight key questions. RESULTS: Diagnostic imaging does not determine suitability for surgery but can guide the planning of surgery in suitable candidates. First-line imaging includes ultrasound and either parathyroid 4DCT or scintigraphy, depending on local availability and expertise. Minimally invasive parathyroidectomy is appropriate in most patients with concordant imaging. Bilateral neck exploration should be considered in those with discordant/negative imaging findings, multi-gland disease and genetic/familial risk factors. Parathyroid surgery, especially re-operative surgery, has better outcomes in the hands of higher volume surgeons. Neuromonitoring is generally not required for initial surgery but should be considered for re-operative surgery. Following parathyroidectomy, calcium and parathyroid hormone levels should be re-checked in the first 24 h and repeated early if there are risk factors for hypocalcaemia. Eucalcaemia at 6 months is consistent with surgical cure; parathyroid hormone levels do not need to be re-checked in the absence of other clinical indications. Longer-term surveillance of skeletal health is recommended. CONCLUSIONS: This position statement provides up-to-date guidance on evidence-based best practice surgical and postoperative management of adults with primary hyperparathyroidism.

Primary hyperparathyroidism in adults-(Part I) assessment and medical management: Position statement of the endocrine society of Australia, the Australian & New Zealand endocrine surgeons, and the Australian & New Zealand bone and mineral society.

OBJECTIVE: To formulate clinical consensus recommendations on the presentation, assessment, and management of primary hyperparathyroidism (PHPT) in adults. METHODS: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing nine key questions. RESULTS: PHPT is a biochemical diagnosis. Serum calcium should be measured in patients with suggestive symptoms, reduced bone mineral density or minimal trauma fractures, and in those with renal stones. Other indications are detailed in the manuscript. In patients with hypercalcaemia, intact parathyroid hormone, 25-hydroxy vitamin D, phosphate, and renal function should be measured. In established PHPT, assessment of bone mineral density, vertebral fractures, urinary tract calculi/nephrocalcinosis and quantification of urinary calcium excretion is warranted. Parathyroidectomy is the only definitive treatment and is warranted for all symptomatic patients and should be considered for asymptomatic patients without contraindications to surgery and with >10 years life expectancy. In patients who do not undergo surgery, we recommend annual evaluation for disease progression. Where the diagnosis is not clear or the risk-benefit ratio is not obvious, multidisciplinary discussion and formulation of a consensus management plan is appropriate. Genetic testing for familial hyperparathyroidism is recommended in selected patients. CONCLUSIONS: These clinical consensus recommendations were developed to provide clinicians with contemporary guidance on the assessment and management of PHPT in adults. It is anticipated that improved health outcomes for individuals and the population will be achieved at a decreased cost to the community.

Body mass, cardiorespiratory fitness, and cardiometabolic risk over time: Findings from the Cooper Center Longitudinal Study.

Few studies have adequately assessed the simultaneous effects of changes in cardiorespiratory fitness (fitness) and body mass on cardiometabolic risk. Hence, the current study's aims were twofold: (1) To determine whether increases in body mass result in higher cardiometabolic risk after controlling for fitness changes; and (2) To assess whether increases in fitness result in lower cardiometabolic risk after controlling for weight changes. The study consisted of 3534 patients who came for preventive medicine visits ≥4 times over any 10-year period (1979-2019). The primary independent variables were body mass and fitness, and the dependent variable was metabolic syndrome (MetS) and its components. Mixed-effects regression was used to model the relationship between changes in body mass, fitness, and MetS. Results indicate that increasing body mass up to a 10-year period was significantly related to increasing risk of MetS while controlling for changes in fitness. Specifically, a 1-kg increase in body mass was associated with a 17% (OR = 1.17; 95% CI 1.15-1.19) increased odds for MetS, while adjusting for fitness changes. A 1-MET increase in fitness was related to a 23% (OR = 0.77; 95% CI 0.70-0.84) decrease in odds for MetS, while adjusting for body mass changes up to 10 years. Moreover, body mass change was significantly related to changes in all cardiometabolic components of MetS. Fitness change was significantly associated with changes in MetS components. Future interventions should focus concurrently on increasing fitness and on body mass loss (or maintenance) to improve cardiometabolic health.

Functional Movement Screening Performance and Association With Key Health Markers in Older Adults.

ABSTRACT: Farrell, SW, Pavlovic, A, Barlow, CE, Leonard, D, DeFina, JR, Willis, BL, DeFina, LF, and Haskell, WL. Functional movement screening performance and association with key health markers in older adults. J Strength Cond Res 35(11): 3021-3027, 2021-We examined Functional Movement Screening (FMS) performance and associations with key health markers among adults aged 55 years or older. Apparently healthy men (n = 425) and women (n = 158) completed a preventive medical examination between 2013 and 2018. Subjects were grouped by age and sex to determine mean scores for individual FMS items as well as total FMS score. We examined partial correlations between total FMS score and key health markers. We computed odds ratios (ORs) for having a total FMS score ≤14. The mean FMS scores for men and women were 11.7 ± 2.8 and 11.9 ± 2.3, respectively. Several differences were found between men who participated in FMS (takers) compared with FMS nontakers, whereas women FMS takers were generally similar to women FMS nontakers. After controlling for age, sex, and smoking, FMS scores were directly associated with physical activity (PA), cardiorespiratory fitness, frequency of resistance training, serum vitamin D, omega-3 index, low-density lipoprotein, and high-density lipoprotein (HDL)-cholesterol, and were inversely associated with body mass index (BMI), waist circumference (WC), blood glucose, HbA1c, and metabolic syndrome (p ≤ 0.02 for each). Adjusted OR for scoring ≤14 was significantly greater for those who were BMI and WC-obese, those with metabolic syndrome, those with low HDL-cholesterol, and those not meeting current PA guidelines. This study provides characteristics and mean values for FMS in a large older population and demonstrates that FMS performance is associated with key health markers. Prospective studies of older adults are needed to determine the utility of FMS in predicting future musculoskeletal injury and other chronic disease-related health outcomes.

The association between serum vitamin d level and cognitive function in older adults: Cooper Center Longitudinal Study.

Low blood level of vitamin D and low physical activity have been linked to the development of cognitive impairment in older adults. The purpose of the present study was to examine the relationship between serum vitamin D and cognition as measured via the Montreal Cognitive Assessment (MoCA) in a healthy, older population. The study sample consisted of 4358 patients from the Cooper Clinic in Dallas, TX. All participants underwent a maximal graded exercise test to determine cardiorespiratory fitness (CRF). Cognitive impairment was defined as a MoCA score <25. Low vitamin D status was defined as serum 25-hydroxyvitamin D <30 ng/mL. Multivariable logistic regression analysis was employed to evaluate the association between vitamin D blood level and MoCA score. A low MoCA score was directly associated with higher age (OR: 1.75, 95% CI: 1.53, 1.99), and inversely associated with female sex (OR: 0.63, 95% CI: 0.51, 0.77), and years of education (OR: 0.87, 95% CI: 0.84, 0.91). When controlling for significant predictors (age, sex, and education), the low vitamin D group had a significantly greater likelihood of having a low MoCA score (OR: 1.26, 95% CI: 1.04, 1.51). The vitamin D effect remained significant when CRF was added to the model (OR: 1.23, 95% CI: 1.02, 1.48). In conclusion, low vitamin D was shown to be associated with cognitive impairment. Therefore, preventive measures such as vitamin D supplementation may play a protective role in memory loss and/or age-associated cognitive decline.

Thyroid nodules: diagnosis and management.

Thyroid nodules are common. Their importance lies in the need to assess thyroid function, degree of and future risk of mass effect, and exclude thyroid cancer, which occurs in 7-15% of thyroid nodules. There are four key components to thyroid nodule assessment: clinical history and examination, serum thyroid stimulating hormone (TSH) measurement, ultrasound and, if indicated, fine-needle aspiration (FNA). If the serum TSH is suppressed, a thyroid scan with 99Tc can distinguish between a solitary hot nodule, a toxic multinodular goitre or, less commonly, thyroiditis or Graves' disease within a coexisting nodular thyroid. Scintigraphically cold nodules are evaluated in the same way as in the setting of normal or elevated serum TSH levels. Thyroid ultrasonography should be performed only for palpable goitre and thyroid nodules and by specialists with expertise in thyroid sonography. Routine thyroid cancer screening is not recommended, except in high risk individuals, as the detection of early thyroid cancer has not been shown to improve survival. FNA may be performed for nodules ≥ 1.0 cm depending on clinical and sonographic risk factors for thyroid cancer. FNA specimens should be read by an experienced cytopathologist and be reported according to the Bethesda Classification System. Molecular analysis of indeterminate FNA samples has potential to better discriminate benign from malignant nodules and thus guide management. Surgery is indicated for FNA findings of malignancy or indeterminate cytology when there is a high risk clinical context. Surgery may also be indicated for suspicion of malignancy; larger nodules, especially with symptoms of mass effect; and in some patients with thyrotoxicosis.

The Relationship between Cardiorespiratory Fitness and Montreal Cognitive Assessment Scores in Older Adults.

BACKGROUND: Relatively little is known regarding the association between objective measures of physical function such as cardiorespiratory fitness (CRF) and cognitive function tests in healthy older adults. OBJECTIVE: To evaluate the relationship between CRF and cognitive function in adults aged 55 and older. METHODS: Between 2008 and 2017, 4,931 men and women underwent a comprehensive preventive physical exam at the Cooper Clinic in Dallas, Texas. CRF was determined by duration of a maximal treadmill exercise test. Cognitive function was evaluated with the Montreal Cognitive Assessment (MoCA). In a multivariate model, adjusted odds ratios with 95% confidence intervals for MoCA scores < 26 (i.e., cognitive impairment) were determined by using CRF as both a continuous and a categorical variable. RESULTS: The mean age of the sample was 61.0 ± 6.0 years; mean maximal MET values were 10.0 ± 2.2. Mean MoCA scores were 26.9 ± 2.2; 23.4% of the sample had MoCA scores indicative of cognitive impairment. The odds ratio for cognitive impairment was 0.93 (0.88-0.97) per 1-MET increment in CRF. When examined as a categorical variable, and using the lowest CRF quintile as the referent, there was a significantly reduced likelihood for cognitive impairment across the remaining ordered CRF categories (p trend = 0.004). CONCLUSION: The association between CRF and MoCA score in older adults suggests that meeting or exceeding public health guidelines for physical activity is likely to increase CRF in low fit individuals, maintain CRF in those with a moderate to high level of CRF, and thereby help to maintain cognitive function in healthy older adults.

Laparoscopic insulinoma enucleation for an uncinate lesion.

How I do laparoscopic insulinoma enucleation. This article discusses a laparoscopic approach for insulinoma enucleation, an approach which offers all the advantages of a laparoscopic approach and which can also be adapted to other pancreatic lesions requiring enucleation.

Clinical protocol using calcium and calcitriol after paediatric total thyroidectomy decreases postoperative hypocalcaemia and inpatient blood tests.

INTRODUCTION: Postoperative hypocalcaemia is common after thyroidectomy. This study aimed to evaluate whether a standardised post-thyroidectomy protocol using prophylactic calcium and calcitriol reduces hypocalcaemia incidence after total thyroidectomy in children and adolescents. METHODS: A cohort children and adolescents ≤18 years of age undergoing total thyroidectomy between January 2016 and October 2022 in one institution were retrospectively identified and divided into pre-protocol and post-protocol groups. The primary outcome measure was hypocalcaemia (total serum calcium of <2.0 mmol/L; ionised serum calcium of 0.9 mmol/L). Secondary outcome measures were the occurrence of hypercalcaemia (serum Calcium >2.7 mmol/L; ionised calcium >1.31 mmol/L), length of hospitalisation and number of postoperative blood tests. RESULTS: There were 22 patients in each group (mean age 11.8; SD 4.3 years, female 36 %). The rate of hypocalcaemia was significantly higher in the pre-protocol group than the post-protocol group (54 % vs 13.6 %, p = 0.010). Patients in the pre-protocol group had more inpatient blood tests (mean 5.4; SD 3.2) than the post-protocol group (mean 3.3; SD 1.8, p = 0.011), although the total postoperative blood test count was similar between the groups. Six (13.6 %) patients developed hypercalcaemia. The rate of hypercalcaemia was similar between groups (pre-protocol 2, 9.1 %; post-protocol 4, 18.1 %; p = 0.664). Length of hospitalisation was similar between groups. CONCLUSION: Our standardized protocol decreased hypocalcemia and inpatient blood tests after total thyroidectomy in children. Future research should explore if incorporating preoperative calcium and calcitriol treatment, along with intraoperative PTH levels for risk management, can further reduce hypocalcemia rates in paediatric patients.

Insulinoma: Metastatic Recurrence 38 Years Following Initial Diagnosis in Pregnancy.

A case of recurrent insulinoma spanning 4 decades is described. Following a delayed diagnosis, hyperinsulinemic hypoglycemia was confirmed in a 24-year-old woman during early pregnancy. Initial surgery, culminating in subtotal pancreatectomy, was noncurative. A 1-cm insulinoma was subsequently resected from the head of the pancreas postpartum, with postoperative resolution of hypoglycemia. However, 32 years later, the patient experienced a recurrence of hypoglycemic symptoms. Eventually, a subcentimeter extrapancreatic lesion was identified anterior to the pancreatic head on gallium-68 DOTA-Exendin-4 positron emission tomography/computed tomography. In 2022, a third operation was performed, with excision of a 4 × 3 mm tumor adjacent to the pancreatic head, and histology confirming insulinoma. She was again cured of symptoms.

Coronary artery calcification and high-volume physical activity: role of lower intensity vs. longer duration of exercise.

AIMS: While high-volume physical activity (PA) has been linked to elevated coronary artery calcification (CAC), the role of intensity vs. duration of PA has not been investigated. The purpose of the study was to examine the role of intensity vs. duration of PA in relation to CAC. METHODS AND RESULTS: Data are from 23 383 apparently healthy men who completed a PA questionnaire and underwent CAC scanning as part of a preventive examination. Self-reported PA was categorized into four groups of average intensity and weekly duration of PA [average intensity: 1, 3-5.9, 6-8.9, and 9-12 metabolic equivalents of task (METs); weekly duration: 0, > 0-<2, 2-<5, and ≥5 h/week]. Mean CAC and CAC ≥ 100 Agatston units (AU) were regressed separately on continuous or categorical average intensity and weekly duration of PA. The mean (standard deviation) age was 51.7 (8.3) years, and mean CAC was 174.8 (543.6) AU with 23.5% of men presenting with CAC ≥ 100 AU. Higher average intensity of PA was related to lower mean CAC [-3.1%/MET, 95% confidence interval (CI): -4.6, -1.6%/MET] and lower relative risk (RR) of CAC ≥ 100 AU (RR: 0.99, 95% CI: 0.98, 1.00/MET). Opposite trend was observed for the duration component wherein higher weekly duration of PA was significantly associated with greater mean CAC and RR of CAC ≥ 100 AU. CONCLUSION: Elevated CAC was associated with lower average intensity and longer duration of PA in men, providing new insight into the complex relationship between leisure-time PA behaviours and risk of CAC.

Does greater extent of coronary artery calcification (CAC) observed at high volumes of leisure-time physical activity relate more to the intensity or the duration of the activity?Higher average intensity of activity is associated with less CAC at any age and weekly duration of activity.Higher weekly duration of activity is associated with more CAC at any age and average intensity of activity.

Utility of Adrenal Vein Sampling With and Without Ultra-Low Dose ACTH Infusion in the Diagnostic Evaluation of Primary Aldosteronism.

BACKGROUND: Adrenal vein sampling (AVS), integral to identifying surgically remediable unilateral primary aldosteronism (PA), is technically challenging and subject to fluctuations in cortisol and aldosterone secretion. Intra-procedural adrenocorticotropic hormone (ACTH), conventionally administered as a 250-µg bolus and/or 50 µg per hour infusion, increases cortisol and aldosterone secretion and can improve AVS success, but may cause discordant lateralisation compared to unstimulated AVS. AIMS: To assess if AVS performed with ultra-low dose ACTH infusion causes discordant lateralisation. METHODS: Here, we describe our preliminary experience using an ultra-low dose ACTH infusion AVS protocol. We retrospectively reviewed the results of consecutive AVS procedures (n = 37) performed with and without ultra-low dose ACTH (1-µg bolus followed by 1.25 µg per hour infusion). RESULTS: Bilateral AV cannulation was successful in 70% of procedures pre-ACTH and 89% post-ACTH (p < 0.01). Sixty-nine percent of studies lateralised pre-ACTH and 55% post-ACTH, improving to 79% when both groups were combined. Lateralisation was discordant in 11 cases, including eight in which lateralisation was present only on basal sampling, and three in which lateralisation occurred only with ACTH stimulation. DISCUSSION: Overall, the decrease in lateralisation rates with ACTH was higher than previously reported for some protocols utilising conventional doses of ACTH. Our results suggest that AVS performed with ultra-low dose ACTH can cause discordant lateralisation similar to AVS performed with conventional doses of ACTH. CONCLUSION: Prospective studies directly comparing low and conventional dose ACTH AVS protocols and long-term patient outcomes are needed to help define the optimal ACTH dose for accurate PA subtyping.

Omega-3 index, cardiorespiratory fitness, and cognitive function in mid-age and older adults.

Higher levels of omega-3 fatty acids in red blood cell membranes (omega-3 index or O3I) and cardiorespiratory fitness (CRF) are each associated with reduced cognitive impairment, but little research has examined the relationship between O3I and cognitive function while accounting for CRF. We analyzed cross-sectional data from 5,464 healthy men and women aged 55-85 years who had preventive medical examinations between 2009 and 2023. Primary exposures included O3I (<4.0%, 4.0-7.9%, or ≥ 8.0%) and age- and sex-based CRF quintile (1 = low, 2-3 = moderate, 4-5 = high). Cognitive impairment was defined as a Montreal Cognitive Assessment score of ≤ 25. We used Poisson regression to estimate relative risks (RR) of cognitive impairment, controlling for covariates. O3I < 4% was associated with increased cognitive impairment relative to ≥ 8.0% (RR, 1.21; 95% CI, 1.01-1.44) in a partially adjusted model. This association did not remain statistically significant in the fully adjusted model which included CRF. Low versus high CRF was associated with cognitive impairment (RR, 1.28; 95% CI, 1.07-1.53), independent of O3I and clinical biomarkers. The interaction between CRF and O3I was not significant (P = 0.8). In joint association analysis, risk of cognitive impairment was elevated with lower omega-3 index or CRF or both. Additional research is needed to fully understand the association between O3I and cognitive function at varying CRF levels.

Association between baseline levels of muscular strength and risk of stroke in later life: The Cooper Center Longitudinal Study.

PURPOSE: Muscular strength is an important component of physical fitness. We evaluated the relationship between baseline muscular strength and risk of stroke among adults who were aged ≥65 years during follow-up. METHODS: We included 7627 healthy adults (mean age = 43.9 years, 86.0% male) underwent a baseline physical examination between 1980 and 1989. Muscular strength was determined by 1-repetition maximum measures for bench press and leg press and categorized into age- and sex-specific tertiles for each measure. Cardiorespiratory fitness (CRF) was assessed via a maximal treadmill exercise test. Those enrolled in fee-for-service Medicare from 1999 to 2019 were included in the analyses. Associations between baseline strength and stroke outcomes were estimated using a modified Cox proportional hazards model. In a secondary analysis, we examined stroke risk by categories of CRF where Quintile 1 = low, Quintiles 2-3 = moderate, and Quintiles 4-5 = high CRF based on age and sex. RESULTS: After 70,072 person-years of Medicare follow-up, there were 1211 earliest indications of incident stroke. In multivariable analyses, the hazard ratio (95% confidence interval (95%CI)) for stroke across bench press categories were 1.0 (referent), 0.96 (0.83-1.11), and 0.89 (0.77-1.04), respectively (p trend = 0.14). The trend across categories of leg press was also non-significant (p trend = 0.79). Adjusted hazard ratio (95%CI) for stroke across ordered CRF categories were 1.0 (referent), 0.90 (0.71-1.13), and 0.72 (0.57-0.92) (p trend < 0.01). CONCLUSION: While meeting public health guidelines for muscular strengthening activities is likely to improve muscular strength as well as many health outcomes in older adults, performing such activities may not be helpful in preventing stroke. Conversely, meeting guidelines for aerobic activity is likely to improve CRF and lower stroke risk.

Associations among cardiorespiratory fitness, C-reactive protein, and all-cause mortality in men and women.

We examined individual and joint associations among high-sensitivity C-reactive protein (CRP), cardiorespiratory fitness (fitness), and mortality in healthy men and women. Between January 1, 2000 and December 31, 2016, 30,077 adults (31.3% women) received a comprehensive physical examination. Fitness was determined from maximal treadmill exercise test duration. Participants were categorized as unfit (Quintile 1) and fit (Quintiles 2-5), and by normal (<2 mg/L) and elevated (≥2 mg/L) CRP categories. Adjusted hazard ratios (HRs) with 95% confidence interval (CI) for all-cause mortality were computed with Cox regression. During an average of 10.1 years of follow-up, 576 deaths occurred. Following adjustment for age, smoking status, sex, exam year, body mass index, systolic blood pressure, total cholesterol, triglyceride:high-density lipoprotein ratio, and fasting glucose, HR (95% CI) for all-cause mortality were 1.0 (referent) and 1.52 (1.14-2.02) for fit and unfit categories, respectively. Corresponding values for normal and elevated CRP categories were 1.0 and 1.50 (1.20-1.89), respectively. When grouped by fitness and CRP category, there was significantly greater mortality risk in the unfit than the fit category within the elevated CRP category (HR = 1.77 (1.14-2.75)), but not in the normal CRP category (HR = 1.38 (0.96-1.98)). Each 1 metabolic equivalent increment in fitness and 1 mg/L increment in CRP were associated with 10.0% (95% CI: 5.1-14.8%) decreased and 7.3% (95% CI: 2.0%-12.9%) increased mortality hazard, respectively. Compared to the unfit, fit individuals have an attenuated mortality risk within each CRP category. Thus, higher fitness appears to provide some protection against all-cause mortality, particularly among those with elevated levels of inflammation.

Cardiorespiratory Fitness and All-Cause Mortality in Women with Metabolic Syndrome.

Purpose: To examine the association between cardiorespiratory fitness (fitness) and all-cause mortality in women with metabolic syndrome (MetSyn). Methods: The sample included 1798 women with MetSyn (mean age 50.2 years) who received a comprehensive preventive baseline examination between 1978 and 2016, with mortality follow-up through December 31, 2017. MetSyn was identified using Adult Treatment Panel-III Guidelines. Fitness was determined by duration of a maximal treadmill exercise test and grouped as fit or unfit on the basis of the upper 80% and lower 20% of the age-standardized fitness distribution. Age- and smoking-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated in a proportional hazards regression model. Results: During a mean follow-up of 16.6 ± 8.7 years, 204 deaths occurred. Crude all-cause mortality rates were 6.8 and 6.9 deaths per 10,000 woman-years in fit and unfit groups, respectively. The adjusted HR (95% CI) for all-cause mortality in unfit versus fit women (referent) with MetSyn was 1.36 (95% CI 1.01-1.83). Conclusions: Higher levels of fitness significantly attenuate the risk of all-cause mortality in women with MetSyn. In accordance with the American Heart Association scientific statement, to more accurately determine mortality risk in this population, health care professionals should measure or estimate fitness and should strongly encourage women to meet current public health guidelines for physical activity with the goal of reaching higher fitness levels.