Associations between Brain Alpha-Tocopherol Stereoisomer Profile and Hallmarks of Brain Aging in Centenarians.

Brain alpha-tocopherol (αT) concentration was previously reported to be inversely associated with neurofibrillary tangle (NFT) counts in specific brain structures from centenarians. However, the contribution of natural or synthetic αT stereoisomers to this relationship is unknown. In this study, αT stereoisomers were quantified in the temporal cortex (TC) of 47 centenarians in the Georgia Centenarian Study (age: 102.2 ± 2.5 years, BMI: 22.1 ± 3.9 kg/m2) and then correlated with amyloid plaques (diffuse and neuritic plaques; DPs, NPs) and NFTs in seven brain regions. The natural stereoisomer, RRR-αT, was the primary stereoisomer in all subjects, accounting for >50% of total αT in all but five subjects. %RRR was inversely correlated with DPs in the frontal cortex (FC) (ρ = -0.35, p = 0.032) and TC (ρ = -0.34, p = 0.038). %RSS (a synthetic αT stereoisomer) was positively correlated with DPs in the TC (ρ = 0.39, p = 0.017) and with NFTs in the FC (ρ = 0.37, p = 0.024), TC (ρ = 0.42, p = 0.009), and amygdala (ρ = 0.43, p = 0.008) after controlling for covariates. Neither RRR- nor RSS-αT were associated with premortem global cognition. Even with the narrow and normal range of BMIs, BMI was correlated with %RRR-αT (ρ = 0.34, p = 0.021) and %RSS-αT (ρ = -0.45, p = 0.002). These results providing the first characterization of TC αT stereoisomer profiles in centenarians suggest that DP and NFT counts, but not premortem global cognition, are influenced by the brain accumulation of specific αT stereoisomers. Further study is needed to confirm these findings and to determine the potential role of BMI in mediating this relationship.

C-reactive protein is a predictor of severe infective complications following gastrectomy-a retrospective analysis.

Background: Post-operative complications are the main contributing factor to increased length of stay, increased cost of care and short-term mortality experienced by patients following gastrectomy. The purpose of this study was to determine the diagnostic accuracy of C-reactive protein (CRP) in predicting complications following gastrectomy. This may assist clinicians to make better informed clinical decisions in the post-operative period. Methods: A retrospective analysis of a prospectively maintained database was performed. Sixty patients who underwent gastrectomy for gastric cancer were included. Demographic information, operative data and post-operative details such as complications, unplanned intensive care unit (ICU) admission and readmission to hospital were analysed. Complications were further analysed based on whether they were either infective or non-infective in nature. Receiver operator characteristic (ROC) analysis was performed to examine the association between CRP and post-operative morbidity. Optimum cut-offs were determined using the Youden's index. Results: From the second post-operative day (POD), CRP levels were able to predict subsequent severe infective (SI) complications following gastrectomy [area under the curve (AUC): 0.789, 95% CI : 0.636-0.941]. An optimum cut-off of 180 mg/L resulted in a sensitivity of 87.50%. The negative predictive value (NPV) at this point was 96.30%. Conclusions: CRP is a strong negative predicter of SI complications following gastrectomy. This suggests early CRP values may be useful in prompting early investigation or facilitating safer, earlier discharge from hospital. Health services may benefit by determining similar cut-offs based on their own unique patient populations.

Oesophageal neuroendocrine tumours-case series of a rare malignancy.

Oesophageal neuroendocrine neoplasms (NENs) are rare tumours. Neuroendocrine carcinomas (NECs) are the highest grade of NENs, with aggressive biological behaviour and poor outcomes. No standardized treatment pathways exist for these tumours, with management being individualized based on patient and tumour factors. We present five cases, four men and one women between 63 and 68 years old, who were diagnosed with symptomatic primary oesophageal NECs. Three were diagnosed with localized disease, and two were diagnosed with metastatic disease. Endoscopy, biopsy and staging scan results are outlined. Two patients received neoadjuvant chemotherapy. Three patients with localized disease underwent oesophagectomy. Two of these patients received neoadjuvant chemotherapy. Four patients have succumbed to their disease, with a median survival following a diagnosis of 18 months (5-34 months). This case series highlights the variability of presentation and stage at diagnosis of oesophageal NECs. Multimodal treatment is commonly utilized; however, outcomes are universally poor. Further research is required to determine the optimal treatment regimen for oesophageal NENS.

Carotenoid-Rich Brain Nutrient Pattern Is Positively Correlated With Higher Cognition and Lower Depression in the Oldest Old With No Dementia.

Background: Healthy dietary patterns are related to better cognitive health in aging populations. While levels of individual nutrients in neural tissues are individually associated with cognitive function, the investigation of nutrient patterns in human brain tissue has not been conducted. Methods: Brain tissues were acquired from frontal and temporal cortices of 47 centenarians from the Georgia Centenarian Study. Fat-soluble nutrients (carotenoids, vitamins A, E, K, and fatty acids [FA]) were measured and averaged from the two brain regions. Nutrient patterns were constructed using principal component analysis. Cognitive composite scores were constructed from cognitive assessment from the time point closest to death. Dementia status was rated by Global Deterioration Scale (GDS). Pearson's correlation coefficients between NP scores and cognitive composite scores were calculated controlling for sex, education, hypertension, diabetes, and APOE ε4 allele. Result: Among non-demented subjects (GDS = 1-3, n = 23), a nutrient pattern higher in carotenoids was consistently associated with better performance on global cognition (r = 0.38, p = 0.070), memory (r = 0.38, p = 0.073), language (r = 0.42, p = 0.046), and lower depression (r = -0.40, p = 0.090). The findings were confirmed with univariate analysis. Conclusion: Both multivariate and univariate analyses demonstrate that brain nutrient pattern explained mainly by carotenoid concentrations is correlated with cognitive function among subjects who had no dementia. Investigation of their synergistic roles on the prevention of age-related cognitive impairment remains to be performed.

Second-generation uncemented total hip arthroplasty: a minimum 20-year follow-up.

AIMS: We present the clinical and radiological results at a minimum follow-up of 20 years using a second-generation uncemented total hip arthroplasty (THA). These results are compared to our previously published results using a first-generation hip arthroplasty followed for 20 years. METHODS: A total of 62 uncemented THAs in 60 patients were performed between 1993 and 1994. The titanium femoral component used in all cases was a Taperloc with a reduced distal stem. The acetabular component was a fully porous coated threaded hemispheric titanium shell (T-Tap ST). The outcome of every femoral and acetabular component with regard to retention or revision was determined for all 62 THAs. Complete clinical follow-up at a minimum of 20 years was obtained on every living patient. Radiological follow-up was obtained on all but one. RESULTS: Two femoral components (3.2%) required revision. One stem was revised secondary to a periprosthetic fracture one year postoperatively and one was revised for late sepsis. No femoral component was revised for aseptic loosening. Six acetabular components had required revision, five for aseptic loosening. One additional acetabular component was revised for sepsis. Radiologically, all femoral components remained well fixed. One acetabular was judged loose by radiological criteria. The mean Harris Hip Score improved from 46 points (30 to 67) preoperatively to 89 points (78 to 100) at final follow-up. With revision for aseptic loosening as the endpoint, survival of the acetabular component was 95% (95% confidence interval (CI) 90 to 98) at 25 years. Femoral component survival was 100%. CONCLUSION: The most significant finding of this report was the low prevalence of aseptic loosening and revision of the femoral component at a mean follow-up of 22 years. A second important finding was the survival of over 90% of the hemispheric threaded ring acetabular components. While these shells remain controversial, in this series they performed well.Cite this article: Bone Jt Open 2021;2(1):33-39.

Exercise and Protein Effects on Strength and Function with Weight Loss in Older Women.

Obesity negatively affects lower extremity physical function (LEPF) in older adults. Exercise and a higher protein diet are both known to positively and independently affect body composition, muscle strength, and LEPF during weight loss; however, their potential interactive effects have not been well characterized in older women. PURPOSE: The aim of this study was to determine the relative efficacy of a higher protein diet with or without exercise to improve body composition, muscle strength, and LEPF in older inactive overweight/obese women after weight loss. METHODS: Postmenopausal women (body mass index = 31.1 ± 5.1 kg·m, 69.2 ± 3.6 yr) completed a 6-month weight loss program after randomization to three groups (n = 72 randomized; 15% dropout): 1) higher protein diet (PRO, ~30% energy from protein; n = 20), 2) PRO plus exercise (PRO + EX; n = 19), or 3) a conventional protein control diet plus EX (CON + EX, ~18% energy from protein; n = 22). EX was supervised, multicomponent (aerobic, muscle strengthening, balance, and flexibility), and three sessions per week. Body composition was measured via dual-energy x-ray absorptiometry, leg strength by isokinetic dynamometry, and LEPF via 6-min walk, 8-ft up and go, and 30-s chair stand tests. RESULTS: Changes in weight (-7.5 ± 4.1 kg; -9.2% ± 4.8%), fat mass, and leg lean mass did not differ among groups (all P > 0.50). Despite weight loss, muscle strength improved in the exercise groups (PRO + EX and CON + EX) but it declined in the PRO group (P = 0.008). For all LEPF measures, the PRO group had attenuated improvements compared with both PRO + EX and CON + EX (all P < 0.01). CONCLUSION: Exercise during weight loss is critical to preserve strength and enhance LEPF; however, a higher protein diet does not appear to influence body composition, muscle strength, or LEPF changes when combined with multicomponent exercise.

Splenic Artery Pseudoaneurysm Causing Massive Hematemesis 10 Years After Necrotizing Pancreatitis.

We report a case of a 54-year-old male presenting to a regional hospital with severe hematemesis and hemodynamic instability. His medical history was significant for a previous episode of alcoholic necrotizing pancreatitis and pseudocyst, requiring cystoenterostomy drainage and debridement 10 years prior. He underwent multiple gastroscopies and one emergency laparotomy which failed to definitively treat the bleeding. A splenic artery pseudoaneurysm was diagnosed with computed tomography angiography, adjacent to the previous cystoenterostomy site. The patient was transferred to a major tertiary center with access to interventional radiology and underwent successful embolization of the pseudoaneurysm.

Trans-hiatal repair for Oesophageal and Junctional perforation: a case series.

BACKGROUND: Oesophageal perforation is a life-threatening condition that requires urgent intervention. Surgical repair is recommended within 24 h of onset to minimise mortality risk, traditionally via an open thoracotomy or a laparotomy. Primary oesophageal repair via a laparoscopic trans-hiatal approach has been seldomly reported due to concerns of inadequate eradication of soilage in the mediastinum and pleural space, as well as poor access and an increased operative time in an unwell population. CASE PRESENTATION: We report a case series of 3 oesophageal and junctional perforations with varying presentations, demonstrating how the laparoscopic trans-hiatal approach can be used successfully to manage oesophageal perforations. CONCLUSIONS: Laparoscopic trans-hiatal repair is an attractive option for oesophageal and junctional perforations, in haemodynamically stable surgical candidates, in the absence of gross contamination of the thoracic cavity.

The Effect of Inorganic Salt on Disintegration of Tablets with High Loading of Amorphous Solid Dispersion Containing Copovidone.

PURPOSE: While including amorphous solid dispersion (ASD) in tablet formulations is increasingly common, tablets containing high ASD loading are associated with slow disintegration, which presents a challenge to control pill burden for less potent compounds. METHODS: We use a model ASD, composed of a hydrophobic drug with copovidone and a non-ionic surfactant, to explore formulation options that can prevent slow disintegration. RESULTS: In addition to the ASD loading, the pH of the disintegration medium and the inclusion of inorganic salts in the tablet also have an impact on the tablet disintegration time. Certain kosmotropic salts, when added in the formulation, can significantly accelerate tablet disintegration, though the rank order in their effectiveness does not exactly follow the Hofmeister series at pH 1.8. The particle size and dissolution rate of the salt can contribute to its overall effectiveness. CONCLUSION: We provided a mechanistic explanation of the disintegration process: fast-dissolving kosmotropic salt results in a concentrated salt solution inside the restrained tablet matrix, thus inhibiting the dissolution of copovidone and preventing polymer gelling which is the main cause leading the slow disintegration. The outcome of this study has enabled the design of a higher ASD loading platform formulation for copovidone based ASD. Graphical Abstract MicroCT aids the mechanistic understanding of the role of inorganic salt in the tablet disintegration of amorphous solid dispersion based formulation.

Concentrations of Circulating Phylloquinone, but Not Cerebral Menaquinone-4, Are Positively Correlated with a Wide Range of Cognitive Measures: Exploratory Findings in Centenarians.

BACKGROUND: Vitamin K (VK) exists in the form of phylloquinone (PK) and menaquinones (MKs). Roles of VK on cognitive health in the elderly are emerging, but there is limited evidence on VK uptake and metabolism in human brain. OBJECTIVES: The primary objective of this study was to characterize VK distribution in brains of an elderly population with varied cognitive function. In addition, associations among circulating (a biomarker of VK intake) and cerebral VK concentrations and cognition were investigated. METHODS: Serum or plasma (n = 27) and brain samples from the frontal cortex (FC; n = 46) and the temporal cortex (TC; n = 33) were acquired from 48 decedents (aged 98-107 y; 25 demented and 23 nondemented) enrolled in the Georgia Centenarian Study. Both circulating and brain VK concentrations were measured using HPLC with fluorescence detection. Cognitive assessment was performed within 1 y prior to mortality. Partial correlations between serum/plasma or cerebral VK concentrations and cognitive function were performed, adjusting for covariates and separating by dementia and antithrombotic use. RESULTS: MK-4 was the predominant vitamer in both FC (mean ± SD = 4.92 ± 2.31 pmol/g, ≥89.15% ± 5.09% of total VK) and TC (4.60 ± 2.11 pmol/g, ≥89.71% ± 4.43% of total VK) regardless of cognitive status. Antithrombotic users had 34.0% and 53.9% lower MK-4 concentrations in FC (P < 0.05) and TC (P < 0.001), respectively. Circulating PK was not correlated with cerebral MK-4 or total VK concentrations. Circulating PK concentrations were significantly associated with a wide range of cognitive measures in nondemented centenarians (P < 0.05). In contrast, cerebral MK-4 concentrations were not associated with cognitive performance, either before or after exclusion of antithrombotic users. CONCLUSIONS: Circulating VK concentrations are not related to cerebral MK-4 concentrations in centenarians. Cerebral MK-4 concentrations are tightly regulated over a range of VK intakes and cognitive function. Circulating PK may reflect intake of VK-rich foods containing other dietary components beneficial to cognitive health. Further investigation of VK uptake and metabolism in the brain is warranted.

Laparoscopic management of chylous ascites posthiatal hernia repair with Toupet fundoplication.

We present a case of chylous ascites in a 69-year-old man 5 months after a laparoscopic Toupet fundoplication (posterior 270°). This was successfully treated with laparoscopic ligation of tissue adjacent to the right crus. Laparoscopic ligation is a management option that should be considered after this rare complication, offering rapid results.

Aorto-oesophageal fistula: a late complication of Boerhaave syndrome.

A 68-year-old woman presented with haematemesis and chest pain 3 months after a spontaneous oesophageal perforation. The patient rapidly progressed to a state of hypovolaemic shock and after resuscitation was found to have aorto-oesophageal fistula on CT aortogram. The patient was treated with a successful thoracic endovascular aortic repair.

Clinico-Neuropathological Findings in the Oldest Old from the Georgia Centenarian Study.

BACKGROUND: Centenarian studies are important sources for understanding of factors that contribute to longevity and healthy aging. Clinico-neuropathological finding is a key in identifying pathology and factors contributing to age-related cognitive decline and dementia in the oldest old. OBJECTIVE: To characterize the cross-sectional relationship between neuropathologies and measures of premortem cognitive performance in centenarians. METHODS: Data were acquired from 49 centenarians (≥98 years) from the Georgia Centenarian Study. Cognitive assessment from the time point closest to mortality was used (<1 year for all subjects) and scores for cognitive domains were established. Neuropathologies [cerebral atrophy, ventricular dilation, atherosclerosis, cerebral amyloid angiopathy (CAA), Lewy bodies, hippocampal sclerosis (HS), hippocampal TDP-43 proteinopathy, neuritic plaque (NP) and neurofibrillary tangle (NFT) counts, Braak staging, and National Institute on Aging-Reagan Institute (NIARI) criteria for the neuropathological diagnosis of Alzheimer's disease (AD)] were compared among subjects with different ratings of dementia. Linear regression was applied to evaluate the association between cognitive domain scores and neuropathologies. RESULTS: Wide ranges of AD-type neuropathological changes were observed in both non-demented and demented subjects. Neocortical NFT and Braak staging were related to clinical dementia rating. Neocortical NFT and NP, Braak and NIARI staging, cerebral and ventricular atrophy, HS, CAA, and TDP-43 proteinopathy were differentially associated with poor performance in multiple cognitive domains and activities of daily living. CONCLUSION: AD-type pathology was associated with severe dementia and poor cognition but was not the only variable that explained cognitive impairment, indicating the complexity and heterogeneity of pathophysiology of dementia in the oldest old.

Position of the Academy of Nutrition and Dietetics and the Society for Nutrition Education and Behavior: Food and Nutrition Programs for Community-Residing Older Adults.

Given the increasing number and diversity of older adults and the transformation of health care services in the United States, it is the position of the Academy of Nutrition and Dietetics and the Society for Nutrition Education and Behavior that all older adults should have access to evidence-based food and nutrition programs that ensure the availability of safe and adequate food to promote optimal nutrition, health, functionality, and quality of life. Registered dietitian nutritionists and nutrition and dietetics technicians, registered, in partnership with other practitioners and nutrition educators, should be actively involved in programs that provide coordinated services between the community and health care systems that include regular monitoring and evaluation of programming outcomes. The rapidly growing older population, increased demand for integrated continuous support systems, and rising cost of health care underscore the need for these programs. Programs must include food assistance and meal programs, nutritional screening and assessment, nutrition education, medical nutrition therapy, monitoring, evaluation, and documentation of evidence-based outcomes. Coordination with long-term care services and support systems is necessary to allow older adults to remain in their homes; improve or maintain their health and manage chronic disease; better navigate transitions of care; and reduce avoidable hospital, acute, or long-term care facility admissions. Funding of these programs requires evidence of their effectiveness, especially regarding health, functionality, and health care-related outcomes of interest to individuals, caregivers, payers, and policy makers. Targeting of food and nutrition programs involves addressing unmet needs for services, particularly among those at high risk for poor nutrition. Registered dietitian nutritionists and nutrition and dietetics technicians, registered must increase programmatic efforts to measure outcomes to evaluate community-based food and nutrition services.

Position of the Academy of Nutrition and Dietetics and the Society for Nutrition Education and Behavior: Food and Nutrition Programs for Community-Residing Older Adults.

Given the increasing number and diversity of older adults and the transformation of health care services in the United States, it is the position of the Academy of Nutrition and Dietetics and the Society for Nutrition Education and Behavior that all older adults should have access to evidence-based food and nutrition programs that ensure the availability of safe and adequate food to promote optimal nutrition, health, functionality, and quality of life. Registered dietitian nutritionists and nutrition and dietetics technicians, registered, in partnership with other practitioners and nutrition educators, should be actively involved in programs that provide coordinated services between the community and health care systems that include regular monitoring and evaluation of programming outcomes. The rapidly growing older population, increased demand for integrated continuous support systems, and rising cost of health care underscore the need for these programs. Programs must include food assistance and meal programs, nutritional screening and assessment, nutrition education, medical nutrition therapy, monitoring, evaluation, and documentation of evidence-based outcomes. Coordination with long-term care services and support systems is necessary to allow older adults to remain in their homes; improve or maintain their health and manage chronic disease; better navigate transitions of care; and reduce avoidable hospital, acute, or long-term care facility admissions. Funding of these programs requires evidence of their effectiveness, especially regarding health, functionality, and health care-related outcomes of interest to individuals, caregivers, payers, and policy makers. Targeting of food and nutrition programs involves addressing unmet needs for services, particularly among those at high risk for poor nutrition. Registered dietitian nutritionists and nutrition and dietetics technicians, registered must increase programmatic efforts to measure outcomes to evaluate community-based food and nutrition services. POSITION STATEMENT: It is the position of the Academy of Nutrition and Dietetics and the Society for Nutrition Education and Behavior that older adults should have access to evidence-based food and nutrition programs that ensure the availability of safe and adequate food to promote optimal nutrition, health, functionality, and quality of life. Registered dietitian nutritionists and nutrition and dietetics technicians, registered, in partnership with other practitioners and nutrition educators, should be actively involved in programs that provide coordinated services between the community and health care systems that include regular monitoring and evaluation of programming outcomes. The rapidly growing older population, increased demand for integrated continuous support systems, and rising cost of health care underscore the need for these programs.

Chondrolipoma of the stomach.

Chondrolipoma, a rare variant of a lipoma, is a benign mesenchymal neoplasm characterised by mature adipocytes with neoplastic hyaline cartilage formation. We describe the first case of a gastric chondrolipoma. The tumour was completely excised via laparoscopic gastric wedge resection with uneventful postoperative recovery. Histology of the tumour demonstrates mature adipose tissue and benign cartilage with patchy calcification.

Cardiovascular health and cognitive functioning among centenarians: a comparison between the Tokyo and Georgia centenarian studies.

ABSTRACTObjectives:Centenarians have survived into very late life, but whether they reach very old age in good health remains unclear. The purpose of this study was to compare the cardiovascular health status and cognitive functioning of centenarians in the United States with centenarians in Japan. DESIGN, SETTING, AND PARTICIPANTS: This cross-national design compared centenarians from the United States and Japan. The sample of U.S. centenarians was recruited from the Georgia Centenarian Study and included 287 centenarians. The sample of Japanese centenarians was recruited from the Tokyo Centenarian Study and included 304 centenarians. MEASUREMENTS: Cognitive functioning was assessed with a mental status questionnaire, and cardiovascular disease by a health history assessment, blood pressure, and selected blood parameters. RESULTS: The results suggest that Tokyo centenarians had lower disease experiences and BMI values, when compared to Georgia centenarians, but blood pressure was higher among Japanese centenarians. Lower levels of hemoglobin in Japanese centenarians and higher levels of C-reactive protein in Georgia were also found. The positive association of hypertension and albumin levels with cognitive functioning and the negative association of stroke occurrence with cognitive functioning were replicated in both countries. Differential effects were obtained for heart problems, BMI, and C-reactive protein (with positive effects for Tokyo centenarians, except for C-reactive protein). CONCLUSION: For extremely old individuals, some markers of cardiovascular disease are replicable across countries, whereas differential effects for cardiovascular health also need to be considered in cardiovascular health.

Serum Carotenoids, Tocopherols, Total n-3 Polyunsaturated Fatty Acids, and n-6/n-3 Polyunsaturated Fatty Acid Ratio Reflect Brain Concentrations in a Cohort of Centenarians.

Investigating the role of nutrition on cognitive health is challenging. Human brain tissue is inaccessible in living humans and is often limited in deceased individuals. Therefore, biomarkers of brain nutrient levels are of interest. The objective of this study was to characterize the relationships between levels of fat-soluble nutrients in serum and matched brain tissues from the frontal and temporal cortices of participants in the Georgia Centenarian Study (n = 47). After adjusting for sex, race, cognitive status (Global Deterioration Scale), body mass index, and presence of hypertension and/or diabetes, there was a significant relationship (p < 0.05) between serum and brain levels of carotenoids (lutein, zeaxanthin, cryptoxanthin, ß-carotene), α-, γ-tocopherols, total n-3 polyunsaturated fatty acids (PUFAs), and n-6/n-3 PUFA ratio. The relationship between serum and brain total n-6 PUFAs was inconsistent among the two brain regions. No significant relationship was identified between serum and brain retinol, total saturated fatty acid, total monounsaturated fatty acid, and trans-fatty acid levels. These findings suggest that serum carotenoids, tocopherols, total n-3 PUFAs, and n-6/n-3 PUFA ratio reflect levels in brain and can be used as surrogate biomarkers in older population.

Hidden Hunger: Solutions for America's Aging Populations.

The global population, including the United States, is experiencing a demographic shift with the proportion of older adults (aged ≥ 65 years) growing faster than any other age group. This demographic group is at higher risk for developing nutrition-related chronic conditions such as heart disease and diabetes as well as infections such as influenza and pneumonia. As a result, an emphasis on nutrition is instrumental for disease risk reduction. Unfortunately, inadequate nutrient status or deficiency, often termed hidden hunger, disproportionately affects older adults because of systematic healthcare, environmental, and biological challenges. This report summarizes the unique nutrition challenges facing the aging population and identifies strategies, interventions, and policies to address hidden hunger among the older adults, discussed at the scientific symposium "Hidden Hunger: Solutions for America's Aging Population", on March 23, 2018.