Higher Dietary Inflammatory Index scores are associated with brain MRI markers of brain aging: Results from the Framingham Heart Study Offspring cohort.

INTRODUCTION: We investigated cross-sectional associations between the Dietary Inflammatory Index (DII) and measures of brain volume and cerebral small vessel disease among participants of the Framingham Heart Study Offspring cohort. METHODS: A total of 1897 participants (mean ± standard deviation, age 62±9) completed Food Frequency Questionnaires and brain magnetic resonance imaging (MRI). RESULTS: Higher (pro-inflammatory) DII scores, averaged across a maximum of three time points, were associated with smaller total brain volume (beta ± standard error: -0.16 ± 0.03; P < .0001) after adjustment for demographic, clinical, and lifestyle covariates. In addition, higher DII scores were associated with smaller total gray matter volume (-0.08 ± 0.03; P = .003) and larger lateral ventricular volume (0.04 ± 0.02; P = .03). No associations were observed with other brain MRI measures. DISCUSSION: Our findings showed associations between higher DII scores and global brain MRI measures. As we are one of the first groups to report on the associations between higher DII scores and brain volume, replication is needed to confirm our findings.

Associations of Modifiable Behavioral Risk Factor Combinations at 65 to 74 Years Old With Cognitive Health Span for 20 Years.

OBJECTIVE: Behavioral risk factors for dementia tend to co-occur and interrelate, especially poor diet, physical inactivity, sleep disturbances, and depression. Having multiple of these modifiable behavioral risk factors (MBRFs) may predict a particularly shortened cognitive health span and therefore may signal high-risk status/high intervention need. METHODS: These secondary analyses of data from the Cardiovascular Health Study included 3149 participants aged 65 to 74 years (mean [standard deviation {SD}] age = 69.5 [2.5] years; 59.6% female). MBRF exposures were self-reports regarding a) diet, b) activity, c) sleep, and d) depression symptoms. We primarily analyzed MBRF counts. For up to 26 years of follow-up, we assessed the a) number of remaining cognitively healthy life-years (CHLYs) and b) percentage of remaining life-years (LYs) that were CHLYs (%CHLY). We estimated CHLYs as time before a dementia diagnosis, cognitive screener scores indicating impairment, proxy report indicating significant cognitive decline, or dementia medication use. RESULTS: Participants averaged a remaining 16 LYs (SD = 7 LYs), 12.2 CHLYs (SD = 6.6 CHLYs), and 78.1% of LYs being CHLYs (SD = 25.6 CHLYs). Compared with having no MBRFs, having one was associated with ~1 less LY and CHLY, but not a relatively lower %CHLY. In contrast, having 3+ MBRFs was associated with about 2 to 3 fewer LYs and CHLYs as well as about 6% lower %CHLY (95% confidence interval = -9.0 to -2.5 %CHLYs; p = .001). CONCLUSIONS: MBRF-related reductions in the cognitive health span are most apparent when people have multiple MBRFs. Future research is needed to determine if/how behavioral risks converge mechanistically and if dementia prevention efficacy improves when targeting MBRF combinations.

Endocrine toxicity in cancer patients treated with nivolumab or pembrolizumab: results of a large multicentre study.

INTRODUCTION: The immune checkpoint inhibitors (ICPIs) agents anti-T lymphocytes-associated antigen 4 (CTLA-4) and anti-programmed cell death protein-1 (PD-1) and its ligands (PD-L1/PD-L2) have opened a new scenario in the treatment of cancer. These agents can induce immuno-related adverse events (irAEs), which may affect the endocrine system. PURPOSE: The aim of this study was to analyze the occurrence and the course of endocrine irAEs in cancer patients treated with anti-PD-1 immunotherapy. METHODS: This was a retrospective, multicentre study, involving cancer patients treated with the PD-1 inhibitors nivolumab or pembrolizumab at reference Oncology Centres. One hundred and seventy-nine consecutive patients with different types of cancer (mostly non-small cell lung cancer, melanoma, kidney cancer) were included in the study. Patients had received nivolumab (70.9%) or pembrolizumab (29.1%) for 2-33 months. The study evaluated clinical data records until the established date of July 15, 2018. The primary end point was the assessment of endocrine toxicity and possible predictive factors. RESULTS: Endocrine toxicity occurred in 54 out of 179 patients (30.2%) and was related to thyroid dysfunction, with the exception of one case of diabetes mellitus. Thyroid toxicity occurred mostly within 2 months from the initiation of immunotherapy (83% of cases). A pre-existing thyroid dysfunction was a significant predictor of disease flare. CONCLUSIONS: Thyroid alterations are frequently associated with anti PD-1 treatment in cancer patients. Regular thyroid assessment should be performed, particularly in the first months of treatment and in patients with a pre-existing thyroid disease.

Adjuvant FOLFOX +/- cetuximab in full RAS and BRAF wildtype stage III colon cancer patients.

Background: RAS mutations have been shown to confer resistance to anti- epidermal growth factor receptor (EGFR) treatment. We analysed the results of the PETACC8 trial (cetuximab + FOLFOX vs FOLFOX) in full RAS and BRAF wildtype (WT) patients (pts) with resected stage III colon cancer. Patients and methods: Exons 2, 3 and 4 of KRAS and NRAS, and BRAF exons 11 and 15, were sequenced using the Ampliseq colon-lung cancer panel version 2, in PETACC8 trial pts who consented to translational research. The impact of cetuximab on time to recurrence (TTR), disease-free survival (DFS) and overall survival (OS) was investigated in pts with tumours harbouring RAS and BRAF WT, and RAS mutations. The prognostic value of each individual mutation was also tested. Results: Among the 2559 pts analysed, 745 pts (29%) were known to have KRAS exon 2 mutations and 163 pts (6.4%) the BRAF V600E mutation. Of the remaining 1651 pts, 1054 were assessed by NGS, showing that a further 227 pts (21%) had KRAS exon 2, 3, 4 or NRAS exon 2, 3, 4 mutations, and that 46 pts (4.4%) had a newly diagnosed BRAF mutation. Cetuximab added to FOLFOX did not significantly improve TTR, DFS or OS in pts with RAS WT or RAS and BRAF WT tumours (HR 0.77-1.03, all P > 0.05). Cetuximab addition was not either significantly deleterious in RAS mutant pts or in pts with rare RAS or BRAF mutations. In the overall trial population, NRAS and KRAS codon 61 mutations were the only rare mutations with the same pejorative prognostic value as KRAS exon 2 or BRAF V600E mutations. Conclusion: Though not significant, the clinically relevant 0.76 adjusted HR observed for DFS in favour of adding cetuximab to FOLFOX, in full RAS and BRAF WT stage III colon cancer pts, may justify a new randomized controlled trial testing EGFR inhibitors in this setting. Clinical trial number: This is an ancillary study of the PETACC8 trial: EUDRACT 2005-003463-23.

Community-Based Healthy Aging Interventions for Older Adults with Arthritis and Multimorbidity.

Examine the impact of programs led by community health workers on health and function in older adults with arthritis and other health conditions. We conducted a cluster-randomized trial of the Arthritis Foundation Exercise Program (AFEP) enhanced with the "10 Keys"™ to Healthy Aging compared with the AFEP program at 54 sites in 462 participants (mean age 73 years, 88 % women, 80 % white). Trained Community health workers delivered the 10-week programs. Outcomes assessed after 6 months included physical performance [Short Physical Performance Battery (SPPB)], Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, and preventive health behaviors. Both groups experienced improvements. Performance improved by 0.3 SPPB points in the AFEP/"10 Keys"™ group and 0.5 in AFEP alone; WOMAC scores declined by 3.0 and 3.9 points respectively. More participants had controlled hypertension at 6 months in both groups (60.1 % baseline to 76.7 % in AFEP/10 Keys and from 76.5 to 84.9 % in AFEP alone) and greater diabetes control (from 15.0 to 34.9 and 15.5 to 34.1 %, respectively). These community-based programs showed similar improvements in preventive health, mobility and arthritis outcomes.

Association of the HLA-G 3'UTR polymorphisms with colorectal cancer in Italy: a first insight.

This study aimed to explore functional and regulatory polymorphisms and haplotypes at the HLA-G 3'UTR region in colorectal cancer development. The presence of nonpolymorphic variants was also evaluated. Three-hundred and eight patients with colorectal cancer and 294 healthy controls were analysed at the germinal level. We found an association with increased risk of colorectal cancer for +2960 14-bp INDEL, +3196 C>G SNPs and UTR-2 haplotype, and a 'protective' role for +3003 T>C, +3010 C>G polymorphisms and UTR-4 haplotype. We detected in 3 distinct patients, a novel nucleotide change (+3037 C>A) and 2 already described rare variants, +3032 G/C (EUR MAF = 0.1%) and +3092 G/T (EUR MAF = 0%). This is the first study showing associations between different polymorphisms in the HLA-G 3'UTR and colorectal cancer susceptibility.

The preventive services use self-efficacy (PRESS) scale in older women: development and psychometric properties.

BACKGROUND: Preventive services offered to older Americans are currently under-utilized despite considerable evidence regarding their health and economic benefits. Individuals with low self-efficacy in accessing these services need to be identified and provided self-efficacy enhancing interventions. Scales measuring self-efficacy in the management of chronic diseases exist, but do not cover the broad spectrum of preventive services and behaviors that can improve the health of older adults, particularly older women who are vulnerable to poorer health and lesser utilization of preventive services. This study aimed to evaluate the psychometric properties of a new preventive services use self-efficacy scale, by measuring its internal consistency reliability, assessing internal construct validity by exploring factor structure, and examining differences in self-efficacy scores according to participant characteristics. METHODS: The Preventive Services Use Self-Efficacy (PRESS) Scale was developed by an expert panel at the University of Pittsburgh Center for Aging and Population Health - Prevention Research Center. It was administered to 242 women participating in an ongoing trial and the data were analyzed to assess its psychometric properties. An exploratory factor analysis with a principal axis factoring approach and orthogonal varimax rotation was used to explore the underlying structure of the items in the scale. The internal consistency of the subscales was assessed using Cronbach's alpha coefficient. RESULTS: The exploratory factor analysis defined five self-efficacy factors (self-efficacy for exercise, communication with physicians, self-management of chronic disease, obtaining screening tests, and getting vaccinations regularly) formed by 16 items from the scale. The internal consistency of the subscales ranged from .81 to .94. Participants who accessed a preventive service had higher self-efficacy scores in the corresponding sub-scale than those who did not. CONCLUSIONS: The 16-item PRESS scale demonstrates preliminary validity and reliability in measuring self-efficacy in the use of preventive services among older women. It can potentially be used to evaluate the impact of interventions designed to improve self-efficacy in the use of preventive services in community-dwelling older women.

MTHFR-1298 A>C (rs1801131) is a predictor of survival in two cohorts of stage II/III colorectal cancer patients treated with adjuvant fluoropyrimidine chemotherapy with or without oxaliplatin.

Adjuvant treatment based on fluoropyrimidines (FL) improves the prognosis of stage II/III colorectal cancer (CRC). Validated predictive/prognostic biomarkers would spare therapy-related morbidity in patients with a good prognosis. We compared the impact of a set of 22 FL-related polymorphisms with the prognosis of two cohorts of CRC patients treated with adjuvant FL with or without OXA, including a total of 262 cases. 5,10-Methylentetrahydrofolate reductase (MTHFR) MTHFR-1298 A>C (rs1801131) polymorphism had a concordant effect: MTHFR-rs1801131-1298CC genotype carriers had a worse disease free survival (DFS) in both the cohorts. In the pooled population MTHFR-rs1801131-1298CC carriers had also a worse overall survival. We computed a clinical score related to DFS including MTHFR-rs1801131, tumor stage, sex and tumor location, where rs1801131 is the most detrimental factor (hazard ratio=5.3, 95% confidence interval=2.2-12.9; P-value=0.0006). MTHFR-rs1801131 is a prognostic factor that could be used as an additional criteria for the choice of the proper adjuvant regimen in stage II/III colorectal cancer patients.

Prognostic value of KRAS mutations in stage III colon cancer: post hoc analysis of the PETACC8 phase III trial dataset.

BACKGROUND: The prognostic value of KRAS mutations in colon adenocarcinoma is controversial. We examined this question as an ancillary study of the PETACC8 phase III trial. PATIENTS AND METHODS: We analyzed the prognostic impact of KRAS exon 2 mutations in stage III colon cancer patients (n = 1657) receiving adjuvant FOLFOX ± cetuximab therapy included in the PETACC8 trial. Patients with BRAF-mutated cancers were excluded and, as no difference was found for time to recurrence (TTR) and disease-free survival (DFS) between treatment arms, both were pooled for analysis. Associations with TTR and DFS were analyzed using a Cox proportional hazards model. RESULTS: KRAS mutations were found in 638 of 1657 tumors and linked to shorter TTR (P < 0.001). However, when specific mutations were compared with wild-type, codon 12 mutations [hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.35-2.04; P < 0.001] but not codon 13 (HR 1.23, 95% CI 0.85-1.79; P = 0.26) were significantly associated with shorter TTR, independently of other covariates. The interaction test showed that, regarding tumor location (distal versus proximal), KRAS genotype affects differently on recurrence (P = 0.02) and DFS (P = 0.042). Subgroup analysis showed that KRAS only affected TTR and DFS in distal tumors (n = 1043; 692 wild type; 351 mutated), with an increased risk of relapse (HR 1.96, 95% CI 1.51-2.56; P < 0.0001) for KRAS codon 12 mutations and a borderline significance for codon 13 mutations (HR 1.59, 95% CI 1.00-2.56; P = 0.051). CONCLUSION: KRAS exon 2 mutations are independent predictors of shorter TTR in patients with resected stage III distal colon cancers receiving adjuvant therapy. Future clinical trials in the adjuvant setting should consider both the tumor location and KRAS mutations as important stratification factors. CLINICAL TRIAL NUMBER: This is an ancillary study of the PETACC8 trial: EUDRACT 2005-003463-23.

Randomized trial on adjuvant treatment with FOLFIRI followed by docetaxel and cisplatin versus 5-fluorouracil and folinic acid for radically resected gastric cancer.

BACKGROUND: Some trial have demonstrated a benefit of adjuvant fluoropirimidine with or without platinum compounds compared with surgery alone. ITACA-S study was designed to evaluate whether a sequential treatment of FOLFIRI [irinotecan plus 5-fluorouracil/folinic acid (5-FU/LV)] followed by docetaxel plus cisplatin improves disease-free survival in comparison with 5-FU/LV in patients with radically resected gastric cancer. PATIENTS AND METHODS: Patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to either FOLFIRI (irinotecan 180 mg/m(2) day 1, LV 100 mg/m(2) as 2 h infusion and 5-FU 400 mg/m(2) as bolus, days 1 and 2 followed by 600 mg/m(2)/day as 22 h continuous infusion, q14 for four cycles) followed by docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, q21 for three cycles (sequential arm) or De Gramont regimen (5-FU/LV arm). RESULTS: From February 2005 to August 2009, 1106 patients were enrolled, and 1100 included in the analysis: 562 in the sequential arm and 538 in the 5-FU/LV arm. With a median follow-up of 57.4 months, 581 patients recurred or died (297 sequential arm and 284 5-FU/LV arm), and 483 died (243 and 240, respectively). No statistically significant difference was detected for both disease-free [hazard ratio (HR) 1.00; 95% confidence interval (CI): 0.85-1.17; P = 0.974] and overall survival (OS) (HR 0.98; 95% CI: 0.82-1.18; P = 0.865). Five-year disease-free and OS rates were 44.6% and 44.6%, 51.0% and 50.6% in the sequential and 5-FU/LV arm, respectively. CONCLUSIONS: A more intensive regimen failed to show any benefit in disease-free and OS versus monotherapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01640782.

Prophylactic mesh reinforcement for midline incisional hernia prevention: systematic review and updated meta-analysis of randomized controlled trials.

BACKGROUND: Incisional hernia (IH) is a common complication after abdominal surgery. Prevention of IH is matter of intense research. Prophylactic mesh reinforcement (PMR) has been shown to be promising in the minimization of IH risk after elective midline laparotomy. METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing PMR vs. primary suture closure (PSC). Risk ratio (RR) and standardized mean difference (MD) were used as pooled effect size measures whereas 95% confidence intervals (95%CI) were used to assess relative inference. RESULTS: Fourteen RCTs (2332 patients) were included. Overall, 1280 (54.9%) underwent PMR while 1052 (45.1%) PSC. Postoperative follow-up ranged from 12 to 67 months. The incidence of IH was reduced for PMR vs. PSC (13.4% vs. 27.5%). The estimated pooled IH RR for PMR vs. PSC is 0.38 (95% CI 0.24-0.58; p < 0.001). Stratified subgroup analysis according to mesh location shows a risk reduction for intraperitoneal (RR = 0.65; 95% CI 0.48-0.89), preperitoneal (RR = 0.18; 95% CI 0.04-0.81), retromuscular (RR = 0.47; 95% CI 0.24-0.92) and onlay (RR = 0.24; 95% CI 0.12-0.51) compared to PSC. The seroma RR was higher for PMR (RR = 2.05; p = 0.0008). No differences were found for hematoma (RR = 1.49; p = 0.34), surgical site infection (SSI) (RR = 1.17; p = 0.38), operative time (OT) (MD = 0.27; p = 0.413), and hospital length of stay (HLOS) (MD = -0.03; p = 0.237). CONCLUSIONS: PMR seems effective in reducing the risk of IH after elective midline laparotomy compared to PSC in the medium-term follow-up. While the risk of postoperative seroma appears higher for PMR, hematoma, SSI, HLOS and OT seems comparable.

Association between dietary inflammatory index score and incident dementia: results from the Framingham heart Study offspring cohort.

Background: The Dietary Inflammatory Index (DII), has been specifically designed to capture the inflammatory content of diet and has shown association with neurodegenerative disease related outcomes. But literature is limited on the role of diet-driven inflammation measured by the DII on incident all-cause dementia and Alzheimer's disease dementia (AD). Objective: We evaluated whether higher DII scores were associated with increased incidence of all-cause dementia and AD over 22.3 years of follow-up in the community-based Framingham Heart Study (FHS) Offspring cohort. Design Setting and Participants: Observational longitudinal study in the FHS Offspring cohort. Dementia surveillance for present study: until 2020. Data were analyzed from December 2020 to June 2022. Participants completed a validated 126-item food frequency questionnaires (FFQ), administered at FHS examination cycle 7 (1998-2001) and examination cycle 5 (1991-1995), and/or 6 (1995-1998). Individuals aged <60 years, with prevalent dementia, no dementia follow-up, other relevant neurological diseases, and/or no FFQ data were excluded. Exposure: A DII score (based on the published method by Shivappa et al. 2014) was created based on previous studies linking individual dietary factors to six inflammatory markers (i.e. C-reactive protein, interleukin (IL)-1ß, IL-4, IL-6, IL-10, and tumor necrosis factor-alpha), consisting of 36 components. A cumulative DII score was calculated by averaging across a maximum of three FFQs. Main outcomes and measures: Incident all-cause dementia and AD. Results: We included 1487 participants (mean±SD, age in years 69 ± 6; 53·2% women; 31·6% college graduates]). 246 participants developed all-cause dementia (including AD n=187) over a median follow up time of 13·1 years. Higher DII scores were associated with an increased incidence of all-cause dementia and AD following adjustment for age and sex (Hazard ratio (HR) 1·16, 95% confidence interval (CI) 1·07 to 1·25, p<.001; HR 1·16, 95% CI 1·06 to 1·26, p=.001). The relationships remained after additional adjustment for demographic, lifestyle, and clinical covariates (HR 1·21, 95% CI 1·10 to 1·33, p<0.001; HR1·20, 95% CI1·07 to 1·35, p=.001). Conclusion and relevance: Higher DII scores were associated with a higher risk of incident all-cause dementia and AD. Although these promising findings need to be replicated and further validated, our results suggest that diets which correlate with low DII scores may prevent late-life dementia.

Tutorials in population neuroimaging: Using epidemiology in neuroimaging research.

Epidemiology is the foundation of all public health research and practice. Epidemiology confers many important uses for the advancement of neuroimaging research. Epidemiology serves as a framework to organize pieces of data and guide critical thinking in the research process from the early stages of study design to the end goal of reaching appropriate inferences. Epidemiology accounts for the profound heterogeneity in populations, thoroughly describes study samples, and identifies consequential threats to study validity. Finally, epidemiology is a discovery tool that can lead researchers to uncover new risk factors, disease states, and subpopulations. The neuroimaging investigator with a grasp of the principles of epidemiology is in a unique position to undertake valid clinical epidemiology and etiological research.

Association of Midlife Depressive Symptoms with Regional Amyloid-ß and Tau in the Framingham Heart Study.

BACKGROUND: Depressive symptoms predict increased risk for dementia decades before the emergence of cognitive symptoms. Studies in older adults provide preliminary evidence for an association between depressive symptoms and amyloid-ß (Aß) and tau accumulation. It is unknown if similar alterations are observed in midlife when preventive strategies may be most effective. OBJECTIVE: The study aim was to evaluate the association between depressive symptoms and cerebral Aß and tau in a predominately middle-aged cohort with examination of the apolipoprotein (APOE) ɛ4 allele as a moderator. METHODS: Participants included 201 adults (mean age 53±8 years) who underwent 11C-Pittsburgh Compound B amyloid and 18F-Flortaucipir tau positron emission tomography (PET) imaging. Depressive symptoms were evaluated with the Center for Epidemiological Studies Depression Scale (CES-D) at the time of PET imaging, as well as eight years prior. Associations between depressive symptoms at both timepoints, as well as depression (CES-D≥16), with regional Aß and tau PET retention were evaluated with linear regression adjusting for age and sex. Interactions with the APOE ɛ4 allele were explored. RESULTS: Depressive symptoms and depression were not associated with PET outcomes in the overall sample. However, among APOE ɛ4 allele carriers, there was a significant cross-sectional association between depressive symptoms and increased tau PET uptake in the entorhinal cortex (ß= 0.446, SE = 0.155, p = 0.006) and amygdala (ß= 0.350, SE = 0.133, p = 0.012). CONCLUSION: Although longitudinal studies are necessary, the results suggest that APOE ɛ4 carriers with depressive symptoms may present with higher susceptibility to early tau accumulation in regions integral to affective regulation and memory consolidation.

Role of novel hormonal therapies in the management of non-metastatic castration-resistant prostate cancer: a literature-based meta-analysis of randomized trials.

BACKGROUND: Novel hormonal therapies have been recently investigated in non-metastatic castration-resistant prostate cancer (CRPC). We performed a meta-analysis to assess the efficacy and safety of novel hormonal therapies in non-metastatic CRPC. MATERIALS AND METHODS: The primary outcome was metastasis-free survival (MFS). The secondary endpoints were overall survival (OS), time to PSA progression and safety. We planned a subgroup analysis according to the PSA doubling time (> 6 vs < 6 months), Eastern Cooperative Oncology Group (ECOG) performance status (1 vs 0) and concomitant use of bone-targeting agent (yes vs no). RESULTS: Pooled analysis of novel hormonal therapies revealed significantly increased MFS compared with placebo (hazard ratio (HR): HR = 0.32, 95% CI 0.25-0.41; p < 0.00001). The subgroup analysis showed a statistically significant MFS advantage in favour of men with the lower ECOG performance status. Other secondary endpoints favoured the novel hormonal therapies. The relative risk (RR) of grade ≥ 3 adverse events and ≥ 3 hypertension was 1.31 and 1.39, respectively. CONCLUSIONS: This study confirmed the efficacy and safety of the novel hormonal therapies in non-metastatic CRPC.

Burden and Patterns of Multimorbidity: Impact on Disablement in Older Adults.

OBJECTIVE: The aim of this study was to assess the impact of the burden and patterns of multimorbidity on disability domains. DESIGN: In a cross-sectional study of 425 older adults from the Boston Rehabilitative Impairment Study of the Elderly, participants self-reported 13 chronic conditions and underwent assessment of body function (leg strength, velocity, and power, trunk extensor endurance, leg range of motion, foot sensation), activities (400-m walk test, Short Physical Performance Battery, Late Life Function and Disability Instrument function scores) and participation (Late Life Function and Disability Instrument participation scores). The association between multimorbidity patterns (identified by latent class analysis) and disablement measures, as well as multimorbidity burden (captured by a multimorbidity score) and disablement measures, was tested. RESULTS: Latent class analysis identified three classes-low multimorbidity, high multimorbidity, and predominantly musculoskeletal conditions. Class membership (multimorbidity pattern) was not associated with disablement measures, but multimorbidity score was associated with poor performance in all domains. A 1-point higher multimorbidity score was associated with lower scores in body functions (by 0.06 SD unit), activities (0.07-0.10 SD units), as well as participation (0.07-0.09 units). CONCLUSION: Multimorbidity counts may be an excellent tool for risk stratification and identification of persons in need of rehabilitation. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to (1) describe and distinguish the effect of multimorbidity burden and multimorbidity patterns on three disability domains in older adults; (2) identify and discuss possible reasons why high multimorbidity burden may result in a restriction among social participation in older adults; and (3) detect disability risk among older patients during clinical assessment by using a simple count of common chronic conditions. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Nanoparticle albumin-bound paclitaxel: a big nano for the treatment of gastric cancer.

Gastric cancer (GC) is the third cause of cancer-related death worldwide. Patients with unresectable GC can be treated with chemotherapy such as paclitaxel, which is a microtubule stabilizer. The use of nanoparticle albumin-bound paclitaxel (nab-ptx) avoids hypersensitivity reactions due to the absence of solvent needed to dissolve paclitaxel and it can be administered at higher doses. The ABSOLUTE randomized phase-3 clinical trial showed the non-inferiority of the nab-ptx used every week compared to the solvent-based paclitaxel used every week. This review describes the current advancements of the use of nab-ptx in GC in preclinical and clinical study investigations. The possibility of combining nab-ptx with other medications to improve response of patients to their specific molecular needs will also be debated.

Neuromuscular Attributes Associated With Lower Extremity Mobility Among Community-Dwelling Older Adults.

BACKGROUND: The Short Physical Performance Battery (SPPB) is advocated as a screening tool in geriatric care for predicting future disability. We aimed to identify the leg neuromuscular attributes to be targeted in rehabilitative care among older adults with poor SPPB scores. METHODS: Boston Rehabilitative Impairment Study of the Elderly (Boston RISE) participants (n = 430) underwent assessment of neuromuscular attributes (leg strength, leg velocity, trunk extensor endurance, knee flexion range of motion [ROM], ankle ROM, and foot sensation). Linear regression models examined association between each neuromuscular attribute and SPPB, adjusting for age, race, gender, comorbidity, body mass index, depression, cognition, and other neuromuscular attributes. RESULTS: Participants with 1 SD unit higher leg strength, leg velocity, and trunk extensor endurance had 0.52, 0.30, and 0.52 points higher SPPB total score. Participants with ankle ROM impairment and foot sensory loss had 0.43 and 0.57 lower SPPB total score compared with those without these. Leg strength and trunk extensor endurance were associated with balance; leg velocity, trunk extensor endurance, and ankle ROM were associated with gait speed; and strength, trunk extensor endurance, knee ROM, and feet sensation were associated with chair stand score. Neuromuscular attributes, along with covariates, explained 40.4% of the variance in the total SPPB score, a substantial increase over the 22.7% variance explained by covariates alone. CONCLUSIONS: Neuromuscular attributes affect mobility performance in older patients as measured by the SPPB. Specific impairments are associated with poor performance in specific component scores. Assessment of the SPPB components and rehabilitation of associated impairments may help improve the functional performance among older adults.

Association of Biomarker and Physiologic Indices With Mortality in Older Adults: Cardiovascular Health Study.

Background: A goal of gerontology is discovering aging phenotypes that reflect biological aging distinct from disease pathogenesis. Biomarkers that strongly and independently associated with mortality and that statistically attenuated chronologic age could be used to define such a phenotype. We determined the association of a Biomarker Index (BI) with mortality and compared it with a validated Physiologic Index (PI) in older adults. Methods: The indices were constructed in the Cardiovascular Health Study, mean (SD) age 74.5 (5.1) years. The BI incorporated circulating levels of new biomarkers, including insulin-like growth factor-1, insulin-like growth factor-binding protein 3, amino-terminal pro-B-type natriuretic peptide, dehydroepiandrosterone sulfate, and interleukin-6, and was built in test (N = 2,197) and validation (N = 1,124) samples. The PI included carotid intima-media thickness, pulmonary capacity, brain white matter grade, cystatin-C, and fasting glucose. Multivariable Cox proportional hazards models predicting death were calculated with 10 years of follow-up. Results: In separate age-adjusted models, the hazard ratio for mortality per point of the BI was 1.30 (95% confidence interval 1.25, 1.34) and the BI attenuated age by 25%. The hazard ratio for the PI was 1.28 (1.24, 1.33; 29% age attenuation). In the same model, the hazard ratio for the BI was 1.23 (1.18, 1.28) and for the PI was 1.22 (1.17, 1.26), and age was attenuated 42.5%. Associations persisted after further adjustment. Conclusions: The BI and PI were significantly and independently associated with mortality. Both attenuated the age effect on mortality substantially. The indices may be feasible phenotypes for developing interventions hoping to alter the trajectory of aging.

Age, Race, and Gender Factors in Incident Disability.

Background: Incident disability rates enable the comparison of risk across populations. Understanding these by age, sex, and race is important for planning for the care of older adults and targeting prevention. Methods: We calculated incident disability rates among older adults in the Cardiovascular Health Study, a study of 5,888 older adults aged ≥ 65 years over 6 years of follow-up. Disability was defined in the following two ways: (i) self-report of disability (severe difficulty or inability) in any of six Activities of Daily Living (ADL), and (ii) mobility difficulty (any difficulty walking half a mile or climbing 10 steps). Incident disability rates were calculated as events per 100 person years for age, gender, and race groups. Results: The incidence of ADL disability, and mobility difficulty were 2.7 (2.5-2.8), and 9.8 (9.4-10.3) events per 100 person years. Women, older participants, and blacks had higher rates in both domains. Conclusion: Incidence rates are considerably different based on the domain examined as well as age, race, and gender composition of the population. Prevention efforts should focus on high risk populations and attempt to ameliorate factors that increase risk in these groups.