Sarcopenia and Sarcopenic Obesity and Mortality Among Older People.

Importance: Sarcopenia and obesity are 2 global concerns associated with adverse health outcomes in older people. Evidence on the population-based prevalence of the combination of sarcopenia with obesity (sarcopenic obesity [SO]) and its association with mortality are still limited. Objective: To investigate the prevalence of sarcopenia and SO and their association with all-cause mortality. Design, Setting, and Participants: This large-scale, population-based cohort study assessed participants from the Rotterdam Study from March 1, 2009, to June 1, 2014. Associations of sarcopenia and SO with all-cause mortality were studied using Kaplan-Meier curves, Cox proportional hazards regression, and accelerated failure time models fitted for sex, age, and body mass index (BMI). Data analysis was performed from January 1 to April 1, 2023. Exposures: The prevalence of sarcopenia and SO, measured based on handgrip strength and body composition (BC) (dual-energy x-ray absorptiometry) as recommended by current consensus criteria, with probable sarcopenia defined as having low handgrip strength and confirmed sarcopenia and SO defined as altered BC (high fat percentage and/or low appendicular skeletal muscle index) in addition to low handgrip strength. Main Outcome and Measure: The primary outcome was all-cause mortality, collected using linked mortality data from general practitioners and the central municipal records, until October 2022. Results: In the total population of 5888 participants (mean [SD] age, 69.5 [9.1] years; mean [SD] BMI, 27.5 [4.3]; 3343 [56.8%] female), 653 (11.1%; 95% CI, 10.3%-11.9%) had probable sarcopenia and 127 (2.2%; 95% CI, 1.8%-2.6%) had confirmed sarcopenia. Sarcopenic obesity with 1 altered component of BC was present in 295 participants (5.0%; 95% CI, 4.4%-5.6%) and with 2 altered components in 44 participants (0.8%; 95% CI, 0.6%-1.0%). An increased risk of all-cause mortality was observed in participants with probable sarcopenia (hazard ratio [HR], 1.29; 95% CI, 1.14-1.47) and confirmed sarcopenia (HR, 1.93; 95% CI, 1.53-2.43). Participants with SO plus 1 altered component of BC (HR, 1.94; 95% CI, 1.60-2.33]) or 2 altered components of BC (HR, 2.84; 95% CI, 1.97-4.11) had a higher risk of mortality than those without SO. Similar results for SO were obtained for participants with a BMI of 27 or greater. Conclusions and Relevance: In this study, sarcopenia and SO were found to be prevalent phenotypes in older people and were associated with all-cause mortality. Additional alterations of BC amplified this risk independently of age, sex, and BMI. The use of low muscle strength as a first step of both diagnoses may allow for early identification of individuals at risk for premature mortality.

Impact of COVID-19 Lockdown on Food Consumption and Behavior in France (COVISTRESS Study).

The COVID-19 pandemic and subsequent lockdowns modified work environments, lifestyles, and food consumption. Eating habits and mood changes in a French population during the first lockdown were examined using an online self-reported questionnaire with REDCap software through the COVISTRESS.ORG website. In 671 French participants, the main changes during lockdown were increased stress levels (64 [23; 86] vs. 3 [0; 18]) and sedentary behavior (7 [4; 9] vs. 5 [3; 8] hours per day), a deterioration in sleep quality (50 [27; 83] vs. 70 [48; 94]) and mood (50 [30; 76] vs. 78 [50; 92]), and less physical activity (2.0 [0.5; 5.0] vs. 3.5 [2.0; 6.0]). Mood was modified, with more anger (56 [39; 76] vs. 31 [16; 50]), more sadness (50 [34; 72] vs. 28 [16; 50]), more agitation (50 [25; 66] vs. 43 [20; 50]), and more boredom (32 [7; 60] vs. 14 [3; 29]). A total of 25% of the participants increased their consumption of alcoholic beverages, 29% their consumption of sugary foods, and 26% their consumption of cocktail snacks. A multiple-correspondence analysis highlights four different profiles according to changes in eating habits, food consumption, lifestyle, and mood. In conclusion, eating habits and lifestyle changes during lockdown periods should be carefully monitored to promote healthy behaviors.

Body Mass Trajectory Affects the Long-Term Occurrence of Metabolic Syndrome in Adult Patients with Severe Obesity.

Independently of absolute BMI values, the amount, onset date, and duration of early body weight gain may influence cardio-metabolic health later in adulthood. Values of cardiac and metabolic variables from a cohort study of morbidly obese patients were retrospectively analyzed to study the association between early weight history and metabolic syndrome (MetS) occurrence in adults. Of 950 patients with severe morbid obesity (age 44.3 ± 13.8 y, BMI 42.5 ± 7.0 kg/m2), 31.4% had started excess weight gain in childhood (CH), 19.9% in adolescence (ADO), and 48.7% in adulthood (AD). Despite different BMI values, MetS prevalence (57.8%) was not significantly different in the three groups (54.4% CH vs. 57.7% ADO vs. 59.8% AD, p = 0.59). The overweight onset period was not significantly associated with the development of MetS in adults (ADO: OR = 1.14 [0.69-1.92], p = 0.60; AD: OR = 0.99 [0.62-1.56], p = 0.95) despite a higher BMI in the early obesity onset group. Weight gain of more than 50% after age 18 years significantly increased the risk of MetS (OR = 1.75 [1.07-2.88], p = 0.026). In addition to crude BMI values, analysis of body mass trajectories is a relevant clinical tool in the assessment of metabolic risk, suggesting that the magnitude of weight gain may be more important for metabolic syndrome progression than the period of obesity onset.

Multicenter randomized phase II study comparing docetaxel plus curcumin versus docetaxel plus placebo in first-line treatment of metastatic castration-resistant prostate cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) patients have a poor prognosis, and curcumin is known to have antineoplastic properties. On the basis of previous phase I and phase II studies, we investigated whether the association of curcumin with docetaxel could improve prognosis among mCRPC patients. METHODS: A total of 50 mCRPC patients (included from June 2014 to July 2016) treated with docetaxel in association with oral curcumin (6 g/d for 7 days every 3 weeks) versus placebo were included in this double-blind, randomized, phase II study. The primary endpoint was to evaluate the time to progression. Among the secondary endpoints, compliance, overall survival, prostate-specific antigen (PSA) response, safety, curcumin absorption, and quality of life were investigated. An interim analysis was planned in the modified intention-to-treat population with data at 6 months (22 patients per arm). RESULTS: Despite good compliance and a verified absorption of curcumin, no difference was shown for our primary endpoint: progression-free survival (PFS) between the placebo and curcumin groups was, respectively, 5.3 months versus 3.7 months, p = 0.75. Similarly, no difference was observed for the secondary objectives: PSA response rate (p = 0.88), overall survival (p = 0.50), and quality of life (p = 0.49 and p = 0.47). CONCLUSION: Even though our previous studies and data in the literature seemed to support an association between curcumin and cancer therapies in order to improve patient outcome and prognosis, the results from this interim analysis clearly showed that adding curcumin to mCRPC patients' treatment strategies was not efficacious. The study was discontinued on the grounds of futility.

A Retrospective Study on the Onset of Menopause after Chemotherapy: Analysis of Data Extracted from the Jean Perrin Comprehensive Cancer Center Database Concerning 345 Young Breast Cancer Patients Diagnosed between 1994 and 2012.

OBJECTIVE: Young breast cancer (BC) patients receiving chemotherapy are at risk of chemotherapy-induced menopause (CIM). We sought to define the incidence rate of premature menopause after chemotherapy and to retrospectively investigate factors related to the onset of menopause. METHODS: We identified BC patients who had received chemotherapy at the Cancer Center (Centre Jean-Perrin). We selected premenopausal women aged between 18 and 50 years at the moment of diagnosis who received chemotherapy between 1994 and 2012. RESULTS: Of the 345 selected patients, the median age was 42 years (interquartile range: 38-46). CIM was defined as amenorrhea for at least 2 years following the end of chemotherapy. A total of 260 premenopausal women versus 85 menopausal women were included. Among the 85 menopausal women, only 46 were in the CIM group (13.3%). This rate increased in the group of women aged >43 years at diagnosis and with early hot flushes. CONCLUSION: CIM occurred in 13.3% of BC patients after chemotherapy. Age >43 years and early hot flushes were significantly associated with the risk of CIM. We suggest that the definition of CIM should be standardized in the literature: "amenorrhea of at least 2 years" seems a good cutoff, although 2 patients recovered their menstrual cycles beyond this limit.

Therapeutic drug monitoring and tyrosine kinase inhibitors.

The therapeutic activity of drugs can be optimized by establishing an individualized dosage, based on the measurement of the drug concentration in the serum, particularly if the drugs are characterized by an inter-individual variation in pharmacokinetics that results in an under- or overexposure to treatment. In recent years, several tyrosine kinase inhibitors (TKIs) have been developed to block intracellular signaling pathways in tumor cells. These oral drugs are candidates for therapeutic drug monitoring (TDM) due to their high inter-individual variability for therapeutic and toxic effects. Following a literature search on PubMed, studies on TKIs and their pharmacokinetic characteristics, plasma quantification and inter-individual variability was studied. TDM is commonly used in various medical fields, including cardiology and psychiatry, but is not often applied in oncology. Plasma concentration monitoring has been thoroughly studied for imatinib, in order to evaluate the usefulness of TDM. The measurement of plasma concentration can be performed by various analytical techniques, with liquid chromatography-mass spectrometry being the reference method. This method is currently used to monitor the efficacy and tolerability of imatinib treatments. Although TDM is already being used for imatinib, additional studies are required in order to improve this practice with the inclusion of other TKIs.

The New Combination Docetaxel, Prednisone and Curcumin in Patients with Castration-Resistant Prostate Cancer: A Pilot Phase II Study.

OBJECTIVES: Favorable phase I results justified this pilot phase II study to assess the efficacy of docetaxel/curcumin in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (CRPC). METHODS: Thirty patients with progressing CRPC and a rising prostate-specific antigen (PSA) received docetaxel/prednisone in standard conditions for 6 cycles in combination with per os curcumin, 6,000 mg/day (day -4 to day +2 of docetaxel). The co-primary endpoint was the overall response rate determined by PSA and target assessments. An ancillary study assessed the seric values of chromogranin A (CgA) and neuron-specific enolase (NSE). RESULTS: Twenty-six patients received the scheduled treatment, 2 progressed and 2 died before the end of treatment. A PSA response was observed in 59% of patients (14% of PSA normalization) and achieved within the first three cycles for 88% of responders. Partial response was reached for 40% of evaluable patients. The regimen was well tolerated, and no adverse event was attributed to curcumin. Twenty patients were 100% curcumin compliant. The PSA level and objective response rate were not correlated with the serum values of CgA and NSE. CONCLUSION: This study produced additional data on curcumin as a treatment for cancer, with a high response rate, good tolerability and patient acceptability, justifying the interest to conduct a randomized trial.

Long-term dietary supplementation with cystathionine improves tissue glutathione in ageing rats.

BACKGROUND: Ageing is associated with decrease in tissue glutathione that can be reduced by food fortification with the amino acid cysteine. However, cysteine is not stable in solution and generates bad taste. Cystathionine, the direct precursor of cysteine, could be a valuable alternative. AIMS: This study aimed to determine whether long-term dietary supplementation with cystathionine induces an increase in glutathione pools. METHODS: Aged rats (20.5-month-old) were fed ad libitum during 29 weeks with either a cystathionine-supplemented diet (7.3 g/kg, n = 90 rats) or a control iso-nitrogenous alanine-supplemented diet (2.9 g/kg, n = 90 rats). RESULTS: Cystathionine was detected in the plasma of the cystathionine-supplemented rats but not in the control alanine-supplemented rats. Cystathionine increased glutathione concentrations in liver, small intestine and gastrocnemius muscle (P < 0.03). No adverse effect was observed. CONCLUSION: Cystathionine supplementation being able to increase moderately glutathione in healthy old rats could be considered as a candidate for nutritional supports aiming to revert the stronger glutathione depletions occurring in unhealthy elderly.

Everolimus in Metastatic Breast Cancer: Clinical Experience as a Late Treatment Line.

BACKGROUND: Everolimus (Afinitor®) plus exemestane are indicated for hormone receptor-positive, HER2/neu-negative metastatic breast cancer (MBC), in menopausal women without symptomatic visceral disease after recurrence or progression following aromatase inhibitors. But everolimus efficacy as late treatment has not been explored. METHODS: Sixty-three MBC patients progressing under hormonotherapy (HT; n = 30) or after chemotherapy (CT; n = 32) received everolimus plus HT (EHT) and were analyzed for safety, efficacy and overall survival (OS). This cohort was compared with our previous 530 MBC patients stratified by line (PMID 21852136). RESULTS: The median duration of EHT was 27.8 weeks at 5-10 mg/day until clinical progression or toxicity. Median OS was not reached (median follow-up 18 months). Twelve-month survival was 100, 79 and 49% for patients treated with 0 (n = 13), 1-2 (n = 18) and >3 CT (n = 32), respectively. Median time-to-treatment failure was 6.4 months. In 62 EHT patients randomly matched 1:7 with 421 previous patients for age and number of CT, OS improved compared with patients receiving a new CT (p = 0.062). In patients pretreated with <2 CT, EHT gave a better OS than in those with a new CT (p = 0.026). CONCLUSIONS: These results may support the use of EHT whatever the number of previous lines.