A decrease in brown adipose tissue activity is associated with weight gain during chemotherapy in early breast cancer patients.

BACKGROUND: A decrease in thermogenesis is suspected to be implicated in the energy expenditure reduction during breast cancer treatment. This study aimed to investigate the impact of chemotherapy on the metabolic activity of brown adipose tissue (BAT) and the link with weight variation. METHODS: This was an ancillary analysis of a multicentre trial involving 109 HER2+ breast cancer patients treated with neoadjuvant chemotherapy. A centralised review of 18F-FDG uptake intensity (SUVmax) in specific BAT regions (cervical and supraclavicular) was conducted on two PET-CT scans for each patient (before and after the first course of chemotherapy). RESULTS: Overall, after one course of chemotherapy a significant decrease of 4.4% in 18F-FDG-uptake intensity was observed. It was not correlated to initial BMI, age or season. During chemotherapy, 10.1% (n = 11) of the patients lost weight (- 7.7 kg ± 3.8 kg; ie, - 9.4% ± 3.7%) and 29.4% (n = 32) gained weight (+ 5.1 kg ± 1.7 kg; ie, + 8.5% ± 2.6%). Among these subgroups, only the patients who had gained weight underwent a significant decrease (13.42%) in 18F-FDG uptake intensity (p = 0.042). CONCLUSION: This study is the first to highlight in a large cohort of patients the negative impact of chemotherapy on brown adipose tissue activity. Weight gain during chemotherapy could thus potentially be explained in part by a decrease in brown adipose tissue activity.

Treatment-Induced Cardiotoxicity in Breast Cancer: A Review of the Interest of Practicing a Physical Activity.

Physical activity is known to prevent the occurrence of cancer and decrease the risk of breast cancer. At diagnosis of breast cancer, fewer than half of the patients reach the international recommendation for physical activity. However, breast cancer patients, and particularly HER2+ breast cancer patients, are exposed to treatment-induced cardiotoxicity because of a side effect of 2 molecules used in standard therapy to treat these tumors, i.e., anthracycline and trastuzumab. Cardiotoxicity can sometimes lead to discontinuation of the treatment and even to the development of cardiovascular diseases. Exercise is known to protect the cardiovascular system in the healthy population. Consequently, being physically active during treatment appears to be a way to prevent the negative impact of cancer treatment on the heart in this population. In particular, aerobic exercising could have a protective effect against treatment-induced cardiotoxicity. A supervised physical activity program seems to be the best way for breast cancer patients to be active during treatment. However, there is very little information, and in particular a lack of guidelines, on exercising available to patients. The interventional trials that have been conducted on this topic are very heterogeneous and no standard recommendations have been made available for cancer patients thus far. An effective physical activity program needs to take each patient's barriers and motivations into account in order to encourage the practice of physical activity throughout treatment. To ensure the success of the program, it is essential to facilitate adherence and especially maintain motivation. Further studies are needed to determine what practice guidelines oncologists should give their patients.

Prospective Study on Body Composition, Energy Balance and Biological Factors Changes in Post-menopausal Women with Breast Cancer Receiving Adjuvant Chemotherapy Including Taxanes.

In breast cancer patients, weight and fat mass changes observed after chemotherapy have been related to poor prognosis but some recent works using modern chemotherapy failed to find this correlation with weight gain. In this study, the extent of changes in weight and body composition (DEXA, impedance) was characterized until six months after current chemotherapy, in 50 post-menopausal women with breast cancer. The evolution of factors contributing to the energy balance and some biological factors were also described. During chemotherapy, 20% of women lost weight due to both fat (-13.1% ± 10.3) and lean soft tissue mass loss (-3.6% ± 4.6). Twenty percent of women gained weight. No significant fat mass gain was observed in these women but significant water gain was highlighted. Six months later, women who gained weight presented a gain in fat mass (15.4% ± 19.0), especially in the abdominal region. Age and initial BMI were negatively correlated with fat mass in multivariate analyzes (r = 0.486, P = 0.0030). No significant variation of the glucose homeostasis, triglycerides, and HDL-Cholesterol was found six months after chemotherapy. These results do not suggest major adverse metabolic disturbances six months after modern chemotherapy and only a mild fat mass gain was observed in women who gained weight.

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.

Brown adipose tissue activity in relation to weight gain during chemotherapy in breast cancer patients: a pilot study.

Weight gain has been reported in early stage breast cancer patients during chemotherapy, but the involved mechanisms remain unclear. A chemotherapy-induced decrease of brown adipose tissue (BAT) activity may partly contribute to weight gain in these patients. A positron emission tomography/computed tomography scan was performed at baseline and after 1 course of docetaxel + trastuzumab treatment in 26 breast cancer women. Variation of the maximal standardized uptake value of BAT in the cervical and supraclavicular regions between the 2 measures was assessed according to weight changes. Overall, (18)F-FDG uptakes in BAT decreased by 11.3% after 1 course of chemotherapy (p = 0.03). No correlation was found between the baseline values of (18)F-FDG uptake and body mass index or age of patients, but as expected (18)F-FDG uptake was dependent on season period. Among the patients, 35% gained weight, 25% lost weight, and 40% remained stable. Women who gained weight during chemotherapy experienced a significant decrease of (18)F-FDG uptake in BAT (p = 0.005). Decreased activity of BAT was associated with body weight gain during chemotherapy. These original data suggest for the first time that BAT modulation by chemotherapy would be a potential contributor to body weight gain through blunted thermogenesis in breast cancer patients.

Ultrafast inactivation of SARS-CoV-2 by 254-nm UV-C irradiation on porous and non-porous media of medical interest using an omnidirectional chamber.

Covid-19 has spurred a renewed interest in decontamination techniques for air, objects and surfaces. Beginning in 2020, urgent effort was done to permit the reuse of UV-C for inactivating SARS-CoV-2. However, those studies diverged widely on the dose necessary to reach this goal; until today, the real value of the sensitivity of the virus to a 254-nm illumination is not known precisely. In this study, decontamination was performed in an original UV-C large decontamination chamber (UVCab, ON-LIGHT, France) delivering an omnidirectional irradiation with an average dose of 50 mJ/cm2 in 60 s. Viral inactivation was checked by both cell culture and PCR test. SARS-CoV-2 was inactivated by UV-C light within 3 s on both porous (disposable gown) and non-porous (stainless steel and apron) surfaces. For the porous surface, an irradiation of 5 min was needed to achieve a completely negative PCR signal. The Z value estimating the sensitivity of SARS-CoV-2 to UV-C in the experimental conditions of our cabinet was shown to be > 0.5820 m2/J. These results illustrate the ability of this apparatus to inactivate rapidly and definitively high loads of SARS-CoV-2 deposited on porous or non-porous supports and opens new perspectives on material decontamination using UV-C.

Screening and management of sleep disorders in patients with fibromyalgia syndrome: a French multicentred, prospective, observational study protocol (FIBOBS).

INTRODUCTION: Sleep disorders are still often underestimated in patient care management even though they are present in the criteria of the American College of Rheumatology for the diagnosis of fibromyalgia syndrome (FMS). The objective of this study will be to assess the current situation of sleep disorders in patients with FMS in France and to estimate its prevalence. METHODS AND ANALYSIS: The FIBOBS study is a multicentred, prospective, observational trial performed by 46 specialised chronic pain structures in France. Patients with FMS visiting for a first consultation or follow-up (if they have already been followed up for less than a year with a pain management service) will be included after giving their informed consent. Data will be collected through the physician questionnaire filled during the inclusion visit. Patient self-questionnaires will be completed from home. The primary outcome of the study will be to estimate the prevalence of sleep disorders classified into three categories: (a) poor sleep quality in general, (b) sleep apnoea syndrome and (c) restless legs syndrome, using self-administered questionnaires. ETHICS AND DISSEMINATION: This protocol is approved by the ethics committee Comité de Protection des Personnes 'Ile de France II' in accordance with French regulations. The results will be disseminated through peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: NCT04775368.

Saliva Quantification of SARS-CoV-2 in Real-Time PCR From Asymptomatic or Mild COVID-19 Adults.

The fast spread of COVID-19 is related to the highly infectious nature of SARS-CoV-2. The disease is suggested to be transmitted through saliva droplets and nasal discharge. The saliva quantification of SARS-CoV-2 in real-time PCR from asymptomatic or mild COVID-19 adults has not been fully documented. This study analyzed the relationship between salivary viral load on demographics and clinical characteristics including symptoms, co-morbidities in 160 adults diagnosed as COVID-19 positive patients recruited between September and December 2020 in four French centers. Median initial viral load was 4.12 log10 copies/mL (IQR 2.95-5.16; range 0-10.19 log10 copies/mL). 68.6% of adults had no viral load detected. A median load reduction of 23% was observed between 0-2 days and 3-5 days, and of 11% between 3-5 days and 6-9 days for the delay from onset of symptoms to saliva sampling. No significant median difference between no-symptoms vs. symptoms patients was observed. Charge was consistently similar for the majority of the clinical symptoms excepted for headache with a median load value of 3.78 log10 copies/mL [1.95-4.58] (P < 0.003). SARS-CoV-2 RNA viral load was associated with headache and gastro-intestinal symptoms. The study found no statistically significant difference in viral loads between age groups, sex, or presence de co-morbidity. Our data suggest that oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.

Use of an antiviral mouthwash as a barrier measure in the SARS-CoV-2 transmission in adults with asymptomatic to mild COVID-19: a multicentre, randomized, double-blind controlled trial.

OBJECTIVES: To determine if commercially available mouthwash with ß-cyclodextrin and citrox (bioflavonoids) (CDCM) could decrease the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) salivary viral load. METHODS: In this randomized controlled trial, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive patients aged 18-85 years with asymptomatic to mild coronavirus disease 2019 (COVID-19) symptoms for <8 days were recruited. A total of 176 eligible patients were randomly assigned (1:1) to CDCM or placebo. Three rinses daily were performed for 7 days. Saliva sampling was performed on day 1 at 09.00 (T1), 13.00 (T2) and 18.00 (T3). On the following 6 days, one sample was taken at 15.00. Quantitative RT-PCR was used to detect SARS-CoV-2. RESULTS: The intention-to-treat analysis demonstrated that, over the course of 1 day, CDCM was significantly more effective than placebo 4 hours after the first dose (p 0.036), with a median percentage (log10 copies/mL) decrease T1-T2 of -12.58% (IQR -29.55% to -0.16%). The second dose maintained the low median value for the CDCM (3.08 log10 copies/mL; IQR 0-4.19), compared with placebo (3.31 log10 copies/mL; IQR 1.18-4.75). At day 7, there was still a greater median percentage (log10 copies/mL) decrease in salivary viral load over time in the CDCM group (-58.62%; IQR -100% to -34.36%) compared with the placebo group (-50.62%; IQR -100% to -27.66%). These results were confirmed by the per-protocol analysis. CONCLUSIONS: This trial supports the relevance of using CDCM on day 1 (4 hours after the initial dose) to reduce the SARS-CoV-2 viral load in saliva. For long-term effect (7 days), CDMC appears to provide a modest benefit compared with placebo in reducing viral load in saliva.

Risk factors associated with day-30 mortality in patients over 60 years old admitted in ICU for severe COVID-19: the Senior-COVID-Rea Multicentre Survey protocol.

INTRODUCTION: With the spread of COVID-19 epidemic, health plans must be adapted continuously. There is an urgent need to define the best care courses of patients with COVID-19, especially in intensive care units (ICUs), according to their individualised benefit/risk ratio. Since older age is associated with poorer short-term and long-term outcomes, prediction models are needed, that may assist clinicians in their ICU admission decision. Senior-COVID-Rea was designed to evaluate, in patients over 60 years old admitted in ICU for severe COVID-19 disease, the impact of age and geriatric and paraclinical parameters on their mortality 30 days after ICU admission. METHODS AND ANALYSIS: This is a multicentre survey protocol to be conducted in seven hospitals of the Auvergne-Rhône-Alpes region, France. All patients over 60 years old admitted in ICU for severe COVID-19 infection (or their legally acceptable representative) will be proposed to enter the study and to fill in a questionnaire regarding their functional and nutritional parameters 1 month before COVID-19 infection. Paraclinical parameters at ICU admission will be collected: lymphocytes and neutrophils counts, high-fluorescent lymphoid cells and immature granulocytes percentages (Sysmex data), D-dimers, C-reactive protein, lactate dehydrogenase (LDH), creatinine, CT scan for lung extension rate as well as clinical resuscitation scores, and the delay between the first signs of infection and ICU admission. The primary outcome will be the overall survival at day 30 post-ICU admission. The analysis of factors predicting mortality at day 30 will be carried out using univariate and multivariate logistic regressions. Multivariate logistic regression will consider up to 15 factors.The ambition of this trial, which takes into account the different approaches of geriatric vulnerability, is to define the respective abilities of different operational criteria of frailty to predict patients' outcomes. ETHICS AND DISSEMINATION: The study protocol was ethically approved. The results of the primary and secondary objectives will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04422340.