Cancer-related pain in head and neck cancer survivors: longitudinal findings from the Head and Neck 5000 clinical cohort.

PURPOSE: Reports suggest pain is common in head and neck cancer (HNC). However, past studies are limited by small sample sizes and design and measurement heterogeneity. Using data from the Head and Neck 5000 longitudinal cohort, we investigated pain over a year post-diagnosis. We assessed: temporal trends; compared pain across HNC treatments, stages, sites and by HPV status; and identified subgroups of patients at increased risk of pain. METHODS: Sociodemographic and clinical data and patient-reported pain (measured by EORTC QLQ-C30 and QLQ-H&N35) were collected at baseline (pre-treatment), 4- and 12- months. Using mixed effects multivariable regression, we investigated time trends and identified associations between (i) clinically-important general pain and (ii) HN-specific pain and clinical, socio-economic, and demographic variables. RESULTS: 2,870 patients were included. At baseline, 40.9% had clinically-important general pain, rising to 47.6% at 4-months and declining to 35.5% at 12-months. HN-specific pain followed a similar pattern (mean score (sd): baseline 26.4 (25.10); 4-months. 28.9 (26.55); 12-months, 17.2 (19.83)). Across time, general and HN-specific pain levels were increased in: younger patients, smokers, and those with depression and comorbidities at baseline, and more advanced, oral cavity and HPV negative cancers. CONCLUSIONS: There is high prevalence of general pain in people living with HNC. We identified subgroups more often reporting general and HN-specific pain towards whom interventions could be targeted. IMPLICATIONS FOR CANCER SURVIVORS: Greater emphasis should be placed on identifying and treating pain in HNC. Systematic pain screening could help identify those who could benefit from an early pain management plan.

Association of insulin resistance with the accumulation of saturated intramyocellular lipid: A comparison with other fat stores.

It has been shown using proton magnetic resonance spectroscopy (1 H MRS) that, in a group of females, whole-body insulin resistance was more closely related to accumulation of saturated intramyocellular lipid (IMCL) than to IMCL concentration alone. This has not been investigated in males. We investigated whether age- and body mass index-matched healthy males differ from the previously reported females in IMCL composition (measured as CH2 :CH3 ) and IMCL concentration (measured as CH3 ), and in their associations with insulin resistance. We ask whether saturated IMCL accumulation is more strongly associated with insulin resistance than other ectopic and adipose tissue lipid pools and remains a significant predictor when these other pools are taken into account. In this group of males, who had similar overall insulin sensitivity to the females, IMCL was similar between sexes. The males demonstrated similar and even stronger associations of IMCL with insulin resistance, supporting the idea that a marker reflecting the accumulation of saturated IMCL is more strongly associated with whole-body insulin resistance than IMCL concentration alone. However, this marker ceased to be a significant predictor of whole-body insulin resistance after consideration of other lipid pools, which implies that this measure carries no more information in practice than the other predictors we found, such as intrahepatic lipid and visceral adipose tissue. As the marker of saturated IMCL accumulation appears to be related to these two predictors and has a much smaller dynamic range, this finding does not rule out a role for it in the pathogenesis of insulin resistance.

Patient experience of telehealth appointments in head and neck cancer services during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic resulted in rapid changes to head and neck cancer (HNC) services. Multidisciplinary team (MDT) face-to-face appointments were converted to telehealth appointments (telephone and video-call) to reduce the risk of COVID-19 transmission. The literature exploring HNC patient experience of these appointment types is limited. AIMS: To explore patient experience of telehealth appointments at one UK centre during the COVID-19 pandemic, as well as the variables that may influence patient preference for virtual or face-to-face appointments. METHODS & PROCEDURES: A survey-based study design was used, with closed questions and open text options to capture the views of the participants. Quantitative data were analysed using descriptive statistics. Open text data was used to add depth to the findings. OUTCOMES & RESULTS: A total of 23 participant surveys were returned. Six categories were identified: Usability; Information receiving & giving; Satisfaction; Emotions and comfort; Rapport; and Travel time and cost. Overall, participants gave positive responses to each category and indicated that telehealth appointments met their needs. Areas for clinical consideration are highlighted. Variables such as age, travel distance from hospital site, fear of COVID-19 and information technology (IT) access did not appear to influence patient preference for appointment type. CONCLUSIONS & IMPLICATIONS: Going forward, telehealth may be considered for use in combination with face-to-face appointments in the HNC pathway. Areas for further development include a 'telehealth screening tool' that may help to identify those patients most appropriate for these appointment types, or who require support to access them. WHAT THIS PAPER ADDS: What is already known on this subject The COVID-19 pandemic resulted in major disruption to HNC centres across the world. Services adapted to meet the needs of patients with many implementing telehealth into pathways. Studies exploring telehealth in speech and language therapy (SLT) services with the HNC population indicate positive results. It is clear telehealth has a role in modern healthcare and should not be viewed as a temporary solution to the pandemic. It is, however, recognized that embedding telehealth into pathways is not straightforward and requires ongoing review and evaluation, which includes patient and clinician perceptions. What this study adds to the existing knowledge The service evaluation gives insight into HNC patient experience of telehealth appointments for MDT clinics (led by SLT, dietician and clinical nurse specialist) during the COVID-19 pandemic. Overall, patients report a positive experience of telehealth in the HNC pathway and are willing to accept this platform into their healthcare. Areas for clinical consideration are highlighted. What are the actual and clinical implications of this work? This findings of this service evaluation can be used to support the co-design of HNC pathways which embed telehealth as an option for patients. Areas that were important to the participants are highlighted; this includes the timing of telehealth appointments in the pathway, the need to meet the MDT face to face and the positive benefit of cost savings. The authors suggest a telehealth appointment screening tool as an area for future development.

Cancer-Related Fatigue in Head and Neck Cancer Survivors: Longitudinal Findings from the Head and Neck 5000 Prospective Clinical Cohort.

Cancer-related fatigue (CRF) is a common side-effect of cancer and its treatments. For head and neck cancer (HNC), CRF may exacerbate the symptom burden and poor quality-of-life. Using data from the Head and Neck 5000 prospective clinical cohort, we investigated clinically important CRF over a year post-diagnosis, assessing temporal trends, CRF by HNC site and treatment received, and subgroups at higher risk of CRF. Recruitment was undertaken in 2011-2014. Socio-demographic and clinical data, and patient-reported CRF (EORTC QLQ-C30 fatigue subscale score ≥39 of a possible 100) were collected at baseline (pre-treatment) and 4- and 12- months post-baseline. Mixed-effects logistic multivariable regression was used to investigate time trends, compare cancer sites and treatment groups, and identify associations between clinical, socio-demographic and lifestyle variables and CRF. At baseline, 27.8% of 2847 patients scored in the range for clinically important CRF. This was 44.7% at 4 months and 29.6% at 12 months. In the multivariable model, after adjusting for time-point, the odds of having CRF over 12 months were significantly increased in females and current smokers; those with stage 3/4 disease, comorbidities and multimodal treatment; and those who had depression at baseline. The high prevalence of clinically important CRF indicates the need for additional interventions and supports for affected HNC patients. These findings also identified patient subgroups towards whom such interventions could be targeted.

Resistance to thyroid hormone induced tachycardia in RTHα syndrome.

Mutations in thyroid hormone receptor α1 (TRα1) cause Resistance to Thyroid Hormone α (RTHα), a disorder characterized by hypothyroidism in TRα1-expressing tissues including the heart. Surprisingly, we report that treatment of RTHα patients with thyroxine to overcome tissue hormone resistance does not elevate their heart rate. Cardiac telemetry in male, TRα1 mutant, mice indicates that such persistent bradycardia is caused by an intrinsic cardiac defect and not due to altered autonomic control. Transcriptomic analyses show preserved, thyroid hormone (T3)-dependent upregulation of pacemaker channels (Hcn2, Hcn4), but irreversibly reduced expression of several ion channel genes controlling heart rate. Exposure of TRα1 mutant male mice to higher maternal T3 concentrations in utero, restores altered expression and DNA methylation of ion channels, including Ryr2. Our findings indicate that target genes other than Hcn2 and Hcn4 mediate T3-induced tachycardia and suggest that treatment of RTHα patients with thyroxine in high dosage without concomitant tachycardia, is possible.

Centile reference chart for resting metabolic rate through the life course.

OBJECTIVE: Reference centile charts are widely used for the assessment of growth and have progressed from describing height and weight to include body composition variables such as fat and lean mass. Here, we present centile charts for an index of resting energy expenditure (REE) or metabolic rate, adjusted for lean mass versus age, including both children and adults across the life course. DESIGN, PARTICIPANTS AND INTERVENTION: Measurements of REE by indirect calorimetry and body composition using dual-energy X-ray absorptiometry were made in 411 healthy children and adults (age range 6-64 years) and serially in a patient with resistance to thyroid hormone α (RTHα) between age 15 and 21 years during thyroxine therapy. SETTING: NIHR Cambridge Clinical Research Facility, UK. RESULTS: The centile chart indicates substantial variability, with the REE index ranging between 0.41 and 0.59 units at age 6 years, and 0.28 and 0.40 units at age 25 years (2nd and 98th centile, respectively). The 50th centile of the index ranged from 0.49 units (age 6 years) to 0.34 units (age 25 years). Over 6 years, the REE index of the patient with RTHα varied from 0.35 units (25th centile) to 0.28 units (<2nd centile), depending on changes in lean mass and adherence to treatment. CONCLUSION: We have developed a reference centile chart for an index of resting metabolic rate in childhood and adults, and shown its clinical utility in assessing response to therapy of an endocrine disorder during a patient's transition from childhood to adult.

Fibromyalgia status and depressive symptoms are linked to body mass index and physical performance in mid to late life.

Fibromyalgia (FM) is a chronic pain condition that is frequently accompanied by comorbid conditions, including depression. Depression is associated with reduced physical functioning and health, disproportionately affecting middle-aged and older adults with FM. This study examined associations between FM status and depressive symptoms with body mass index (BMI) and several physical performance indicators among middle-aged and older adults. Participants included 239 community-dwelling middle-aged and older adults with or without FM. Depressive symptoms were measured using the Beck Depression Inventory-II (BDI-II), BMI was objectively assessed, and physical performance was measured using the Fullerton Advanced Balance scale, 6-minute walk test, 30-second chair stand, and 8-foot up and go test. A path model using structural equation modeling yielded good fit and revealed that, compared to pain-free adult controls, participants with FM reported more depressive symptoms, which were in turn associated with reduced physical performance across all indicators except BMI, after adjusting for age and symptom severity. Findings suggest that individuals with FM demonstrate disproportionately higher depressive symptoms compared to non-FM controls, which may diminish physical performance after accounting for age and symptom severity. This study supports FM status and depressive symptoms as important considerations when evaluating the health and disability risk of aging adults.

The effect of weight loss interventions for obesity on fertility and pregnancy outcomes: A systematic review and meta-analysis.

BACKGROUND: Weight loss could improve fertility, perhaps by reducing insulin resistance. OBJECTIVES: To assess the effect of weight loss interventions on fertility in women with obesity not recruited because of known infertility. SEARCH STRATEGY: Three databases during 1966-2020, trial registry. SELECTION CRITERIA: Randomized controlled trials (RCTs) with a follow-up of 1 year or more, with a mean cohort BMI of 30 kg/m2 or above. DATA COLLECTION AND ANALYSIS: A systematic review and meta-analysis was conducted. The primary outcome was pregnancy. The secondary outcome was weight change. MAIN RESULTS: A total of 27 RCTs (5938 women) were included. Weight loss interventions showed no statistically significant increase in pregnancies compared to control interventions (24 trials, 97 women with pregnancy; risk ratio [RR] 1.43, 95% confidence interval [CI] 0.91-2.23); weight change (mean difference [MD] -2.36 kg, 21 trials, 95% CI -3.17 to -1.55). Compared with low-fat diets, very-low-carbohydrate diets showed no statistically significant effect on women with pregnancy (three trials, 14 women with pregnancy; RR 1.37, 95% CI 0.49-3.84) or weight change (MD -0.32 kg, 95% CI -3.84 to 3.21). CONCLUSIONS: Diet-based weight loss interventions for women with obesity not recruited because of infertility were effective at producing long-term weight loss. The effects on fertility were not statistically significant, but few trials provided data. Weight loss trials should routinely collect fertility outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017078819.

The role of pain intensity and depressive symptoms in the relationship between sleep quality and postural control among middle-aged and older adults with Fibromyalgia.

OBJECTIVE: Fibromyalgia (FM) is a chronic pain condition often accompanied by sleep problems and depression that are each associated with reduced physical ability including postural control. Research supports a sequential association between pain intensity and depression in FM, and poor sleep quality may play a key role in this relationship. This study aimed to verify a serial pattern of associations among sleep quality, pain intensity, and depressive symptoms and quantify these effects on objective postural control. DESIGN: Community-residing adults diagnosed with FM (n = 155; Mage = 61.08, SD = 7.70; 93% female; 79% White) were included in this cross-sectional study. MAIN OUTCOMES: Participants self-rated sleep quality (restorative sleep, sleep waking, and sleep latency), pain intensity, and depressive symptoms, and the Fullerton Advanced Balance (FAB) scale and 8-Foot Up and Go Test (8FUPGT) measured objective postural control. RESULTS: Findings indicated that the serial association between pain intensity and depressive symptoms fully mediated the relationship between sleep quality and both FAB (95% CI [-.125, -.013]), and 8FUPGT (95% CI [.002, .033]) performance. CONCLUSION: Findings highlight the serial association of pain intensity and depressive symptoms with objective postural control performance and the potential for sleep and depression interventions that may maximize functional outcomes in FM.

Development of the remote 100 ml water swallow test versus clinical assessment in patients with head and neck cancer: Do they agree?

BACKGROUND: The 100 ml water swallow test (WST) is a validated swallow assessment used in head and neck cancer (HNC). We aimed to determine the level of agreement when completing the 100 ml WST via clinician-graded video-testing or patient self-testing compared to standard face-to-face assessment (FTF). METHODS: Convenience sampling from four UK centers. INCLUSION CRITERIA: patients with HNC treated with any modality prior to, or within 5 years of treatment. Participants were recruited to complete the 100 ml WST by video-testing or self-testing and compared with FTF. RESULTS: Sixty-three patients were recruited; 1 was unable to perform the task; 30 in video-testing; and 32 in self-testing. There was no difference in swallow capacity (p = 0.424) and volume (p = 0.363) for the video-testing or the self-testing swallow capacity (p = 0.777) and volume (p = 0.445). CONCLUSIONS: This study demonstrates that video-testing and self-testing are reliable methods of completing the 100 ml WST for this sample of patients with HNC.

A prospective study of risk factors associated with seroprevalence of SARS-CoV-2 antibodies in healthcare workers at a large UK teaching hospital.

OBJECTIVES: To describe the risk factors for SARS-CoV-2 infection in UK healthcare workers (HCWs). METHODS: We conducted a prospective sero-epidemiological study of HCWs at a major UK teaching hospital using a SARS-CoV-2 immunoassay. Risk factors for seropositivity were analysed using multivariate logistic regression. RESULTS: 410/5,698 (7·2%) staff tested positive for SARS-CoV-2 antibodies. Seroprevalence was higher in those working in designated COVID-19 areas compared with other areas (9·47% versus 6·16%) Healthcare assistants (aOR 2·06 [95%CI 1·14-3·71]; p=0·016) and domestic and portering staff (aOR 3·45 [95% CI 1·07-11·42]; p=0·039) had significantly higher seroprevalence than other staff groups after adjusting for age, sex, ethnicity and COVID-19 working location. Staff working in acute medicine and medical sub-specialities were also at higher risk (aOR 2·07 [95% CI 1·31-3·25]; p<0·002). Staff from Black, Asian and minority ethnic (BAME) backgrounds had an aOR of 1·65 (95% CI 1·32 - 2·07; p<0·001) compared to white staff; this increased risk was independent of COVID-19 area working. The only symptoms significantly associated with seropositivity in a multivariable model were loss of sense of taste or smell, fever, and myalgia; 31% of staff testing positive reported no prior symptoms. CONCLUSIONS: Risk of SARS-CoV-2 infection amongst HCWs is highly heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors.

Replenishment of myeloid-derived suppressor cells (MDSCs) overrides CR-mediated protection against tumor growth in a murine model of triple-negative breast cancer.

Caloric restriction (CR) is the leading non-pharmacological intervention to delay induced and spontaneous tumors in pre-clinical models. These effects of CR are largely attributed to canonical inhibition of pro-growth pathways. However, our recent data suggest that CR impairs primary tumor growth and cancer progression in the murine 4T1 model of triple negative breast cancer (TNBC), at least in part, through reduced frequency of the myeloid-derived suppressor cells (MDSC). In the present study, we sought to determine whether injection of excess MDSCs could block regression in 4T1 tumor growth and metastatic spread in BALB/cJ female mice undergoing daily CR. Our findings show that MDSC injection impeded CR-mediated protection against tumor growth without increasing lung metastatic burden. Overall, these results reveal that CR can slow cancer progression by affecting immune suppressive cells.Impact statement: Inoculation of MDSCs from donor mice effectively impedes the ability of calorie restriction to protect against primary tumor growth without impacting lung metastatic burden in recipient animals.

Household income, fetal size and birth weight: an analysis of eight populations.

BACKGROUND: The age at onset of the association between poverty and poor health is not understood. Our hypothesis was that individuals from highest household income (HI), compared to those with lowest HI, will have increased fetal size in the second and third trimester and birth. METHODS: Second and third trimester fetal ultrasound measurements and birth measurements were obtained from eight cohorts. Results were analysed in cross-sectional two-stage individual patient data (IPD) analyses and also a longitudinal one-stage IPD analysis. RESULTS: The eight cohorts included 21 714 individuals. In the two-stage (cross-sectional) IPD analysis, individuals from the highest HI category compared with those from the lowest HI category had larger head size at birth (mean difference 0.22 z score (0.07, 0.36)), in the third trimester (0.25 (0.16, 0.33)) and second trimester (0.11 (0.02, 0.19)). Weight was higher at birth in the highest HI category. In the one-stage (longitudinal) IPD analysis which included data from six cohorts (n=11 062), head size was larger (mean difference 0.13 (0.03, 0.23)) for individuals in the highest HI compared with lowest category, and this difference became greater between the second trimester and birth. Similarly, in the one-stage IPD, weight was heavier in second highest HI category compared with the lowest (mean difference 0.10 (0 .00, 0.20)) and the difference widened as pregnancy progressed. Length was not linked to HI category in the longitudinal model. CONCLUSIONS: The association between HI, an index of poverty, and fetal size is already present in the second trimester.

Patient experience of the acute post-surgical period following total laryngectomy during the COVID-19 era.

BACKGROUND: Total laryngectomy (TL) results in permanent functional changes requiring rapid development of complex new skills. A significant portion of this learning happens in the acute post-surgical stage. There is increasing interest in enhanced recovery after surgery (ERAS) protocols in TL; however, implementation has been difficult. COVID-19 has placed significant pressures on acute services, requiring rapid service changes for TL patients. AIMS: To understand the acute patient experience of having a TL both before and during COVID-19. METHODS & PROCEDURES: Semi-structured interviews using a pre-designed topic guide were conducted with 10 people who had undergone a TL within the last 2 years. Participants were recruited by their speech and language therapists using purposive sampling. Braun and Clarke's iterative approach to data collection and thematic analysis was used to generate key themes from the data. OUTCOMES & RESULTS: Thematic analysis identified four main themes: (1) pre-operative information-giving: 'it was just words'; (2) decision-making influences: 'I just wanted them to get it all out and get it over with'; (3) coping with adjustment to the new normal: 'this is part of me now'; and (4) the importance of relationship-building: 'when you've had something like this, you need some care and understanding'. CONCLUSIONS & IMPLICATIONS: The need for an individualized approach to TL intervention which incorporates medical and psycho-social approaches from pre-treatment to acute discharge is vital. ERAS models should be reviewed to shift beyond the medical model alone. Rapid service changes due to COVID-19 did not contribute any major changes to the acute patient-reported experience. WHAT THIS PAPER ADDS: What is already known on the subject We know that ERAS protocols have the potential to improve patient outcomes following TL. However, the research does not consider anything other than the early oral feeding debate and it has therefore been difficult to implement ERAS protocols in current service models. COVID19 required head and neck cancer services to make quick changes to surgical pathways, with the potential that some ERAS protocols had been adopted inadvertently. In order to understand the impact of this, we need to understand the patient experience following TL both before and during COVID19. What this paper adds to existing knowledge This paper used qualitative interviews to understand the acute patient experience following TL both during and before COVID19. Findings from these interviews highlighted that people were on the most part, well prepared for the functional changes they would experience after surgery. However, people felt there were gaps in service delivery at the pre-treatment and early discharge home period. Overall, the gaps identified were from a more psycho-social need suggesting that future ERAS models of care should consider both medical and psycho-social principles to enhance patient experience and outcome. What are the potential or actual clinical implications of this work? Pre-treatment services provided to people who have a TL could be reviewed to help maximize long-term adjustment to life. Areas which could be reviewed include the method and mode of information delivery. Further work needs to be done in partnership with community services to improve the immediate discharge home experience.

Distress as a mediator for pain and activities of daily living in older adults with fibromyalgia.

Introduction: Pain, distress, and activities of daily living impact the lives of those with chronic pain. This study investigated distress (depressive symptoms, anxiety) on the relationship between pain (intensity and pain interference) and activities of daily living in individuals with fibromyalgia while controlling for age. Methods: The current cross-sectional investigation focused on data from 123 men and women with fibromyalgia. Pain intensity, pain interference and anxiety were measured on 0-10 Likert type scales from the National Fibromyalgia Assessment Questionnaire. Depressive symptoms were assessed using the Beck Depression Inventory II. Activities of daily living (basic, instrumental) were measured with the Physical Activity Inventory Scale. Results: It was hypothesized that the relationships between pain intensity and pain interference and activities of daily living in individuals with fibromyalgia would be mediated by the construct of distress while controlling for age. Mediation significantly occurred in both models as predicted. However, those who were older reported lower levels of pain intensity and distress than their younger counterparts, which may be related to time since diagnosis or other factors. Discussion: Results of this study suggest that individuals with chronic pain conditions would benefit from treatment options which address distress, specifically depressive symptoms and anxiety.

Associations between markers of social functioning and depression and quality of life in survivors of head and neck cancer: Findings from the Head and Neck Cancer 5000 study.

OBJECTIVE: To investigate associations between markers of social functioning (trouble with social eating and social contact), depression and health-related quality of life (QOL) among head and neck cancer survivors. METHODS: This cross-sectional analysis included individuals with oral cavity, oropharynx, larynx, salivary gland and thyroid cancers from Head and Neck 5000 alive at 12 months. Trouble with social eating and social contact were measured using items from EORTC QLQ-H&N35 and QOL using EORTC QLQ-C30; responses were converted into a score of 0-100, with a higher score equalling more trouble or better QOL. A HADS subscale score of ≥8 was considered significant depression. Associations between tertiles of trouble with social eating and social contact and depression and QoL were assessed using multivariable logistic and linear regression (with robust errors), respectively. RESULTS: Of 2561 survivors, 23% reported significant depression. The median QOL score was 75.0 (interquartile range 58.3-83.3). For trouble with social eating, after confounder adjustment, those in the intermediate and highest tertiles had higher odds of depression (intermediate: OR = 4.5, 95% CI 3.19-6.45; high: OR = 21.8, 15.17-31.18) and lower QOL (intermediate:ß = -8.7, 95% CI -10.35 to -7.14; high: ß = -24.8, -26.91 to -22.77). Results were similar for trouble with social contact. CONCLUSION: We found strong clinically important associations between markers of social functioning and depression and QOL. More effective interventions addressing social eating and contact are required. These may help survivors regain their independence, reduce levels of isolation and loneliness, and depression, and improve QOL outcomes generally.

Pain intensity and physical performance among individuals with fibromyalgia in mid-to-late life: The influence of depressive symptoms.

This study investigated the mediating role of depressive symptoms among 147 middle-aged and older adults with FM in the relationship between pain intensity and 4 objective measures of physical performance: Fullerton Advanced Balance scale (FAB), 6-Minute Walk Test (6MWT), 30-Second Chair Stand (30SCS), and 8-Foot Up and Go Test (8FUPGT). Asymptotic mediation analyses revealed that depressive symptoms fully mediated the relationship between pain intensity and FAB (95% CI [-0.40, -0.10]) and 8FUPGT (CI [0.02, 0.11]) and partially mediated the relationship to 6MWT (CI [-9.15, -2.20]) and 30SCS (CI [-0.29, -0.06]). Findings support the evaluation of co-morbid depression in FM.

Diet composition influences the metabolic benefits of short cycles of very low caloric intake.

Diet composition, calories, and fasting times contribute to the maintenance of health. However, the impact of very low-calorie intake (VLCI) achieved with either standard laboratory chow (SD) or a plant-based fasting mimicking diet (FMD) is not fully understood. Here, using middle-aged male mice we show that 5 months of short 4:10 VLCI cycles lead to decreases in both fat and lean mass, accompanied by improved physical performance and glucoregulation, and greater metabolic flexibility independent of diet composition. A long-lasting metabolomic reprograming in serum and liver is observed in mice on VLCI cycles with SD, but not FMD. Further, when challenged with an obesogenic diet, cycles of VLCI do not prevent diet-induced obesity nor do they elicit a long-lasting metabolic memory, despite achieving modest metabolic flexibility. Our results highlight the importance of diet composition in mediating the metabolic benefits of short cycles of VLCI.

Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition.

Cancer incidence increases with age and is a leading cause of death. Caloric restriction (CR) confers benefits on health and survival and delays cancer. However, due to CR's stringency, dietary alternatives offering the same cancer protection have become increasingly attractive. Short cycles of a plant-based diet designed to mimic fasting (FMD) are protective against tumorigenesis without the chronic restriction of calories. Yet, it is unclear whether the fasting time, level of dietary restriction, or nutrient composition is the primary driver behind cancer protection. Using a breast cancer model in mice, we compare the potency of daily CR to that of periodic caloric cycling on FMD or an isocaloric standard laboratory chow against primary tumor growth and metastatic burden. Here, we report that daily CR provides greater protection against tumor growth and metastasis to the lung, which may be in part due to the unique immune signature observed with daily CR.

Racism as a Preventable Harm.

Since 1619, racism has been a preexisting condition placing Black people at higher risk of death in America. Generational harm done to the Black community has eroded trust in the health care system. Racial biases, largely unconscious, held by health care professionals can directly result in morbidity and mortality. These biases are amenable to intervention, and thus, these events are preventable. Health care institutions must choose to view racism as a preventable harm and address it with the same fervency devoted to other preventable harms that have been prioritized for decades. Prior attempts to address racism in health care institutions have not resulted in sustained cultural change because unconscious racial biases have not been addressed. Antiracism bundle elements are proposed as evidence-based, conscious tools for subverting unconscious racial biases held by health care providers, thus empowering leaders and staff to prevent further trauma to Black patients and families, with the goal of decreasing racialized health disparities.