[Interpretation of specification for service of cancer screening for workers].

As the backbone force of China's social and economic construction, the health status of workers is closely related to the nation's productivity and social development. Currently, cancers have become one of the major diseases threatening the health of workers. However, there are still many shortcomings in the cancer screening services for the workers. To standardize cancer screening services for workers, ensure the quality of screening services, and improve the overall screening effectiveness, 19 institutions, including Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, have jointly formulated the Group Standard "Specification for service of cancer screening for workers (T/CHAA 023-2023)". This standard follows the principles of "legality, scientific rigor, advancement, and feasibility" and combines the frontier scientific advances in cancer screening. It clarifies the relevant requirements for service principles, service design, service delivery, service management, service evaluation, and improving worker cancer screening. Implementing this group standard will help connect the common screening needs of workers, employers, and cancer screening service providers, standardize the screening process, improve screening quality, and ultimately increase the early diagnosis rate and survival rate of cancer patients. Consequently, this group standard will help safeguard workers' health rights and interests, ensure the labor force resources, promote the comprehensive coordinated and sustainable development of society, and contribute to realizing the "Healthy China 2030" strategic policy.

Red Meat Intake and the Risk of Cardiovascular Diseases: A Prospective Cohort Study in the Million Veteran Program.

BACKGROUND: Red meat consumption was associated with an increased risk of cardiovascular disease (CVD) in prospective cohort studies and a profile of biomarkers favoring high CVD risk in short-term controlled trials. However, several recent systematic reviews and meta-analyses concluded with no or weak evidence for limiting red meat intake. OBJECTIVES: To prospectively examine the associations between red meat intake and incident CVD in an ongoing cohort study with diverse socioeconomic and racial or ethnic backgrounds. METHODS: Our study included 148,506 participants [17,804 female (12.0%)] who were free of cancer, diabetes, and CVD at baseline from the Million Veteran Program. A food frequency questionnaire measured red meat intakes at baseline. Nonfatal myocardial infarction and acute ischemic stroke were identified through a high-throughput phenotyping algorithm, and fatal CVD events were identified by searching the National Death Index. RESULTS: Comparing the extreme categories of intake, the multivariate-adjusted relative risks of CVD was 1.18 (95% CI: 1.01, 1.38; P-trend < 0.0001) for total red meat, 1.14 (95% CI: 0.96, 1.36; P-trend = 0.01) for unprocessed red meat, and 1.29 (95% CI: 1.04, 1.60; P-trend = 0.003) for processed red meat. We observed a more pronounced positive association between red meat intake and CVD in African American participants than in White participants (P-interaction = 0.01). Replacing 0.5 servings/d of red meat with 0.5 servings/d of nuts, whole grains, and skimmed milk was associated with 14% (RR: 0.86; 95% CI: 0.83, 0.90), 7% (RR: 0.93; 95% CI: 0.89, 0.96), and 4% (RR: 0.96; 95% CI: 0.94, 0.99) lower risks of CVD, respectively. CONCLUSIONS: Red meat consumption is associated with an increased risk of CVD. Our findings support lowering red meat intake and replacing red meat with plant-based protein sources or low-fat dairy foods as a key dietary recommendation for the prevention of CVD.

Transcriptional Heterogeneity Overcomes Super-Enhancer Disrupting Drug Combinations in Multiple Myeloma.

Multiple myeloma (MM) is a malignancy that is often driven by MYC and that is sustained by IRF4, which are upregulated by super-enhancers. IKZF1 and IKZF3 bind to super-enhancers and can be degraded using immunomodulatory imide drugs (IMiD). Successful IMiD responses downregulate MYC and IRF4; however, this fails in IMiD-resistant cells. MYC and IRF4 downregulation can also be achieved in IMiD-resistant tumors using inhibitors of BET and EP300 transcriptional coactivator proteins; however, in vivo these drugs have a narrow therapeutic window. By combining IMiDs with EP300 inhibition, we demonstrate greater downregulation of MYC and IRF4, synergistic killing of myeloma in vitro and in vivo, and an increased therapeutic window. Interestingly, this potent combination failed where MYC and IRF4 expression was maintained by high levels of the AP-1 factor BATF. Our results identify an effective drug combination and a previously unrecognized mechanism of IMiD resistance. SIGNIFICANCE: These results highlight the dependence of MM on IKZF1-bound super-enhancers, which can be effectively targeted by a potent therapeutic combination pairing IMiD-mediated degradation of IKZF1 and IKZF3 with EP300 inhibition. They also identify AP-1 factors as an unrecognized mechanism of IMiD resistance in MM. See related article by Neri, Barwick, et al., p. 56. See related commentary by Yun and Cleveland, p. 5. This article is featured in Selected Articles from This Issue, p. 4.

Impact of 8 lifestyle factors on mortality and life expectancy among United States veterans: The Million Veteran Program.

BACKGROUND: Lifestyle medicine has been proposed as a way to address the root causes of chronic disease and their associated health care costs. OBJECTIVE: This study aimed to estimate mortality risk and longevity associated with individual lifestyle factors and comprehensive lifestyle therapy. METHODS: Age- and sex-specific mortality rates were calculated on the basis of 719,147 veterans aged 40-99 y enrolled in the Veteran Affairs Million Veteran Program (2011-2019). Hazard ratios and estimated increase in life expectancy were examined among a subgroup of 276,132 veterans with complete data on 8 lifestyle factors at baseline. The 8 lifestyle factors included never smoking, physical activity, no excessive alcohol consumption, restorative sleep, nutrition, stress management, social connections, and no opioid use disorder. RESULTS: On the basis of 1.12 million person-years of follow-up, 34,247 deaths were recorded. Among veterans who adopted 1, 2, 3, 4, 5, 6, 7, and 8 lifestyle factors, the adjusted hazard ratios for mortality were 0.74 (0.60-0.90), 0.60 (95% CI: 0.49, 0.73), 0.50 (95% CI: 0.41, 0.61), 0.43 (95% CI: 0.35, 0.52), 0.35 (95% CI: 0.29, 0.43), 0.27 (95% CI: 0.22, 0.33), 0.21 (95% CI: 0.17, 0.26), and 0.13 (95% CI: 0.10, 0.16), respectively, as compared with veterans with no adopted lifestyle factors. The estimated life expectancy at age 40 y was 23.0, 26.5, 28.8, 30.8, 32.7, 35.1, 38.3, 41.3, and 47.0 y among males and 27.0, 28.8, 33.1, 38.0, 39.2, 41.4, 43.8, 46.3, and 47.5 y for females who adopted 0, 1, 2, 3, 4, 5, 6, 7, and 8 lifestyle factors, respectively. The difference in life expectancy at age 40 y was 24.0 y for male veterans and 20.5 y for female veterans when comparing adoption of 8-9 lifestyle factors. CONCLUSIONS: A combination of 8 lifestyle factors is associated with a significantly lower risk of premature mortality and an estimated prolonged life expectancy.

Validity and Reproducibility of a Semiquantitative Food Frequency Questionnaire for Measuring Intakes of Foods and Food Groups.

We evaluated the validity and reproducibility of a semiquantitative food frequency questionnaire (FFQ) for measuring intakes of 149 foods and 25 food groups among 736 participants of the Women's Lifestyle Validation Study (WLVS, 2010-2012) and 649 participants of the Men's Lifestyle Validation Study (MLVS, 2011-2013). Validity of the FFQ compared with two 7-day dietary records measured 6 months apart and the reproducibility between 2 FFQs administered 1 year apart (FFQ1 and FFQ2) were assessed using Spearman correlations and intraclass correlation coefficients. The average 1-year reproducibility of FFQ-measured foods was 0.64 in both the WLVS and MLVS. Reproducibility of the food groups (mean = 0.71 among women and 0.72 among men) was generally higher than that for individual foods. Among women, the average validity correlation for individual foods was 0.59 when comparing FFQ2 with the 7-day dietary records. Among men, the corresponding average validity correlation was 0.61. Compared with individual foods, food groups had slightly higher validity correlations in both women (range, 0.45-0.92; mean = 0.61) and men (range, 0.46-0.88; mean = 0.65). This study reaffirms that the FFQ performs well in measuring most foods and food groups and provides data to adjust for measurement errors in epidemiologic studies of foods and food groups.

Successful weight regain attenuation by autologous fecal microbiota transplantation is associated with non-core gut microbiota changes during weight loss; randomized controlled trial.

We previously reported that autologous-fecal-microbiota-transplantation (aFMT), following 6 m of lifestyle intervention, attenuated subsequent weight regain and insulin rebound for participants consuming a high-polyphenol green-Mediterranean diet. Here, we explored whether specific changes in the core (abundant) vs. non-core (low-abundance) gut microbiome taxa fractions during the weight-loss phase (0-6 m) were differentially associated with weight maintenance following aFMT. Eighty-two abdominally obese/dyslipidemic participants (age = 52 years; 6 m weightloss = -8.3 kg) who provided fecal samples (0 m, 6 m) were included. Frozen 6 m's fecal samples were processed into 1 g, opaque and odorless aFMT capsules. Participants were randomly assigned to receive 100 capsules containing their own fecal microbiota or placebo over 8 m-14 m in ten administrations (adherence rate > 90%). Gut microbiome composition was evaluated using shotgun metagenomic sequencing. Non-core taxa were defined as ≤ 66% prevalence across participants. Overall, 450 species were analyzed. At baseline, 13.3% were classified as core, and Firmicutes presented the highest core proportion by phylum. During 6 m weight-loss phase, abundance of non-core species changed more than core species (P < .0001). Subject-specific changes in core and non-core taxa fractions were strongly correlated (Jaccard Index; r = 0.54; P < .001). Following aFMT treatment, only participants with a low 6 m change in core taxa, and a high change in non-core taxa, avoided 8-14 m weight regain (aFMT = -0.58 ± 2.4 kg, corresponding placebo group = 3.18 ± 3.5 kg; P = .02). In a linear regression model, low core/high non-core 6 m change was the only combination that was significantly associated with attenuated 8-14 m weight regain (P = .038; P = .002 for taxa patterns/treatment intervention interaction). High change in non-core, low-abundance taxa during weight-loss might mediate aFMT treatment success for weight loss maintenance.ClinicalTrials.gov: NCT03020186.

Association Between Bowel Movement Pattern and Cognitive Function: Prospective Cohort Study and a Metagenomic Analysis of the Gut Microbiome.

BACKGROUND AND OBJECTIVES: Little is known regarding the association between intestinal motility patterns and cognitive function in individuals who are baseline cognitively healthy. The gut microbiome may contribute to the association. We examined the association between bowel movement (BM) pattern and cognitive function and explored the role of the gut microbiome in explaining this association. METHODS: In this prospective study, we leveraged 3 cohort studies, Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS). Participants reported BM frequency and subjective cognitive function. In a subset of NHSII participants, we assessed cognitive function using an objective neuropsychological battery. We profiled the gut microbiome in a subset of participants using whole-genome shotgun metagenomics. General linear models, Poisson regression, and logistic regression were used to quantify the association of BM frequency with different cognitive measurements. RESULTS: We followed 112,753 men and women (women: 87.6%) with a mean age of 67.2 years at baseline (NHS: 76 years, NHSII: 59 years, HPFS: 75 years) for a median follow-up of 4 years (NHSII and HPFS: 4 years, NHS: 2 years). Compared with those with BM once daily, participants with BM frequency every 3+ days had significantly worse objective cognitive function, equivalent to 3.0 (95% confidence interval [CI],1.2-4.7) years of chronological cognitive aging. We observed similar J-shape dose-response relationships of BM frequency with the odds of subjective cognitive decline and the likelihood of having more subsequent subjective cognitive complaints (both p nonlinearity < 0.001). BM frequencies of every 3+ days and ≥twice/day, compared with once daily, were associated with the odds ratios of subjective cognitive decline of 1.73 (95% CI 1.60-1.86) and 1.37 (95% CI 1.33-1.44), respectively. BM frequency and subjective cognitive decline were significantly associated with the overall gut microbiome configuration (both p < 0.005) and specific microbial species in the 515 participants with microbiome data. Butyrate-producing microbial species were depleted in those with less frequent BM and worse cognition, whereas a higher abundance of proinflammatory species was associated with BM frequency of ≥twice/day and worse cognition. DISCUSSION: Lower BM frequency was associated with worse cognitive function. The gut microbial dysbiosis may be a mechanistic link underlying the association.

Consumption of Ultraprocessed Food and Risk of Depression.

This cohort study examines the consumption of ultraprocessed food and risk of depression among 31 172 US females aged 42 to 62 years.

Associations of dietary sugar types with coronary heart disease risk: a prospective cohort study.

BACKGROUND: Higher intake of total sugar has been linked with coronary heart disease (CHD) risk, but the role of individual sugars, particularly fructose, is uncertain. OBJECTIVES: This study aimed to investigate the associations of individual dietary sugars with CHD risk. METHODS: In prospective cohort studies, we followed 76,815 women (Nurses' Health Study, 1980-2020) and 38,878 men (Health Professionals Follow-up Study, 1986-2016). Sugar and carbohydrate intake, including total fructose equivalents ([TFE] from fructose monosaccharides and sucrose), total glucose equivalents ([TGE] from glucose monosaccharides, disaccharides, and starch), and other sugar types, was measured every 2 to 4 y by semiquantitative food frequency questionnaires. RESULTS: We documented 9,723 incident CHD cases over 40 years. In isocaloric substitution models with total fat as a comparison nutrient, comparing extreme quintiles of intake, hazard ratios (HRs), 95% confidence interval [CI]) for CHD risk were 1.31 (1.20 to 1.42; Ptrend < 0.001) for TGE and 1.03 (0.94 to 1.11; Ptrend = 0.25) for TFE. TFE from fruits and vegetables was not associated with CHD risk (Ptrend = 0.70), but TFE from added sugar and juice was associated with CHD risk (HR: 1.12, 95% CI: 1.04 to 1.20; Ptrend < 0.01). Intakes of total sugars and added sugar were positively associated with CHD risk (HRs: 1.16, 95% CI: 1.07 to 1.26, Ptrend < 0.001; 1.08, 95% CI: 0.99 to 1.16, Ptrend = 0.04). CONCLUSIONS: Intakes of TGE, total sugar, added sugar, and fructose from added sugar and juice were associated with higher CHD risk, but TFE and fructose from fruits and vegetables were not.

The gut microbiome modifies the associations of short- and long-term physical activity with body weight changes.

BACKGROUND: The gut microbiome regulates host energy balance and adiposity-related metabolic consequences, but it remains unknown how the gut microbiome modulates body weight response to physical activity (PA). METHODS: Nested in the Health Professionals Follow-up Study, a subcohort of 307 healthy men (mean[SD] age, 70[4] years) provided stool and blood samples in 2012-2013. Data from cohort long-term follow-ups and from the accelerometer, doubly labeled water, and plasma biomarker measurements during the time of stool collection were used to assess long-term and short-term associations of PA with adiposity. The gut microbiome was profiled by shotgun metagenomics and metatranscriptomics. A subcohort of 209 healthy women from the Nurses' Health Study II was used for validation. RESULTS: The microbial species Alistipes putredinis was found to modify the association between PA and body weight. Specifically, in individuals with higher abundance of A. putredinis, each 15-MET-hour/week increment in long-term PA was associated with 2.26 kg (95% CI, 1.53-2.98 kg) less weight gain from age 21 to the time of stool collection, whereas those with lower abundance of A. putredinis only had 1.01 kg (95% CI, 0.41-1.61 kg) less weight gain (pinteraction = 0.019). Consistent modification associated with A. putredinis was observed for short-term PA in relation to BMI, fat mass%, plasma HbA1c, and 6-month weight change. This modification effect might be partly attributable to four metabolic pathways encoded by A. putredinis, including folate transformation, fatty acid ß-oxidation, gluconeogenesis, and stearate biosynthesis. CONCLUSIONS: A greater abundance of A. putredinis may strengthen the beneficial association of PA with body weight change, suggesting the potential of gut microbial intervention to improve the efficacy of PA in body weight management. Video Abstract.

[Impact of sinonasal anatomic changes after endoscopic anterior skull base surgery on nasal airflow and air conditioning: a computational fluid dynamics study].

Objective: To analyze the impact of the sinonasal anatomic changes after endonasal endoscopic anterior skull base surgery on the nasal airflow and heating and humidification by computational fluid dynamics (CFD), and to explore the correlation between the postoperative CFD parameters and the subjective symptoms of the patients. Methods: The clinical data in the Rhinology Department of the First Affiliated Hospital of Zhengzhou University from 2016 to 2021 were retrospectively analyzed. The patients received the endoscopic resection of the anterior skull base tumor were selected as the case group, and the adults whose CT scans had no sinonasal abnormalities were chosen as the control group. The CFD simulation was performed on the sinonasal models after reconstructed from the patients' sinus CT images during the post-surgical follow-up. All the patients were asked to complete the Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) to assess the subjective symptoms. The comparison between two independent groups and the correlation analysis were carried out by using the Mann-Whitney U test and the Spearman correlation test in the SPSS 26.0 software. Results: Nineteen patients (including 8 males and 11 females, from 22 to 67 years old) in the case group and 2 patients (a male of 38 years old and a female of 45 years old) in the control group were enrolled in this study. After the anterior skull base surgery, the high-speed airflow moved to the upper part of the nasal cavity, and the lowest temperature shifted upwards on the choana. Comparing with the control group, the ratio of nasal mucosal surface area to nasal ventilation volume in the case group decreased [0.41 (0.40, 0.41) mm-1 vs 0.32 (0.30, 0.38) mm-1; Z=-2.04, P=0.041], the air flow in the upper and middle part of the nasal cavity increased [61.14 (59.78, 62.51)% vs 78.07 (76.22, 94.43)%; Z=-2.28, P=0.023], the nasal resistance decreased [0.024 (0.022, 0.026) Pa·s/ml vs 0.016 (0.009, 0.018) Pa·s/ml; Z=-2.29, P=0.022], the lowest temperature in the middle of the nasal cavity decreased [28.29 (27.23, 29.35)℃ vs 25.06 (24.07, 25.50)℃; Z=-2.28, P=0.023], the nasal heating efficiency decreased [98.74 (97.95, 99.52)% vs 82.16 (80.24, 86.91)%; Z=-2.28, P=0.023], the lowest relative humidity decreased [(79.62 (76.55, 82.69)% vs 73.28 (71.27, 75.05)%; Z=-2.28, P=0.023], and the nasal humidification efficiency decreased [99.50 (97.69, 101.30)% vs 86.09 (79.33, 87.16)%; Z=-2.28, P=0.023]. The ENS6Q total scores of all patients in the case group were less than 11 points. There was a moderate negative correlation between the proportion of the inferior airflow in the post-surgical nasal cavity negatively and the ENS6Q total scores (rs=-0.50, P=0.029). Conclusions: The sinonasal anatomic changes after the endoscopic anterior skull base surgery alter the nasal airflow patterns, reducing the efficiency of nasal heating and humidification. However, the post-surgical occurrence tendency of the empty nose syndrome is weak.

Healthy Eating Patterns and Risk of Total and Cause-Specific Mortality.

Importance: The current Dietary Guidelines for Americans recommend multiple healthy eating patterns. However, few studies have examined the associations of adherence to different dietary patterns with long-term risk of total and cause-specific mortality. Objective: To examine the associations of dietary scores for 4 healthy eating patterns with risk of total and cause-specific mortality. Design, Setting, and Participants: This prospective cohort study included initially healthy women from the Nurses' Health Study (NHS; 1984-2020) and men from the Health Professionals Follow-up Study (HPFS; 1986-2020). Exposures: Healthy Eating Index 2015 (HEI-2015), Alternate Mediterranean Diet (AMED) score, Healthful Plant-based Diet Index (HPDI), and Alternate Healthy Eating Index (AHEI). Main Outcomes and Measures: The main outcomes were total and cause-specific mortality overall and stratified by race and ethnicity and other potential risk factors. Results: The final study sample included 75 230 women from the NHS (mean [SD] baseline age, 50.2 [7.2] years) and 44 085 men from the HPFS (mean [SD] baseline age, 53.3 [9.6] years). During a total of 3 559 056 person-years of follow-up, 31 263 women and 22 900 men died. When comparing the highest with the lowest quintiles, the pooled multivariable-adjusted HRs of total mortality were 0.81 (95% CI, 0.79-0.84) for HEI-2015, 0.82 (95% CI, 0.79-0.84) for AMED score, 0.86 (95% CI, 0.83-0.89) for HPDI, and 0.80 (95% CI, 0.77-0.82) for AHEI (P < .001 for trend for all). All dietary scores were significantly inversely associated with death from cardiovascular disease, cancer, and respiratory disease. The AMED score and AHEI were inversely associated with mortality from neurodegenerative disease. The inverse associations between these scores and risk of mortality were consistent in different racial and ethnic groups, including Hispanic, non-Hispanic Black, and non-Hispanic White individuals. Conclusions and Relevance: In this cohort study of 2 large prospective cohorts with up to 36 years of follow-up, greater adherence to various healthy eating patterns was consistently associated with lower risk of total and cause-specific mortality. These findings support the recommendations of Dietary Guidelines for Americans that multiple healthy eating patterns can be adapted to individual food traditions and preferences.

Plant-based diets and the incidence of cardiovascular disease: the Million Veteran Program.

Background: A healthful plant-based diet was associated with lower risks of coronary heart disease and type 2 diabetes, and a favourable profile of adiposity-associated biomarkers, while an unhealthful plant-based diet was associated with elevated risk of cardiometabolic disease in health professional populations. However, little is known about the associations between plant-based dietary patterns and risk of cardiovascular disease (CVD) in US veterans. Methods: The study population consisted of 148 506 participants who were free of diabetes, CVD and cancer at baseline in the Veterans Affairs (VA) Million Veteran Program. Diet was assessed using a Food Frequency Questionnaire at baseline. We calculated an overall Plant-Based Diet Index (PDI), a healthful PDI (hPDI) and an unhealthful PDI (uPDI). The CVD endpoints included non-fatal myocardial infarction (MI) and acute ischaemic stroke (AIS) identified through high-throughput phenotyping algorithms approach and fatal CVD events identified by searching the National Death Index. Results: With up to 8 years of follow-up, we documented 5025 CVD cases. After adjustment for confounding factors, a higher PDI was significantly associated with a lower risk of CVD (HR comparing extreme quintiles=0.75, 95% CI 0.68 to 0.82, P trend<0.0001). We observed an inverse association between hPDI and the risk of CVD (HR comparing extreme quintiles=0.71, 95% CI 0.64 to 0.78, P trend<0.001), whereas uPDI was positively associated with the risk of CVD (HR comparing extreme quintiles=1.12, 95% CI 1.02 to 1.24, P trend<0.001). We found similar associations of hPDI with subtypes of CVD; a 10-unit increment in hPDI was associated with HRs (95% CI) of 0.81 (0.75 to 0.87) for fatal CVD, 0.86 (0.79 to 0.94) for non-fatal MI and 0.86 (0.78 to 0.95) for non-fatal AIS. Conclusions: Plant-based dietary pattern enriched with healthier plant foods was associated with a substantially lower CVD risk in US veterans.

Health and environmental impacts of plant-rich dietary patterns: a US prospective cohort study.

BACKGROUND: Diets that are rich in animal-based foods threaten planetary and human health, but plant-rich diets have varied health and environmental effects. We aimed to characterise a healthy dietary index and three plant-based indices by their environmental impacts and associations with risk of cardiovascular disease. METHODS: In this prospective cohort study, we used data from a food-frequency questionnaire in the US-based Nurses' Health Study II. Participants were categorised by quintiles of four dietary indices, including the alternative healthy eating index-2010 (AHEI), plant-based diet index (PDI), unhealthy PDI, and healthy PDI. We calculated environmental impacts (greenhouse gas emissions and irrigation water, nitrogenous fertiliser, and high-quality cropland needs), and relative risks (RRs) of cardiovascular disease from 1991-2017, comparing quintiles. FINDINGS: We included 90 884 participants in the health-impact analysis and 65 625 participants in the environmental-impact analysis. Comparing the top and bottom quintiles, higher AHEI scores were associated with a decreased cardiovascular disease risk (relative risk 0·77 [95% CI 0·66-0·89]); 30% lower greenhouse gas emissions (Q5 2·6 kg CO2 equivalent vs Q1 3·7 kg CO2 equivalent); and lower fertiliser, cropland, and water needs (all ptrends<0·0001). Similarly, the highest healthy PDI and PDI quintiles were associated with a decreased cardiovascular disease risk (healthy PDI 0·71 [0·60-0·83] and PDI 0·74 [0·63-0·85]) and lower environmental impacts (PDI water needs ptrend=0·0014; all other ptrends<0·0001). Conversely, the highest unhealthy PDI quintile had a higher cardiovascular disease risk compared with the lowest unhealthy PDI quintile (1·15 [1·00-1·33]; ptrend=0·023) and required more cropland (ptrend<0·0001) and fertiliser (ptrend=0·0008). INTERPRETATION: Dietary patterns that are associated with better health had lower greenhouse gas emissions and nitrogenous fertiliser, cropland, and irrigation water needs. Not all plant-based diets conferred the same health and environmental benefits. US dietary guidelines should include nuanced consideration of environmental sustainability. FUNDING: US National Institutes of Health.

Rare lysosomal disease registries: lessons learned over three decades of real-world evidence.

Lysosomal storage disorders (LSD) are rare diseases, caused by inherited deficiencies of lysosomal enzymes/transporters, that affect 1 in 7000 to 1 in 8000 newborns. Individuals with LSDs face long diagnostic journeys during which debilitating and life-threatening events can occur. Clinical trials and classical descriptions of LSDs typically focus on common manifestations, which are not representative of the vast phenotypic heterogeneity encountered in real-world experience. Additionally, recognizing that there was a limited understanding of the natural history, disease progression, and real-world clinical outcomes of rare LSDs, a collaborative partnership was pioneered 30 years ago to address these gaps. The Rare Disease Registries (RDR) (for Gaucher, Fabry, Mucopolysaccharidosis type I, and Pompe), represent the largest observational database for these LSDs. Over the past thirty years, data from the RDRs have helped to inform scientific understanding and the development of comprehensive monitoring and treatment guidelines by creating a framework for data collection and establishing a standard of care, with an overarching goal to improve the quality of life of affected patients. Here, we highlight the history, process, and impact of the RDRs, and discuss the lessons learned and future directions.

[Comparison of application effects of colonoscopy, fecal immunochemical test and a novel risk-adapted screening approach in colorectal cancer screening in Xuzhou population].

Objective: To compare the application effect of the colonoscopy, fecal immunochemical test (FIT) and novel risk-adapted screening approach in colorectal cancer screening in Xuzhou population. Methods: From May 2018 to April 2019, 4 280 subjects aged 50-74 were recruited from Gulou district, Yunlong district and Quanshan district of Xuzhou. They were randomly assigned to the colonoscopy group (n=863), FIT group (n=1 723) and novel risk-adapted screening approach group (n=1 694) according to the ratio of 1∶2∶2. For the novel risk-adapted screening approach group, after the risk assessment, high-risk subjects were invited to undergo colonoscopy and low-risk subjects were invited to undergo FIT examination. All FIT positive subjects were invited to undergo colonoscopy. Colonoscopy participation rate [(the number of colonoscopies completed/the number of colonoscopies invited to participate)×100%], detection rate of colorectal lesions [(the number of diagnosed patients/the number of colonoscopies completed)×100%], colonoscopy resource load (the number of colonoscopies completed/the number of diagnosed advanced tumors) and FIT resource load in each group were calculated and compared. Results: The age of all subjects was (61±6) years old, including 1 816 males (42.43%). There was no statistically significant difference in the socio-demographic characteristics of the subjects in different screening groups. The colonoscopy participation rate was 22.60% (195/863) in the colonoscopy group, 57.04% (77/135) in the FIT group, and 33.94% (149/439) in the novel risk-adapted screening approach group, respectively. The colonoscopy participation rate was higher in the FIT group than in the colonoscopy group and the novel risk-adapted screening approach group (P<0.001). The colonoscopy participation rate of novel risk-adapted screening group was significantly higher than the colonoscopy group (P<0.001). The detection rates of advanced tumors were 6.67% (13/195), 9.09% (7/77) and 8.72% (13/149), respectively, and the difference was not statistically significant (P>0.05). The colonoscopy resource load (95%CI) was 15 (13-17) in the colonoscopy group, 11 (9-14) in the FIT group and 11 (10-13) in the novel risk-adapted screening approach group, respectively. Among them, the colonoscopy resource load of high-risk individuals in the novel risk-adapted screening approach group was 12 (9-15). FIT resource loads (95%CI) were 207 (196-218) and 88 (83-94) in the FIT group and the novel risk-adapted screening approach group. Conclusion: The combined application of risk-adapted screening approach and FIT may have a good application effect in colorectal cancer screening.

Dietary quality and risk of heart failure in men.

BACKGROUND: Due to the increasing disease burden, strategies to predict and prevent heart failure (HF) are urgently needed. OBJECTIVE: We aimed to investigate whether the Alternative Healthy Eating Index (AHEI) and the clinically abbreviated Prime Diet Quality Score (PDQS) are associated with the risk of overall HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). METHODS: Our study included 44,525 men from the Health Professionals Follow-up Study (HPFS) who were free from cardiovascular disease and cancer at baseline. The AHEI and PDQS were computed based on dietary data repeatedly measured using semiquantitative FFQs. HF, HFpEF, and HFrEF were adjudicated based on review of medical records through 2008. Associations of diet quality with incident HF were estimated with multivariate-adjusted Cox proportional hazards models. RESULTS: During 929,911 person-years of follow-up, 803 HF cases were documented, including 184 with HFpEF and 181 with HFrEF among those with ejection fraction (EF) data. Adjusting for potential confounders, we did not observe a significant association between the AHEI and overall HF (HR per SD: 0.96; 95% CI: 0.89, 1.04; P-trend = 0.57) or between the PDQS and overall HF (HR per SD: 0.98; 95% CI: 0.91, 1.06; P-trend = 0.82). Both dietary indices were not significantly associated with HFpEF. However, a higher AHEI was associated with lower risk of HFrEF upon comparison of the extreme quintiles (HR per SD: 0.81; 95% CI: 0.69, 0.96; P-trend = 0.02). Every SD increment in the PDQS was associated with 20% lower risk of HFrEF (HR per SD: 0.80; 95% CI: 0.68, 0.95; P-quadratic = 0.03). CONCLUSIONS: A healthy overall diet was associated with lower risk of HFrEF, and associations were similar with the AHEI and PDQS. We did not observe a significant association between dietary indices and either overall HF or HFpEF.

[Clinical effects of en bloc resection and debridement combined with gluteus maximus muscle flap in the treatment of ischial tubercle pressure ulcer complicated with chronic osteomyelitis].

Objective: To investigate the clinical effects of en bloc resection and debridement combined with gluteus maximus muscle flap in the treatment of ischial tubercle pressure ulcer complicated with chronic osteomyelitis. Methods: A retrospective observational study was conducted. From May 2018 to February 2020, 8 patients with pressure ulcers on the ischial tuberosity combined with chronic osteomyelitis who met the inclusion criteria were admitted to Fuyang Minsheng Hospital, including 5 males and 3 females, aged 38-69 years, with unilateral lesions in 6 patients and bilateral lesions in 2 patients. According to the anatomical classification of Cierny-Mader osteomyelitis, there were 6 patients (7 sides) with focal type, and 2 patients (3 sides) with diffuse type. The wound areas were 3 cm×2 cm to 12 cm×9 cm on admission. The pressure ulcer and chronic osteomyelitis lesions were completely removed by en bloc resection and debridement. The chronic infectious lesions were transformed into sterile incisions like fresh wounds by one surgical procedure, and the gluteus maximus muscle flaps with areas of 10 cm×6 cm to 15 cm×9 cm were excised to transfer and fill the ineffective cavity. The wounds of 5 patients were sutured directly, and the wounds of 3 patients were closed by local flap transfer. The intraoperative blood loss volume and blood transfusion, and length of hospital stay of patients were recorded. The incision healing and flap survival of patients were observed after operation. The recurrence of pressure ulcer and osteomyelitis, the appearance of the affected area, and the secondary dysfunction and deformity of the muscle flap donor site of patients were observed during followed up. Results: The intraoperative blood loss volume of the 8 patients was 220 to 900 (430±150) mL; 5 patients received intraoperative blood transfusion, of which 2 patients received 3 U suspended red blood cells and 3 patients received 2 U suspended red blood cells. The length of hospital stay was 18 to 29 (23.5±2.0) d for the 8 patients. In this group of patients, the incisions of 7 patients healed, while in one case, the incision suture was torn off during turning over and healed after secondary suture. The flaps survived well in 3 patients who underwent local flap transfer. During the follow-up period of 6-20 months, no recurrence of pressure ulcer or osteomyelitis occurred in 8 patients, the affected part had skin with good texture, mild pigmentation, and no sinus tract formation, and no secondary dysfunction or deformity occurred in the donor site. Conclusions: The en bloc resection and debridement combined with gluteus maximus muscle flap has good clinical effects on ischial tubercle pressure ulcer complicated with chronic osteomyelitis. Neither pressure ulcer nor osteomyelitis recurs post operation. The skin texture and appearance of the affected area are good, and the donor site has no secondary dysfunction or deformity.

Dietary Sodium and Potassium Intake and Risk of Non-Fatal Cardiovascular Diseases: The Million Veteran Program.

Objective: To examine the association between intakes of sodium and potassium and the ratio of sodium to potassium and incident myocardial infarction and stroke. Design, Setting and Participants: Prospective cohort study of 180,156 Veterans aged 19 to 107 years with plausible dietary intake measured by food frequency questionnaire (FFQ) who were free of cardiovascular disease (CVD) and cancer at baseline in the VA Million Veteran Program (MVP). Main outcome measures: CVD defined as non-fatal myocardial infarction (MI) or acute ischemic stroke (AIS) ascertained using high-throughput phenotyping algorithms applied to electronic health records. Results: During up to 8 years of follow-up, we documented 4090 CVD cases (2499 MI and 1712 AIS). After adjustment for confounding factors, a higher sodium intake was associated with a higher risk of CVD, whereas potassium intake was inversely associated with the risk of CVD [hazard ratio (HR) comparing extreme quintiles, 95% confidence interval (CI): 1.09 (95% CI: 0.99−1.21, p trend = 0.01) for sodium and 0.87 (95% CI: 0.79−0.96, p trend = 0.005) for potassium]. In addition, the ratio of sodium to potassium (Na/K ratio) was positively associated with the risk of CVD (HR comparing extreme quintiles = 1.26, 95% CI: 1.14−1.39, p trend < 0.0001). The associations of Na/K ratio were consistent for two subtypes of CVD; one standard deviation increment in the ratio was associated with HRs (95% CI) of 1.12 (1.06−1.19) for MI and 1.11 (1.03−1.19) for AIS. In secondary analyses, the observed associations were consistent across race and status for diabetes, hypertension, and high cholesterol at baseline. Associations appeared to be more pronounced among participants with poor dietary quality. Conclusions: A high sodium intake and a low potassium intake were associated with a higher risk of CVD in this large population of US veterans.