DNA Methylation Age Mediates Effect of Metabolic Profile on Cardiovascular and General Aging.

BACKGROUND: Alterations in lipid metabolism and DNA methylation are 2 hallmarks of aging. Connecting metabolomic, epigenomic, and aging outcomes help unravel the complex mechanisms underlying aging. We aimed to assess whether DNA methylation clocks mediate the association of circulating metabolites with incident atherosclerotic cardiovascular disease (ASCVD) and frailty. METHODS: The China Kadoorie Biobank is a prospective cohort study with a baseline survey from 2004 to 2008 and a follow-up period until December 31, 2018. We used the Infinium Methylation EPIC BeadChip to measure the methylation levels of 988 participants' baseline blood leukocyte DNA. Metabolite profiles, including lipoprotein particles, lipid constituents, and various circulating metabolites, were measured using quantitative nuclear magnetic resonance. The pace of DNA methylation age acceleration (AA) was calculated using 5 widely used epigenetic clocks (the first generation: Horvath, Hannum, and Li; the second generation: Grim and Pheno). Incident ASCVD was ascertained through linkage with local death and disease registries and national health insurance databases, supplemented by active follow-up. The frailty index was constructed using medical conditions, symptoms, signs, and physical measurements collected at baseline. RESULTS: A total of 508 incident cases of ASCVD were documented during a median follow-up of 9.5 years. The first generation of epigenetic clocks was associated with the risk of ASCVD (P<0.05). For each SD increment in LiAA, HorvathAA, and HannumAA, the corresponding hazard ratios for ASCVD risk were 1.16 (1.05-1.28), 1.10 (1.00-1.22), and 1.17 (1.04-1.31), respectively. Only LiAA mediated the association of various metabolites (lipids, fatty acids, histidine, and inflammatory biomarkers) with ASCVD, with the mediating proportion reaching up to 15% for the diameter of low-density lipoprotein (P=1.2×10-2). Regarding general aging, a 1-SD increase in GrimAA was associated with an average increase of 0.10 in the frailty index (P=2.0×10-3), and a 33% and 63% increased risk of prefrailty and frailty at baseline (P=1.5×10-2 and 5.8×10-2), respectively; this association was not observed with other clocks. GrimAA mediated the effect of various lipids, fatty acids, glucose, lactate, and inflammatory biomarkers on the frailty index, with the mediating proportion reaching up to 22% for triglycerides in very small-sized very low-density lipoprotein (P=6.0×10-3). CONCLUSIONS: These findings suggest that epigenomic mechanisms may play a role in the associations between circulating metabolites and the aging process. Different mechanisms underlie the first and second generations of DNA methylation age in cardiovascular and general aging.

Long-Term Exposure to Fine Particulate Matter and Incidence of Esophageal Cancer: A Prospective Study of 0.5 Million Chinese Adults.

BACKGROUND & AIMS: Evidence is sparse and inconclusive on the association between long-term fine (≤2.5 µm) particulate matter (PM2.5) exposure and esophageal cancer. We aimed to assess the association of PM2.5 with esophageal cancer risk and compared the esophageal cancer risk attributable to PM2.5 exposure and other established risk factors. METHODS: This study included 510,125 participants without esophageal cancer at baseline from China Kadoorie Biobank. A high-resolution (1 × 1 km) satellite-based model was used to estimate PM2.5 exposure during the study period. Hazard ratios (HR) and 95% CIs of PM2.5 with esophageal cancer incidence were estimated using Cox proportional hazard model. Population attributable fractions for PM2.5 and other established risk factors were estimated. RESULTS: There was a linear concentration-response relationship between long-term PM2.5 exposure and esophageal cancer. For each 10-µg/m3 increase in PM2.5, the HR was 1.16 (95% CI, 1.04-1.30) for esophageal cancer incidence. Compared with the first quarter of PM2.5 exposure, participants in the highest quarter had a 1.32-fold higher risk for esophageal cancer, with an HR of 1.32 (95% CI, 1.01-1.72). The population attributable risk because of annual average PM2.5 concentration ≥35 µg/m3 was 23.3% (95% CI, 6.6%-40.0%), higher than the risks attributable to lifestyle risk factors. CONCLUSIONS: This large prospective cohort study of Chinese adults found that long-term exposure to PM2.5 was associated with an elevated risk of esophageal cancer. With stringent air pollution mitigation measures in China, a large reduction in the esophageal cancer disease burden can be expected.

Reproductive factors and risk of lung cancer among 300,000 Chinese female never-smokers: evidence from the China Kadoorie Biobank study.

BACKGROUND: Lung cancer is the leading cause of cancer mortality among Chinese females despite the low smoking prevalence among this population. This study assessed the roles of reproductive factors in lung cancer development among Chinese female never-smokers. METHODS: The prospective China Kadoorie Biobank (CKB) recruited over 0.5 million Chinese adults (0.3 million females) from 10 geographical areas in China in 2004-2008 when information on socio-demographic/lifestyle/environmental factors, physical measurements, medical history, and reproductive history collected through interviewer-administered questionnaires. Cox proportional hazard regression was used to estimate adjusted hazard ratios (HRs) of lung cancer by reproductive factors. Subgroup analyses by menopausal status, birth year, and geographical region were performed. RESULTS: During a median follow-up of 11 years, 2,284 incident lung cancers occurred among 282,558 female never-smokers. Ever oral contraceptive use was associated with a higher risk of lung cancer (HR = 1.16, 95% CI: 1.02-1.33) with a significant increasing trend associated with longer duration of use (p-trend = 0.03). Longer average breastfeeding duration per child was associated with a decreased risk (0.86, 0.78-0.95) for > 12 months compared with those who breastfed for 7-12 months. No statistically significant association was detected between other reproductive factors and lung cancer risk. CONCLUSION: Oral contraceptive use was associated with an increased risk of lung cancer in Chinese female never-smokers. Further studies are needed to assess lung cancer risk related to different types of oral contraceptives in similar populations.

Chronic Hepatitis B Virus Infection and Risk of Stroke Types: A Prospective Cohort Study of 500†000 Chinese Adults.

BACKGROUND: Stroke is a leading cause of mortality and permanent disability in China, with large and unexplained geographic variations in rates of different stroke types. Chronic hepatitis B virus infection is prevalent among Chinese adults and may play a role in stroke cause. METHODS: The prospective China Kadoorie Biobank included >500 000 adults aged 30 to 79 years who were recruited from 10 (5 urban and 5 rural) geographically diverse areas of China from 2004 to 2008, with determination of hepatitis B surface antigen (HBsAg) positivity at baseline. During 11 years of follow-up, a total of 59 117 incident stroke cases occurred, including 11 318 intracerebral hemorrhage (ICH), 49 971 ischemic stroke, 995 subarachnoid hemorrhage, and 3036 other/unspecified stroke. Cox regression models were used to estimate adjusted hazard ratios (HRs) for risk of stroke types associated with HBsAg positivity. In a subset of 17 833 participants, liver enzymes and lipids levels were measured and compared by HBsAg status. RESULTS: Overall, 3.0% of participants were positive for HBsAg. HBsAg positivity was associated with an increased risk of ICH (adjusted HR, 1.29 [95% CI, 1.16-1.44]), similarly for fatal (n=5982; adjusted HR, 1.36 [95% CI, 1.16-1.59]) and nonfatal (n=5336; adjusted HR, 1.23 [95% CI, 1.06-1.44]) ICH. There were no significant associations of HBsAg positivity with risks of ischemic stroke (adjusted HR, 0.97 [95% CI, 0.92-1.03]), subarachnoid hemorrhage (adjusted HR, 0.87 [95% CI, 0.57-1.33]), or other/unspecified stroke (adjusted HR, 1.12 [95% CI, 0.89-1.42]). Compared with HBsAg-negative counterparts, HBsAg-positive individuals had lower lipid and albumin levels and higher liver enzyme levels. After adjustment for liver enzymes and albumin, the association with ICH from HBsAg positivity attenuated to 1.15 (0.90-1.48), suggesting possible mediation by abnormal liver function. CONCLUSIONS: Among Chinese adults, chronic hepatitis B virus infection is associated with an increased risk of ICH but not other stroke types, which may be mediated through liver dysfunction and altered lipid metabolism.

Genetic influences on alcohol flushing in East Asian populations.

BACKGROUND: Although it is known that variation in the aldehyde dehydrogenase 2 (ALDH2) gene family influences the East Asian alcohol flushing response, knowledge about other genetic variants that affect flushing symptoms is limited. METHODS: We performed a genome-wide association study meta-analysis and heritability analysis of alcohol flushing in 15,105 males of East Asian ancestry (Koreans and Chinese) to identify genetic associations with alcohol flushing. We also evaluated whether self-reported flushing can be used as an instrumental variable for alcohol intake. RESULTS: We identified variants in the region of ALDH2 strongly associated with alcohol flushing, replicating previous studies conducted in East Asian populations. Additionally, we identified variants in the alcohol dehydrogenase 1B (ADH1B) gene region associated with alcohol flushing. Several novel variants were identified after adjustment for the lead variants (ALDH2-rs671 and ADH1B-rs1229984), which need to be confirmed in larger studies. The estimated SNP-heritability on the liability scale was 13% (S.E. = 4%) for flushing, but the heritability estimate decreased to 6% (S.E. = 4%) when the effects of the lead variants were controlled for. Genetic instrumentation of higher alcohol intake using these variants recapitulated known associations of alcohol intake with hypertension. Using self-reported alcohol flushing as an instrument gave a similar association pattern of higher alcohol intake and cardiovascular disease-related traits (e.g. stroke). CONCLUSION: This study confirms that ALDH2-rs671 and ADH1B-rs1229984 are associated with alcohol flushing in East Asian populations. Our findings also suggest that self-reported alcohol flushing can be used as an instrumental variable in future studies of alcohol consumption.

Duration-dependent impact of cardiometabolic diseases and multimorbidity on all-cause and cause-specific mortality: a prospective cohort study of 0.5 million participants.

BACKGROUND: The association of incident cardiometabolic multimorbidity (CMM) with mortality risk is rarely studied, and neither are the durations of cardiometabolic diseases (CMDs). Whether the association patterns of CMD durations with mortality change as individuals progress from one CMD to CMM is unclear. METHODS: Data from China Kadoorie Biobank of 512,720 participants aged 30-79 was used. CMM was defined as the simultaneous presence of two or more CMDs of interest, including diabetes, ischemic heart disease, and stroke. Cox regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the duration-dependent associations of CMDs and CMM with all-cause and cause-specific mortality. All information on exposures of interest was updated during follow-up. RESULTS: During a median follow-up of 12.1 years, 99,770 participants experienced at least one incident CMD, and 56,549 deaths were documented. Among 463,178 participants free of three CMDs at baseline, compared with no CMD during follow-up, the adjusted HRs (95% CIs) between CMM and all-cause mortality, mortality from circulatory system diseases, respiratory system diseases, cancer, and other causes were 2.93 (2.80-3.07), 5.05 (4.74-5.37), 2.72 (2.35-3.14), 1.30 (1.16-1.45), and 2.30 (2.02-2.61), respectively. All CMDs exhibited a high mortality risk in the first year of diagnosis. Subsequently, with prolonged disease duration, mortality risk increased for diabetes, decreased for IHD, and sustained at a high level for stroke. With the presence of CMM, the above association estimates inflated, but the pattern of which remained. CONCLUSION: Among Chinese adults, mortality risk increased with the number of the CMDs and changed with prolonged disease duration, the patterns of which varied among the three CMDs.

Conventional and genetic associations of adiposity with 1463 proteins in relatively lean Chinese adults.

Adiposity is associated with multiple diseases and traits, but little is known about the causal relevance and mechanisms underlying these associations. Large-scale proteomic profiling, especially when integrated with genetic data, can clarify mechanisms linking adiposity with disease outcomes. We examined the associations of adiposity with plasma levels of 1463 proteins in 3977 Chinese adults, using measured and genetically-instrumented BMI. We further used two-sample bi-directional MR analyses to assess if certain proteins influenced adiposity, along with other (e.g. enrichment) analyses to clarify possible mechanisms underlying the observed associations. Overall, the mean (SD) baseline BMI was 23.9 (3.3) kg/m2, with only 6% being obese (i.e. BMI ≥ 30 kg/m2). Measured and genetically-instrumented BMI was significantly associated at FDR < 0.05 with levels of 1096 (positive/inverse: 826/270) and 307 (positive/inverse: 270/37) proteins, respectively, with FABP4, LEP, IL1RN, LSP1, GOLM2, TNFRSF6B, and ADAMTS15 showing the strongest positive and PON3, NCAN, LEPR, IGFBP2 and MOG showing the strongest inverse genetic associations. These associations were largely linear, in adiposity-to-protein direction, and replicated (> 90%) in Europeans of UKB (mean BMI 27.4 kg/m2). Enrichment analyses of the top > 50 BMI-associated proteins demonstrated their involvement in atherosclerosis, lipid metabolism, tumour progression and inflammation. Two-sample bi-directional MR analyses using cis-pQTLs identified in CKB GWAS found eight proteins (ITIH3, LRP11, SCAMP3, NUDT5, OGN, EFEMP1, TXNDC15, PRDX6) significantly affect levels of BMI, with NUDT5 also showing bi-directional association. The findings among relatively lean Chinese adults identified novel pathways by which adiposity may increase disease risks and novel potential targets for treatment of obesity and obesity-related diseases.

Tobacco smoking and solid fuels for cooking and risk of liver cancer: A prospective cohort study of 0.5 million Chinese adults.

Previous research found tobacco smoking and solid fuel use for cooking to increase the risk of chronic liver disease mortality, but previous cohort studies have not investigated their independent and joint associations with liver cancer incidence in contemporary China. The China Kadoorie Biobank (CKB) study recruited 0.5 million adults aged 30 to 79 years from 10 areas across China during 2004 to 2008. Participants reported detailed smoking and fuel use information at baseline. After an 11.1-year median follow-up via electronic record linkage, we recorded 2997 liver cancer cases. Overall, 29.4% participants were current smokers. Among those who cooked at least once per month, 48.8% always used solid fuels (ie, coal or wood) for cooking. Tobacco smoking and solid fuel use for cooking were independently associated with increased risks of liver cancer, with hazard ratios (95% confidence intervals [CIs]) of 1.28 (1.15-1.42) and 1.25 (1.03-1.52), respectively. The more cigarettes consumed each day, the earlier the age of starting smoking or the longer duration of solid fuels exposure, the higher the risk (Ptrend < .001, =.001, =.018, respectively). Compared with never smokers who had always used clean fuels (ie, gas or electricity), ever-smokers who had always used solid fuels for cooking had a 67% (95% CIs: 1.29-2.17) higher risk. Among Chinese adults, tobacco smoking and solid fuel use for cooking were independently associated with higher risk of liver cancer incidence. Stronger association was observed with higher number of daily cigarette consumption, the earlier age of starting smoking and longer duration of solid fuel use.

Maintaining healthy sleep patterns and frailty transitions: a prospective Chinese study.

BACKGROUND: Little is known about the effects of maintaining healthy sleep patterns on frailty transitions. METHODS: Based on 23,847 Chinese adults aged 30-79 in a prospective cohort study, we examined the associations between sleep patterns and frailty transitions. Healthy sleep patterns included sleep duration at 7 or 8 h/d, without insomnia disorder, and no snoring. Participants who persisted with a healthy sleep pattern in both surveys were defined as maintaining a healthy sleep pattern and scored one point. We used 27 phenotypes to construct a frailty index and defined three statuses: robust, prefrail, and frail. Frailty transitions were defined as the change of frailty status between the 2 surveys: improved, worsened, and remained. Log-binomial regression was used to calculate the prevalence ratio (PR) to assess the effect of sleep patterns on frailty transitions. RESULTS: During a median follow-up of 8.0 years among 23,847 adults, 45.5% of robust participants, and 10.8% of prefrail participants worsened their frailty status, while 18.6% of prefrail participants improved. Among robust participants at baseline, individuals who maintained sleep duration of 7 or 8 h/ds, without insomnia disorder, and no-snoring were less likely to worsen their frailty status; the corresponding PRs (95% CIs) were 0.92 (0.89-0.96), 0.76 (0.74-0.77), and 0.85 (0.82-0.88), respectively. Similar results were observed among prefrail participants maintaining healthy sleep patterns. Maintaining healthy sleep duration and without snoring, also raised the probability of improving the frailty status; the corresponding PRs were 1.09 (1.00-1.18) and 1.42 (1.31-1.54), respectively. Besides, a dose-response relationship was observed between constantly healthy sleep scores and the risk of frailty transitions (P for trend < 0.001). CONCLUSIONS: Maintaining a comprehensive healthy sleep pattern was positively associated with a lower risk of worsening frailty status and a higher probability of improving frailty status among Chinese adults.

External validation of models for predicting risk of colorectal cancer using the China Kadoorie Biobank.

BACKGROUND: In China, colorectal cancer (CRC) incidence and mortality have been steadily increasing over the last decades. Risk models to predict incident CRC have been developed in various populations, but they have not been systematically externally validated in a Chinese population.  This study aimed to assess the performance of risk scores in predicting CRC using the China Kadoorie Biobank (CKB), one of the largest and geographically diverse prospective cohort studies in China. METHODS: Nine models were externally validated in 512,415 participants in CKB and included 2976 cases of CRC. Model discrimination was assessed, overall and by sex, age, site, and geographic location, using the area under the receiver operating characteristic curve (AUC). Model discrimination of these nine models was compared to a model using age alone. Calibration was assessed for five models, and they were re-calibrated in CKB. RESULTS: The three models with the highest discrimination (Ma (Cox model) AUC 0.70 [95% CI 0.69-0.71]; Aleksandrova 0.70 [0.69-0.71]; Hong 0.69 [0.67-0.71]) included the variables age, smoking, and alcohol. These models performed significantly better than using a model based on age alone (AUC of 0.65 [95% CI 0.64-0.66]). Model discrimination was generally higher in younger participants, males, urban environments, and for colon cancer. The two models (Guo and Chen) developed in Chinese populations did not perform better than the others. Among the 10% of participants with the highest risk, the three best performing models identified 24-26% of participants that went on to develop CRC. CONCLUSIONS: Several risk models based on easily obtainable demographic and modifiable lifestyle factor have good discrimination in a Chinese population. The three best performing models have a higher discrimination than using a model based on age alone.

Metacarpal shaft fixation: a biomechanical comparison of dorsal plating, lag screws, and headless compression screws.

BACKGROUND: Metacarpal shaft fractures are common and can be treated nonoperatively. Shortening, angulation, and rotational deformity are indications for surgical treatment. Various forms of treatment with advantages and disadvantages have been documented. The purpose of the study was to determine the stability of fracture fixation with intramedullary headless compression screws in two types of metacarpal shaft fractures and compare them to other common forms of rigid fixation: dorsal plating and lag screw fixation. It was hypothesized that headless compression screws would demonstrate a biomechanical stronger construct. METHODS: Five matched paired hands (age 60.9 ± 4.6 years), utilizing non-thumb metacarpals, were used for comparative fixation in two fracture types created by an osteotomy. In transverse diaphyseal fractures, fixation by headless compression screws (n = 7) and plating (n = 8) were compared. In long oblique diaphyseal fractures, headless compression screws (n = 8) were compared with plating (n = 8) and lag screws (n = 7). Testing was performed using an MTS frame producing an apex dorsal, three point bending force. Peak load to failure and stiffness were calculated from the load-displacement curve generated. RESULTS: For transverse fractures, headless compression screws had a significantly higher stiffness and peak load to failure, means 249.4 N/mm and 584.8 N, than plates, means 129.02 N/mm and 303.9 N (both p < 0.001). For long oblique fractures, stiffness and peak load to failure for headless compression screws were means 209 N/mm and 758.4 N, for plates 258.7 N/mm and 518.5 N, and for lag screws 172.18 N/mm and 234.11 N. There was significance in peak load to failure for headless compression screws vs plates (p = 0.023), headless compression screws vs lag screws (p < 0.001), and plates vs lag screws (p = 0.009). There was no significant difference in stiffness between groups. CONCLUSION: Intramedullary fixation of diaphyseal metacarpal fractures with a headless compression screw provides excellent biomechanical stability. Coupled with lower risks for adverse effects, headless compression screws may be a preferable option for those requiring rapid return to sport or work. LEVEL OF EVIDENCE: Basic Science Study, Biomechanics.

High Clinical Failure Rate After Latissimus Dorsi Transfer for Revision Massive Rotator Cuff Tears.

PURPOSE: To evaluate the clinical success rate, along with risk factors for failure, in patients undergoing latissimus dorsi transfer for the treatment of massive, irreparable, previously failed rotator cuff tears. METHODS: We performed a retrospective chart review of prospectively collected data from an institutional shoulder outcome registry. All patients who underwent latissimus dorsi transfer for previously failed rotator cuff repair between 2006 and 2013 with a minimum follow-up period of 1 year were included in the study. The indications for inclusion were large (≥2 tendons), retracted, chronic rotator cuff tears with fatty infiltration or atrophy for which prior surgical repair had failed. Preoperative and postoperative American Shoulder and Elbow Surgeons (ASES) and Simple Shoulder Test scores were collected, along with postoperative Single Assessment Numerical Evaluation scores. Complications and clinical failures (Δ in ASES score <17) were recorded. Patient demographic and tear characteristics were evaluated as potential risk factors for failure. RESULTS: A total of 22 patients (mean age, 53 ± 6 years) were included in the study, with a mean follow-up time of 3.4 ± 1.1 years. Over 63% of patients (n = 14) reported undergoing 2 or more prior failed rotator cuff repairs. Patients undergoing latissimus dorsi transfer showed significant improvements in ASES scores (from 35.2 ± 21.9 preoperatively to 55.8 ± 22.9 postoperatively, P = .001), Simple Shoulder Test scores (from 3.5 ± 3.1 preoperatively to 5.2 ± 3.4 postoperatively, P = .002), and pain scores (from 5.9 ± 2.8 preoperatively to 4.6 ± 4.3 postoperatively, P = .002) at final follow-up. The complication rate after latissimus transfer was 27%. The rate of revision to reverse total shoulder arthroplasty was 13.6% (n = 3) after a mean of 2.7 years, and the clinical failure rate was 41% (n = 9) at final follow-up. An acromiohumeral interval of less than 7 mm (P = .04) and high-grade fatty infiltration (grade 3 or greater, P = .004) were significant preoperative risk factors for clinical failure. CONCLUSIONS: Latissimus dorsi tendon transfer resulted in a clinical failure rate of 41% and complication rate of 27%, with an acromiohumeral interval of less than 7 mm and high-grade fatty infiltration being associated with postoperative failure. LEVEL OF EVIDENCE: Level IV.

Headless Compression Screw Versus Kirschner Wire Fixation for Metacarpal Neck Fractures: A Biomechanical Study.

PURPOSE: This study aimed to determine the biomechanical stability of headless compression screws in the fixation of metacarpal neck fractures and to compare them with another common, less invasive form of fixation, K-wires. The hypothesis was that headless compression screws would show higher stiffness and peak load to failure than K-wire fixation. METHODS: Eight matched-paired hands (n = 31), using the ring and little finger metacarpals, had metacarpal fractures simulated at the physeal scar. Each group was stabilized with either a 3.5-mm headless compression screw or 2 0.045-in (1.1-mm) K-wires. Nineteen metacarpals were tested in 3-point bending and 12 in axial loading. Peak load to failure and stiffness were calculated from the load displacement curve. Bone mineral density was recorded for each specimen. RESULTS: Bone mineral density was similar in the 2 groups tested for 3-point bending and axial loading. Stiffness was not significantly different in 3-point bending for headless compression screws and K-wires (means, 141.3 vs 194.5 N/mm) but it was significant in axial loading (means, 178.0 vs 111.6 N/mm). Peak load to failure was significantly higher in headless compression screws in 3-point bending (means, 401.2 vs 205.3 N) and axial loading (means, 467.5 vs 198.3 N). CONCLUSIONS: Compared with K-wires, headless compression screws for metacarpal neck fractures are biomechanically superior in load to failure, 3-point bending, and axial loading. CLINICAL RELEVANCE: Headless compression screws demonstrate excellent biomechanical stability in metacarpal neck fractures. In conjunction with promising clinical studies, these data suggest that headless compression screws may be an option for treating metacarpal neck fractures.

Surgeon-rated visualization in shoulder arthroscopy: a randomized blinded controlled trial comparing irrigation fluid with and without epinephrine.

PURPOSE: The objective of the current study was to compare surgeon-rated visualization in shoulder arthroscopy using irrigation fluid with and without epinephrine. METHODS: Eighty-three patients were randomized to receive irrigation fluid with (44 patients) or without (39 patients) epinephrine during their arthroscopic shoulder procedures. After each procedure, the blinded senior author (G.F.C.) evaluated visualization based on a visual analog scale (VAS), and all clinically important procedure variables were recorded. RESULTS: Eighty-three arthroscopic shoulder procedures were included in the study. Fifty-four of these procedures were arthroscopic rotator cuff repairs, allowing a subset analysis of this specific procedure. There was a significant difference, with improved visualization in the epinephrine group versus the group without epinephrine when comparing all procedures (P < .0001) and when comparing only rotator cuff repairs (P < .0001). However, there was no statistical difference in other clinically important variables, including operative time and amount of irrigation fluid used. CONCLUSIONS: The addition of epinephrine to irrigation fluid significantly improves surgeon-rated visualization in shoulder arthroscopy. Without an observed significant difference in operative time or volume of irrigation fluid used, the clinical significance of this improved visualization is unclear, and the use of irrigation fluid without epinephrine remains a viable option in the hands of an experienced surgeon. LEVEL OF EVIDENCE: Level I, high-quality randomized controlled trial with statistically significant difference.

The effect of anesthesia type on nonsurgical operating room time.

PURPOSE: To determine the effect of local-only anesthesia on nonsurgical time compared with monitored anesthesia care (MAC)/local and general anesthesia. Our hypothesis was that local-only anesthesia cases would have lower nonsurgical times compared with MAC/local and general anesthesia. METHODS: We retrospectively reviewed the surgical records of 1,179 patients undergoing elective hand surgery. For each case, we recorded the type of anesthesia used (general, MAC/local, or local-only anesthesia) and in-room presurgical time, in-room postsurgical time, and, if relevant, room turnover time. We did not record room turnover times for the first case of the day or for cases after procedures that did not meet inclusion criteria. We also recorded the presence of any anesthesia providers (anesthesiologist vs anesthesia-assistant [certified registered nurse anesthetist]). RESULTS: A total of 566 cases performed on 501 patients met inclusion criteria. Room turnover times were not calculated for 304 cases. The choice of anesthesia had a significant effect on nonsurgical operating room time. Local anesthesia cases had significantly less nonsurgical time compared with general anesthesia and MAC/local. Cases performed under MAC/local anesthesia also had significantly reduced nonsurgical time compared with general anesthesia. The presence of a certified anesthesia assistant had no effect on any time metrics recorded. CONCLUSIONS: Choice of local anesthesia, when appropriate, may facilitate rapid operating room turnover and improve overall facility efficiency with lower costs. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

The efficiency of a dedicated staff on operating room turnover time in hand surgery.

PURPOSE: To evaluate the effect of orthopedic and nonorthopedic operating room (OR) staff on the efficiency of turnover time in a hand surgery practice. METHODS: A total of 621 sequential hand surgery cases were retrospectively reviewed. Turnover times for sequential cases were calculated and analyzed with regard to the characteristics of the OR staff being primarily orthopedic or nonorthopedic. RESULTS: A total of 227 turnover times were analyzed. The average turnover time with all nonorthopedic staff was 31 minutes, for having only an orthopedic surgical technician was 32 minutes, for having only an orthopedic circulator was 25 minutes, and for having both an orthopedic surgical technician and a circulator was 20 minutes. Statistical significance was seen when comparing only an orthopedic surgical technician versus both an orthopedic circulator and a surgical technician and when comparing both nonorthopedic staff versus both an orthopedic circulator and a surgical technician. CONCLUSIONS: OR efficiency is being increasingly evaluated for its effect on hospital revenue and OR staff costs. Reducing turnover time is one aspect of a multifaceted solution in increasing efficiency. Our study showed that, for hand surgery, orthopedic-specific staff can reduce turnover time. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic/Decision Analysis III.

Dietary factors and patterns in relation to risk of later-onset ulcerative colitis in Chinese: A prospective study of 0.5 million people.

BACKGROUND: There is limited evidence on the associations of dietary factors and patterns with risk of later-onset ulcerative colitis (UC) in Chinese adults. AIMS: To investigate the associations of dietary factors and patterns with risk of later-onset UC in Chinese. METHODS: The prospective China Kadoorie Biobank cohort study recruited 512,726 participants aged 30-79. Dietary habits were assessed using food frequency questionnaires. Dietary patterns were derived by factor analysis with a principal component method. Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 12.1 years, 312 cases of newly diagnosed UC were documented (median age of diagnosis 60.1 years). Egg consumption was associated with higher risk of UC (HR for daily vs. never or rarely: 2.29 [95% CI: 1.26-4.16]), while spicy food consumption was inversely associated with risk of UC (HR: 0.63 [0.45-0.88]). The traditional northern dietary pattern, characterised by high intake of wheat and low intake of rice, was associated with higher risk of UC (HR for highest vs. lowest quartile of score: 2.79 [1.93-4.05]). The modern dietary pattern, characterised by high intake of animal-origin foods and fruits, was associated with higher risk of UC (HR: 2.48 [1.63-3.78]). Population attributable fraction was 13.04% (7.71%-19.11%) for daily/almost daily consumption of eggs and 9.87% (1.94%-18.22%) for never/rarely consumption of spicy food. CONCLUSIONS: The findings highlight the importance of evaluating dietary factors and patterns in the primary prevention of later-onset UC in Chinese adults.

The Role of Active and Passive Smoking in Chronic Obstructive Pulmonary Disease and Systemic Inflammation: A 12-year Prospective Study in China.

BACKGROUND: There is no consensus on the cause and effect of systemic chronic inflammation (SCI) regarding chronic obstructive pulmonary disease (COPD). The impact of second-hand smoke (SHS) on COPD has reached inconsistent conclusions. METHODS: The China Kadoorie Biobank cohort was followed up from the 2004-08 baseline survey to 31 December 2018. Among the selected 445,523 participants in the final analysis, Cox and linear regressions were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of tobacco exposure with COPD risk and baseline levels of log-transformed inflammatory factors [ßs (95% CIs)], respectively. RESULTS: Participants were followed up for a median of 12.1 years and 11,825 incident COPD events were documented. Ever-smokers were associated with a higher risk of COPD than non-smokers with non-weekly SHS exposure. A younger age to start smoking, a greater amount of daily tobacco consumption, and deeper inhalation were associated with increased risk of COPD and correlated with elevated levels of plasma high-sensitivity C-reactive protein (hs-CRP, all Ptrend < 0.001) even two years before COPD onset. Among former smokers, COPD risk declined with longer smoking cessation (Ptrend < 0.001) and those quitting smoking for over ten years presented no difference in COPD risk and hs-CRP level from non-smokers [HR (95% CI) = 1.05 (0.89, 1.25), ß (95% CI) = 0.17 (- 0.09, 0.43)]. Among non-smokers, weekly SHS exposure was associated with a slightly higher COPD risk [HR (95% CI) = 1.06 (1.01, 1.12)]. CONCLUSIONS: Incremental exposure to tobacco smoke was related to elevated SCI level before COPD onset, then an increase in COPD susceptibility. Quitting smoking as early as possible is suggested as a practical approach to reducing COPD risk in smokers. Given the high prevalence of both COPD and SHS exposure, the risk associated with SHS exposure deserves attention.

Predictive value of 8-year blood pressure measures in intracerebral haemorrhage risk over 5 years.

AIMS: The relationships between long-term blood pressure (BP) measures and intracerebral haemorrhage (ICH), as well as their predictive ability on ICH, are unclear. In this study, we aim to investigate the independent associations of multiple BP measures with subsequent 5-year ICH risk, as well as the incremental value of these measures over a single-point BP measurement in ICH risk prediction. METHODS AND RESULTS: We included 12 398 participants from the China Kadoorie Biobank (CKB) who completed three surveys every 4-5 years. The following long-term BP measures were calculated: mean, minimum, maximum, standard deviation, coefficient of variation, average real variability, and cumulative BP exposure (cumBP). Cox proportional hazard models were used to examine the associations between these measures and ICH. The potential incremental value of these measures in ICH risk prediction was assessed using Harrell's C statistics, continuous net reclassification improvement (cNRI), and relative integrated discrimination improvement (rIDI). The hazard ratios (95% confidence intervals) of incident ICH associated with per standard deviation increase in cumulative systolic BP and cumulative diastolic BP were 1.62 (1.25-2.10) and 1.59 (1.23-2.07), respectively. When cumBP was added to the conventional 5-year ICH risk prediction model, the C-statistic change was 0.009 (-0.001, 0.019), the cNRI was 0.267 (0.070-0.464), and the rIDI was 18.2% (5.8-30.7%). Further subgroup analyses revealed a consistent increase in cNRI and rIDI in men, rural residents, and participants without diabetes. Other long-term BP measures showed no statistically significant associations with incident ICH and generally did not improve model performance. CONCLUSION: The nearly 10-year cumBP was positively associated with an increased 5-year risk of ICH and could significantly improve risk reclassification for the ICH risk prediction model that included single-point BP measurement.

This prospective cohort study of Chinese adults investigated the independent associations of multiple blood pressure (BP) measures with subsequent 5-year intracerebral haemorrhage (ICH) risk, as well as the incremental value of these measures over a single-point BP measurement in ICH risk prediction.The cumulative BP exposure (cumBP) was positively associated with subsequent 5-year risk of ICH, independent of the recent single-point systolic BP and diastolic BP levels.The cumBP could improve the risk reclassification of the conventional 5-year ICH risk prediction model that included single-point BP measurement for all participants, as well as for men, rural residents, and participants without diabetes.