The timing of intravenous antibiotics and clinical outcomes of Mycobacterium abscessus complex lung diseases.

BACKGROUND: The importance of early intravenous (IV) antibiotic use for Mycobacterium abscessus complex lung diseases (MABC-LD) treatment remains unknown. METHODS: A retrospective multi-centre observational study was conducted in Taiwan. Patients who were diagnosed with and received treatment for MABC-LD from January 2007 to April 2021 were included. Treatment outcome was defined as modified microbiological cure of MABC-LD.RESULTS: Of the 89 enrolled patients, 34 (38.2%) received IV antibiotics as part of the treatment regimen. The median time to IV initiation was 1 day (IQR 1???49); 24 (70.6%) of these patients received IV agents within 4 weeks, defined as early-use. Forty-two (47.2%) patients achieved modified microbiological cure. In the multivariable logistic analysis, early IV antibiotic use was an independent factor associated with modified microbiological cure (aOR 5.32, 95% CI 1.66???17.00), whereas high radiological score (aOR 0.86, 95% CI 0.73???1.00) demonstrated negative association.CONCLUSIONS: In the present study, early use of effective IV antibiotic was prescribed in a low percentage (27%) for MABC-LD. By contrast, early IV antibiotic use was correlated with higher microbiological cure than were late or non-use. Future larger and prospective studies are needed to validate the association.

Impact of prior extrapulmonary cancer on survival after lung cancer: a systematic review and meta-analysis.

OBJECTIVE: This review aimed to examine the impact of previous extrapulmonary malignancies on the overall survival (OS) of lung cancer patients. MATERIALS AND METHODS: The online databases of PubMed, Embase, Scopus, and Web of Science were explored for studies published up to 22nd December 2022 and comparing outcomes of first lung cancer vs. second primary lung cancer with a history of previous extrapulmonary malignancy. Studies were to report adjusted data on OS. Meta-analysis was performed in a random-effects model. RESULTS: Nine retrospective studies were eligible. A total of 267,892 lung cancer patients with prior extrapulmonary malignancy and 1,351,245 primary lung cancer patients were analyzed in the studies. Meta-analysis of all studies showed that prior extrapulmonary malignancy results in poor OS in lung cancer patients as compared to those with no history of such cancer (HR: 1.27 95% CI: 1.07, 1.50 I2=83%). The results did not change on sensitivity analysis. No publication bias was noted. CONCLUSIONS: The result of this meta-analysis indicates that a history of prior extrapulmonary malignancy results in poor OS in patients with lung cancer. Caution is needed in the interpretation of the results owing to high interstudy heterogeneity. Further research is needed to assess how factors like the type of extrapulmonary malignancy, time interval of diagnosis, cancer stage, and treatment modality impact this relationship.

The Effect of Renin-Angiotensin-Aldosterone System Inhibitors on Outcomes of Patients Treated with Immune Checkpoint Inhibitors: a Retrospective Cohort Study.

AIMS: Renin-angiotensin-aldosterone system inhibitors (RAASi) are associated with improved survival outcomes in patients receiving immune checkpoint inhibitors (ICIs), but the data on the response to treatment and tumour-based endpoints across different tumour types are unknown. MATERIALS AND METHODS: We carried out a retrospective study at two tertiary referral centres in Taiwan. All adult patients treated with ICIs between January 2015 and December 2021 were included. The primary outcome was overall survival and the secondary outcomes were progression-free survival (PFS) and clinical benefit rates. RESULTS: In total, 734 patients were enrolled in our study, of which 171 were RAASi users and 563 were non-users. Compared with non-users, RAASi users had a longer median overall survival [26.8 (interquartile range 11.3-not reached) versus 15.2 (interquartile range 5.1-58.4) months, P < 0.001] and PFS [12.2 (interquartile range 3.9-34.5) versus 5.0 (interquartile range 2.2-15.2) months, P < 0.001]. In univariate Cox proportional hazard analyses, the use of RAASi was associated with a 40% reduction in the risk of mortality [hazard ratio 0.58 (95% confidence interval 0.44-0.76), P < 0.001] and disease progression [hazard ratio 0.62 (95% confidence interval 0.50-0.77), P < 0.001]. The association remained significant after adjusting for underlying comorbidities and cancer therapy in multivariate Cox analyses. A similar trend was observed for PFS. Furthermore, RAASi users experienced a greater clinical benefit rate than non-users (69% versus 57%, P = 0.006). Importantly, the use of RAASi before ICI initiation was not associated with improved overall survival and PFS. RAASi were not associated with an increased risk of adverse events. CONCLUSION: The use of RAASi is associated with improved survival outcomes, treatment response and tumour-based endpoints in patients undergoing immunotherapy.

Influence of Nutritional Status on a Family-Centered Care Intervention for Older Adults with Cognitive Impairment following Hip-Fracture Surgery: Secondary Data Analysis of a Randomized Controlled Trial.

OBJECTIVES: In Taiwan, older adults with cognitive impairment who undergo hip-fracture surgery are routinely cared for by family members. This study aimed to determine if nutritional status influenced the effects of a family-centered intervention for older adults with cognitive impairment recovering from hip-fracture surgery. DESIGN: Secondary data analysis of data from a randomized controlled trial was conducted to examine the influences of nutritional status 1 month after hospital discharge on the effects of a family-centered care intervention model, which was designed for older adults with hip fracture and cognitive impairment. Outcomes were compared among participants according to nutrition status (well-nourished/poorly-nourished) and treatment approach (control/intervention). SETTING: The original study was conducted at a 3000-bed medical center from July 2015 to October 2019. PARTICIPANTS: Participants were older adults with cognitive impairment who had undergone hip-fracture surgery. Participants were assessed as poorly-nourished or well-nourished with the Mini-Nutritional Assessment (MNA) 1-month post-discharge and were then randomly assigned to either the intervention group or control group. INTERVENTION: A family-centered intervention model for family caregivers of older adults with cognitive impairment recovering from hip-fracture surgery was implemented. The intervention was delivered by geriatric nurses, which included instructions for family caregivers in overseeing exercises for strengthening the hip, understanding dietary requirements, and managing behavioral problems associated with cognitive impairment. MEASUREMENTS: Outcome measures included activities of daily living (ADLs), instrumental ADLs, hip range of motion, hip muscle strength, depression, measured with the Geriatric Depressive Scale, and physical and mental health related quality of life, measured with the Short Form Survey (SF-36), Taiwanese version. Participants were assessed at 1-, 3-, 6-, and 12-months post-discharge. RESULTS: Most of the 134 participants were assessed as poorly nourished (n = 122); 57 were the control group and 65 received the intervention. For the well-nourished participants (n = 12), four were in the intervention group and eight were controls. There were no significant differences in any outcome variables for poorly nourished participants who received the intervention compared with controls. For the sample of well-nourished participants, those who received the intervention performed significantly better in outcomes of IADLs (b = 1.74, p < .05), hip muscle strength (b = 9.64, p < .01), and physical health related quality of life (b = 10.47, p < .01). CONCLUSION: The family-centered care intervention was only effective for older adults with cognitive impairment recovering from hip-fracture surgery who were well-nourished at 1 month following hospital discharge, but not for those at risk of malnutrition. Interventions should focus on enhancing nutritional status following hip surgery which could allow the family-centered in-home intervention to be beneficial for more older adults with cognitive impairment recovering from hip-fracture surgery.

Risk of thromboembolism in non-small-cell lung cancers patients with different oncogenic drivers, including ROS1, ALK, and EGFR mutations.

BACKGROUND: Anaplastic lymphoma kinase-positive (ALK+) and ROS proto-oncogene 1 (ROS1)-positive (ROS1+) lung cancers have been reported to be associated with an elevated risk of thromboembolic events. This study aimed to assess the long-term risk of developing thromboembolism (TE) in ROS1+ lung cancer and to compare it with other oncogenic drivers in the Asian population. MATERIALS AND METHODS: We retrospectively enrolled a cohort of ROS1+ lung adenocarcinoma in a medical center in Taiwan and a comparison cohort of ALK+ and epidermal growth factor receptor-positive (EGFR+) lung cancers. Venous and arterial TEs were identified throughout the cancer course, and the incidence rate was calculated. RESULTS: We enrolled 44 ROS1+, 98 ALK+, and 168 EGFR+ non-small-cell lung cancer (NSCLC) patients. A total of 11 (25%), 36 (36.7%), and 38 (22.6%) patients in the ROS1, ALK, and EGFR cohorts, respectively, were diagnosed with thromboembolic events throughout the follow-up course of the disease (P = 0.042). The incidence rates were 99.0, 91.9, and 82.5 events per 1000 person-years for the ROS1, ALK, and EGFR cohorts, respectively. The majority of thrombosis events in the ROS1 (91.6%) and ALK (85.4%) cohorts were venous. On the contrary, 43.2% of thromboembolic events were arterial in the EGFR cohort. A higher proportion of thromboembolic events were noted during cancer diagnosis in the ROS1 cohort (36.3%) than in the ALK (16.7%) and EGFR (10.5%) cohorts. The stage was the only clinical variable associated with thromboembolic risk. There was a significant difference in survival between patients with and without TE in the EGFR cohort, but not in the ALK and ROS1 cohorts. CONCLUSIONS: Although ROS1+ and ALK+ NSCLCs had a higher cumulative incidence of TE than EGFR+ NSCLC, the person-year incidence rates were similar among the three groups. EGFR-mutated NSCLC had more arterial events. Nevertheless, ALK+ lung cancer had higher venous events than EGFR-mutated lung cancer.

Effects of daily almond consumption for six months on cognitive measures in healthy middle-aged to older adults: a randomized control trial.

BACKGROUND: Age-related cognitive decline is a major public health issue. Almonds are rich in nutrients that benefit cognitive function. OBJECTIVE: To investigate the impact of almonds on cognition in elderly adults. DESIGN: In a six-month, single-blinded, randomized-controlled trial, the effects of an almond intervention on cognition in healthy, middle-aged/older adults (50-75 years) was tested. Subjects were assigned to one of three groups: 1.5 oz/d almond (n = 19), 3 oz/d almond (n = 24), or 3.5 oz/d snack (control, matched for macronutrients in 3.0 oz almonds, (n = 17). Serum analyses for tocopherols, oxidative status and inflammation, and cognition were assessed at baseline (M0), three (M3), and six (M6) months. RESULTS: At M6, serum alpha-tocopherol concentrations increased by 8% from M0 (p < 0.05) in the 3 oz almond group but did not increase in the other groups. Serum markers of inflammation and oxidative stress were not significantly different throughout the study among the groups. There was no difference in change over time in cognitive tests among the groups. However, there was a significant improvement in visuospatial working memory (p = 0.023), visual memory and learning (p = 0.017), and spatial planning and working memory (p < 0.001) in subjects receiving 3 oz/d almonds at M6, while the snack group showed no improvement. CONCLUSIONS: Almonds did not significantly improve cognitive function in cognitively intact middle-aged/older adults over six months. However, a significant improvement at M6 in cognitive measures was observed with 3 oz/d almonds. While these results are encouraging, a study of longer duration in subjects at risk for age-related cognitive decline is warranted.Trial registration: ClinicalTrials.gov identifier: NCT03093896.

Correlation between inflammatory cytokines and liver cancer stem cell markers in DEN-induced liver cancer rats.

OBJECTIVE: To study the association of inflammatory factors and hepatocarcinoma stem cells of induced liver cancer rats. MATERIALS AND METHODS: 30 SD male healthy rats were selected. 10 rats were given water as normal control group. 10 rats only were implemented laparotomy as sham operation group. The remaining 10 rats were the liver cancer model group and treated with diethylnitrosamine (DEN) to induce liver cancer. Real-time quantitative PCR was used to detect the related inflammatory factors in HCC tissues, including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-ß1 (TGF-ß), human interleukin-1α (IL-1α), human interleukin 1ß (IL-1ß) and levels of hepatocarcinoma stem cells indicators CD90, CD133, Alpha-fetoprotein (AFP). Correlation analysis was used to analyze the correlation between inflammatory factors and hepatocarcinoma stem cells markers CD90 and CD133. RESULTS: The expression levels of IL-6, MCP-1 and TGF-ß of HCC tissues in liver cancer model group were significantly higher than those in the control group and the sham operation group. The expression levels of CD90 and CD133 of tissues in the liver cancer model group were significantly higher than those in the control group and the sham operation group. The differences were statistically significant (p<0.001). By inhibiting related inflammatory factors, the growth, migration and invasion of liver cancer cells were significantly inhibited, and apoptosis was promoted. Correlation analysis results showed that the expression changes of IL-6, MCP-1 and TGF-ß were significantly positively correlated with CD90 up-regulation (p<0.05), while the expression changes of IL-6, MCP-1 and TGF-ß were significantly positively correlated with CD133 up-regulation (p<0.05). CONCLUSIONS: The inflammatory factors IL-6, MCP-1 and TGF-ß are closely related to hepatocarcinoma stem cells, which play an important role in promoting the occurrence and deterioration of liver cancer.

Situational risk factors for fall-related vertebral fractures in older men and women.

Situational factors might help explain why most vertebral fractures occur in older people without a previous osteoporosis diagnosis. After adjusting for predisposing risk factors, the activity before the fall, type of fall, and falling direction remained as strong determinants of fall-related vertebral fractures in older men and women. INTRODUCTION: A matched case-control study was conducted to investigate the effects of situational factors, in addition to predisposing factors, on clinical vertebral fractures in older men and women in Taiwan. METHODS: Cases were community-dwelling individuals aged ≥ 65 years who visited emergency departments (EDs) of two university-affiliated hospitals due to a fall and had a primary diagnosis of a vertebral fracture during a 1-year period in 2017. Five control patients per case, matched by the time of falling, gender, and age, who sought care in the same ED due to a fall resulting in a soft tissue injury were selected. A total of 64 men (age range: 65 ~ 99 years) and 194 women (age range: 65 ~ 100 years), diagnosed with a vertebral fracture, participated in the study. RESULTS: Multivariable logistic models were conducted separately for men and women. Results suggested that the following factors were significantly associated with an increased risk of vertebral fractures in men: a low educational level (adjusted odds ratio [OR] = 1.95; 95% confidence interval (CI), 1.02 ~ 3.71), asthma (OR = 2.96; 95% CI, 1.35 ~ 6.92), depression (OR = 4.31; 95% CI, 1.03 ~ 17.5), toileting (OR = 2.30; 95% CI, 1.04 ~ 4.94), slipping (OR = 5.27; 95% CI, 1.80 ~ 15.4), stepping down (OR = 3.99; 95% CI, 1.40 ~ 11.4), sudden leg weakness (OR = 3.73; 95% CI, 1.13 ~ 12.4), and falling backwards (OR = 3.78; 95% CI, 1.83 ~ 7.80); and in women: a fracture history (OR = 2.00; 95% CI, 1.07 ~ 3.76), osteoporosis (OR = 1.94; 95% CI, 1.15 ~ 3.49), getting in/out of the bed/chair (OR = 1.90; 95% CI, 1.07 ~ 3.39), stepping down (OR = 2.10; 95% CI, 1.17 ~ 3.77), and falling backwards (OR = 4.00; 95% CI, 2.39 ~ 6.68) and sideways (OR = 2.61; 95% CI, 1.38 ~ 4.96). CONCLUSIONS: The combination of predisposing and situational risk factors may display a more comprehensive risk profile for the occurrence of VFs, and thus, interventions that add both types of risk factors may result in greater risk reduction of VFs, although those specifically targeted at situational risk factors during falls are limited and their effectiveness and efficiency remained to be explored.

CUL4A promotes the invasion of cervical cancer cells by regulating NF-κB signaling pathway.

OBJECTIVE: The aim of this study was to investigate the effects of cullin 4A (CUL4A) on promoting the proliferation and inhibiting the apoptosis of cervical cancer (CC) cells by regulating the nuclear factor-kappa B (NF-κB) signaling pathway. PATIENTS AND METHODS: The protein expressions of CUL4A and NF-κB in 75 CC tissues were detected through immunohistochemistry. The correlation between the expressions of the two proteins in CC tissues was analyzed via Spearman's correlation test. Meanwhile, the prognostic significance of CUL4A expression for CC patients was analyzed by Kaplan-Meier curve. CUL4A small interfering ribonucleic acid (siRNA) was transfected into CC cells (HeLa) to downregulate the expression level of CUL4A. Subsequently, the effects of CUL4A on the proliferation and apoptosis of HeLa cells were detected by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Finally, the effect of CUL4A on the activity of the NF-κB signaling pathway was analyzed through quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). RESULTS: The protein expressions of CUL4A and NF-κB in CC tissues were significantly higher than those in normal tissues (p<0.01). The results of the survival curve showed that the prognosis of CC patients with highly expressed CUL4A is poor (p<0.001). Meanwhile, lowly expressed CUL4A protein significantly inhibited the proliferation and promoted the apoptosis of HeLa cells (p<0.01). QRT-PCR results indicated that the relative messenger RNA (mRNA) expression levels of downstream genes of the NF-κB signaling pathway were significantly lower in CC cells than those in the control group (p<0.001). In addition, CUL4A expression was positively correlated with NF-κB expression in CC (p<0.001). CONCLUSIONS: CUL4A promotes the invasion of CC cells through the NF-κB signaling pathway.

The Mortality After Release from Incarceration Consortium (MARIC): Protocol for a multi-national, individual participant data meta-analysis.

INTRODUCTION: More than 30 million adults are released from incarceration globally each year. Many experience complex physical and mental health problems, and are at markedly increased risk of preventable mortality. Despite this, evidence regarding the global epidemiology of mortality following release from incarceration is insufficient to inform the development of targeted, evidence-based responses. Many previous studies have suffered from inadequate power and poor precision, and even large studies have limited capacity to disaggregate data by specific causes of death, sub-populations or time since release to answer questions of clinical and public health relevance. OBJECTIVES: To comprehensively document the incidence, timing, causes and risk factors for mortality in adults released from prison. METHODS: We created the Mortality After Release from Incarceration Consortium (MARIC), a multi-disciplinary collaboration representing 29 cohorts of adults who have experienced incarceration from 11 countries. Findings across cohorts will be analysed using a two-step, individual participant data meta-analysis methodology. RESULTS: The combined sample includes 1,337,993 individuals (89% male), with 75,795 deaths recorded over 9,191,393 person-years of follow-up. CONCLUSIONS: The consortium represents an important advancement in the field, bringing international attention to this problem. It will provide internationally relevant evidence to guide policymakers and clinicians in reducing preventable deaths in this marginalized population. KEY WORDS: Mortality; incarceration; prison; release; individual participant data meta-analysis; consortium; cohort.

Effects of food supplementation on cognitive function, cerebral blood flow, and nutritional status in young children at risk of undernutrition: randomized controlled trial.

OBJECTIVE: To assess the effects of food supplementation on improving working memory and additional measures including cerebral blood flow in children at risk of undernutrition. DESIGN: Randomized controlled trial. SETTING: 10 villages in Guinea-Bissau. PARTICIPANTS: 1059 children aged 15 months to 7 years; children younger than 4 were the primary population. INTERVENTIONS: Supervised isocaloric servings (≈1300 kJ, five mornings each week, 23 weeks) of a new food supplement (NEWSUP, high in plant polyphenols and omega 3 fatty acids, within a wide variety and high fortification of micronutrients, and a high protein content), or a fortified blended food (FBF) used in nutrition programs, or a control meal (traditional rice breakfast). MAIN OUTCOME MEASUREMENTS: The primary outcome was working memory, a core executive function predicting long term academic achievement. Additional outcomes were hemoglobin concentration, growth, body composition, and index of cerebral blood flow (CBFi). In addition to an intention-to-treat analysis, a predefined per protocol analysis was conducted in children who consumed at least 75% of the supplement (820/925, 89%). The primary outcome was assessed by a multivariable Poisson model; other outcomes were assessed by multivariable linear mixed models. RESULTS: Among children younger than 4, randomization to NEWSUP increased working memory compared with the control meal (rate ratio 1.20, 95% confidence interval 1.02 to 1.41, P=0.03), with a larger effect in the per protocol population (1.25, 1.06 to 1.47, P=0.009). NEWSUP also increased hemoglobin concentration among children with anemia (adjusted mean difference 0.65 g/dL, 95% confidence interval 0.23 to 1.07, P=0.003) compared with the control meal, decreased body mass index z score gain (-0.23, -0.43 to -0.02, P=0.03), and increased lean tissue accretion (2.98 cm2, 0.04 to 5.92, P=0.046) with less fat (-5.82 cm2, -11.28 to -0.36, P=0.04) compared with FBF. Additionally, NEWSUP increased CBFi compared with the control meal and FBF in both age groups combined (1.14 mm2/s×10-8, 0.10 to 2.23, P=0.04 for both comparisons). Among children aged 4 and older, NEWSUP had no significant effect on working memory or anemia, but increased lean tissue compared with FBF (4.31 cm2, 0.34 to 8.28, P=0.03). CONCLUSIONS: Childhood undernutrition is associated with long term impairment in cognition. Contrary to current understanding, supplementary feeding for 23 weeks could improve executive function, brain health, and nutritional status in vulnerable young children living in low income countries. Further research is needed to optimize nutritional prescriptions for regenerative improvements in cognitive function, and to test effectiveness in other vulnerable groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT03017209.

Phylogenetic placement of Paratrichaptum and reconsideration of Gloeophyllales.

Paratrichaptum accuratum is a large conspicuous polypore fungus growing on dead or living angiosperm trees in subtropical-boreal areas of China, Indonesia, Japan, and Taiwan. The present study places P. accuratum in the family Gloeophyllaceae that belongs to the order Gloeophyllales within Agaricomycetes (Basidiomycota), based on evidence derived from morphological and ecological characteristics, and phylogenetic analyses of sequences of nuclear rDNA regions (5.8S, nuc 18S, nuc 28S) and protein-coding genes (rpb1, rpb2, and tef1). The analyses presented in this study also give strong support for including Jaapia in Gloeophyllaceae and Gloeophyllales. Thus, the names Jaapiaceae and Jaapiales are considered here as synonyms of Gloeophyllaceae and Gloeophyllales. Since Paratrichaptum represents the earliest diverging lineage in Gloeophyllales, pileate basidiocarps and brown rot appear to be ancestral states of Gloeophyllales. Paratrichaptum accuratum may represent a relic species, according to its phylogenetic position, peculiar distribution pattern and rare occurrence.

Fruits, vegetables, and health: A comprehensive narrative, umbrella review of the science and recommendations for enhanced public policy to improve intake.

Fruit and vegetables (F&V) have been a cornerstone of healthy dietary recommendations; the 2015-2020 U.S. Dietary Guidelines for Americans recommend that F&V constitute one-half of the plate at each meal. F&V include a diverse collection of plant foods that vary in their energy, nutrient, and dietary bioactive contents. F&V have potential health-promoting effects beyond providing basic nutrition needs in humans, including their role in reducing inflammation and their potential preventive effects on various chronic disease states leading to decreases in years lost due to premature mortality and years lived with disability/morbidity. Current global intakes of F&V are well below recommendations. Given the importance of F&V for health, public policies that promote dietary interventions to help increase F&V intake are warranted. This externally commissioned expert comprehensive narrative, umbrella review summarizes up-to-date clinical and observational evidence on current intakes of F&V, discusses the available evidence on the potential health benefits of F&V, and offers implementation strategies to help ensure that public health messaging is reflective of current science. This review demonstrates that F&V provide benefits beyond helping to achieve basic nutrient requirements in humans. The scientific evidence for providing public health recommendations to increase F&V consumption for prevention of disease is strong. Current evidence suggests that F&V have the strongest effects in relation to prevention of CVDs, noting a nonlinear threshold effect of 800 g per day (i.e., about 5 servings a day). A growing body of clinical evidence (mostly small RCTs) demonstrates effects of specific F&V on certain chronic disease states; however, more research on the role of individual F&V for specific disease prevention strategies is still needed in many areas. Data from the systematic reviews and mostly observational studies cited in this report also support intake of certain types of F&V, particularly cruciferous vegetables, dark-green leafy vegetables, citrus fruits, and dark-colored berries, which have superior effects on biomarkers, surrogate endpoints, and outcomes of chronic disease.

Ubiquinol (Reduced Coenzyme Q10) and Cellular Oxygen Consumption in Patients Undergoing Coronary Artery Bypass Grafting.

Ubiquinol is a fundamental component of cellular metabolism. Low ubiquinol levels have been associated with mortality. This was a substudy of a randomized trial in patients undergoing coronary artery bypass grafting. We drew blood before and after surgery. Ubiquinol or placebo was added to peripheral blood mononuclear cells for oxygen consumption (OCR) measurements. In vivo ubiquinol levels were lower postsurgery compared to presurgery (0.16 µmol/L [quartiles: 0.02-0.39], P = .01), although the difference disappeared when adjusting for hemoglobin levels (P = .30). There was no difference in presurgical basal (1.0 mL/min/mg [95% confidence interval [CI]: -0.9 to 2.2], P = .08) and maximal (0.5 mL/min/mg [95% CI: -4.3 to 7.3], P = .56) OCR in cells receiving ubiquinol or placebo. There was a difference in postsurgical basal (1.1 mL/min/mg [95% CI: 0.9-1.6], P < .001) and maximal (4.2 mL/min/mg [95% CI: 0.3-7.0], P = .01) OCR between the groups. We found no association between ubiquinol and OCR levels (all P > .05).

The effect of egg consumption on cardiometabolic health outcomes: an umbrella review.

OBJECTIVE: This umbrella review provides an overview of the consistency and gaps in the evidence base on eggs and cardiometabolic health. DESIGN: PubMed, Web of Science, Cochrane Library, the Nutrition Evidence Systematic Review and Agency for Healthcare Research and Quality databases were screened for evidence-based reviews in English that assessed human studies on egg consumption and cardiometabolic outcomes. RESULTS: Seven systematic reviews and fifteen meta-analyses were identified, with eighteen of these published since 2015. Overall, the systematic reviews were of low quality, while meta-analyses were of moderate- to high-quality. No association of increased egg intake and risks of heart disease or stroke in the general population were found in the meta-analyses. Increased risk of heart failure was noted in two meta-analyses that analysed the same three cohort studies. Five recent meta-analyses reported no increased risk of type 2 diabetes mellitus (T2DM) in the general population, although increased risk in US-based populations only has been reported. Older (<2013) meta-analyses reported increased risks of cardiovascular disease (CVD) or heart disease in T2DM populations, and no recent evidence-based reviews were identified. Finally, only one meta-analysis reported intervention studies specifically on eggs and biomarkers (i.e. lipids), and the results contradicted those from observation studies. CONCLUSIONS: Recent evidence-based reviews conclude that increased egg consumption is not associated with CVD risk in the general population. More research is needed on the positive associations between egg consumption and heart failure and T2DM risk, as well as CVD risk in diabetics, before firm conclusions can be made.

Efficacy and safety of high-dose vs low-dose leucovorin in patients with colorectal cancer: systematic review and meta-analysis.

AIM: The clinical benefits of a combination of leucovorin and fluorouracil have been established in the treatment of colorectal cancer. Due to a leucovorin shortage in 2008, many institutions revised their protocols to reduce the dose of leucovorin. After the shortage was resolved, some hospitals still maintained their modified protocols. Thus, we conducted a systematic review to evaluate the efficacy and safety of low- vs high-dose leucovorin in the treatment of colorectal cancer. METHOD: The PubMed, Embase and Cochrane databases were searched for studies published before May 2019. The meta-analysis was performed to estimate the pooled effect sizes by using a random effect model. The primary outcomes were median survival time and tumour response rate. Secondary outcomes were haematological and nonhaematological toxicities. RESULTS: Eight randomized controlled trials and four retrospective studies were reviewed. The pooled median survival time was similar between the two dose levels (standard mean difference -0.06, 95% CI -0.19 to 0.08). The pooled tumour response rate was comparatively higher in the high-dose leucovorin regimen (OR 0.81; 95% CI 0.55-1.18). No statistically significant difference was found between the haematological and nonhaematological toxicities of the two groups. However, there were fewer diarrhoea events in the low-dose leucovorin regimen. CONCLUSION: Low-dose leucovorin regimens seemed feasible approaches for colorectal cancer treatment when the shortage happened, because both regimens manifested comparable outcomes in survival time and tumour response rate.

Helicobacter pylori infection and the risk of colorectal cancer: a nationwide population-based cohort study.

BACKGROUND: The role of Helicobacter pylori (H. pylori) infection in the development of colorectal neoplasia has been a matter of scientific debate with controversial findings. AIMS: This study examined the association between H. pylori infection and colorectal cancer (CRC) in a nationwide population-based Chinese cohort study. METHODS: A total of approximately 3936 individuals with newly diagnosed H. pylori infection (the H. pylori-infected cohort) and 15 744 age- and sex-matched patients with diagnoses absence of H. pylori infection (the comparison cohort) from 2000 to 2005 were identified from Taiwan's National Health Insurance Research Database. The Kaplan-Meier method was used for measuring the cumulative incidence of CRC in each cohort. Cox proportional hazards models were used to compute hazard ratios (HRs) and accompanying 95% confidence intervals (CIs) for the estimation of the association between H. pylori infection and CRC. RESULTS: The cumulative incidence of CRC was higher in H. pylori-infected cohort than that in the comparison cohort (log-rank test, P < 0.001). After adjustment for potential confounders, H. pylori infection was associated with a significantly increased risk of CRC (adjusted HR 1.87; 95% CI 1.37-2.57). In addition, the HR of CRC appeared to increase with increasing frequency of clinical visits for H. pylori infection. CONCLUSIONS: Our study demonstrated that H. pylori infection was associated with an increased risk of CRC, which warrants confirmation and exploration of the underlying biologic mechanisms by future studies.

Lycopene Inhibits Smoke-Induced Chronic Obstructive Pulmonary Disease and Lung Carcinogenesis by Modulating Reverse Cholesterol Transport in Ferrets.

Chronic obstructive pulmonary disease (COPD) and lung cancer share the same etiologic factor, cigarette smoking. Higher consumption of dietary lycopene has been associated with lower risks of COPD and lung cancer in smokers. We investigated whether lycopene feeding protects against COPD and lung cancer in ferrets, a nonrodent model that closely mimics cigarette smoke (CS)-induced chronic bronchitis, emphysema, and lung tumorigenesis in human. We also explored whether the protective effect of lycopene is associated with restoring reverse cholesterol transport (RCT), a key driver in persistent inflammation with CS exposure. Ferrets (4 groups, n = 12-16/group) were exposed to a combination of tobacco carcinogen (NNK) and CS with or without consuming lycopene at low and high doses (equivalent to ∼30 and ∼90 mg lycopene/day in human, respectively) for 22 weeks. Results showed that dietary lycopene at a high dose significantly inhibited NNK/CS-induced chronic bronchitis, emphysema, and preneoplastic lesions, including squamous metaplasia and atypical adenomatous hyperplasia, as compared with the NNK/CS alone (P < 0.05). Lycopene feeding also tended to decrease the lung neoplastic lesions. Furthermore, lycopene feeding significantly inhibited NNK/CS-induced accumulation of total cholesterol, and increased mRNA expression of critical genes related to the RCT (PPARα, LXRα, and ATP-binding cassette transporters ABCA1 and ABCG1) in the lungs, which were downregulated by the NNK/CS exposure. The present study has provided the first evidence linking a protective role of dietary lycopene against COPD and preneoplastic lesions to RCT-mediated cholesterol accumulation in lungs.