Ultra-Processed Food Consumption and Long-Term Risk of Irritable Bowel Syndrome: A Large-Scale Prospective Cohort Study.

BACKGROUND & AIMS: The considerable disease burden of irritable bowel syndrome (IBS) has coincided with the increase of ultraprocessed food (UPF) consumption over the past few decades. However, epidemiologic evidence for an association is lacking. We aimed to examine the long-term risk of IBS associated with UPF consumption in a large-scale prospective cohort. METHODS: Participants who completed 24-hour dietary recalls during 2009 to 2012 from the UK Biobank, and free of IBS, celiac disease, inflammatory bowel disease, and any cancer at baseline, were included (N = 178,711; 53.1% female). UPF consumption was defined according to the NOVA food classification system, expressed as a percentage of UPF content in the total diet intake (as grams per day). The primary outcome was incident IBS. A Cox proportional hazard model was performed to estimate associated risk. RESULTS: The mean UPF consumption was 21.0% (SD, 11.0%) of the total diet. During a median of 11.3 years of follow-up, 2690 incident IBS cases were identified. An 8% higher risk of IBS (hazard ratio, 1.08; 95% CI, 1.04-1.12) was associated with every 10% increment of UPF consumption. Compared with the lowest quartile of UPF consumption, the highest quartile was associated with a significantly increased risk of incident IBS (hazard ratio, 1.19; 95% CI, 1.07-1.33; Ptrend < .001). Subgroup analyses by age, sex, body mass index, smoking, and alcohol drinking status also showed similar results, except for the never/previous drinking subgroup. Further sensitivity analyses confirmed the positive association with a higher UPF consumption. CONCLUSIONS: Our findings provide evidence that a higher UPF consumption is associated with an increased risk of incident IBS, with a significant dose-response relationship.

The optimal threshold of PD-L1 combined positive score to predict the benefit of PD-1 antibody plus chemotherapy for patients with HER2-negative gastric adenocarcinoma: a meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line treatment of metastatic gastric and gastroesophageal adenocarcinomas (GEACs). This study aims to figure out the optimal combined positive score (CPS) cutoff value. METHODS: We searched for randomized phase III trials to investigate the efficacy of ICIs plus chemotherapy for metastatic GEACs compared with chemotherapy alone. Pooled analyses of hazard ratios (HRs) based on PD-L1 expression were performed. RESULTS: A total of six trials (KEYNOTE-062, KEYNOTE-590, KEYNOTE-859, ATTRACTION-04, CheckMate 649, and ORIENT-16) were included, comprising 5,242 patients. ICIs plus chemotherapy significantly improved OS (HR: 0.79, 95% CI 0.72-0.86 in global patients; HR: 0.75, 95% CI 0.57-0.98 in Asian patients) and PFS (HR: 0.74, 95% CI 0.68-0.82 in global patients; HR: 0.64, 95% CI 0.56-0.73 in Asian patients) compared with chemotherapy alone. The differences in OS (ratio of HR: 1.05, 95% CI 0.79-1.40; predictive value: - 5.1%) and PFS (ratio of HR: 1.16, 95% CI 0.98-1.36; predictive value: - 13.5%) were not statistically significant between the global and Asian patients. Subgroup analyses indicated that the optimal CPS threshold was at ≥ 5 for OS and ≥ 10 for PFS with the highest predictive values. CONCLUSIONS: The benefit derived from ICIs plus chemotherapy is similar between Asian and global GEAC patients. However, those with a PD-L1 CPS < 5 or CPS < 10 may not have significant benefits from ICIs therapy. Therefore, it is advisable to routinely assess PD-L1 expression in GEAC patients considered for ICIs treatment.

Disheveled3 enhanced EMT and cancer stem-like cells properties via Wnt/ß-catenin/c-Myc/SOX2 pathway in colorectal cancer.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) and cancer stem-like cells (CSLCs) play crucial role in tumor metastasis and drug-resistance. Disheveled3 (DVL3) is involved in malignant behaviors of cancer. However, the role and potential mechanism of DVL3 remain elusive in EMT and CSLCs of colorectal cancer (CRC). METHODS: UALCAN and PrognoScan databases were employed to evaluate DVL3 expression in CRC tissues and its correlation with CRC prognosis, respectively. Transwell, sphere formation and CCK8 assay were used to assess metastasis, stemness and drug sensitivity of CRC cells, respectively. Western blotting and dual luciferase assay were performed to analyze the protein expression and Wnt/ß-catenin activation, respectively. Lentiviral transfection was used to construct the stable cell lines. Animal studies were performed to analyze the effect of silencing DVL3 on tumorigenicity and metastasis of CRC cells in vivo. RESULTS: DVL3 was overexpressed in CRC tissues and several CRC cell lines. DVL3 expression was also higher in CRC tissues with lymph node metastasis than tumor tissues without metastasis, and correlated with poor prognosis of CRC patients. DVL3 positively regulated the abilities of migration, invasion and EMT-like molecular changes in CRC cells. Moreover, DVL3 promoted CSLCs properties and multidrug resistance. We further identified that Wnt/ß-catenin was crucial for DVL3-mediated EMT, stemness and SOX2 expression, while silencing SOX2 inhibited DVL3-mediated EMT and stemness. Furthermore, c-Myc, a direct target gene of Wnt/ß-catenin, was required for SOX2 expression and strengthened EMT and stemness via SOX2 in CRC cells. Finally, knockdown of DVL3 suppressed tumorigenicity and lung metastasis of CRC cells in nude mice. CONCLUSION: DVL3 promoted EMT and CSLCs properties of CRC via Wnt/ß-catenin/c-Myc/SOX2 axis, providing a new strategy for successful CRC treatment.

Azvudine and nirmatrelvir-ritonavir in hospitalized patients with moderate-to-severe COVID-19: Emulation of a randomized target trial.

To examine the effectiveness of azvudine and nirmatrelvir-ritonavir in treating hospitalized patients with moderate-to-severe COVID-19. We emulated a target trial with a multicenter retrospective cohort of hospitalized adults with moderate-to-severe COVID-19 without contraindications for azvudine or nirmatrelvir-ritonavir between December 01, 2022 and January 19, 2023 (during the Omicron BA.5.2 variant wave). Exposures included treatment with azvudine or nirmatrelvir-ritonavir for 5 days versus no antiviral treatment during hospitalization. Primary composite outcome (all-cause death and initiation of invasive mechanical ventilation), and their separate events were evaluated. Of the 1154 patients, 27.2% were severe cases. In the intent-to-treat analyses, azvudine reduced all-cause death (Hazard ratio [HR]: 0.31; 95% CI: 0.12-0.78), and its composite with invasive mechanical ventilation (HR: 0.47; 95% CI: 0.24-0.92). Nirmatrelvir-ritonavir reduced invasive mechanical ventilation (HR: 0.42; 95% CI: 0.17-1.05), and its composite with all-cause death (HR: 0.38; 95% CI: 0.18-0.81). The study did not identify credible subgroup effects. The per-protocol analyses and all sensitivity analyses confirmed the robustness of the findings. Both azvudine and nirmatrelvir-ritonavir improved the prognosis of hospitalized adults with moderate-to-severe COVID-19.

Prevalence of incidental colorectal cancer and polyps in autopsies of different populations: a systematic review with meta-regression analysis.

The colorectal cancer (CRC) and polyps incidentally found in autopsies represent the lesions that have not actually caused problems throughout the lifetime and thus may not need to be removed during screening. This study aimed to investigate the prevalence of incidental CRC (iCRC) and polyps in autopsies of different populations. A systematic search was performed on 19 August 2022 to identify autopsy studies that provided data on prevalence of iCRC, adenomatous polyps, hyperplastic polyps, and/or all polyps combined. The prevalence was pooled with the random-effects model. Subgroup and multivariable meta-regression analyses were conducted to investigate the heterogeneity. Forty-three eligible studies including 59,656 autopsies were identified, with 94% conducted before 1990 when CRC screening was uncommon or not available. The pooled prevalence was 0.7% (95% confidence interval [CI], 0.3-1.2%) for iCRC, 18.4% (95% CI, 13.3-24.1%) for adenomatous polyps, 16.4% (95% CI, 8.7-25.9%) for hyperplastic polyps, 26.3% (95% CI, 15.4-38.8%) for all polyps combined, and 29.9% (95% CI, 14.8-47.6%) for iCRC plus polyps. The prevalence of iCRC was higher (1.2%) in white-predominant populations but lower (0.4%) after excluding low-quality studies. Multivariable analyses showed that the prevalence of polyps was higher in white-predominant populations and higher-quality studies, increased with age, and showed a downward trend from "before 1975" through "after 1985". In conclusion, the prevalence of iCRC in autopsies was not low, considering the average lifetime risk of CRC, while incidental polyps were common. Both varied greatly in different populations. These findings may have implications when weighing the benefits and harms of screening.

Proanthocyanidins inhibited colorectal cancer stem cell characteristics through Wnt/ß-catenin signaling.

BACKGROUND: Cancer stem cells (CSCs) play a key role in tumor cell growth, drug resistance, recurrence, and metastasis. Proanthocyanidins (PC) is widely existed in plants and endowed with powerful antioxidant and anti-aging effects. Interestingly, recent studies have found that PC exhibits the inhibitory effect on tumor growth. However, the role of PC in CSCs of colorectal cancer (CRC) and molecular mechanism remain unclear. METHODS: CCK-8, colony, and tumorsphere formation assay were used to evaluate cancer cell viability and stemness, respectively. Western blotting was used to detect the protein expression. Tumor xenograft experiments were employed to examine the tumorigenicity of CRC cells in nude mice. RESULTS: PC decreased the proliferation of CRC cells (HT29 and HCT-116), and improved the sensitivity of CRC cells to oxaliplatin (L-OHP), as well as inhibited tumor growth in nude mice. Further studies showed that PC also down-regulated CSCs surface molecular and stemness transcriptional factors, while suppressed the formations of tumorspheres and cell colony in CRC. In addition, PC-impaired proteins expressions of p-GSK3ß, ß-catenin and DVL1-3. LiCl, an activator of the Wnt/ß-catenin signaling, rescued PC-induced downregulation of CSCs markers, and reduction of tumorspheres and cell colony formation abilities in CRC cells. Furthermore, the effects of PC on inhibiting cell proliferation and enhancing L-OHP sensitivity were impaired by LiCl. CONCLUSIONS: PC exerted an inhibitory effect on CSCs via Wnt/ß-catenin in CRC, and may be a potential new class of natural drug for CRC treatment.

Dihydroartemisinin inhibited stem cell-like properties and enhanced oxaliplatin sensitivity of colorectal cancer via AKT/mTOR signaling.

Colorectal cancer (CRC) is a common tumor with high morbidity and mortality. The use of oxaliplatin (L-OHP) as a first-line treatment for CRC is limited due to chemoresistance. Growing evidence have revealed that the existence of cancer stem-like cells (CSLCs) is one of the important reasons for drug resistance and recurrence of cancers. Dihydroartemisinin (DHA), a derivative of artemisinin, has showed anticancer effects on a variety of malignancies, in addition to its antimalarial effects. However, the effect and mechanism of DHA on CSLCs and chemosensitivity in CRC cells remains unclear. In this study, we found that DHA inhibited cell viability in HCT116 and SW620 cells. Moreover, DHA decreased cell clonogenicity, and improved L-OHP sensitivity. Furthermore, DHA treatment attenuated tumor sphere formation, and the expressions of stem cell surface marker (CD133 and CD44) and stemness-associated transcription factor (Nanog, c-Myc, and OCT4). Mechanistically, the present findings showed that DHA inhibited of AKT/mTOR signaling pathway. The activation of AKT/mTOR signaling reversed DHA-decreased cell viability, clonogenicity, L-OHP resistance, tumor sphere, and expressions of stemness-associated protein in CRC. The inhibitory effect of DHA on tumorigenicity of CRC cells has also been demonstrated in BALB/c nude mice. In conclusion, this study revealed that DHA inhibited CSLCs properties in CRC via AKT/mTOR signaling, suggesting that DHA may be used as a potential therapeutic agent for CRC.

Direct Catalytic Asymmetric and Regiodivergent N1- and C3-Allenylic Alkylation of Indoles.

Herein we report a Pd-catalyzed asymmetric allenylic alkylation strategy for the direct functionalization of 1H-indoles by employing P-chiral BIBOP-type ligands. The regioselectivity (N1/C3) of this process can be switched efficiently. Using Cs2 CO3 at elevated temperatures in MeCN, N1-alkylated indoles bearing axial chirality with a stereocenter non-adjacent (ß) to the nitrogen are produced in good yields with high enantioselectivity and complete N1-regioselectivity regardless of the electronic properties and substitution patterns of diverse indoles. Using K2 CO3 at room temperature in CH2 Cl2 , chiral C3-alkylated indoles can also be obtained. Notably, we introduce a new class of tri-substituted allenylic electrophiles that proceeded through different pathways from di-substituted allenylic electrophiles.

Ruthenium/TiO2 -Catalyzed Hydrogenolysis of Polyethylene Terephthalate: Reaction Pathways Dominated by Coordination Environment.

Polyethylene terephthalate (PET) hydrogenolysis can produce benzene, toluene, and xylene (BTX), where the selectivity control is challenging. We report a reaction pathway dictated by the Ru coordination environment by examining the binding geometries of adsorbates on differently coordinated Ru centers and their evolution during PET hydrogenolysis. A BTX yield of 77 % was obtained using a Ru/TiO2 with a Ru coordination number of ca. 5.0 where edge/corner sites are dominant, while more gas and saturated products were formed for Ru/TiO2 containing primarily terrace sites. Density functional theory and isotopic labelling revealed that under-coordinated Ru edge sites favor "upright" adsorption of aromatic adsorbates while well-coordinated Ru sites favor "flat-lying" adsorption, where the former mitigates ring hydrogenation and opening. This study demonstrates that reaction pathways can be directed through controlled reactant/intermediate binding via tuning of the Ru coordination environment for efficient conversion of PET to BTX.

Irritable Bowel Syndrome and Long-Term Risk of Cancer: A Prospective Cohort Study Among 0.5 Million Adults in UK Biobank.

INTRODUCTION: To investigate the prospective association of irritable bowel syndrome (IBS) with long-term risk of overall, site-specific cancer and cancer-specific mortality in general population. METHODS: Participants free of inflammatory bowel disease, celiac disease, and any cancer at baseline from the UK Biobank were included, with patients with IBS as the exposure group and non-IBS patients as the reference group. The primary outcome was the incidence of overall cancer and cancer-specific mortality. Secondary outcomes included site-specific cancers and types of digestive cancers. The Cox proportional hazard model was used to investigate the associated risk of incident malignancies and related mortality. RESULTS: Among 449,595 participants, 22,338 (5.0%) were diagnosed with IBS. During a median of 12.2-year follow-up, 2,937 cases of incident cancer were identified in patients with IBS (11.47 per 1,000 person-years), compared with 60,556 cases in reference individuals (12.51 per 1,000 person-years). Of these cases, 512 and 12,282 cancer-specific deaths occurred in IBS and non-IBS groups. Compared with non-IBS, the adjusted hazard ratio for overall cancer and cancer-specific mortality was 0.97 (95% confidence interval: 0.93-1.00, P = 0.062) and 0.83 (0.76-0.91, P < 0.001) among patients with IBS. Specifically, decreased risk of digestive (0.79 [0.71-0.89]), particularly colon (0.75 [0.62-0.90]) and rectal (0.68 [0.49-0.93]), cancers was observed in patients with IBS. Further sensitivity analysis and subgroup analysis by age and sex indicated similar results. DISCUSSION: Compared with the general population, IBS does not increase the overall risk of cancer. Conversely, IBS is associated with lower risk of incident colorectal cancer and cancer-specific mortality.

Non-alcoholic fatty liver is associated with increased risk of irritable bowel syndrome: a prospective cohort study.

BACKGROUND: The relationship between non-alcoholic fatty liver degree as well as non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS) remains poorly understood. We aimed to investigate the prospective association of non-alcoholic fatty liver degree as well as NAFLD with incident IBS in a large-scale population-based cohort. METHODS: Participants free of IBS, coeliac disease, inflammatory bowel disease, alcoholic liver disease, and any cancer at baseline from the UK Biobank were included. Non-alcoholic fatty liver degree was measured by a well-validated fatty liver index (FLI), with FLI ≥ 60 as an indicator of NAFLD. Primary outcome was incident IBS. Cox proportional hazard model was used to investigate the associated risk of incident IBS. RESULTS: Among 396,838 participants (mean FLI was 48.29 ± 30.07), 153,203(38.6%) were with NAFLD diagnosis at baseline. During a median of 12.4-year follow-up, 7129 cases of incident IBS were identified. Compared with non-NAFLD, NAFLD patients showed a 13% higher risk of developing IBS (HR = 1.13, 95%CI: 1.05-1.17) after multivariable adjustment. Compared with the lowest, the highest FLI quartile was associated with a significantly increased risk of IBS (HRQ4 VS Q1 = 1.21, 1.13-1.30, Ptrend < 0.001). Specifically, the positive association between non-alcoholic fatty liver degree and IBS was also observed by per SD change of FLI (adjusted HR = 1.08, 1.05-1.10). Further sensitivity analysis and subgroup analysis indicated similar results, with the positive association particularly observed in females, but not in males. CONCLUSIONS: High degree of non-alcoholic fatty liver as well as non-alcoholic fatty liver disease is associated with increased risk of incident IBS. Further studies are warranted to confirm the findings and elucidate the underlying biological mechanisms.

Association of major blood lipids with post-stroke dementia: A community-based cohort study.

BACKGROUND AND PURPOSE: The roles of blood low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides in the development of post-stroke dementia remain uncertain. This study was to investigate their potential associations. METHODS: A retrospective cohort study was conducted using the Clinical Practice Research Datalink. Patients with first-ever stroke but no prior dementia were followed up for 10 years. Cox regression was used to examine the association of baseline LDL-C, HDL-C and triglycerides with post-stroke dementia. RESULTS: Amongst 63,959 stroke patients, 15,879 had complete baseline data and were included in our main analysis. 10.8% developed dementia during a median of 4.6 years of follow-up. The adjusted hazard ratio of dementia for LDL-C (per log mmol/l increase) was 1.29 (95% confidence interval [CI] 1.14-1.47), with a linear increasing trend (p trend <0.001). The counterpart for triglycerides was 0.79 (95% CI 0.69-0.89), with a linear decreasing trend (p trend <0.001). For HDL-C, there was no association with dementia (adjusted hazard ratio 0.89, 95% CI 0.74-1.08) or a linear trend (p trend = 0.22). CONCLUSIONS: Blood lipids may affect the risk of post-stroke dementia in different ways, with higher risk associated with LDL-C, lower risk associated with triglycerides, and no association with HDL-C.

A water-soluble fluorescent probe for real-time visualization of γ-glutamyl transpeptidase activity in living cells.

γ-glutamyl transpeptidase (GGT) is a kind of cell-surface enzyme that is overexpressed in many cancer cells. It is of great significance to develop an ideal tool for the diagnosis of GGT-rich cancer cells. Here, we reported a simple-structured but effective imaging probe for the detection of GGT activity. In the presence of GGT, the γ-glutamyl linkage could be cleaved specifically to produce amino-substituted product, resulting in significant fluorescence enhancement at 578 nm. Moreover, we successfully employed the probe to monitor GGT activity in HepG2 cells. We envisaged that such a simple but effective imaging tool could improve the practical applications for bioimaging.

The hsa_circ_0039857/miR-338-3p/RAB32 axis promotes the malignant progression of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a prevalent malignancy of the gastrointestinal. Circular RNAs (circRNAs) act as important roles in CRC malignant progression. However, the role of circ_0039857 in CRC is still unclear. Therefore, this study aimed to explore the function and mechanism of hsa_circ_0039857 in the CRC. METHODS: The mRNA and protein expression were measured via RT-qPCR. RNase R assay and Actinomycin D were employed to evaluate the stability of circ_0039857. Functional experiments, such as proliferation and apoptosis, were applied to study the function of circ_0039857 in CRC cells. The underlying mechanisms of circ_0039857 were then analyzed by bioinformatics, dual-luciferase reporter gene assay, RNA pull-down and rescue experiments. RESULTS: We revealed that circ_0039857 was significantly enhanced in CRC. Circ_0039857 was stabler than linear RNA in cells and valuable for the disease diagnosis. In addition, circ_0039857 knockdown inhibited proliferation and promoted apoptosis. Mechanistically, circ_0039857 positively regulated the expression of RAB32 via sponging miR-338-3p. CONCLUSION: This study demonstrated that circ_0039857 knockdown suppressed CRC malignant progression through miR-338-3p/RAB32 axis. Most importantly, this will help us to better understand the circRNA network in CRC, and may find potential biomarkers and targets for CRC clinical treatment.

Statin use is associated with lower risk of dementia in stroke patients: a community-based cohort study with inverse probability weighted marginal structural model analysis.

Current evidence is inconclusive on cognitive benefits or harms of statins among stroke patients, who have high risk of dementia. This observational cohort study investigated the association between statin use and post-stroke dementia using data from the Clinical Practice Research Datalink. Patients without prior dementia who had an incident stroke but received no statins in the preceding year were followed for up to 10 years. We used inverse probability weighted marginal structural models to estimate observational analogues of intention-to-treat (ITT, statin initiation vs. no initiation) and per-protocol (PP, sustained statin use vs. no use) effects on the risk of dementia. To explore potential impact of unmeasured confounding, we examined the risks of coronary heart disease (CHD, positive control outcome), fracture and peptic ulcer (negative control outcomes). In 18,577 statin initiators and 14,613 non-initiators (mean follow-up of 4.2 years), the adjusted hazard ratio (aHR) for dementia was 0.70 (95% confidence interval [CI] 0.64-0.75) in ITT analysis and 0.55 (95% CI 0.50-0.62) in PP analysis. The corresponding aHRITT and aHRPP were 0.87 (95% CI 0.79-0.95) and 0.70 (95% CI 0.62-0.80) for CHD, 1.03 (95% CI 0.82-1.29) and 1.09 (95% CI 0.77-1.54) for peptic ulcer, and 0.88 (95% CI 0.80-0.96) and 0.86 (95% CI 0.75-0.98) for fracture. Statin initiation after stroke was associated with lower risk of dementia, with a potentially greater benefit in patients who persisted with statins over time. The observed association of statin use with post-stroke dementia may in part be overestimated due to unmeasured confounding shared with the association between statin use and fracture.

Translation and validation of the Chinese version of the MD Anderson symptom inventory for measuring perioperative symptom burden in patients with gynecologic cancer.

BACKGROUND: Gynecologic cancers are among the most prevalent malignancies in China. Cervical and uterine cancer respectively account for the sixth and eighth highest incidence of cancer among Chinese women. Abdominal surgery is one of the important treatment methods for gynecological tumors. However, the tumor- and surgery-related symptom burden are not well studied owing to a lack of a standardized and validated assessment tool in the Chinese population. The study aimed to translate and validate the MD Anderson Symptom Inventory for measuring perioperative symptom burden in gynecologic cancer patients (MDASI-PeriOp-GYN) and examine the utility of the Chinese version of MDASI-PeriOp-GYN. METHODS: The MDASI-PeriOp-GYN was translated in a stepwise manner. First, two native speakers independently translated the 9 PeriOp-GYN symptom items. Then the nine items were translated back into English by two different bilingual translators. After discussion and revision, the four translators reached an agreement. Finally, the finalized Chinese version was administered to women with three common gynecologic cancer types (cervical, ovarian, and endometrial cancers) recruited from the gynecological oncology department of Sichuan Cancer Hospital & Institute between July and October 2019. The reliability and validity of the translated version were assessed. RESULTS: Overall, 324 women with gynecologic cancers were enrolled. Cronbach's α values were 0.826 and 0.735 for the symptom severity and interference scales, respectively. Test-retest reliability values were 0.885, 0.873, and 0.914 for symptom severity, PeriOp-GYN, and interference scales. Significant correlations were found between the MDASI-PeriOp-GYN-C and EORTC QLQ-C30 along with the QLQ-OV28 module (- 0.608-0.871, P < 0.001). Known-group validity was supported by significant differences in the scores of the four scales grouped by time intervals, surgery type, and functional status (all P < 0.01). CONCLUSIONS: The MDASI-PeriOp-GYN-C is a valid and reliable tool for measuring symptoms in Chinese patients undergoing surgery for gynecologic cancers. The tool could be used in clinical practice and clinical trials to instantly gather patients' health and quality of life data.

Sulphonylureas monotherapy and risk of hospitalization for heart failure in patients with type 2 diabetes mellitus: A population-based cohort study in China.

PURPOSE: The risk of heart failure associated with sulphonylureas is unclear. We evaluated the association between sulphonylureas and hospitalization of heart failure (HHF) in patients with type 2 diabetes mellitus (T2DM) in China. METHODS: A retrospective cohort study was implemented using the Yinzhou Regional Health Care Database (YRHCD). We identified 15 752 adult patients with T2DM who were newly exposed to sulphonylurea monotherapy (N = 12 487) or acarbose monotherapy (N = 3265) from January 2010 to September 2016. Cox proportional hazards models weighted by inverse probability of treatment weights were used to compare the risk of HHF between initiators of sulphonylurea and acarbose. RESULTS: During a median follow-up of 0.55 (0.49, 1.11) and 0.49 (0.35, 0.70) years for sulphonylureas and acarbose initiators separately, 320 patients developed HHF, with 279 events in sulphonylureas group, and 41 events in acarbose group. The incidence rates of HHF among sulphonylureas initiators and acarbose initiators were 22.2 (95% CI 19.6-24.9) and 18.3 (95% CI 13.2-24.9) per 1000 person-years, respectively. The adjusted hazard ratio (aHR) of HHF for sulphonylureas vs acarbose was 1.61 (95% CI 1.14-2.27). When stratified by history of heart failure, aHR was 1.55 (95% CI 0.79-3.06) in patients with a history of heart failure, and 1.64 (95% CI 1.10-2.45) in patients with no history of heart failure. CONCLUSIONS: Our study suggested that use of sulphonylureas monotherapy compared with acarbose monotherapy for initial treatment of T2DM for approximately 0.5 years are significantly associated with a higher risk of HHF.

Topical benzoyl peroxide for acne.

BACKGROUND: Acne is a common, economically burdensome condition that can cause psychological harm and, potentially, scarring. Topical benzoyl peroxide (BPO) is a widely used acne treatment; however, its efficacy and safety have not been clearly evaluated. OBJECTIVES: To assess the effects of BPO for acne. SEARCH METHODS: We searched the following databases up to February 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of relevant randomised controlled trials (RCTs) and systematic reviews. SELECTION CRITERIA: We included RCTs that compared topical BPO used alone (including different formulations and concentrations of BPO) or as part of combination treatment against placebo, no treatment, or other active topical medications for clinically diagnosed acne (used alone or in combination with other topical drugs not containing BPO) on the face or trunk. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. Primary outcome measures were 'participant global self-assessment of acne improvement' and 'withdrawal due to adverse events in the whole course of a trial'. 'Percentage of participants experiencing any adverse event in the whole course of a trial' was a key secondary outcome. MAIN RESULTS: We included 120 trials (29,592 participants randomised in 116 trials; in four trials the number of randomised participants was unclear). Ninety-one studies included males and females. When reported, 72 trials included participants with mild to moderate acne, 26 included participants with severe acne, and the mean age of participants ranged from 18 to 30 years. Our included trials assessed BPO as monotherapy, as add-on treatment, or combined with other active treatments, as well as BPO of different concentrations and BPO delivered through different vehicles. Comparators included different concentrations or formulations of BPO, placebo, no treatment, or other active treatments given alone or combined. Treatment duration in 80 trials was longer than eight weeks and was only up to 12 weeks in 108 trials. Industry funded 50 trials; 63 trials did not report funding. We commonly found high or unclear risk of performance, detection, or attrition bias. Trial setting was under-reported but included hospitals, medical centres/departments, clinics, general practices, and student health centres. We reported on outcomes assessed at the end of treatment, and we classified treatment periods as short-term (two to four weeks), medium-term (five to eight weeks), or long-term (longer than eight weeks). For 'participant-reported acne improvement', BPO may be more effective than placebo or no treatment (risk ratio (RR) 1.27, 95% confidence interval (CI) 1.12 to 1.45; 3 RCTs; 2234 participants; treatment for 10 to 12 weeks; low-certainty evidence). Based on low-certainty evidence, there may be little to no difference between BPO and adapalene (RR 0.99, 95% CI 0.90 to 1.10; 5 RCTs; 1472 participants; treatment for 11 to 12 weeks) or between BPO and clindamycin (RR 0.95, 95% CI 0.68 to 1.34; 1 RCT; 240 participants; treatment for 10 weeks) (outcome not reported for BPO versus erythromycin or salicylic acid). For 'withdrawal due to adverse effects', risk of treatment discontinuation may be higher with BPO compared with placebo or no treatment (RR 2.13, 95% CI 1.55 to 2.93; 24 RCTs; 13,744 participants; treatment for 10 to 12 weeks; low-certainty evidence); the most common causes of withdrawal were erythema, pruritus, and skin burning. Only very low-certainty evidence was available for the following comparisons: BPO versus adapalene (RR 1.85, 95% CI 0.94 to 3.64; 11 RCTs; 3295 participants; treatment for 11 to 24 weeks; causes of withdrawal not clear), BPO versus clindamycin (RR 1.93, 95% CI 0.90 to 4.11; 8 RCTs; 3330 participants; treatment for 10 to 12 weeks; causes of withdrawal included local hypersensitivity, pruritus, erythema, face oedema, rash, and skin burning), erythromycin (RR 1.00, 95% CI 0.07 to 15.26; 1 RCT; 60 participants; treatment for 8 weeks; withdrawal due to dermatitis), and salicylic acid (no participants had adverse event-related withdrawal; 1 RCT; 59 participants; treatment for 12 weeks). There may be little to no difference between these groups in terms of withdrawal; however, we are unsure of the results because the evidence is of very low certainty. For 'proportion of participants experiencing any adverse event', very low-certainty evidence leaves us uncertain about whether BPO increased adverse events when compared with placebo or no treatment (RR 1.40, 95% CI 1.15 to 1.70; 21 RCTs; 11,028 participants; treatment for 10 to 12 weeks), with adapalene (RR 0.71, 95% CI 0.50 to 1.00; 7 RCTs; 2120 participants; treatment for 11 to 24 weeks), with erythromycin (no participants reported any adverse events; 1 RCT; 89 participants; treatment for 10 weeks), or with salicylic acid (RR 4.77, 95% CI 0.24 to 93.67; 1 RCT; 41 participants; treatment for 6 weeks). Moderate-certainty evidence shows that the risk of adverse events may be increased for BPO versus clindamycin (RR 1.24, 95% CI 0.97 to 1.58; 6 RCTs; 3018 participants; treatment for 10 to 12 weeks); however, the 95% CI indicates that BPO might make little to no difference. Most reported adverse events were mild to moderate, and local dryness, irritation, dermatitis, erythema, application site pain, and pruritus were the most common. AUTHORS' CONCLUSIONS: Current evidence suggests that BPO as monotherapy or add-on treatment may be more effective than placebo or no treatment for improving acne, and there may be little to no difference between BPO and either adapalene or clindamycin. Our key efficacy evidence is based on participant self-assessment; trials of BPO versus erythromycin or salicylic acid did not report this outcome. For adverse effects, the evidence is very uncertain regarding BPO compared with adapalene, erythromycin, or salicylic acid. However, risk of treatment discontinuation may be higher with BPO compared with placebo or no treatment. Withdrawal may be linked to tolerability rather than to safety. Risk of mild to moderate adverse events may be higher with BPO compared with clindamycin. Further trials should assess the comparative effects of different preparations or concentrations of BPO and combination BPO versus monotherapy. These trials should fully assess and report adverse effects and patient-reported outcomes measured on a standardised scale.

Orbital teratoma in the foetus: a rare case without proptosis.

BACKGROUND: Congenital orbital teratoma is relatively rare, and few reports of prenatal ultrasound findings in such cases have been published. CASE PRESENTATION: A rare case of congenital orbital teratoma at 24 + 2 weeks of gestation was previously diagnosed as microphthalmia, noting how orbital teratoma without proptosis is different from microphthalmia, retinoblastoma and intracranial teratoma. Ultrasound examination, analysis of gross specimens, and histopathological evaluation confirmed the diagnosis of orbital teratoma. CONCLUSION: Prenatal ultrasound examination is useful for diagnosis and differential diagnosis of congenital orbital teratoma.

The effects of incretin-based therapies on ß-cell function and insulin resistance in type 2 diabetes: A systematic review and network meta-analysis combining 360 trials.

AIM: To evaluate the comparative effects of incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 inhibitors (DPP-4Is), on ß-cell function and insulin resistance in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Medline, Embase, the Cochrane Library and www.clinicaltrials.gov were searched for randomized controlled trials (RCTs) with a duration of at least 4 weeks. Network meta-analysis was performed, followed by subgroup analysis and meta-regression. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the quality of evidence. Outcomes of interest include homeostasis model assessment for ß cell function (HOMA-ß) and insulin resistance (HOMA-IR), fasting C-peptide and fasting plasma glucose (FPG). Weighted mean difference (WMD) with 95% confidence interval (CI) was calculated as the measure of effect size. RESULTS: A total of 360 RCTs (74% at least double-blinded) with 157 696 patients were included. Incretin-based therapies were compared with six other classes of glucose-lowering drugs or with placebo. Compared with placebo, a significant increase in HOMA-ß and fasting C-peptide was detected for GLP-1RAs (WMD = 20.31 [95% CI, 16.34-24.39] with low quality; WMD = 0.16 ng/mL [95% CI, 0.03-0.29] with low quality) and for DPP-4Is (WMD = 9.90 [95% CI, 8.27-11.61] with moderate quality; WMD = 0.09 ng/mL [95% CI, 0.04-0.14] with moderate quality) separately, while a significant reduction in HOMA-IR and FPG were found in favour of GLP-1RAs (WMD = -0.67 [95% CI, -1.08 to -0.27] with low quality; WMD = -1.04 mmol/L [95% CI, -1.26 to -0.83] with moderate quality) and DPP-4Is (WMD = -0.23 [95% CI, -0.38 to -0.08] with low quality; WMD = -0.77 mmol/L [95% CI, -0.98 to -0.57] with moderate quality), respectively. CONCLUSIONS: Incretin-based therapies not only show an increase in HOMA-ß and fasting C-peptide level, but also achieve a reduction in HOMA-IR and FPG in comparison with placebo. Although GRADE scores indicate low to moderate for most comparisons, incretin-based therapies seem to be an advisable option for long-term treatment to preserve ß-cell function.