Evening versus morning dosing regimen drug therapy for hypertension.

BACKGROUND: Variation in blood pressure levels display circadian rhythms. Complete 24-hour blood pressure control is the primary goal of antihypertensive treatment and reducing adverse cardiovascular outcomes is the ultimate aim. This is an update of the review first published in 2011. OBJECTIVES: To evaluate the effectiveness of administration-time-related effects of once-daily evening versus conventional morning dosing antihypertensive drug therapy regimens on all-cause mortality, cardiovascular mortality and morbidity, total adverse events, withdrawals from treatment due to adverse effects, and reduction of systolic and diastolic blood pressure in people with primary hypertension. SEARCH METHODS: We searched the Cochrane Hypertension Specialised Register via Cochrane Register of Studies (17 June 2022), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6, 2022); MEDLINE, MEDLINE In-Process and MEDLINE Epub Ahead of Print (1 June 2022); Embase (1 June 2022); ClinicalTrials.gov (2 June 2022); Chinese Biomedical Literature Database (CBLD) (1978 to 2009); Chinese VIP (2009 to 7 August 2022); Chinese WANFANG DATA (2009 to 4 August 2022); China Academic Journal Network Publishing Database (CAJD) (2009 to 6 August 2022); Epistemonikos (3 September 2022) and the reference lists of relevant articles. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the administration-time-related effects of evening with morning dosing monotherapy regimens in people with primary hypertension. We excluded people with known secondary hypertension, shift workers or people with white coat hypertension. DATA COLLECTION AND ANALYSIS: Two to four review authors independently extracted data and assessed trial quality. We resolved disagreements by discussion or with another review author. We performed data synthesis and analyses using Review Manager Web for all-cause mortality, cardiovascular mortality and morbidity, serious adverse events, overall adverse events, withdrawals due to adverse events, change in 24-hour blood pressure and change in morning blood pressure. We assessed the certainty of the evidence using GRADE. We conducted random-effects meta-analysis, fixed-effect meta-analysis, subgroup analysis and sensitivity analysis. MAIN RESULTS: We included 27 RCTs in this updated review, of which two RCTs were excluded from the meta-analyses for lack of data and number of groups not reported. The quantitative analysis included 25 RCTs with 3016 participants with primary hypertension. RCTs used angiotensin-converting enzyme inhibitors (six trials), calcium channel blockers (nine trials), angiotensin II receptor blockers (seven trials), diuretics (two trials), α-blockers (one trial), and ß-blockers (one trial). Fifteen trials were parallel designed, and 10 trials were cross-over designed. Most participants were white, and only two RCTs were conducted in Asia (China) and one in Africa (South Africa). All trials excluded people with risk factors of myocardial infarction and strokes. Most trials had high risk or unclear risk of bias in at least two of several key criteria, which was most prominent in allocation concealment (selection bias) and selective reporting (reporting bias). Meta-analysis showed significant heterogeneity across trials. No RCTs reported on cardiovascular mortality and cardiovascular morbidity. There may be little to no differences in all-cause mortality (after 26 weeks of active treatment: RR 0.49, 95% CI 0.04 to 5.42; RD 0, 95% CI -0.01 to 0.01; very low-certainty evidence), serious adverse events (after 8 to 26 weeks of active treatment: RR 1.17, 95% CI 0.53 to 2.57; RD 0, 95% CI -0.02 to 0.03; very low-certainty evidence), overall adverse events (after 6 to 26 weeks of active treatment: RR 0.89, 95% CI 0.67 to 1.20; I² = 37%; RD -0.02, 95% CI -0.07 to 0.02; I² = 38%; very low-certainty evidence) and withdrawals due to adverse events (after 6 to 26 weeks active treatment: RR 0.76, 95% CI 0.47 to 1.23; I² = 0%; RD -0.01, 95% CI -0.03 to 0; I² = 0%; very low-certainty evidence), but the evidence was very uncertain. AUTHORS' CONCLUSIONS: Due to the very limited data and the defects of the trials' designs, this systematic review did not find adequate evidence to determine which time dosing drug therapy regimen has more beneficial effects on cardiovascular outcomes or adverse events. We have very little confidence in the evidence showing that evening dosing of antihypertensive drugs is no more or less effective than morning administration to lower 24-hour blood pressure. The conclusions should not be assumed to apply to people receiving multiple antihypertensive drug regimens.

Artificial intelligence for diagnosing microvessels of precancerous lesions and superficial esophageal squamous cell carcinomas: a multicenter study.

BACKGROUND: Intrapapillary capillary loop (IPCL) is an important factor for predicting invasion depth of esophageal squamous cell carcinoma (ESCC). The invasion depth is closely related to the selection of treatment strategy. However, diagnosis of IPCLs is complicated and subject to interobserver variability. This study aimed to develop an artificial intelligence (AI) system to predict IPCLs subtypes of precancerous lesions and superficial ESCC. METHODS: Images of magnifying endoscopy with narrow band imaging from three hospitals were collected retrospectively. IPCLs subtypes were annotated on images by expert endoscopists according to Japanese Endoscopic Society classification. The performance of the AI system was evaluated using internal and external validation datasets (IVD and EVD) and compared with that of the 11 endoscopists. RESULTS: A total of 7094 images from 685 patients were used to train and validate the AI system. The combined accuracy of the AI system for diagnosing IPCLs subtypes in IVD and EVD was 91.3% and 89.8%, respectively. The AI system achieved better performance than endoscopists in predicting IPCLs subtypes and invasion depth. The ability of junior endoscopists to diagnose IPCLs subtypes (combined accuracy: 84.7% vs 78.2%, P < 0.0001) and invasion depth (combined accuracy: 74.4% vs 67.9%, P < 0.0001) were significantly improved with AI system assistance. Although there was no significant differences, the performance of senior endoscopists was slightly elevated. CONCLUSIONS: The proposed AI system could improve the diagnostic ability of endoscopists to predict IPCLs classification of precancerous lesions and superficial ESCC.

Successful cholangioscopic electrocoagulation for biliary papillomatosis: Report covering six cases (with video).

BACKGROUND: Biliary papillomatosis is a rare type of papillomatosis. Depending on the location of the disease, radical surgical resection or liver transplants are the treatment of choice. These radical surgical options may be unrealistic in patients who are not surgical candidates or who are unwilling to consider surgery. AIMS: To evaluate the effectiveness of endoscopic electrocoagulation for the biliary papillomatosis. METHODS: In this case series, we report six patients with unresectable biliary papillomatosis who underwent cholangioscopic electrocoagulation using needle knife and their clinic follow up information. RESULTS: After patients received cholangioscopy with electrocoagulation of the residual biliary papilloma, the daily T-tube drainage volume increased to 200-400ml with improvement in the drainage content and significant relief of clinical symptoms, such as jaundice and abdominal pain. CONCLUSION: This method of using electrocoagulation to directly target and destroy tumor tissue is a safe and effective alternative for those with unresectable disease, and this method has shown to enhance T-tube drainage volume and improve patients' overall clinical symptoms.

Real-time automated diagnosis of precancerous lesions and early esophageal squamous cell carcinoma using a deep learning model (with videos).

BACKGROUND AND AIMS: We developed a system for computer-assisted diagnosis (CAD) for real-time automated diagnosis of precancerous lesions and early esophageal squamous cell carcinomas (ESCCs) to assist the diagnosis of esophageal cancer. METHODS: A total of 6473 narrow-band imaging (NBI) images, including precancerous lesions, early ESCCs, and noncancerous lesions, were used to train the CAD system. We validated the CAD system using both endoscopic images and video datasets. The receiver operating characteristic curve of the CAD system was generated based on image datasets. An artificial intelligence probability heat map was generated for each input of endoscopic images. The yellow color indicated high possibility of cancerous lesion, and the blue color indicated noncancerous lesions on the probability heat map. When the CAD system detected any precancerous lesion or early ESCCs, the lesion of interest was masked with color. RESULTS: The image datasets contained 1480 malignant NBI images from 59 consecutive cancerous cases (sensitivity, 98.04%) and 5191 noncancerous NBI images from 2004 cases (specificity, 95.03%). The area under curve was 0.989. The video datasets of precancerous lesions or early ESCCs included 27 nonmagnifying videos (per-frame sensitivity 60.8%, per-lesion sensitivity, 100%) and 20 magnifying videos (per-frame sensitivity 96.1%, per-lesion sensitivity, 100%). Unaltered full-range normal esophagus videos included 33 videos (per-frame specificity 99.9%, per-case specificity, 90.9%). CONCLUSIONS: A deep learning model demonstrated high sensitivity and specificity for both endoscopic images and video datasets. The real-time CAD system has a promising potential in the near future to assist endoscopists in diagnosing precancerous lesions and ESCCs.

Risk factors for distal migration of biliary plastic stents and related duodenal injury.

BACKGROUND: The risk factors of duodenal injury from distal migrated biliary plastic stents remain uncertain. The aim of this study was to determine the risk factors of distal migration and its related duodenal injury in patients who underwent placement of a single biliary plastic stent for biliary strictures. METHODS: We retrospectively reviewed all patients with biliary strictures who underwent endoscopic placement of a single biliary plastic stent from January 2006 to October 2017. RESULTS: Two hundred forty-eight patients with 402 endoscopic retrograde cholangiopancreatography procedures were included. The incidence of distal migration was 6.2%. The frequency of duodenal injury was 2.2% in all cases and 36% in cases with distal migration. Benign biliary strictures (BBS), length of the stent above the proximal end of the stricture (> 2 cm), and duration of stent retention (< 3 months) were independently associated with distal migration (p = 0.018, p = 0.009, and p = 0.016, respectively). Duodenal injury occurred more commonly in cases with larger angle (≥ 30°) between the distal end of the stent and the centerline of the patient's body (p = 0.018) or in cases with stent retention < 3 months (p = 0.031). CONCLUSIONS: The risk factors of distal migration are BBS and the length of the stent above the proximal end of the stricture. The risk factor of duodenal injury due to distal migration is large angle (≥ 30°) between the distal end of the stent and the centerline of the patient's body. Distal migration and related duodenal injury are more likely to present during the early period after biliary stenting.

Transcriptional response of USP18 predicts treatment outcomes of interferon-alpha in HBeAg-positive chronic hepatitis B patientsefere.

Ubiquitin-specific protease 18 (USP18) is an important inhibitor of interferon (IFN) antiviral activity, and the aim of this study was to investigate the association between the USP18 mRNA level change in peripheral blood mononuclear cells (PBMCs) when stimulated with IFN in vitro before initiating treatment and the treatment outcomes in HBeAg-positive chronic hepatitis B (CHB) patients treated with IFN. A total of 44 patients who received standard IFN-based anti-HBV therapy and follow-up were enrolled in the study. The in vitro IFN-induced USP18 mRNA change (USP18IFN-N ) was measured via comparison of quantitative PCR-determined USP18 transcription levels of BPMCs cultured with and without IFN stimulation. Either for virological (VR) or serological response (SR), the baseline USP18IFN-N was significantly higher (P = 0.018 for VR, P = 0.008 for SR) among nonresponders (n = 23 for VR, n = 33 for SR) than that of responders (n = 21 for VR, n = 11 for SR). Multivariate analyses revealed baseline USP18IFN-N was a novel independent predictor for either VR (OR = 0.292, 95% CI = 0.102-0.835, P = 0.022) or SR (OR = 0.173, 95% CI = 0.035-0.849, P = 0.031) in our cohort. In addition, baseline USP18IFN-N in combination with HBV DNA loads or HBeAg levels showed improved accuracy of pretreatment prediction for VR or SR responders, respectively. Baseline USP18IFN-N levels are associated with both virological and serological response, and have the potential to become a clinical predictor for treatment outcomes in HBeAg-positive CHB patients before initiating IFN-α therapy.

A pilot single-center prospective randomized trial to assess the short-term effect of a flashing warning light on reducing fluoroscopy time and radiation exposure during ERCP.

BACKGROUND AND AIMS: ERCP has the risk of exposure to ionizing radiation. Performers may unconsciously increase fluoroscopy time (FT) because of a lack of radiation protection awareness. This study investigates whether a flashing warning light adopted as a behavioral intervention for performers reduces FT and radiation exposure during ERCP. METHODS: We conducted a prospective randomized trial of 200 therapeutic ERCPs. A flashing warning light was placed on top of the endoscopy monitor. Cases were consecutively enrolled and randomly assigned to 2 groups in a 1:1 ratio. In the warning light group, the light was on when the fluoroscopy foot pedal was depressed; in the control group, the light was off. Fluoroscopy and procedure-related data were recorded. RESULTS: The median FT and dose-area product (DAP) for the warning light group versus the control group were 142.5 seconds versus 175.0 seconds (P = .045) and 856.8 µGy∙m2 versus 1054.4 µGy∙m2 (P = .043). In a multivariable analysis, the use of the warning light was found to reduce FT by 15.4% (-27.0 seconds; P = .042). DAP reduction because of the decreased FT was 15.2% (160.3 µGy∙m2). The reduction in patient effective dose per case was .42 mSv, equivalent to 21 chest radiographs. No adverse events or interference with the procedures because of the warning light were noted. CONCLUSIONS: The use of a flashing warning light is a feasible way to reduce FT and radiation exposure during ERCP. (Clinical trial registration number: ChiCTR-IPR-14005349.).

Optimization of dosage ratio of chlorogenic acid and gardenia glycosides in the treatment of rats with fatty liver disease induced by high-fat feed.

OBJECTIVE: To investigate the optimal dosage ratio of chlorogenic acid and gardenia glycosides in treating the rates with fatty liver disease induced by high-fat feed. METHODS: A rat model of non-alcoholic fatty liver disease (NAFLD) was established by using a high-fat diet. According to mathematical model "uniform design", varying doses of chlorogenic acid and gardenia glycosides have been combined to form 6 medications for the treatment of NAFLD. Samples were then taken to observe pathological changes of the liver tissue (HE staining); changes in the fat metabolism pathway e.g. triglyceride (TG) and free fatty acid (FFA) content; alterations in liver function, i.e. serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity; and differences in Malondialdehyde (MDA) and superoxide dismutase (SOD) content in the liver tissue. Multiple regression analysis was conducted to test the optimal dosage ratio of chlorogenic acid and gardenia glycosides. RESULTS: Fatty degeneration and vacuole-like changes of different degrees occurred in hepatic cells of the model group. Markers for fat metabolism, serum ALT and AST activities, and expression of MDA in liver tissue significantly increased, while SOD decreased. Combination of 90 mg chlorogenic acid and 90 mg Gardenia glycosides was the optimal dosage ratio of chlorogenic acid and gardenia glycosides in the treatment of rats with fatty liver induced by high-fat diet. CONCLUSION: Chlorogenic acid of 90 mg plus gardenia glycosides of 90 mg was the best combination in the treatment of fatty liver disease in rats induced by high-fat feed.

Inhibitory Effect of Gardenoside on Free Fatty Acid-Induced Steatosis in HepG2 Hepatocytes.

Gardenoside is one of the most important effective extractions of a herb for its hepatoprotective properties. The aim of this study was to address the mechanism of Gardenoside on HepG2 cellular steatosis induced by free fatty acids (FFAs). The model of HepG2 steatosis was duplicated by oleic and palmitic acid at the proportion of 2:1 (FFAs mixture) for 24 h, then lipid toxicity was induced. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) were used to detect cell viability and Oil Red O staining method was used to judge the lipid accumulation respectively. Inflammatory cytokines TNF-α, IL-1ß, IL-6 and intracellular NFκB were measured after 24 h. The steatosis was significantly decreased after Gardenoside treatment without cytotoxicity. TNF-α, IL-1ß, IL-6 were modulated to HepG2 cells by treatment of Gardenoside. In the meantime, the activation of NFκB was inhibited by Gardenoside. Gardenoside has a protective effect on FFA-induced cellular steatosis in HepG2 cells which indicates that Gardenoside might be a potential therapeutic herb against NASH by suppressed supernatant inflammatory cytokine production and intracellular NFkB activity.