Exploring charge generation and separation in tandem organic light-emitting diodes based on magneto-electroluminescence.

5,6,11,12-tetraphenylnaphthacene (rubrene) exhibits resonant energy properties (ES1,rub≈ 2ET1,rub), resulting in rubrene-based organic light-emitting diode (OLED) devices that undergo the singlet fission (STT) process at room temperature. This unique process gives rise to a distinct magneto-electroluminescence (MEL) profile, differing significantly from the typical intersystem crossing (ISC) process. Therefore, in this paper, we investigate charge generation and separation in the interconnector, and the mechanism of charge transport in tandem OLEDs at room temperature using MEL tools. We fabricate tandem OLEDs comprising green (Alq3) and yellow (Alq3:rubrene) electroluminescence (EL) units using different interconnectors. The results demonstrate that all devices exhibited significant rubrene emission. However, the MEL did not exhibit an STT process with an increasing magnetic field, but rather a triplet-triplet annihilation (TTA) process. This occurrence is attributed to direct carrier trapping within doped EL units, which hinders the transport of rubrene trapped charges, consequently prolonging the lifetime of triplet excitons (T1,rub). Thus, the increased T1,rubconcentration causes TTA to occur at room temperature, causing the rapid decrease of MEL in all devices under high magnetic fields. In devices where only the TTA process occurs, the TTA increases with the increasing current. Consequently, the high magnetic field of devices A-C is only related to TTA. Notably, there exists a high magnetic field TTA of device D in the Alq3/1,4,5,8,9,11-Hexaazatriphenylene-hexacarbonitrile interconnector regardless of the current. This occurs because both EL units in the device emit simultaneously, resulting in the triplet-charge annihilation process of Alq3in the high magnetic field of the MEL. Moreover, the rapid increase in MEL at low magnetic field across all devices is attributed to the ISC between Alq3polaron pairs. This entire process involves Förster and Dexter energy transfer. This article not only provides novel insights into charge generation and separation in the interconnector but also enhances our understanding of the microscopic mechanisms in tandem OLED devices.

Study on Risk Factors and Receiver Operator Characteristic Curve of Iatrogenic Withdrawal Syndrome in Pediatric Intensive Care Units: A Retrospective Study.

INTRODUCTION: The aims of this study were to investigate the independent risk factors associated with iatrogenic withdrawal syndrome in pediatric intensive care units (PICUs) and to establish receiver operator characteristic (ROC) curve to facilitate the diagnosis of iatrogenic withdrawal syndrome in clinical settings. METHODS: Pediatric patients who received analgesic and sedative medication at a tertiary hospital in the southern Zhejiang region of China between January 2016 and December 2022 were selected for the study. Clinical case data were retrospectively analyzed to gather information including age, gender, weight, total dose of analgesic and sedative medication, total treatment duration, average maintenance dose, and other relevant parameters. Medically induced withdrawal symptom scores were assessed using the Sophia Observation Scale for Withdrawal Symptoms (SOS). Univariate and multivariate logistic regression analyses were conducted on the above indicators to identify the risk factors for iatrogenic withdrawal, and an ROC curve was constructed. RESULTS: The study encompassed a total of 104 pediatric patients, comprising 47 patients in the SOS score ≥4 group and 57 patients in the SOS score ≤3 group. The incidence of iatrogenic withdrawal was 45.19%. Univariate analysis identified cumulative total dose of fentanyl, average daily dose of fentanyl, average daily dose of midazolam, and patient weight (p < 0.05) as factors associated with iatrogenic withdrawal syndrome. The logistic multiple regression analysis revealed that the average daily dose of fentanyl was an independent risk factor for the occurrence of iatrogenic withdrawal syndrome in critically ill children (p < 0.05). ROC curve analysis indicated an area under the curve of 0.711 (95% CI: 0.610-0.811) with sensitivity and specificity of 73.7% and 61.7%, respectively. CONCLUSION: The average daily maintenance dose of fentanyl holds significant clinical value in diagnosing and evaluating the prognosis of iatrogenic withdrawal syndrome and can provide a scientific foundation for enhancing sedative and analgesic management in clinical practice.

Effects of Five-Step Nutritional Interventions Conducted by a Multidisciplinary Care Team on Gastroenteric Cancer Patients Undergoing Chemotherapy: A Randomized Clinical Trial.

The present study aims to report a five-step nutritional intervention conducted by a multidisciplinary care team as well as to investigate its effects on the nutritional status and quality of life of gastroenteric cancer patients undergoing chemotherapy. A total of 176 patients with newly diagnosed gastroenteric cancer were enrolled in the observational study. The nutritional status of the patients was assessed using Patient-Generated Subjective Global Assessment (PG-SGA) and Nutritional Risk Screening-2002 (NRS-2002), and anthropometry and biological tests were performed. Patients were randomly divided into intervention group (n = 40) and control group (n = 38). Patients in the intervention group received five-step nutrition intervention, while the control group received routine nutrition management. In the newly diagnosed patients with gastroenteric cancer, 50% presented mild to moderate malnutrition, 29.5% presented severe malnutrition, while only 20.5% of patients were in good nutritional status. Nutritional interventions reduced the progression of malnutrition after 10 weeks. Anthropometric parameters increased as well as function and symptoms improved; therefore, controlled the decline in quality of life. To sum up, five-step nutritional interventions conducted by a multidisciplinary care team improved the nutritional status of patients with gastroenteric cancer undergoing chemotherapy, and showed positive impacts on quality of life.

Synthesis of Aryl Amides from Acyl-Bunte Salts and Aryl Azides.

In this study, we developed an efficient method for the synthesis of aryl amides from sodium thiosulfate pentahydrate, organic anhydrides, and aryl azides. Sodium thiosulfate may be used as the sulfur source, which reacts with anhydrides to generate acyl-Bunte salt; this salt reacts with aryl azides via the in situ generation of thiocarboxylate. Using our method, we successfully synthesized a key bioactive compound. The advantages of one-pot two-step reactions include operational simplicity, structurally diverse products with favorable yields, use of less toxic odorless reagents, and easy applicability to large-scale operations.

Realizing high efficiency and luminance in green, yellow and blue organic light emitting diode by deoxyribonucleic acid.

Although the effect of the electron blocking layer (EBL) material, deoxyribonucleic acid (DNA), on the electroluminescence (EL) performance of organic light-emitting diodes (OLEDs) has been studied, the process of DNA regulation of exciton recombination region within the device is still unclear. Herein, devices with and without EBL were fabricated using different DNA spin-coating speeds, and the photoelectric performance of device were measured. By using DNA compounded with cetyltrimethyl ammonium (CTMA) as the EBL and hole buffer layer, so-called BioLEDs. The DNA-based green Alq3BioLEDs achieve higher luminance (39 000 cd m-2) and higher current efficiency (8.4 cd A-1), which are increased by 49% and 54%, respectively, compared to the reference OLEDs without the addition of DNA. Similarly, the maximum luminance and efficiency of yellow Rubrene BioLEDs is increased by 64% (from 12 120 to 19 820 cd m-2) and 74% (from 1.36 to 2.36 cd A-1), the luminance and efficiency of blue TCTA BioLEDs is increased by 101% and 245%. Specifically, we found that as the thickness of DNA-CTMA increases, the exciton recombination region moves towards the interface between the emitting layer (EML) and the hole transport layer (HTL). By better confining excitons within the EML, the current efficiency of the BioLEDs is effectively improved. Accordingly, we provide a possible idea for achieve high performance DNA-based BioLEDs by adding DNA-CTMA EBL and hole buffer layers. Meanwhile, as the DNA thickness increases, the exciton recombination region moves towards the EML/HTL interface, thereby enhancing the efficiency of the DNA-based BioLEDs.

Investigations on exciton recombination and annihilation in TmPyPB-ETL OLEDs using magnetic field effects.

Although the effect of the electron transport layer (ETL) material TmPyPb on the electroluminescence performance of organic light-emitting diodes (OLEDs) has been extensively studied, the process of TmPyPb regulating exciton recombination and annihilation within the device is still unclear. Here, we fabricated devices of various TmPyPb thicknesses with and without ETL. Subsequently, we measured the magneto-electroluminescence (MEL) of these devices. Specifically, at the same luminance, the triplet-charge annihilation (TQA) process is more likely to occur as the thickness of TmPyPb increases, resulting in a decrease in the maximum luminance of devices. Due to electron leakage and exciton recombination region moving towards the cathode, leading to a decrease in luminance efficiency at first and then an enhancement with an increase in the thickness of TmPyPb. Furthermore, at room temperature, the application of a large bias voltage suppresses singlet fission (SF) processes by modulating the dissociation of singlet polaron pairs (PPS) and the concentration of triplet exciton (T1). This leads to the conversion of SF to the TQA process. At low temperatures, the bias voltage and temperature can regulate the concentration and lifetime of PPS and T1. Therefore, as the temperature decreases, the transition of SF → TQA → triplet-triplet annihilation (TTA) and TQA coexistence → TTA process occurs. Moreover, MEL responses of the TmPyPb-ETL device show a W-linear pattern owing to the combined effect of the hyperfine interaction (HFI) and Zeeman splitting at 145 K. Accordingly, we explored the electroluminescence (EL) performance of TmPyPB-ETL OLEDs and investigated the evolution of SF, TQA, and TTA processes using MEL. Our study revealed the effect of exciton recombination and annihilation in OLEDs with varying thicknesses of TmPyPb.

Can Axillary Lymph Node Dissection be Omitted in Breast Cancer Patients with Metastatic Sentinel Lymph Nodes Undergoing Mastectomy? A Systematic Review and Meta-Analysis of Real-World Evidence.

BACKGROUND: The omission of axillary lymph node dissection (ALND) in patients with breast cancer who have metastatic sentinel lymph nodes (SLNs) undergoing mastectomy remains controversial. This meta-analysis explored the clinicopathological factors affecting the selection of ALND and the influences of ALND on survival outcomes in patients receiving mastectomy with positive SLNs. METHODS: Eligible studies published prior to 31 December 2022 were selected by searching the Embase, Web of Science and PubMed databases. Pooled analyses were performed using the number of events for clinicopathological parameters and HRs with 95% CIs for survival outcomes including disease-free survival (DFS), overall survival (OS), distant recurrence-free survival (DRFS) and locoregional recurrence-free survival (LRFS). RESULTS: A total of 10 retrospective studies enrolling only breast cancer patients with limited SLN metastases (no more than 3 positive SLNs or micrometastatic SLNs) undergoing mastectomy were included. Performing ALND in mastectomy patients who had limited SLN metastases was significantly correlated with invasive ductal carcinomas, larger tumors, lymphovascular invasion, higher tumor grade, macrometastatic SLNs, more positive SLNs, extranodal extension, positive surgical margins, negative ER, administration of adjuvant chemotherapy and nonwhite race (P < 0.05). However, performing ALND did not result in significantly longer OS, DFS, LRFS or DRFS (P > 0.05) in these patients. CONCLUSION: The present meta-analysis indicated that ALND may be safely avoided in patients with breast cancer who had limited SLN metastases undergoing mastectomy. Further well-designed randomized clinical trials are warranted to validate our results.

COMPARING FUNCTIONAL AND VASCULAR LAYER OUTCOMES OF LASER PHOTOCOAGULATION VERSUS SUBTHRESHOLD MICROPULSE LASER FOR DIABETIC MACULAR EDEMA: An OCT-Angiography Study.

PURPOSE: To compare the efficacy of conventional laser and subthreshold micropulse laser (SML) in treating diabetic macular edema in terms of functional outcomes and changes in quantitative metrics for the retinal capillary and choriocapillary vascular layers. METHODS: Fifty-two eyes from 52 patients with treatment-naive, clinically significant macular edema were randomly assigned to the conventional laser group or SML group in a 1:1 ratio. Best-corrected visual acuity, central macular thickness (CMT), and optical coherence tomography angiography scans were measured at baseline, 1, 3, and 6 months after treatment. RESULTS: The SML group showed rapid visual recovery, improving from baseline of 0.320 ± 0.31 logarithm of the minimum angle of resolution (20/42 Snellen) to 0.270 ± 0.22 logarithm of the minimum angle of resolution (20/37 Snellen) at 1 month ( P = 0.038) and had significant improvements in CMT at 6-month post-treatment (353.88-301.00 µ m, P = 0.005). Statistically significant changes were detected across all optical coherence tomography angiography metrics, including vessel density, vessel length density, vessel diameter index, and fractal dimension, at 6 months for both groups in the deep capillary plexus and choriocapillary plexus. CONCLUSION: Subthreshold micropulse laser resulted in early visual recovery and sustained macular thickness improvement in the treatment of diabetic macular edema. Microvascular perfusion parameters, including vessel density, vessel length density, and fractal dimension, improved in the deep capillary plexus and choriocapillary plexus for both treatment groups at 6 months post-treatment.

Icariin inhibits epithelial mesenchymal transition of renal tubular epithelial cells via regulating the miR-122-5p/FOXP2 axis in diabetic nephropathy rats.

Epithelial mesenchymal transition (EMT) of renal tubular epithelial cells (RTECs) dominates the pathology of diabetic nephropathy (DN). microRNAs (miRNAs) can influence the fate of DN via regulation of EMT. This study aimed to analyze the role of Icariin (ICA) in EMT of RTECs, hoping to provide theoretical basis for DN management. The DN rat model was established using streptozocin, followed by ICA treatment, histopathological observation, and detection of creatinine and blood urea nitrogen. In vitro cell models were established using high glucose (HG), followed by assessment of cell proliferation, apoptosis, and migration, and E-cadherin, α-SMA, miR-122-5p, and FOXP2 expressions. Cells were transfected with miR-122-5p mimics or si-FOXP2 for joint experiments with ICA. The targeting relationship between miR-122-5p and FOXP2 was verified. ICA repaired renal dysfunctions and glomerular structure abnormities of DN rats in a dose-dependent manner. In vitro, ICA improved proliferation while suppressed migration, apoptosis, and EMT of RTECs. miR-122-5p was up-regulated in DN rats and suppressed by ICA, and miR-122-5p targeted FOXP2. miR-122-5p up-regulation or FOXP2 down-regulation reversed the protective effects of ICA on HG-induced RTECs. Overall, our finding ascertained that ICA inhibited miR-122-5p to promote FOXP2 transcription, thereby attenuating EMT of RTECs and renal injury in DN rats.

1-Sulfonylated 1,2,3,4-tetrahydroquinoline-6-carboxylic acids as simple, readily-accessible MCL-1 inhibitors.

MCL-1 is a member of the BCL-2 family of proteins that regulates the mitochondrial pathway of apoptosis. Overexpression of MCL-1 is associated with the development and progression of a range of human cancers, and is also responsible for the onset of resistance to conventional chemotherapies. Although several MCL-1 inhibitors have now advanced to clinical trials, recent suspensions and terminations reveal the urgency with which new inhibitor chemotypes must be discovered. Building on our previous studies of a chiral, isomeric lead, we report the discovery of a new chemotype to inhibit MCL-1: 1-sulfonylated 1,2,3,4-tetrahydroquinoline-6-carboxylic acid. The nature of the sulfonyl moiety contributed significantly to the resulting inhibitory ability. For example, transforming a phenylsulfonyl group into a 4-chloro-3,5-dimethylphenoxy)phenyl)sulfonyl moiety elicited more than a 73-fold enhancement in inhibiton of MCL-1, possibly through targeting the p2 pocket in the BH3-binding groove, and so it is anticipated that further structure-activity studies here will lead to continued improvements in binding. It should be underscored that this class of MCL-1 inhibitors is readily accessible in four simple steps, is achiral and offers many avenues for optimization, all factors that are welcomed in the search for safe and effective inhibitors of this driver of cancer cell survival.

Vitamin D and Ocular Diseases: A Systematic Review.

The contributory roles of vitamin D in ocular and visual health have long been discussed, with numerous studies pointing to the adverse effects of vitamin D deficiency. In this paper, we provide a systematic review of recent findings on the association between vitamin D and different ocular diseases, including myopia, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), dry eye syndrome (DES), thyroid eye disease (TED), uveitis, retinoblastoma (RB), cataract, and others, from epidemiological, clinical and basic studies, and briefly discuss vitamin D metabolism in the eye. We searched two research databases for articles examining the association between vitamin D deficiency and different ocular diseases. One hundred and sixty-two studies were found. There is evidence on the association between vitamin D and myopia, AMD, DR, and DES. Overall, 17 out of 27 studies reported an association between vitamin D and AMD, while 48 out of 54 studies reported that vitamin D was associated with DR, and 25 out of 27 studies reported an association between vitamin D and DES. However, the available evidence for the association with other ocular diseases, such as glaucoma, TED, and RB, remains limited.

Delay in Retreatment of Helicobacter pylori Infection Increases Risk of Upper Gastrointestinal Bleeding.

BACKGROUND & AIMS: Little is known about risk of upper gastrointestinal bleeding (UGIB) in patients failed by Helicobacter pylori eradication therapy. We investigated the effects of different time until retreatment, after failure of initial H pylori eradication therapy, on subsequent risk of UGIB. METHODS: We performed a territory-wide retrospective cohort study of 70,518 patients with H pylori infection who had received their first course of clarithromycin-based triple therapy from January 2003 through December 2012 in Hong Kong. Patients who required retreatment after failed initial therapy (n = 8330, 11.8%) were categorized based on time between initial and final H pylori eradication (3 months or less, 3-12 months, and more than 12 months). We collected clinical data from 30 days after prescription of the last course of H pylori therapy until hospitalization for non-variceal UGIB, death, or the end of the study (30 Jun 2016; median follow-up time, 7.65 years). The primary outcome was difference in development UGIB (determined from ICD-9 codes) between patients who required retreatment and those who did not (reference group). RESULTS: Compared with the reference group, patients who required retreatment had an overall higher risk of UGIB, even after last eradication therapy (adjusted hazard ratio (HR), 1.50, 95% CI, 1.34-1.69). There was a progressive increase in risk of UGIB with longer time from initial until final eradication therapy: hazard ratio for time less than 3 months, 1.16; 95% CI, 0.88-1.54, hazard ratio for time 3-12 months, 1.35; 95% CI, 1.07-1.69, and hazard ratio for time more than 12 months, 1.68; 95% CI, 1.46-1.94 (P for trend = .038). CONCLUSION: In a retrospective study of patients in Hong Kong, we found that those failed by initial H pylori eradication have an increased risk of UGIB, compared to patients who responded to the initial therapy. Risk increased progressively with longer time until retreatment. Early retreatment within 3 months should be considered to minimize subsequent UGIB risk.

Mechanistic Analysis of an Extracellular Signal-Regulated Kinase 2-Interacting Compound that Inhibits Mutant BRAF-Expressing Melanoma Cells by Inducing Oxidative Stress.

Constitutively active extracellular signal-regulated kinase (ERK) 1/2 signaling promotes cancer cell proliferation and survival. We previously described a class of compounds containing a 1,1-dioxido-2,5-dihydrothiophen-3-yl 4-benzenesulfonate scaffold that targeted ERK2 substrate docking sites and selectively inhibited ERK1/2-dependent functions, including activator protein-1-mediated transcription and growth of cancer cells containing active ERK1/2 due to mutations in Ras G-proteins or BRAF, Proto-oncogene B-RAF (Rapidly Acclerated Fibrosarcoma) kinase. The current study identified chemical features required for biologic activity and global effects on gene and protein levels in A375 melanoma cells containing mutant BRAF (V600E). Saturation transfer difference-NMR and mass spectrometry analyses revealed interactions between a lead compound (SF-3-030) and ERK2, including the formation of a covalent adduct on cysteine 252 that is located near the docking site for ERK/FXF (DEF) motif for substrate recruitment. Cells treated with SF-3-030 showed rapid changes in immediate early gene levels, including DEF motif-containing ERK1/2 substrates in the Fos family. Analysis of transcriptome and proteome changes showed that the SF-3-030 effects overlapped with ATP-competitive or catalytic site inhibitors of MAPK/ERK Kinase 1/2 (MEK1/2) or ERK1/2. Like other ERK1/2 pathway inhibitors, SF-3-030 induced reactive oxygen species (ROS) and genes associated with oxidative stress, including nuclear factor erythroid 2-related factor 2 (NRF2). Whereas the addition of the ROS inhibitor N-acetyl cysteine reversed SF-3-030-induced ROS and inhibition of A375 cell proliferation, the addition of NRF2 inhibitors has little effect on cell proliferation. These studies provide mechanistic information on a novel chemical scaffold that selectively regulates ERK1/2-targeted transcription factors and inhibits the proliferation of A375 melanoma cells through a ROS-dependent mechanism. SIGNIFICANCE STATEMENT: Constitutive activation of the extracellular signal-regulated kinase (ERK1/2) pathway drives the proliferation and survival of many cancer cell types. Given the diversity of cellular functions regulated by ERK1/2, the current studies have examined the mechanism of a novel chemical scaffold that targets ERK2 near a substrate binding site and inhibits select ERK functions. Using transcriptomic and proteomic analyses, we provide a mechanistic basis for how this class of compounds inhibits melanoma cells containing mutated BRAF and active ERK1/2.

The clinical presentation and treatment outcomes of ocular tuberculosis: a 5-year experience in an endemic area.

PURPOSE: To report the clinical presentations of ocular tuberculosis infection (OTB) and the treatment regimen and outcome in an endemic area. METHODS: This is a retrospective case series of patients with presumed OTB treated in a tertiary teaching hospital in Hong Kong in 2014-2019. RESULTS: Among the nineteen patients recruited, the most common clinical presentation of OTB was retinal vasculitis (42.1%), followed by scleritis, intermediate uveitis, and choroidal tuberculoma (15.8% respectively). 94.7% and 94.4% of the subjects were treated with ATT and steroid, respectively, and 31.6% were put on systemic immunosuppressant prior to the initiation of ATT. Apart from those suffering from intermediate uveitis, most demonstrated good clinical response within 8 weeks of ATT initiation. CONCLUSION: Ocular involvement of TB has been increasingly recognized, especially in endemic regions like Hong Kong. High index of suspicion is recommended for OTB in typical clinical phenotypes or recurrent/resistant ocular inflammation unresponsive to conventional therapy. TB retinal vasculitis was the most common presentation of OTB in this study and OTB generally requires treatment with either regional or systemic steroid together with ATT.

Incidences, temporal trends and risks of hospitalisation for gastrointestinal bleeding in new or chronic low-dose aspirin users after treatment for Helicobacter pylori: a territory-wide cohort study.

OBJECTIVE: The risk of GI bleeding (GIB) in aspirin users after Helicobacter pylori (HP) eradication remains poorly defined. We characterised the incidences and temporal trends of hospitalisations for all GIB in aspirin users after HP eradication therapy. DESIGN: Based on a territory-wide health database, we identified all patients who had received the first course of clarithromycin-based triple therapy between 2003 and 2012. Patients were divided into three cohorts according to aspirin use: new users (commenced after HP eradication), chronic users (commenced before and resumed after HP eradication) and non-users. The primary outcome was to determine the risk of hospitalisation for GIB. RESULTS: We included 6985 new aspirin users, 5545 chronic users and 48 908 non-users. The age-adjusted and sex-adjusted incidence of hospitalisation for all GIB in new, chronic and non-users was 10.4, 7.2 and 4.6 per 1000 person-years, respectively. Upper and lower GIB accounted for 34.7% and 45.3% of all bleeding, respectively. Compared with chronic users, new users had a higher risk of GIB (HR with propensity score matching: 1.89; 95% CI 1.29 to 2.70). Landmark analysis showed that the increased risk in new aspirin users was only observed in the first 6 months for all GIB (HR 2.10, 95% CI 1.41 to 3.13) and upper GIB (HR 2.52, 95% CI 1.38 to 4.60), but not for lower GIB. CONCLUSION: New aspirin users had a higher risk of GIB than chronic aspirin users, particularly during the initial 6 months. Lower GIB is more frequent than upper GIB in aspirin users who had HP eradicated.

Linked color imaging versus narrow-band imaging for colorectal polyp detection: a prospective randomized tandem colonoscopy study.

BACKGROUND AND AIMS: Linked color imaging (LCI) is a newly available image-enhanced endoscopy (IEE) system that emphasizes the red mucosal color. No study has yet compared LCI with other available IEE systems. Our aim was to investigate polyp detection rates using LCI compared with narrow-band imaging (NBI). METHODS: This is a prospective randomized tandem colonoscopy study. Eligible patients who underwent colonoscopy for symptoms or screening/surveillance were randomized in a 1:1 ratio to receive tandem colonoscopy with both colonoscope withdrawals using LCI or NBI. The primary outcome was the polyp detection rate. RESULTS: Two hundred seventy-two patients were randomized (mean age, 62 years; 48.2% male; colonoscopy for symptoms, 72.8%) with 136 in each arm. During the first colonoscopy, the polyp detection rate (71.3% vs 55.9%; P = .008), serrated lesion detection rate (34.6% vs 22.1%; P = .02), and mean number of polyps detected (2.04 vs 1.35; P = .02) were significantly higher in the NBI group than in the LCI group. There was also a trend of higher adenoma detection rate in the NBI group compared with the LCI group (51.5% vs 39.7%, respectively; P = .05). Multivariable analysis confirmed that use of NBI (adjusted odds ratio, 1.99; 95% confidence interval, 1.09-3.68) and withdrawal time >8 minutes (adjusted odds ratio, 5.11; 95% confidence interval, 2.79-9.67) were associated with polyp detection. Overall, 20.5% of polyps and 18.1% of adenomas were missed by the first colonoscopy, but there was no significant difference in the miss rates between the 2 groups. CONCLUSION: NBI was significantly better than LCI for colorectal polyp detection. However, both LCI and NBI missed 20.5% of polyps. (Clinical trial registration number: NCT03336359.).

Probable catastrophic antiphospholipid syndrome secondary to chronic myelomonocytic leukaemia in an adult patient and a mini review.

Catastrophic antiphospholipid syndrome (CAPS) is a rare and life-threatening form of antiphospholipid syndrome (APS), which could be triggered by malignancy. Chronic myelomonocytic leukaemia (CMML) is an uncommon hematologic malignancy. We report a case of a 49-year-old male patient who presented multiple thromboses with a high titre of anti-ß2-glycoprotein-I antibody. Unexpectedly, there was persistent monocytosis combined with <20% blasts in his bone marrow. Thus, a diagnosis of probable CAPS and CMML was made. After treatment with prednisone, hydroxychloroquine and warfarin, the thromboses dissolved, and an improved presentation of peripheral blood and bone marrow was observed. Here, we also provide a mini review of cases of APS complicated with CMML identified from searches of MEDLINE, EMBASE and Web of Science databases. The review describes the clinical characteristics, laboratory data, treatments and outcomes.

Statins reduce the progression of non-advanced adenomas to colorectal cancer: a postcolonoscopy study in 187 897 patients.

BACKGROUND AND AIMS: Postcolonoscopy colorectal cancer (PCCRC) accounts for up to 9% of all CRCs. Statins have been shown to be associated with a lower CRC risk. We aimed to investigate whether PCCRC risk was also lower among statin users. METHODS: This is a retrospective cohort study using a territory-wide electronic healthcare database in Hong Kong including patients aged 40 years or above who had undergone colonoscopies between 2005 and 2013. Exclusion criteria included prior colorectal cancer (CRC), inflammatory bowel disease, prior colectomy and CRC detected within 6 months of index colonoscopy. We defined statin use as at least 90-day use before index colonoscopy. Medication use was traced up to 5 years before index colonoscopy. PCCRC-3y was defined as cancer diagnosed between 6 and 36 months after index colonoscopy. Sites of CRC were categorised as proximal (proximal to splenic flexure) and distal cancer. The subdistribution HR (SHR) of PCCRC-3y with statin use was derived by propensity score matching based on covariates (including patient factors, concurrent medication use and endoscopy centre's performance). RESULTS: Of 187 897 eligible subjects, 854 (0.45%) were diagnosed with PCCRC-3y. Statin use was associated with a lower PCCRC-3y risk (SHR: 0.72; 95% CI 0.55 to 0.95; p=0.018). Subgroup analysis shows that SHRs were 0.50 (95% CI 0.28 to 0.91; p=0.022) for proximal and 0.80 (95% CI 0.59 to 1.09; p=0.160) for distal cancer. Older (>60 years) patients, women and those without diabetes mellitus or polyps appeared to benefit more from statins. CONCLUSIONS: Statins were associated with a lower PCCRC risk, particularly for proximal cancer.

Effects of Helicobacter pylori Treatment on Incidence of Gastric Cancer in Older Individuals.

BACKGROUND & AIMS: Although eradication of Helicobacter pylori infection reduces the risk of gastric cancer, few data are available on its effects in older subjects. We compared the age-specific risk of gastric cancer in a large cohort of subjects who received H pylori eradication therapy vs a matched general population. METHODS: We searched the Hospital Authority database of Hong Kong to identify individuals with H pylori infection who had received a course of clarithromycin-containing eradication therapy from January 2003 through December 2012. We compared the gastric cancer incidence in this cohort with the expected incidence for the local general population by retrieving the gastric cancer incidence of the age- and sex-matched population from 2003 through 2014 (the latest available year) from the Hong Kong Cancer Registry. The primary outcome was the incidence of gastric cancer development in the cohort treated for H pylori infection vs the expected number of gastric cancer cases in the general population. Analyses were conducted by a priori age groups of less than 40 years, 40-59 years, and 60 years or older. RESULTS: Among 73,237 subjects infected with H pylori who received eradication therapy, 200 (0.27%) developed gastric cancer during a median follow-up time of 7.6 years. Compared with the matched general population, the gastric cancer risk was significantly lower in subjects 60 years or older who had received H pylori treatment (standardized incidence ratio [SIR], 0.82; 95% confidence interval [CI], 0.69-0.97; P = .02) but not in younger groups. When data were stratified based on time from H pylori treatment (less than 5 years, 5-9 years, and 10 or more years), the risk of gastric cancer was significantly lower than the general population 10 or more years after eradication in the group 40-59 years old (SIR 0.32; 95% CI, 0.08-0.88; P = .04) and the group 60 years or older (SIR, 0.42; 95% CI, 0.42-0.84; P = .02) than the other age groups. CONCLUSIONS: In an analysis of data from a public hospital database on Hong Kong, we associated treatment of H pylori infection with a lower risk of gastric cancer, particularly in older subjects, 10 or more years after treatment.

Mutant RAMP2 causes primary open-angle glaucoma via the CRLR-cAMP axis.

PURPOSE: Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide and mutations in known genes can only explain 5-6% of POAG. This study was conducted to identify novel POAG-causing genes and explore the pathogenesis of this disease. METHODS: Exome sequencing was performed in a Han Chinese cohort comprising 398 sporadic cases with POAG and 2010 controls, followed by replication studies by Sanger sequencing. A heterozygous Ramp2 knockout mouse model was generated for in vivo functional study. RESULTS: Using exome sequencing analysis and replication studies, we identified pathogenic variants in receptor activity-modifying protein 2 (RAMP2) within three genetically diverse populations (Han Chinese, German, and Indian). Six heterozygous RAMP2 pathogenic variants (Glu39Asp, Glu54Lys, Phe103Ser, Asn113Lysfs*10, Glu143Lys, and Ser171Arg) were identified among 16 of 4763 POAG patients, whereas no variants were detected in any exon of RAMP2 in 10,953 control individuals. Mutant RAMP2s aggregated in transfected cells and resulted in damage to the AM-RAMP2/CRLR-cAMP signaling pathway. Ablation of one Ramp2 allele led to cAMP reduction and retinal ganglion cell death in mice. CONCLUSION: This study demonstrated that disruption of RAMP2/CRLR-cAMP axis could cause POAG and identified a potential therapeutic intervention for POAG.