Bleeding Risk of Cold Versus Hot Snare Polypectomy for Pedunculated Colorectal Polyps Measuring 10 mm or Less: Subgroup Analysis of a Large Randomized Controlled Trial.

INTRODUCTION: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions. METHODS: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial. Immediate postpolypectomy bleeding (IPPB), defined as the perioperative use of a clip for bleeding, was evaluated through polyp-level analysis. Delayed postpolypectomy bleeding (DPPB), defined as bleeding occurring within 2 weeks postoperatively, was assessed at the patient-level among patients whose polyps were all ≤10 mm, including at least one 0-Ip polyp. RESULTS: A total of 647 0-Ip polyps (CSP: 306; HSP: 341) were included for IPPB analysis and 386 patients (CSP: 192; HSP: 194) for DPPB analysis. CSP was associated with a higher incidence of IPPB (10.8% vs 3.2%, P < 0.001) but no adverse clinical events. The procedure time of all polypectomies was shorter for CSP than for HSP (123.0 ± 117.8 vs 166.0 ± 237.7 seconds, P = 0.003), while the procedure time of polypectomies with IPPB were similar (249.8 ± 140.2 vs 227.4 ± 125.9 seconds, P = 0.64). DPPB was observed in 3 patients (1.5%) in the HSP group, including one patient (0.5%) with severe bleeding, but not in the CSP group. DISCUSSION: Despite CSP being associated with more IPPB events, it could be timely treated without adverse outcomes. Notably, no delayed bleeding occurred in the CSP group. Our findings support the use of CSP for 0-Ip polyps ≤ 10 mm.

Chromium iodate: the structure and origin of optical second harmonic generation.

Iodate crystal materials are some of the important candidates for mid-infrared nonlinear optical (NLO) crystals. Almost all the structures and NLO properties of monometallic iodates have been studied, except for a few difficult to synthesize crystalline phases. In this work, crystalline Cr(IO3)3 was synthesized and its optical properties were studied. Cr(IO3)3 has a strong powder second-harmonic generation (SHG) effect (1.3 × AgGaS2) and a large birefringence (0.24) at 2100 nm. Theoretical calculations indicate that the 3d orbital of Cr3+ is strongly involved in the SHG process, and the contribution of the metal cation centered unit CrO6 to the SHG response is much greater than that of the non-metal cation centered unit IO3. This study provides a new case among the few NLO materials in which the SHG response is dominated by metal cation centered groups.

Anhydrous Aluminum Iodate: Strong Second Harmonic Generation Effect Contributed by Unbonded and Antibonding Orbitals.

Exploring materials that balance the second harmonic generation (SHG) effect and laser-induced damage threshold (LIDT) is the frontier of nonlinear optical (NLO) crystal research at present. In this work, the NLO property of anhydrous aluminum iodate is extensively explored and discussed first. It exhibits a strong SHG intensity of 18.3 × KH2PO4 (KDP) and a high-powder LIDT of 1.4 × KDP at 1064 nm. Combining experimental and theoretical studies at the atomic level and electronic levels, it is found that the cations in the structure are replaced by cations with small radius and high valence, enabling the production of materials with large SHG responses. Unbonded and antibonding orbitals play a crucial positive role in the SHG response of the structure, whereas bonding orbitals produce a large negative contribution. This provides a scarce example of materials in which bonding orbitals make significant negative contributions.

Muscle activation patterns during active external rotation after reverse total shoulder arthroplasty: an electrophysiological study of the teres minor and associated musculature.

BACKGROUND: Preoperative teres minor insufficiency has been identified as a risk factor for poor restoration of external rotation (ER) after reverse total shoulder arthroplasty (RTSA). However, there has been little investigation regarding muscle activation patterns generating ER. This prospective study sought to determine the timing and activation levels of the shoulder girdle musculature during ER in well-functioning RTSAs with an intact teres minor using a lateralized design. METHODS: Patients who underwent RTSA ≥1 year previously with functional ER, an American Shoulder and Elbow Surgeons (ASES) score >70, superior rotator cuff deficiency, and an intact teres minor were identified. Electrophysiological and kinematic analyses were performed during ER in the modified neutral position (arm at side with 90° of elbow flexion) and in abduction (AB) (shoulder abducted 90° with 90° of elbow flexion). Dynamometer-recorded torque and position were pattern matched to electromyography during ER. The root-mean-square and integrated electromyography (in microvolts × milliseconds with standard deviation [SD]), as well as median frequency (MF) (in hertz with SD), were calculated to determine muscle recruitment. Pair-wise t test analysis compared muscle activation (P < .05 indicated significance). RESULTS: After an a priori power analysis, 16 patients were recruited. The average ASES score, visual analog scale pain score, and ASES subscore for ER in AB ("comb hair") were 87.7, 0.5, and 2.75 of 3, respectively. In AB, muscle activation began with the upper trapezius, middle trapezius, and latissimus dorsi, followed by the anterior deltoid activating to neutral. With ER beyond neutral, the teres major (9.6 µV × ms; SD, 9.2 µV × ms) initiated ER, followed by the teres minor (14.1 µV × ms; SD, 18.2 µV × ms) and posterior deltoid (11.1 µV × ms; SD, 9.3 µV × ms). MF analysis indicated equal contributions of the teres major (1.1 Hz; SD, 0.5 Hz), teres minor (1.2 Hz; SD, 0.4 Hz), and posterior deltoid (1.1 Hz; SD, 0.4 Hz) in ER beyond neutral. In the modified neutral position, the upper trapezius and middle trapezius were not recruited to the same level as in AB. For ER beyond neutral, the teres major (9.5 µV × ms [SD, 9 µV × ms]; MF, 1.1 Hz [SD, 0.5 Hz]), teres minor (11.4 µV × ms [SD, 15.1 µV × ms]; MF, 1.1 Hz [SD, 0.5 Hz]), and posterior deltoid (8.5 µV × ms [SD, 8 µV × ms]; MF, 1.2 Hz [SD, 0.3 Hz]) were activated in similar sequence and intensity as AB. No differences in muscle activation duration or intensity were noted among the teres major, teres minor, and posterior deltoid (P > .05). CONCLUSION: Active ER after RTSA is complex and is not governed by a single muscle-tendon unit. This study establishes a sequence, duration, and intensity of muscle activation for ER in well-functioning RTSAs. In both tested positions, the teres major, teres minor, and posterior deltoid function equally and sequentially to power ER.

Meta-analysis for the relationship between circulating pregnancy-associated plasma protein A and placenta accreta spectrum.

BACKGROUND: Changes in circulating pregnancy-associated plasma protein A (PAPP-A) have been observed in women with a placenta accreta spectrum (PAS). However, no consensus has been reached according to the previous studies. Our study investigated the relationship between circulating PAPP-A and PAS risk through a systematic review and meta-analysis. METHODS: Studies comparing the circulating level of PAPP-A between pregnant women with and without PAS were obtained by searching the Medline, Cochrane Library, Embase, CNKI, and Wanfang databases from the inception of the databases until February 12, 2023. Heterogeneity was considered in the pooling of results via a random-effects model. RESULTS: Eight observational studies were obtained for the meta-analysis, which included 243 pregnant women with PAS and 1599 pregnant women without PAS. For all these women, the first-trimester circulating level of PAPP-A was measured by immunoassay and reported as multiples of the median (MoM) values. The pooled results showed that compared to those who did not develop PAS, women with PAS had significantly higher first-trimester serum level PAPP-A (mean difference: 0.43 MoM, 95% confidence interval [CI]: 0.30 to 0.56, P < .001; I2 = 32%). Furthermore, a high first-trimester serum PAPP-A level was related to a high PAS risk (odds ratio: 2.89, 95% CI: 2.13 to 3.92, P < .001; I2 = 0%). Sensitivity analysis which excluded one study at a time, also obtained similar results (p all < 0.05). CONCLUSION: Pregnant women with a high serum PAPP-A level in the first trimester may be at an increased risk for PAS.

Anti-leukemia effects of omipalisib in acute myeloid leukemia: inhibition of PI3K/AKT/mTOR signaling and suppression of mitochondrial biogenesis.

Omipalisib (GSK2126458), a potent dual PI3K/mTOR inhibitor, is reported to exhibit anti-tumor effect in several kinds of cancers. More than 50% of acute myeloid leukemia (AML) patients display a hyperactivation of PI3K/AKT/mTOR signaling. We investigated the anti-proliferative effect of omipalisib in AML cell lines with varied genetic backgrounds. The OCI-AML3 and THP-1 cell lines had a significant response to omipalisib, with IC50 values of 17.45 nM and 8.93 nM, respectively. We integrated transcriptomic profile and metabolomic analyses, and followed by gene set enrichment analysis (GSEA) and metabolite enrichment analysis. Our findings showed that in addition to inhibiting PI3K/AKT/mTOR signaling and inducing cell cycle arrest at the G0/G1 phase, omipalisib also suppressed mitochondrial respiration and biogenesis. Furthermore, omipalisib downregulated several genes associated with serine, glycine, threonine, and glutathione metabolism, and decreased their protein and glutathione levels. In vivo experiments revealed that omipalisib significantly inhibited tumor growth and prolonged mouse survival without weight loss. Gedatolisib and dactolisib, another two PI3K/mTOR inhibitors, exerted similar effects without affecting mitochondria biogenesis. These results highlight the multifaceted anti-leukemic effect of omipalisib, revealing its potential as a novel therapeutic agent in AML treatment.

Fabrication of three-dimensional orthodontic force detecting brackets and preliminary clinical test for tooth movement simulation.

This study aimed to develop an ultraminiature pressure sensor array to measure the force exerted on teeth. Orthodontic force plays an important role in effective, rapid, and safe tooth movement. However, owing to the lack of an adequate tool to measure the orthodontic force in vivo, it remains challenging to determine the best orthodontic loading in clinical and basic research. In this study, a three-dimensional (3D) orthodontic force detection system based on piezoresistive absolute pressure sensors was designed. The 3D force sensing array was constructed using five pressure sensors on a single chip. The size of the sensor array was only 4.1 × 2.6 mm, which can be placed within the bracket base area. Based on the barometric calibration, conversion formulas for the output voltage and pressure of the five channels were constructed. Subsequently, a 3D linear mechanical simulation model of the voltage and stress distribution was established using 312 tests of the applied force in 13 operating modes. Finally, the output voltage was first converted to pressure and then to the resultant force. The 3D force-detection chip was then tested to verify the accuracy of force measurement on the teeth. Based on the test results, the average output force error was only 0.0025 N (0.7169%) (p = 0.958), and the average spatial positioning error was only 0.058 mm (p = 0.872) on the X-axis and 0.050 mm (p = 0.837) on the Y-axis. The simulation results were highly consistent with the actual force applied (intraclass correlation efficient (ICC): 0.997-1.000; p < 0.001). Furthermore, through in vivo measurements and a finite element analysis, the movement trends generated when the measured orthodontic forces that acted on the teeth were simulated. The results revealed that the device can accurately measure the orthodontic force, representing the first clinical test of an orthodontic-force monitoring system. Our study provides a hardware basis for clinical research on efficient, safe, and optimal orthodontic forces, and has considerable potential for application in monitoring the biomechanics of tooth movement.

Biomimetic Carbon Sequestration and Cyanate Detoxification Using Heat-Purified Carbonic Anhydrase from Sulfurihydrogenibium yellowstonense.

The reaction condition for purifying carbonic anhydrase from Sulfurihydrogenibium yellowstonense (SspCA) by direct heating without prior cell lysis was optimized; heating at 70 °C for 5 min resulted in the highest total activity of 23,460 WAU (Wilbur-Anderson unit) from a 50 mL culture. Heat-purified SspCA was examined for its capability to increase the rate of the mineralization of CO2; compared with an uncatalyzed control, the onset time of CaCO3 formation was shortened by up to 71%. Cyanase can be used to degrade toxic cyanate; however, one of the limitations of this biomimetic process is that the reaction needs HCO3- as a substrate. Heat-purified SspCA was combined with heat-purified cyanase from Thermomyces lanuginosus to alleviate the HCO3- dependence; in industrial wastewater, the HCO3- required was reduced by 50% when 0.75 WAU of SspCA was added. Heat-purified SspCA is stable at 4 °C; 88% of the initial activity was retained for up to five weeks. Partially purified SspCA can be obtained with ease and applied to a variety of applications.

Distinctive lower incidence rates of cutaneous melanoma on the hips and lower extremities of men.

BACKGROUND: Cutaneous melanomas (CMs) are more frequently found on the trunk in men, and on the hip and lower extremities (legs) in women. This discrepancy has been attributed to greater exposure to ultraviolet (UV) radiation of women's legs due to their dressing habits. OBJECTIVES: To understand the sex difference in the bodily distribution of CMs, especially those on the legs. METHODS: This was a cancer registry-based cohort study. CM incidences, relative tumour density and tumour mutational burdens (TMBs) were compared among different body sites in different sex and racial groups using the SEER (Surveillance, Epidemiology, and End Results) and TCGA SKCM (The Cancer Genome Atlas skin cutaneous melanoma) databases. RESULTS: White men had lower rates and lower relative tumour density (RTD) of CMs on their legs compared with the rest of their body sites, or compared with White women. Men classified by SEER into racial groups other than White did not show such a trend. White women had comparable RTDs among different body sites. The ratios between the 'White' and the 'other' groups were used to evaluate the approximate effect of sun exposure at different body sites, which further validated a distinct protective effect of men's legs in melanoma. TMB on leg melanomas was lower than on other sites in both sexes. CONCLUSIONS: The legs of both sexes in White patients show lower RTDs and lower levels of TMB, suggesting a weaker association with UV exposure. Furthermore, White men are especially protected against CM on their legs, suggesting an unknown intrinsic protective factor as compared with women.

Biomechanical evaluation of an osteoporotic anatomical 3D printed posterior lumbar interbody fusion cage with internal lattice design based on weighted topology optimization.

In this study, we designed and manufactured a posterior lumbar interbody fusion cage for osteoporosis patients using 3D-printing. The cage structure conforms to the anatomical endplate's curved surface for stress transmission and internal lattice design for bone growth. Finite element (FE) analysis and weight topology optimization under different lumbar spine activity ratios were integrated to design the curved surface (CS-type) cage using the endplate surface morphology statistical results from the osteoporosis patients. The CS-type and plate (P-type) cage biomechanical behaviors under different daily activities were compared by performing non-linear FE analysis. A gyroid lattice with 0.25 spiral wall thickness was then designed in the internal cavity of the CS-type cage. The CS-cage was manufactured using metal 3D printing to conduct in vitro biomechanical tests. The FE analysis result showed that the maximum stress values at the inferior L3 and superior L4 endplates under all daily activities for the P-type cage implantation model were all higher than those for the CS-type cage. Fracture might occur in the P-type cage because the maximum stresses found in the endplates exceeded its ultimate strength (about 10 MPa) under flexion, torsion and bending loads. The yield load and stiffness of our designed CS-type cage fall into the optional acceptance criteria for the ISO 23089 standard under all load conditions. This study approved a posterior lumbar interbody fusion cage designed to have osteoporosis anatomical curved surface with internal lattice that can achieve appropriate structural strength, better stress transmission between the endplate and cage, and biomechanically tested strength that meets the standard requirements for marketed cages.

Gene-level association analysis of bivariate ordinal traits with functional regressions.

In genetic studies, many phenotypes have multiple naturally ordered discrete values. The phenotypes can be correlated with each other. If multiple correlated ordinal traits are analyzed simultaneously, the power of analysis may increase significantly while the false positives can be controlled well. In this study, we propose bivariate functional ordinal linear regression (BFOLR) models using latent regressions with cumulative logit link or probit link to perform a gene-based analysis for bivariate ordinal traits and sequencing data. In the proposed BFOLR models, genetic variant data are viewed as stochastic functions of physical positions, and the genetic effects are treated as a function of physical positions. The BFOLR models take the correlation of the two ordinal traits into account via latent variables. The BFOLR models are built upon functional data analysis which can be revised to analyze the bivariate ordinal traits and high-dimension genetic data. The methods are flexible and can analyze three types of genetic data: (1) rare variants only, (2) common variants only, and (3) a combination of rare and common variants. Extensive simulation studies show that the likelihood ratio tests of the BFOLR models control type I errors well and have good power performance. The BFOLR models are applied to analyze Age-Related Eye Disease Study data, in which two genes, CFH and ARMS2, are found to strongly associate with eye drusen size, drusen area, age-related macular degeneration (AMD) categories, and AMD severity scale.

Defecation enhances cerebral perfusion and delays fatigue in elite triathletes.

BACKGROUND: Rectal distension increases regulatory burden to autonomic nervous system in the brain. PURPOSE: To determine the effect of rectal defecation on endurance performance and blood supply to the prefrontal brain and sub-navel regions of elite triathletes. METHODS: Thirteen elite triathletes completed a cycling time trial (80% VO2max) under defecated and non-defecated conditions, using a counterbalanced crossover design. Oxygenation and blood distribution in prefrontal brain and sub-navel regions were monitored by near-infrared spectroscopy (NIRS) during cycling. RESULTS: Defecation moderately decreased systolic blood pressure (-4 mmHg, p < 0.05, d = 0.71), suggesting an alleviation of autonomic nervous activity. During the exercise trials, fatigue (cycling time to exhaustion) occurred when cerebral oxygenation decreased to ~ 5 % below baseline regardless of treatment conditions, suggesting a critical deoxygenation point for sustaining voluntary exertions. Cerebral blood (estimated by total hemoglobin) increased progressively throughout the entire exercise period. Defecation decreased sub-navel oxygenation levels below the non-defecated level, suggesting an increased sub-navel oxygen consumption. Exercise also decreased sub-navel blood distribution, with minimal difference between non-defecated and defecated conditions. Defecation improved blood pooling in the prefrontal brain during exercise (p < 0.05) and enhanced cycling performance in triathletes (Non-defecated: 1624 ± 138 s vs. defecated: 1902 ± 163 s, d = 0.51, p < 0.05). CONCLUSION: Our results suggest that improved exercise performance after defecation is associated with greater blood availability to compensate deoxygenation in the prefrontal brain region during exercise. Further investigation is needed to examine the role of increasing sub-navel oxygen consumption in the performance improvement after defecation.

Attitude and influencing factors to receive the COVID-19 vaccine among university students in Sichuan Province, China: A cross-sectional study.

AIMS: To explore the university students' attitude and the potential influencing factors to receive the coronavirus disease 2019 (COVID-19) vaccine in Sichuan Province, China. DESIGN: A cross-sectional study. METHODS: The self-designed questionnaire was distributed among university students online in June 2021. SPSS software was used for statistical analysis of the data. Descriptive statistics, Chi-square, two independent samples t-tests, one-way analysis of variance (ANOVA), multivariate linear regression, and content analysis were performed. RESULTS: A total of 397 questionnaires were analysed, involving 316 (79.6%) respondents have received at least one dose of a COVID-19 vaccine and 81 (20.4%) have not taken the vaccine. The total mean score of university students' vaccination attitude was 25.97 (standard deviation [SD] = 3.720), and the total scoring rate was 74.2%. Main factors influencing students' attitude included education level, major, living style, with chronic disease or not, self-reported vaccination status, and number of medical units that can provide vaccination within 3 km of residence. Students were more willing to choose Chinese-manufactured vaccines (66.8%) and participate in collective vaccination programs organized by the school (71.3%). The desired vaccine protection period was 5-10 years (42.1%). The top three reasons for refusing the vaccine or vaccine hesitancy were as follows: concern about the side effects of vaccine (44.8%), lack of information about vaccine (31.0%), and concern about the efficacy of vaccine (29.3%). CONCLUSION: In general, most of the participants had relatively high level of positive attitude to receive the COVID-19 vaccine. Nevertheless, more attention should be paid to postgraduate students, non-medical students, those living alone, those with chronic disease, those have not received the COVID-19 vaccine, and those living far away from the vaccination medical units. Findings of this study can help educational institutions in developing effective interventions to improve the vaccination rate in the university student population.

Tumor Androgen Receptor Protein Level Is Positively Associated with a Better Overall Survival in Melanoma Patients.

Androgen receptor (AR) is expressed in numerous tissues and serves important biologic functions in skin, prostate, immune, cardiovascular, and neural systems, alongside sexual development. Several studies have associated AR expression and patient survival in various cancers, yet there are limited studies examining the relationship between AR expression and cutaneous melanoma. This study used genomics and proteomics data from The Cancer Proteome Atlas (TCPA) and The Cancer Genome Atlas (TCGA), with 470 cutaneous melanoma patient data points. Cox regression analyses evaluated the association between AR protein level with overall survival and revealed that a higher level of AR protein was positively associated with a better overall survival (OS) (p = 0.003). When stratified by sex, the AR association with OS was only significant for both sexes. The multivariate Cox models with justifications of sex, age of diagnosis, stage of disease, and Breslow depth of the tumor confirmed the AR-OS association in all patients. However, the significance of AR was lost when ulceration was included in the model. When stratified by sex, the multivariate Cox models indicated significant role of AR in OS of female patients but not in males. AR-associated genes were identified and enrichment analysis revealed shared and distinct gene network in male and female patients. Furthermore, AR was found significantly associated with OS in RAS mutant subtypes of melanoma but not in BRAF, NF1, or triple-wild type subtypes of melanoma. Our study may provide insight into the well-known female survival advantage in melanoma patients.

Seven-day vonoprazan-based triple therapy as first-lineHelicobacter pylori treatment in comparison with extended sequential therapy.

Background and Aim: Vonoprazan as a new acid blocker has more potency and longer lasting acid suppression than proton pump inhibitors. Whether the efficacy of vonoprazan-based triple therapy is comparable with or even better than that of currently recommended first-line therapies is still unknown. Our study aims to compare the eradication rate and major adverse effects between 7-day vonoprazan-based triple therapy with high-dose amoxicillin and 14-day extended sequential therapy. Methods: We performed a retrospective analysis from the database of 13C-urea breath test at Fu Jen Catholic University Hospital. All patients with a definite diagnosis of Helicobacter pylori infection by rapid urease test, urea breath test, stool antigen test, or pathology report were recruited. Patients receiving first-line regimens with vonoprazan-based triple therapy or extended sequential therapy were included. The respective eradication rate determined by 13C-urea breath test and major adverse effects were demonstrated. Results: Totally, 106 patients were recruited in the vonoprazan-based triple therapy group and 357 in the extended sequential therapy group. There was no significant difference in eradication rate between vonoprazan-based triple therapy with high-dose amoxicillin and extended sequential therapy (83.0 vs 88.8%, P = 0.12). Major adverse effects occurred in 13 of the extended sequential therapy group but none in the other group (0% vs 3.6%, P = 0.046). Conclusions: Seven-day vonoprazan-based triple therapy with high-dose amoxicillin is a potential first-line anti-Helicobacter pylori regimen alternative to current standard treatment, with the advantages of simplicity, short treatment duration, low pill burden, and fewer major adverse effects.

Cold Versus Hot Snare Polypectomy for Small Colorectal Polyps : A Pragmatic Randomized Controlled Trial.

BACKGROUND: Although cold snare polypectomy (CSP) is considered effective in reducing delayed postpolypectomy bleeding risk, direct evidence supporting its safety in the general population remains lacking. OBJECTIVE: To clarify whether CSP would reduce delayed bleeding risk after polypectomy compared with hot snare polypectomy (HSP) in the general population. DESIGN: Multicenter randomized controlled study. (ClinicalTrials.gov: NCT03373136). SETTING: 6 sites in Taiwan, July 2018 through July 2020. PARTICIPANTS: Participants aged 40 years or older with polyps of 4 to 10 mm. INTERVENTION: CSP or HSP to remove polyps of 4 to 10 mm. MEASUREMENTS: The primary outcome was the delayed bleeding rate within 14 days after polypectomy. Severe bleeding was defined as a decrease in hemoglobin concentration of 20 g/L or more, requiring transfusion or hemostasis. Secondary outcomes included mean polypectomy time, successful tissue retrieval, en bloc resection, complete histologic resection, and emergency service visits. RESULTS: A total of 4270 participants were randomly assigned (2137 to CSP and 2133 to HSP). Eight patients (0.4%) in the CSP group and 31 (1.5%) in the HSP group had delayed bleeding (risk difference, -1.1% [95% CI, -1.7% to -0.5%]). Severe delayed bleeding was also lower in the CSP group (1 [0.05%] vs. 8 [0.4%] events; risk difference, -0.3% [CI, -0.6% to -0.05%]). Mean polypectomy time (119.0 vs. 162.9 seconds; difference in mean, -44.0 seconds [CI, -53.1 to -34.9 seconds]) was shorter in the CSP group, although successful tissue retrieval, en bloc resection, and complete histologic resection did not differ. The CSP group had fewer emergency service visits than the HSP group (4 [0.2%] vs. 13 [0.6%] visits; risk difference, -0.4% [CI, -0.8% to -0.04%]). LIMITATION: An open-label, single-blind trial. CONCLUSION: Compared with HSP, CSP for small colorectal polyps significantly reduces the risk for delayed postpolypectomy bleeding, including severe events. PRIMARY FUNDING SOURCE: Boston Scientific Corporation.

Sofosbuvir/velpatasvir/voxilaprevir for patients with chronic hepatitis C virus infection previously treated with NS5A direct-acting antivirals: a real-world multicenter cohort in Taiwan.

BACKGROUND: Real-world data are scarce about the effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for retreating East Asian patients with hepatitis C virus (HCV) infection who previously received NS5A direct-acting antivirals (DAAs). We conducted a multicenter study to assess the performance of SOF/VEL/VOX in patients who were not responsive to prior NS5A inhibitors in Taiwan. METHODS: Between September 2021 and May 2022, 107 patients who failed NS5A inhibitor-containing DAAs with SOF/VEL/VOX salvage therapy for 12 weeks were included at 16 academic centers. The sustained virologic response at off-treatment week 12 (SVR12) was assessed in the evaluable (EP) and per-protocol (PP) populations. The safety profiles were also reported. RESULTS: All patients completed 12 weeks of treatment and achieved an end-of-treatment virologic response. The SVR12 rates were 97.2% (95% confidence interval (CI) 92.1-99.0%) and 100% (95% CI 96.4-100%) in EP and PP populations. Three (2.8%) patients were lost to off-treatment follow-up and did not meet SVR12 in the EP population. No baseline factors predicted SVR12. Two (1.9%) not-fatal serious adverse events (AE) occurred but were unrelated to SOF/VEL/VOX. Sixteen (15.0%) had grade 2 total bilirubin elevation, and three (2.8%) had grade 2 alanine transaminase (ALT) elevation. Thirteen (81.3%) of the 16 patients with grade 2 total bilirubin elevation had unconjugated hyperbilirubinemia. The estimated glomerular filtration rates (eGFR) were comparable between baseline and SVR12, regardless of baseline renal reserve. CONCLUSIONS: SOF/VEL/VOX is highly efficacious and well-tolerated for East Asian HCV patients previously treated with NS5A inhibitor-containing DAAs. CLINICAL TRIALS REGISTRATION: The study was not a drug trial. There was no need for clinical trial registration.

Impact of patient and provider nudges on addressing herpes zoster vaccine series completion.

OBJECTIVES: To determine the combined impact of provider-facing and text message-based, patient nudges on herpes zoster vaccine series completion. METHODS: Following a period during which Kroger Health implemented provider facing nudges, select US patients that initiated herpes zoster vaccination were randomized to receive timed text messages when the second dose was due and available as part of a quality improvement exercise. Main comparisons were between patients intervened by provider nudge only and those intervened by both provider and patient nudges. Data were assessed by GEE-basedlogistic and linear regression, controlling for available patient- and store-level characteristics, and geospatial analyses. RESULTS: During the baseline period, 100,627 adults received at least one HZ vaccine dose and 83.9% completed the series within 6 months over 88.6 days (SD: 26.53) on average. In the intervention period, 120,339 adults were vaccinated at least once and series completion was 88.3% (both provider nudges and text messaging) and 85.3% (not texted) during this observation window (both p < 0.0001). Time between doses was shorter for those who received text messages compared to both the baseline period and those in the intervention period that were not texted (both p < 0.001). Controlling for multiple characteristics, the odds of completion improved in the intervention period compared to baseline (OR: 1.07; 95% CI: 1.033-1.111), but a noticeably higher completion odds was observed amongst patients who received a text message in the intervention period (OR: 1.35; 95% CI: 1.286-1.414). Adjusting for patient and pharmacy factors, those who were texted received their second herpes zoster vaccine dose 8.6 days sooner (95% CI: -9.08 - -8.17, p < 0.0001) compared to those intervened by the provider nudge only. CONCLUSION: The combined use of clinical and patient-focused nudges is a simple mechanism by which pharmacies and other health care access points can address the multi-dose vaccine needs of diverse patient populations.

Second-line levofloxacin-based quadruple therapy versus bismuth-based quadruple therapy for Helicobacter pylori eradication and long-term changes to the gut microbiota and antibiotic resistome: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Levofloxacin-based therapy or bismuth-based quadruple therapy are the recommended second-line regimens for Helicobacter pylori eradication after failure of clarithromycin-based therapy. However, resistance to levofloxacin has increased in the past decade. Furthermore, little is known about the long-term effects of H pylori eradication on the antibiotic resistome. In this study, we compared these second-line eradication therapies for efficacy, tolerability, and short-term and long-term effects on the gut microbiota, antibiotic resistome, and metabolic parameters. METHODS: We did a multicentre, open-label, parallel group, randomised controlled trial at eight hospitals in Taiwan. Adult patients (age ≥20 years) with persistent H pylori infection after first-line clarithromycin-based therapy were randomly assigned (1:1, permuted block sizes of four) to receive levofloxacin-based sequential quadruple therapy for 14 days (EAML14; esomeprazole 40 mg and amoxicillin 1 g for 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for 7 days, all twice-daily) or bismuth-based quadruple therapy for 10 days (BQ10; esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). All investigators were masked to the randomisation sequence. The primary endpoint was H pylori eradication rate measured by 13C urea breath test 6 weeks after second-line treatment according to both intention-to-treat (ITT) and per-protocol analysis. The microbiota composition and antibiotic resistome of faecal samples collected at baseline (before treatment) and at 2 weeks, 8 weeks, and 1 year after eradication therapy was profiled by shotgun metagenomic sequencing and 16S rRNA gene sequencing. The frequency of adverse effects and changes in the gut microbiota and antibiotic resistome were assessed in all participants with available data. The trial is complete and registered with ClinicalTrails.gov, NCT03148366. FINDINGS: Between Feb 25, 2015, and Dec 11, 2020, 560 patients were randomly assigned to receive EAML14 or BQ10 (n=280 per group; 261 [47%] men and 299 [53%] women). Mean age was 55·9 years (SD 12·7) in the EAML14 group and 54·9 years (12·3) in the BQ10 group. Eradication of H pylori was achieved in 246 (88%) of 280 participants in the EAML14 group and 245 (88%) of 280 in the BQ10 group according to ITT analysis (risk difference -0·4%, 95% CI -5·8 to 5·1; p=0·90). In the per-protocol analysis, 246 (90%) of 273 participants in the EAML14 group and 245 (93%) of 264 participants in the BQ10 group achieved H pylori eradication (risk difference 2·7%, 95% CI -0·2 to 7·4; p=0·27). Transient perturbation of faecal microbiota diversity at week 2 was largely restored to basal state 1 year after EAML14 or BQ10. Diversity recovery was slower with BQ10, and recovery in species abundance was partial after both therapies. On shotgun sequencing, we observed significant increases in total resistome after EAML14 (p=0·0002) and BQ10 (p=4·3 × 10-10) at week 2, which were restored to pretreatment level by week 8. The resistance rates of Escherichia coli and Klebsiella pneumonia to levofloxacin, ciprofloxacin, ampicillin (ampicillin-sulbactam for K pneumonia), and various cephalosporins were significantly increased in the EAML14 group compared with in the BQ10 group at week 2, which were restored to pretreatment levels and showed no significant differences at week 8 and 1 year. The frequency of any adverse effects was significantly higher after BQ10 therapy (211 [77%] of 273 participants) than after EAML14 therapy (134 [48%] of 277; p<0·0001). INTERPRETATION: We found no evidence of superiority between levofloxacin-based quadruple therapy and bismuth-based quadruple therapy in the second-line treatment of H pylori infection. The transient increase in the antibiotic resistome and perturbation of faecal microbiota diversity were largely restored to pretreatment state from 2 months to 1 year after eradication therapy. FUNDING: The Ministry of Science and Technology of Taiwan, the Ministry of Health and Welfare of Taiwan, National Taiwan University Hospital, Taipei Veteran General Hospital, and the Australian Federal Government through the St George and Sutherland Medical Research Foundation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Stable Expression of Coagulation Factors by RPS6 Promoter / 中国实验血液学杂志

OBJECTIVE@#To screen better promoters and provide more powerful tools for basic research and gene therapy of hemophilia.@*METHODS@#Bioinformatics methods were used to analyze the promoters expressing housekeeping genes with high abundance, so as to select potential candidate promoters. The GFP reporter gene vector was constructed, and the packaging efficiency of the novel promoter was investigated with EF1 α promoter as control, and the transcription and activities of the reporter gene were investigated too. The activity of the candidate promoter was investigated by loading F9 gene.@*RESULTS@#The most potential RPS6 promoter was obtained by screening. There was no difference in lentiviral packaging between EF1 α-LV and RPS6-LV, and their virus titer were consistent. In 293T cells, the transduction efficiency and mean fluorescence intensity of RPS6pro-LV and EF1 αpro-LV were proportional to the lentiviral dose. The transfection efficiency of both promoters in different types of cells was in the following order: 293T>HEL>MSC; Compared with EF1 αpro-LV, RPS6pro-LV could obtain a higher fluorescence intensity in MSC cells, and RPS6pro-LV was more stable in long-term cultured HEL cells infected with two lentiviruses respectively. The results of RT-qPCR, Western blot and FIX activity (FIX∶C) detection of K562 cell culture supernatant showed that FIX expression in the EF1 α-F9 and RPS6-F9 groups was higher than that in the unloaded control group, and there was no significant difference in FIX expression between the EF1 α-F9 and RPS6-F9 groups.@*CONCLUSION@#After screening and optimization, a promoter was obtained, which can be widely used for exogenous gene expression. The high stability and viability of the promoter were confirmed by long-term culture and active gene expression, which providing a powerful tool for basic research and clinical gene therapy of hemophilia.