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Objective: Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer, with a 5-year survival rate of only 11%. Surgery is the only potential cure for PDAC, but approximately 85% of patients present with unresectable tumors at diagnosis. The difficulty in early detection is attributed to the fact that early PDACs cause few or nonspecific symptoms and are frequently obscure or even invisible in imaging studies such as computed tomography (CT). This review aims to briefly summarize the status of screening/surveillance for PDAC and elaborate on the potential windows of opportunity for early detection through PDAC-induced paraneoplastic phenomena and artificial intelligence (AI)-augmented image analysis. Data Sources: Relevant studies and review articles were searched in PubMed. Study Selection: Studies and articles on human subjects were selected. Results: Surveillance for high-risk individuals with imaging-based tools (endoscopic ultrasound and magnetic resonance image) is now advocated, whereas screening for asymptomatic general populations is not warranted at present. Paraneoplastic syndromes, including pancreatic cancer-associated diabetes and cachexia, are prevalent in PDAC patients and may provide windows of opportunity for early detection. S100A9 and galectin-3 are novel PDAC-derived factors mediating pancreatic cancer-associated diabetes and have shown promise in facilitating the early detection of PDAC. Novel computer-aided detection tools based on AI technologies, including deep learning and radiomic analysis with machine learning, have achieved accurate detection and might supplement human interpretation to improve the sensitivity for early PDAC on CT images. Conclusion: Novel blood-based biomarkers and AI-augmented image analysis may be complementary and hold promise for the early detection of PDAC. [ABSTRACT FROM AUTHOR]

Background: Cancer cachexia, occurring in ~ 80% pancreatic cancer (PC) patients overall, is a paraneoplastic syndrome mediated by cancer-induced systemic inflammation and characterized by weight loss and skeletal muscle wasting. Identifying clinically relevant PC-derived pro-inflammatory factors with cachexigenic potential may provide novel insights and therapeutic strategies. Methods: Pro-inflammatory factors with cachexigenic potential in PC were identified by bioinformatic analysis. The abilities of selected candidate factors in inducing skeletal muscle atrophy were investigated. Expression levels of candidate factors in tumors and sera was compared between PC patients with and without cachexia. Associations between serum levels of the candidates and weight loss were assessed in PC patients. Results: S100A8, S100A9, and S100A8/A9 were identified and shown to induce C2C12 myotube atrophy. Tumors of PC patients with cachexia had markedly elevated expression of S100A8 (P = 0.003) and S100A9 (P < 0.001). PC patients with cachexia had significantly higher serum levels of S100A8, S100A9 and S100A8/A9. Serum levels of these factors positively correlated with percentage of weight loss [correlation coefficient: S100A8: 0.33 (P < 0.001); S100A9: 0.30 (P < 0.001); S100A8/A9: 0.24 (P = 0.004)] and independently predicted the occurrence of cachexia [adjusted odds ratio (95% confidence interval) per 1ng/ml increase: S100A8 1.11 (1.02–1.21), P = 0.014; S100A9 1.10 (1.04–1.16), P = 0.001; per 1 µg/ml increase: S100A8/A9 1.04 (1.01–1.06), P = 0.009]. Conclusions: Atrophic effects of S100A8, S100A9, and S100A8/A9 indicated them as potential pathogenic factors of PC-induced cachexia. In addition, the correlation with the degree of weight loss and prediction of cachexia in PC patients implicated their potential utility in the diagnosis of PC-induced cachexia. [ABSTRACT FROM AUTHOR]

Surgical removal is the treatment of choice for many neoplasms of the parotid gland. This meta-analysis aimed to evaluate the differences between parotidectomy using a modified facelift incision (MFI) and parotidectomy using a modified Blair incision (MBI). A systematic search of the available literature in PubMed, Embase and the Cochrane Library was performed. Studies of adult patients who underwent open parotidectomy with presumed benign parotid neoplasms based on preoperative examinations were reviewed. The surgical outcomes of the MFI and MBI groups were collected. Intraoperative and postoperative parameters, including operative time, tumor size, cosmetic satisfaction, and incidences of facial palsy, Frey's syndrome and salivary complications, were compared. Dichotomous data and continuous data were analyzed by calculating the risk difference (RD) and the mean difference (MD) with the 95% confidence interval (CI), respectively. Seven studies were included in the final analysis. The pooled analysis demonstrated that the cosmetic satisfaction score was significantly higher in the MFI group (MD = 1.66; 95% CI 0.87–2.46). The operative duration in the MFI group was significantly longer than that in the MBI group (MD = 0.07; 95% CI 0.00–0.14). The MFI group exhibited a smaller tumor size (MD = − 2.27; 95% CI − 4.25 to − 0.30) and a lower incidence of Frey's syndrome (RD = − 0.18; 95% CI − 0.27 to − 0.10). The incidence of postoperative temporary facial palsy (RD = − 0.05; 95% CI − 0.12 to 0.03), permanent facial palsy (RD = − 0.01; 95% CI − 0.06 to 0.03) and salivary complications (RD = − 0.00; 95% CI − 0.05 to 0.05) was comparable between the two groups. Based on these results, MFI may be a feasible technique for improving the cosmetic results of patients who need parotidectomy when oncological safety can be ensured. [ABSTRACT FROM AUTHOR]

Polyamines play a major role in biosilicification reactions in diatoms and sponges. While the effects of polyamines on silicic acid oligomerization and precipitation are well known, the impact of polyamines chain length on silica particle growth is unclear. We studied the effects of polyamine chain length on silica particle growth and condensation in a known, simple, and salt-free biphasic reaction system; with tetraethyl orthosilicate as organic phase and polyamine dissolved in the aqueous phase. The particles at various growth stages were characterized by Cryo- Transmission Electron Microscopy, Scanning Electron Microscopy, Thermogravimetric Analysis, Zeta Potential, and solid-state NMR analysis. Polyamines were found co-localized within silica particles and the particle diameter increased with an increase in polyamine chain length, whereas silica condensation showed the opposite trend. Particle growth is proposed to progress via a coacervate intermediate while the final particles have a core shell structure with an amine-rich core and silica-rich shell. The results presented in this paper would of interest for researchers working in the field of bioinspired materials. Polyamines play an important role in biogenic silica formation, however, their effects on silica particle size and condensation have not been well described. Here the authors show that bioinspired polyamine length affects silica particle size and extent of condensation. [ABSTRACT FROM AUTHOR]

Objective: The overnight rostral fluid shift from the lower limbs is one of the causes of obstructive sleep apnea (OSA). Compression stockings (CS) prevent lower limb fluid retention and have been reported to decrease nighttime fluid shift. The aim of this study is to evaluate the effect of CS on fluid shift and the severity of OSA.Methods: A systematic literature search was performed in the PubMed, EMBASE and Cochrane Library databases. The data were analyzed using Comprehensive Meta-Analysis software (Version 3; Biostat, Englewood, NJ). Studies evaluating the effect of CS on the overnight fluid shift and OSA severity were included in the analysis.Results: A total of 4 studies were included in this meta-analysis. The pooled analysis showed that the apnea-hypopnea index (AHI) of the overall study group was significantly lower after using CS (SMD, -1.08; 95% CI, -1.49 to -0.67). Decreases in the AHI were also observed in the normal fluid status (SMD, -1.05; 95% CI, -1.73 to -0.37) and fluid overload status (SMD, -1.17; 95% CI, -1.76 to -0.58) populations. The overall study group had significant decreases in overnight changes in neck circumference (SMD, -1.05; 95% CI, -2.06 to -0.03) and leg fluid volume (SMD, -1.14; 95% CI, -1.88 to -0.41) after using CS. However, no significant differences in overnight changes in neck circumference and leg fluid volume were observed in normal fluid status patients.Conclusion: CS may help decrease overnight fluid shift and could be a treatment option for OSA. [ABSTRACT FROM AUTHOR]

Here we present our observations on a peculiar kinetic behavior observed at low catalyst loadings for the metathesis of internal olefins on a highly active silica‐supported tungsten oxo alkylidene prepared through surface organometallic chemistry (SOMC). The observed kinetic profile is comprised of two consecutive regimes, which support the presence of two different active sites on the surface of such catalysts. We propose that the more active site is operational in the beginning of the reaction but deactivates very fast, and the second one initiates over time due to the presence of ethylene formed subsequently under the reaction conditions. A combination of spectroscopic techniques and computations was used to identify the possible nature of these sites. Solid‐state NMR, EXAFS and DFT calculations are consistent with the esence of two distinct surface species that likely originate from the occurrence of slightly different local environments on the surface, that is, metal sites with a different number of nearby siloxane bridges. This data highlights the effects that may arise from the amorphous nature of the supports like silica and the difficulties to obtain truly single‐site catalysts – one of the ultimate goals of SOMC. [ABSTRACT FROM AUTHOR]

Objectives: The irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) afatinib and dacomitinib are approved for first-line treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and dacomitinib in this setting. Materials and methods: Between September 2020 and March 2023, we retrospectively recruited patients diagnosed with advanced-stage EGFR-mutant NSCLC who were treated with first-line irreversible EGFR-TKIs. The enrolled patients were assigned to two groups based on whether they received afatinib or dacomitinib. Results: A total of 101 patients were enrolled in the study (70 to afatinib and 31 to dacomitinib). The partial response rates (PR) for first-line treatment with afatinib and dacomitinib were 85.7 and 80.6% (p = 0.522). The median progression-free survival (PFS) (18.9 vs. 16.3 months, p = 0.975) and time to treatment failure (TTF) (22.7 vs. 15.9 months, p = 0.324) in patients with afatinib and dacomitinib treatment were similar. There was no significant difference observed in the median PFS (16.1 vs. 18.9 months, p = 0.361) and TTF (32.5 vs. 19.6 months, p = 0.182) between patients receiving the standard dose and those receiving the reduced dose. In terms of side effects, the incidence of diarrhea was higher in the afatinib group (75.8% vs. 35.5%, p < 0.001), while the incidence of paronychia was higher in the dacomitinib group (58.1% vs. 31.4%, p = 0.004). The PFS (17.6 vs. 24.9 months, p = 0.663) and TTF (21.3 vs. 25.1 months, p = 0.152) were similar between patients younger than 75 years and those older than 75 years. Conclusion: This study showed that afatinib and dacomitinib had similar effectiveness and safety profiles. However, they have slightly different side effects. Afatinib and dacomitinib can be safely administered to patients across different age groups with appropriate dose reductions. [ABSTRACT FROM AUTHOR]

Surface modification with polyphenolic molecules has been pursued in biomedical materials owing to their antioxidant, anti‐inflammatory, and antimicrobial characteristics. Recently, the use of silicic acid (Siaq) as a mediator for efficient surface deposition of tannic acid (TA) was reported, but the postulated Si‐TA polymeric networks were not characterized. Herein, we present unambiguous evidence for silicate‐TA networks that involve Si−O−C motifs by using solid‐state NMR spectroscopy, further supported by XPS and ToF‐SIMS. By using QCM‐D we demonstrate the advantages of Siaq, compared to using transition‐metal ions, to improve the coating efficiency under mildly acidic conditions. The presented homogenous coating buildup and validated applicability in inorganic buffers broadens the use of TA for surface modifications in technological and biomedical applications. [ABSTRACT FROM AUTHOR]

Dynamic Nuclear Polarization Surface Enhanced NMR spectroscopy has been demonstrated to significantly improve NMR sensitivity on materials by 1 to 2 orders of magnitude at high magnetic fields. The preferential surface enhancement also allows for selectively probing the solid surface. In this review, we will briefly describe the main mechanism used nowadays, i.e. cross effect, for DNP enhanced solid-state NMR. We will show the typical protocols of sample formulation leading to effective DNP surface enhancements and the key experimental factors in performing DNP SENS experiments. Other important developments in DNP, i.e. shielded polarizing agents for reactive surfaces, hyperpolarizing solid matrices, and high-temperature and high-field DNP, will be discussed as well. Finally, we close the review with a short summary and our perspectives on the directions of future developments in this field. [ABSTRACT FROM AUTHOR]

Background: The patient population with stage III non-small-cell lung cancer (NSCLC) is heterogeneous, with varying staging characteristics and diverse treatment options. Despite the potential practice-changing implications of randomized controlled trials evaluating the efficacy of perioperative epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), concerns have been raised due to conflicting overall survival (OS) results. Few real-world studies have examined the survival outcomes of patients with resected EGFR-mutant stage III adenocarcinoma receiving perioperative chemotherapy and EGFR–TKIs. Methods: In this retrospective observational study, we enrolled patients with resected stage III adenocarcinoma with EGFR mutations between January 2011 and December 2021. Patients were classified into two groups: perioperative chemotherapy and perioperative EGFR–TKIs. Outcomes and prognostic factors were analyzed using Cox proportional hazards regression analysis. Results: Eighty-four patients were enrolled in the analysis. Perioperative EGFR-TKIs led to longer progression-free survival (PFS) than chemotherapy (38.6 versus 14.2 months; p = 0.019). However, only pathological risk factors predicted poor PFS in multivariate analysis. Patients receiving perioperative chemotherapy had longer OS than those receiving EGFR-TKIs (111.3 versus 50.2 months; p = 0.052). Multivariate analysis identified perioperative treatment with EGFR-TKIs as an independent predictor of poor OS (HR: 3.76; 95% CI: 1.22–11.54). Conclusion: Our study demonstrates that chemotherapy should be considered in the perioperative setting for high-risk patients, when taking pathological risk factors into consideration, and that optimized sequencing of EGFR–TKIs might be the most critical determinant of OS. [ABSTRACT FROM AUTHOR]

Methanol synthesis by CO2 hydrogenation is a key process in a methanol-based economy. This reaction is catalyzed by supported copper nanoparticles and displays strong support or promoter effects. Zirconia is known to enhance both the methanol production rate and the selectivity. Nevertheless, the origin of this observation and the reaction mechanisms associated with the conversion of CO2 to methanol still remain unknown. A mechanistic study of the hydrogenation of CO2 on Cu/ZrO2 is presented. Using kinetics, in situ IR and NMR spectroscopies, and isotopic labeling strategies, surface intermediates evolved during CO2 hydrogenation were observed at different pressures. Combined with DFT calculations, it is shown that a formate species is the reaction intermediate and that the zirconia/copper interface is crucial for the conversion of this intermediate to methanol. [ABSTRACT FROM AUTHOR]

Methanol synthesis by CO2 hydrogenation is a key process in a methanol-based economy. This reaction is catalyzed by supported copper nanoparticles and displays strong support or promoter effects. Zirconia is known to enhance both the methanol production rate and the selectivity. Nevertheless, the origin of this observation and the reaction mechanisms associated with the conversion of CO2 to methanol still remain unknown. A mechanistic study of the hydrogenation of CO2 on Cu/ZrO2 is presented. Using kinetics, in situ IR and NMR spectroscopies, and isotopic labeling strategies, surface intermediates evolved during CO2 hydrogenation were observed at different pressures. Combined with DFT calculations, it is shown that a formate species is the reaction intermediate and that the zirconia/copper interface is crucial for the conversion of this intermediate to methanol. [ABSTRACT FROM AUTHOR]

In recent years, various protocols on preparing Lewis acidic Sn- β zeolite hydrothermally and postsynthetically have been reported. However, very little is known about the effects of different synthesis protocols on the Sn( IV) speciation in the final material. Even the effects of individual synthesis parameters within a certain preparation method have not been studied systematically. Here, we demonstrate that hydrothermally synthesized Sn- β zeolites prepared via very similar recipes show significantly different 119Sn- NMR spectra, suggesting different Sn site speciation. Among postsynthetically prepared Sn- β zeolites, less variation in the resulting 119Sn- NMR spectra have been observed, indicating a more reproducible synthesis procedure compared to hydrothermal synthesis in fluoride media. This work highlights the importance of 119Sn- NMR measurements to elucidate the precise local geometry of the Sn heteroatoms in Sn- β, and the need to quantify the number of reactive Sn sites on each sample that participate in a given catalytic reaction, in order to accurately compare materials prepared by different routes. [ABSTRACT FROM AUTHOR]

Obtaining detailed structural information of reaction intermediates remains a key challenge in heterogeneous catalysis because of the amorphous nature of the support and/or the support interface that prohibits the use of diffraction-based techniques. Combining isotopic labeling and dynamic nuclear polarization (DNP) increases the sensitivity of surface enhanced solid-state NMR spectroscopy (SENS) towards surface species in heterogeneous alkene metathesis catalysts; this in turn allows direct determination of the bond connectivity and measurement of the carbon-carbon bond distance in metallacycles, which are the cycloaddition intermediates in the alkene metathesis catalytic cycle. Furthermore, this approach makes possible the understanding of the slow initiation and deactivation steps in these heterogeneous metathesis catalysts. [ABSTRACT FROM AUTHOR]

Obtaining detailed structural information of reaction intermediates remains a key challenge in heterogeneous catalysis because of the amorphous nature of the support and/or the support interface that prohibits the use of diffraction-based techniques. Combining isotopic labeling and dynamic nuclear polarization (DNP) increases the sensitivity of surface enhanced solid-state NMR spectroscopy (SENS) towards surface species in heterogeneous alkene metathesis catalysts; this in turn allows direct determination of the bond connectivity and measurement of the carbon-carbon bond distance in metallacycles, which are the cycloaddition intermediates in the alkene metathesis catalytic cycle. Furthermore, this approach makes possible the understanding of the slow initiation and deactivation steps in these heterogeneous metathesis catalysts. [ABSTRACT FROM AUTHOR]

Gastric cancer is the second leading cause of cancer-related death worldwide. The correlation of Helicobacter pylori and the etiology of gastric cancer was substantially certain. Cholesterol-rich microdomains (also called lipid rafts), which provide platforms for signaling, are associated with H. pylori-induced pathogenesis leading to gastric cancer. Patients who have been prescribed statins, inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, have exhibited a reduced risk of several types of cancer. However, no studies have addressed the effect of statins on H. pylori-associated gastric cancer from the antineoplastic perspective. In this study, we showed that treatment of gastric epithelial cells with simvastatin reduced the level of cellular cholesterol and led to attenuation of translocation and phosphorylation of H. pylori cytotoxin-associated gene A (CagA), which is recognized as a major determinant of gastric cancer development. Additionally, a nationwide case-control study based on data from the Taiwanese National Health Insurance Research Database (NHIRD) was conducted. A population-based case-control study revealed that patients who used simvastatin exhibited a significantly reduced risk of gastric cancer (adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.70–0.83). In patients exhibiting H. pylori infection who were prescribed simvastatin, the adjusted OR for gastric cancer was 0.25 (95% CI = 0.12–0.50). Our results combined an in vitro study with a nationwide population analysis reveal that statin use might be a feasible approach to prevent H. pylori-associated gastric cancer. [ABSTRACT FROM AUTHOR]

Objectives: The role of advanced bronchoscopic diagnostic techniques in the detection and staging of lung cancer has increased sharply in recent years. The development of endobronchial ultrasound (EBUS) improved minimally invasive mediastinal staging and diagnosis of peripheral lung lesions (PLLs). We investigated the impact of using EBUS as a diagnostic method for tissue acquisition in lung cancer patients. Methods: In a single center observational retrospective study, 3712 subjects were diagnosed with lung cancer from 2003 to 2013 (EBUS was introduced in 2008). Thus, we divided the data into two periods: the conventional bronchoscopy period (2003 to 2007) and the EBUS period (2008 to 2013). Results: A total of 3712 patients were included in the analysis. Comparing the conventional bronchoscopy period with the EBUS period data, there has been a significant reduction in the use of diagnostic modalities: CT-guided biopsy (P < 0.0001) and pleural effusion cytology (P < 0.0001). The proportion of subjects diagnosed using bronchoscopy significantly increased from 39.4% in the conventional period to 47.4% in the EBUS period (P < 0.0001). In the EBUS period, there has also been a significant increase in the proportion of patients proceeding directly to diagnostic surgery (P < 0.0001). Compared to bronchoscopy, the incidence of complications was higher in those who underwent CT guide biopsy. The incidence of iatrogenic pneumothorax significantly decreased in the EBUS period. Conclusions: Advanced bronchoscopic techniques are widely used in the diagnosis of lung cancer. At our institution, the increasing use of EBUS for providing lung cancer diagnosis has led to a significant reduction in other diagnostic modalities, namely CT-guided biopsy and pleural effusion cytology. These changes in practice also led to a reduction in the incidence of complications. [ABSTRACT FROM AUTHOR]

Background: Volume of para-esophageal varices (PEV) correlates with esophageal varices recurrence. The effect of propranolol on volumetric change of PEV has not been studied. The relation between EV recurrence and volumetric change of PEV in patients undergoing endoscopic variceal ligation (EVL) with and without propranolol are studied. Methods: Sixty-six patients who achieved EV eradication by primary EVL were randomly allocated to a propranolol group ( n = 33) or control group ( n = 33). The endpoints of the study were EV recurrence and volumetric change of PEV assessed by using endoscopic ultrasonography (EUS) at 3-month intervals for 2 years. Results: The cumulative probability of recurrence at two years was 28 % in the propranolol group ( n = 9) and 68 % in the control group ( n = 20) ( p = 0.005, log-rank test). Difference of the volumetric change of PEV became significant as early as at the third month [−0.12 (−0.38-0.34) vs. 0.14 (−0.06-0.57), p < 0.001] between the two groups. Regression of PEV was achieved in 20 patients of the propranolol group at a median time of three months (range 3-12 months), and no EV recurrence was found at the end of follow-up for two years. On multivariate analysis, the volumetric change of PEV at the third month and use of propranolol were determinants of EV recurrence. Conclusions: Propranolol may reduce both EV recurrence rate and volume of PEV in patients achieving endoscopic eradication. Regression of PEV is a predictor of durable eradication of EV without recurrence in patients using propranolol. EUS is an objective and useful tool to measure PEV and predict recurrence of EV. [ABSTRACT FROM AUTHOR]

Although lymphoma and thymoma are common etiologies of anterior mediastinal masses (AMMs), smaller percentages and numbers of patients with these diseases have been enrolled in previous ultrasound-guided biopsy studies. To date, there has been no study of color Doppler sonographic features to support the differentiation of AMMs. For this retrospective cohort study, a search of the database of the China Medical University Hospital using the clinical coding “ultrasound-guided biopsy” was conducted for the period December 2003 to February 2013. We selected patients diagnosed with AMMs (not cysts) using radiographic records. This search yielded a list of 80 cases. Real-time ultrasound-guided core needle biopsy (CNB) was performed in all but 5 patients without a sufficient safety range. In 89% (67/75) of these ultrasound-guided CNB cases, the diagnostic accuracy achieved subclassification. Fine-needle aspiration cytology achieved subclassification in only 10% of cases. On color Doppler sonography, 71% of lymphomas were characterized as “rich vascular with central/crisscross collocations” and 29% as “avascular or localized/scattered peripheral vessels.” However, decreased proportions of “rich vascular with central/crisscross collocations” were found in lung cancer (4% [1/23], odds ratio = 0.018, 95% confidence interval: 0.002–0.154, p < 0.001) and thymoma/thymic carcinoma (25% [4/16]; odds ratio = 0.133, 95% confidence interval: 0.035–0.514, p = 0.003) compared with the lymphoma group. We conclude that the vessels in lymphoma AMMs have specific patterns on color Doppler sonography. Ultrasound-guided CNB of AMMs had an accuracy of ≤89% in diagnosis and subclassification. Fine-needle aspiration cytology itself cannot aid in the diagnosis. Color Doppler sonographic evaluation of AMMs followed by real-time CNB is a more efficient method. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is a major contributor to cardiovascular disease, and may cause severe morbidity and mortality. Recent studies have indicated that OSA patients exhibited elevated platelet activity, fibrinogen levels, and platelet aggregation. Objectives We investigated the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients diagnosed with OSA compared with age- and sex-matched unaffected people. Patients/Methods This longitudinal, nationwide, population-based cohort study was conducted using data from Taiwan National Health Insurance Research Database (NHIRD) recorded between January 2000 and December 2011. The study consisted of 3511 patients with OSA and 35110 matched comparison individuals. A Cox proportional hazard regression was used to compute the risk of DVT and PE in patients with OSA compared with those without OSA. Results The DVT and PE risks were 3.50- and 3.97-fold higher (95% CI=1.83-6.69 and 1.85-8.51) respectively, in the OSA cohort than in the reference cohort after we adjusted for age, sex, and comorbidities. Conclusion This nationwide population-based cohort study indicates that patients with OSA exhibit a higher risk of subsequent DVT and PE. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is the third-leading cause of mortality globally, significantly affecting people over 40 years old. COPD is often comorbid with mood disorders; however, they are frequently neglected or undiagnosed in COPD management, thus resulting in unintended treatment outcomes and higher mortality associated with the disease. Although the exact link between COPD and mood disorders remains to be ascertained, there is a broader opinion that inflammatory reactions in the lungs, blood, and inflammation-induced changes in the brain could orchestrate the onset of mood disorders in COPD. Although the current management of mood disorders such as depression in COPD involves using antidepressants, their use has been limited due to tolerability issues. On the other hand, as omega-3 polyunsaturated fatty acids (n-3 PUFAs) play a vital role in regulating inflammatory responses, they could be promising alternatives in managing mood disorders in COPD. This review discusses comorbid mood disorders in COPD as well as their influence on the progression and management of COPD. The underlying mechanisms of comorbid mood disorders in COPD will also be discussed, along with the potential role of n-3 PUFAs in managing these conditions. [ABSTRACT FROM AUTHOR]

Summary: Background: Major adjuvant treatments for pancreatic adenocarcinoma include fluorouracil, gemcitabine, chemoradiation, and chemoradiation plus fluorouracil or gemcitabine. Since the optimum regimen remains inconclusive, we aimed to compare these treatments in terms of overall survival after tumour resection and in terms of grade 3–4 toxic effects with a systematic review and random-effects Bayesian network meta-analysis. Methods: We searched PubMed, trial registries, and related reviews and abstracts for randomised controlled trials comparing the above five treatments with each other or observation alone before April 30, 2013. We estimated relative hazard ratios (HRs) for death and relative odds ratios (ORs) for toxic effects among different therapies by combining HRs for death and survival durations and ORs for toxic effects of included trials. We assessed the effects of prognostic factors on survival benefits of adjuvant therapies with meta-regression. Findings: Ten eligible articles reporting nine trials were included. Compared with observation, the HRs for death were 0·62 (95% credible interval 0·42–0·88) for fluorouracil, 0·68 (0·44–1·07) for gemcitabine, 0·91 (0·55–1·46) for chemoradiation, 0·54 (0·15–1·80) for chemoradiation plus fluorouracil, and 0·44 (0·10–1·81) for chemoradiation plus gemcitabine. The proportion of patients with positive lymph nodes was inversely associated with the survival benefit of adjuvant treatments. After adjustment for this factor, fluorouracil (HR 0·65, 0·49–0·84) and gemcitabine (0·59, 0·41–0·83) improved survival compared with observation, whereas chemoradiation resulted in worse survival than fluorouracil (1·69, 1·12–2·54) or gemcitabine (1·86, 1·04–3·23). Chemoradiation plus gemcitabine was ranked the most toxic, with significantly higher haematological toxic effects than second-ranked chemoradiation plus fluorouracil (OR 13·33, 1·01–169·36). Interpretation: Chemotherapy with fluorouracil or gemcitabine is the optimum adjuvant treatment for pancreatic adenocarcinoma and reduces mortality after surgery by about a third. Chemoradiation plus chemotherapy is less effective in prolonging survival and is more toxic than chemotherapy. Funding: None. [ABSTRACT FROM AUTHOR]

A series of oligomers and polymers having dimethylsilylene-spacedalternating 4-aminostyrene donor and stilbene acceptor chromophores(two to one) are regioselectively synthesized, and the two donor chromophoresare separated by different bridges between two donors. Photophysicaltools have been used to examine the folding behavior of these copolymers.Both steady-state and time-resolved fluorescence spectroscopic measurementswere examined. The relative intensities (ICT/ILE) between emission from charge-separatedstate (CT emission) and local excited emission of acceptor chromophore(LE emission) increase with increasing number of repeating units,and reach a plateau, when the linkers between the two aminostyrenechromophores are trimethylene bridges. Replacements of these by dimethyleneor tetramethylene linker reduce the relative intensities of CT emissionof the polymers, owing to the different folding behavior of thesepolymers. The CT emission intensity of the polymer with rigid piperazinelinkers is much lower than that with trimethylene-bridged copolymerof the same degree of polymerization. Slight conformational changeof these polymers would lead to slight variation of the distance betweendonor and acceptor chromophores so that the nonadiabatic interactionsin the excited state between donor–acceptor pairs in theseoligomers and polymers would be perturbed by such change of conformations. [ABSTRACT FROM AUTHOR]

This real-world study evaluated the efficacy of once-daily long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations (FDCs) for improving lung function in patients with chronic obstructive pulmonary disease (COPD). Patients with COPD who were treated with once-daily LABA/LAMA FDCs for 12 months were included. We evaluated their lung function improvement after 12 months of treatment with different LABA/LAMA FDCs. A total of 198 patients with COPD who were treated with once-daily LABA/LAMA FDCs were analyzed. A total of 114 patients were treated with umeclidinium/vilanterol (UMEC/VIL); 34 patients were treated with indacaterol/glycopyrronium (IND/GLY); and 50 patients were treated with tiotropium/olodaterol (TIO/OLO). The forced expiratory volume in 1 s (FEV1) was significantly increased in the patients treated with all three once-daily FDCs (55.2% to 60.9%, p = 0.012 for UMEC/VIL, 58.2% to 63.6%, p = 0.023 for IND/GLY, and 54.1% to 57.7%, p = 0.009 for TIO/OLO). The treatment of COPD patients with TIO/OLO resulted in a significant improvement in both forced vital capacity (FVC%) (71.7% to 77.9%, p = 0.009) and residual volume (RV%) (180.1% to 152.5%, p < 0.01) compared with those treated with UMEC/VIL (FVC%: 75.1% to 81.5%, p < 0.001; RV%:173.8% to 165.2%, p = 0.231) or IND/GLY (FVC%: 73.9% to 79.3%, p = 0.08; RV%:176.8% to 168.3%, p = 0.589). Patients treated with UMEC/VIL or TIO/OLO showed significant improvement in FVC. In addition, those receiving TIO/OLO also showed significant improvement in RV reduction. [ABSTRACT FROM AUTHOR]

Abstract: Biodegradability of fluorene and the versatility of fluorene metabolite (i.e. phenol) in fluorene biodegradation by a sulfate-reducing enrichment culture were investigated. Batch experiments (with 5mgl−1 fluorene) were designed via the central composite design to examine the effects of sulfate (5–35mM) and biomass (5–50mgl−1) concentrations (variables) on fluorene degradation (response). The experimental results revealed that fluorene removal was more influenced by the biomass concentration than the sulfate concentration. The optimal sulfate and biomass concentrations for fluorene biodegradation (90% removal) were found to be 14.4mM and 37.8mgl−1, respectively. Under the optimal conditions, a set of biodegradation experiments were repeated to evaluate both the biodegradability of fluorene metabolite and the potential effect of phenol accumulation on fluorene degradation. The outcomes indicated a slow phenol degradation rate, i.e. 0.02mgl−1 d−1. Moreover, a small reduction in the fluorene biodegradation efficiency was observed in the presence and accumulation of phenol. However, this sulfate reducing culture is a valuable resource for the simultaneous degradation of fluorene and phenol. [Copyright &y& Elsevier]

Statins exert cholesterol-independent beneficial effects, including immunomodulatory effects. In this study, we attempted to investigate the association between statin therapy and the risk of viral infection. We conducted a retrospective cohort study using data from Taiwan's National Health Insurance Research Database. We identified patients with hyperlipidemia and divided them into two cohorts: statin users and statin nonusers. A 1:1 propensity score matching was conducted between the two cohorts, and a Cox proportional hazards model was used to evaluate the risk of viral infection. Overall, a total of 20,202 patients were included in each cohort. The median follow-up durations were 4.41 and 6.90 years for statin nonusers and users, respectively. The risk of viral infection was 0.40-fold (95% confidence interval = 0.38–0.41) in statin users than in statin nonusers after adjustment for potential confounders. Statin treatment was associated with a significantly lower risk of viral infection in all age groups older than 18 years in both men and women. Moreover, the risk of viral infection substantially reduced as the duration of statin treatment increased. Our findings suggest that statin therapy is associated with a significantly lower risk of viral infection in patients with hyperlipidemia. [ABSTRACT FROM AUTHOR]

Background: The addition of anti-angiogenesis drugs to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) or chemotherapy in patients with EGFR-mutant non-small cell lung cancer (NSCLC) can improve disease control. We conducted a study to evaluate the efficacy of combination therapeutic strategies and identify patients who could benefit from combination therapy.Methods: This study enrolled patients with stage IV EGFR-mutant NSCLC treated with first-line EGFR-TKIs between January 2014 and December 2020. We divided patients into three groups: patients who received an anti-angiogenesis drug as first-line combination therapy, those who received an anti-angiogenesis drug as further-line combination therapy, and those with no anti-angiogenesis therapy.Results: A total of 204 patients were enrolled in the final analysis. Progression-free survival (PFS) in patients receiving first-line anti-angiogenesis plus EGFR-TKI combination therapy was longer (18.2 months) than those treated with first-line EGFR-TKI monotherapy (10.0 months for both, p < 0.001). No difference in overall survival (OS) was observed among these three groups (30.5 vs. 42.6 vs. 33.7 months, p = 0.326). Multivariate Cox regression analysis revealed L858R mutation, pleural, liver, and bone metastasis as independent prognostic factors for poor OS. However, the addition of anti-angiogenesis therapy to patients with these poor prognostic factors improved OS to levels similar to those without these poor prognostic factors.Conclusion: First-line combination EGFR-TKI plus anti-angiogenesis therapy improves PFS in patients with stage IV EGFR-mutant NSCLC. Adding an anti-angiogenesis drug at any line to patients harboring L858R mutation with pleural, liver, or bone metastases can provide survival benefits. [ABSTRACT FROM AUTHOR]

The coronavirus disease (COVID-19) pandemic has resulted in an increasing population that is experiencing a wide range of long-lasting symptoms after recovery from the acute infection. Long COVID refers to this specific condition and is associated with diverse symptoms, such as fatigue, myalgias, dyspnea, headache, cognitive impairment, neurodegenerative symptoms, anxiety, depression, and a sense of despair. The potential of hyperbaric oxygen therapy (HBOT) to improve chronic fatigue, cognitive impairments, and neurological disorders has been established; therefore, the use of HBOT to treat long COVID has also been studied. We conducted a literature search between 1 January 2019 and 30 October 2023, focusing on the clinical efficacy and utility of HBOT for treating long COVID and found ten clinical studies that fit the review topic, including one case report, five one-group pretest-posttest design studies, one safety report from a randomized controlled trial (RCT), and three complete reports of RCTs. Most studies found that HBOT can improve quality of life, fatigue, cognition, neuropsychiatric symptoms, and cardiopulmonary function. Although HBOT has shown some benefits for long COVID symptoms, further rigorous large-scale RCTs are required to establish precise indications, protocols, and post-treatment evaluations. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine the clinical characteristics of bone metastasis (BoM) in patients with non‐small cell lung cancer (NSCLC) who have an epidermal growth factor receptor (EGFR) mutation and to identify the most effective treatment strategy using EGFR–tyrosine kinase inhibitors (TKIs). Methods: The study included patients with stage IV EGFR‐mutated NSCLC who were receiving first‐line treatment with EGFR–TKIs between January 2014 and December 2020. These patients were divided into two groups based on the presence or absence of BoM at the time of initial diagnosis. The BoM group was further subdivided based on whether they received denosumab or not. Results: The final analysis included 247 patients. Those with BoM at initial diagnosis had shorter progression‐free survival (12.6 vs. 10.5 months, p = 0.002) and overall survival (OS) (49.7 vs. 30.9 months, p = 0.002) compared to those without BoM. There was a difference in the location of metastatic sites between the two groups, with a higher incidence of extrathoracic metastasis in the BoM group (p < 0.001). The incidence of T790M was higher in patients with BoM than in those without (47.4% vs. 33.9%, p = 0.042). Multivariate Cox regression analysis revealed that sequential osimertinib treatment and the addition of antiangiogenic therapy (AAT) and denosumab therapy improved OS in patients with BoM. Conclusions: The presence of BoM is a negative prognostic factor for NSCLC patients with an EGFR mutation, possibly due to the presence of extrathoracic metastases. However, adding AAT and denosumab, along with sequential osimertinib, to the treatment regimen for patients with BoM can improve survival outcomes. [ABSTRACT FROM AUTHOR]

Objective Preterm infants are at high risk of neuromotor disorders. Recent advances in digital technology and machine learning algorithms have enabled the tracking and recognition of anatomical key points of the human body. It remains unclear whether the proposed pose estimation model and the skeleton-based action recognition model for adult movement classification are applicable and accurate for infant motor assessment. Therefore, this study aimed to develop and validate an artificial intelligence (AI) model framework for movement recognition in full-term and preterm infants. Methods This observational study prospectively assessed 30 full-term infants and 54 preterm infants using the Alberta Infant Motor Scale (58 movements) from 4 to 18 months of age with their movements recorded by 5 video cameras simultaneously in a standardized clinical setup. The movement videos were annotated for the start/end times and presence of movements by 3 pediatric physical therapists. The annotated videos were used for the development and testing of an AI algorithm that consisted of a 17-point human pose estimation model and a skeleton-based action recognition model. Results The infants contributed 153 sessions of Alberta Infant Motor Scale assessment that yielded 13,139 videos of movements for data processing. The intra and interrater reliabilities for movement annotation of videos by the therapists showed high agreements (88%–100%). Thirty-one of the 58 movements were selected for machine learning because of sufficient data samples and developmental significance. Using the annotated results as the standards, the AI algorithm showed satisfactory agreement in classifying the 31 movements (accuracy = 0.91, recall = 0.91, precision = 0.91, and F1 score = 0.91). Conclusion The AI algorithm was accurate in classifying 31 movements in full-term and preterm infants from 4 to 18 months of age in a standardized clinical setup. Impact The findings provide the basis for future refinement and validation of the algorithm on home videos to be a remote infant movement assessment. [ABSTRACT FROM AUTHOR]

Objective: Pancreatic cancer-associated diabetes (PCDM) is a paraneoplastic phenomenon accounting for 1% of new-onset diabetes. We aimed to identify the mediators of PCDM and evaluate their usefulness in distinguishing PCDM from type 2 diabetes.Research Design and Methods: Secreted proteins of MIA PaCa-2 cells were identified by proteomics, and those with ≥10-fold overexpression in transcriptome analysis were assessed by bioinformatics and glucose uptake assay to identify candidate factors. Expression of factors was compared between tumors with and without PCDM by immunohistochemistry. Serum levels were measured in a training set including PC with and without PCDM, type 2 diabetes, pancreatitis, other pancreatic/peripancreatic tumors, and control subjects (n = 50 each). Cutoff values for differentiation between PCDM and type 2 diabetes from the training set were validated in a test set (n = 41 each).Results: Galectin-3 and S100A9 were overexpressed in tumors with PCDM and dose-dependently suppressed insulin-stimulated glucose uptake in C2C12 myotubes. In the training set, serum galectin-3 and S100A9 levels were exclusively increased in patients with PCDM and distinguished PCDM from type 2 diabetes (area under the curve [AUC] galectin-3: 0.73 [95% CI 0.64-0.83]; S100A9: 0.79 [95% CI 0.70-0.87]). Similar results were observed in the test set (AUC galectin-3: 0.83 [95% CI 0.74-0.92]; S100A9: 0.77 [95% CI 0.67-0.87]), with sensitivity and specificity 72.1% and 86.1%, respectively, for galectin-3 and 69.8% and 58.1% for S100A9 in differentiating between PCDM and type 2 diabetes.Conclusions: Galectin-3 and S100A9 are overexpressed in PCDM tumors and mediate insulin resistance. Galectin-3 and S100A9 distinguish PCDM from type 2 diabetes in subjects with new-onset diabetes. [ABSTRACT FROM AUTHOR]

Glass‐ceramics are multi‐phase materials that are comprised of one amorphous phase and at least one crystalline phase. Their versatile performance and properties can be engineered by alterations of the three fundamental steps – formulation and production of the amorphous base glass, nucleation, and crystallization. Efforts have been made on syntheses of glass‐ceramics with different components, yet little is known about the details of nucleation and crystallization processes that are essential for tailoring glass‐ceramic properties. Herein, we investigate the nucleation and crystallization mechanisms of a multi‐component, that is SiO2‐Al2O3‐CaO‐Li2O‐K2O‐P2O5‐F, glass‐ceramic system by a combined use of powder X‐ray diffraction (pXRD), solid‐state nuclear magnetic resonance (NMR), and electron microscopic (EM) techniques. The role of P2O5 in the nucleation and crystallization processes is particularly studied. We show that the formation of lithium silicate crystals being independent of the P2O5‐associated crystals, and the separation of P2O5 phases into individual growth domains of lithium orthophosphate and fluorapatite. We also observe the non‐uniform distribution of fluorapatite particles that explains the opalescence effect of this glass‐ceramic. [ABSTRACT FROM AUTHOR]

Background: Selective deep biliary cannulation is the first and the most important step before further biliary therapy. Transpancreatic sphincterotomy (TPS), and needle knife fistulotomy (NKF) were commonly used in patients with difficult cannulation, but few studies compare the outcome between TPS and NKF.Methods: A total of 78 patients who met the criteria of difficult cannulation in the National Taiwan University hospital from October 2015 to October 2017 were retrospectively reviewed. Their baseline demographics, success rate of biliary cannulation, and the rate of adverse events were assessed.Results: 31 patients and 47 patients underwent TPS and NKF for difficult biliary access, respectively. The characteristics of the 2 groups were similar, but patients in TPS group had more frequent pancreatic duct cannulation. Bile duct cannulation was successful in 23 patients (74.2%) in the TPS group and 39 (83.0%) in the NKF group (P = 0.34). There was no difference between the TPS and NKF in the rate of adverse events, including post-ERCP pancreatitis (PEP) (16.1% vs. 6.4%, p = 0.17), and hemorrhage (3.2% vs. 8.5%, p = 0.35). No perforation occurred.Conclusions: Both TPS and NKF have good biliary access rate in patient with difficult cannulation. TPS has acceptable successful rate and similar complication rate, compared with NKF. [ABSTRACT FROM AUTHOR]

Fischer and Schrock carbenes display highly deshielded carbon chemical shifts (>250 ppm), in particular Fischer carbenes (>300 ppm). Orbital analysis of the principal components of the chemical shift tensors determined by solid-state NMR spectroscopy and calculated by a 2-component DFT method shows specific patterns that act as fingerprints for each type of complex. The calculations highlight the role of the paramagnetic term in the shielding tensor especially in the two most deshielded components (σ11 and σ22). The paramagnetic term of σ11 is dominated by coupling σ(M=C) with π*(M=C) through the angular momentum operator perpendicular to the σ and π M=C bonds. The highly deshielded carbon of Fischer carbenes results from the particularly low-lying π*(M=C) associated with the CO ligand. A contribution of the coupling of π(M=C) with σ*(M=C) is found for Schrock and Ru-based carbenes, indicating similarities between them, despite their different electronic configurations (d0 vs. d6). [ABSTRACT FROM AUTHOR]

Fischer and Schrock carbenes display highly deshielded carbon chemical shifts (>250 ppm), in particular Fischer carbenes (>300 ppm). Orbital analysis of the principal components of the chemical shift tensors determined by solid-state NMR spectroscopy and calculated by a 2-component DFT method shows specific patterns that act as fingerprints for each type of complex. The calculations highlight the role of the paramagnetic term in the shielding tensor especially in the two most deshielded components (σ11 and σ22). The paramagnetic term of σ11 is dominated by coupling σ(M=C) with π*(M=C) through the angular momentum operator perpendicular to the σ and π M=C bonds. The highly deshielded carbon of Fischer carbenes results from the particularly low-lying π*(M=C) associated with the CO ligand. A contribution of the coupling of π(M=C) with σ*(M=C) is found for Schrock and Ru-based carbenes, indicating similarities between them, despite their different electronic configurations (d0 vs. d6). [ABSTRACT FROM AUTHOR]

Patients with hematologic malignancies (HMs) have a significantly elevated risk of mortality compared to other cancer patients treated in the intensive care unit (ICU). The prognostic impact of numerous poor outcome indicators has changed, and research has yielded conflicting results. This study aims to determine the ICU and hospital outcomes and risk factors that predict the prognosis of critically ill patients with HMs. In this retrospective study, conducted at a referral hospital in Taiwan, 213 adult patients with HMs who were admitted to the medical ICU were evaluated. We collected clinical data upon hospital and ICU admission. Using a multivariate regression analysis, the predictors of ICU and hospital mortality were assessed. Then, a scoring system (Hospital outcome of critically ill patients with Hematological Malignancies (HHM)) was built to predict hospital outcomes. Most HMs (76.1%) were classified as high grade, and more than one-third of patients experienced a relapsed or refractory disease. The ICU and hospital mortality rates were 55.9% and 71.8%, respectively. Moreover, the disease severity was high (median Sequential Organ Failure Assessment (SOFA) score: 11 and Acute Physiology and Chronic Health Evaluation (APACHE II) score: 28). The multivariate analysis revealed that high-grade HMs, invasive mechanical ventilation requirement, renal replacement therapy initiation in the ICU, and a high SOFA score correlated with ICU mortality. Furthermore, a higher HHM score predicted hospital mortality. This study demonstrates that ICU mortality primarily correlates with the severity of organ dysfunction, whereas the disease status markedly influences hospital outcomes. Furthermore, the HHM score significantly predicts hospital mortality. [ABSTRACT FROM AUTHOR]

Background: Anti-reflux mucosal intervention (ARMI), including anti-reflux mucosectomy (ARMS) and anti-reflux mucosal ablation (ARMA), is a promising endoscopic treatment for gastroesophageal reflux disease (GERD). Few studies reported a detailed analysis of the objective reflux parameters. Methods: Patients with chronic PPI-dependent GERD and receiving ARMI were prospectively enrolled. Comprehensive clinical symptom profiles, endoscopy results, and 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring were collected and analyzed before and 3 months after ARMI. Results: Twenty-three patients undergoing ARMI (11 ARMS and 12 ARMA) were enrolled. The median (IQR) operative time and post-procedure stays were 50 (46–56) min and 2 (2–2) days without major complications. 73.9% of patients reported subjective global improvement. A significant decrease in the total reflux symptom index score was noted from 12 (5–19) to 8 (4–12) (P = 0.010). The esophageal acid exposure time (AET) significantly decreased from 4.6 (2.8–6.9) to 2.1 (1.1–5.6) (P = 0.013), and the number of acid refluxes and DeMeester score were significantly reduced. Three patients (13%) had increased AET (3.4% to 6.1%, 6.3% to 15.4%, and 3.2% to 5.6%); however, all reported global improvement and two patients could discontinue PPI subjectively. One patient (4.3%) had worsened erosive esophagitis and reflux symptoms. 56.5% of patients stopped PPI. Conclusions: ARMI is generally effective and safe in PPI-dependent patients. However, possible negative effects of ARMI exist in some patients; further application of MII-pH is necessitated to evaluate the treatment response after ARMI and avoid the detrimental effect of PPI discontinuation. Graph. [ABSTRACT FROM AUTHOR]

Simple Summary: The addition of bevacizumab or ramucirumab to systemic therapy for EGFR-mutated non-small-cell lung cancer (NSCLC) patients provides survival benefits. No study to date has compared the efficacy and safety of these two antiangiogenic therapies (AATs). This study enrolled patients with stage IIIB to IV EGFR-mutated NSCLC who were treated with first-line EGFR-TKIs between January 2014 and May 2022. The progression-free survival (PFS) of patients who received front-line AATs combined with EGFR-TKI therapy was longer than that of patients receiving later-line AATs combined with other therapies (19.6 vs. 10.0 months, p < 0.001). Bevacizumab and ramucirumab did not differ in PFS (24.1 vs. 15.7 months, p = 0.454). No difference in overall survival (OS) was observed between front-line and later-line therapy (non-reach vs. 44.0 months, p = 0.261) or between the two AATs (48.6 vs. 43.0 months, p = 0.924). The incidence of some adverse events such as bleeding and hepatitis was higher for bevacizumab than for ramucirumab but it was not significant. The effectiveness and safety of the two AATs were similar. The combination of bevacizumab or ramucirumab with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy, chemotherapy, or immunotherapy for non-small-cell lung cancer (NSCLC) patients with EGFR mutations could have survival benefits. However, no study, to date, has been conducted to compare the efficacy and safety of these two antiangiogenic therapies (AATs). Stage IIIB to IV EGFR-mutated NSCLC patients who received first-line EGFR-TKIs between January 2014 and May 2022 were enrolled. These patients were divided into two groups: those receiving bevacizumab and those receiving ramucirumab as a combination therapy in any line of treatment. Ninety-six patients were enrolled in this study's final analysis. The progression-free survival (PFS) of patients who received front-line AATs combined with EGFR-TKI therapy was longer than that of patients receiving later-line AATs combined with other therapies (19.6 vs. 10.0 months, p < 0.001). No difference in overall survival (OS) was observed between front-line and later-line therapy (non-reach vs. 44.0 months, p = 0.261). Patients who received these two different AATs did not differ in PFS (24.1 vs. 15.7 months, p = 0.454) and OS (48.6 vs. 43.0 months, p = 0.924). In addition, these two AATs showed similar frequencies of the T790M mutation (43.6% vs. 38.2%; p = 0.645). Multivariate Cox regression analysis indicated several AAT cycles as an independent good prognostic factor in OS. The incidence of some adverse events such as bleeding and hepatitis was higher for bevacizumab than for ramucirumab but it was not significant. Front-line AAT and EGFR-TKI combination therapy improved the PFS of stage IV EGFR-mutated NSCLC patients. The effectiveness and safety of the two AATs were similar. [ABSTRACT FROM AUTHOR]

Background: CT is the major detection tool for pancreatic cancer (PC). However, approximately 40% of PCs < 2 cm are missed on CT, underscoring a pressing need for tools to supplement radiologist interpretation. Methods: Contrast-enhanced CT studies of 546 patients with pancreatic adenocarcinoma diagnosed by histology/cytology between January 2005 and December 2019 and 733 CT studies of controls with normal pancreas obtained between the same period in a tertiary referral center were retrospectively collected for developing an automatic end-to-end computer-aided detection (CAD) tool for PC using two-dimensional (2D) and three-dimensional (3D) radiomic analysis with machine learning. The CAD tool was tested in a nationwide dataset comprising 1,477 CT studies (671 PCs, 806 controls) obtained from institutions throughout Taiwan. Results: The CAD tool achieved 0.918 (95% CI, 0.895–0.938) sensitivity and 0.822 (95% CI, 0.794–0.848) specificity in differentiating between studies with and without PC (area under curve 0.947, 95% CI, 0.936–0.958), with 0.707 (95% CI, 0.602–0.797) sensitivity for tumors < 2 cm. The positive and negative likelihood ratios of PC were 5.17 (95% CI, 4.45–6.01) and 0.10 (95% CI, 0.08–0.13), respectively. Where high specificity is needed, using 2D and 3D analyses in series yielded 0.952 (95% CI, 0.934–0.965) specificity with a sensitivity of 0.742 (95% CI, 0.707–0.775), whereas using 2D and 3D analyses in parallel to maximize sensitivity yielded 0.915 (95% CI, 0.891–0.935) sensitivity at a specificity of 0.791 (95% CI, 0.762–0.819). Conclusions: The high accuracy and robustness of the CAD tool supported its potential for enhancing the detection of PC. [ABSTRACT FROM AUTHOR]

Background: CT is the major detection tool for pancreatic cancer (PC). However, approximately 40% of PCs < 2 cm are missed on CT, underscoring a pressing need for tools to supplement radiologist interpretation. Methods: Contrast-enhanced CT studies of 546 patients with pancreatic adenocarcinoma diagnosed by histology/cytology between January 2005 and December 2019 and 733 CT studies of controls with normal pancreas obtained between the same period in a tertiary referral center were retrospectively collected for developing an automatic end-to-end computer-aided detection (CAD) tool for PC using two-dimensional (2D) and three-dimensional (3D) radiomic analysis with machine learning. The CAD tool was tested in a nationwide dataset comprising 1,477 CT studies (671 PCs, 806 controls) obtained from institutions throughout Taiwan. Results: The CAD tool achieved 0.918 (95% CI, 0.895–0.938) sensitivity and 0.822 (95% CI, 0.794–0.848) specificity in differentiating between studies with and without PC (area under curve 0.947, 95% CI, 0.936–0.958), with 0.707 (95% CI, 0.602–0.797) sensitivity for tumors < 2 cm. The positive and negative likelihood ratios of PC were 5.17 (95% CI, 4.45–6.01) and 0.10 (95% CI, 0.08–0.13), respectively. Where high specificity is needed, using 2D and 3D analyses in series yielded 0.952 (95% CI, 0.934–0.965) specificity with a sensitivity of 0.742 (95% CI, 0.707–0.775), whereas using 2D and 3D analyses in parallel to maximize sensitivity yielded 0.915 (95% CI, 0.891–0.935) sensitivity at a specificity of 0.791 (95% CI, 0.762–0.819). Conclusions: The high accuracy and robustness of the CAD tool supported its potential for enhancing the detection of PC. [ABSTRACT FROM AUTHOR]

In contrast to the "one‐size‐fits‐all" approach, precision medicine focuses on providing health care tailored to individual variabilities. Implementing precision medicine in endoscopy practice involves selecting the appropriate procedures among the endoscopic armamentarium in the diagnosis and management of patients in a logical sequence, jointly considering the pretest probabilities of possible diagnoses, patients' comorbidities and preference, and risk–benefit ratio of the individual procedures given the clinical scenario. The aim of this review is to summarize evidence‐supported strategies and measures that may enhance precision medicine in general endoscopy practice. [ABSTRACT FROM AUTHOR]

We performed the present study to investigate the role of computed tomography (CT) radiomics in differentiating nonfunctional adenoma and aldosterone-producing adenoma (APA) and outcome prediction in patients with clinically suspected primary aldosteronism (PA). This study included 60 patients diagnosed with essential hypertension (EH) with nonfunctional adenoma on CT and 91 patients with unilateral surgically proven APA. Each whole nodule on unenhanced and venous phase CT images was segmented manually and randomly split into training and test sets at a ratio of 8:2. Radiomic models for nodule discrimination and outcome prediction of APA after adrenalectomy were established separately using the training set by least absolute shrinkage and selection operator (LASSO) logistic regression, and the performance was evaluated on test sets. The model can differentiate adrenal nodules in EH and PA with a sensitivity, specificity, and accuracy of 83.3%, 78.9% and 80.6% (AUC = 0.91 [0.72, 0.97]) in unenhanced CT and 81.2%, 100% and 87.5% (AUC = 0.98 [0.77, 1.00]) in venous phase CT, respectively. In the outcome after adrenalectomy, the models showed a favorable ability to predict biochemical success (Unenhanced/venous CT: AUC = 0.67 [0.52, 0.79]/0.62 [0.46, 0.76]) and clinical success (Unenhanced/venous CT: AUC = 0.59 [0.47, 0.70]/0.64 [0.51, 0.74]). The results showed that CT-based radiomic models hold promise to discriminate APA and nonfunctional adenoma when an adrenal incidentaloma was detected on CT images of hypertensive patients in clinical practice, while the role of radiomic analysis in outcome prediction after adrenalectomy needs further investigation. [ABSTRACT FROM AUTHOR]

Background: The treatment options for epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancer (NSCLC) with brain metastases (BMs) include EGFR‐tyrosine kinase inhibitors (TKIs), stereotactic radiosurgery (SRS), whole‐brain radiotherapy, brain surgery, and antiangiogenesis therapy. As treatment options evolve, redefining optimal treatment strategies to improve survival are crucial. Methods: A total of 150 EGFR‐mutant NSCLC patients with BMs who received first‐ or second‐generation EGFR‐TKIs as first‐line treatment between January 2012 and October 2019 were included in this analysis. Results: After multivariate analysis, patients with the graded prognostic assessment for lung cancer using molecular markers (Lung‐mol GPA) ≥3 (hazard ratio [HR]: 0.538, 95% confidence interval [CI]: 0.35–0.83), who received afatinib or erlotinib as first‐line treatment (HR: 0.521, 95% CI: 0.33–0.82), underwent SRS therapy (HR: 0.531, 95% CI: 0.32–0.87), or were sequentially treated with osimertinib (HR: 0.400, 95% CI: 0.23–0.71) were associated with improved overall survival (OS). Furthermore, SRS plus EGFR‐TKI provided more OS benefits in patients with Lung‐mol GPA ≥3 compared with EGFR‐TKI alone in our patient cohort (44.9 vs. 26.7 months, p = 0.005). The OS in patients who received sequential osimertinib therapy was significantly longer than those without osimertinib treatment (43.5 vs. 24.3 months, p < 0.001), regardless of T790 mutation status (positive vs. negative vs. unknown: 40.4 vs. 54.6 vs.43.4 months, p = 0.227). Conclusions: The study demonstrated that EGFR‐mutant NSCLC patients with BMs could be precisely treated with SRS according to Lung‐mol GPA ≥3. Sequential osimertinib was associated with prolonged survival, regardless of T790M status. [ABSTRACT FROM AUTHOR]

Background: Most studies of prognostic factors after a variceal hemorrhage have either excluded or only involved a few patients with bleeding from gastric variceal bleeding (GVB) and hepatocellular carcinoma (HCC). We have investigated risk factors for early re-bleeding and mortality in patients with GVB and HCC and attempted to determine the effect of HCC characteristics on portal hypertension-related re-bleeding. Methods: This was a retrospective study of data complied on 109 patients with GVB and concomitant HCC in prospectively collected databases. HCC patients were divided into those with recently developed HCC (rd-HCC; HCC diagnosed within 2 months before or after GVB) and those with previously diagnosed HCC (pd-HCC; HCC diagnosed 2 months before GVB). Predictors for 5-day portal hypertension re-bleeding, 30-day and 5-year mortality were analyzed. Results: The cumulative 5-day re-bleeding rates in the rd-HCC group versus the pd-HCC group was 23.5 versus 10.0% ( P = 0.019). rd-HCC, a high model for end-stage liver disease (MELD) score (>15), and active bleeding were predictors for 5-day re-bleeding. The cumulative 30-day and 5-year survival for the rd-HCC group versus the pd-HCC group were 76.0 versus 76.5% ( P = 0.980) and 16.0 versus 4.7% ( P = 0.099), respectively. Advanced tumor stage, high MELD score (>15), and elevated alanine transaminase were predictors of mortality. Conclusion: Patients with GVB and concomitant HCC are associated with poor outcomes. Recently developed HCC, a high MELD score, active bleeding, advanced tumor stage, and elevated alanine transaminase are poor prognostic predictors. Apart from pharmacological and endoscopic treatments for GVB, careful investigation of a recently developed HCC in these patients is mandatory. [ABSTRACT FROM AUTHOR]

The application of artificial intelligence (AI) in medicine has increased rapidly with respect to tasks including disease detection/diagnosis, risk stratification, and prognosis prediction. With recent advances in computing power and algorithms, AI has shown promise in taking advantage of vast electronic health data and imaging studies to supplement clinicians. Machine learning and deep learning are the most widely used AI methodologies for medical research and have been applied in pancreatobiliary diseases for which diagnosis and treatment selection are often complicated and require joint consideration of data from multiple sources. The aim of this review is to provide a concise introduction of the major AI methodologies and the current landscape of AI research in pancreatobiliary diseases. [ABSTRACT FROM AUTHOR]

Distal biliary strictures (DBS) are common and may be caused by both malignant and benign pathologies. While endoscopic procedures play a major role in their management, a comprehensive review of the subject is still lacking. Our consensus statements were formulated by a group of expert Asian pancreatico‐biliary interventional endoscopists, following a proposal from the Digestive Endoscopy Society of Taiwan, the Thai Association for Gastrointestinal Endoscopy, and the Tokyo Conference of Asian Pancreato‐biliary Interventional Endoscopy. Based on a literature review utilizing Medline, Cochrane library, and Embase databases, a total of 19 consensus statements on DBS were made on diagnosis, endoscopic drainage, benign biliary stricture, malignant biliary stricture, and management of recurrent biliary obstruction and other complications. Our consensus statements provide comprehensive guidance for the endoscopic management of DBS. [ABSTRACT FROM AUTHOR]

Background: It has been unclear whether diabetes mellitus (DM) is positively associated with a risk of venous thromboembolism (VTE). In addition, whether the risk of VTE is altered in patients with type 1 diabetes (T1DM) has rarely been explored. Aim: We investigated whether patients with T1DM are at a relatively high risk of VTE development. Methods: We retrieved data from the National Health Insurance Research Database of Taiwan to conduct this retrospective cohort study. The T1DM group consisted of 4967 patients diagnosed as having T1DM before 2003. The non-T1DM group comprised 19 868 age- and sex-matched enrollees without T1DM. Cox proportional hazard regression analysis was used to investigate the hazard ratio of VTE in patients with T1DM relative to those without T1DM. Results: During a mean follow-up period of 8.61 years, the risk of VTE in the T1DM group was 5.33-fold higher than in the non-T1DM group after adjusting for dyslipidemia, hypertension, stroke, lower leg fracture or surgery, and obesity. Further stratified analysis revealed that the risk of VTE was significantly high in both sexes and in all age groups below the age of 60. Conclusion: T1DM appears to be an independent risk factor for VTE development. [ABSTRACT FROM AUTHOR]

Background and Aim: Local complications of acute pancreatitis (AP) carry risks of morbidity/mortality. This study aimed to assess whether urinary trypsinogen‐2 levels and Bedside Index for Severity in Acute Pancreatitis (BISAP) score on admission predicted subsequent local complications. Methods: One hundred and forty‐four consecutive patients with AP were prospectively followed till 6 months after discharge. Urinary trypsinogen‐2 levels were measured within 24 h of admission. Local complications (acute peripancreatic fluid collection, acute necrotic collection, pseudocyst, and walled‐off necrosis) were diagnosed by abdominal computed tomography. Cut‐off for trypsinogen‐2 level was assessed using receiver operating characteristic curve, and predictors of local complications were analyzed by logistic regression. Results: Thirty‐seven (25.7%) patients developed local complications. Urinary trypsinogen‐2 levels were significantly higher in patients with local complications compared with those without local complications (median [interquartile range], 3210 [620–9764.4] μg/L vs 627.3 [72.3–5895] μg/L, P = 0.006). Urinary trypsinogen‐2 significantly outperformed BISAP score in predicting local complications (area under the receiver operating characteristic curve 0.65 [95% CI: 0.55–0.75] vs 0.48 [95% CI: 0.38–0.58], P = 0.005). At the optimal cut‐off of 500 μg/L, the sensitivity, specificity, positive predictive value, and negative predictive value of trypsinogen‐2 level were 78.4%, 45.8%, 33.3%, and 86.0%, respectively. Urinary trypsinogen‐2 level > 500 μg/L was an independent predictor of local complications (adjusted odds ratio, 3.72; 95% CI: 1.42–9.76; P = 0.007). By contrast, BISAP score ≥ 3 and pleural effusion predicted organ failure but not local complications. Conclusion: In a prospective cohort, urinary trypsinogen‐2 level > 500 μg/L independently predicted local complications of AP. [ABSTRACT FROM AUTHOR]

• A computer-aided diagnosis (CAD) system was proposed to diagnose the lung cancer in endobronchial ultrasound (EBUS) images. • In this study, a CAD system using the convolutional neural network (CNN) was proposed to automatically differentiate benign and malignant lesions for early detecting lung cancer. • The results of our CAD system show that the accuracy, sensitivity, specificity, and the area under ROC achieved 85.4%, 87.0%, 82.1%, and 0.8705, respectively. • Our study has demonstrated that CAD system based on the CNN architecture could provide an automatic method to differentiate benign and malignant lesions in patients with lung cancer. In the United States, lung cancer is the leading cause of cancer death. The survival rate could increase by early detection. In recent years, the endobronchial ultrasonography (EBUS) images have been utilized to differentiate between benign and malignant lesions and guide transbronchial needle aspiration because it is real-time, radiation-free and has better performance. However, the diagnosis depends on the subjective judgment from doctors. In some previous studies, which using the grayscale image textures of the EBUS images to classify the lung lesions but it belonged to semi-automated system which still need the experts to select a part of the lesion first. Therefore, the main purpose of this study was to achieve full automation assistance by using convolution neural network. First of all, the EBUS images resized to the input size of convolution neural network (CNN). And then, the training data were rotated and flipped. The parameters of the model trained with ImageNet previously were transferred to the CaffeNet used to classify the lung lesions. And then, the parameter of the CaffeNet was optimized by the EBUS training data. The features with 4096 dimension were extracted from the 7th fully connected layer and the support vector machine (SVM) was utilized to differentiate benign and malignant. This study was validated with 164 cases including 56 benign and 108 malignant. According to the experiment results, applying the classification by the features from the CNN with transfer learning had better performance than the conventional method with gray level co-occurrence matrix (GLCM) features. The accuracy, sensitivity, specificity, and the area under ROC achieved 85.4% (140/164), 87.0% (94/108), 82.1% (46/56), and 0.8705, respectively. From the experiment results, it has potential ability to diagnose EBUS images with CNN. [ABSTRACT FROM AUTHOR]