Background & Aims
This multicenter cohort study aimed to compare the real‐world biochemical response rates during tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) ...treatment in chronic hepatitis B virus (HBV) infection patients.
Methods
Overall, 1282 treatment‐naïve patients with CHB who commenced TAF (n = 270), TDF (n = 617), or ETV (n = 395) were analysed for biochemical response rates during the antiviral treatment using a time‐dependent Cox proportional hazard model after the inverse probability of treatment weighting (IPTW).
Results
Patients treated with ETV were older (55.1 ± 11.5 years) than TAF or TDF (P < .0001). ETV was more frequently prescribed to patients with diabetes mellitus (DM, P = .003), hypertension (P < .0001), chronic kidney disease (P < .0001), and negative e‐antigen (P < .0001). Cumulative biochemical response rate was independently lower in patients with radiologic fatty liver (HR, 0.75; 95% CI, 0.61‐0.94) and obese patients without DM (HR, 0.85; 95% CI, 0.68‐0.98) according to multivariable Cox analyses based on time‐dependent variables after IPTW for age, sex, liver cirrhosis, baseline e‐antigen, ALT, and HBV DNA levels. ETV treated patients (HR, 1.38; 95% CI, 1.13‐1.68) showed higher biochemical response rates compared with TAF‐ or TDF‐treated patients after adjusting for similar parameters.
Conclusions
In real‐world practice, ETV was preferable for older, hepatitis B e‐antigen negative patients with underlying comorbidities. Biochemical responses in patients treated with ETV, TAF, and TDF were significantly affected by metabolic factors such as fatty liver, obesity, and DM. However, the mechanism behind the higher biochemical response rate in patients treated with ETV should be investigated further.
Diagnosis of lymphoma involving the central nervous system (CNS) is challenging. This study aimed to explore the abnormal vestibular and ocular motor findings in CNS lymphoma.
A retrospective search ...of the medical records identified 30 patients with CNS lymphoma presenting ocular motor and vestibular abnormalities from four neurology clinics of university hospitals in South Korea (22 men, age range 14-81 years, mean 60.6 ± 15.2). The demographic and clinical features and the results of laboratory, radiological and pathological evaluation were analyzed.
Patients presented with diplopia (13/30, 43%), vestibular symptoms (15/30, 50%) or both (2/30, 7%). In 15 patients with diplopia, abnormal ocular motor findings included ocular motor nerve palsy (n = 10, 67%), internuclear ophthalmoplegia (n = 2, 13%), external ophthalmoplegia (n = 2, 13%) and exophoria (n = 1, 7%). The vestibular abnormalities were isolated in 14 (82%) of 17 patients with vestibular symptoms and included combined unilateral peripheral and central vestibulopathy in three from lesions involving the vestibular nuclei. CNS lymphoma involved the brainstem (53%), cerebellum (33%), leptomeninges (30%), deep gray nuclei (23%) or cranial nerves (17%). Two patients showed the "double-panda" sign by involving the midbrain.
This study expands the clinical and radiological spectra of CNS lymphoma. Neuro-ophthalmological and neuro-otological evaluation may guide the early diagnosis of CNS lymphoma.
Abstract
Background
Tumor necrosis factor (TNF) inhibitors use in patients with rheumatoid arthritis (RA) has raised safety concerns about cancer risk, but study results remain controversial. This ...largest nationwide study to date compared cancer risk in TNF inhibitor users to non-biologic disease-modifying anti-rheumatic drug (nbDMARD) users in Korean patients with RA.
Methods
Data on all the eligible patients diagnosed with RA between 2005 and 2016 were retrieved from the Korean National Health Information Database. The one-to-one matched patients consisted of the matched cohort. The risks for developing all-type and site-specific cancers were estimated using incidence and incidence rate (IR) per 1000 person-years. Adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using a Cox regression model.
Results
Of the 22,851 patients in the before matching cohort, 4592 patients were included in the matched cohort. Treatment with TNF inhibitors was consistently associated with a lower risk of cancer than in the nbDMARD cohort (IR per 1000 person-years, 6.5 vs. 15.6; adjusted HR, 0.379; 95% CI, 0.255–0.563). The adjusted HR (95% CI) was significantly lower in the TNF inhibitor cohort than the nbDMARD cohort for gastrointestinal cancer (0.432; 0.235–0.797), breast cancer (0.146; 0.045–0.474), and genitourinary cancer (0.220; 0.059–0.820).
Conclusions
The use of TNF inhibitors was not associated with an increased risk of cancer development, and rather associated with a lower cancer incidence in Korean patients with RA. Cautious interpretation is needed not to oversimplify the study results as cancer-protective effects of TNF inhibitors. A further study linking claims and clinical data is needed to confirm our results.
To investigate the patterns of imaging appearance of hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced magnetic resonance (MR) images and to assess their potential value as prognostic markers ...of HCC associated with tumor recurrence after surgery.
The institutional review board approved this retrospective study and informed consent was waived. A total of 216 patients with 304 pathologically proved HCCs underwent gadoxetic acid-enhanced MR imaging prior to surgery and were included in the study. Two reviewers, blinded to the clinical data, evaluated in consensus the imaging patterns of HCC according to enhancement patterns on dynamic phase images and signal intensity on hepatobiliary phase (HBP) images. The association of imaging features with clinical-pathologic findings was evaluated by using the Student t test, χ(2) test, Mann-Whitney U test, and linear-by-linear association. The dependence of time to tumor recurrence (TTR) after surgery was evaluated by using the Kaplan-Meier method, log-rank test, and Cox proportional hazard model.
HCCs with atypical enhancement pattern (P = .0167, P = .0450, P < .0001, respectively) and iso- to hyperintensity on HBP images (P = .0001, P = .0002, P < .0001, respectively) had smaller tumor size, lower histologic grade, and worse Child-Pugh class. The log-rank test (P = .0064) and Cox proportional hazards model (hazard ratio, 5.676; P = .0158) revealed that HCCs with iso- to hyperintensity on HBP images had significantly longer TTR than HCCs with hypointensity on HBP images.
HCCs can be classified into several imaging patterns on gadoxetic acid-enhanced MR images, which are associated with tumor aggressiveness and outcome. In addition, iso- to hyperintensity on HBP images may be a useful imaging biomarker to indicate longer TTR after surgery. .
Background In estrogen receptor (ER)-positive breast cancer (BC), young age is associated with poor prognosis. While very young patients respond better to chemotherapy, chemotherapy is less effective ...in ER-positive tumors than in ER-negative tumors. The authors tried to evaluate chemotherapy response of very young patients with ER-positive BC by pathologic complete response (pCR) after neoadjuvant chemotherapy excluding the effect of endocrine treatment to the extent possible. Methods We collected individual patient data from 1992 to 2013 from the Korean Breast Cancer Society (KBCS). Total 1048 ER-positive and 797 ER-negative patients aged < 50 years who had been treated with neoadjuvant chemotherapy were included for analysis. We compared pCR rate between patients aged < 35 years with ER-positive tumors and the other groups. Results The proportion of patients aged < 35 years was 14.0% of patients with ER-positive BC in this cohort of under 50 years old, and 16.8% of patients with ER-negative BC in this cohort of under 50 years old. Although most characteristics of tumors according to age were comparable, tumors with high Ki-67 expression were more common in patients aged < 35 years than in patients aged 35-49 years in both ER-positive and -negative group (P = 0.001). Breast conservation rates were not significantly different according to age (44.2% vs. 46.8% in ER-positive group, 55.2% vs. 48.0% in ER-negative group). pCR rate was not different according to age in ER-positive group (P = 0.71) but significantly better in patients aged < 35 years in ER-negative group (P = 0.009). After adjusting for confounding variables, young patients maintained the higher probability of pCR than older patients in ER-negative tumors. However, pCR rate did not differ according to age in ER-positive tumors. In multivariate analysis, young age (< 35 years) was correlated with poor overall survival (P = 0.003, HR = 1.98) and there was only one event in a few patients achieved pCR in ER-positive group. Conclusions Chemotherapy response based on pCR was not better in young patients (< 35 years) with ER-positive BC than in older premenopausal patients with non-metastatic ER-positive BC. Young age cannot be a predictive factor of response to neoadjuvant chemotherapy in ER-positive BC. Different biological characteristics such as high proliferative index should be considered. Trial registration Retrospectively registered. Keywords: Breast cancer, Young patients, Neoadjuvant chemotherapy, ER-positive, Pathologic complete response
Background and purpose
The temporal characteristics of stroke risks were evaluated in emergency department patients who had a diagnosis of peripheral vertigo. It was also attempted to reveal the ...stroke risk factor amongst those with peripheral vertigo.
Methods
This is a parallel‐group cohort study in a tertiary referral hospital. After assigning each of 4367 matched patients to the comparative set of peripheral vertigo and appendicitis‐ureterolithiasis groups and each of 4911 matched patients to the comparative set of peripheral vertigo and ischaemic stroke groups, the relative stroke risk was evaluated. In addition, to predict the individual stroke risk in patients with peripheral vertigo, any association between the demographic factors and stroke events was evaluated in the peripheral vertigo group.
Results
The peripheral vertigo group had a higher stroke risk than the appendicitis‐ureterolithiasis group (hazard ratio 1.73, 95% confidence interval 1.18–2.55) but a lower risk than the ischaemic stroke group (hazard ratio 0.30, 95% confidence interval 0.24–0.37). The stroke risk of the peripheral vertigo group was just below that of small vessel stroke. The stroke risk of the peripheral vertigo group differed markedly by time: higher within 7 days, moderate between 7 days and 1 year, and diminished thereafter. Old age (>65 years), male gender and diabetes mellitus were the risk factors for stroke in the peripheral vertigo group.
Conclusion
Patients with a diagnosis of peripheral vertigo in the emergency department showed a moderate future stroke risk and so a stroke preventive strategy tailored to the timing of symptom onset and individual risk is required.
Patients with a diagnosis of peripheral vertigo in the emergency department showed a moderate future stroke risk, distinct from other nonvascular medical conditions. The risk was higher within 7 days and moderate between 7 days and 1 year; old age (>65 years), male gender and diabetes mellitus appeared to be stroke risk factors. The results highlight a stroke preventive strategy tailored to the timing of symptom onset and individual risk for peripheral vertigo patients in the emergency department.
Large amounts of microplastics are discharged into wastewater treatment plants (WWTPs), from where some of them are released into natural waterbodies on account of their not being fully eliminated by ...WWTPs. To investigate the behavior and emission of microplastics from WWTPs, we selected four WWTPs with different treatment technologies, including anaerobic-anoxic-aerobic (A2O), sequence batch reactor (SBR), media, and membrane bioreactor (MBR). The number of microplastics detected using Fourier transform infrared (FT-IR) spectroscopy ranged from 520 to 1820 particles/L in influent and from 0.56 to 2.34 particles/L in effluent. The microplastic removal efficiencies of four WWTPs were over 99%, indicating that the type of treatment technologies did not significantly affect the removal rate of microplastics. In the unit process for each WWTP, the major stages relating to microplastic removal were the secondary clarifier and tertiary treatment processes. Most microplastics detected were categorized as fragments and fibers, while other types were hardly detected. The size of more than 80% of microplastic particles detected in WWTPs ranged between 20 and 300 μm, indicating that they were significantly smaller than the size threshold defined for microplastics. Therefore, we used thermal extraction-desorption coupled with gas chromatography-mass spectroscopy (TED-GC-MS) to evaluate the microplastic mass content in all four WWTPs, and the results were compared with those of the FT-IR analysis. In this method, only four components, namely polyethylene, polypropylene, polystyrene, and polyethylene terephthalate, were analyzed because of the analysis limitation, and the total microplastic concentration represented the sum of four components concentrations. The influent and effluent microplastic concentrations estimated by TED-GC-MS ranged from not detectable to 160 μg/L and 0.04–1.07 μg/L, respectively, indicating a correlation coefficient of 0.861 (p < 0.05) between the TED-GC-MS and FT-IR results, when compared to the combined abundance of the four microplastic components by FT-IR analysis.
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•All of the wastewater treatment technologies had effect on microplastic removal rates.•Most microplastics detected were fragments and fibers measuring 20–300 μm.•Major microplastic removal stages were secondary clarifier and tertiary treatment.•The results analyzed by spectroscopic and thermo-analytical methods show correlation coefficient of 0.861.•Future research should broaden the analysis of microplastics using thermo-analytical methods.
Silicon monoxide (SiO), which exhibits better cyclability compared to silicon while delivering higher capacity than that of graphite, is an adequate material for the development of lithium-ion ...batteries (LIBs) having higher energy densities. However, incorporating silicon-based materials including SiO into stable graphite anode inevitably degrades not only cycle life but also calendar life of LIBs, while little is known about their aging mechanisms. Here, SiO-induced thermal instability of the graphite/SiO composite anode is investigated. We reveal that under thermal exposure, SiO accelerates the loss of lithium inventory and concomitantly facilitates the lithium de-intercalation from graphite. This self-discharge phenomenon, which is weakly observed in the graphite anode without SiO, is the result of preferential parasitic reaction on the SiO interface and spontaneous electron and lithium-ion migration to equilibrate the electron energy imbalance between graphite and SiO. Understanding this underlying electron-level interplay between graphite and SiO in the composite anode will contribute toward improving shelf life of SiO-containing LIBs in actual operating conditions.
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