CONTEXT Tumor recurrence is a major issue for patients with hepatocellular carcinoma (HCC) following curative liver resection. OBJECTIVE To investigate the association between nucleoside analogue use ...and risk of tumor recurrence in patients with hepatitis B virus (HBV)−related HCC after curative surgery. DESIGN, SETTING, AND PARTICIPANTS A nationwide cohort study between October 2003 and September 2010. Data from the Taiwan National Health Insurance Research Database. Among 100 938 newly diagnosed HCC patients, we identified 4569 HBV-related HCC patients who received curative liver resection for HCC between October 2003 and September 2010. MAIN OUTCOME MEASURES The risk of first tumor recurrence was compared between patients not taking nucleoside analogues (untreated cohort, n = 4051) and patients taking nucleoside analogues (treated cohort, n = 518). Cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing mortality. RESULTS The treated cohort had a higher prevalence of liver cirrhosis when compared with the untreated cohort (48.6% vs 38.7%; P < .001), but lower risk of HCC recurrence (n = 106 20.5% vs n = 1765 43.6%; P < .001), and lower overall death (n = 55 10.6% vs n = 1145 28.3%; P < .001). After adjusting for competing mortality, the treated cohort had a significantly lower 6-year HCC recurrence rate (45.6%; 95% CI, 36.5%-54.6% vs untreated, 54.6%; 95% CI, 52.5%-56.6%; P < .001). Six-year overall mortalities for treated cohorts were 29.0% (95% CI, 20.0%-38.0%) and for untreated 42.4% (95% CI, 40.0%-44.7%; P < .001). On modified Cox regression analysis, nucleoside analogue use (HR, 0.67; 95% CI, 0.55-0.81; P < .001), statin use (HR, 0.68; 95% CI, 0.53-0.87; P = .002), and nonsteroidal anti-inflammatory drugs or aspirin use (HR, 0.80; 95% CI, 0.73-0.88; P < .001) were independently associated with a reduced risk of HCC recurrence. Multivariable stratified analyses verified the association in all subgroups of patients, including those who were noncirrhotic (HR, 0.56; 95% CI, 0.42-0.76) and diabetic (HR, 0.52; 95% CI, 0.31-0.89). CONCLUSION Nucleoside analogue use was associated with a lower risk of HCC recurrence among patients with HBV-related HCC after liver resection.
Nonalcoholic fatty liver disease (NAFLD) may be a cause of hepatocellular carcinoma (HCC), but its high prevalence challenges current surveillance strategies. We aimed to evaluate HCC incidences in ...different risk stratifications for noncirrhotic NAFLD. Using Taiwan's National Health Insurance Research Database, we located 31,571 patients with NAFLD between the years 1998 and 2012. After excluding other causes of hepatitis, underlying cirrhosis or malignancy, 18,080 patients were recruited for final analysis. Cumulative incidences of HCC were analyzed after adjusting for competing mortality. With a median follow-up duration of 6.32 years in the study cohort, the 10-year cumulative incidence of HCC was 2.73% 95% confidence interval (CI): 1.69-3.76%. Hepatoprotectant was used as a surrogate marker for elevated serum alanine transaminase (ALT). After adjusting for age, gender, hypertension, hypercholesterolemia, diabetes mellitus, gout, statin use, metformin use and aspirin use, elevated ALT was independently associated with an increased HCC risk hazard ratio (HR) 6.80, 95% CI: 3.00-15.42; p < 0.001. Multivariate stratified analysis verified this association in all subgroups (HR> 1.0). Moreover, increased age (HR 1.08 per year, 95% CI: 1.05-1.11) and statin use (HR 0.29, 95% CI: 0.12-0.68) were also identified as independent risk factors. The 10-year cumulative HCC incidence was highest in older (age >55 years) patients with ALT elevation (12.41%, 95% CI: 5.99-18.83%), but lowest in younger patients without ALT elevation (0.36%, 95% CI: 0-1.08%). The incidence of HCC was relatively low in patients with clinically noncirrhotic NAFLD, however, HCC risk was significantly increased in older patients experiencing an elevated serum ALT.
Diet and exercise are conventional methods for controlling body weight and are linked to alterations in gut microbiota. However, the associations of diet, exercise, and gut microbiota in the control ...of obesity remain largely unknown. In the present study, using 16S rRNA amplicon sequencing and fecal microbiota transplantation (FMT), normal fat diet (NFD), exercise and their combination resulted in improved metabolic profiles in comparison to sedentary lifestyle with high fat diet (HFD). Moreover, diet exerted more influence than exercise in shaping the gut microbiota. HFD-fed mice receiving FMT from NFD-exercised donors not only showed remarkably reduced food efficacy, but also mitigated metabolic profiles (p < 0.05). The transmissible beneficial effects of FMT were associated with bacterial genera Helicobacter, Odoribacter and AF12 and overrepresentation of oxidative phosphorylation and glycolysis genes. Our findings demonstrate that the beneficial effects of diet and exercise are transmissible via FMT, suggesting a potential therapeutic treatment for obesity.
A safe, practical and eco-friendly method for the switchable synthesis of sulfoxides and sulfones through visible-light-initiated oxygenation of sulfides at ambient temperature under ...transition-metal-, additives-free and minimal solvent conditions. The synergistic catalytic efforts between CF3SO2Na and 2-butoxyethyl ether represents the key promoting factor for the reaction.
The development of eco-friendly and switchable catalytic systems for the conversion of a sole raw-material into distinct high-value products is a particularly attractive concept and a daunting ...synthetic challenge. In the present work, the first example of efficient and selective oxidation of sulfides to sulfones and sulfoxides using molecular oxygen under clean conditions was established.
The first example of selective oxidation of sulfides to sulfones and sulfoxides using molecular oxygen under clean conditions was established. The desired products could be easily collected through recrystallization in large-scale preparation.
A practical protocol for the preparation of quinoxaline‐2,3(1H,4H)‐diones through direct C(sp2)−H hydroxylation of quinoxalin‐2(1H)‐ones in recyclable DL‐α‐Tocopherol methoxypolyethylene glycol ...succinate solution (2 wt% in water) (TPGS‐750‐M/H2O) was developed. The target products were exclusively generated and could be collected through extraction and recrystallization.
Summary
Background
Finite nucleos(t)ide analogue (NUC) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB).
Aim
To quantify the incidence of severe hepatitis ...flares following NUC cessation in everyday clinical practice.
Methods
This population‐based cohort study enrolled 10,192 patients (male 71.7%, median age 50.9 years, cirrhosis 10.7%) who had received first‐line NUCs for at least 1 year before discontinuing treatment. The primary outcome was severe flare with hepatic decompensation. We used competing risk analyses to assess event incidences and associated risk factors.
Results
During a median follow‐up of 2.2 years, 132 patients developed severe flares with hepatic decompensation, yielding a 4‐year cumulative incidence of 1.8% (95% confidence interval CI, 1.5%–2.2%). Significant risk factors were cirrhosis (adjusted sub‐distributional hazard ratio aSHR, 2.74; 95% CI, 1.82–4.12), manifestations of portal hypertension (aSHR, 2.46; 95% CI, 1.45–4.18), age (aSHR, 1.21 per 10 years; 95% CI, 1.03–1.42) and male sex (aSHR, 1.58; 95% CI, 1.04–2.38). In patients without cirrhosis or portal hypertension (n = 8863), the 4‐year cumulative incidence of severe withdrawal flares stood at 1.3% (95% CI, 1.0%–1.7%). For those patients with available data confirming adherence to the standard stopping rules (n = 1274), the incidence was 1.1% (95% CI, 0.6%–2.0%).
Conclusions
Severe flares with hepatic decompensation were observed in 1%–2% of patients with CHB after stopping NUC therapy in daily practice. Risk factors included older age, cirrhosis, portal hypertension and male sex. Our findings argue against NUC cessation as part of routine clinical care.
A nationwide population‐based cohort study revealed that severe hepatitis flares complicated with hepatic decompensation occurred in 1–2% of patients with chronic hepatitis B after discontinuing nucleos(t)ide analogue therapy.
There was much evidence suggesting that the serum lactate dehydrogenase (LDH) levels reflect the extent of various pathophysiological processes. However, the current information about dynamic change ...of LDH in COVID-19 pneumonia has not been well investigated.
Study was performed in 87 cases confirmed by COVID-19 infection. The serum LDH levels were determined at diagnosis and follow-up visits. The evaluation of clinical response to therapy was based on chest CT scan. We selected the value of LDH around the data of chest CT scan (- 1 ~ + 1 day).
At diagnosis, significant differences in LDH levels were found between non-severe and severe group (P < 0.05). It was demonstrated that increase or decrease of LDH was indicative of radiographic progress or improvement (P < 0.05). The time to LDH normalization (5.67 ± 0.55, days) was positively correlated with the time to radiographic absorption (5.57 ± 0.65 days, r = 0.53, P < 0.05). Applying the cut-off value of the increase in LDH has good specificity to predict disease progression.
Serum LDH was validated for its potential usefulness as markers for evaluating clinical severity and monitoring treatment response in COVID-19 pneumonia.
LINKED CONTENT
This article is linked to Ogawa et al papers. To view these articles, visit
https://doi.org/10.1111/apt.17107
and
https://doi.org/10.1111/apt.17693
.
An efficient and eco-friendly protocol for synthesizing difluoromethylated oxindoles through a visible-light-induced one-pot tandem reaction of N-arylacrylamides, difluoroacetic acid and PhI(OAc)2 ...was developed. This reaction proceeded in the absence of any additive, base, metal-catalyst and external photosensitizer, using cheap CHF2CO2H as a difluoromethylation reagent and bulk biomass-derived 2-MeTHF as a solvent.
Display omitted
An efficient and eco-friendly protocol for synthesizing difluoromethylated oxindoles through a visible-light induced one-pot tandem reaction of N-arylacrylamides, difluoroacetic acid and PhI(OAc)2 was developed. This reaction proceeded in the absence of any additive, base, metal-catalyst and external photosensitizer, using cheap and easily available CHF2CO2H as the difluoromethylation reagent and bulk biomass-derived 2-MeTHF as the sole solvent. 26 Examples of N-arylacrylamide substrates were investigated, and all of them successfully underwent difluoromethylation to deliver the target products in good to excellent yields.
PDF
