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•The hepatocellular carcinoma risk was not statistically different between the ETV and TDF groups.•The death or liver transplant risk was not statistically different between the 2 ...groups.•These results were consistently reproduced after adjusting for confounding variables.
It is currently unclear which antiviral agent, entecavir (ETV) or tenofovir disoproxil fumarate (TDF), is superior for improving prognosis in patients with chronic hepatitis B (CHB). Here, we assessed the ability of these 2 antivirals to prevent liver-disease progression in treatment-naïve patients with CHB.
From 2012 to 2014, treatment-naïve patients with CHB who received ETV or TDF as a first-line antiviral agent were recruited from 4 academic teaching hospitals. Patients with decompensated cirrhosis or hepatocellular carcinoma (HCC) at enrollment were excluded. Cumulative probabilities of HCC and death or orthotopic liver transplant (OLT) were assessed.
In total, 2,897 patients (1,484 and 1,413 in the ETV and TDF groups, respectively) were recruited. The annual HCC incidence was not statistically different between the ETV and TDF groups (1.92 vs. 1.69 per 100 person-years PY, respectively; adjusted hazard ratio HR 0.975 p = 0.852 by multivariate analysis). Propensity score (PS)-matched and inverse probability of treatment weighting (ITPW) analyses yielded similar patterns of results (HR 1.021 p = 0.884 and 0.998 p = 0.988, respectively). The annual incidence of death or OLT was not statistically different between the ETV and TDF groups (0.52 vs. 0.53 per 100 PY, respectively; adjusted HR 1.202 p = 0.451). PS-matched and ITPW analyses yielded similar patterns of results (HR 1.248 p = 0.385 and 1.239 p = 0.360, respectively). These findings were consistently reproduced in patients with compensated cirrhosis (all p >0.05).
The overall prognosis in terms of HCC and death or OLT was not statistically different between the ETV and TDF groups. Further studies are needed to validate our results.
It is currently unclear which antiviral agent, entecavir or tenofovir disoproxil fumarate, is superior for improving prognosis in patients with chronic hepatitis B virus infection. In this analysis we found that there was no difference in terms of overall prognosis, including risk of hepatocellular carcinoma, death, or the need for a liver transplant, in patients receiving either antiviral.
Filamentous fungal mycoproteins have gained increasing attention as sustainable alternatives to animal and plant‐based proteins. This comprehensive review summarizes the nutritional characteristics, ...toxicological aspects, and health‐promoting effects of mycoproteins, focusing on those derived from filamentous fungi, notably Fusarium venenatum. Mycoproteins are characterized by their high protein content, and they have a superior essential amino acid profile compared to soybeans indicating excellent protein quality and benefits for human nutrition. Additionally, mycoproteins offer enhanced digestibility, further highlighting their suitability as a protein source. Furthermore, mycoproteins are rich in dietary fibers, which have been associated with health benefits, including protection against metabolic diseases. Moreover, their fatty acids profile, with significant proportions of polyunsaturated fatty acids and absence of cholesterol, distinguishes them from animal‐derived proteins. In conclusion, the future of mycoproteins as a health‐promoting protein alternative and the development of functional foods relies on several key aspects. These include improving the acceptance of mycoproteins, conducting further research into their mechanisms of action, addressing consumer preferences and perceptions, and ensuring safety and regulatory compliance. To fully unlock the potential of mycoproteins and meet the evolving needs of a health‐conscious society, continuous interdisciplinary research, collaboration among stakeholders, and proactive engagement with consumers will be vital.
To determine if continuous bilateral erector spinae plane (ESP) blocks would improve the postoperative analgesia in the first 48 h after laparoscopic donor hepatectomy, compared to intrathecal ...morphine (ITM).
Prospective, randomized controlled trial.
A single tertiary care center from October 2019 and September 2020.
A total of 60 donors scheduled to undergo elective laparoscopic right hepatectomy.
Sixty donors were randomized to receive either bilateral continuous T8 ESP blocks with a programmed intermittent bolus regimen of 10 mL 0.2% ropivacaine every 3 h for 48 h (n = 30) or 400 μg ITM (n = 30), in addition to IV fentanyl PCA and multimodal analgesia.
The primary outcome was cumulative opioid consumption over the first 48 h, expressed as IV morphine equivalents. Secondary outcomes included pain scores, Quality of Recovery-15 scores, ambulation within 24 h, time to first flatus, and opioid-related adverse drug events over 72 h.
Fifty-nine donors were analyzed. Cumulative 48-h opioid consumption was similar between the ITM and ESP groups (29.8 ± 18.2 vs. 35.1 ± 21.9 mg, mean difference (ESP-ITM) (95% CI), 5.3 (−11.5 to 22) mg; p > 0.99). Resting pain scores at 48 and 72 h postoperatively were significantly lower in the ESP group (0 0–2 vs. 3 1.5–3, and 0 0–2 vs. 3 1–3 respectively, both p<0.001) (Goldaracena and Barbas, 2019; Ko et al., 2009; Choi et al., 2007 1–3) respectively, both p < 0.001). The ESP group had significantly lower incidences of postoperative nausea, vomiting, and pruritus at all timepoints. There were no differences in recovery outcomes.
Continuous ESP blocks did not reduce cumulative 48-h opioid consumption compared to 400 μg ITM after laparoscopic donor hepatectomy, but it was associated with a significantly reduced risk of postoperative nausea, vomiting and pruritus.
Clinical Trial Registry of Korea; https://cris.nih.go.kr/cris/index.jsp and identifier: KCT0004313; date of registration: October 15, 2019; principal investigator's name: Justin Sangwook Ko.
•Intrathecal morphine (ITM) provides effective postoperative analgesia in liver surgery.•High incidences of postoperative nausea and vomiting remains concerns with ITM.•Erector spinae plane block (ESP) provides adequate postoperative abdominal analgesia.•Continuous ESP block did not reduce cumulative 48 h opioid consumption compared to ITM.•Continuous ESP block reduced risk of postoperative nausea, vomiting, and pruritus.
The root of Platycodon grandiflorum (PG) has long been used as a traditional herbal medicine in Asian country. Platycondin D (PD), triterpenoid saponin that is a main constituent of PG, exhibits ...various biological activities such as anti-inflammatory, anti-oxidant, anti-diabetic, and anti-cancer effects. A previous study showed that PD had cholesterol-lowering effects in mice that develop hypercholesterolemia, but the underlying molecular mechanisms have not been elucidated during the last decade. Here, we demonstrated that both PG and PD markedly increased levels of cell surface low-density lipoprotein receptor (LDLR) by down-regulation of the E3 ubiquitin ligase named inducible degrader of the LDLR (IDOL) mRNA, leading to the enhanced uptake of LDL-derived cholesterol (LDL-C) in hepatic cells. Furthermore, cycloheximide chase analysis and in vivo ubiquitination assay revealed that PD increased the half-life of LDLR protein by reducing IDOL-mediated LDLR ubiquitination. Finally, we demonstrated that treatment of HepG2 cells with simvastatin in combination with PG and PD had synergistic effects on the improvement of LDLR expression and LDL-C uptake. Together, these results provide the first molecular evidence for anti-hypercholesterolemic activity of PD and suggest that PD alone or together with statin could be a potential therapeutic option in the treatment of atherosclerotic cardiovascular disease.
BRAF mutations are relatively uncommon in lung cancer. However, the majority of therapies targeting BRAF mutations have been developed exclusively for lung cancer patients with V600E mutations, ...limiting their effectiveness in treating tumors with the non-V600E BRAF mutations. As a result, there is a need to explore effective therapeutic strategies for patients with lung cancer carrying non-V600 BRAF mutations. Therefore, this study aims to identify a combination treatment approach that effectively targets lung cancer with G469A non-V600 BRAF alteration.
The efficacy of drug treatments was assayed using a patient-derived xenograft (PDX) mouse model. Histological analysis was performed using hematoxylin and eosin and immunohistochemical staining. Cell viability and growth were determined using the WST-8 and colony formation assays. Protein levels and apoptosis were analyzed using western blot and flow cytometry, respectively.
We demonstrated that the lung cancer cells harboring the non-V600E G469A mutation were responsive to the combination of SH003 and dabrafenib. By utilizing patient-derived xenograft (PDX) models, we identified that this combined treatment induces apoptosis and exhibits antitumor effects through the reduction of ERK signals. The synergistic effect of the combination treatment on BRAF G469A lung cancer cells was consistent with its effects on PDX models, suggesting that the molecular mechanism of apoptosis involves a decrease in the MEK/ERK signaling pathway.
The SH003 and dabrafenib combination can be potentially developed as an effective treatment strategy for addressing lung cancer patients with the BRAF G469A mutation.
To compare the therapeutic outcomes of laparoscopic hepatic resection (LHR) and laparoscopic radiofrequency ablation (LRFA) for single subcapsular hepatocellular carcinoma (HCC).
We screened 244 ...consecutive patients who had received either LHR or LRFA between January 2014 and December 2016. The feasibility of LRFA in patients who underwent LHR was retrospectively assessed by two interventional radiologists. Finally, 60 LRFA-feasible patients who had received LHR and 29 patients who had received LRFA as the first treatment for a solitary subcapsular HCC between 1 cm and 3 cm were finally included. We compared the therapeutic outcomes, including local tumor progression (LTP), recurrence-free survival (RFS), and overall survival (OS) between the two groups before and after propensity score (PS) matching. Multivariable Cox proportional hazard regression was also used to evaluate the difference in OS and RFS between the two groups for all 89 patients.
PS matching yielded 23 patients in each group. The cumulative LTP and OS rates were not significantly different between the LHR and LRFA groups after PS matching (
= 0.900 and 0.003, respectively). The 5-year LTP rates were 4.6% and 4.4%, respectively, and OS rates were 100% and 90.7%, respectively. The RFS rate was higher in LHR group without statistical significance (
= 0.070), with 5-year rates of 78.3% and 45.3%, respectively. OS was not significantly different between the LHR (reference) and LRFA groups in multivariable analyses, with a hazard ratio (HR) of 1.33 (95% confidence interval, 0.12-1.54) (
= 0.818). RFS was higher in LHR (reference) than in LRFA without statistical significance in multivariable analysis, with an HR of 2.01 (0.87-4.66) (
= 0.102).
There was no significant difference in therapeutic outcomes between LHR and LRFA for single subcapsular HCCs measuring 1-3 cm. The difference in RFS should be further evaluated in a larger study.
Abstract
Objective
This study aimed to evaluate the relationship between laryngopharyngeal reflux (LPR) and anxiety in patients with LPR.
Design
Prospective, case–control study.
Setting
This study ...was conducted at a tertiary care center.
Participants
Sixty‐four patients with LPR and 60 healthy controls.
Methods
Patients with LPR and healthy individuals (
N
= 64 and
N
= 60) were enrolled in this study. The Beck Anxiety Inventory (BAI) and reflux symptom index (RSI) were used to evaluate anxiety and reflux‐related symptoms, respectively. The BAI can be classified into somatic and subjective symptom scales. The prevalence of anxiety was compared between patients with LPR and healthy individuals. This study evaluated the relationship between BAI and RSI scores.
Results
No statistical difference was found in the prevalence of anxiety between patients with LPR and healthy individuals (42.2% vs. 33.3%). However, the somatic anxiety symptom score was statistically higher in patients with LPR than in healthy individuals (
p
= .047). We observed a correlation between RSI and somatic anxiety scores of BAI in patients with LPR (rho = 0.286,
p
= .021).
Conclusion
Patients with LPR had more severe somatic anxiety symptoms, and somatic anxiety was associated with their LPR‐related symptoms.
Background
Intrathecal morphine (ITM) injection is an effective postoperative analgesic strategy in open or laparoscopic donor hepatectomy; however, the optimal dose has not been determined. In this ...trial, we compared the post‐operative analgesic effects of two doses (300 vs. 400 μg) of ITM injections.
Methods
In this prospective randomized non‐inferiority trial, 56 donors were divided into either the 300 μg or 400 μg ITM group (n = 28, each). The primary outcome was the resting pain score at 24 h postoperatively. Pain scores, cumulative opioid consumption, and side effects (postoperative nausea and vomiting PONV) were compared up to 48 h postoperatively.
Results
Fifty‐five donors participated in the entire study. The mean resting pain scores at 24 h after surgery were 1.7 ± 1.6 and 1.7 ± 1.1 in the ITM 300 and ITM 400 groups, respectively (mean difference, 0 95% CI, −.8 to .7, p = .978). The upper limit of the 95% CI was lower than the prespecified non‐inferiority margin (δ = 1), indicating that non‐inferiority had been established. The incidence of PONV was lower in the ITM 300 group than in the ITM 400 group at 18 (p = .035) and 24 h postoperatively (p = .015). There were no significant differences in the resting and coughing pain scores and cumulative opioid consumption at any time point.
Conclusion
For laparoscopic donor hepatectomy, preoperative ITM 300 μg exhibited non‐inferior postoperative analgesic effects compared to ITM 400 μg, with a lower incidence of PONV.
Background
This study aimed to evaluate the risk factors related to a technical failure after laparoscopic radiofrequency ablation (RFA) for subcapsular hepatocellular carcinomas (HCCs).
Materials ...and methods
A total of 110 patients with 114 HCCs who underwent laparoscopic RFA for HCCs (new HCC
n
= 85 and local tumor progression LTP
n
= 29) between January 2013 and December 2018 were included. We evaluated the incidence of technical failure on immediate post-RFA CT images. Risk factors for a technical failure after laparoscopic RFA were assessed using univariable logistic regression analyses. The cumulative LTP rate was estimated using the Kaplan–Meier method.
Results
Technical failure was noted in 3.5% (4/114) of the tumors. All four tumors that showed a technical failure were cases of LTP from previous treatment and were invisible on laparoscopy. On univariate analysis, LTP lesion, invisibility of the index tumor on laparoscopy, and peri-hepatic vein location of the tumor were identified as risk factors for a technical failure. The cumulative LTP rates at 1, 3, and 5 years were estimated to be 2.8%, 4.8%, and 4.8%, respectively.
Conclusions
LTP lesion, invisibility of the index tumor on laparoscopy, and peri-hepatic vein location of the tumor were identified as the risk factors for a technical failure after laparoscopic RFA.
Synaptic adhesion molecules orchestrate synaptogenesis. The presynaptic leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) regulate synapse development by interacting ...with postsynaptic Slit- and Trk-like family proteins (Slitrks), which harbour two extracellular leucine-rich repeats (LRR1 and LRR2). Here we identify the minimal regions of the LAR-RPTPs and Slitrks, LAR-RPTPs Ig1-3 and Slitrks LRR1, for their interaction and synaptogenic function. Subsequent crystallographic and structure-guided functional analyses reveal that the splicing inserts in LAR-RPTPs are key molecular determinants for Slitrk binding and synapse formation. Moreover, structural comparison of the two Slitrk1 LRRs reveal that unique properties on the concave surface of Slitrk1 LRR1 render its specific binding to LAR-RPTPs. Finally, we demonstrate that lateral interactions between adjacent trans-synaptic LAR-RPTPs/Slitrks complexes observed in crystal lattices are critical for Slitrk1-induced lateral assembly and synaptogenic activity. Thus, we propose a model in which Slitrks mediate synaptogenic functions through direct binding to LAR-RPTPs and the subsequent lateral assembly of LAR-RPTPs/Slitrks complexes.
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