Nickel (Ni), which is a carcinogenic workplace hazard, increases the risk of lung cancer. Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional cytokine that is involved in both angiogenesis and ...metastasis, but its role in lung cancer is still not clear. In this study, we assessed the role of ANGPTL4 in lung carcinogenesis under nickel exposure and investigated the effects of the antidiabetic drug metformin on ANGPTL4 expression and lung cancer chemoprevention. Our results showed that ANGPTL4 is increased in NiCl
-treated lung cells in a dose- and time-course manner. The expression of ANGPTL4 and HIF-1α induced by NiCl
were significantly repressed after metformin treatment. The downregulation of HIF-1α expression by ROS savenger and HIF-1α inhibitor or knockdown by lentiviral shRNA infection diminished NiCl
-activated ANGPTL4 expression. Chromatin immunoprecipitation and the luciferase assay revealed that NiCl
-induced HIF-1α hypoxia response element interactions activate ANGPTL4 expression, which is then inhibited by metformin. In conclusion, the increased presence of ANGPTL4 due to HIF-1α accumulation that is caused by nickel in lung cells may be one mechanism by which nickel exposure contributes to lung cancer progression. Additionally, metformin has the ability to prevent NiCl
-induced ANGPTL4 through inhibiting HIF-1α expression and its binding activity. These results provide evidence that metformin in oncology therapeutics could be a beneficial chemopreventive agent.
Several randomized controlled trials and real‐world cohort studies have demonstrated the efficacies of nirmatrelvir plus ritonavir (NMV‐r) and molnupiravir (MOV) in at‐risk patients with COVID‐19; ...however, the effectiveness of antisevere acute respiratory syndrome‐coronavirus 2 treatments on older patients (≥65 years) remains unclear. This retrospective cohort study aimed to assess the clinical effectiveness of the oral antiviral agents, MOV and NMV‐r, in older patients (≥65 years) infected with severe acute respiratory syndrome‐coronavirus 2. Nonhospitalized older patients with COVID‐19 between January 1, 2022, and December 31, 2022, were recruited from the TriNetX Research Network. Propensity score matching (PSM) was used to match patients who received either NMV‐r or MOV treatment with those who did not receive any oral antiviral agents. Hazard ratios (HRs) for composite all‐cause hospitalization or death during the 30‐day follow‐up period were calculated. PSM revealed two cohorts with 28 824 patients each having balanced baseline characteristics. The antiviral group was associated with significantly lower risk of the primary composite outcome of all‐cause hospitalization or death than the control group (241 vs. 801; HR, 0.307; 95% confidence interval (CI), 0.27–0.36) during the follow‐up period. For the secondary outcome, the antiviral group had a significantly lower risk of all‐cause hospitalization (288 vs. 725; HR, 0.322; 95% CI, 0.28–0.37) and mortality (16 vs. 94; HR, 0.176; 95% CI, 0.10–0.30) than the control group. Moreover, the reduced risk of all‐cause hospitalization or death remained consistent in patients receiving NMV‐r (HR, 0.279; 95% CI, 0.24–0.33) and MOV (HR, 0.279; 95% CI, 0.21–0.38). Our results revealed that NMV‐r and MOV decreased the all‐cause hospitalization and death rates among older patients with COVID‐19, supporting the use of antivirals in this vulnerable population.
This systematic review and meta-analysis aimed to investigate the clinical efficacy and safety of systemic corticosteroids in the treatment of patients with severe community-acquired pneumonia ...(sCAP).
A comprehensive search was conducted using the Medline, Embase, ClinicalTrials.gov, and Scopus databases for articles published until April 24, 2023. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of adjunctive corticosteroids for treating sCAP were included. The primary outcome was the 30-day all-cause mortality.
A total of severe RCTs involving 1689 patients were included in this study. Overall, the study group had a lower mortality rate at day 30 than the control group (risk ratio RR, 0.61; 95% CI 0.44 to 0.85; p < 0.01) with low heterogeneity (I
= 0%, p = 0.42). Compared to the control group, the study group had a lower risk of the requirement of mechanical ventilation (RR 0.57; 95% CI 0.45 to 0.73; p < 0.001), shorter length of intensive care unit (MD - 0.8; 95% CI - 1.4 to - 0.1; p = 0.02), and hospital stay (MD - 1.1; 95% CI - 2.0 to - 0.1; p = 0.04). Finally, no significant difference was observed between the study and the control groups in terms of gastrointestinal tract bleeding (RR 1.03; 95% CI 0.49 to 2.18; p = 0.93), healthcare-associated infection (RR 0.89; 95% CI 0.60 to 1.32; p = 0.56), and acute kidney injury (RR 0.68; 95% CI 0.21 to 2.26; p = 0.53).
In patients with sCAP, adjunctive corticosteroids can provide survival benefits and improve clinical outcomes without increasing adverse events. However, because the pooled evidence remains inconclusive, further studies are required.
PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) regulates components of the cell cycle, including cell growth, immune responses, DNA damage repair, apoptosis, and inflammation. ...PBK/TOPK may also accelerate tumorigenesis in colorectal cancer.
We investigated the impact of PBK/TOPK on the clinical outcome of colorectal cancer patients to further identify its role in colorectal cancer. PBK/TOPK immunoreactivity was analyzed by immunohistochemistry in 162 cancer specimens from primary colorectal cancer patients.
The mean follow-up time after surgery was 5.4 years (medium: 3.9 years; range 0.01 to 13.1 years). The prognostic value of PBK/TOPK on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. PBK/TOPK was expressed in both the cytoplasm and nucleus. High PBK/TOPK expression in tumor cells was significantly associated with advanced T value. The 5-year survival rate was greater for patients with high total PBK/TOPK expression than with low PBK/TOPK expression (58.3% vs 34.4%, P = 0.005). Multivariate analyses showed that low-scoring cytoplasmic PBK/TOPK, negative nuclear PBK/TOPK, low total PBK/TOPK, and advanced tumor stage were correlated with poor overall patient survival.
We suggest that PBK/TOPK expression, detected by IHC staining, could be used as an independent prognostic marker for colorectal cancer patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A Rare Cause of Sister Mary Joseph Nodule Wang, Yu-Chia; Hsu, Hui-Ting; Yen, Hsu-Heng
Clinical gastroenterology and hepatology,
04/2023, Letnik:
21, Številka:
4
Journal Article
The aim of this study was to investigate the clinical efficacy of a combination of nirmatrelvir and ritonavir (NMV‐r) for treating COVID‐19 in patients with diabetes mellitus (DM). This retrospective ...cohort study used the TriNetX research network to identify adult diabetic patients with COVID‐19 between January 1, 2020, and December 31, 2022. Propensity score matching was used to match patients who received NMV‐r (NMV‐r group) with those who did not receive NMV‐r (control group). The primary outcome was all‐cause hospitalization or death during the 30‐day follow‐up period. Two cohorts comprising 13 822 patients with balanced baseline characteristics were created using propensity score matching. During the follow‐up period, the NMV‐r group had a lower risk of all‐cause hospitalization or death than the control group (1.4% n = 193 vs. 3.1% n = 434; hazard ratio HR, 0.497; 95% confidence interval CI, 0.420–0.589). Compared with the control group, the NMV‐r group also had a lower risk of all‐cause hospitalization (HR, 0.606; 95% CI, 0.508–0.723) and all‐cause mortality (HR, 0.076; 95% CI, 0.033–0.175). This lower risk was consistently observed in almost all subgroup analyses, which examined sex (male: 0.520 0.401–0.675; female: 0.586 0.465–0.739), age (age 18–64 years: 0.767 0.601–0.980; ≥65 years: 0.394 0.308–0.505), level of HbA1c (<7.5%: 0.490 0.401–0.599; ≥7.5%: 0.655 0.441–0.972), unvaccinated (0.466 0.362–0.599), type 1 DM (0.453 0.286–0.718) and type 2 DM (0.430 0.361–0.511). NMV‐r can help reduce the risk of all‐cause hospitalization or death in nonhospitalized patients with DM and COVID‐19.
Summary Background Both end-stage renal disease and chronic kidney disease are increasing worldwide; however, the full effect of chronic kidney disease is unknown because mortality risks for all five ...stages are unavailable. We assessed prevalence and mortality risks for all stages of chronic kidney disease and quantified its attributable mortality in Taiwan. Methods The cohort consisted of 462 293 individuals aged older than 20 years who participated in a standard medical screening programme since 1994. As of Dec 31, 2006, we identified 14 436 deaths. Chronic kidney disease was determined by glomerular filtration rate and urinary protein. We estimated national prevalence in Taiwan from the cohort by adjusting age and educational levels. Hazard ratios (HRs) were calculated with Cox proportionate hazards model. We calculated mortality attributable to chronic kidney disease for national population and for low socioeconomic status. Findings The national prevalence of chronic kidney disease was 11·93% (95% CI 11·66–12·28), but only 3·54% (3·37–3·68) of participants in the cohort were aware of their disorder. Prevalence was substantially higher in the group with low socioeconomic status than in the high status group (19·87% 19·84–19·91 vs 7·33% 7·31–7·35). 56 977 (12%) of cohort participants had chronic kidney disease; those with disease had 83% higher mortality for all cause (HR 1·83 1·73–1·93) and 100% higher for cardiovascular diseases (2·00 1·78–2·25), in a cohort that was observed for 13 years with median follow-up of 7·5 years (IQR 4·0–10·1). 10·3% (95% CI 9·57–11·03) of deaths in the entire population were attributable to chronic kidney disease, but 17·5% (16·27–18·67) of deaths in the low socioeconomic status population. 2350 (39%) deaths occurred before 65 years of age in those with chronic kidney disease. Regular users of Chinese herbal medicines had a 20% (odds ratio 1·20 1·16–1·24) increased risk of developing chronic kidney disease. Interpretation The high prevalence of chronic kidney disease and its associated all-cause mortality, especially in people with low socioeconomic status, make reduction of this disorder a public-health priority. Promotion of its recognition through the general public knowing their glomerular filtration rate and testing their urine is crucial to reduce premature deaths from all causes and to attenuate this global epidemic. Funding None.
Activin/SMAD signaling in human embryonic stem cells (hESCs) ensures
expression and stem cell pluripotency. In the presence of Wnt ligand, the Activin/SMAD transcription network switches to cooperate ...with Wnt/β-catenin and induce mesendodermal (ME) differentiation genes. We show here that the Hippo effector YAP binds to the
gene enhancer and prevents the gene from being induced by Activin in proliferating hESCs. ChIP-seq (chromatin immunoprecipitation ChIP combined with high-throughput sequencing) data show that YAP impairs SMAD recruitment and the accumulation of P-TEFb-associated RNA polymerase II (RNAPII) C-terminal domain (CTD)-Ser7 phosphorylation at the
gene. CRISPR/
knockout of YAP in hESCs enables Activin to induce Wnt3 expression and stabilize β-catenin, which then synergizes with Activin-induced SMADs to activate a subset of ME genes that is required to form cardiac mesoderm. Interestingly, exposure of YAP
hESCs to Activin induces cardiac mesoderm markers (
and
) without activating Wnt-dependent cardiac inhibitor genes (
and
). Moreover, canonical Wnt target genes are up-regulated only modestly, if at all, under these conditions. Consequently, YAP-null hESCs exposed to Activin differentiate precisely into beating cardiomyocytes without further treatment. We conclude that YAP maintains hESC pluripotency by preventing
expression in response to Activin, thereby blocking a direct route to embryonic cardiac mesoderm formation.
The effect of nirmatrelvir plus ritonavir (NMV‐r) on post‐acute COVID‐19 sequelae beyond 3 months of SARS‐CoV‐2 infection remains unknown. This retrospective cohort study utilized data from the ...TriNetX Research Network. We identified nonhospitalized adult patients with COVID‐19 receiving a diagnosis between January 1 and July 31, 2022. Propensity score matching (PSM) was used to create two matched cohorts: NMV‐r and non‐NMV‐r groups, respectively. We measured the primary outcomes using a composite of all‐cause emergency room (ER) visits or hospitalization and a composite of post‐COVID‐19 symptoms according to the WHO Delphi consensus, which also stated that post COVID‐19 condition occurs usually 3 months from the onset of COVID‐19, during the follow‐up period between 90 days after the index diagnosis of COVID‐19 and the end of follow‐up (180 days). Initially, we identified 12 247 patients that received NMV‐r within 5 days of diagnosis and 465 135 that did not. After PSM, 12 245 patients remained in each group. During the follow‐up period, patients treated with NMV‐r had a lower risk of all‐cause hospitalization and ER visits compared with untreated patients (659 vs. 955; odds ratio OR, 0.672; 95% confidence interval CI, 0.607–0.745; p < 0.0001). However, the overall risk of post‐acute COVID‐19 symptoms did not significantly differ between the two groups (2265 vs. 2187; OR, 1.043; 95% CI, 0.978–1.114; p = 0.2021). The reduced risk of all‐cause ER visits or hospitalization in the NMV‐r group and the similarities in the risk of post‐acute COVID‐19 symptoms between the two groups were consistent in the subgroups stratified by sex, age, and vaccination status. Early NMV‐r treatment of nonhospitalized patients with COVID‐19 was associated with reduced risk of hospitalization and ER visits during the period of 90–180 days after diagnosis compared with no NMV‐r treatment; however, post‐acute COVID‐19 symptoms and mortality risk did not differ significantly between the groups.
During the COVID-19 surge in Taiwan, the Far East Memorial Hospital established a system including a centralized quarantine unit and triage admission protocol to facilitate acute care surgical ...inpatient services, prevent nosocomial COVID-19 infection and maintain the efficiency and quality of health care service during the pandemics.
This retrospective cohort study included patients undergoing acute care surgery. The triage admission protocol was based on rapid antigen tests, Liat® PCR and RT-PCT tests. Type of surgical procedure, patient characteristics, and efficacy indices of the centralized quarantine unit and emergency department (ED) were collected and analyzed before (Phase I: May 11 to July 2, 2021) and after (Phase II: July 3 to July 31, 2021) the system started.
A total of 287 patients (105 in Phase I and 182 in Phase II) were enrolled. Nosocomial COVID-19 infection occur in 27 patients in phase I but zero in phase II. More patients received traumatological, orthopedic, and neurologic surgeries in phase II than in phase I. The patients' surgical risk classification, median total hospital stay, intensive care unit (ICU) stay, intraoperative blood loss, operation time, and the number of patients requiring postoperative ICU care were similar in both groups. The duration of ED stay and waiting time for acute care surgery were longer in Phase II (397 vs. 532 minutes, p < 0.0001). The duration of ED stay was positively correlated with the number of surgical patients visiting the ED (median = 66 patients, Spearman's ρ = 0.207) and the occupancy ratio in the centralized quarantine unit on that day (median = 90.63%, Spearman's ρ = 0.191).
The triage admission protocol provided resilient quarantine needs and sustainable acute care surgical services during the COVID-19 pandemic. The efficiency was related to the number of medical staff dedicated to the centralized quarantine unit and number of surgical patients visited in ED.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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