Efficacy and Safety of Surgical Resection in Elderly Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Background/Aims: : With increased life expectancy, the management of elderly hepatocellular carcinoma (HCC) patients became a crucial issue, yet it is still challenging due to comorbidities and high surgical risks. While surgical resection is considered as primary treatment for eligible HCC patients, systematic evidence on its outcomes in elderly patients remains scarce. In this review, we aimed to analyze the efficacy and safety outcomes of surgical resection in elderly HCC patients. Methods: : The studies included in this meta-analysis were selected from Ovid-MEDLINE, Ovid-Embase, CENTRAL, KoreaMed, KMbase, and KISS databases following a predefined protocol. Efficacy outcomes included overall survival and disease-free survival, while the safety outcomes included postoperative mortality and complications. Results: : Patients in the elderly group (≥65 years) who underwent surgery exhibited non-inferior overall survival (hazard ratio [HR], 1.26; 95% confidence interval [CI], 0.92 to 1.74) and disease-free survival (HR, 1.03; 95% CI, 0.99 to 1.08) compared to the non-elderly group. Overall postoperative mortality exhibited no statistical difference (odds ratio [OR], 1.07; 95% CI, 0.87 to 1.31), but 30-day, 90-day, and in-hospital mortality were higher in the elderly group. The incidence of overall complications was higher in the elderly group (OR, 1.44; 95% CI, 1.22 to 1.69). Sensitivity analysis for the super elderly group (≥80 years) showed significantly higher in-hospital mortality compared to the non-super elderly group (OR, 2.51; 95% CI, 1.16 to 5.45). Conclusions: : The efficacy outcome of surgical resection in the elderly HCC patients was not worse than that in the non-elderly HCC patients, while in-hospital mortality and complications rates were higher. Therefore, surgical resection should be purposefully considered in the elderly population, with careful candidate selection.

Psychiatric adverse events associated with the COVID-19 vaccines approved in the Republic of Korea: a systematic review.

This systematic review evaluated psychiatric adverse events (AEs) following vaccination against coronavirus disease 2019 (COVID-19). We included studies that reported or investigated psychiatric AEs in individuals who had received an approved COVID-19 vaccine in the Republic of Korea. Systematic electronic searches of Ovid-Medline, Embase, CENTRAL, and KoreaMed databases were conducted on March 22, 2023. Risk of bias was assessed using the Risk of Bias Assessment Tool for Non-randomized Studies 2.0. The study protocol was registered in the International Prospective Register of Systematic Reviews (CRD42023449422). Of the 301 articles initially selected, 7 were included in the final analysis. All studies reported on sleep disturbances, and 2 highlighted anxiety-related AEs. Sleep disorders like insomnia and narcolepsy were the most prevalent AEs, while depression was not reported. Our review suggests that these AEs may have been influenced by biological mechanisms as well as the broader psychosocial context of the COVID-19 pandemic. Although this study had limitations, such as a primary focus on the BNT162b2 vaccine and an observational study design, it offered a systematic, multi-vaccine analysis that fills a critical gap in the existing literature. This review underscores the need for continued surveillance of psychiatric AEs and guides future research to investigate underlying mechanisms, identify risk factors, and inform clinical management.

Radiofrequency Ablation versus Surgical Resection in Elderly Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Although the disease burden of elderly cancer patients is rapidly increasing, reliable scientific information, value and preference information of domestic patients, and standardized guidelines for determining the treatment of elderly cancer patients are lacking. The aim of this study is to compare the therapeutic effects of radiofrequency ablation (RFA) and surgery in hepatocellular carcinoma (HCC) patients aged 65 years or older. For the meta-analysis, the databases including PubMed (MEDLINE), EMBASE, OVID Medline, and the Cochrane Library were systematically searched. After the abstract-based review by two investigators, selected manuscripts were read in detail. The surgery group showed higher overall survival (OS) (HR 1.44, 95% CI 1.22-1.70) and disease-free survival (DFS) (HR 1.40, 95% CI 1.00-1.97) than the RFA group. This was also shown in small HCC of less than 3 cm (OS, HR 1.42, 95% CI 1.00-2.03; DFS, HR 1.32, 95% CI 0.91-1.91). This might be related to the high local recurrence in the RFA group (OR 4.90, 95% 2.16-11.08). On the other hand, adverse events were significantly lower in the RFA group (OR 0.22, 95% CI 0.14-0.36), which led to a decrease in the duration of hospital stay (mean difference -14.88 days, 95% CI -22.44--7.32). In elderly HCC patients, survival in the surgery group was significantly higher than in the RFA group, but various complications tended to increase; so, appropriate patient selection is required.

The effects of remdesivir on mortality and the requirement for mechanical ventilation in patients with COVID-19: a systematic review stratified by disease severity.

BACKGROUND/AIMS: The effectiveness of remdesivir treatment in reducing mortality and the requirement for mechanical ventilation (MV) remains uncertain, as randomized controlled trials (RCTs) have produced conflicting results. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other data resources to find RCTs published prior to April 10, 2023. The selection of studies, assessment of risk of bias, and meta-analysis were conducted according to PRISMA guidelines. The primary outcomes were all-cause mortality and the need to initiate MV. RESULTS: A total of 5,068 articles were screened, from eight RCTs comprising 11,945 patients. The meta-analysis found that, compared to standard care or placebo, remdesivir treatment provided no significant all-cause mortality benefit (pooled risk ratio [RR], 0.93; 95% confidence interval [CI], 0.85-1.02; 8 studies; high certainty evidence), while subgroup analyses revealed a trend towards reduced mortality among patients requiring oxygen but not MV (pooled RR, 0.88; 95% CI, 0.77-1.00; 6 studies; I2 = 4%). The need to initiate MV (pooled RR, 0.74; 95% CI, 0.59-0.94; 7 studies; moderate certainty evidence) in remdesivir-treated patients was also reduced compared to controls. Remdesivir significantly increased clinical improvement and discharge and significantly reduced serious adverse events. CONCLUSION: In this systematic review and meta-analysis of RCTs, it was found that remdesivir treatment did not show a substantial decrease in the risk of mortality. However, it was linked to a reduction in the necessity for additional ventilatory support, suggesting remdesivir could be beneficial for COVID-19 patients, particularly those who are not on MV.

Correction: Clinical efficacy and safety of interferon (Type I and Type III) therapy in patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

[This corrects the article DOI: 10.1371/journal.pone.0272826.].

Clinical efficacy of inhaled corticosteroids in patients with coronavirus disease 2019: A living review and meta-analysis.

Inhaled corticosteroids are known to be relatively safe for long-term use in inflammatory respiratory diseases and it has been repurposed as one of the potential therapies for outpatients with coronavirus disease 2019 (COVID-19). However, inhaled corticosteroids have not been accepted for COVID-19 as a standard therapy because of its lack of proven benefits. Therefore, this study aimed to evaluate the effectiveness of inhaled corticosteroids in patients with COVID-19. Randomized controlled trials comparing the efficacy of inhaled corticosteroid treatment in patients with COVID-19 were identified through literature electronic database searches up to March 10, 2023. Meta-analyses were conducted for predefined outcomes, and the certainty of evidence was graded using the grading of recommendations, assessment, development, and evaluation approach. Overall, seven trials (eight articles) were included in this systematic review. Compared with usual care, inhaled corticosteroids was associated with significantly improved clinical recovery at 7 and 14 days in patients with COVID-19. In subgroup analysis, only budesonide showed significant efficacy in clinical recovery, whereas no significant benefit was observed for ciclesonide. Moreover, inhaled corticosteroids use was not significantly associated with all-cause hospitalization, all-cause mortality, admission to intensive care unit, or the use of mechanical ventilation. Our systematic review used evidence with very low to moderate certainty. Although based on limited evidence, our results suggest that inhaled corticosteroids treatment, especially budesonide, improves the clinical recovery of patients with COVID-19. More trials and meta-analyses are needed to assess the efficacy of inhaled corticosteroids for COVID-19 treatment.

Clinical efficacy and safety of SARS-CoV-2-neutralizing monoclonal antibody in patients with COVID-19: A living systematic review and meta-analysis.

This study evaluated the efficacy and safety of neutralizing monoclonal antibodies (mAbs) with usual care in patients with coronavirus disease 2019 (COVID-19). Randomized controlled trials comparing the efficacy and safety of neutralizing mAb treatment in patients with COVID-19 were identified using electronic database searches through March 10, 2023. This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Overall, 13 trials (23 articles) involving 25,646 patients were included in this systematic review. Compared with usual care, neutralizing mAbs were associated with significantly reduced all-cause mortality in outpatients with COVID-19 (pooled risk ratios [RR], 0.41; 95% confidence interval (CI), 0.20-0.83; 12 studies), but not in inpatients. In the subgroup analysis, only outpatients infected prior to the emergence of Delta variant or those with mAb-VOC match had significantly reduced mortality, while no significant benefit was observed in patients infected with Delta and post-Delta variants or mAb-VOC mismatch. Moreover, the rate of hospitalization and number of hospital visits had significantly reduced only in outpatients infected prior to the emergence of the Delta variant and those with mAb-VOC match. Our systematic review used majority of the high-certainty evidence. Our study found neutralizing mAbs were beneficial for outpatients infected prior to Delta variant or mAb-VOC match. In the face of the continuous emergence of new COVID-19 variants, additional clinical data are needed to determine whether neutralizing mAb treatment will be effective for the newly emerging variants.

Two Years of Experience and Methodology of Korean COVID-19 Living Clinical Practice Guideline Development.

BACKGROUND: In Korea, during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, we responded to the uncertainty of treatments under various conditions, consistently playing catch up with the speed of evidence updates. Therefore, there was high demand for national-level evidence-based clinical practice guidelines for clinicians in a timely manner. We developed evidence-based and updated living recommendations for clinicians through a transparent development process and multidisciplinary expert collaboration. METHODS: The National Evidence-based Healthcare Collaborating Agency (NECA) and the Korean Academy of Medical Sciences (KAMS) collaborated to develop trustworthy Korean living guidelines. The NECA-supported methodological sections and 8 professional medical societies of the KAMS worked with clinical experts, and 31 clinicians were involved annually. We developed a total of 35 clinical questions, including medications, respiratory/critical care, pediatric care, emergency care, diagnostic tests, and radiological examinations. RESULTS: An evidence-based search for treatments began in March 2021 and monthly updates were performed. It was expanded to other areas, and the search interval was organized by a steering committee owing to priority changes. Evidence synthesis and recommendation review was performed by researchers, and living recommendations were updated within 3-4 months. CONCLUSION: We provided timely recommendations on living schemes and disseminated them to the public, policymakers and various stakeholders using webpages and social media. Although the output was successful, there were some limitations. The rigor of development issues, urgent timelines for public dissemination, education for new developers, and spread of several new COVID-19 variants have worked as barriers. Therefore, we must prepare systematic processes and funding for future pandemics.

Clinical efficacy and safety of interferon (Type I and Type III) therapy in patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

Interferon (IFN) has been highlighted in several randomized controlled trials as an attractive therapeutic candidate based plausible mode of action, suppressed response in severe COVID-19, and inhibition of SARS-CoV-2 replication. This study investigated the efficacy and safety of IFN in patients with COVID-19 according to clinical severity. Randomized controlled trials evaluating the efficacy and safety of IFN (systemic or inhaled IFN-α, -ß, and -λ) treatment in adult patients with COVID-19 were identified by systematically searching electronic databases until January 2023. Risk of bias were assessed using the Cochrane risk of bias tool, meta-analysis, and certainty of evidence grading were followed for the systematic review. We included 11 trials comprising 6,124 patients. Compared with exclusive standard care or placebo, IFN therapy did not provide significant clinical benefits for mortality at day 28 (pooled risk ratio [RR] = 0.86, 95% confidence interval [CI]: 0.62-1.18, 9 studies, low-certainty evidence) and progression to mechanical ventilation (pooled RR = 1.08, 95% CI: 0.81-1.43, 6 studies, low-certainty evidence) in patients with COVID-19. IFN therapy resulted in significantly increased hospital discharge on day 14 relative to the control arm (pooled RR = 1.29, 95% CI: 1.04-1.59). These results were inconsistent compared to other comparable outcomes such as recovery at day 14 and time to clinical improvement. The IFN-treated arm was as safe as the control arm, regardless of clinical severity (pooled RR = 0.87, 95% CI: 0.64-1.19, 9 studies, low-certainty evidence). In conclusion, IFN therapy was safe but did not demonstrate favorable outcomes for major clinical indices in patients with COVID-19, particularly those with higher than moderate severity. IFN therapy was not associated with worsening outcomes in patients with severe COVID-19. Future clinical trials should evaluate the clinical efficacy of IFN therapy in patients with mild COVID-19 or at an earlier stage. Trial registration: The protocol for this review was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42022301413.

Total Knee Replacement After Arthroscopic Meniscectomy in Knee Osteoarthritis: A Nationwide Population-Based Cohort Study.

BACKGROUND: Recent studies raise concerns that arthroscopic meniscectomy (AM) for degenerative tear may be detrimental to the maintenance of the joint structure. This study was performed to examine the rate of total knee replacement (TKR) among patients with knee osteoarthritis (OA) who underwent AM for meniscal tears and compare this rate with those who did not. METHODS: A retrospective cohort study was conducted using the National Health Insurance Database of South Korea. Among knee OA patients aged 50-79, those who were treated with AM due to meniscal damage from 2007 to 2009 were selected as the AM group while those not treated with AM despite the presence of meniscal damage were selected as control group. Both were matched based on a propensity score and followed-up until the earliest occurrence of: TKR, death, or 10 years. Cox proportional hazards models were used to compare the outcome. RESULTS: A total of 36,974 patients were included in AM groups and non-AM group after 1:1 matching. TKR occurred in 9.62% and 7.64% in AM and non-AM groups with the average duration after meniscectomy of 5.88 ± 2.77 and 5.50 ± 2.94 years, respectively. After adjustment for baseline confounders, the TKR rate in the AM group was calculated to be 25% higher than that in the non-AM group (subdistribution hazard ratio, 1.25; 95% confidence interval, 1.16-1.34). The mortality rate was 5.20%, which did not significantly differ between groups. CONCLUSION: OA patients who underwent AM for the meniscal injury had higher incidence of TKR up to 10 years of follow-up than the non-operated group. The greater TKR utilization observed in patients undergoing AM merits caution when treating OA patients with meniscal injury.

Clinical efficacy and safety of interleukin-6 receptor antagonists (tocilizumab and sarilumab) in patients with COVID-19: a systematic review and meta-analysis.

This study investigated the efficacy and safety of interleukin-6 (IL-6) receptor antagonists with standard care treatment in patients with coronavirus disease 2019 (COVID-19). The randomized controlled trials were identified through systematic searches of electronic databases through February 10, 2022. In total, 17 trials comprising 8,614 patients were included. Compared with exclusive standard care or placebo, IL-6 receptor antagonists with standard of care treatment were associated with a significantly reduced all-cause mortality at 28 days (pooled risk ratios [RR], 0.88; 95% confidence interval (CI), 0.82-0.95; 17 studies) and progression to invasive mechanical ventilation (RR, 0.79; 95% CI, 0.71-0.88; nine studies). Particularly, the subgroup of patients with moderate-to-severe COVID-19 showed a significant mortality benefit (RR, 0.89; 95% CI, 0.81-0.96; four studies) and a reduced risk for mechanical ventilation (RR, 0.80; 95% CI, 0.70-0.91; three studies) with tocilizumab treatment. The frequency of serious adverse events was lower in the tocilizumab treatment group than in the standard of care treatment group (RR, 0.83; 95% CI, 0.71-0.97; 11 studies), with no significant difference in the sarilumab treatment group (RR, 1.12; 95% CI, 0.89-1.40; four studies). Our meta-analysis demonstrated that tocilizumab treatment showed promising results in reducing 28-day mortality and progression to mechanical ventilation in patients with moderate-to-severe COVID-19, without the burden of serious adverse events.Trial registration: Clinical Trials Registry India identifier: CTRI/2020/05/025369.The proper registration is PROSPERO: registration number CRD42021294120.

Arthroscopic Partial Meniscectomy versus Physical Therapy for Degenerative Meniscal Tear: a Systematic Review.

BACKGROUND: Meniscal tears are commonly observed in patients with knee osteoarthritis (OA), however, clinical significance of such lesions detected by magnetic resonance imaging is in many cases unclear. This study aimed to determine the clinical effectiveness of arthroscopic partial meniscectomy (APM) compared with non-operative care in patients with knee OA. METHOD: We used existing systematic reviews with updates of latest studies. Three randomized controlled studies were selected, where two studies compared the effects of APM plus physical therapy (PT) with PT alone and one compared APM alone and PT alone. While 1 study exclusively included OA patients, 2 studies included 21.1 and 12% of patients with no radiographic OA. Patients with knee locking were unanimously excluded. RESULTS: Upon comparison of APM plus PT and PT alone, there was no significant difference observed in knee function, physical activity, or adverse events. Knee pain was observed to be significantly lower in the APM plus PT group at 6 months, but there was no difference between the two groups at 12 and 24 months. With respect to the comparison between APM alone and PT alone, PT was non-inferior based on the criteria for knee function during 24 months; however, knee pain was significantly reduced in the APM alone group. CONCLUSIONS: Our study showed that knee pain was significantly improved in the APM group compared to non-operative care group at 6 months and over 24 months. Our result was based on only 3 randomized controlled trials (RCTs) revealing a significant knowledge gap, hence demanding more high-quality RCTs in OA patients. TRIAL REGISTRATION: PROSPERO Identifier: CRD42020215965.

Revised Korean Society of Infectious Diseases/National Evidence-based Healthcarea Collaborating Agency Guidelines on the Treatment of Patients with COVID-19.

Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives. There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily. Some effective treatment options, albeit of variable efficacy, have been discovered. Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly. Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence.

Dissecting phenotypic responses of the druggable targetome in cancers.

Although a large amount of screening data comprising target genes and/or drugs tested against cancer cell line panels are available, different assay conditions and readouts limit the integrated analysis and batch-to-batch comparison of these data. Here, we systematically produced and analyzed the anticancer effect of the druggable targetome to understand the varied phenotypic outcomes of diverse functional classes of target genes. A library of siRNAs targeting ~4,800 druggable genes was screened against cancer cell lines under 2D and/or 3D assay conditions. The anticancer effect was simultaneously measured by quantifying cell proliferation and/or viability. Hit rates varied significantly depending on assay conditions and/or phenotypic readouts. Functional classes of hit genes were correlated with the microenvironment difference between the 2D monolayer cell proliferation and 3D sphere formation assays. Furthermore, multiplexing of cell proliferation and viability measures enabled us to compare the sensitivity and resistance responses to the gene knockdown. Many target genes that inhibited cell proliferation increased the single-cell-level viability of surviving cells, leading to an increase in self-renewal potential. In this study, combinations of parallel 2D/3D assays and multiplexing of cell proliferation and viability measures provided functional insights into the varied phenotypic outcomes of the cancer targetome.