Clinical effectiveness of nirmatrelvir plus ritonavir on the short- and long-term outcome in high-risk children with COVID-19.

This study investigated the clinical effectiveness of nirmatrelvir plus ritonavir (NMV-r) on short-term outcome and the risk of postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) among pediatric patients with coronavirus disease 2019 (COVID-19). This retrospective cohort study used the TriNetX research network to identify pediatric patients between 12 and 18 years with COVID-19 between January 1, 2022 and August 31, 2023. The propensity score matching (PSM) method was used to match patients receiving NMV-r (NMV-r group) with those who did not receive NMV-r (control group). Two cohorts comprising 633 patients each (NMV-r and control groups), with balanced baseline characteristics, were identified using the PSM method. During the initial 30 days, the NMV-r group showed a lower incidence of all-cause hospitalization, mortality, or ED visits (hazard ratio [HR] = 0.546, 95% confidence interval [CI]: 0.372-0.799, p = 0.002). Additionally, the NMV-r group had a significantly lower risk of all-cause hospitalization compared with the control group (HR = 0.463, 95% CI: 0.269-0.798), with no deaths occurring in either group. In the 30-180-day follow-up period, the NMV-r group exhibited a non-significantly lower incidence of post-acute sequelae of SARS-CoV-2 infection (PASC), encompassing symptoms such as fatigue, cardiopulmonary symptoms, pain, cognitive impairments, headache, dizziness, sleep disorders, anxiety, and depression, compared to the control group. This study underscores the potential effectiveness of NMV-r in treating high-risk pediatric patients with COVID-19, demonstrating significant reductions in short-term adverse outcomes such as emergency department visits, hospitalization, or mortality within the initial 30-day period. Additionally, NMV-r shows promise in potentially preventing the development of PASC.

Effect of hydrocortisone-fludrocortisone combination on mortality in septic shock: a systematic review and meta-analysis.

BACKGROUND: This study assessed the effect of hydrocortisone-fludrocortisone combination therapy on the mortality of patients with septic shock. METHODS: A literature search was conducted using Medline, Embase, the Cochrane Library, ClinicalTrials.gov, and other databases for articles published until October 1, 2023. Only clinical studies that assessed the clinical efficacy and safety of hydrocortisone-fludrocortisone therapy for the treatment of septic shock were included. The primary outcome was the in-hospital mortality rate. RESULTS: Seven studies with a total of 90, 756 patients were included. The study group exhibited lower in-hospital mortality rates (40.8% vs. 42.8%; OR, 0.86; 95% CI, 0.80-0.92). Compared to the control group, the study group also had lower intensive care unit (ICU) mortality (OR, 0.77; 95% CI, 0.63-0.95), 28-day mortality (OR, 0.85; 95% CI, 0.72-1.00), 90-day mortality (OR, 0.85; 95% CI, 0.71-1.01), 180-day mortality (OR, 0.82; 95% CI, 0.68-0.90), and one-year mortality (OR, 0.70; 95% CI, 0.42-1.16). Subgroup analyses showed a similar trend, particularly prominent in the pooled analysis of randomized clinical trials, multicenter studies, and ICU patients, the study drug regimen involved hydrocortisone at a dose of 50 mg every 6 h in combination with fludrocortisone at 50 µg daily, with the control group receiving either placebo or standard care. Hydrocortisone-fludrocortisone also increased vasopressor-free days and reduced vasopressor duration, without elevating the risk of adverse events. CONCLUSIONS: This study emphasizes the potential survival benefits of hydrocortisone-fludrocortisone combination therapy for patients with septic shock and its additional advantages, including reduced vasopressor use.

Association between vitamin D deficiency and post-acute outcomes of SARS-CoV-2 infection.

OBJECTIVES: This study aimed to investigate the association between vitamin D deficiency (VDD) and post-acute outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: This retrospective study used the TriNetX research network to identify COVID-19 patients between January 1 and November 30, 2022. Patients were matched using propensity score matching (PSM) and divided into VDD (< 20 ng/mL) and control (≥ 20 ng/mL) groups. The primary outcome was a composite of post-COVID-19 condition (identified by ICD-10 code), all-cause emergency department (ED) visits, hospitalization, and death during the follow-up period (90-180 days) after the diagnosis of COVID-19. RESULTS: From an initial recruitment of 42,674 non-hospitalized patients with COVID-19 and known 25(OH)D status, a VDD group of 8300 was identified and propensity matched with 8300 controls. During the follow-up period, the VDD group had a higher risk of the primary outcome than did the control group [hazard ratio (HR) = 1.122; 95% confidence interval (CI) = 1.041-1.210]. The VDD group also had a higher risk of all-cause ED visits (HR = 1.114; 95% CI = 1.012-1.226), all-cause hospitalization (HR = 1.230; 95% CI = 1.105-1.369), and all-cause death (HR = 1.748; 95% CI = 1.047-2.290) but not post-COVID-19 condition (HR = 0.980; 95% CI = 0.630-1.523), individually. CONCLUSION: Among the COVID-19 patients, VDD might be associated with a higher risk of all-cause ED visits, hospitalization, and death during the post-acute phase.

Nutritional deficiency anemia and post-acute sequelae in patients with severe acute respiratory syndrome coronavirus 2 infection: A six-month retrospective cohort analysis of 30 892 patients.

The effect of anemia on the post-acute outcome of patients with severe acute respiratory syndrome coronavirus 2 infection was unclear. This study aimed to investigate the potential association between nutritional deficiency anemia (NDA) status and post-acute sequelae of patients with SARS-CoV-2 infection. This retrospective cohort study included patients with coronavirus disease (COVID-19) from January 1, 2022 to November 30, 2022 using the TriNetX research network. The patients were grouped into the NDA group comprising patients diagnosed with NDA and the control group comprising patients without NDA, and propensity score matching (PSM) was performed to balance the two groups. The primary outcome was a composite of post-COVID-19 condition, all-cause hospitalization, and all-cause death. The secondary outcomes were any individual outcomes of the primary composite. The follow-up period was set at 90-180 days after COVID-19 diagnosis. Two cohorts comprising 15 446 nonhospitalized patients with COVID-19 in each group with balanced baseline characteristics were created using PSM. During the follow-up period, the NDA group demonstrated a higher risk of the composite primary outcome, including post-COVID-19 condition, all-cause hospitalization, or all-cause death (hazard ratio [HR], 1.896; 95% confidence interval [CI] = 1.757-2.045). Regarding secondary outcomes, the NDA group was associated with worse outcomes, including post-COVID-19 condition (HR, 1.992; 95% CI = 1.403-2.828), all-cause hospitalization (HR, 1.856; 95% CI = 1.714-2.009), and all-cause death (HR, 3.922; 95% CI = 2.910-5.285) compared to the control group. Among nonhospitalized patients with COVID-19, NDA was associated with a higher risk of post-COVID-19 condition, all-cause hospitalization, and all-cause death during the 90-180-day follow-up period.

Clinical efficacy of nirmatrelvir and ritonavir combination for treating diabetic patients with COVID-19.

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.

Efficacy and safety of adjunctive corticosteroids in the treatment of severe community-acquired pneumonia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: 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). METHODS: 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. RESULTS: 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 (I2 = 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). CONCLUSIONS: 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.

Nosocomial transmission of chickenpox and varicella zoster virus seroprevalence rate amongst healthcare workers in a teaching hospital in China.

BACKGROUND: Varicella zoster virus (VZV) is a highly contagious herpesvirus with potential for nosocomial transmission. However, the importance of nosocomial chickenpox outbreak in China has often been ignored. With the increasing immunocompromised population in China, a thorough review of issues related to nosocomial transmission and the seroprevalence rate of VZV among healthcare workers is necessary. METHODS: Retrospective case finding for nosocomial transmission of chickenpox was conducted between January 1, 2013 and December 31, 2017. Cases were identified based on clinical features compatible with chickenpox. A cross-sectional study on the seroprevalence rate of VZV among healthcare workers (HCWs) was conducted between January 1, 2014 and December 31, 2017. The serum VZV antibodies of 1804 HCWs were measured by enzyme-linked immunosorbent assay (ELISA). The seroprevalence rate of VZV antibodies, the positive predictive value and negative predictive value of self-reported history of varicella were analyzed. The economic impact associated with nosocomial transmission of VZV was also assessed. RESULTS: A total of 8 cases of chickenpox were identified in three nosocomial transmissions, including 4 HCWs who were infected nosocomially. The overall seroprevalence rate of VZV was 88.4%, which significantly increased with age (P < 0.01). The seroprevalence rates of HCWs with different genders and occupations showed no statistically significant differences. The positive and negative predictive values of a self-reported history of varicella were 80.8 and 10.6% respectively. An estimation of 163.3 person-days of work were lost in each nosocomial transmission and 86.7 infection control unit person-hours were required for each outbreak investigation. The cost of VZV IgG ELISA screening was estimated to be 83 USD per nosocomial transmission. CONCLUSIONS: Nosocomial transmission of VZV occurred repeatedly in the hospital setting. An alarming 11.6% of HCWs were seronegative for VZV, which might increase the risk of nosocomial infection and outbreak for other susceptible co-workers and patients. This is especially important in the setting of a teaching hospital where many immunocompromised patients were managed. Furthermore, the positive predictive value of self-reported varicella on seroprevalence rate in our study was lower than those reported in other countries, therefore serological testing of VZV antibodies with subsequent vaccination for all non-immune HCWs should be considered.

Reduced expression of p21-activated protein kinase 1 correlates with poor histological differentiation in pancreatic cancer.

BACKGROUND: P21-activated protein kinase 1 (PAK1), a main downstream effector of small Rho GTPases, is overexpressed in many malignancies. PAK1 overexpression is associated with poor prognosis in some tumor types, including breast cancer, gastric cancer, and colorectal cancer. However, the expression and clinical relevance of PAK1 expression in human pancreatic cancer remains unknown. METHODS: The present study investigated the clinical and prognostic significance of PAK1 expression in pancreatic carcinoma. We examined and scored the expression of PAK1 by immunohistochemistry in 72 primary pancreatic carcinoma samples and 20 liver metastatic samples. The relationships between PAK1 and clinicopathological parameters and prognosis in primary and metastatic pancreatic cancer were analyzed. RESULTS: Among the total 92 cases, primary pancreatic cancer samples had a significantly higher rate (38/72, 52.8%) of high PAK1 expression than liver metastatic samples (5/20, 25.0%) (P=0.028). Among the 72 primary pancreatic cancer patients, high PAK1 expression was associated with younger age (P=0.038) and moderately or well differentiated tumor (P=0.007). Moreover, a positive relationship was found between high PAK1 expression and overall survival (OS) (P<0.005). Patients with high PAK1 expression had a better OS than those with low PAK1 expression. Univariate and multivariate analysis by Cox regression including PAK1 and other prognostic pathological markers demonstrated high PAK1 immunostaining as a prognostic factor for survival in pancreatic cancer patients (P<0.005). CONCLUSIONS: We report for the first time that PAK1 is a novel prognostic marker for pathologically confirmed human pancreatic cancer. Reduced expression of PAK1 correlates with poor histological differentiation in pancreatic cancer.

Machine Learning to Predict the Risk of Malnutrition in Hospitalized Patients with Pneumonia and Analysis of Related Prognostic Factor.

This study explored machine learning's potential in predicting the nutritional status and outcomes for pneumonia patients. It focused on 4,368 patients in a Taiwan medical center from Jan 2016 to Feb 2022, excluding ICU cases. The average age was 77.6 years, with 10.2% well-nourished, 76.3% at-risk, and 13.5% malnourished. Machine learning models, particularly LightGBM and XGBoost, showed high accuracy in predicting hospital stays, mortality rates, and readmissions. These findings emphasize the role of data-driven methods in enhancing patient care and managing conditions like pneumonia more effectively.

Effects of perioperative magnesium on postoperative analgesia following thoracic surgery: a meta-analysis of randomised controlled trials.

To evaluate the analgesic effects of intravenous magnesium in patients undergoing thoracic surgery. Randomised clinical trials (RCTs) were systematically identified from MEDLINE, EMBASE, Google Scholar and the Cochrane Library from inception to May 1st, 2023. The primary outcome was the effect of intravenous magnesium on the severity of postoperative pain at 24 hours following surgery, while the secondary outcomes included association between intravenous magnesium and pain severity at other time points, morphine consumption, and haemodynamic changes. Meta-analysis of seven RCTs published between 2007 and 2019, involving 549 adults, showed no correlation between magnesium and pain scores at 1-4 (standardized mean difference [SMD]=-0.06; p=0.58), 8-12 (SMD=-0.09; p=0.58), 24 (SMD=-0.16; p=0.42), and 48 (SMD=-0.27; p=0.09) hours post-surgery. Perioperative magnesium resulted in lower equivalent morphine consumption at 24 hours post-surgery (mean difference [MD]=-25.22 mg; p=0.04) and no effect at 48 hours (MD=-4.46 mg; p=0.19). Magnesium decreased heart rate (MD = -5.31 beats/min; p=0.0002) after tracheal intubation or after surgery, but had no effect on postoperative blood pressure (MD=-6.25 mmHg; p=0.11). There was a significantly higher concentration of magnesium in the magnesium group compared with that in the placebo group (MD = 0.91 mg/dL; p<0.00001). This meta-analysis provides evidence supporting perioperative magnesium as an analgesic adjuvant at 24 hours following thoracic surgery, but no opioid-sparing effect at 48 hours post-surgery. The severity of postoperative pain did not significantly differ between any of the postoperative time points, irrespective of magnesium. Further research on perioperative magnesium in various surgical settings is needed.

The clinical outcomes and effectiveness of antiviral agents among underweight patients with COVID-19.

OBJECTIVES: This study investigated the outcomes of underweight patients with COVID-19 and the effectiveness of antiviral agents in this population. METHODS: A retrospective cohort study using theTriNetX research network was conducted. Propensity score matching (PSM) was employed to balance the first cohort involving COVID-19 patients with underweight and normal-weight. In the second cohort, underweight patients receiving antiviral agents and untreated individuals were matched using PSM. The primary outcome was a composite of all-cause hospitalization and death during the 7-30-day follow-up period. RESULTS: After PSM, the first cohort including each group of 13,502 patients with balanced baseline characteristics were identified for comparing the outcome of patients with underweight and normal weight. The underweight group had a higher risk of the composite primary outcome than those with normal weight (hazard ratio [HR], 1.251; 95% confidence interval [CI], 1.132-1.382). The second cohort included each 884 underweight patients with and without receiving antivirals.Compared with untreated patients, those receiving antiviral treatment had a lower risk of composite primary outcomes (HR, 0.426; 95% CI, 0.278-0.653). CONCLUSION: Underweight status may be associated with a higher risk of all-cause hospitalization and death in patients with COVID-19.Among underweight patients, antiviral agents demonstrated clinically beneficial effects.

Clinical effectiveness of oral antiviral agents for treating non-hospitalized COVID-19 patients with chronic kidney disease.

OBJECTIVES: This study examined the effectiveness of nirmatrelvir plus ritonavir (NMV-r) and molnupiravir (MOV) in treating COVID-19 among chronic kidney disease (CKD) patients. METHODS: This retrospective cohort study, using the TriNetX research network, identified stage 3-5 CKD and end-stage kidney disease (ESKD) patients with non-hospitalized COVID-19 between 1 January 2022, and 31 May 2023. Propensity score matching (PSM) was used to compare patients on NMV-r or MOV (antiviral group) against those not receiving these treatments (control group). The primary composite outcome was the cumulative hazard ratio (HR) for all-cause hospitalization or death within the 30-day follow-up. RESULTS: After PSM, two balanced cohorts of 6,275 patients each were established. The antiviral group exhibited a lower incidence of all-cause hospitalization or mortality (5.93% vs. 9.53%; HR: 0.626; 95% CI: 0.550-0.713) than controls. Additionally, antiviral recipients were associated with a lower risk of all-cause hospitalization (HR: 0.679; 95% CI: 0.594-0.777) and mortality (HR: 0.338; 95% CI: 0.227-0.504). The beneficial effects of antiviral agents were consistent across sex, age, vaccination status, antiviral type, and CKD stage. CONCLUSION: Oral antiviral agents could be associated with lower rates of all-cause hospitalization or death among non-hospitalized COVID-19 patients with CKD.

Implementing a Novel Machine Learning System for Nutrition Education in Diabetes Mellitus Nutritional Clinic: Predicting 1-Year Blood Glucose Control.

(1) Background: Persistent hyperglycemia in diabetes mellitus (DM) increases the risk of death and causes cardiovascular disease (CVD), resulting in significant social and economic costs. This study used a machine learning (ML) technique to build prediction models with the factors of lifestyle, medication compliance, and self-control in eating habits and then implemented a predictive system based on the best model to forecast whether blood glucose can be well-controlled within 1 year in diabetic patients attending a DM nutritional clinic. (2) Methods: Data were collected from outpatients aged 20 years or older with type 2 DM who received nutrition education in Chi Mei Medical Center. Multiple ML algorithms were used to build the predictive models. (3) Results: The predictive models achieved accuracies ranging from 0.611 to 0.690. The XGBoost model with the highest area under the curve (AUC) of 0.738 was regarded as the best and used for the predictive system implementation. SHAP analysis was performed to interpret the feature importance in the best model. The predictive system, evaluated by dietitians, received positive feedback as a beneficial tool for diabetes nutrition consultations. (4) Conclusions: The ML prediction model provides a promising approach for diabetes nutrition consultations to maintain good long-term blood glucose control, reduce diabetes-related complications, and enhance the quality of medical care.

Association between nirmatrelvir plus ritonavir and the outcomes of non-hospitalized obese patients with COVID-19.

OBJECTIVE: To investigate the association between nirmatrelvir plus ritonavir (NMV-r) and the outcomes of non-hospitalized obese patients with coronavirus disease 2019 (COVID-19). METHODS: This retrospective cohort study used the TriNetX research network to identify non-hospitalized obese adult patients with COVID-19 between 1 January 2022 and 30 June 2023. Propensity score matching was used to match patients receiving NMV-r (NMV-r group) with those not receiving NMV-r (control group). The primary outcome was the compositive outcome of all-cause emergency department (ED) visits, hospitalization or death during the 30-day follow-up period. RESULTS: Using propensity score matching methods, two cohorts of 30,969 patients each with balanced baseline characteristics were identified. During the follow-up period, the NMV-r group had a lower risk of all-cause ED visits, hospitalization or death [4.80% (n=1489) vs 5.50% (n=1705); hazard ratio (HR) 0.900, 95% confidence interval (CI) 0.839-0.965]. Compared with the control group, the NMV-r group had a lower risk of all-cause ED visits (HR 0.812, 95% CI 0.740-0.891) and all-cause mortality (HR 0.089, 95% CI 0.027-0.288). The lower risk in the NMV-r group compared with the control group was observed consistently in most subgroup analyses according to body mass index (30.0-34.9 kg/m2: HR 0.68, 95% CI 0.55-0.82; 35.0-39.9 kg/m2: HR 0.67, 95% CI 0.52-0.87), age (4-64 years: HR 0.83, 95% CI 0.75-0.92; ≥65 years: HR 0.88, 95% CI 0.79-0.98), sex (men: HR 0.69, 95% CI 0.60-0.79; women: HR 0.69, 95% CI 0.63-0.76) and vaccination status (unvaccinated: HR 0.75, 95% CI 0.70-0.81). CONCLUSION: NMV-r is associated with reduced risk of all-cause ED visits, hospitalization and death for non-hospitalized obese patients with COVID-19. Accordingly, these findings support the use of NMV-r in obese patients.

An iRGD-conjugated photothermal therapy-responsive gold nanoparticle system carrying siCDK7 induces necroptosis and immunotherapeutic responses in lung adenocarcinoma.

Although immunotherapy has improved the clinical treatment of lung adenocarcinoma (LUAD), many tumors have poor responses to immunotherapy. In this study, we confirmed that high expression of Cyclin-Dependent Kinase 7 (CDK7) promoted an immunosuppressive macrophage phenotype and macrophage infiltration in LUAD. Thus, we have developed an internalizing-RGD (iRGD)-conjugated gold nanoparticle (AuNP) system which carries siCDK7 to activate the antitumor immune response. The iRGD-conjugated AuNP/siCDK7 system exhibited good tumor targeting performance and photothermal effects. The AuNP/siCDK7 system with excellent biosafety exerted a significant photothermal antitumor effect by inducing tumor cell necroptosis. Furthermore, the AuNP/siCDK7 system ameliorated the immunosuppressive microenvironment and enhanced the efficacy of anti-PD-1 treatment by increasing CD8+ T cell infiltration and decreasing M2 macrophage infiltration. Hence, this iRGD-conjugated AuNP/siCDK7 system is a potential treatment strategy for lung adenocarcinoma, which exerts its effects by triggering tumor cell necroptosis and immunotherapeutic responses.

Clinical efficacy of enteral nutrition feeding modalities in critically ill patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: In intensive care units (ICUs), both continuous and intermittent feeding are commonly used for early enteral nutrition (EN). However, whether continuous feeding is a preferable feeding modality compared to intermittent feeding remains unclear. Therefore, this meta-analysis assessed the clinical efficacy of both EN feeding modalities in critically ill patients. METHODS: The PubMed, Embase, and Cochrane Library databases were searched from their inception dates to December 29, 2022. The search did not involve language restrictions (PROSPERO CRD42022371756). Randomized controlled trials (RCTs) comparing the clinical efficacy and safety of continuous feeding and intermittent feeding in critically ill patients in ICUs were included. RESULTS: We included 13 RCTs involving 785 patients. Compared with intermittent feeding, continuous feeding was associated with a lower mortality rate (relative risk [RR], 0.68; 95% confidence interval [CI], 0.47, 0.98; p = 0.04) but a higher risk of constipation (RR, 1.57; 95% CI, 1.02, 2.43; p = 0.04). Trial sequential analysis (TSA) for mortality rate presented a cumulative Z-curve crossing the traditional boundary, but the curve did not cross the TSA boundary for benefit. No significant differences were found in the aspiration/pneumonia rate (RR, 1.19; 95% CI, 0.51, 2.75; p = 0.69), diarrhea rate (RR, 0.82; 95% CI, 0.58, 1.16; p = 0.26), or increased gastric residual volumes (RR, 1.05; 95% CI, 0.58, 1.90; p = 0.86) between the groups. CONCLUSION: Despite the low certainty of evidence, compared with intermittent feeding, continuous feeding may reduce the mortality rate in critically ill patients in ICU. Additional studies are needed to provide more evidence and validate the findings.

The Hirsch-index in self-citation rates with articles in Medicine (Baltimore): Bibliometric analysis of publications in two stages from 2018 to 2021.

BACKGROUND: The Hirsch-index (h-index) is a measure of academic productivity that incorporates both the quantity and quality of an author's output. However, it is still affected by self-citation behaviors. This study aims to determine the research output and self-citation rates (SCRs) in the Journal of Medicine (Baltimore), establishing a benchmark for bibliometrics, in addition to identifying significant differences between stages from 2018 to 2021. METHODS: We searched the PubMed database to obtain 17,912 articles published between 2018 and 2021 in Medicine (Baltimore). Two parts were carried out to conduct this study: the categories were clustered according to the medical subject headings (denoted by midical subject headings [MeSH] terms) using social network analysis; 3 visualizations were used (choropleth map, forest plot, and Sankey diagram) to identify dominant entities (e.g., years, countries, regions, institutes, authors, categories, and document types); 2-way analysis of variance (ANOVA) was performed to differentiate outputs between entities and stages, and the SCR with articles in Medicine (Baltimore) was examined. SCR, as well as the proportion of self-citation (SC) in the previous 2 years in comparison to SC were computed. RESULTS: We found that South Korea, Sichuan (China), and Beijing (China) accounted for the majority of articles in Medicine (Baltimore); ten categories were clustered and led by 3 MeSh terms: methods, drug therapy, and complications; and more articles (52%) were in the recent stage (2020-2021); no significant difference in counts was observed between the 2 stages based on the top ten entities using the forest plot (Z = 0.05, P = .962) and 2-way ANOVA (F = 0.09, P = .76); the SCR was 5.69% (<15%); the h-index did not differ between the 2 collections of self-citation inclusion and exclusion; and the SC in the previous 2 years accounted for 70% of the self-citation exclusion. CONCLUSION: By visualizing the characteristics of a given journal, a breakthrough was made. Subject categories can be classified using MeSH terms. Future bibliographical studies are recommended to perform the 2-way ANOVA and then compare the outputs from 2 stages as well as the changes in h-indexes between 2 sets of self-citation inclusion and exclusion.

LncRNA NFYC-AS1 promotes the development of lung adenocarcinomas through autophagy, apoptosis, and MET/c-Myc oncogenic proteins.

BACKGROUND: Nuclear transcription factor Y subunit C antisense RNA 1 (NFYC-AS1) was revealed to be a potential prognostic biomarker in lung adenocarcinoma (LAUD) by analyzing The Cancer Genome Atlas (TCGA) database. However, the function of NFYC-AS1 has not been verified in cancers, including LAUD. We plan to verify the function of NFYC-AS1 in LAUD through this study. METHODS: We determined NFYC-AS1 expression in 4 LAUD cell lines, and 1 normal lung cell line (HBE) by quantitative real-time reverse transcription PCR (qRT-PCR). small interfering RNA (siRNA) was employed to specifically knockdown NFYC-AS1 in H1299 and PC9 cell lines. Cell growth and invasion activity of LAUD cells was assessed by WST-1, colony formation and transwell assay, respectively. The effect of NFYC-AS1 expression on cell apoptosis was then assessed by flow cytometry assay. Furthermore, the expression of downstream proteins of NFYC-AS1 was investigated by Western blot. RESULTS: The proliferation, migration, and invasion of cells were inhibited and apoptosis was increased after NFYC-AS1 knockdown in LAUD cells. The cells transfected with NFYC-AS1 siRNA had a higher rate of apoptosis compared with that in control cells. The apoptosis-related proteins p53 and PARP were upregulated. These suggested NFYC-AS1 could inhibit the apoptosis of LAUD cells. In terms of the expression of major autophagy proteins, p62 was downregulated while Beclin 1 was upregulated after NFYC-AS1 knockdown, which suggested that autophagy was activated. The expression of oncogenic proteins MET and c-Myc was downregulated. CONCLUSIONS: In summary, the above results suggest that NFYC-AS1 may promote the proliferation of LAUD through autophagy and apoptosis.

LAMC2 promotes the proliferation of cancer cells and induce infiltration of macrophages in non-small cell lung cancer.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is the most prevalent cancer worldwide. Tumor microenvironment (TME) plays a very important role in the cancer development. Thus, it is urgent to find the change of TME that contributes to NSCLC carcinogenesis and progression. METHODS: The bioinformatics analysis approach was applied to evaluate the change of TME and screen the differentially immune cells in NSCLC tissue based on The Cancer Genome Atlas (TCGA) data. Meanwhile, the association of differentially immune cells with tumor stage and prognosis of NSCLC was evaluated. Then, we screen the different expression genes between macrophages infiltration high group and low group. After that, the expression of LAMC2 was detected in 48 cases of NSCLC tissues and paired normal tissues. The function of LAMC2 was detected through cell experiments in vitro. Immunohistochemistry assay was used to detect the correlation between LAMC2 expression and macrophages infiltration in NSCLC tissue. LAMC2-related pathways were identified by gene set enrichment analysis. RESULTS: Compared with early stage, middle-advanced stage of NSCLC exhibited lower immune score. Macrophages were the main component of different immune cells and correlated with poor outcome. The results of immunohistochemistry indicated that the expression of LAMC2 in NSCLC tissues was higher than paired normal tissues. Down-regulation of LAMC2 inhibited the proliferation, migration and invasion of NSCLC cells in vitro. Overexpression of LAMC2 was positively associated with macrophages infiltration in NSCLC tissues. Inhibition of LAMC2 expression in NSCLC cells could reduce THP-1 infiltration, and LAMC2 protein could promote the infiltration of THP-1. The Gene Set Enrichment Analysis results showed that high expression of LAMC2 was correlated with focal adhesion and extracellular matrix receptor interaction. CONCLUSIONS: Immune suppression and macrophages infiltration were correlated with poor outcomes in NSCLC. LAMC2 promoted macrophages infiltration and extracellular matrix remolding in NSCLC. Our studies suggested an oncogenic role of LAMC2 in NSCLC progression and it perhaps serve as a potential immune therapy target for NSCLC.