MicroRNA-155-5p inhibition alleviates irritable bowel syndrome by increasing claudin-1 and ZO-1 expression.

Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disease. Emerging studies have demonstrated that microRNAs (miRNAs) are commonly dysregulated in patients with IBS, and aberrant miRNAs are implicated in IBS occurrence. Although miR-155-5p participates in inflammatory bowel disease (IBD) and intestinal barrier dysfunction, the role of miR-155-5p in IBS is unclear. Methods: In the present study, colon samples were obtained from IBS patients and IBS mice induced by trinitrobenzenesulfonic acid (TNBS), and the levels of miR-155-5p, claudin-1 (CLDN1), and zonula occludens-1 (ZO-1) were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical analysis. The regulatory role of miR-155-5p in CLDN1 and ZO-1 expression was validated using dual luciferase reporter assay. Results: We found that miR-155-5p levels were upregulated in colon samples of IBS patients and mice compared with healthy subjects and normal mice, respectively. Meanwhile, the levels of CLDN1 and ZO-1 were decreased in colon samples of IBS patients and mice. Importantly, forced expression of miR-155-5p inhibited CLDN1 and ZO-1 expression. In IBS mice, intraperitoneal injection with miR-155-5p inhibitor increased CLDN1 and ZO-1 expression in intestinal mucosal epithelium, enhanced visceral response thresholds, and decreased myeloperoxidase (MPO) activity. Conclusions: In summary, these results suggested that miR-155-5p participated in the pathogenesis of IBS, at least in part by inhibiting CLDN1 and ZO-1 expression, indicating that miR-155-5p may be a potential therapeutic target for IBS.

Effects of high-dose opioid analgesia on survival, pain relief, quality of life and adverse drug reactions in cancer and neuropathic pain patients: a retrospective cohort study in real-world clinical practice.

Background: Pain is a common symptom among cancer patients and directly affects their prognosis. As the leading drug for pain management, opioids are widely prescribed. So it is necessary to get people a correct understanding and application of opioids. In order to examine whether the use of high-dose opioids might affect survival and quality of life, this retrospective cohort study was performed to explore the outcomes of patients receiving high-dose opioids for pain management in a first-class tertiary hospital in China. Methods: We retrospectively searched medical records of inpatients and outpatients with pain who were treated with opioids in The First Affiliated Hospital, Zhejiang University School of Medicine from July to December 2021. Forty-three cases who were treated with high-dose opioids meeting inclusion criteria. Among these patients, 37 had cancer pain and 6 had neuropathic pain. All patients had regular follow-up when readmission until to April 7, 2022. Medical records of patients on high-dose opioids (equivalent to morphine ≥300 mg/d) was collected, including numerical rating scale (NRS), Karnofsky performance score (KPS), survival and adverse drug reactions (ADRs). Pain relief, quality of life, survival, and ADRs of patients after pain treatment were analyzed and evaluated. Results: The NRS score was significantly reduced and pain was relieved after high-dose opioid treatment. The before and after average NRS score of cancer pain was 5.2±1.6 vs. 2.2±1.1 points (P<0.001), neuropathic pain was 5.0±2.2 vs. 1.3±1.2 points (P<0.05), respectively. Although there is no statistical difference, quality of life showed a trend of improvement compared with before treatment. The before and after average KPS scores of cancer pain patients was 55.7±17.3 vs. 62.4±20.0, and neuropathic pain patients was 71.7±9.0 vs. 83.3±4.7. There were no intolerable ADRs. The median survival time was 238 days and 83 days in patients with cancer pain who received high-dose opioids and ultra-high dose opioids (equivalent to morphine ≥600 mg/d). Conclusions: Multimodal high-dose opioid pain treatments are important approaches to effectively relieve moderate to severe pain and improve the quality of life of patients. This study provides a clinical basis for future pain treatment with high-dose opioids.

Progress, Challenges, and Prospects of Research on the Effect of Gene Polymorphisms on Adverse Reactions to Opioids.

The abuse of opioids has become one of the most serious concerns in the world. Opioid use can cause serious adverse reactions, including respiratory depression, postoperative nausea and vomiting, itching, and even death. These adverse reactions are also important complications of clinical application of opioid drugs that may affect patient safety and recovery. Due to the fear of adverse reactions of opioids, clinicians often do not dare to use opioids in an adequate or appropriate amount, thus affecting the clinical medication strategy and the quality of treatment for patients. The prediction of adverse reactions to opioids is one of the most concerned problems in clinical practice. At present, the correlation between gene polymorphism and the efficacy of opiates has been widely studied and preliminarily confirmed, but the research on the effect of gene polymorphism on the adverse reactions of opiates is relatively limited. Existing studies have made encouraging progress in predicting the incidence and severity of adverse opioid reactions and clinical management by using genetic testing, but most of these studies are single-center, small-sample clinical studies or animal experiments, which have strong limitations. When the same receptor or enzyme is studied by different experimental methods, different or even opposite conclusions can be drawn. These phenomena indicate that the correlation between gene polymorphism and adverse opioid reaction still needs further research and demonstration. At present, it is still too early to use genetic testing to predict opioid adverse reactions in clinic. In this paper, the correlation between gene polymorphism and adverse opioid reactions and a small number of clinical applications were reviewed in terms of pharmacokinetics and pharmacodynamics, in order to provide some suggestions for future research and clinical drug decision making.

Population pharmacokinetics of polymyxin B: a systematic review.

Background: Polymyxin B (PMB) is a basic cyclic polypeptide antibiotic produced by Bacillus polymyxa, and is one of the last options for treating multi-drug-resistant negative bacterial infections in clinical practice. In recent years, many population pharmacokinetic studies of PMB have been conducted. This paper sought to comprehensively summarize the characteristics of population pharmacokinetic models of PMB and provide a theoretical basis for the individualized use of PMB. Methods: In this review, we systematically searched the PubMed and Embase databases to find articles on population pharmacokinetic models published from database establishment to August 2021. Results: A total of 10 studies were included in this review, including studies on various types of severe infections caused by multi-drug-resistant bacteria, hospital-acquired infections with fibrosis and other male and female populations, and a study of 2 continuous renal replacement therapy (CRRT) patients, aged 16-94 years, who received PMB doses of 10-360 mg/day (0.13-3.45 mg/kg/day), at an administration time of 0.5-6 hours. First-order linear elimination was used in all the studies; a 1-compartment model was used in 5 studies, and a 2-compartment model was used in 5 studies. The most common covariates were creatinine clearance (CrCL) and body weight. Discussion: Although these studies included several covariates and total clearance (CL) was close, but the external validation of some models was poorly correlated between the actual and predicted value. Novel or potential covariates represent important directions for further study.

MTHFR polymorphism's influence on the clinical features and therapeutic effects in patients with migraine: An observational study.

Objective: Our study aimed to evaluate the influence of methylenetetrahydrofolate reductase (MTHFR) polymorphism on the clinical features and therapeutic effects in patients with migraine. Methods: The data of 135 patients with migraine were collected from January 2021 to December 2021. The MTHFR C677T polymorphism was analyzed. The pain intensity was evaluated using a numerical rating scale (NRS) during treatment. The levels of folic acid, homocysteine (Hcy), vitamin B12, interleukin-2 (IL-2), IL-4, and ferritin, and changes of NRS were compared between folic acid and conventional treatment groups stratified by different genotypes of MTHFR in migraine patients. Results: The levels of Hcy and ferritin in male patients were higher than that in female patients (P < 0.05); Compared with CC and CT genotype groups, the TT genotype group showed significantly higher Hcy levels (P < 0.05) and lower folic acid levels (P < 0.05); In both folic acid and conventional treatment groups, a significant decrease in NRS score was observed in different genotypes post-treatment (P < 0.05). Patients with TT genotype in the folic acid treatment group showed better therapeutic efficacy than conventional treatment group (P < 0.05). There is no significant difference in the therapeutic efficacy in other genotypes between the two groups (P > 0.05). Conclusion: The MTHFR C677T genotyping may provide a new method to guide and optimize individualized medication for migraine patients.

A Facile Low-Dose Photosensitizer-Incorporated Dissolving Microneedles-Based Composite System for Eliciting Antitumor Immunity and the Abscopal Effect.

Nanomedicine-based photodynamic therapy (PDT) for melanoma treatment has attracted great attention. However, the complex design of polymer nanoparticles and high doses of photosensitizers used in intravenous injections (for sufficient accumulation of drugs in tumor lesions) pose a huge challenge to the commercialization and further clinical application. Herein, we fabricated the carrier-free nanoassemblies of a chlorin e6 (L-Ce6 NAs)-integrated fast-dissolving microneedles patch (L-Ce6 MNs) enriching only about 3 µg of Ce6 in the needle tips via a facile fabrication method. The L-Ce6 MNs had sufficient mechanical strength to penetrate the skin and facilitated the transportation of L-Ce6 NAs to a depth of 200-500 µm under the skin, thereby achieving efficient and accurate drug delivery to tumor lesions. In a xenograft mouse melanoma model, the L-Ce6 MNs-based PDT with low dose of Ce6 (0.12 mg/kg) exerted efficient ablation of the primary lesions in situ through reactive oxygen species (ROS) generation. More importantly, a significant abscopal effect was also elicited by activating immunogenic cell death (ICD) and releasing danger-associated molecular patterns (DAMPs), which in turn promoted dendritic cells (DCs) maturation and the subsequent antigen presentation, thereby facilitating the T-cell-mediated immune response without synergetic immunotherapies. Collectively, our findings indicate the facile, controllable, and fast-dissolving microneedles patch with a low dose of photosensitizers presented great therapeutic potential for enhanced photoimmunotherapy.

Pharmacist-led quality control circle in sustained reduction of carbapenem-resistance at a Chinese tertiary teaching hospital.

BACKGROUND: The spread of carbapenem-resistant Gram-negative bacteria poses a substantial threat to morbidity and mortality worldwide, which is mainly attributed to the overuse of carbapenem. This study aimed to evaluate the use of a quality control circle (QCC) in controlling the overuse of carbapenems and improving the state of carbapenem resistance at a Chinese tertiary teaching hospital. METHODS: A pharmacist-led multidisciplinary QCC project was carried out and the plan-do-check-act (PDCA) method was applied for 12 months. The data on carbapenem consumption, bacterial identification, and antibacterial susceptibility testing were collected to evaluate the effect of this project. RESULTS: The antibiotics use density (AUD) of carbapenems exhibited a decreasing trend over time (P<0.001), and the AUD of meropenem, imipenem, and biapenem decreased by 30.20%, 42.45%, and 78.05% after the intervention, respectively. The total AUD of carbapenems decreased from 7.37 to 3.96, which included the decrease in the irrational use of carbapenems by 1.61, accounting for 47.21% of the total. Moreover, the positive correlations were discovered between the resistance rate of carbapenem-resistant Klebsiella pneumonia (CRKP)/Acinetobacter baumannii (CRAB) and the AUD of carbapenems (P<0.05). The resistance rate of CRKP and CRAB decreased from 51.93% and 89.21% to 32.94% and 60.66%, respectively, following QCC project implementation. CONCLUSIONS: This is the first study to highlight the success of a multifaceted intervention QCC project and PDCA method, which led to a significant reduction in the AUD and resistance rate of carbapenems. QCC is a feasible and effective management tool for improving the quality of carbapenem use in medical institutions.

Efficacy and safety of roxadustat in the treatment of renal allograft anemia patients: a case series.

BACKGROUND: To observe the efficacy and safety of roxadustat, an inhibitor of proline hydroxylase, in renal allograft anemia patients. METHODS: This prospective study collected the clinical data of renal transplant patients treated with roxadustat for anemia at the Kidney Disease Center of the First Affiliated Hospital of Zhejiang University from April to August 2020. The patients were followed up every 2 weeks, and the changes in their hemoglobin index and any adverse reactions were recorded during 10 weeks of treatment. The efficacy of roxadustat for treatment of anemia after kidney transplantation was analyzed by comparing the change and increase in average hemoglobin levels before and after treatment. Rates of treatment response and achievement of the standard hemoglobin level were statistically analyzed. In addition, any potential adverse events and the glomerular filtration rate were recorded for 10 weeks to assess the safety of roxadustat in renal allograft anemia patients. RESULTS: After 10 weeks of roxadustat treatment, the mean hemoglobin level was 10.4±3.9 g/dL, which was significantly higher than at baseline. Over the entire period, treatment was observed to have a therapeutic effect at weeks 2-4, with mean hemoglobin levels increasing as treatment time increased. At the 10-week endpoint, the percentage of patients reaching the standard hemoglobin level and exhibiting a response to treatment was 52.4% and 71.4%, respectively. During the treatment, there was no rejection, and the glomerular filtration rate was stable. Only one person showed symptoms of fatigue, and there were no other obvious adverse reactions reported. CONCLUSIONS: Roxadustat significantly improves hemoglobin levels and can be safely used in renal transplant anemia patients.

Oral delivery of infliximab using nano-in-microparticles for the treatment of inflammatory bowel disease.

The anti-tumor necrosis factor-α (anti-TNF-α) blocker, has shown great efficacy for the treatment of inflammatory bowel disease (IBD). However, systemic exposure to it can cause considerable safety problems due to reduced suppression of the systemic immune response and loss of response to the production of anti-drug antibodies. Thus, we try to devise a targeted vehicle system for oral administration of anti-TNF-α antibodies for the treatment of IBD. In the present study, we developed an oral Infliximab (IFX) loaded nano-in-microparticles, based on chitosan (CS)/carboxymethyl chitosan (CMC) and alginate (Alg), which could protect IFX from the harsh environment of the gastrointestinal tract and produce targeted drug delivery to the inflamed intestine. In vivo studies demonstrated that the IFX loaded nano-in-micro vehicle can alleviate colitis by ameliorating inflammation and maintaining the intestinal epithelial barrier.

Reliability and validity of a modified 8-item Morisky Medication Adherence Scale in patients with chronic pain.

BACKGROUND: The 8-item Morisky Medication Adherence Scale (MMAS-8) is a simple, economic and easy tool to evaluate the medication compliance of chronic disease. The reliability and validity of the MMAS-8 in patients with chronic pain were unclear. Therefore, we aimed to validate the MMAS-8 for detecting nonadherent patients with chronic pain. METHODS: A modified MMAS-8 was used to assess the medication compliance of patients with chronic pain who were treated at our hospital from July 2018 to October 2018. Cronbach's α was used to evaluate the internal consistency, and a factor analysis was used to examine the construct validity. Convergent validity was assessed by comparing the MMAS-8 and a medication adherence visual analog score (MA-VAS) through Pearson's correlation coefficient. RESULTS: A total of 113 patients were evaluated. The (t-test) results revealed that there was a significant difference in average scores between the low-score group (who scored less than 5 points) and the high-score group (who scored 8 points or above), indicating that the scale displayed a good degree of discrimination. Except for Items 4 and 5, all the other items exhibited a good correlation with the total score (correlation coefficient >0.5; P<0.05). The Cronbach's α coefficient was 0.625, indicating that the scale's internal consistency was relatively satisfactory. Two common factors, which explained 62.978% of the total variance, were extracted by factor analysis to examine the construct validity of the MMAS-8, and the load of the 6 items was greater than 0.4. The Pearson correlation coefficient was 0.845 (P<0.001); thus, convergent validity was high. CONCLUSIONS: The modified MMAS-8 exhibited acceptable reliability and validity in evaluating medication compliance in patients with chronic pain; thus, it can be applied to detect nonadherent patients with chronic pain.

The molecular and cellular insight into the toxicology of bortezomib-induced peripheral neuropathy.

The proteasome inhibitor bortezomib (BTZ) is a first-line antitumor drug, mainly used for multiple myeloma treatment. However, BTZ shows prominent toxicity in the peripheral nervous system, termed BTZ-induced peripheral neuropathy (BIPN). BIPN is characterized by neuropathic pain, resulting in a dose reduction or even treatment withdrawal. To date, the pathological mechanism of BIPN has not been elucidated. There is still no effective strategy to prevent or treat BIPN. This review summarizes the pathological mechanisms of BIPN, which involves the pathological changes of Schwann cells, neurons, astrocytes and macrophages. A better knowledge of the pathological mechanisms of BIPN would provide new ideas for therapeutic interventions of BIPN patients.

Ceria Nanozyme-Integrated Microneedles Reshape the Perifollicular Microenvironment for Androgenetic Alopecia Treatment.

Androgenetic alopecia (AGA) is highly prevalent in current society but lacks effective treatments. The dysregulation of the hair follicle niche induced by excessive reactive oxygen species (ROS) and insufficient vascularization in the perifollicular microenvironment is the leading cause of AGA. Herein, we designed a ceria nanozyme (CeNZ)-integrated microneedles patch (Ce-MNs) that can alleviate oxidative stress and promote angiogenesis simultaneously to reshape the perifollicular microenvironment for AGA treatment. On the basis of the excellent mechanical strength of Ce-MNs, the encapsulated CeNZs with catalase- and superoxide-mimic activities can be efficiently delivered into skin to scavenge excessive ROS. Moreover, the mechanical stimulation induced by the administration of MNs can remodel the microvasculature in the balding region. Compared with minoxidil, a widely used clinical drug for AGA treatment, Ce-MNs exhibited accelerated hair regeneration in the AGA mouse model at a lower administration frequency without inducing significant skin damage. Consequently, such a safe and perifollicular microenvironment-shaping MNs patch shows great potential for clinical AGA treatment.

Continuous improvement on the rationality of prophylactic injectable PPIs usage by a clinical pharmacist-led guidance team at a Chinese tertiary teaching hospital.

OBJECTIVE: We aimed to evaluate the effects of a clinical pharmacist-led-guidance-team (CPGT) on improving rational prophylactic injectable proton pump inhibitor use (PIPU) and to explore the application of the Plan-Do-Check-Act (PDCA) method in promoting rational PIPU. METHODS: We conducted a retrospective study among 814 patients at a Chinese tertiary teaching hospital from January 2017 to December 2018. We enrolled 98 patients before the PDCA; 297 and 419 patients were included in first- and second-round PDCA cycles, respectively. The CPGT established the criteria for PIPU and conducted interventions, including medical record reviews, provision of feedback, clinician education, and outcome analysis. We analyzed the appropriateness and costs of PIPU before and after establishment of the PDCA cycle. RESULTS: Implementation of continuous CPGT-led intervention and a PDCA cycle significantly decreased the rate of irrational PIPU (53.06% vs. 8.57%), including duration, administration route, indication, and dosing frequency. Costs of total (USD 211.28 ± 162.33 vs. 53.17 ± 22.32) and inappropriate (USD 76.70 ± 59.78 vs. 2.25 ± 3.86) PIPU per patient were significantly reduced. The target compliance rate was 107.56%. CONCLUSION: A CPGT can have an effective role in improving rational PIPU and optimizing administration through a PDCA cycle, to attain improved clinical and economic outcomes.

Cost effectiveness of immune checkpoint inhibitors for treatment of non-small cell lung cancer: A systematic review.

BACKGROUND: Immune checkpoint inhibitors (ICIs) for treatment of non-small cell lung cancer (NSCLC) have been rapidly evolving. ICIs are likely to be more effective but also lead to escalating healthcare costs. OBJECTIVES: The aim of this study was to evaluate the cost effectiveness of immune checkpoint inhibitors (ICIs) for treatment of non-small cell lung cancer (NSCLC). METHODS: We searched the PubMed, Web of Science, and Cochrane Library for studies comparing the cost effectiveness of ICIs for NSCLC. Potential studies identified were independently checked for eligibility by two authors, with disagreement resolved by a third reviewer. Quality of the included studies was evaluated using Consolidated Health Economic Evaluation Reporting Standards checklists. RESULTS: A total of 22 economic studies were included. Overall reporting of the identified studies largely met CHEERS recommendations. In the first-line setting, for advanced or metastatic NSCLC patients with PD-L1 ≥ 50%, pembrolizumab appeared cost-effective compared with platinum-based chemotherapy in the US and Hong Kong (China), but not in the UK and China. The cost-effectiveness of pembrolizumab versus chemotherapy for first-line treatment of NSCLC in PD-L1 ≥ 1% patients remained obscure. Regardless of PD-L1 expression status, pembrolizumab in combination with chemotherapy could be a cost-effective first-line therapy in the US. On the contrary, addition of atezolizumab to the combination of bevacizumab and chemotherapy was not cost-effective for patients with metastatic non-squamous NSCLC from the US payer perspective. In the second-line setting compared with docetaxel, pembrolizumab was cost-effective; though nivolumab was not cost-effective in the base case, it could be by increased PD-L1 threshold. Results of the cost-effectiveness of atezolizumab second-line treatment remained inconsistent. In addition, the adoption of durvalumab consolidation therapy after chemoradiotherapy could be cost-effective versus no consolidation therapy for patients with stage III NSCLC. CONCLUSIONS: Immunotherapy can be a cost-effective option for treatment of NSCLC in several scenarios. A discount of the agents or the use of PD-L1 expression as a biomarker improves the cost-effectiveness of immunotherapy.

Video Education Reduces Pain and Anxiety Levels in Cancer Patients Who First Use Fentanyl Transdermal Patch: A Randomized Controlled Trial.

OBJECTIVE: We sought to evaluate the efficacy of using a quick response (QR) code within video education to guide proper use of fentanyl transdermal patches and control pain, depression, and anxiety levels in cancer patients. METHODS: Patients using a fentanyl transdermal patch for the first time were enrolled in the study and then given an information leaflet as well as an informed consent form. We asked them to complete the first questionnaire (Q1) prior to first use of the fentanyl transdermal patch, and then used a random number table to randomize those who completed it into two groups. Participants in group A received a QR code (to make it easier for them to obtain additional video information) and a traditional information leaflet, whereas those in group B (control group) only received a traditional information leaflet. Thereafter, we requested all participants to complete standard questionnaires, which comprised a Numeric Rating Scale (NRS), a Spielberger State-Trait Anxiety Inventory (STAI), as well as a Hospital Anxiety and Depression Scale (HADS). The resulting continuous (with a normal distribution) and categorical data were analyzed using Student's t- and chi-square tests, respectively. We also recorded parameters such as NRS, STAI, and HADS, as well as the frequency of rescue medication in both groups. RESULTS: A total of 154 cancer patients who first used a fentanyl transdermal patch were recruited during the study period, from April to May 2020. Among these, 138 completed follow-up, with 70 and 68 in group A and B, respectively. Participants in both groups had similar baseline and clinical characteristics, whereas significant differences were observed between the groups with regard to the other parameters. Specifically, participants in group A recorded a lower STAI state (38.2 vs 38.9, P=0.027) and HADS (3.9 vs 4.2, P=0.001) anxiety scores, as well as NRS (2.1 vs 2.4, P=0.025) and frequency of rescue medication (0.4 vs 1.4, P<0.001) than those in group B, following 14 days of using a fentanyl transdermal patch. CONCLUSION: Our results indicated that incorporating a QR code within additional video education leads to proper use of a fentanyl transdermal patch and relieves pain and anxiety levels in patients with cancer. Based on this, we recommend a new style of education during care of cancer patients who first use a fentanyl transdermal patch.

Site-specific targeted drug delivery systems for the treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis and manifests as a complex and dysregulated immune response. To date, there is no cure for IBD; thus, lifelong administration of maintenance drugs is often necessary. Since conventional IBD treatment strategies do not target the sites of inflammation, only limited efficacy is observed with their use. Moreover, the possibility of severe side effects resulting from systemic drug redistribution is high when conventional drug treatments are used. Therefore, a straightforward disease-targeted drug delivery system is desirable. Based on the pathophysiological changes associated with IBD, novel site-specific targeted drug delivery strategies that deliver drugs directly to the inflammation sites can enhance drug accumulation and decrease side effects. This review summarizes novel inflammation targeted delivery systems in the management of IBD. It also discusses the challenges and new perspectives in this field.

Liver Injury in Critically Ill and Non-critically Ill COVID-19 Patients: A Multicenter, Retrospective, Observational Study.

Background: Liver injury commonly occurs in patients with COVID-19. There is limited data describing the course of liver injury occurrence in patients with different disease severity, and the causes and risk factors are unknown. We aim to investigate the incidence, characteristics, risk factors, and clinical outcomes of liver injury in patients with COVID-19. Methods: This retrospective observational study was conducted in three hospitals (Zhejiang, China). From January 19, 2020 to February 20, 2020, patients confirmed with COVID-19 (≥18 years) and without liver injury were enrolled and divided into non-critically ill and critically ill groups. The incidence and characteristics of liver injury were compared between the two groups. Demographics, clinical characteristics, treatments, and treatment outcomes between patients with or without liver injury were compared within each group. The multivariable logistic regression model was used to explore the risk factors for liver injury. Results: The mean age of 131 enrolled patients was 51.2 years (standard deviation [SD]: 16.1 years), and 70 (53.4%) patients were male. A total of 76 patients developed liver injury (mild, 40.5%; moderate, 15.3%; severe, 2.3%) with a median occurrence time of 10.0 days. Critically ill patients had higher and earlier occurrence (81.5 vs. 51.9%, 12.0 vs. 5.0 days; p < 0.001), greater injury severity (p < 0.001), and slower recovery (50.0 vs. 61.1%) of liver function than non-critically ill patients. Multivariable regression showed that the number of concomitant medications (odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.05-1.21) and the combination treatment of lopinavir/ritonavir and arbidol (OR: 3.58, 95% CI: 1.44-9.52) were risk factors for liver injury in non-critically ill patients. The metabolism of arbidol can be significantly inhibited by lopinavir/ritonavir in vitro (p < 0.005), which may be the underlying cause of drug-related liver injury. Liver injury was related to increased length of hospital stay (mean difference [MD]: 3.2, 95% CI: 1.3-5.2) and viral shedding duration (MD: 3.0, 95% CI: 1.0-4.9). Conclusions: Critically ill patients with COVID-19 suffered earlier occurrence, greater injury severity, and slower recovery from liver injury than non-critically ill patients. Drug factors were related to liver injury in non-critically ill patients. Liver injury was related to prolonged hospital stay and viral shedding duration in patients with COVID-19. Clinical Trial Registration: World Health Organization International Clinical Trials Registry Platform, ChiCTR2000030593. Registered March 8, 2020.

Enhanced recovery after surgery (ERAS) might be a standard care in radical prostatectomy: a systematic review and meta-analysis.

BACKGROUND: Several enhanced recovery after surgery (ERAS) protocols for radical prostatectomy (RP) have been reported in recent years. Nonetheless, there is no sufficient evidence to support the implementation of ERAS as a standard of care modality. METHODS: A search was done in the PubMed, Embase, Clinical Trials.gov, Cochrane Library, CNKI Library databases and reference lists to identify relevant studies from inception until May 2019 to be included in the study. A systematic review of five randomized controlled trials (RCTs), one prospective cohort study and four retrospective studies covering 3,803 patients, comparing ERAS with conventional care was performed. Outcomes of interest for the study were intraoperative outcomes (operation time and blood loss), postoperative outcomes (hospital stay, catheter stay, first defecation and first anal exhaust) and postoperative complications. Random events meta-analyses were performed. Sensitivity analysis was also performed to determine whether the results of the meta-analysis were robust. RESULTS: Notably, ERAS group had significantly shorter hospital stay [overall standardized mean difference (SMD) =-1.65, 95% confidence interval (CI): -2.53, -0.76, P<0.001], shorter time to first defecation (overall SMD =-1.56, 95% CI: -2.71, -0.42, P=0.008), shorter time to first anal exhaust (overall SMD =-1.23, 95% CI: -1.97, -0.50, P=0.001) and lower incidence of nausea [overall risk ratio (RR) =0.62, 95% CI: 0.40, 0.94, P=0.024] compared to the conventional group. There was no statistical difference in intraoperative outcomes, catheter stay and other postoperative complications between the two groups (P>0.05). CONCLUSIONS: The data presented so far consistently show that ERAS may be utilized as a standard of care in RP treatment.