The impact of COVID-19 on the epidemiology of non-airborne/droplet-transmitted notifiable infectious diseases in Taiwan: A descriptive study.

BACKGROUND: This study was conducted to compare the number of cases of non-airborne/droplet-transmitted notifiable infectious disease (NID) before and after COVID-19 pandemic. METHODS: This study used an open database - National Notifiable Diseases Surveillance System to collect the epidemiological data of NIDs. Ten fecal-oral-, six vector-borne-, four direct-contact, and four sexually-transmitted NIDs between pandemic period (defined as from January 2020 to December 2021) and the pre-pandemic period (defined as the period from January 2018 to December 2019) were included for the analysis. RESULTS: Overall, the annual case number of these 24 non-airborne/droplet-transmitted NIDs was 19,186, 19,101, 19,567, and 19,863 in 2018, 2019, 2020 and 2021, respectively. The overall case number in the pandemic period was higher than those in pre-pandemic period (39,430 vs 38,287) and the monthly case number was significantly higher in pandemic period than pre-pandemic period (1643 vs 1595, p < 0.05). However, the lower case number in the pandemic period than those in pre-pandemic period was observed in overall ten fecal-oral-transmitted NIDs (1278 vs 1775), six vector-borne-NIDs (922 vs 2210), and four direct-contact transmitted NIDs (196 vs 344). In contrast, the case number of sexually-transmitted NIDs in the pandemic period was higher than those in pre-pandemic period (37,034 vs 33,958), particularly for gonorrhea (14,463 vs 8732). CONCLUSIONS: Most of the fecal-oral-, vector-borne, and direct-contact transmitted NIDs had declined during pandemic in Taiwan. In contrast, gonorrhea had large increase, and other NPIs were needed.

Accelerated-strategy renal replacement therapy for critically ill patients: A systematic review and meta-analysis.

BACKGROUND: The aim of this study was to investigate the clinical effect and safety of accelerated-strategy initiation of renal replacement therapy (RRT) in critically ill patients. METHODS: PubMed, Embase, OVID, EBSCO, and the Cochrane Library databases were searched for relevant articles from inception to December 30, 2020. Only RCTs that compared the clinical efficacy and safety between accelerated-strategy RRT and standard-strategy RRT among critically ill adult patients with acute kidney injury (AKI) were included. The primary outcome was 28-day mortality. RESULTS: A total of 5279 patients in 12 RCTs were included in this meta-analysis. The 28-day mortality rates of patients treated with accelerated and standard RRT were 37.3% (969/2596) and 37.9% (976/2573), respectively. No significant difference was observed between the groups (OR, 0.92; 95% CI, 0.70-1.12; I2 = 60%). The recovery rates of renal function were 54.5% and 52.5% in the accelerated- and standard-RRT groups, respectively, with no significant difference (OR, 1.03; 95% CI, 0.89-1.19; I2 = 56%). The rate of RRT dependency was similar in the accelerated- and standard-RRT strategies (6.7% vs 5.0%; OR, 1.11; 95% CI, 0.71-1.72; I2 = 20%). The accelerated-RRT group displayed higher risks of hypotension, catheter-related infection, and hypophosphatemia than the standard-RRT group (hypotension: OR, 1.26; 95% CI, 1.10-1.45; I2 = 36%; catheter-related infection: OR, 1.90; 95% CI, 1.17-3.09; I2 = 0%; hypophosphatemia: OR, 2.11; 95% CI, 1.43-3.15; I2 = 67%). CONCLUSIONS: Accelerated RRT does not reduce the risk of death and does not improve the recovery of kidney function among critically ill patients with AKI. In contrast, an increased risk of adverse events was observed in patients receiving accelerated RRT. However, these findings were based on low quality of evidence. Further large-scale RCTs is warranted.

Effect of colchicine on the outcomes of patients with COVID-19: a systematic review and meta-analysis of randomised controlled trials.

AIM: This meta-analysis aimed to assess the usefulness of colchicine in patients with COVID-19. METHODS: PubMed, Web of Science, Ovid MEDLINE, the Cochrane Library, Embase, and Clinicaltrials.gov were searched for relevant randomised controlled trials (RCTs) published between database inception and November 12, 2021. Only RCTs that compared the clinical efficacy and safety of colchicine with other alternative treatments or placebos in patients with COVID-19 were included. RESULTS: Overall, 7 RCTs involving 16,024 patients were included; 7,794 patients were in the study group receiving colchicine and 8,230 were in the control group receiving placebo or standard treatment. The study and control groups had similar risk of mortality (odds ratio [OR], 1.00; 95% CI, 0.91-1.09; I2 = 0%). No significant difference was observed between the study and control groups in terms of the need for non-invasive ventilation (OR, 0.92; 95% CI, 0.83-1.03; I2 = 0%), the need for mechanical ventilation (OR, 0.64; 95% CI, 0.32-1.32; I2 = 58%), and length of hospital stay (mean difference, -0.42 days; 95% CI, -1.95 to 1.11; I2 = 62%). In addition, colchicine was associated with significantly higher risks of gastrointestinal adverse events (OR, 1.81; 95% CI, 1.56-2.11; I2 = 0%) and diarrhoea (OR, 2.12; 95% CI, 1.75-2.56; I2 = 9%). CONCLUSIONS: Colchicine does not improve clinical outcomes in patients with COVID-19, so it did not support the additional use of colchicine in the treatment of patients with COVID-19.Key messageColchicine could not reduce the mortality of patients with COVID-19.No significant difference was observed between the colchicine and comparators in terms of the need for non-invasive ventilation, need for mechanical ventilation, and length of hospital stay.Colchicine was associated with a higher risk of gastrointestinal adverse events.

Pro-, pre- and synbiotics for the prevention of incidental ventilator-associated pneumonia among critically ill patients: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This study investigated the preventive effects of pro-, pre- and synbiotics on ventilator-associated pneumonia (VAP) among critically ill patients. METHODS: The PubMed, Web of Science, Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for relevant articles written before 19 February 2022. Only randomized controlled trials (RCTs) comparing the clinical efficacy of pro-, pre- and synbiotics with placebos or standard treatments for the prevention of incidental VAP were included. RESULTS: A total of 15 RCTs were included. Patients receiving pro-, pre- and synbiotics had a lower risk than the control group of contracting VAP (risk ratio [RR], 0.70; 95% CI, 0.57-0.85; I2 = 67%). The duration of mechanical ventilation was significantly shorter in the study group than in the control group (mean difference [MD], -1.61 days; 95% CI, -2.72 to -0.50; I2 = 86%), and the study group had a shorter duration of stay in the intensive care unit than the control group did (MD, -1.72 days; 95% CI, -3.22 to -0.23; I2 = 87%). CONCLUSIONS: Pro-, pre- and synbiotics can prevent VAP and the use of probiotics for patients who are critically ill should be supported.

Favipiravir-based treatment for outcomes of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This meta-analysis of randomized controlled trials (RCTs) investigated the clinical efficacy and safety of favipiravir for patients with mild-to-critical COVID-19. METHODS: PubMed, Web of Science, Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials were searched for RCTs published before 30 October 2021. Only RCTs that compared the clinical efficacy and safety of favipiravir -based antiviral regimens (study group) with other alternative treatments or placebos (control group) in patients with COVID-19 were included. RESULTS: Overall, the clinical improvement rate was significantly higher in the study group than in the control group at the assessment conducted after 14 days (OR, 1.83; 95% CI, 1.12-2.98). The rate of virological eradication was significantly higher in the study group than in the control group at the assessment conducted after 28 days (OR, 2.09; 95% CI, 1.15-3.78). No significant difference was observed in the rates of invasive mechanical ventilation requirement or ICU admission, mortality, or risk of an adverse event between the study and control groups. CONCLUSIONS: Except the clinical improvement rate within 14 days and the virological eradication rate within 28 days, favipiravir-based treatment did not provide significantly additional benefit for patients with COVID-19. Therefore, more evidence is necessary.

Effect of sofosbuvir-based treatment on clinical outcomes of patients with COVID-19: a systematic review and meta-analysis of randomised controlled trials.

This systematic review and meta-analysis examined the efficacy of sofosbuvir-based antiviral treatment against COVID-19 (coronavirus disease 2019). PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched from inception to 15 August 2021. Studies comparing the clinical efficacy and safety of sofosbuvir-based antiviral regimens (study group) with other antivirals or standard of care (control group) in patients with COVID-19 were included. Overall, 687 patients with COVID-19 were included, of which 377 patients received sofosbuvir-based treatment. Mortality was lower in the study group than in the control group [odds ratio (OR) = 0.49, 95% confidence interval (CI) 0.30-0.79; I2 = 0%]. The overall clinical recovery rate was higher in the study group than in the control group (OR = 1.82, 95% CI 1.20-2.76; I2 = 28%). The study group presented a lower requirement for mechanical ventilation (OR = 0.33, 95% CI 0.13-0.89; I2 = 0%) and intensive care unit admission (OR = 0.42, 95% CI 0.25-0.70; I2 = 0%) than the control group. Furthermore, the study group exhibited a shorter hospital length of stay [mean deviation (MD), -1.49, 95% CI -2.62 to -0.37; I2 = 56%] and recovery time (MD, -1.34, 95% CI -2.29 to -0.38; I2 = 46%) than the control group. Sofosbuvir-based treatment may help reduce mortality in patients with COVID-19 and improve associated clinical outcomes. Furthermore, sofosbuvir-based treatment was as safe as the comparator in patients with COVID-19. However, further large-scale studies are warranted to validate these findings.

The impact of neutralizing monoclonal antibodies on the outcomes of COVID-19 outpatients: A systematic review and meta-analysis of randomized controlled trials.

To assess the clinical efficacy and safety of neutralizing monoclonal antibodies (mABs) for outpatients with coronavirus disease 2019 (COVID-19). PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (ICTRP) databases were searched from inception to July 19, 2021. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of neutralizing mABs in the treatment of COVID-19 outpatients were included. The Cochrane risk-of-bias tool was used to assess the quality of the included RCTs. The primary outcome was the risk of COVID-19-related hospitalization or emergency department (ED) visits. The secondary outcomes were the risk of death and adverse events (AEs). Five articles were included, in which 3309 patients received neutralizing mAB and 2397 patients received a placebo. A significantly lower rate of hospitalization or ED visits was observed among patients who received neutralizing mABs than those who received a placebo (1.7% vs. 6.5%, odds ratios (OR): 0.26; 95% confidence interval (CI): 0.19-0.36; I2 = 0%). In addition, the rate of hospitalization was significantly lower in the patients who received neutralizing mABs than in the control group (OR: 0.24; 95% CI: 0.17-0.34; I2 = 0%). The mortality rate was also significantly lower in the patients who received neutralizing mABs than in the control group (OR: 0.16; 95% CI: 0.05-0.58; I2 = 3%). Neutralizing mABs were associated with a similar risk of any AE (OR: 0.81; 95% CI: 0.64-1.01; I2 = 52%) and a lower risk of serious AEs (OR: 0.37; 97% CI: 0.19-0.72; I2 = 45%) compared with a placebo. Neutralizing mABs can help reduce the risk of hospitalization or ED visits in COVID-19 outpatients. For these patients, neutralizing mABs are safe and not associated with a higher risk of AEs than a placebo.

Clinical efficacy and safety of ceftobiprole in the treatment of acute bacterial skin and skin structure infection: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To investigate the clinical efficacy and safety of ceftobiprole for acute bacterial skin and skin structure infections (ABSSSIs). METHODS: PubMed, Web of Science, EBSO, Ovid Medline, ClinicalTrial.gov and Cochrane Library were searched until 25 December 2020. Only randomized controlled trials that compared the treatment efficacy of ceftobiprole with that of other antibiotics for adult patients with ABSSSIs were included in this meta-analysis. RESULTS: The 3 RCTs involving 2291 adult patients with ABSSSIs were included. No significant difference in clinical success, as measured by the TOC, was observed between ceftobiprole and comparators among the intention-to-treat population (OR, 1.06; 95% CI, 0.85-1.33; I2 = 0%) and clinical evaluable population (OR, 1.17; 95% CI, 0.76-1.79; I2 = 17%). Ceftobiprole was associated with a similar risk of adverse events (AEs) to that of comparators. CONCLUSIONS: Ceftobiprole can achieve similar clinical and microbiological responses as alternative antibiotics in patients with ABSSSIs. In addition, ceftobiprole shares a similar safety profile to comparators.

Janus kinase inhibitors for hospitalized patients with COVID-19: a meta-analysis of randomized controlled trials.

BACKGROUND: This meta-analysis of randomized controlled trials (RCTs) investigated the usefulness of Janus kinase (JAK) inhibitors among hospitalized patients with COVID-19. METHODS: PubMed, Web of Science, the Cochrane Library, and Ovid MEDLINE were searched for RCTs published before 7 September 2021. Only RCTs that compared the clinical efficacy and safety of JAK inhibitors with other alternative treatments or placebos in the treatment of hospitalized patients with COVID-19 were included. RESULTS: Overall, patients receiving JAK inhibitors exhibited a lower 28-day mortality rate than the control group (risk ratio [RR], 0.60; 95% CI, 0.47-0.77; I2 = 0%). Compared with the control group, the study group also had a lower 14-day mortality rate (RR, 0.60; 95% CI, 0.42-0.85; I2 = 0%), a higher rate of clinical improvement (RR, 1.05; 95% CI, 1.02-1.09; I2 = 0%), and less need of mechanical ventilation or extracorporeal membrane oxygenation (RR, 0.64; 95% CI, 0.50-0.84; I2 = 0%). Finally, JAK inhibitor use was associated with a similar risk of adverse events and infections as that observed in the control group. CONCLUSIONS: JAK inhibitors can help reduce mortality and improve clinical outcomes among hospitalized patients with COVID-19. Additionally, JAK inhibitors can be used safely in this clinical entity.

Clinical efficacy and safety of interferon-ß-containing regimens in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this systematic review and meta-analysis of randomized controlled trials(RCTs) was to investigate the efficacy of interferon (IFN)-ß-containing regimens in treating patients with COVID-19. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to 17 July 2021. RCTs comparing the clinical efficacy and safety of IFN-ß-containing regimens (study group) to other antiviral treatment options or placebo (control group) in treating patients with COVID-19 were included. RESULTS: Eight RCTs were included. No significant difference in the 28-day all-cause mortality rate was observed between the study and control groups (OR, 0.74; 95% CI, 0.44-1.24; I2 = 51%). The study groups had a lower rate of intensive care unit (ICU) admissions than the control groups (OR 0.58, 95% CI 0.36-0.95; I2 = 0%). Furthermore, INF-ß was not associated with an increased risk of any adverse event (AE) or serious AE when compared with the control group. CONCLUSIONS: IFN-ß does not appear to provide an increased survival benefit in hospitalized patients with COVID-19 but may help reduce the risk of ICU admission. Moreover, IFN-ß is a safe agent for use in the treatment of COVID-19.

Novel ß-lactam/ß-lactamase inhibitor combinations versus alternative antibiotics in adults with hospital-acquired pneumonia or ventilator-associated pneumonia: an integrated analysis of three randomised controlled trials.

OBJECTIVES: This study assessed the efficacy and safety of novel ß-lactam/ß-lactamase inhibitor (BL/BLI) combinations in adult patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). METHODS: PubMed, Web of Science, the Cochrane Library, Ovid MEDLINE, Embase and EBSCO databases were searched for randomised controlled trials (RCTs) published before 13 September 2020. Only RCTs comparing the treatment efficacy of novel BL/BLI combinations with other antibiotics for HAP/VAP in adult patients were included in this integrated analysis. RESULTS: Three RCTs were included and no significant difference in clinical cure rate of test of cure was observed between the novel BL/BLI combinations and comparators [odds ratio (OR) = 1.01, 95% confidence interval (CI) 0.81-1.27; I2 = 35%]. The 28-day all-cause mortality was 16.2% and 17.6% for patients receiving novel BL/BLI combinations and comparators, respectively, and no significant difference was noted (OR = 0.90, 95% CI 0.69-1.16; I2 = 11%). Compared with comparators, novel BL/BLI combinations were associated with a similar microbiological response (OR = 1.06, 95% CI 0.73-1.54; I2 = 64%) and a similar risk of adverse events (AEs) [treatment-emergent AEs (TEAEs): OR = 1.04, 95% CI 0.83-1.30; I2 = 0%; serious AEs: OR = 1.14, 95% CI 0.79-1.63; I2 = 68%; treatment discontinuation for TEAE: OR = 0.90, 95% CI 0.62-1.31; I2 = 11%). CONCLUSION: Clinical and microbiological responses of novel BL/BLI combinations in the treatment of HAP/VAP were similar to those of other available antibiotics. These combinations also shared a similar safety profile to comparators.

The effect of tocilizumab on COVID-19 patient mortality: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to investigate the clinical efficacy and safety of tocilizumab for treating patients with COVID-19. METHODS: The PubMed, Embase, Cochrane Library, Clinicaltrials.gov, WHO International Clinical Trials Registry Platform and the preprint server of medRxiv.org were searched from their inception to February 20, 2021. Only RCTs that compared the treatment efficacy and safety of tocilizumab with the placebo or the standard of care for adult patients with COVID-19 were included in this meta-analysis. The primary outcome was 28-day mortality. RESULTS: This meta-analysis included eight RCTs which enrolled a total of 6314 patients for randomization, in which 3267 and 3047 patients were assigned to the tocilizumab and control groups, respectively. The mortality at day 28 was 24.4% and 29.9% in patients in the tocilizumab and control groups, respectively, meaning there was no significant difference observed between these two groups (OR, 0.92; 95% CI, 0.66-1.28; I2 = 62). This finding did not change in the subgroup analysis according to the initial use of MV or steroid while enrollment. The patients receiving tocilizumab had a lower rate of mechanical ventilation (MV) and intensive care unit (ICU) admission at day 28 compared with the control group (MV use: OR, 0.75; 95% CI, 0.62-0.90; I2 = 11; ICU admission: OR, 0.51; 95% CI, 0.28-0.92; I2 = 30). There were no significant differences between these two treatment groups in terms of the risk of treatment-emergent adverse events (AEs) (OR, 1.03; 95% CI, 0.71-1.49; I2 = 43), serious AEs (OR, 0.86; 95% CI, 0.67-1.12; I2 = 0) or infection (OR, 0.87; 95% CI, 0.63-1.20; I2 = 0). CONCLUSIONS: Tocilizumab does not provide a survival benefit for patients with COVID-19, but it may help reduce the risk of MV and ICU admission. In addition, tocilizumab is a safe agent to use for the treatment of COVID-19.

Vitamin D supplementation and the outcomes of critically ill adult patients: a systematic review and meta-analysis of randomized controlled trials.

This meta-analysis assessed the association between vitamin D supplementation and the outcomes of critically ill adult patients. A literature search was conducted using the PubMed, Web of Science, EBSCO, Cochrane Library, Ovid MEDLINE, and Embase databases until March 21, 2020. We only included randomized controlled trials (RCTs) comparing the efficacy of vitamin D supplementation with placebo in critically ill adult patients. The primary outcome was their 28-day mortality. Overall, 9 RCTs with 1867 patients were included. In the pooled analysis of the 9 RCTs, no significant difference was observed in 28-day mortality between the vitamin D supplementation and placebo groups (20.4% vs 21.7%, OR, 0.73; 95% CI, 0.46-1.15; I2 = 51%). This result did not change as per the method of vitamin D supplementation (enteral route only: 19.9% vs 18.2%, OR, 1.19; 95% CI, 0.88-1.57; I2 = 10%; intramuscular or intravenous injection route: 25.6% vs 40.8%, OR, 0.48; 95% CI, 0.21-1.06; I2 = 19%) or daily dose (high dose: 20.9% vs 19.8%, OR, 0.83; 95% CI, 0.51-1.36; I2 = 53%; low dose: 15.6% vs 21.3%, OR, 0.74; 95% CI, 0.32-1.68; I2 = 0%). No significant difference was observed between the vitamin D supplementation and placebo groups regarding the length of ICU stay (standard mean difference [SMD], - 0.30; 95% CI, - 0.61 to 0.01; I2 = 60%), length of hospital stay (SMD, - 0.17; 95% CI, - 041 to 0.08; I2 = 65%), and duration of mechanical ventilation (SMD, - 0.41; 95% CI, - 081 to 0.00; I2 = 72%). In conclusion, this meta-analysis suggested that the administration of vitamin D did not provide additional advantages over placebo for critically ill patients. However, additional studies are needed to confirm our findings.

Five-day antibiotic treatment for community-acquired bacterial pneumonia: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This systematic review and meta-analysis of randomized controlled trials (RCTs) investigated whether the clinical efficacy of a 5-day antibiotic course is comparable to that of a longer (≥7 d) course for treating adults with community-acquired bacterial pneumonia (CABP). METHODS: The PubMed, Web of Science, Cochrane Library, Ovid MEDLINE, and Embase. were searched before January 18, 2020. RCTs comparing the efficacy of a 5-day antibiotic course with a longer course (≥7 d) for CABP treatment were included. Primary outcomes included the clinical response, microbiological response, and risk of adverse events (AEs). RESULTS: In this meta-analysis, 7 RCTs were included, and the 5-day antibiotic courses group, and a longer course group comprised 1499 and 1522 patients, respectively. The difference in the overall clinical response rates between the 5-day and longer courses (88.3% vs 88.8%, odds ratio [OR], 0.95, 95% confidence interval [CI], 0.70-1.28, I2 = 19%) was nonsignificant. Additionally, the microbiological eradication rates did not differ significantly between the groups, at 94.8% and 95.8% in the 5-day and longer courses groups, respectively (OR, 0.84, 95% CI, 0.38-1.87, I2 = 0%). Finally, all-cause mortality did not differ between the 2 groups (OR, 0.91, 95% CI, 0.31-2.66, I2 = 0%). CONCLUSIONS: Five-day treatment and longer antibiotic courses for CABP yield similar clinical and microbiological responses and exhibit similar safety profiles.

Novel ß-Lactam/ß-Lactamase inhibitor combinations vs alternative antibiotics in the treatment of complicated urinary tract infections: A meta-analysis of randomized controlled trials.

OBJECTIVES: This meta-analysis assessed the efficacy and safety of novel ß-lactam/ß-lactamase inhibitor combinations in the treatment of complicated urinary tract infection (cUTI)/acute pyelonephritis (APN). METHODS: PubMed, Web of Science, EBSCO (Elton B. Stephens Co.), Cochrane Library, Ovid MEDLINE, and Embase databases were accessed until November 21, 2019. In this meta-analysis, only randomized controlled trials comparing the treatment efficacy of novel ß-lactam/ß-lactamase inhibitor combinations with other antibiotics for cUTI/APN in adult patients were included. The outcomes included the clinical and microbiological responses, and risk of adverse events (AEs). RESULTS: Overall, the experimental group treated with a novel ß-lactam/ß-lactamase inhibitor combination and the control group comprised 1346 and 1376 patients, respectively. No significant difference in the clinical response rate at test-of-cure was observed between the novel ß-lactam/ß-lactamase inhibitor combination and comparators among the microbiological modified intent-to-treat population (89.1% vs 88.3%, OR, 1.04; 95% confidence interval [CI], 0.76-1.42; I = 28%) and the microbiologically evaluable population (95.2% vs 94.7%, OR, 1.12; 95% CI, 0.68-1.84; I = 0%). Additionally, the novel ß-lactam/ß-lactamase inhibitor combination was associated with a better microbiological response at test-of-cure than the comparators among the microbiological modified intent-to-treat population (74.4% vs 68.5%, OR, 1.34; 95% CI, 1.04-1.72; I = 45%) and microbiologically evaluable population (80.1% vs 72.5%, OR, 1.49; 95% CI, 1.06-2.10; I = 58%). Finally, the risk of AEs associated with the novel ß-lactam/ß-lactamase inhibitor combination was similar to that associated with the comparators (treatment-emergent adverse events [TEAE], OR, 1.04; 95% CI, 0.87-1.23; I = 19%; serious AEs, OR, 1.21; 95% CI, 0.82-1.76; I = 0%; treatment discontinuation for drug-related TEAE, OR, 077; 95% CI, 0.38-1.56, I = 5%). The all-cause mortality did not differ between the novel ß-lactam/ß-lactamase inhibitor combination and comparators (OR, 1.19; 95% CI, 0.37-3.81; I = 0%). CONCLUSIONS: The clinical and microbiological responses of novel ß-lactam/ß-lactamase inhibitor combinations in the treatment of cUTI/APN are similar to those of other available antibiotics. These combinations also share a safety profile similar to that of other antibiotics.

miR-429 expression in bladder cancer and its correlation with tumor behavior and clinical outcome.

We previously showed that microRNA-429 (miR-429) played an important role in epithelial-mesenchymal transition (EMT) of urothelial cell carcinoma of the bladder. We herein evaluated the expression of miR-429 in bladder cancer and its potential relevance to clinicopathological characteristics and patient survival. Relative expression levels of miR-429 in surgical bladder cancer tissue specimens obtained from 76 patients with bladder cancer were measured by chromogenic in situ hybridization. miR-429 expression was significantly higher in specimens from alive patients than expired patients in both of 5-year overall survival (OS) (0.59 ± 0.09 vs. 0.27 ± 0.12; p < 0.05) and 5-year recurrence-free survival (RFS) (0.63 ± 0.10 vs. 0.33 ± 0.10; p < 0.05). The univariate Cox proportional hazards analysis revealed that tumor grade, stage, and miR-429 expression were significantly associated with patient survival. In multivariate analysis, tumor stage and miR-429 expression were significantly associated with 5-year OS (hazard ratio [HR] 4.70, p < 0.001) and 5-year-RFS (HR 2.20, p < 0.05). The Kaplan-Meier analysis showed that patients with miR-429 expression had significantly better 5-year OS and 5-year RFS rates than those without miR-429 expression (84.4% vs. 61.4%, p < 0.05 and 71.9% vs. 45.5%, p < 0.05, respectively). miR-429 may be considered as an adjunctive prognostic marker in addition to tumor grade and stage in bladder cancer.

Chinese nomogram to predict probability of positive initial prostate biopsy: a study in Taiwan region.

Several nomograms for prostate cancer detection have recently been developed. Because the incidence of prostate cancer is lower in Chinese men, nomograms based on other populations cannot be directly applied to Chinese men. We, therefore, developed a model for predicting the probability of a positive initial prostate biopsy using clinical and laboratory data from a Chinese male population. Data were collected from 893 Chinese male referrals, 697 in the derivation set and 196 in the external validation set, who underwent initial prostate biopsies as individual screening. We analyzed age, prostate volume, total prostate-specific antigen (PSA), PSA density (PSAD), digital rectal examinations (DRE) and transrectal ultrasound (TRUS) echogenicity. Logistic regression analysis estimated odds ratio, 95% confidence intervals and P values. Independent predictors of a positive biopsy result included advanced age, small prostate volume, elevated total PSA, abnormal digital rectal examination, and hyperechoic or hypoechoic TRUS echogenicity. We developed a predictive nomogram for an initial positive biopsy using these variables. The area under the receiver-operating characteristic curve for the model was 88.8%, which was greater than that of the prediction based on total PSA alone (area under the receiver-operating characteristic curve 74.7%). If externally validated, the predictive probability was 0.827 and the accuracy rate was 78.1%, respectively. Incorporating clinical and laboratory data into a prebiopsy nomogram improved the prediction of prostate cancer compared with predictions based solely on the individual factors.

Pneumothorax as a Presenting Clinical Manifestation of Metastatic Prostate Cancer.

Pulmonary metastases are not encountered commonly in patients with prostate cancer. Pulmonary metastases with pneumothorax as a presenting clinical manifestation in newly diagnosed prostate cancer are very rare. Here, we present the case of an 82-year-old patient who was admitted to our center with a chief complaint of worsening dyspnea over the past few days. The chest X-ray and computed tomography (CT) showed left pneumothorax and bilateral lung opacities as well as generalized lymphadenopathy and diffuse bony metastases. After a series of workup including cervical lymph node biopsy with immunohistochemical staining, abdomen CT, serum prostate-specific antigen (PSA), and transrectal ultrasonography (TRUS), he was proved to have prostate cancer with multiple lung, bone and lymph node metastases. This case is reported because of the rarity for a prostate carcinoma presented clinically with an unusual pulmonary manifestation.

CXCL1/GROα increases cell migration and invasion of prostate cancer by decreasing fibulin-1 expression through NF-κB/HDAC1 epigenetic regulation.

Inflammatory tumor microenvironments play pivotal roles in the development of cancer. Inflammatory cytokines such as CXCL1/GROα exert cancer-promoting activities by increasing tumor angiogenesis. However, whether CXCL1/GROα also plays a role in the progression of prostate cancer, particularly in highly invasive castration-resistant prostate cancer (CRPC), has not been investigated. We explored whether CXCL1/GROα enhances cell migration and invasion in PC-3 and DU145 CRPC. Induction of PC-3 and DU145 cancer progression by CXCL1/GROα is associated with increased AKT activation and IκB kinase α (IKKα) phosphorylation, resulting in nuclear factor-kappaB (NF-κB) activation. Activated NF-κB interacts with histone deacetylase 1 (HDAC1) to form a gene-silencing complex, which represses the expression of fibulin-1D by decreasing the acetylation of histone H3 and H4 on the NF-κB-binding site of the fibulin-1D promoter. Blockade of AKT2 by small hairpin RNA (shRNA) decreases IKKα phosphorylation, NF-κB nuclear translocation and cell migration, indicating that AKT is required in CXCL1/GROα-mediated NF-κB activation and cell migration. In addition, NF-κB and HDAC1 shRNA decrease the effect of CXCL1/GROα on fibulin-1D downregulation, migration and invasion, suggesting that the NF-κB/HDAC1 complex is also involved in CXCL1/GROα-mediated cancer progression. Our findings provide the first evidence that CXCL1/GROα decreases fibulin-1D expression in prostate cancer cells and also reveals novel insights into the mechanism by which CXCL1/GROα regulates NF-κB activation through the AKT pathway. Our results also clearly establish that co-operation of NF-κB and HDAC1 regulates fibulin-1D expression by epigenetic modification. Our study suggests that inhibition of CXCL1/GROα-mediated AKT/NF-κB signaling may be an attractive therapeutic target for CRPC.

Acacetin, a flavonoid, inhibits the invasion and migration of human prostate cancer DU145 cells via inactivation of the p38 MAPK signaling pathway.

Acacetin (5,7-dihydroxy-4'-methoxyflavone), a flavonoid compound, has anti-peroxidative and anti-inflammatory effects. The effect of acacetin on antimetastasis in human prostate cancer DU-145 cells was investigated. First, the result demonstrated acacetin could exhibit an inhibitory effect on the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay, wound-healing assay, and Boyden chamber assay. Data also showed acacetin could inhibit the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) involved in the downregulation of the expressions of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (u-PA) at both the protein and mRNA levels. Next, acacetin significantly decreased the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, the treatment with acacetin to DU145 cells also leads to a dose-dependent inhibition on the binding ability of NF-kappaB and activator protein-1 (AP-1). Furthermore, the treatment of inhibitors specific for p38 MAPK (SB203580) to DU145 cells could cause reduced expressions of MMP-2, MMP-9, and u-PA. These results showed acacetin could inhibit the invasion and migration abilities of DU145 cells by reducing MMP-2, MMP-9, and u-PA expressions through suppressing p38 MAPK signaling pathway and inhibiting NF-kappaB- or AP-1-binding activity. These findings proved acacetin might be offered further application as an antimetastatic agent.