Comparative efficacy and safety of anti-PD-1 therapies used in metastatic colorectal cancer: a systematic review and network meta-analysis

Objective: Systemic studies on anti-PD-1 therapy in patients with metastatic colorectal cancer (mCRC) with microsatellite instability or mismatch repair defects are lacking. We aimed to summarize the evidence regarding the efficacy and safety of pembrolizumab, nivolumab, ipilimumab, and tislelizumab in mCRC. Methods: Network meta-analyses (NMAs) can provide comparative efficacy and safety data for clinical decision-making. In this NMA, eligible publications from PubMed, EMBASE, Web of Science, and Cochrane Library from 2016 to April 2023 were identified through a systematic literature review. Literature screening and data extraction were performed according to established criteria. The quality of the literature was evaluated using the Cochrane risk of bias tool, and statistical analysis was performed using Revman5.4 and R language. The main outcome indicators, DCR, ORR, PFS, and OS, were used to evaluate the effectiveness of the drugs, and the main outcome indicators AE and SAE were used to evaluate the safety of each program. Results: Fifteen studies with a sample size of 798 patients were included. In terms of effectiveness, the disease control rate DCR of PD-1 inhibitors was 0.727[95% CI:0.654-0.794]; objective response rate ORR was 0.448[95% CI:0.382-0.514]; and the 1-year progression-free survival rate was 0.551[95% CI:0.458-0.642]. The 1-year overall survival rate was 0.790[95% CI:0.705-0.865]. The adverse events associated with anti-PD-1 were 0.567[95% CI:0.344-0.778] in terms of safety. The total incidence of grade 3 or higher adverse events was 0.241[95% CI:0.174-0.313]. In the subgroup analysis results, the incidence of DCR in the nivolumab + ipilimumab group was 0.826[95% CI:0.780-0.869], the ORR was 0.512[95% CI:0.377-0.647], and the PFS was 0.668[95% CI:0.516-0.804]. The incidence of AE was 0.319 [95% CI:0.039-0.700] and SAE was 0.294 [95% CI:0.171-0.433]... (AU)

Effect of medication therapy management on discharged patient with Ulcerative Colitis with initial stage biotherapy: a randomized study

Purpose: The aim of this study was to explore the effects of medication therapy management in improving perception, medication adherence, and disease control in UC patients with first-stage of biotherapy. Subjects and Methods: A total of 120 patients with UC who received first-stage biotherapy participated in this study. The patients were divided into MTM group and CFU group. Both groups received three times follow-up, which were carried out at first, third, and sixth discharged month, Group A was followed with the MTM method, and Group B received conventional follow-up. MDRKT was used to assess patient perception, adherence to treatment was assessed by MMSA-8, and we also explored disease control and patient satisfaction. Results: A total of 116 patients completed the survey, the MTM group showed a significant improvement in perception, 84.2% of patients can correctly handle ADEs and 82.5% of patients knew what to do when they leak medication, 87.8% of patients in the MTM group had better adherence than 71.2% in the CPU group (P<0.05). The evaluation of disease control showed that 56.1% of patients in the Group A were in remission which was significantly higher than 32.2% in the Group B (P<0.05). Furthermore, the result of the questionnaire survey showed that perception, ADE, self-management, anxiety, and satisfaction were better in the MTM group than in the CPU group (P<0.05). Conclusion: The MTM group was effective in improving medication adherence, perception, and satisfaction in the patient with ulcerative colitis treated with first-stage biotherapy, and the disease control significantly improved (AU)

Giant breast phyllodes tumor with silent thromboembolism: A case report.

BACKGROUND: Phyllodes tumor (PT) is a solid fibroepithelial breast lesion with proliferation of stromal and epithelial elements, usually presents with a rapidly expanding feature. Venous thromboembolism (VTE) have been reported to increase the burden in terms of mortality and morbidity of malignant tumor, and associate with worsened survival. However, benign PTs with silent thromboembolism that have not yet been reported, we report an unusual case of massive benign PT that grew on the left side of the breast in a cauliflower-shaped form and presented severe chronic blood loss and deep VTE. CASE: A 37-year-old woman with uncontrolled pain presented a rapidly enlarging left breast mass, measuring approximately 30 × 20 × 15 cm3 that first started 25 years ago. color Doppler ultrasound showed a large mass lesion on the left breast and deep VTE, several enlarged lymph nodes in the left axilla and mediastinum, which presented a malignant character. However, the biopsies of the mass did not show evidence of malignancy and the pathology result was considered to be benign PT. The patient was treated with an inferior vena cava and anticoagulation, the operation was arranged according to the surgical procedure, the patient recovered very well after mastectomy. CONCLUSION: This case is unique in that the giant breast mass presented with malignant character, was eventually pathologically confirmed to be benign PT, and it's rare that the benign tumor accompanied with silent thromboembolism. This finding describes the atypia features of giant benign PT and reminds the surgeon to consider the factor of VTE and risk when encountering ulcerative benign breast tumor and avoid excessive treatment.

Treatment of amoxicillin-containing wastewater by Trichoderma strains selected from activated sludge.

This study screened a Trichoderma strain (Trichoderma pubescens DAOM 166162) from activated sludge to solve the limitation of traditional biological processes in the treatment of amoxicillin (AMO) containing wastewater. The mechanism of the removal of AMO wastewater by T. pubescens DAOM 166162 (TPC) was studied. AMO resulted in a higher protein percentage in the extracellular polymeric substances (EPS) secreted by TPC, which facilitated the removal of AMO from the wastewater. Fourier transform infrared spectroscopy and excitation-emission matrix were used to characterize EPS produced by metabolizing different carbon sources. It was found that the hydroxyl group was the primary functional group in EPS. The life activity of TPC was the cause of the pH rise. The main pathway of degradation of AMO by TPC was the hydroxyl group uncoupling the lactam ring and the hydrolysis of AMO in an alkaline environment. The removal efficiency of AMO in wastewater by TPC was >98 % (24 h), of which the biodegradation efficiency was 70.01 ± 1.48 %, and the biosorption efficiency was 28.44 ± 2.97 %. In general, TPC is an effective strain for treating wastewater containing AMO. This research provides a new idea for AMO wastewater treatment.

Enantioselective toxicity, degradation and transformation of the chiral insecticide fipronil in two algae culture.

The occurrence of pesticides and their metabolites in the environment can alter the ecological relationships between aquatic food chains. Fipronil is a broad-spectrum insecticide which release in the environment may harm the non-target organisms. However, the toxicity and biotransformation of its two enantiomers are far from fully understood. The present study aimed to investigate the aquatic toxicity and environmental behavior of fipronil at enantiomeric level using two freshwater algae, Scenedesmus quaclricauda (S. quaclricauda), and Chlorella vulgaris (C. vulgaris) through an integrative approach the transformation process of the individual enantiomer isolated and in racemic form. The 72 h-EC50 values of rac-, R-, S-fipronil varied from 3.27 to 7.24 mg L-1 with R-fipronil posing a more significant effect on algal growth inhibition. Chlorophyll a was more susceptible to fipronil exposure than chlorophyll b and carotenoids. Enantioselective alterations on physiological and biochemical parameters (chlorophyll a, chlorophyll b, carotenoids, and the activities of antioxidant enzyme catalase (CAT) and superoxide dismutase (SOD)) were also observed. The half-lives (T1/2) of R-fipronil and S-fipronil in algae culture were 3.4-3.5 d and 4.0-4.9 d, respectively. By the end of the 17-d exposure, the enantiomer fractions (EFs) increased to 0.59, indicating a preferential depuration of R-fipronil. The metabolites monitoring showed the fipronil sulfide was the main metabolite followed by fipronil sulfone. The results revealed that the enantiomers of fipronil pose enantiospecific behaviors induced by these two algae, with the R-enantiomer more toxic to algal growth and favorable in degradation. These analyses are beneficial for understanding the ecological effect of chiral pesticide in aquatic environment, and the enantiomeric differences of the toxicity, degradation and the formation of toxic metabolites could be helpful for the eco-environmental risk evaluation.

Exploring antibiotic consumption between urban and sub-urban catchments using both parent drugs and related metabolites in wastewater-based epidemiology.

Consumption of antibiotics leads to the dissemination of antimicrobial resistance worldwide. Better knowledge of temporal and spatial consumption of antibiotics helps public health authorities to control their usage and combat antimicrobial resistance. However, measuring antibiotic consumption with population surveys, sales data, and production statistics remains challenging due to the complexity of prescription preference, patient compliance, and direct disposal of unused drugs. With the approach of wastewater-based epidemiology (WBE), this study aims to evaluate the consumption of eight commonly-used antibiotics between developed urban and developing sub-urban catchments in China and to characterise the ratios of parent drugs to metabolites in studying the consumption. Seven parent antibiotics were detected in all the wastewater samples (n = 56), whereas some metabolites were detected sporadically. The ratios of parent chemicals to metabolites varied among locations and were often higher than the ratios in pharmacokinetic studies. Estimated consumption of antibiotics ranged from 3.2 ± 2.0 mg/day/1000 inhabitants for trimethoprim to 28,400 ± 7800 mg/day/1000 inhabitants for roxithromycin in the studied catchments. Higher consumption of sulfapyridine, sulfadiazine and roxithromycin was observed in urban than suburban catchments, while consumption of sulfamethoxazole, norfloxacin, and trimethoprim was higher in suburban than in urban catchments. Using the literature data, we found more than 95% reduction of antibiotic use in an urban catchment. Our study revealed the geographical pattern in antibiotic use across different urban and suburban catchments via WBE, and the potential of monitoring parent-to-metabolite ratios for WBE in estimating antibiotic use. These results provide a basis for health authorities to plan different drug-specific control policies between urban and suburban catchments, and for future WBE studies to be aware of other sources, such as animal husbandry and disposals of unused drugs, that can influence the estimated consumption.

Effects of different carbon sources on the removal of ciprofloxacin and pollutants by activated sludge: Mechanism and biodegradation.

This research investigated the effects of ciprofloxacin (CIP) (0.5, 5, and 20 mg/L) on SBR systems under different carbon source conditions. Microbial community abundance and structure were determined by quantitative PCR and high-throughput sequencing, respectively. The biodegradation production of CIP and possible degradation mechanism were also studied. Results showed that CIP had adverse effects on the nutrient removal from wastewater. Compared with sodium acetate, glucose could be more effectively used by microorganisms, thus eliminating the negative effects of CIP. Glucose stimulated the microbial abundance and increased the removal rate of CIP by 18%-24%. The mechanism research indicated that Proteobacteria and Acidobacteria had a high tolerance for CIP. With sodium acetate as a carbon source, the abundance of nitrite-oxidizing bacterial communities decreased under CIP, resulting in the accumulation of nitrite and nitrate. Rhodanobacter and Microbacterium played a major role in nitrification and denitrification when using sodium acetate and glucose as carbon sources. Dyella and Microbacterium played positive roles in the degradation process of CIP and eliminated the negative effect of CIP on SBR, which was consistent with the improved removal efficiency of pollutants.

[Effects of stabilization treatment on migration and transformation of heavy metals in mineral waste residues].

Different forms of heavy metals in soil will produce different environmental effects, and will directly influence the toxicity, migration and bioavailability of heavy metals. This study used lime, fly ash, dried sludge, peanut shells as stabilizers in the treatment of heavy metals in mineral waste residues. Morphological analyses of heavy metal, leaching experiments, potted plant experiments were carried out to analyze the migration and transformation of heavy metals. The results showed that after adding stabilizers, the pH of the acidic mineral waste residues increased to more than neutral, and the organic matter content increased significantly. The main existing forms of As, Pb, and Zn in the mineral waste residues were the residual. The contents of exchangeable and organic matter-bound As decreased by 65.6% and 87.7% respectively after adding fly ash, dried sludge and peanut shells. Adding lime, fly ash and peanut shells promoted the transformation of As from the Fe-Mn oxide-bound to the carbonate-bound, and adding lime and fly ash promoted the transformation of Pb and Zn from the exchangeable, Fe-Mn oxide-bound, organic matter-bound to the residual. After the early stage of the stabilization treatment, the contents of As, Pb and Zn in the leachate had varying degrees of decline, and adding peanut shells could reduce the contents of As, Pb and Zn in the leachate further. Among them, the content of As decreased most significantly after treatment with fly ash, dried sludge and peanut shells, with a decline of 57.4%. After treatment with lime, fly ash and peanut shells, the content of Zn decreased most significantly, by 24.9%. The addition of stabilizers was advantageous to the germination and growth of plants. The combination of fly ash, dried sludge and peanut shell produced the best effect, and the Vetiveria zizanioides germination rate reached 76% in the treated wasted mineral residues.