Model-based dosing optimization and therapeutic drug monitoring practices of teicoplanin in patients with complicated or non-complicated methicillin-resistant staphylococcus aureus infection.

AIMS: This study aims to establish a population pharmacokinetic (PK) model of teicoplanin in Chinese adult patients to evaluate the dosing regimen in the label sheet and optimize it. METHODS: Nonlinear mixed-effects modelling was used to estimate PK parameters. Monte Carlo simulations were used to evaluate the attainment of various dosing regimens in achieving the target trough concentrations in patients with normal or decreased renal function. RESULTS: A total of 115 patients were enrolled in this retrospective study. Creatinine clearance (CrCL) and albumin (ALB) were identified as covariates on the clearance of teicoplanin. For the treatment of non-complicated methicillin-resistant Staphylococcus aureus (MRSA) infections in patients with normal renal function and serum ALB concentration, the recommended dosing regimen was 600 mg q12h with five administrations as the loading dose followed by 600 mg qd as the maintenance dose; for the treatment of serious and/or complicated MRSA infections, the recommended dosing regimen was 800 mg q12h with five administrations as the loading dose followed by 800 mg qd as the maintenance dose. It is worth noting that both the loading and maintenance doses ought to be modified based on the patient's renal function and serum ALB concentration. In addition, trough concentrations of teicoplanin were significantly increased every other week. CONCLUSIONS: Both loading dosing and maintenance dosing regimens were recommended to be adjusted according to patient's renal function and serum ALB concentration. In addition, it is necessary to perform follow-up therapeutic drug monitoring of teicoplanin at least once every week.

[Prediction of quality markers and medicinal value of sea buckthorn leaves based on network pharmacology, content determination, and activity evaluation].

The leaves of sea buckthorn(Hippophae rhamnoides), considered as common food raw materials, have records of medicinal use and diverse pharmacological activities, showing a potential medicinal value. However, the active substances in the sea buckthorn leaves and their mechanisms of action remain unclear. In addition, due to the extensive source and large variety variations, the quality evaluation criteria of sea buckthorn leaves remain to be developed. To solve the problems, this study predicted the main active components, core targets, key pathways, and potential pharmacological effects of sea buckthorn leaves by network pharmacology and molecular docking. Furthermore, ultra-performance liquid chromatography with diode-array detection(UPLC-DAD) was employed to determine the content of active components and establish the chemical fingerprint, on the basis of which the quality markers of sea buckthorn leaves were predicted and then verified by the enzyme activity inhibition method. The results indicated that sea buckthorn leaves had potential therapeutic effects on a variety of digestive tract diseases, metabolic diseases, tumors, and autoimmune diseases, which were consistent with the ancient records and the results of modern pharmacological studies. The core targets of sea buckthorn leaves included PTPN11, AKT1, PIK3R1, ESR1, and SRC, which were mainly involved in the PI3K-AKT, MAPK, and HIF-1 signaling pathways. In conclusion, the active components of sea buckthorn leaves are associated with the rich flavonoids and tannins, among which quercitrin, narcissoside, and ellagic acid can be used as the quality markers of sea buckthorn leaves. The findings provide a reference for the quality control and further development and utilization of sea buckthorn leaves as medicinal materials.

[Research progress on chemical constituents and pharmacological activities of Viola plants].

There are 500 species of Viola(Violaceae) worldwide, among which 111 species are widely distributed in China and have a long medicinal history and wide varieties. According to the authors' statistics, a total of 410 compounds have been isolated and identified from plants of this genus, including flavonoids, terpenoids, phenylpropanoids, organic acids, nitrogenous compounds, sterols, saccharides and their derivatives, volatile oils and cyclotides. The medicinal materials from these plants boast anti-microbial, anti-viral, anti-oxidant and anti-tumor activities. This study systematically reviewed the chemical constituents and pharmacological activities of Viola plants to provide a basis for further research and clinical application.

Safety and clinical efficacy of linezolid in children: a systematic review and meta-analysis.

BACKGROUND: We aimed to evaluate the tolerability and efficacy of linezolid in children for treating suspected and diagnosed Gram-positive bacterial infections. METHODS: A systematic literature search was conducted up to April 23, 2021, using linezolid and its synonyms as search terms. Two reviewers independently identified and extracted relevant randomized controlled trials and prospective cohort studies. The extracted studies were included in a single-rate meta-analysis of adverse events and clinical outcomes using random-effects models. RESULTS: A total of 1082 articles were identified, and nine studies involving 758 children were included in the meta-analysis. The overall proportion of adverse events was 8.91% [95% confidence interval (CI) = 1.64%-36.52%], with diarrhea (2.24%), vomiting (2.05%), and rash (1.72%) being the most common. The incidences of thrombocytopenia and anemia were 0.68% and 0.16%, respectively. Some specific adverse events, including rash and gastrointestinal events, were more frequent in the oral administration subgroup. In terms of efficacy, the overall proportion of clinical improvement was 88.80% (95% CI = 81.31%-93.52%). Children with a history of specific bacteriological diagnosis or concomitant antibiotic therapy had a 1.13-fold higher clinical improvement than children without such histories. The proportion of microbial eradication was 92.68% (95% CI = 84.66%-96.68%). The proportion of all-cause mortality was 0.16% (95% CI = 0.00%-7.75%). CONCLUSIONS: Linezolid was well-tolerated in pediatric patients and was associated with a low frequency of adverse events, such as anemia, thrombocytopenia, and neutropenia. Moreover, linezolid was effective in children with diagnosed and suspected Gram-positive infections.

Three new compounds with their anti-glioma effects from the roots of Arnebia guttata Bunge.

Three new compounds, arneatas A-C (1-3), together with three known compounds (4-6) were isolated from the roots of Arnebia guttata Bunge. The structures were established on the basis of extensive spectroscopic data including NMR and HRESIMS. All the new compounds (1-3) were tested for their cytotoxic activity against two glioma cell lines (U118-MG and U373-MG) in vitro after treatment for 48 h. Compound 1 exhibited moderate cytotoxic activity against U118-MG and U373-MG glioma cell lines, with IC50 values of 10.4 and 17.5 µM, respectively.

Modification of Vancomycin Dosing in Cardiac Surgery With Cardiopulmonary Bypass.

This study aims to assess the risk factors for insufficient vancomycin concentrations for its prophylactic use in adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and to modify the dosing regimen to achieve appropriate plasma concentrations. A total of 27 patients with vancomycin dosing of 1 to 1.5 g based on a weight cutoff of 67 kg were included, of which only 13 (48.15%) had vancomycin plasma concentration >15 mg/L at surgical closure. Risk factors of vancomycin concentration <15 mg/L at surgical-site closure were confirmed by multivariate logistic regression analysis, which showed that CPB duration was an independent predictor. Patients with CPB duration >4 hours had significantly lower vancomycin concentrations and lower proportion in achieving target vancomycin concentration at the end of CPB and surgical closure. For patients with CPB >4 hours, the modified dosing regimen that a second dose of 0.5 to 0.75 g added at 4 hours since the onset of CPB improved the target achievement of vancomycin concentration at surgical closure. Taken together, CPB duration >4 hours was the risk factor for insufficient vancomycin concentration at surgical closure, while our modified dosing could improve the vancomycin concentrations for its prophylactic use in patients undergoing cardiac surgery with CPB.

Complex ecological and socioeconomic impacts on medicinal plant diversity.

Medicinal plant diversity (MPD) is an important component of plant diversity. Over-collection based on medicinal and economic value has the potential to damage the stability of the regional ecosystem. It is important to understand the current distribution of MPD and the factors influencing it. However, it is still unclear whether environmental and socioeconomic conditions have an impact on their distribution. We selected the Inner Mongolia as a representative study area which covers a wide area, accounting for 12.29% of China's national land area and 0.79% of the world's land area. At the same time, the region is a long-standing traditional medicinal area for Mongolians in China. Therefore, the region is significantly influenced by changes in environmental factors and socio-economic factors. We used 9-years field survey of the distribution of medicinal plants in Inner Mongolia for assessing the distribution of MPD as influenced by environmental and socioeconomic activities by combining spatial analyses, species distribution models, and generalized additive models. The results from the spatial analysis show that the western region of Inner Mongolia is the main cold spot area of the MPD, and the central-eastern and northeastern regions of Inner Mongolia are the main hot spot areas of the MPD. At the same time, the distribution of cold spots and hot spots of MPD is more obvious at large spatial scales, and with the refinement of spatial scales, the cold spots in scattered areas are gradually revealed, which is indicative for the conservation and development of MPD at different spatial scales. Under the future climate change of shared socioeconomic pathways (SSP), areas with high habitat suitability for medicinal plants remain mainly dominated by the Yellow River, Yin Mountains, and Greater Khingan Range. Notably, the SSP245 development pathway remains the most significant concern in either long- or short-term development. The nonlinear relationship between the driving factors of MPD at different spatial scales shows that temperature, precipitation and socioeconomic development do have complex effects on MPD. The presence of a certain temperature, altitude, and precipitation range has an optimal facilitation effect on MPD, rather than a single facilitation effect. This complex nonlinear correlation provides a reference for further studies on plant diversity and sustainable development and management. In this study, the spatial distribution of medicinal plant resources and the extent to which they are driven by ecological and socioeconomic factors were analyzed through a macroscopic approach. This provides a reference for larger-scale studies on the environmental and socioeconomic influences on the distribution of plant resources.

Population pharmacokinetic analysis, renal safety, and dosing optimization of polymyxin B in lung transplant recipients with pneumonia: A prospective study.

Objectives: This study aims to characterize the population pharmacokinetics of polymyxin B in lung transplant recipients and optimize its dosage regimens. Patients and methods: This prospective study involved carbapenem-resistant organisms-infected patients treated with polymyxin B. The population pharmacokinetic model was developed using the NONMEM program. The clinical outcomes including clinical treatment efficacy, microbiological efficacy, nephrotoxicity, and hyperpigmentation were assessed. Monte Carlo simulation was performed to calculate the probability of target attainment in patients with normal or decreased renal function. Results: A total of 34 hospitalized adult patients were included. 29 (85.29%) patients were considered of clinical cure or improvement; 14 (41.18%) patients had successful bacteria elimination at the end of the treatment. Meanwhile, 5 (14.71%) patients developed polymyxin B-induced nephrotoxicity; 19 (55.88%) patients developed skin hyperpigmentation. A total of 164 concentrations with a range of 0.56-11.66 mg/L were obtained for pharmacokinetic modeling. The pharmacokinetic characteristic of polymyxin B was well described by a 1-compartment model with linear elimination, and only creatinine clearance was identified as a covariate on the clearance of polymyxin B. Monte Carlo simulations indicated an adjusted dosage regimen might be needed in patients with renal insufficiency and the currently recommended dose regimens by the label sheet of polymyxin B may likely generate a subtherapeutic exposure for MIC = 2 mg/L. Conclusion: Renal function has a significant effect on the clearance of polymyxin B in lung transplant recipients, and an adjustment of dosage was needed in patients with renal impairments.

Population Pharmacokinetics of Colistin Sulfate in Critically Ill Patients: Exposure and Clinical Efficacy.

Background: Presently, colistin is commercially available in two different forms, namely, colistin sulfate and its sulphomethylated derivative, colistimethate sodium (CMS). However, in the currently reported studies, most of the clinical studies on colistin for parenteral use are referred to as CMS. Data on the pharmacokinetics (PK), clinical efficacy, and side effects of colistin sulfate in clinical use have not been reported. Methods: This retrospective study was performed on carbapenem-resistant organism (CRO)-infected patients treated with colistin sulfate for more than 72 h. The population pharmacokinetic model was developed using the NONMEM program. The clinical outcomes including clinical treatment efficacy, microbiological eradication, and nephrotoxicity were assessed. Monte Carlo simulation was utilized to calculate the probability of target attainment (PTA) in patients with normal or decreased renal function. Results: A total of 42 patients were enrolled, of which 25 (59.52%) patients were considered clinical treatment success and 29 (69.06%) patients had successful bacteria elimination at the end of treatment. Remarkably, no patient developed colistin sulfate-related nephrotoxicity. A total of 112 colistin concentrations with a range of 0.28-6.20 mg/L were included for PK modeling. The PK characteristic of colistin was well illustrated by a one-compartment model with linear elimination, and creatinine clearance (CrCL) was identified as a covariate on the clearance of colistin sulfate that significantly explained inter-individual variability. Monte Carlo simulations showed that the recommended dose regimen of colistin sulfate, according to the label sheet, of a daily dose of 1-1.5 million IU/day, given in 2-3 doses, could attain PTA > 90% for MICs ≤ 0.5 µg/mL, and that a daily dose of 1 million IU/day could pose a risk of subtherapeutic exposure for MIC ≥1 µg/ml in renal healthy patients. Conclusion: Renal function significantly affects the clearance of colistin sulfate. A dose of 750,000 U every 12 h was recommended for pathogens with MIC ≤1 µg/ml. The dosage recommended by the label inserts had a risk of subtherapeutic exposure for pathogens with MIC ≥2 µg/ml. Despite higher exposure to colistin in patients with acute renal insufficiency, dose reduction was not recommended.

Acupuncture mechanism studies employing task-based fMRI: a scoping review protocol.

BACKGROUND: Acupuncture is a widely used alternative and complementary therapy. Functional magnetic resonance imaging (fMRI) is an important technique to explore the underlying mechanism of acupuncture, and the task-based fMRI can reflect the instant effects or sustained effects of acupuncture in the brain. This scoping review aims to summarize the characteristics of acupuncture mechanism studies employing task-based fMRI and conclude a reference for future studies. METHODS/DESIGN: This review will follow the Guidance for Conducting Scoping Reviews. Eligible articles will be collected from 7 databases (PubMed, Embase, Cochrane, CNKI, WanFang, VIP, and CBM) with the related keywords such as "Acupuncture" and "fMRI"; those articles should be published from January 1, 2000, to December 31, 2021; and the language should be restricted in English or Chinese. Each research step will involve at least two reviewers. The PRISMA-ScR (Preferred Reporting Items for Systemic Reviews and Meta-Analysis Extension for Scoping Reviews) will be used to organize the review. Data will be extracted from the illegible articles, and findings will be presented in tables and narrative form. A descriptive qualitative approach to analysis will be conducted to form the scoping review. DISCUSSION: This review aims to clarify the extent of acupuncture mechanism studies employing task-based fMRI. It is supposed to make a critical evaluation or propose quality requirements for future studies by summarizing the objectives and designs of eligible studies. What is more, directional suggestions will be provided for further studies. SCOPING REVIEW REGISTRATION: Open Science Framework https://osf.io/zjrdc/ .

Efficacy and Pharmacodynamic Target Attainment for Ceftazidime-Avibactam Off-Label Dose Regimens in Patients with Continuous or Intermittent Venovenous Hemodialysis: Two Case Reports.

Limited data are available for ceftazidime-avibactam (CZA) dosing in patients receiving renal replacement therapy, especially the data on the dosing in patients receiving intermittent hemodialysis (IHD). In this report, we firstly described a case in which CZA was administered as 2.5 g after each time of IHD, and a dose of 1.25 g was added on the 48th-hour for the 72-h interdialytic interval. Plasma concentrations of CZA measured at different time indicated that > 50% of administered ceftazidime and avibactam were removed during the 4-h hemodialysis. In addition, we described another case on continuous venovenous hemodialysis (CVVHD), in which CZA was administered as 2.5 g q12h in 2-h infusions. The dose regimen for these two cases could achieve trough concentration of ceftazidime higher than fourfold of the MIC and trough concentration of avibactam higher than the threshold of 1 µg/mL during the treatment, and exert efficient antimicrobial effect.

Dosage Strategy of Linezolid According to the Trough Concentration Target and Renal Function in Chinese Critically Ill Patients.

Background: Linezolid is associated with myelosuppression, which may cause failure in optimally treating bacterial infections. The study aimed to define the pharmacokinetic/toxicodynamic (PK/TD) threshold for critically ill patients and to identify a dosing strategy for critically ill patients with renal insufficiency. Methods: The population pharmacokinetic (PK) model was developed using the NONMEM program. Logistic regression modeling was conducted to determine the toxicodynamic (TD) threshold of linezolid-induced myelosuppression. The dosing regimen was optimized based on the Monte Carlo simulation of the final model. Results: PK analysis included 127 linezolid concentrations from 83 critically ill patients at a range of 0.25-21.61 mg/L. Creatinine clearance (CrCL) was identified as the only covariate of linezolid clearance that significantly explained interindividual variability. Thirty-four (40.97%) of the 83 patients developed linezolid-associated myelosuppression. Logistic regression analysis showed that the trough concentration (Cmin) was a significant predictor of myelosuppression in critically patients, and the threshold for Cmin in predicting myelosuppression with 50% probability was 7.8 mg/L. The Kaplan-Meier plot revealed that the overall median time from the initiation of therapy to the development of myelosuppression was 12 days. Monte Carlo simulation indicated an empirical dose reduction to 600 mg every 24 h was optimal to balance the safety and efficacy in critically ill patients with CrCL of 30-60 ml/min, 450 mg every 24 h was the alternative for patients with CrCL <30 ml/min, and 600 mg every 12 h was recommended for patients with CrCL ≥60 ml/min. Conclusion: Renal function plays a significant role in linezolid PKs for critically ill patients. A dose of 600 mg every 24 h was recommended for patients with CrCL <60 ml/min to minimize linezolid-induced myelosuppression.

Intraventricular colistin sulphate as a last resort therapy in a patient with multidrug-resistant Acinetobacter baumannii induced post-neurosurgical ventriculitis.

Limited therapeutic options exist for multidrug-resistant/extensively drug-resistant Acinetobacter baumannii (MDR/XDR-Ab) meningitis/ventriculitis. A combination of intravenous and intraventricular (IVT)/intrathecal (IT) polymyxins achieves good therapeutic outcomes for cases of healthcare-associated MDR/XDR-Ab meningitis/ventriculitis. Colistin is commercially available as colistin sulphate and its sulphomethylated derivative. However, the effect and safety of colistin sulphate in the treatment of MDR/XDR-Ab meningitis/ventriculitis has not been reported. We report on a 66-year-old male patient who developed post-neurosurgical ventriculitis caused by MDR-Ab. IVT concomitant intravenous colistin sulphate was used as a last-resort antimicrobial therapy, the patient's ventriculitis was dramatically improved, and the concentrations of CSF colistin were higher than the MIC breakpoint throughout the treatment. Meanwhile, no nephrotoxicity or neurotoxicity was observed during the treatment.

Trough polymyxin B plasma concentration is an independent risk factor for its nephrotoxicity.

AIMS: Data regarding clinical pharmacokinetic/toxicodynamic (PK/TD) of polymyxin B is short of direct quantitative data. This study aims to investigate the risk factors of polymyxin B associated acute kidney injury (AKI) and to assess the relationship between polymyxin B plasma levels and its nephrotoxicity. METHODS: A retrospective study was performed in adult patients treated with polymyxin B. Risk factors associated with AKI and plasma trough concentrations of polymyxin B were identified via medical record review. A multivariate logistic regression model was established and the risk of polymyxin B-associated AKI were predicted by a receiver operating characteristic curve, with maximal Youden index used to identify safety thresholds among the study population. RESULTS: Fifty-four adult patients were included in the study. AKI was detected in 14 patients during polymyxin B treatment (25.9%, 14 out of 54). Cmin (odds ratio [OR] 2.071; 95% confidence interval [CI] 1.235-3.472) and baseline serum creatinine (OR 1.024; 95% CI 1.005-1.043) were significant independent risk factors for developing AKI. The area under the ROC curve of the combined predictor was larger based on the above factors. When the Youden index was at maximum, the optimal cut-off point was 6.678 of the ROC curve. When Cmin ≥ 3.13 mg/L, the probability of AKI was more than 50%. CONCLUSION: In this study, when the calculated combined predictor value was >6.678, there was an increased risk of AKI. Maintaining a polymyxin B Cmin level below 3.13 mg/L may be helpful in reducing the incidence of polymyxin B associated nephrotoxicity.

Efficacy and safety of induction chemotherapy with daunorubicin or idarubicin in the treatment of an adult with acute lymphoblastic leukemia.

BACKGROUND: Anthracyclines are dispensable components of chemotherapy of patients with acute lymphoblastic leukemia (ALL). OBJECTIVE: To analyze the efficacy and safety of induction with idarubicin (IDA) or liposoma daunorubicin (L-DNR) in treatment of adults with high-risk ALL (HR-ALL) (presence of mixed lineage leukemia gene [MLL] rearrangements, t[1;19], or prednisone poor response). METHODS: Among 58 enrolled patients, 29 cases were defined as the IDA group and the other 29 patients were put into the L-DNR group. Both overall survival (OS) and progression-free survival (PFS) were estimated and overall response rate (ORR) was compared between the groups. RESULTS: The L-DNR group's OS and PFS were insignificantly higher than in the IDA group (P=0.261 and P=0.247). Although not significantly different, the ORR of adults with HR-ALL receiving L-DNR regimens was also higher than in the IDA group (P=0.085). Comprehensive cytogenetic analysis revealed that patients harboring MLL rearrangement, E2A-PBX1, and P53 mutation had poorer prognosis than others. All 58 patients experienced hematologic response in this study; however, the length of hematologic response in the IDA group was significantly longer than in the L-DNR group (P=0.005). The incidence of bleeding and infection was without significant difference between the groups (both P>0.05). CONCLUSION: L-DNR proved to be an effective drug within a multiagent approach, which shows a favorable overall profile, as well as similar adverse events when compared with IDA in HR-ALL. Patients with E2A-PBX1 are much more sensitive to L-DNR than IDA. Despite some progress made, outcomes in MLL rearrangement or P53 mutation carriers remain unsatisfactory, and intensive treatment will be critical.

Plant Pharmacophylogeny: Review and Future Directions.

Medicinal plants have provided numerous medicinal active ingredients for thousands of years and these ingredients have been used in Chinese medicine (CM) and traditional pharmacologies worldwide. Recently, the exploitation and utilisation of medicinal plant resources has increased significantly. The results of the studies have led to the identification of many active components, such as steroidal alkaloids, saponins, terpenoids, and glycosides, in various medicinal plants with different evolutionary levels. Moreover, research on the chemical classification, molecular phylogeny, and pharmacological activity of medicinal plants is increasing in popularity. Pharmacophylogeny is an interdisciplinary topic that studies the correlation between plant phylogeny, chemical composition, and curative effects (pharmacological activity and the traditional curative effect) of medicinal plants. In addition, it provides the basic tools to enable research and development of CM resources. This literature review, based on the genetic relationship between phytogroup and species, highlights the formation process, research content, applications, and future directions of pharmacophylogeny.

[Panlong acupuncture combined with Xingnao Kaiqiao acupuncture for post-stroke fatigue: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of Panlong (dragon-like) acupuncture combined with Xingnao Kaiqiao (regaining consciousness and opening orifice) acupuncture on post-stroke fatigue. METHODS: Sixty patients with post-stroke fatigue were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 2 cases dropped off). The patients in the control group were treated with Xingnao Kaiqiao acupuncture at Neiguan (PC 6), Shuigou (GV 26), etc. for 30 min; based on the treatment of the control group, the patients in the observation group were treated with Panlong acupuncture at Jiaji (EX-B 2) of T1 to L5 for 15 min. The two groups were treated once a day, 6 times a week, for a total of 4 weeks. The scores of fatigue assessment instrument (FAI), energy of stroke-specific quality of life (SS-QOL), and modified Barthel index (MBI) in the two groups were compared before and after treatment, and the clinical efficacy was evaluated. RESULTS: Compared before treatment, the total score and each item score of FAI in the observation group were reduced after treatment (P<0.05), while the total score and FAI-1 and FAI-4 scores in the control group were reduced after treatment (P<0.05). The total score of FAI and FAI-1, FAI-2 and FAI-4 scores in the observation group were lower than those in the control group (P<0.05). After treatment, the SS-QOL energy scores and MBI scores of the two groups were increased compared before treatment (P<0.05), and the SS-QOL energy score in the observation group was higher than that in the control group (P<0.01). The total effective rate was 72.4% (21/29) in the observation group, which was better than 46.4% (13/28) in the control group (P<0.05). CONCLUSION: The Panlong acupuncture combined with Xingnao Kaiqiao acupuncture could effectively alleviate the fatigue symptoms and improve quality of life in patients with post-stroke fatigue.

Insufficient procedural anticoagulation during leadless pacing led to catheter-related thrombosis in a hemodialysis patient.

BACKGROUND: Leadless pacemaker was a promising innovation than traditional transvenous pacemaker, the procedural complications were prone to be bleeding-related. However, very few reports also concerned about the thrombus formation during the procedure. CASE PRESENTATION: A hemodialysis patient with diabetic gangrene of right foot suffered from catheter-related thrombosis during leadless pacing, resulting in failure of recapture the pacemaker. A low activated clotting time (ACT) level of 104 s confirmed the insufficiency of anticoagulation. Finally, the whole delivery catheter had to be removed from the delivery sheath, another new pacemaker system was applied and successfully implanted after adjusting the ACT level to 248 s. CONCLUSION: Catheter-related thrombosis could be a large obstacle for leadless pacemaker implantation. In addition to routine anticoagulation, ACT monitoring might be necessary during the procedure.