Monitoring environmental drug-resistance genes (DRGs) plays a pivotal role in preventing the transmission of antimicrobial resistance, thereby reducing public health risks. In this study, a one-pot recombinase polymerase amplification (RPA)/clustered regularly interspaced short palindromic repeat (CRISPR) assay was developed for monitoring DRGs in river water. To overcome compatibility challenges between RPA and CRISPR systems, four glycosaminoglycans (heparin sodium, nadroparin calcium, dalteparin sodium, and chondroitin sulfate A sodium salt) with different molecular weights or negative charge density were evaluated as Cas-enzyme activity modulators. Among them, heparin sodium with the high molecular weight and high strong negative charge density exhibited the best performance in the one-pot DRG detection assay. In the system, CRISPR-Cas12a activity was temporarily inhibited during the RPA amplification phase. When sufficient amplicons were accumulated, Cas12a was activated for signal readout, thereby achieving orderly coupling and precise control of both reactions. To further simplify and improve the reliability of environmental DRG monitoring, a pretreatment method that can eliminate nucleic acid extraction was developed and integrated with the inhibitor-controlled one-pot platform. This assay achieved high sensitivity and specificity when it was applied to river samples, matching the performance of qPCR. The developed assay is simple to operate, has high sensitivity, and is widely adaptable, providing a robust tool for rapid antimicrobial resistance surveillance and exhibiting promise for public health management applications.

Background: Venous thromboembolism (VTE), particularly in the context of cancer-associated thrombosis (CAT), is a major cause of morbidity and mortality in patients with malignancy. While apixaban has emerged as a potential alternative to low-molecular-weight heparins (LMWHs), uncertainty remains regarding the consistency of its safety profile across different LMWH agents. Methods: This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. A comprehensive literature search was performed across PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials. Results: Six randomized controlled trials were included. Apixaban was associated with a reduced risk of recurrent VTE (RR 0.66, 95% CI 0.45-0.96). However, safety outcomes varied depending on the LMWH comparator. Compared with dalteparin, apixaban was associated with a higher risk of clinically relevant non-major bleeding (CRNMB) (log RR 0.38; 95% CI 0.02 to 0.75), whereas, compared with enoxaparin, it was associated with a lower risk (log RR -0.49; 95% CI -0.96 to -0.02). Conclusions: These findings suggest potential differences in safety profiles across individual LMWH agents. However, given the limited number of included trials and clinical heterogeneity, the results should be interpreted cautiously. Further large-scale studies are required to confirm these observations.

Venous thromboembolism is a common cause of maternal mortality. Many women need regional anaesthesia during vaginal delivery or caesarean section. However, the risk of epidural or spinal haematoma is increased if regional anaesthesia is administered during ongoing thromboprophylaxis with low molecular weight heparin (LMWH). The aims of this pilot study are to evaluate the anticoagulant effect of LMWH during pregnancy by thrombelastography and anti-factor Xa (FXa) activity and their correlations. Sixteen pregnant women were administered dalteparin or tinzaparin from early pregnancy until six weeks postpartum. The anticoagulant effect was determined immediately before and three hours after injection. The target anti-FXa activity was 0.1-0.2 IU/ml pre-injection and less than 0.45 IU/ml post-injection. Thrombelastography variables were assessed at the same time. The correlations between anti-FXa activity and thrombelastography variables were modest, with correlation coefficients at 0.4-0.5. The thrombelastography variable best correlated to anti-FXa activity <0.1 IU/ml was thrombelastography K. The area under the receiver operating characteristic curve for thrombelastography K against anti-FXa activity <0.1 IU/ml was 0.77 (95% confidence intervals 0.64 to 0.91) with sensitivity 0.76 and specificity 0.81. The correlations increased as pregnancy progressed. The anticoagulant effect of LMWH can be measured either by analysis of anti-FXa activity or with thrombelastography. However, the correlation between the two methods is too low to allow replacement of one by the other. Further studies are necessary to determine which of the methods best predicts anticoagulant effect and increased risk of bleeding complications related to delivery or regional anaesthesia.

Livedoid vasculopathy is a rare, chronic thrombo-occlusive disease characterized by recurrent livedoid skin changes, atrophic white plaques, and ulceration. It most commonly affects the dermal vessels of the distal lower extremities, ankles, and feet, bilaterally. While it is commonly associated with hypercoagulable states, systemic autoimmune diseases, and malignancies, we report a case of a previously healthy 31-year-old female with a history of moderate COVID-19 infection during pregnancy, two years before the onset of livedoid skin changes. The patient presented to a hematologist with a two-month history of erythematous to violaceous macules and patches on the dorsum of the feet, ankles, and lower extremities, along with mild ankle swelling. Multiple punch biopsies of the affected skin demonstrated thrombi, fibrinoid vascular changes, fibrosis, and hyalinization of the vessel walls - findings consistent with vasculopathy. Initial treatment included subcutaneous low-molecule weight heparin (dalteparin). This case highlights the importance of early recognition, the performance of a skin biopsy with subsequent histopathologic diagnosis, and appropriate management of this rare, but potentially debilitating condition.

Headaches in pregnancy are a common occurrence, and most differentials are benign but cerebral venous thrombosis (CVT) is a life-threatening secondary headache that is more common in pregnancy and postpartum. CVT is caused by an occlusion of the dural venous sinus and/or cerebral veins and presents with various non-specific presentations and has numerous causes and risk factors which make clinical diagnosis difficult. A woman in her late 30s was diagnosed with extensive CVT at 34 weeks gestation after reporting a persistent headache, visual disturbance and intermittent right-sided paraesthesia. This was her second pregnancy and it had been classed as high risk due to body mass index >40 and history of caesarean section. The woman was being managed in the joint obstetric-endocrinology clinic due to gestational diabetes. Diagnosis of CVT was made on magnetic resonance venogram, which revealed a dural sinus thrombosis involving the left transverse, left sigmoid, left jugular bulb and upper part of left internal jugular vein. She was referred to a tertiary centre for joint care of neurology and obstetrics. Treatment with a two times per day dosing regimen of dalteparin was commenced until elective caesarean section at 37 weeks gestation, after which treatment was changed to warfarin therapy for a further 6 months. Her follow-up recovery was good; she remains asymptomatic. This case highlights difficulties in detecting CVT and treatment of CVT in the third trimester of pregnancy.