Comparison of drug retention of TNF inhibitors, other biologics and JAK inhibitors in RA patients who discontinued JAK inhibitor therapy.

OBJECTIVES: JAK Inhibitors (JAKi) are recommended DMARDs for patients with moderate-to-severe RA who failed first-line therapy with methotrexate. There is a lack of data allowing an evidence-based choice of subsequent DMARD therapy for patients who had discontinued JAKi treatment. We aimed to compare the effectiveness of TNF inhibitor (TNFi) therapy vs JAKi vs other mode of action (OMA) biologic DMARD (bDMARD) in RA patients who were previously treated with a JAKi. METHODS: RA patients who discontinued JAKi treatment within the Swiss RA registry SCQM were included for this observational prospective cohort study. The primary outcome was drug retention for either TNFi, OMA bDMARD or JAKi. The hazard ratio for treatment discontinuation was calculated adjusting for potential confounders. A descriptive analysis of the reasons for discontinuation was performed. RESULTS: Four hundred treatment courses of JAKi were included, with a subsequent switch to either JAKi, TNFi or OMA bDMARD. The crude overall drug retention was higher in patients switching to another JAKi as compared with TNFi and comparable to OMA. A significant difference of JAKi vs TNFi persisted after adjusting for potential confounders. CONCLUSION: In a real-world population of RA patients who discontinued treatment with a JAKi, switching to another JAKi resulted in a higher drug retention than switching to a TNFi. A switch to a second JAKi seems an effective therapeutic option.

Beyond the visible spectrum - applying 3D multispectral full-body imaging to the VirtoScan system.

Multispectral photography offers a wide range of applications for forensic investigations. It is commonly used to detect latent evidence and to enhance the visibility of findings. Additionally, three-dimensional (3D) full-body documentation has become much easier and more affordable in recent years. However, the benefits of performing 3D imaging beyond the visible (VIS) spectrum are not well known, and the technique has not been widely used in forensic medical investigations. A multicamera setup was used to employ multispectral photogrammetry between 365 and 960 nm in postmortem investigations. The multicamera setup included four modified digital cameras, ultraviolet (UV) and near-infrared (NIR) light sources and supplemental lens filters. Full-body documentation was performed in conjunction with the use of a medical X-ray computed tomography (CT) scanner to automate the imaging procedure. Textured 3D models based on multispectral datasets from four example cases were reconstructed successfully. The level of detail and overall quality of the 3D reconstructions varied depending on the spectral range of the image data. Generally, the NIR datasets showed enhanced visibility of vein patterns and specific injuries, whereas the UV-induced datasets highlighted foreign substances on the skin. Three-dimensional multispectral full-body imaging enables the detection of latent evidence that is invisible to the naked eye and allows visualization, documentation and analysis of evidence beyond the VIS spectrum.

Detectability of bloodstains after machine washing.

Bloodstains on textiles can provide useful information for the forensic reconstruction of a crime. Surprisingly, little is known about the applicability of bloodstain traces after a textile was machine washed. In this study, we investigated the effect of machine washing on bloodstains on both cotton and polyester cloths. The influence of the washing detergent, the type of washing machine, the washing temperature, and the duration of drying of the bloodstain prior to washing as well as the drying temperature was investigated. Additionally, the molecular analyses of a subsample of the experiments were conducted. We found that although the primary morphology of the traces is often blurred, the presence of blood on the textiles can still be detected in many cases. Blood can also be transmitted to previously blood-free textiles during the washing process, leading to a positive Luminol or Combur® reaction of these samples. When traces of blood can be detected via the Luminol reaction, a molecular identification of the blood donor was successful in 28% of the cases.

A new approach to the investigation of sexual offenses-cytoskeleton analysis reveals the origin of cells found on forensic swabs.

There are forensic inquiries in which an identification of epithelial cell types would provide important probative evidence. In cancer diagnosis, this information is yielded by histological examination of cytokeratin (Ck). Therefore, we tested 19 antibodies against different Cks (Ck1, Ck2e, Ck4, Ck5-6, Ck7, Ck8, Ck9, CK10, Ck13, Ck14, Ck15, Ck16, Ck17, Ck18, Ck19, Ck20, Ck903, PanCkAE1_3, and CAM5-2) on histological sections of epidermis, buccal mucosa, vaginal mucosa, penis, urogenital tract, and rectum and could identify two antigens unique to buccal-cell and vaginal-cell (Ck4) and skin epithelial-cell (Ck10) cytokeratin. Subsequently, we developed an immunocytological technique for distinguishing swabbed skin and mucosal cells up to at least 1 year after sampling. By the detection of the Ck4 and Ck10 mRNAs in biopsy and laser capture microdissection collected samples via quantitative real-time polymerase chain reaction, we were able to confirm our immunological findings. Hence, this study offers techniques to discriminate between skin and mucosal cells (buccal and vaginal) in forensic casework.

Prox-1 promotes invasion of kaposiform hemangioendotheliomas.

Kaposi's sarcoma (KS) is the most frequently occurring malignant tumor in patients infected with HIV. Recent studies have revealed that infection of vascular endothelial cells with KS-associated herpes virus in vitro results in a lymphatic reprogramming of these cells, with potent induction of the lymphatic marker genes podoplanin and vascular endothelial growth factor receptor-3, which is mediated by upregulation of the transcription factor Prox1. However, the potential effects of Prox1 expression on the biology of KS and, in particular, on the aggressive and invasive behavior of KS tumors in vivo have remained unknown. We stably expressed Prox1 cDNA in the two mouse hemangioendothelioma cell lines EOMA and Py-4-1, well-established murine models for kaposiform hemangioendothelioma. Surprisingly, we found that expression of Prox1 was sufficient to induce a more aggressive behavior of tumors growing in syngenic mice, leading to enhanced local invasion into the muscular layer and to cellular anaplasia in vivo, and increased migration rate in vitro. This enhanced malignant phenotype was associated with upregulation of several genes involved in proteolysis, cell adhesion, and migration. Together, these results indicate that Prox1 plays an important, previously unanticipated role in mediating the aggressive behavior of vascular neoplasms such as KS.

The use of a tunable light source (Mini-Crimescope MCS-400, SPEX Forensics) in dissecting microscopic detection of cryptic epithelial particles.

As skin particles are often deposited by even a single skin contact, the detection of skin debris is important for evidence collection and DNA testing. Unfortunately, even when a dissecting microscope is used by an experienced examiner, epidermal particles are often hard to find and these traces of evidence might escape DNA analysis. Fluorescence is defined as the property of absorbing short-wavelength light and emitting longer-wavelength light. By virtue of the fluorescence characteristics of many target materials, tunable light sources assist in the macroscopic search of crime scenes and items. We combined the dissecting microscope and an alternate light source to examine the fluorescence characteristics of skin and skin particles. In a comparative study, small skin scales were hidden between sand, fibers, and soil probes, and it proved possible to search more successfully with less time and effort. On staged casework exhibits, the efficiency of the screening aid was again tested and the usability of the new procedure shown.

Detection of colchicine by means of LC-MS/MS after mistaking meadow saffron for bear's garlic.

The accidental ingestion of plant material containing colchicines is a rare cause of lethal poisoning. The death of a married couple who mistook colchicines for Bear's garlic (Allium ursinum) and prepared the latter as a salad is the tragic topic of this article. After discussing the specificity of the histological findings, a chemicotoxicological method using liquid chromatographic mass spectrometric (LC-MS/MS) is presented. Toxicological analyses using LC-MS/MS revealed colchicine concentrations between 36.6 ng/mL and 98.3 ng/mL in the heart blood and between 22.7 ng/mL and 78.4 ng/mL in the femoral blood of the victims.