Secreted proteins, such as hormones or cytokines, are key mediators in multicellular organisms. Response of protein secretion based on transcriptional control is rather slow, as it requires transcription, translation and transport from the endoplasmic reticulum (ER) to the plasma membrane via the conventional protein secretion (CPS) pathway. An alternative regulation to provide faster response would be valuable. Here we present two genetically encoded orthogonal regulatory secretion systems, which rely on the retention of pre-synthesized proteins on the ER membrane (membER, released by a cytosolic protease) or inside the ER lumen (lumER, released by an ER-luminal protease), respectively, and their release by the chemical signal-regulated proteolytic removal of an ER-retention signal, without triggering ER stress due to protein aggregates. Design of orthogonal chemically-regulated split proteases enables the combination of signals into logic functions. Its application was demonstrated on a chemically regulated therapeutic protein secretion and regulated membrane translocation of a chimeric antigen receptor (CAR) targeting cancer antigen. Regulation of the ER escape represents a platform for the design of fast-responsive and tightly-controlled modular and scalable protein secretion system for mammalian cells.

Osteoarthritis is age-related and the most common form of arthritis. The main characteristics of the disease are progressive loss of cartilage and secondary synovial inflammation, which finally result in pain, joint stiffness, and functional disability. Similarly, joint degeneration is characteristic of systemic inflammatory diseases such as rheumatoid arthritis and gout, with the associated secondary type of osteoarthritis. Studies suggest that inflammation importantly contributes to the progression of the disease. Particularly, cytokines TNFα and IL-1β drive catabolic signaling in affected joints. IL-1β is a product of inflammasome activation. Inflammasomes are inflammatory multiprotein complexes that propagate inflammation in various autoimmune and autoinflammatory conditions through cell death and the release of inflammatory cytokines and damage-associated molecule patterns. In this article, we review genetic, marker, and animal studies that establish inflammasomes as important drivers of secondary arthritis and discuss the current evidence for inflammasome involvement in primary osteoarthritis. The NLRP3 inflammasome has a significant role in the development of secondary osteoarthritis, and several studies have provided evidence of its role in the development of primary osteoarthritis, while other inflammasomes cannot be excluded. Inflammasome-targeted therapeutic options might thus provide a promising strategy to tackle these debilitating diseases.

Background: Corynebacterium spp. is a rare culprit in periprosthetic joint infections (PJIs), with limited data available on outcomes and appropriate treatment course. The aim of this study was to evaluate the success rate of a clinical cohort of patients with PJI, where Corynebacterium spp. was the causative organism (CPJI), treated according to an institutional algorithm based upon European Bone and Joint Infection Society guidelines. Methods: From the institutional bone infection registry, 44 patients treated for CPJI between 2007 and 2023 were identified. CPJIs were divided into 2 groups according to the isolated microbes: monomicrobial (14 [32%]) and polymicrobial (30 [68%]). Patients were treated with debridement, antibiotics, and implant retention (DAIR; 14 [32%]) or with 1- or 2-stage implant exchange (reimplantation group; 30 [68%]). In 13 (30%) cases, antibiotic combination with rifampicin was used. Results: Out of 44 patients, 4 required further treatment. In monomicrobial CPJI, the treatment course was successful in all patients, whereas in polymicrobial CPJI it was successful in 87%. Antibiotic combination including rifampicin was used in 4 monomicrobial cases (29%) and 9 polymicrobial (30%) cases. In the polymicrobial group, DAIR was successful in 90% (9/10), while the reimplantation group had an 85% (17/20) success rate. Conclusions: In contrast with the previously published papers on CPJI, the results in our cohort were good, with the total cure rate being 91%. The cure rate was slightly lower in the polymicrobial group compared with the monomicrobial: 87% and 100%, respectively. Surgical therapy according to the established institutional algorithm resulted in a high success rate.

Introduction: Greater trochanteric pain syndrome (GTPS) denotes several disorders around the lateral aspect of the hip. GTPS may develop in native hips as well as after total hip arthroplasty (THA). It is estimated that 5−12% of patients suffer from GTPS after primary THA. Despite the prevalence of GTPS, it is hard to diagnose and manage it properly. The VISA-G questionnaire was developed as a patient-reported outcome measurement tool for evaluation of GTPS. The aims of the present study were to evaluate the reliability of the VISA-G Slovenian and its construct and criterion validity. Methods: After the finalization of the VISA-G Slovenian translation procedure, 59 patients with a painful trochanteric region planned for THA filled in the VISA-G Slovenian at the hospital on two occasions 5−7 days apart. On the first occasion, each patient also filled in the EQ-5D-5L questionnaire and the Harris Hip Score (HHS) was completed by the physiotherapist. Results: The VISA-G Slovenian was found to have a test-retest reliability of ICC 0.977; 95% CI [0.96; 0.986]. Internal consistency was assessed with Cronbach’s alpha 0.79. The statistically significant, but low, correlation between the HHS and VISA-G (r=0.48) was obtained. Concurrent validity of the VISA-G with the EQ-5D-5L showed moderate to strong correlations in Mobility, Self-Care, Usual Activities, Pain, EQ-5D-5L Index and EQ VAS, but low correlation in the Anxiety subscale. No floor and ceiling effect were obtained. Conclusions: The VISA-G Slovenian has excellent psychometric properties needed to measure gluteal tendinopathy-related disability of patients in Slovenia. Thus, we recommend using the questionnaire for measuring trochanteric hip pain.

For clinicians dealing with such infections. Case: A 64-year-old male patient sustained a fracture of the humeral diaphysis on falling from a bicycle. During surgery, pus drainage from the intramedullary canal indicated infection, and cultures were positive for pansensitive Clostridium perfringens. After initial stabilization, imaging showed inadequate fragment contact, leading to referral to our bone infection unit. A revision surgery with plate osteosynthesis was performed. Intravenous and oral antibiotic therapy was administered. Oral antibiotics were continued until 12 weeks postoperatively. At the 26-month follow-up, the patient presented with a good functional outcome....