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contralateral control ulnae, and observed that IL-6 KO resulted in only modest alterations to the gene expression response to stress fracture (SFx). Wnt1 was more highly upregulated in IL-6 KO SFx callus at both day 1 (fold change 12.5 in KO vs. 5.7 in WT) and day 3 (fold change 4.7 in KO vs. 1.9 in WT). Finally, using tibial compression to induce bone formation without bone injury, we found that IL-6 KO directly impacted osteoblast function, increasing the propensity for woven bone formation. In summary, we report that IL-6 knockout enhanced formation of callus and bone following stress fracture injury, likely through direct action on the osteoblast’s ability to produce woven bone. This suggests a novel role of IL-6 as a suppressor of intramembranous bone formation.Clostridioides difficile is the main cause of healthcare-associated diarrhea worldwide. It is proposed that certain C. difficile toxinotypes with distinct pathogenicity locus (PaLoc) variants are associated with disease severity and outcomes. Additionally, few studies have described the common C. difficile toxinotypes, and also little is known about the tcdC variants in Iranian isolates. We characterized the toxinotypes and the tcdC genotypes from a collection of Iranian clinical C. difficile tcdA+B+ isolates with known ribotypes (RTs). Fifty C. difficile isolates with known RTs and carrying the tcdA and tcdB toxin genes were analyzed. Toxinotyping was carried out based on a PCR-RFLP analysis of a 19.6 kb region encompassing the PaLoc. Genetic diversity of the tcdC gene was determined by the sequencing of the gene. Of the 50 C. difficile isolates investigated, five distinct toxinotypes were recognized. Toxinotypes 0 (33/50, 66%) and V (11/50, 22%) were the most frequently found. C. difficile isolates of the toxinotype 0 mostly belonged to RT 001 (12/33, 36.4%), whereas toxinotype V consisted of RT 126 (9/11, 81.8%). The tcdC sequencing showed six variants (35/50, 70%); tcdC-sc3 (24%), tcdC-A (22%), tcdC-sc9 (18%), tcdC-B (2%), tcdC-sc14 (2%), and tcdC-sc15 (2%). The remaining isolates were wild-types (15/50, 30%) in the tcdC gene. The present study demonstrates that the majority of clinical tcdA+B+ isolates of C. difficile frequently harbor tcdC genetic variants. We also found that the RT 001/toxinotype 0 and the RT 126/toxinotype V are the most common types among Iranian isolates. Further studies are needed to investigate the putative association of various tcdC genotypes with CDI severity and its recurrence.Clostridioides difficile is an obligate anaerobe ubiquitous in the environment and is of particular interest in the healthcare setting as a cause of healthcare associated infection usually presenting with colitis. Extracolonic manifestations of C. difficile infection are less common with only rare reports of septic arthritis primarily in the setting of relative or overt immunocompromise. This report details the case of a 31-year-old immunocompetent male presenting with clinical features of septic arthritis, three weeks post right knee anterior cruciate ligament (ACL) reconstruction using a native hamstring tendon graft. Phenazine methosulfate clinical trial C. difficile was isolated from two different samples of the synovial tissue from a subsequent arthroscopic washout and synovectomy. The ACL graft was retained. The isolate underwent whole genome sequencing and was found to be tcdA and tcdB gene deficient. Susceptibility testing showed susceptibility to benzylpenicillin and metronidazole. The patient received a two-week course of intravenous benzylpenicillin and four weeks of oral metronidazole. At one-year post cessation of antibiotics the patient has no clinical evidence of recurrence. This is the first known reported case of C. difficile septic arthritis in an immunocompetent patient. It demonstrates successful treatment of post-ACL septic arthritis with a graft retention strategy.

TNF receptor-associated periodic syndrome (TRAPS) is a rare autoinflammatory disease caused by dominant mutation of the TNF super family receptor 1A (TNFRSF1A) gene. Data regarding long-term treatment outcomes are lacking.

To assess correlations of genotype-phenotypes in patients with TRAPS, as defined by the International Study Group for Systemic Autoinflammatory Diseases (INSAID) classification and Eurofever criteria, with treatment responses.

Data from 226 patients with variants of the TNFRSF1A gene and enrolled in the Eurofever registry were classified according to the INSAID classification in groups A (pathogenic or likely pathogenic variants), B (variants of uncertain significance or not classified variants), and C (benign or likely benign variants) and screened for Eurofever criteria.

In group A (127 of 226 patients, 56%), all fulfilled Eurofever criteria and 20 of 127 patients (16%) developed AA amyloidosis. In group B (78 of 226 patients, 35%), 40 of 78 patients (51%) did not fulfill Eurofeve fulfilling Eurofever criteria and group C, and colchicine may be preferable as the first maintenance treatment.

Uterine contractions are recognized as a potential manifestation of anaphylaxis, but literature on their proper management is limited. It is widely recognized that anaphylactic reactions can cause uterine contractions, but little is known about their optimal management.

Review potential treatments for painful uterine contractions associated with anaphylaxis or mast cell activation.

This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. PubMed, Embase, and Cochrane were searched in English, French, and Spanish for reports of uterine anaphylaxis published up until July 2020. The search strategy used a combination of Boolean operators and included the following Medical Subject Heading terms and keywords hypersensitivity; anaphylaxis; mastocytosis; uterus; uterine contraction; pelvic pain; labor, obstetric; labor, premature; and endometriosis.

This systematic review identified 19 studies reporting on 31 cases of painful uterine contras and on their optimal management. In the absence of counterindication, use of a beta-2 agonist and premedication with nonsteroidal anti-inflammatory drugs could be the preferred options.

There is a lack of quality data on painful uterine contractions occurring in the context of anaphylactic reactions and on their optimal management. In the absence of counterindication, use of a beta-2 agonist and premedication with nonsteroidal anti-inflammatory drugs could be the preferred options.