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Variants within genes encoding structural and regulatory elements of ligaments have been associated with musculoskeletal soft tissue injury risk. The role of intron 4‐exon 5 variants within the α1 chain of type V collagen (COL5A1) gene and genes of the transforming growth factor‐β (TGF‐β) family, TGFBR3 and TGFBI, was investigated on the risk of anterior cruciate ligament (ACL) ruptures. A case‐control genetic association study was performed on 210 control (CON) and 249 participants with surgically diagnosed ruptures (ACL), of which 147 reported a noncontact mechanism of injury (NON). Whole‐exome sequencing data were used to prioritize variants of potential functional relevance. Genotyping for COL5A1 (rs3922912 G>A, rs4841926 C>T, and rs3124299 C>T), TGFBR3 (rs1805113 G>A and rs1805117 T>C), and TGFBI (rs1442 G>C) was performed using Taqman SNP genotyping assays. Significant overrepresentation of the G allele of TGFBR3 rs1805113 was observed in CON vs ACL (P = .014) and NON groups (P = .021). Similar results were obtained in a female with the G allele (CON vs ACL: P = .029; CON vs NON: P = .016). The TGFBI rs1442 CC genotype was overrepresented in the female ACL vs CON (P = .013). Associations of inferred allele combinations were observed in line with the above results. COL5A1 intron 4‐exon 5 genomic interval was not associated with the risk of ACL ruptures. Instead, this novel study is the first to use this approach to identify variants within the TGF‐β signaling pathway to be implicated in the risk of ACL ruptures. A genetic susceptibility interval was identified to be explored in the context of extracellular matrix remodeling.

Background Up to a quarter of inpatients in high-income countries self-report beta-lactam allergy (BLA), which if incorrect, can increase use of alternative antibiotics that impact on bacterial resistance.. The epidemiology of BLA in low- and middle-income African countries is unknown. Methods Point-prevalence surveys were conducted at seven hospitals (adult, pediatric, government and private-funded, district- and tertiary-level) in Cape Town, South Africa between April 2019 and June 2021. Ward prescription records and interviews were conducted to identify BLA patients. De-labeling was attempted at the tertiary allergy clinic at Groote Schuur hospital. Findings A total of 1486 hospital inpatients were surveyed (1166 adults; 308 children). Only 48 (3.2%) patients self-reported a BLA with a higher rate amongst private- versus government-funded hospitals [6.3% vs 2.8%, p=0.014]. Using the PEN-FAST tool, only 10.4% (5/48) of self reported BLA patients were classified as high risk for true penicillin hypersensitivity. Antibiotics were prescribed to 70.8% (34/48) of self reported BLA patients, with 64.7% (22/34) receiving a beta-lactam. Despite three attempts to contact patients for de-labelling at the allergy clinic, only 3/36 underwent in vivo testing, with no positive results and one patient proceeded toa negative oral challenge. Interpretation Unlike high-income countries, self-reported BLA is low amongst inpatients in South Africa. The majority of self-reported BLA were low risk for type 1 hypersensitivity, but out-patient de-labeling efforts were largely unsuccessful. Funding None