IL-1 ß gene (+3954 C/T, exon 5, rs1143634) and NOS2 (exon 22) polymorphisms associate with early aseptic loosening of arthroplasties.

Aseptic prosthetic loosening (APL) and prosthetic joint infections (PJI) are frequent complications of hip and knee implants. Polymorphisms of cytokines and nitric oxide (NO), key inflammatory molecules in APL and PJI pathogenesis, could explain individual susceptibility to these complications. Three cytokines (IL-1-a, IL-1-ß, TNF-α) and two nitric oxide synthase (NOS2, NOS3) genes polymorphisms were genotyped in 77 APL and 117 PJI patients and 145 controls with aseptic hip or knee implants that were implanted for > 16 years. Plasma cytokines and nitrate-nitrite (NOx) levels also were measured. The TT genotype and T allele of (+3954 C/T, exon 5, rs1143634) IL-1ß polymorphism were more frequent in APL patients compared to controls (P = 0.03 and P = 0.02, respectively). No genotypic associations in PJI patients were observed. Plasma IL-6, TNF-α and NOx were significantly different between APL and controls (P < 0.0001). Plasma IL-1ß and IL-6 were significantly higher in APL T allele carriers vs. non-carriers (P < 0.03). Knee implant (HR 2.488, 95% CI 1.307-4.739, P = 0.005), male gender (HR 2.252, 95% CI 1.121-4.525, P = 0.023), carriages of the TT genotype of the (+3954 C/T) IL-1ß polymorphism (HR 3.704, 95% CI 1.274-10.753, P = 0.016) and AA genotype of the (exon 22) NOS2 polymorphism (HR 3.509, 95% CI 1.266-9.709, P = 0.016) were independently associated with a shorter implant survival by Cox regression. No genotypic associations in PJI patients were observed. Genotyping of IL-1ß (+3954 C/T, exon 5, rs1143634) and NOS2 (exon 22) polymorphisms could be useful as predictors of early hip or knee APL.

Instability after reverse total shoulder arthroplasty: risk factors and how to avoid them.

Instability after RTSA (4'7%) remains a complication with limited salvage options... or not? We conducted a study of the incidence, predisposing factors, and treatment of RTSA instability to risk stratify patient and identify the most reliable treatment methods. We retrospectively searched for RTSAs performed between 2008 and 2017 at our institution by one surgeon using the same technique. We identified post- operative dislocations or symptoms of instability. 103 patients underwent 103 RTSAs (97 primary, 6 revision). 6 patients had 5 dislocations (3 in primary RTSAs, 3 in revision RTSAs). Mean time from surgery to diagnosis was 32.6 days (range, 10-60 days). One dislocation occurred immediately after surgery, 0 after falls, 3 from low-energy mechanisms of injury, and 2 without known inciting events. All dislocations were treated in the operating room; no dislocation was successfully treated with simple closed reduction in the clinic. Although dislocation after RTSA is uncommon, the risk is higher for patients with higher BMI and for patients undergoing revision surgery. The highest risk of instability occurs in RTSAs done for severe proximal humerus fracture; where the anatomy of the shoulder is changed. In these cases, approximately one in four patients will have a recurrent dislocation. In patients with persistent instability or with risk factors for instability, consideration should be given for use of larger glenospheres and increasing the lateral offset at the time of RTSA. Besides, peri- glenoid release, the suitable tension of the soft tissues tend to be the key of the stability.

The NOS3 (27-bp repeat, intron 4) polymorphism is associated with susceptibility to osteomyelitis.

Cytokines generate nitric oxide (NO) in osteoblasts and neutrophils through the induction of NO synthase isoforms, endothelial (NOS3) and inducible (NOS2), thereby producing bone loss. In osteomyelitis (OM), a chronic infection of the bone, homozygosity for the NOS3 (27-bp repeat, intron 4 polymorphism) 4 allele was significantly more frequent among the 80 patients than in 300 healthy controls (p=0.044). No significant differences were found for other polymorphisms of the NOS genes such as NOS3, the promoter (-786T/C), and the missense change (E298D) in exon 7, and for NOS2, the G/A substitution at position 37498 in exon 22, the (CCTTT)(n), and (TAAA)(n) micro-satellites and the -954G/C in the promoter. Serum NO levels were significantly higher only in the OM patients homozygous for the NOS3 (27-bp repeat, intron 4 polymorphism) 4 allele, compared to controls. In the presence of bacteria or bacterial products, the neutrophils of these patients produced more NO. However, immunolabelling of osteoblasts for NOS3 in biopsy tissues did not correlate with the carriage of a determined NOS polymorphism but with the presence of bone inflammation. This is the first report of an association between a NOS3 polymorphism and the risk of developing OM.