Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder caused by several distinct defects in genes responsible for ciliary beating, leading to defective mucociliary clearance often associated with randomization of left/right body asymmetry. Individuals with PCD caused by defective radial spoke (RS) heads are difficult to diagnose owing to lack of gross ultrastructural defects and absence of situs inversus. Thus far, most mutations identified in human radial spoke genes (RSPH) are loss-of-function mutations, and missense variants have been rarely described. We studied the consequences of different RSPH9, RSPH4A, and RSPH1 mutations on the assembly of the RS complex to improve diagnostics in PCD. We report 21 individuals with PCD (16 families) with biallelic mutations in RSPH9, RSPH4A, and RSPH1, including seven novel mutations comprising missense variants, and performed high-resolution immunofluorescence analysis of human respiratory cilia. Missense variants are frequent genetic defects in PCD with RS defects. Absence of RSPH4A due to mutations in RSPH4A results in deficient axonemal assembly of the RS head components RSPH1 and RSPH9. RSPH1 mutant cilia, lacking RSPH1, fail to assemble RSPH9, whereas RSPH9 mutations result in axonemal absence of RSPH9, but do not affect the assembly of the other head proteins, RSPH1 and RSPH4A. Interestingly, our results were identical in individuals carrying loss-of-function mutations, missense variants, or one amino acid deletion. Immunofluorescence analysis can improve diagnosis of PCD in patients with loss-of-function mutations as well as missense variants. RSPH4A is the core protein of the RS head.

Background Limb lengthening with magnetically driven intramedullary lengthening nails is a fast-developing field and represents an alternative to external fixators. Although previous studies have assessed the application of magnetically driven intramedullary lengthening nails, these studies have been heterogenous regarding the nailing approach, the bone treated, and the implant type; they also have

Introduction: D-dimer is a diagnostic criterion for periprosthetic joint infection (PJI) of the Musculoskeletal Infection Society (MSIS) in 2018. The aim of this study was to evaluate the serum D-dimer values in comparison to C-reactive protein (CRP) and interleukin-6 (IL-6) for the diagnosis of PJI. Materials and Methods: We included 119 patients (50 women, 69 men; 71 knees, 48 hips) undergoing revision arthroplasty with preoperative assessment of CRP, IL-6, and serum D-dimer. Cases were classified as infected or aseptic based on the MSIS criteria of 2018. Receiver operating curves and Youden’s index were used to define an ideal cut-off value and sensitivity and specificity for the individual parameters, and respective combinations were calculated using cross-tables. Results: The median D-dimer level (2320 vs. 1105 ng/mL; p < 0.001), the median CRP level (4.0 vs. 0.5 mg/dL; p < 0.001), and the median IL-6 level (21.0 vs. 5.0 pg/mL; p < 0.001) were significantly higher in the group of PJI compared to the group with aseptic failure. The calculated optimal cut-off values were 2750 ng/mL (AUC 0.767) for D-dimer, 1.2 mg/dL (AUC 0.914) for CRP, and 10.0 pg/mL (AUC 0.849) for IL-6. D-dimer showed a sensitivity of 38% and specificity of 94%, whereas the CRP and IL-6 had sensitivities of 88% and 76%, and specificities of 87% and 92%, respectively. Conclusion: In comparison with CRP and IL-6, serum D-dimer showed low sensitivity and specificity in our cohort. While CRP and IL-6 combination had the highest sensitivity, a combination of Il-6 and D-dimer or CRP and IL-6 had the highest specificity.

Purpose Megaprosthetic distal femoral reconstruction (DFR) is a limb-salvage procedure to address bone loss following two-stage revision for periprosthetic knee joint infection (PJI). The purpose of this study was to analyze the survival of DFR compared to hinged total knee arthroplasty (TKA). It was hypothesized that DFR was associated with a poorer survival. Methods In this retrospective single-center study, 97 subjects who underwent two-stage revision of chronic knee PJI were included. Among these, 41 were DFR. The diagnosis of PJI was established using the Musculoskeletal Infection Society (MSIS) criteria. Implant survival was calculated using Kaplan–Meier method and compared with the log-rank test as well as multivariate Cox regression at a minimum follow-up period of 24 months. Results The median follow-up period was 59 (interquartile range (IQR) 45–78) months. Overall, 24% (23/97) of patients required revision surgery for infection. The infection-free survival of rotating hinge revision TKA was 93% (95% Confidence Interval (CI) 86–100%) at five years compared to 50% (95% CI 34–66%) for DFR. In multivariate analysis, the risk factors for reinfection were DFR reconstruction (HR 4.7 (95% CI 1–22), p = 0.048), length of megaprosthesis (HR 1.006 (95% CI 1.001–1.012), p = 0.032) and higher BMI (HR 1.066, 95% CI 1.018–1.116), p = 0.007). 10% (4/41) of patients undergoing DFR underwent amputation to treat recurrent infection. Conclusion Megaprosthetic DFR as part of a two-stage exchange for PJI is a salvage treatment that has a high risk for reinfection compared to non-megaprosthetic TKA. Patients must therefore be counseled accordingly. Level of evidence Retrospective observational study, Level IV.

Different approaches for intramedullary lengthening nails can be used in children and adolescents to correct leg length discrepancy with or without concomitant deformities. The treatment is limited by the size of the available nails, the residual growth and extent of the deformity. Larger trials will be needed to further validate the application of lengthening nails in skeletally immature patients.