Abstract Background Interest exists in finding alternatives to current management strategies in periprosthetic joint infections (PJI), which typically include a two-stage revision with placement of ...an antibiotic spacer and delayed placement of a new implant. We studied the efficacy of autoclaving, ultrasonication, and mechanical scrubbing for sterilization and biofilm eradication on infected cobalt-chrome (CoCr) discs. Methods Strains of Staphylococcus aureus MRSA252 or Staphylococcus epidermidis RP62A were grown on the discs. For each strain, discs were divided into 5 groups (5 discs each) and exposed to several sterilization and biofilm eradication treatments: (1) autoclave, (2) autoclave + sonication; (3) autoclave + saline scrub; (4) autoclave + 4% chlorhexidine (CHC) scrub; and (5) autoclave + sonication + CHC scrub. Sterilization and biofilm eradication were quantified with crystal violet assays and scanning electron microscopy (SEM). Results Relative to non-treated controls, autoclaving alone reduced biofilm load by 33.9% and 54.7% for MRSA252 and RP62A strains, respectively. Biofilm removal was maximized with the combined treatment of autoclaving and CHC-scrub for MRSA252 (100%) and RP62A (99.5%). The addition of sonication between autoclaving and CHC-scrubbing resulted in no statistically significant improvement in biofilm removal. High resolution SEM revealed no cells or biofilm for this combined treatment. Conclusions Using two commonly encountered bacterial strains in PJI, infected cobalt-chrome discs were sterilized and eradicated of residual biofilm with a combination of autoclaving and CHC scrubbing.
Abstract Background Primary total knee arthroplasty (TKA) for valgus knee deformities can be challenging. Soft tissue releases are often necessary to achieve a well-balanced knee. We reviewed the ...frequency of soft tissue releases including lateral retinacular release (LRR) as it pertains to pre-operative limb alignment. Post-operatively, we evaluated limb alignment, knee range of motion (ROM), and complications. Methods From 2010 to 2016, 214 primary TKAs with valgus deformity were performed by a single surgeon. 181 patients had an average follow up of 24 months. For these patients, clinical data including pre- and post-operative ROM, complications, and revision rates were collected. Soft tissue releases, pre and post-operative limb axis deviation, and level of prosthetic constraint were recorded in all patients regardless of length of follow up. Results There were 33 knees (15%) that required 1 release, 69 knees (32%) required 2 releases, 81 knees (38%) required 3 releases, and 31 knees (14%) that required 4 or more releases. The average preoperative mechanical axis was 9.4°, and the average post-operative mechanical axis was 0.13°. There were 85 knees (40%) that required a LRR. Increased severity of pre-operative deformity correlated with the need for more soft tissue release, but did not correlate with the need for LRR. No knees were revised for instability. No patella complications resulted from LRR. Conclusion Selective soft tissue release for primary valgus TKA was effective without increasing prosthetic constraint. Severe deformities required more soft tissue releases. Lateral retinacular release can be frequently utilized with minimal complications.
Abstract Antibiotic spacer designs have proven effective at eradicating infection during a two-stage revision arthroplasty. Temporary reuse of the steam-sterilized femoral component and a new all ...poly tibia component has been described as an effective articulating antibiotic spacer, but sterility concerns persist. Six explanted cobalt chrome femurs from patients with grossly infected TKA's and six stock femurs inoculated with different bacterial species were confirmed to be bacteria-free after autoclaving under a standard gravity-displacement cycle. The effect of steam sterilization on cobalt chrome fragments contaminated with MRSA biofilm was analyzed microscopically to quantify remaining biofilm. The autoclave significantly reduced the biofilm burden on the cobalt chrome fragments. This study confirmed sterility of the femur after a standard gravity–displacement cycle (132 °C, 27 PSIG, 10 minutes).
The risk of periprosthetic joint infection (PJI) subsequently developing at a second site after an initial PJI has been documented to be approximately 18%-20%. To the best of our knowledge, only a ...single study has evaluated the incidence in ipsilateral joints and if the risk of infection would be different. While this was the only other study to evaluate this specific subfield, we set to re-evaluate and confirm the incidence of developing a second PJI in the setting of an ipsilateral prosthesis and possible associated risk factors.
We retrospectively reviewed all patients treated surgically for lower-extremity PJI at our institution by 5 surgeons from 2015 to 2021. Patients with multiple arthroplasties on the ipsilateral extremity were included. Time between initial and subsequent infection, risk factors for infection, bacterial source, and bacteremia were identified.
Of 392 patients treated for PJI, 179 (45.6%) had multiple prosthetic joints. Forty-seven of those 179 patients had ipsilateral extremity prosthesis, which made up our study population. Three patients (6.4%) developed a separate infection at an ipsilateral TJA. In total, 10 patients (21.3%) developed a separate PJI. Patients on immunosuppressants had a higher likelihood of developing second PJI on the ipsilateral extremity (P = .02).
Our study identified the risk of developing an ipsilateral PJI to not be any greater than that in patients with contralateral TJAs. It appears that sharing an extremity with an infected TJA does not pose substantially increased risk of subsequent infection of the un-involved prosthesis. Furthermore, immunosuppressant use may increase the risk of a separate ipsilateral PJI.
Total hip arthroplasty (THA) for developmental hip dysplasia (DDH) often requires a subtrochanteric shortening derotational osteotomy (SDO) to limit leg lengthening, mitigate risk of peripheral nerve ...palsy, and reduce excessive femoral anteversion. Few studies exist detailing long-term clinical outcomes and survivorship. The aim of this study is to analyze the long-term outcomes and survivorship of an SDO-THA cohort.
We retrospectively reviewed all patients who underwent cementless THA with femoral osteotomy due to Crowe I-IV DDH between 1991 and 2001. Primary outcome measures included revision surgery for any reason and functional outcome measures using modified Harris Hip scores. Secondary outcome measures included mode of implant failure and radiographic assessment for osteotomy union, polyethylene wear, osteolysis, and implant loosening.
Our review resulted in 24 SDO-THA cases in 20 patients with a mean follow-up of 19 years (range, 8-27 years). Overall survivorship was 67%. All 8 failures were treated with acetabular revision at a mean time to revision of 11 years (range, 1-25 years). Of the failures, there were 5 cases due to polyethylene wear (62.5%), 2 cases due to acetabular loosening (25%), and 1 case due to recurrent instability (12.5%). The mean postoperative modified Harris Hip score was 76 (range, 52-91) with long-term improvement of 43 points maintained (P < .001).
THA with SDO can produce durable long-term outcomes for the patient with DDH. It is important to consider some common reasons for revision, namely polyethylene wear and osteolysis, acetabular loosening, and recurrent acetabular dislocations.
Background During IgE-mediated immediate hypersensitivity reactions, vascular endothelial cells permeabilize in response to mast cell mediators. We have demonstrated previously that patients and mice ...with signal transducer and activator of transcription 3 (STAT3) mutations (autosomal dominant hyper-IgE syndrome AD-HIES) are partially protected from anaphylaxis. Objectives We sought to study the mechanism by which STAT3 contributes to anaphylaxis and determine whether small-molecule inhibition of STAT3 can prevent anaphylaxis. Methods Using unaffected and STAT3-inhibited or genetic loss-of-function samples, we performed histamine skin prick tests, investigated the contribution of STAT3 to animal models of anaphylaxis, and measured endothelial cell permeability, gene and protein expression, and histamine receptor–mediated signaling. Results Although mouse mast cell degranulation was minimally affected by STAT3 blockade, mast cell mediator–induced anaphylaxis was blunted in Stat3 mutant mice with AD-HIES and in wild-type mice subjected to small-molecule STAT3 inhibition. Histamine skin prick test responses were diminished in patients with AD-HIES. Human umbilical vein endothelial cells derived from patients with AD-HIES or treated with a STAT3 inhibitor did not signal properly through Src or cause appropriate dissolution of the adherens junctions made up of the proteins vascular endothelial–cadherin and β-catenin. Furthermore, we found that diminished STAT3 target microRNA17-92 expression in human umbilical vein endothelial cells from patients with AD-HIES is associated with increased phosphatase and tensin homolog (PTEN) expression, which inhibits Src, and increased E2F transcription factor 1 expression, which regulates β-catenin cellular dynamics. Conclusions These data demonstrate that STAT3-dependent transcriptional activity regulates critical components for the architecture and functional dynamics of endothelial junctions, thus permitting vascular permeability.
Background Identifying genetic syndromes that lead to significant atopic disease can open new pathways for investigation and intervention in allergy. Objective We sought to define a genetic syndrome ...of severe atopy, increased serum IgE levels, immune deficiency, autoimmunity, and motor and neurocognitive impairment. Methods Eight patients from 2 families with similar syndromic features were studied. Thorough clinical evaluations, including brain magnetic resonance imaging and sensory evoked potentials, were performed. Peripheral lymphocyte flow cytometry, antibody responses, and T-cell cytokine production were measured. Whole-exome sequencing was performed to identify disease-causing mutations. Immunoblotting, quantitative RT-PCR, enzymatic assays, nucleotide sugar, and sugar phosphate analyses, along with matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry of glycans, were used to determine the molecular consequences of the mutations. Results Marked atopy and autoimmunity were associated with increased TH 2 and TH 17 cytokine production by CD4+ T cells. Bacterial and viral infection susceptibility were noted along with T-cell lymphopenia, particularly of CD8+ T cells, and reduced memory B-cell numbers. Apparent brain hypomyelination resulted in markedly delayed evoked potentials and likely contributed to neurologic abnormalities. Disease segregated with novel autosomal recessive mutations in a single gene, phosphoglucomutase 3 ( PGM3 ). Although PGM3 protein expression was variably diminished, impaired function was demonstrated by decreased enzyme activity and reduced uridine diphosphate–N-acetyl-D-glucosamine, along with decreased O- and N-linked protein glycosylation in patients' cells. These results define a new congenital disorder of glycosylation. Conclusions Autosomal recessive hypomorphic PGM3 mutations underlie a disorder of severe atopy, immune deficiency, autoimmunity, intellectual disability, and hypomyelination.
Background We investigated whether the outcome of bone disease of primary hyperparathyroidism differs in multiple endocrine neoplasia type 1–associated disease and sporadic hyperparathyroidism at ...1-year postoperatively. Methods Multiple endocrine neoplasia type 1/hyperparathyroidism and sporadic hyperparathyroidism patients who underwent parathyroidectomy from 1990 to 2013 and dual-energy x-ray absorptiometry at baseline and 1-year postoperatively were included. Preoperative and postoperative dual-energy x-ray absorptiometry measurements (bone mineral density and Z-score at the lumbar spine, total hip, and femoral neck) were analyzed. Results We evaluated 14 multiple endocrine neoplasia type 1/hyperparathyroidism and 104 sporadic hyperparathyroidism patients. The preoperative Z-scores at the lumbar spine, total hip, and femoral neck were lower in the multiple endocrine neoplasia type 1/hyperparathyroidism group ( P = .05, P = .04, and P = .0081, respectively). Comparison of preoperative and postoperative dual-energy x-ray absorptiometry measurements demonstrated that the multiple endocrine neoplasia type 1/hyperparathyroidism group had a significantly higher Z-score at the lumbar spine ( P = .02) at 1 year after operation, whereas the sporadic hyperparathyroidism group had a significantly higher Z-score at the lumbar spine, total hip, and femoral neck ( P < .0001, P = .0004, and P = .0001) and higher bone mineral density at the lumbar spine ( P = .0001). Conclusion Long-term monitoring of these patients using dual-energy x-ray absorptiometry is required to assess outcomes and facilitate decisions on the timing of operative intervention.
Objectives To compare registry and electronic health record (EHR) data mining approaches for cohort ascertainment in patients with pediatric pulmonary hypertension (PH) in an effort to overcome some ...of the limitations of registry enrollment alone in identifying patients with particular disease phenotypes. Study design This study was a single-center retrospective analysis of EHR and registry data at Boston Children's Hospital. The local Informatics for Integrating Biology and the Bedside (i2b2) data warehouse was queried for billing codes, prescriptions, and narrative data related to pediatric PH. Computable phenotype algorithms were developed by fitting penalized logistic regression models to a physician-annotated training set. Algorithms were applied to a candidate patient cohort, and performance was evaluated using a separate set of 136 records and 179 registry patients. We compared clinical and demographic characteristics of patients identified by computable phenotype and the registry. Results The computable phenotype had an area under the receiver operating characteristics curve of 90% (95% CI, 85%-95%), a positive predictive value of 85% (95% CI, 77%-93%), and identified 413 patients (an additional 231%) with pediatric PH who were not enrolled in the registry. Patients identified by the computable phenotype were clinically distinct from registry patients, with a greater prevalence of diagnoses related to perinatal distress and left heart disease. Conclusions Mining of EHRs using computable phenotypes identified a large cohort of patients not recruited using a classic registry. Fusion of EHR and registry data can improve cohort ascertainment for the study of rare diseases. Trial registration ClinicalTrials.gov : NCT02249923.
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