Surgical approach significantly affects the complication rates associated with total hip arthroplasty.

AIMS: A variety of surgical approaches are used for total hip arthroplasty (THA), all with reported advantages and disadvantages. A number of common complications can occur following THA regardless of the approach used. The purpose of this study was to compare five commonly used surgical approaches with respect to the incidence of surgery-related complications. PATIENTS AND METHODS: The electronic medical records of all patients who underwent primary elective THA at a single large-volume arthroplasty centre, between 2011 and 2016, with at least two years of follow-up, were reviewed. After exclusion, 3574 consecutive patients were included in the study. There were 1571 men (44.0%) and 2003 women (56.0%). Their mean age and body mass index (BMI) was 63.0 years (sd 11.8) and 29.1 kg/m2 (sd 6.1), respectively. Data gathered included the age of the patient, BMI, the American Society of Anesthesiologists (ASA) score, estimated blood loss (EBL), length of stay (LOS), operating time, the presence of intra- or postoperative complications, type of complication, and the surgical approach. The approaches used during the study were posterior, anterior, direct lateral, anterolateral, and the northern approach. The complications that were recorded included prolonged wound drainage without infection, superficial infection, deep infection, dislocation, aseptic loosening, and periprosthetic fracture. Finally, the need for re-operation was recorded. Means were compared using analysis of variance (ANOVA) and Student's t-tests where appropriate and proportions were compared using the chi-squared test. RESULTS: A total of 248 patients had 263 complications related to the surgery, with an incidence of 6.94%. The anterior approach had the highest incidence of complications (8.5% (113/1329)) and the posterior approach had the lowest, at 5.85% (97/1657; p = 0.006). Most complications were due to deep infection (22.8%), periprosthetic fracture (22.4%), and prolonged wound drainage (21.3%). The rate of dislocation was 0.84% (14/1657) with the posterior approach and 1.28% (17/1329) with the anterior approach (p = 0.32). CONCLUSION: Overall, THA has a relatively low complication rate. However, the surgical approach plays a role in the incidence of complications. We found that the posterior approach had a significantly lower overall complication rate compared with the anterior approach, with an equal dislocation rate. Periprosthetic fracture and surgical site infection contributed most to the early complication rates. Cite this article: Bone Joint J 2019;101-B:646-651.

Can some early revision total hip arthroplasties be avoided?

AIMS: Studying the indications for revision total hip arthroplasty (THA) may enable surgeons to change their practice during the initial procedure, thereby reducing the need for revision surgery. The aim of this study was to identify and describe the potentially avoidable indications for revision THA within five years of the initial procedure. PATIENTS AND METHODS: A retrospective review of 117 patients (73 women, 44 men; mean age 61.5 years (27 to 88)) who met the inclusion criteria was conducted. Three adult reconstruction surgeons independently reviewed the radiographs and medical records, and they classified the revision THAs into two categories: potentially avoidable and unavoidable. Baseline demographics, perioperative details, and quality outcomes up to the last follow-up were recorded. RESULTS: A total of 60 revision THAs (51.3%) were deemed potentially avoidable and 57 (48.7%) were deemed unavoidable. The following were identified as avoidable factors: suboptimal positioning of the acetabular component (29; 48%), intraoperative fracture or a fracture missed on an intraoperative radiograph (20; 33%), early (less than two weeks) aseptic loosening (seven; 11.7%), and symptomatic leg length discrepancy of > 1 cm (four; 6.7%). CONCLUSION: A surprisingly large proportion of acute revision THAs are potentially avoidable. Surgeons must carefully evaluate the indications for revision THAs in their practice and identify new methods to address these issues. Cite this article: Bone Joint J 2019;101-B(6 Supple B):97-103.

2019 Frank Stinchfield Award: A comparison of prosthetic joint infection rates between direct anterior and non-anterior approach total hip arthroplasty.

AIMS: We studied the impact of direct anterior (DA) versus non-anterior (NA) surgical approaches on prosthetic joint infection (PJI), and examined the impact of new perioperative protocols on PJI rates following all surgical approaches at a single institution. PATIENTS AND METHODS: A total of 6086 consecutive patients undergoing primary total hip arthroplasty (THA) at a single institution between 2013 and 2016 were retrospectively evaluated. Data obtained from electronic patient medical records included age, sex, body mass index (BMI), medical comorbidities, surgical approach, and presence of deep PJI. There were 3053 male patients (50.1%) and 3033 female patients (49.9%). The mean age and BMI of the entire cohort was 62.7 years (18 to 102, sd 12.3) and 28.8 kg/m2 (13.3 to 57.6, sd 6.1), respectively. Infection rates were calculated yearly for the DA and NA approach groups. Covariates were assessed and used in multivariate analysis to calculate adjusted odds ratios (ORs) for risk of development of PJI with DA compared with NA approaches. In order to determine the effect of adopting a set of infection prevention protocols on PJI, we calculated ORs for PJI comparing patients undergoing THA for two distinct time periods: 2013 to 2014 and 2015 to 2016. These periods corresponded to before and after we implemented a set of perioperative infection protocols. RESULTS: There were 1985 patients in the DA group and 4101 patients in the NA group. The overall rate of PJI at our institution during the study period was 0.82% (50/6086) and decreased from 0.96% (12/1245) in 2013 to 0.53% (10/1870) in 2016. There were 24 deep PJIs in the DA group (1.22%) and 26 deep PJIs in the NA group (0.63%; p = 0.023). After multivariate analysis, the DA approach was 2.2 times more likely to result in PJI than the NA approach (OR 2.2 (95% confidence interval 1.1 to 3.9); p = 0.006) for the overall study period. CONCLUSION: We found a higher rate of PJI in DA versus NA approaches. Infection prevention protocols such as use of aspirin, dilute povidone-iodine lavage, vancomycin powder, and Gram-negative coverage may have been positively associated with diminished PJI rates observed for all approaches over time. Cite this article: Bone Joint J 2019;101-B(6 Supple B):2-8.

C5aR antagonist inhibits occurrence and progression of complement C5a induced inflammatory response of microglial cells through activating p38MAPK and ERK1/2 signaling pathway.

OBJECTIVE: To discuss the effect of complement C52 (C5a) and complement C5a receptor (C5aR) antagonists on inflammatory status of mouse microglial cells. MATERIALS AND METHODS: Primary culture was performed on mouse microglial cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to detect effect of C5a and C5aR antagonists on vitality of microglial cells. The effect of C5a and C5aR antagonists on mRNA expression of p38MAPK and ERK1/2 was determined using quantitative PCR (qPCR). Enzyme linked immunosorbent assay (ELISA) was used to measure expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in cells. RESULTS: According to quantitative fluorescent PCR, relative expression of p38MAPK and ERK1/2 mRNA in C5a antagonist treatment group was significantly higher compared to normal group and C5a+C5aR antagonist treatment group (p<0.05). However, the relative expression of the C5a+C5aR antagonist treatment group was significantly lower compared to that of the normal group (p<0.05). Expression of Iba1, p-p38MAPK and p-ERK1/2 proteins in C5a antagonist treatment group was significantly higher than normal group, in C5a+C5aR antagonist treatment group was lower than C5a antagonist treatment group (p<0.05). There were significant differences for IL-6 and TNF-α levels among 5 groups (p<0.05). Expression of cytokines was the highest in 100 nM C5a antagonist treatments and lowest in normal group. CONCLUSIONS: Complement C5a upregulated expression of inflammatory factors in mouse microglial cells, while C5aR antagonist inhibited occurrence and progression of inflammatory status. This was achieved by affecting transcriptional and translational processes of different factors in p38MAPK and ERK1/2 signaling pathway.

A government purchaser perspective: TennCare--strengthening the safety net.

BACKGROUND: On January 1, 1994, in response to escalating Medicaid costs, the State of Tennessee implemented TennCare, a statewide managed health care system for three population groups: Medicaid eligibles, uninsurable individuals, and people who lacked access to insurance through their place of employment. METHODS: Under the TennCare program, the State contracts with ten managed care organizations to provide a comprehensive benefit package to each enrollee. Preventive services are exempt from copayment or deductible requirements. Each patient is assigned to a primary care provider who is responsible for assuring that the enrollee receives preventive services. RESULTS: More than 400,000 previously uninsured and uninsurable persons now receive health care coverage through the TennCare program. An extensive quality assurance program monitors managed care organization service delivery, with particular emphasis on prevention and access. Effective case management, combined with an enrollment cap, have enabled the program to grow at a predictable rate, without exceeding the annual rate of growth of state revenues. CONCLUSIONS: The TennCare program has been successful in using the savings experienced during the shift from a fee-for-service to a managed care Medicaid program to expand coverage to previously uninsured populations.

Characterization of a soluble stable human cytomegalovirus protease and inhibition by M-site peptide mimics.

The human cytomegalovirus (HCMV) protease is a potential target for antiviral chemotherapeutics; however, autoprocessing at internal sites, particularly at positions 143 and 209, hinders the production of large quantities of stable enzyme for either screening or structural studies. Using peptides encompassing the sequence of the natural M-site substrate (P5-P5', GVVNA/SCRLA), we previously demonstrated that substitution of glycine for valine at the P3 position in the substrate abrogates processing by the recombinant protease in vitro. We now demonstrate that introduction of the V-to-G substitution in the P3 positions of the two major internal processing sites, positions 143 and 209, in the mature HCMV protease renders the enzyme stable to autoprocessing. When expressed in Escherichia coli, the doubly substituted protease was produced almost exclusively as the 30-kDa full-length protein. The full-length V141G, V207G (V-to-G changes at positions 141 and 207) protease was purified as a soluble protein by a simple two-step procedure, ammonium sulfate precipitation followed by DEAE ion-exchange chromatography, resulting in 10 to 15 mg of greater than 95% pure enzyme per liter. The stabilized enzyme was characterized kinetically and was indistinguishable from the wild-type recombinant protease, exhibiting Km and catalytic constant values of 0.578 mM and 13.18/min, respectively, for the maturation site (M-site) peptide substrate, GVVNASCRLARR (underlined residues indicate additions to or substitutions from peptides derived from the wild-type substrate). This enzyme was also used to perform inhibition studies with a series of truncated and/or substituted maturation site peptides. Short nonsubstrate M-site-derived peptides were demonstrated to be competitive inhibitors of cleavage in vitro, and these analyses defined amino acids VVNA, P4 through P1 in the substrate, as the minimal substrate binding and recognition sequence for the HCMV protease.

Peptide substrate cleavage specificity of the human cytomegalovirus protease.

The human cytomegalovirus UL80 gene encodes an 80-kDa precursor polyprotein whose N-terminal 256-amino acid domain is a protease. This enzyme cleaves a specific peptide bond that results in its own release from the precursor, as well as a peptide bond near the C terminus of the viral assembly protein. The latter cleavage is apparently required for encapsidation of the viral genomic DNA and maturation of the viral capsid. A series of peptide substrates, representing the assembly protein cleavage site, was used to study the enzyme's substrate requirements and specificity. It was found that efficient cleavage minimally required the amino acid residues spanning the P4 to P4' positions. Substitution at any of these residues adversely affected the reaction. Conservation of the hydrophobic residues at P3 and P4 was essential. In addition, cleavage of a peptide representing the protease domain release site was reduced almost 100-fold relative to cleavage of the assembly protein maturation site peptide substrate.

Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat. Characterization and comparison with tumor necrosis factor.

The diversity of infectious agents capable of inducing meningitis and blood-brain barrier (BBB) injury suggests the potential for a common host mediator. The inflammatory polypeptides, IL-1 and TNF, were tested in an experimental rat model as candidate mediators for induction of meningitis and BBB injury. Intracisternal challenge of rIL-1 beta into rats induced neutrophil emigration into cerebrospinal fluid (CSF) and significantly increased BBB permeability to systemically administered 125I-BSA as early as 3 h later (P less than 0.05). This injury was reversible, dose dependent and significantly inhibited by prior induction of systemic neutropenia (via intraperitoneal cyclophosphamide) or preincubation of the rIL-1 beta inoculum (50 U) with an IgG monoclonal antibody to rIL-1 beta. Similar kinetics and reversibility of CSF inflammation and BSA permeability were observed using equivalent dose inocula of rIL-1 alpha. rTNF-alpha was less effective as an independent inducer of meningitis or BBB injury over an inoculum range of 10(1) U (0.0016 micrograms/kg)-10(6) U (160 micrograms/kg) when injected intracisternally, but inoculum combinations of low concentrations of rTNF alpha (10(3) U) and rIL-1 beta (0.0005-5.0 U) were synergistic in inducing both meningitis and BBB permeability to systemic 125I-BSA. These data suggest that in situ generation of interleukin-1 within CSF (with or without TNF) is capable of mediating both meningeal inflammation and BBB injury seen in various central nervous system infections.

Effects of culture media on murine hybridomas: definition of optimal conditions for hybridoma viability, cellular proliferation, and antibody production.

Different cell culture media were compared for their ability to support and promote the growth of stable hybridoma cell lines derived from three commonly used parental murine myelomas. Supplemented Dulbecco's modified Eagle's media (DMEM) and RPMI 1640 media were studied. The DMEM-based media were found to support greater numbers of cells for longer time periods than were the RPMI 1640-based media. Aminopterin supplemented medium was shown to be significantly less effective in supporting hybridoma reproduction and viability than medium without aminopterin. Antibody levels were directly related to cell concentration and viability regardless of the medium used for the hybridoma culture. An optimally formulated DMEM-based medium is suggested as the medium of choice for hybridoma propagation and maintenance.

Neutralizing monoclonal antibodies to hepatitis A virus: partial localization of a neutralizing antigenic site.

BALB/c mice were immunized with purified preparations of hepatitis A virus (HAV) isolated after 21 days of growth in LLC-MK2 cells. The HAV antigen was isolated from CsCl gradients and consisted primarily of the following three proteins as analyzed after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Coomassie blue staining: VP-1 at 33,000 daltons, VP-2 at 29,000 to 30,000 daltons, and VP-3 at 27,000 daltons. The spleen cells isolated from two BALB/c mice, immunized with two inoculations of HAV, were fused with SP 2/0 myeloma cells and grown in hypoxanthine-aminopterin-thymidine medium. Of 270 hybridomas initially screened, 72 were positive for binding HAV by a noncompetitive radioimmunoassay. All 72 were tested for the ability to neutralize the infectivity of HAV in an in vitro cell culture assay that was adapted for microtiter plates and that used detergent-treated virus for improved neutralization sensitivity and newborn cynomolgus monkey kidney cells for rapid growth. Eighteen hybridomas were positive for neutralization; 16 remained stable. Of the 16, 9 were able to compete with labeled polyclonal serum for binding to HAV. The nine competing hybridomas could be separated into two groups which appear to be directed towards two different sites on HAV and could complement each other in the competitive radioimmunoassay against polyclonal sera. Of the original 16 neutralizing hybridomas, 4 were subcloned through two cycles of limit dilutions. All four monoclonal antibodies retained their original neutralizing and competitive properties; three were immunoglobulin G2a, and one was immunoglobulin G1. All four monoclonal antibodies readily precipitate whole 125I-labeled HAV but are not able to recognize the disrupted proteins of the virus (as tested by immune precipitations of heat- and detergent-disrupted virions or Western blot analyses). However, the heterobifunctional cross-linking reagent toluene-2,4-diisocyanate was used to cross-link purified Fab fragments of two different monoclonal antibodies (2D2 and 6A5) to HAV before disruption. This reagent demonstrated a specific reaction of the monoclonal antibodies to the VP-1 of HAV, suggesting this major surface protein contains at least one of the major neutralization sites for HAV.

Experience with a cholinesterase histochemical technique for rectal suction biopsies in the diagnosis of Hirschsprung's disease.

Cryostat sections from 160 rectal suction biopsies were stained for cholinesterases by the method of Karnovsky and Roots (1964) in an attempt to facilitate the diagnosis of Hirschsprung's disease. The method proved at least as reliable as experienced assessment of paraffin haematoxylin-eosin sections, and appeared to offer the advantages of reduced scanning fatigue and superior demonstration of the increased cholinesterase-positive nerves in Hirschprung's disease. Contrary to the findings of Meier-Ruge (1971) it was not possible to base a diagnosis on mucosal cholinesterase activity.