Efficacy of a Novel Intraoperative Surgical Irrigant in Preventing Periprosthetic Joint Infections in Primary Knee, Hip, and Shoulder Arthroplasties: A Retrospective Analysis.

OBJECTIVE: Primary joint arthroplasty (JA) is one of the most common operating room (OR) procedures, with knee and hip arthroplasties being listed in the top five most frequent OR procedures and while not as common, shoulder arthroplasties are increasing at greater rates than knee and hip arthroplasties. Periprosthetic joint/shoulder infections (PJI/PSI) are a devastating complication of primary JAs with infection prevention deemed as the single most important strategy in combating them. The objective of this study was to retrospectively evaluate the efficacy of XPERIENCE® Advanced Surgical Irrigation (XP) in preventing PJI following primary joint arthroplasty. METHODS: This is a retrospective study of primary knee, hip and shoulder arthroplasties that were performed by multiple orthopedic surgeons at a single hospital setting. XPERIENCE was used as an intraoperative surgical irrigant either solely, or with other intraoperative practices for prevention of infection. Incidence of acute PJI occurring within 90 days of index surgery were retrospectively collated. RESULTS: Four hundred and twenty-three (423) primary joint replacement surgeries treated intraoperatively with XP, were evaluated for acute PJI incidence. Retrospective evaluations determined that 95% of the subjects had at least one risk factor predisposing them to PJI. There were zero PJIs diagnosed in the knee and hip arthroplasty cohorts and zero PSIs diagnosed in the shoulder arthroplasty cohorts. CONCLUSION: The absence of PJI/PSI diagnoses in the JA cohorts treated intraoperatively with XP indicates that it could be an efficacious antimicrobial irrigant in preventing PJI, and warrants being evaluated in prospective, randomized controlled clinical trials as the sole intraoperative irrigant, as well as in combination with the other intraoperative infection prevention regimens evaluated in this retrospective study.

Acute toxic shock syndrome associated with intra-operative debridement and instrumentation removal for chronic osteomyelitis: A report of two cases.

Gram-positive organisms are known causative agents in toxic shock syndrome (TSS), an acute disease caused by bacterial exotoxins. During routine instrumentation removal for chronic osteomyelitis, intraoperative debridement, reaming, and irrigation can lead to cell lysis and subsequent dissemination of the bacterium exotoxin, which can result in acute cardiovascular compromise. We present two cases of chronic osteomyelitis in healed long-bone fractures that were treated with deep instrumentation removal and surgical debridement using a reamer-irrigator-aspirator (RIA) system. Both patients had positive Streptococcus agalactiae wound cultures and both developed acute intraoperative hypotension during the reaming/irrigation portion of the procedure. Case 1 experienced cardiac arrest and was resuscitated for several days in the ICU. Case 2 underwent intra-operative hypotension and was resuscitated appropriately. The RIA or standard reaming systems must be used with caution during debridement of osteomyelitis in the presence of known toxin producing bacteria. The risk of iatrogenic spread of infection or extravasation of intramedullary contents is present; a high index of suspicion with any change in vital signs and prompt response can help mitigate the effect of adverse outcomes associated with acute and severe intraoperative hypotension.

Superficial Surgical Site Infections in Primary Total Joint Arthroplasty: A Retrospective Analysis of Topical Anti-Biofilm Therapy.

Introduction Surgical site infections (SSI) following orthopedic procedures can cause significant morbidity and mortality, particularly in total joint arthroplasty. Biofilm formation in surgical wounds has made it difficult to prevent and treat these infections. SURGX® Antimicrobial Wound Gel (Next Science, Jacksonville, Florida, USA) was developed to disrupt biofilm formation but has not been evaluated in prophylactic use in total joint arthroplasty to prevent superficial SSI. Methods A retrospective chart review was performed at a single institution comparing the rate of SSI in patients undergoing primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). SSI data were collected from patients with standard postoperative dressings (Group A: Control) and patients with SURGX® applied as part of a standardized dressing following THA/TKA (Group B: Study). Rates of SSI were compared.  Results SURGX® was administered to 120 patients, including 91 TKAs and 29 THAs. The overall infection rate in this cohort was 2.5%. No superficial site infections developed. The control group constituted 566 patients, with 386 TKAs and 180 THAs. The infection rate was 1.24%, which included one superficial infection. Binary logistic regression did not show different odds of developing infections with the use of SURGX® (OR = 2.23, 95% CI: 0.54-9.13, p = 0.27). Conclusion In our small retrospective study, Next Science SURGX® Antimicrobial Wound Gel did not demonstrate a statistically significant difference in the rate of superficial SSI in total joint arthroplasty; however, Group B did not have any superficial SSI.

Routine postoperative computed tomography (CT) scans following acetabulum open reduction internal fixation (ORIF): A survey of orthopaedic traumatologists.

OBJECTIVE: The purpose of this study was to assess the practices related to obtaining postoperative pelvic CT scans following acetabular ORIF and revision surgery rates. DESIGN: A 20-question survey published on the Orthopaedic Trauma Association (OTA) website assessed each surgeon's preference and rationale for or against the routine use of postoperative CT scans for acetabular fractures. PARTICIPANTS: Fellowship-trained orthopaedic traumatologists. MAIN OUTCOME MEASUREMENTS: We examined the percentage of surgeons ordering routine postoperative CT scans, surgeon demographics, and revision surgery rates based on these routine CT scan results. RESULTS: Responses were received from 57 surgeons. Practices varied regarding postoperative CT scans, with 16 surgeons (28%, Group A) routinely ordering them and 41 surgeons (72%, Group B) not ordering them on all patients. No significant difference in surgeon demographics were found between the groups. Majority of Group A report a revision surgery rate of <1% based on the results of the postoperative CT. Group A report routine postoperative scans were obtained to assess reduction, hardware placement, identify intra-articular fragments, and for educational purposes. Group B did not obtain routine postoperative CTs due to the following: unlikely to change postoperative treatment, adequate reduction and instrumentation placement assessed intraoperatively and by postoperative radiographs, and increased radiation exposure and cost to patients. Group B did report obtaining postop CT scans on select patients, with inadequate intraoperative imaging and postoperative neurological changes being the most common indications. CONCLUSION: The routine use of postoperative CTs following open reduction internal fixation of acetabular fractures is a controversial topic. While we recognize the role for postoperative CT scans in select patients, our study questions the clinical utility of these scans in all patients and in conclusion do not recommend this protocol.

Routine Postoperative Computed Tomography Scans Following Posterior Pelvic Fixation of Pelvic Ring Fractures: A Survey of (OTA) Orthopaedic Traumatologists.

OBJECTIVE: To assess practices related to ordering computed tomography (CT) scans routinely after posterior pelvic ring fixation and revision surgery rates. DESIGN: A 20-question cross-sectional survey. PARTICIPANTS: Fellowship-trained orthopaedic traumatologists. MAIN OUTCOME MEASUREMENTS: (1) Percentage of surgeons ordering a routing postoperative CT after posterior pelvic ring fixation, (2) Revision surgery rates based on routine CT scan results. RESULTS: Responses were received from 57 surgeons. Practices varied regarding postoperative CT scans, with 20 surgeons (35%, group A) routinely ordering them and 37 surgeons (65%, group B) not ordering them on all patients. Group A were younger and with less years of experience than those in Group B. Most group A surgeons report a revision surgery rate of <1% based on results of the postoperative CT. Group A report routine postoperative scans were obtained to assess reduction, instrumentation placement, and for educational purposes. Group B did not obtain routine postoperative CTs because of the following: unlikely to change postoperative treatment course, adequate reduction and instrumentation placement assessed intraoperatively and by postoperative radiographs, and increased radiation exposure and cost to patients. Group B did report obtaining postop CT scans on select patients, with postoperative neurological deficit being the most common indication. CONCLUSIONS: The routine use of postoperative CTs following posterior fixation of pelvic ring fractures is a controversial topic. Although we recognize the role for postoperative CT scans in select patients, our study questions the clinical utility of these scans in all patients and in conclusion do not recommend this protocol.

Molecular basis of carcinogenicity of tungsten alloy particles.

The tungsten alloy of 91% tungsten, 6% nickel and 3% cobalt (WNC 91-6-3) induces rhabdomyosarcoma when implanted into a rat thigh muscle. To investigate whether this effect is species-specific human HSkMc primary muscle cells were exposed to WNC 91-6-3 particles and responses were compared with those from a rat skeletal muscle cell line (L6-C11). Toxicity was assessed by the adenylate kinase assay and microscopy, DNA damage by the Comet assay. Caspase 3 enzyme activity was measured and oligonucleotide microarrays were used for transcriptional profiling. WNC 91-6-3 particles caused toxicity in cells adjacent to the particles and also increased DNA strand breaks. Inhibition of caspase 3 by WNC 91-6-3 occurred in rat but not in human cells. In both rat and human cells, the transcriptional response to WNC 91-6-3 showed repression of transcripts encoding muscle-specific proteins with induction of glycolysis, hypoxia, stress responses and transcripts associated with DNA damage and cell death. In human cells, genes encoding metallothioneins were also induced, together with genes related to angiogenesis, dysregulation of apoptosis and proliferation consistent with pre-neoplastic changes. An alloy containing iron, WNF 97-2-1, which is non-carcinogenic in vivo in rats, did not show these transcriptional changes in vitro in either species while the corresponding cobalt-containing alloy, WNC 97-2-1 elicited similar responses to WNC 91-6-3. Tungsten alloys containing both nickel and cobalt therefore have the potential to be carcinogenic in man and in vitro assays coupled with transcriptomics can be used to identify alloys, which may lead to tumour formation, by dysregulation of biochemical processes.

Improving the passive permeability of macrocyclic peptides: Balancing permeability with other physicochemical properties.

A number of methods to improve the passive permeability of a set of cyclic peptides have been investigated using 6- and 7-mer macrocyclic templates. In many cases the peptides were designed by molecular dynamics calculations to evaluate the methods. The aim of this study was not only to improve passive permeability, but also to balance permeability with other physicochemical properties with the goal of understanding and applying the knowledge to develop active cyclic peptides into drug candidates. Evaluation of the methods herein suggest that increasing passive permeability often occurs at the expense of solubility and lipophilicity. Computational methods can be useful when attempting to predict and design features to balance these properties, though limitations were observed.

High coating of Ru(II) complexes on gold nanoparticles for single particle luminescence imaging in cells.

Gold nanoparticles are efficiently labelled with a luminescent ruthenium complex, producing 13 and 100 nm diameter, monodisperse red-emissive imaging probes with luminescence lifetimes prolonged over the molecular unit. Single, 100 nm particles are observed in whole cell luminescence imaging which reveals their biomolecular association with chromatin in the nucleus of cancer cells.

Full-time orthopedic traumatologists enhance rural trauma center pelvic fracture outcomes and financials.

We hypothesized that full-time orthopedic traumatologists would increase interfacility transfer patients with pelvic ring injuries at a trauma center seeking American College of Surgeons Level I verification. A trauma registry query identified 790 patients with pelvic ring injuries admitted to a trauma service over 10 years. The study groups included 173 patients 3 years before and 405 patients 3 years after recruitment of two full-time orthopedic traumatologists. Interfacility transfers of patients with pelvic ring injuries requiring operative procedures were increased over 230 per cent (P < 0.01) with full-time orthopedic traumatologists. Financial analysis showed enhanced hospital margin per patient and decreased direct costs (P < 0.01). Complications, mortality rates, and length of stay were decreased (P < 0.01). Full-time orthopedic traumatologists enhance pelvic ring injury patient interfacility transfers, operative procedures, outcomes, and financials at a Level I trauma center in a rural setting.

Concise syntheses of the natural products (+)-sylvaticin and (+)-cis-sylvaticin.

Two concise syntheses of the natural products cis-sylvaticin and sylvaticin are reported, using oxidative cyclization methodology as the key step. A sequential solvolysis/hydride shift/intramolecular reduction cascade was used to establish the trans stereochemistry of one of the THF rings of sylvaticin.

Fatigue strength of common tibial intramedullary nail distal locking screws.

BACKGROUND: Premature failure of either the nail and/or locking screws with unstable fracture patterns may lead to angulation, shortening, malunion, and IM nail migration. Up to thirty percent of all unreamed nail locking screws can break after initial weight bearing is allowed at 8-10 weeks if union has not occurred. The primary problem this presents is hardware removal during revision surgery. The purposes of our study was to evaluate the relative fatigue resistance of distal locking screws and bolts from representative manufacturers of tibial IM nail systems, and develop a relative risk assessment of screws and materials used. Evaluations included quantitative and qualitative measures of the relative performance of these screws. METHODS: Fatigue tests were conducted to simulate a comminuted fracture that was treated by IM nailing assuming that all load was carried by the screws. Each screw type was tested ten times in a single screw configuration. One screw type was tested an additional ten times in a two-screw parallel configuration. Fatigue tests were performed using a servohydraulic materials testing system and custom fixturing that simulated screws placed in the distal region of an appropriately sized tibial IM nail. Fatigue loads were estimated based on a seventy-five kilogram individual at full weight bearing. The test duration was one million cycles (roughly one year), or screw fracture, whichever occurred first. Failure analysis of a representative sample of titanium alloy and stainless steel screws included scanning electron microscopy (SEM) and quantitative metallography. RESULTS: The average fatigue life of a single screw with a diameter of 4.0 mm was 1200 cycles, which would correspond roughly to half a day of full weight bearing. Single screws with a diameter of 4.5 mm or larger have approximately a 50 percent probability of withstanding a week of weight bearing, whereas a single 5.0 mm diameter screw has greater than 90 percent probability of withstanding more than a week of weight bearing. If two small diameter screws are used, our tests showed that the probability of withstanding a week of weight bearing increases from zero to about 20 percent, which is similar to having a single 4.5 mm diameter screw providing fixation. CONCLUSION: Our results show that selecting the system that uses the largest distal locking screws would offer the best fatigue resistance for an unstable fracture pattern subjected to full weight bearing. Furthermore, using multiple screws will substantially reduce the risk of premature hardware failure.

Mitochondrial complex activity in donor renal grafts, cold ischemia time, and recovery of graft function.

Indexed mitochondrial complex activities (MCAi) were determined in biopsies obtained from 52 donor kidneys at the end of cold ischemia (8-32 hr) to see if longer anoxia affected MCAi and accounted for the increased risk of delayed graft function (DGF) in recipients of grafts with longer cold ischemia time (CIT) or from non-heart-beating donors (NHBD). CITs were significantly different between those with and without DGF (P=0.02), being shorter in the latter, but MCAi were similar. CIT was correlated (r=0.43, P=0.003) with the time taken for creatinine concentration to fall to half the perioperative value (Crt(1/2)) but not with MCAi. Frequency of DGF, greater in NHBD, was significantly different from that of heart-beating donors (P=0.04), but CIT and MCAi were similar. However, Crt(1/2), was significantly different being longer in NHBD. Thus, the frequency of DGF increased and the speed of recovery diminished with longer CIT, whereas MCAi remained stable suggesting other factors determined tissue recovery.

Inhibition of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase by flavonoids: a quantitative structure-activity relationship study.

Flavonoids are commonly found in fruit and vegetables and have been shown to reach concentrations of several micromolars in human blood plasma. Flavonoids are also believed to have cancer chemoprotective properties. One hypothesis is that flavonoids are able to initiate apoptosis, especially in cancer cells, via a Ca(2+)-dependent mitochondrial pathway. This pathway can be activated through an exaggerated elevation of cytosolic [Ca(2+)], and sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPases (SERCA) play an essential role in ameliorating such changes. In this study, we demonstrate that flavonoids (especially flavones) can inhibit the activity of Ca(2+)-ATPases isoforms SERCA1A and SERCA2B in the micromolar concentration range. Of the 25 flavonoids tested, 3,6-dihydroxyflavone (IC(50), 4.6 microM) and 3,3',4',5,7-pentahydroxyflavone (quercetin) (IC(50), 8.9 microM) were the most potent inhibitors. We show that polyhydroxylation of the flavones are important for inhibition, with hydroxylation at position 3 (for SERCA1A) and position 6 (for SERCA2B) being particularly relevant.

Endocrine disrupting alkylphenols: structural requirements for their adverse effects on Ca2+ pumps, Ca2+ homeostasis & Sertoli TM4 cell viability.

Alkylphenols such as nonylphenol are pollutants that are widely dispersed within our environment. They bio-accumulate within man, with levels in the muM concentration range reported in human tissues. These chemicals act as endocrine disruptors, having xenoestrogenic activity. More recently alkylphenols have also been shown to affect Ca2+ signalling pathways. Here we show that alkylphenols are potent inhibitors of sarcoplasmic-endoplasmic reticulum Ca2+-ATPase (SERCA) activity. For linear chain alkylphenols the potency of inhibition is related to chain length, with the IC50 values for inhibition ranging from 8 microM for 4-n-nonylphenol (C9) to 1.3 mM for 4-n-propylphenol (C3). Branched chain alkylphenols generally had lower potencies than their linear chain counterparts, however, good correlations for all alkylphenols were observed between their Ca2+ pump inhibition and hydrophobicity, molecular volume and flexibility, indicating that these parameters are all important factors. Alkylphenols cause abnormal elevations of intracellular [Ca2+] within TM4 Sertoli cells (cells involved in sperm maturation) depolarise their mitochondria and induce cell death in these cells, in an alkyl chain size-dependent manner.

Total synthesis of (+)-cis-sylvaticin: double oxidative cyclization reactions catalyzed by osmium.

The double oxidative cyclization of dienes is a viable procedure for making complex natural products containing cis-THF units. A double deprotection/double oxidative cyclization strategy using catalytic osmium tetroxide was used to construct the bisheterocyclic core of cis-sylvaticin and ultimately confirm its structure. The natural product was then prepared by a short sequence of reactions that is exceptionally concise: the final route being just 13 linear steps and 19 chemical operations in total.

New osmium-based reagent for the dihydroxylation of alkenes.

The cis dihydroxylation of alkenes is most efficiently accomplished by reaction with osmium tetroxide. Recently, the expense and toxicity of osmium tetroxide have led to a number of attempts to harness alternative osmium-based reagents, including microencapsulation and solid support techniques. We describe here the development of a new nonvolatile, stable, and recoverable osmium-based reagent devised for the stoichiometric cis dihydroxylation of alkenes. Although attempts to make this new dihydroxylation work with catalytic amounts of this reagent were unsuccessful, we did develop a sensitive test for free osmium tetroxide leached from the reagent in situ: this test may well have uses in probing future applications of derivatized osmium reagents.

A methodology for assessing blast protection in explosive ordnance disposal bomb suits.

To reduce human casualties associated with explosive ordnance disposal, a wide range of protective wear has been designed to shield against the blast effects of improvised explosive devices and munitions. In this study, 4 commercially available bomb suits, representing a range of materials and armor masses, were evaluated against 0.227 and 0.567 kg of spherical C-4 explosives to determine the level of protection offered to the head, neck, and thorax. A Hybrid III dummy, an instrumented human surrogate [1], was tested with and without protection from the 4 commercially available bomb suits. 20 tests with the dummy torso mounted to simulate a kneeling position were performed to confirm repeatability and robustness of the dummies, as well as to evaluate the 4 suits. Correlations between injury risk assessments based on past human or animal injury model data and various parameters such as bomb suit mass, projected area, and dummy coverage area were drawn.

Blast injury research: modeling injury effects of landmines, bullets, and bombs.

Terrorist blasts and landmine injuries have become more common in the past several decades generating thousands of casualties. Preventive and prognostic measures are limited by the lack of knowledge of these complex events. Previous blast research has focused on primary blast injuries that involve the lung, despite musculoskeletal injuries being the most common. Through the use of instrumented cadavers, Hybrid III test dummies, and other surrogates, unique models of these events have been created. The investigations studied the effectiveness of antimine footwear, forces and injury mechanisms in temporary shelters subjected to blast, modeling of blast-induced glass fragmentation, and helmet deformation and injury potential under ballistic load. Despite blasts being much higher rate events than those seen in automotive blunt trauma, we were able to measure forces and create injury models. We found that antimine footwear will require additional development to be effective. Guidelines for shelter placement have been altered, and tempered glass seems to offer no protection when compared with annealed glass. Although these models are in their nascent phase, the thorough understanding of the biomechanical nature of these blast injuries will assist in developing strategies to reduce injuries and in the creation of forecasting models.

Environmental endocrine disrupters dysregulate estrogen metabolism and Ca2+ homeostasis in fish and mammals via receptor-independent mechanisms.

Xenoestrogen endocrine disrupters (EDs) in the environment are thought to be responsible for a number of examples of sexual dysfunction that have recently been reported in several species. There is growing concern that these compounds may also cause abnormalities of the male reproductive tract and reduced spermatogenesis in man. Whilst some effects of EDs may be receptor-mediated, there is growing evidence that these compounds can exert potent effects in vivo by directly interacting with cellular enzyme targets. Here we report on, and review, the effects of alkylphenols and other EDs on two such enzymes: (1) sulfotransferases, which convert active estrogenic steroids to inactive steroid sulfates; and (2) Ca(2+)-ATPases, which are responsible for maintaining low, physiological, intracellular Ca(2+) concentrations. These enzymes are potently inhibited by EDs in both fish and mammalian species. The increased concentrations of active estrogens and the likely cytotoxic effects of elevated concentrations of intracellular Ca(2+) arising from these effects may underlie some of the endocrine disrupting potential of these widespread industrial pollutants.