Faculty Bibliography

Substance P (SP), a neurotransmitter released after injury, has been linked to deregulated tissue repair and fibrosis in musculoskeletal tissues and other organs. Although SP inhibition is an effective treatment for nausea, it has not been previously considered as an anti-fibrotic therapy. Although there are extensive medical records of individuals who have used SP antagonists, our analysis of human registry data revealed that patients receiving these antagonists and arthroplasty are exceedingly rare, thus precluding a clinical evaluation of their potential effects in the context of arthrofibrosis. Therefore, we pursued in vivo studies to assess the effect of SP inhibition early after injury on pro-fibrotic gene expression and contractures in an animal model of post-traumatic joint stiffening. Skeletally mature rabbits (n = 24) underwent surgically induced severe joint contracture, while injected with either fosaprepitant (a selective SP antagonist) or saline (control) early after surgery (3, 6, 12, and 24 h). Biomechanical testing revealed that differences in mean contracture angles between the groups were not statistically significant (P = 0.27), suggesting that the drug neither mitigates nor exacerbates joint contracture. However, microarray gene expression analysis revealed that mRNA levels for proteins related to cell signaling, pro-angiogenic, pro-inflammatory, and collagen matrix production were significantly different between control and fosaprepitant treated rabbits (P < 0.05). Hence, our study demonstrates that inhibition of SP alters expression of pro-fibrotic genes in vivo. This finding will motivate future studies to optimize interventions that target SP to reduce the formation of post-traumatic joint contractures.

BACKGROUND During total hip arthroplasty (THA) drainage is used by most surgeons. However, the optimal drainage strategy remains controversial. The aim of this prospective cohort study was to determine the safety and efficacy of a four-hour drainage clamping technique in patients undergoing THA. MATERIAL AND METHODS There were 64 patients who underwent THA from March 2012 to December 2015 who were enrolled in the study; 32 patients were randomly assigned to four hours of a drainage clamping technique (clamping group); 32 patients were treated with a non-clamping drainage technique (non-clamping group). All perioperative clinical details were recorded for comparative analysis. RESULTS The postoperative drainage volume and calculated blood loss were significantly greater in the drainage non-clamping group, p<0.001 and p=0.028, respectively. Significantly more patients in the drainage non-clamping group required a blood transfusion, seven cases versus one case (p=0.023). Significantly more units of blood were transfused in the drainage non-clamping group (p=0.001). No significant differences were found for all other clinical outcome factors. CONCLUSIONS The four-hour drainage clamping technique following THA, compared with drainage non-clamping technique reduced blood loss and requirement for blood transfusion. There was no increase in adverse clinical events using the four-hour drainage clamping method. Therefore, four-hour drainage clamping has the potential for routine use in THA.

BACKGROUND:Patient-reported outcomes are increasingly used to capture the patients' perspective in total hip arthroplasty (THA). They can potentially be used to streamline post-THA follow-up to high-risk patients. We aimed to determine whether the long-term revision risk in THA relates to patient-reported measures at 2 and 5 years. METHODS:In a single-institution cohort of primary THA procedures, we examined the association between 2-year and 5-year pain and Mayo Hip Scores and the risk of revision. RESULTS:The absolute scores at 2 and 5 years were both significantly associated with the risk of revisions. Every 10-unit decline in the 2-year Mayo Hip Score <60 was associated with a significant 50% increase in the risk of revision (hazard ratio, 1.5 per 10 units; 95% confidence interval, 1.3-1.8). Similarly, every 10-unit decline in the 5-year Mayo Hip Score <60 was associated with almost doubling of the risk of revision (hazard ratio, 1.9 per 10 units; 95% confidence interval, 1.7-2.1). CONCLUSION:We conclude that patient-reported outcomes in THA have prognostic importance and can be taken into account when planning frequency of aftercare. This will improve the efficiency of follow-up in large registry-based follow-up efforts.

AIMS/OBJECTIVE:The length of the tourniquet time during total knee arthroplasty (TKA) is related to the incidence of post-operative deep vein thrombosis (DVT). Our aim in this study was to investigate the effect of the early release of the tourniquet on the incidence of DVT in patients undergoing TKA. METHODS:A total of 200 patients who underwent TKA between November 2015 and November 2016 were prospectively enrolled. The tourniquet was inflated before surgery and released immediately after the introduction of the components (early release group). This group was compared with a retrospective cohort of 200 primary TKAs, in which the tourniquet was released after the dressings had been applied (late release group). The presence of a DVT was detected using bilateral lower limb ultrasonography. Peri-operative clinical and follow-up data were collected for analysis. RESULTS:The incidence of DVT in the early release group (9 of 196, 4.6%) was significantly lower compared with the late release group (24 of 200, 12%; odds ratio (OR) 0.35, 95% confidence interval (CI) 0.16 to 0.78, p = 0.008). The incidence of proximal DVT in the early release group (1 of 196 (0.5%)) was significantly lower than in the late release group (8 of 196, 4%; OR 0.12, 95% CI 0.02 to 0.99, p = 0.020). Although the mean intra-operative blood loss was higher in the early release group, the mean post-operative drainage, total blood loss, transfusion requirements and complications were not significantly different in the two groups. CONCLUSION/CONCLUSIONS:2017;6:535-541.

We evaluated recently published articles relevant to the biological effects of titanium dioxide (TiO₂) particles on local endogenous cells required for normal bone homeostasis, repair, and implant osseointegration. Structural characteristics, size, stability, and agglomeration of TiO₂ particles alter the viability and behavior of multiple bone-related cell types. Resulting shifts in bone homeostasis may increase bone resorption and lead to clinical incidents of osteolysis, implant loosening, and joint pain. TiO₂ particles that enter cells (through endocytosis or Trojan horse mechanism) may further disrupt implant retention. We propose that cellular responses to titanium-based nanoparticles contribute to pathological mechanisms underlying the aseptic loosening of titanium-based metal implants.

BACKGROUND:Factors that determine recurrence and complications following primary tissue repair of umbilical hernias (UHs) and the approach to repair UHs in obese patients need further analysis. METHODS:A retrospective review of UH repair (UHR) conducted at our institution was undertaken. Patients were grouped by body mass index (BMI) and compared for recurrence and complications. Univariate and multivariate analyses were performed. RESULTS:In total, 199 patients (BMI 32.3 kg/m(2), 97% male, 77% Caucasian, American Society of Anesthesiologists class III/IV 59.2%) underwent primary tissue UHR. There were 8 recurrences (4.0%); average follow-up 3.9 ± 2.4 years (range 30 days to 9.2 years). There were no recurrences among normal BMI patients (0/11); 3 in overweight (3/54), 2 in class I obese (2/73), 2 in class II obese (2/47), and 1 in morbidly obese (1/14) patients (P = .84). Albumin and American Society of Anesthesiologists were similar in all groups. Recurrence rates among obese and nonobese patients were not significantly different (3.7% vs 4.6%, P = .72). There were 18 (9.0%) complications. BMI was not associated with complications. CONCLUSION/CONCLUSIONS:Primary tissue repair is a feasible approach for UHR in obese patients.

Digital papillary adenocarcinoma (DPA) is a rare malignant tumor of the sweat glands that often presents as a solitary painless mass on the digits of the hands or feet. We present a rare case of DPA on the ankle in a 54 year-old African American man. Although the most common location for digital papillary adenocarcinoma is on the hands and feet, it can present in other locations. Treatment modalities and concerns such as the level of margin resection, degree of negative margins, and the need for a sentinel lymph node biopsy might be different if the tumor is encountered in locations other than the digits. In the following manuscript, we discuss the natural history of this rare tumor including a review of the current literature with emphasis on documented treatment strategies as well as the approach in treating patients with a unique presentation.

The effects of chrysene and the ozonated byproducts on in vitro gap junctional intercellular communication (GJIC) were evaluated using the scrape loading/dye transfer (SL/DT) technique. A 1 mM solution of chrysene was ozonated at dosages of 1.75, 3, 4.25, and 5 mol O3/mol chrysene (Chr). The early ozonation mixture, 1.75 mol O3/mol Chr, exhibited greater inhibition to GJIC than chrysene and irreversible damage to cells leading to cell death. To determine the compounds potentially responsible for the increase in toxicity, the byproducts formed upon treatment with 1.44 mol O3/mol Chr were separated into 14 fractions using RP-HPLC. The major compounds identified in the fractions were 2-(2'-formyl) phenyl-1-naphthaldehyde, 2-(2'formyl) phenyl-1-naphthoic acid, and 2-2-carboxyphenyl-1-naphthoic acid. 2-(2'-Formyl) phenyl-1-naphthaldehyde was determined to be the compound causing GJIC inhibition in sample fractions and byproduct mixtures.

AIM/OBJECTIVE:To study the reversal effects of droloxifene (DRO) on multidrug resistance (MDR) in K562 cell line resistant to adriamycin (ADR). METHODS:K562 cell line resistant to ADR (K562/A02) and K562 cell line sensitive to ADR (K562) were treated with DRO. Using MTT assay, chemosensitivity to ADR in DRO-treated K562 cell lines was studied. Before and after the treatment with DRO 10 micromol/L, MDR1 and GSTpi gene expression were assayed by reverse transcription-polymerase chain reaction and immunocytochemistry assay. Flow cytometry was used to determine intracellular ADR concentration. RESULTS:DRO significantly reversed MDR in K562/A02 (P < 0.01). After treatment of DRO 20, 10, and 5 micromol/L, the chemosensitivity to ADR was increased to 14, 13, and 4 folds, respectively. The reversal activity of DRO was similar to that of verapamil (VRP). After treated with DRO 10 micromol/L, both MDR1 and GSTpi mRNA expression began to decline on the 2nd day, and significantly decreased on the 5th day (P<0.01). The changes in P-gp and GSTpi protein expression were similar to that of their mRNA expression. Two hours after treatment of DRO 20, 10, and 5 micromol/L, intracellular ADR concentration in K562/A02 was increased to 2.9, 2.3, and 1.5 folds, respectively. However, DRO did not markedly increase ADR accumulation in K562. CONCLUSION/CONCLUSIONS:DRO had strong reversal effect on MDR in K562/A02, which was comparable to that of VRP, but the reversal effect was via different pathways.