Mid-term outcomes of routine proximal row carpectomy compared with proximal row carpectomy with dorsal capsular interposition arthroplasty for the treatment of late-stage arthropathy of the wrist.

AIMS: The aims of this study were to compare the mid-term outcomes of patients with late-stage arthritis of the wrist treated with proximal row carpectomy (PRC) and dorsal capsular interposition (DCI) arthroplasty with a matched cohort treated with routine PRC alone. PATIENTS AND METHODS: A total of 25 arthritic wrists (24 patients) with pre-existing degenerative changes of the proximal capitate and/or the lunate fossa of the radius were treated with PRC + DCI over a ten-year period. This group of patients were matched 1:2 with a group of 50 wrists (48 patients) without degenerative changes in the capitate or lunate fossa that were treated with a routine PRC alone during the same period. The mean age of the patients at the time of surgery was 56.8 years (25 to 81), and the demographics and baseline range of movement of the wrist, grip strength, Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, and Patient-Rated Wrist Evaluation (PRWE) score were similar in both groups. RESULTS: At a mean follow-up of 5.9 years (1.8 to 11.8), significant improvements in mean grip strength, the flexion-extension arc of movement of the wrist, QuickDASH, and PRWE scores were seen in both groups. There was no diifference between the groups for any of the outcomes. One patient in the PRC + DCI group required additional surgery for a deep infection, while two in the PRC group had complications (one wound dehiscence requiring revision closure, one transient radial sensory neuritis). One patient in each group required total arthrodesis of the wrist for progressive degenerative radiocarpal changes. A total of 70 patients (93%) were satisfied with the outcomes. CONCLUSION: PRC with DCI is an effective form of treatment for late-stage arthritis of the wrist involving the capitolunate joint, with mid-term outcomes that are similar to those in patients without degenerative changes affecting the capitate or lunate fossa who are treated with a routine PRC alone. Cite this article: Bone Joint J 2018;100-B:197-204.

Mobilan: a recombinant adenovirus carrying Toll-like receptor 5 self-activating cassette for cancer immunotherapy.

Toll-like receptor 5 (TLR5) is considered an attractive target for anticancer immunotherapy. TLR5 agonists, bacterial flagellin and engineered flagellin derivatives, have been shown to have potent antitumor and metastasis-suppressive effects in multiple animal models and to be safe in both animals and humans. Anticancer efficacy of TLR5 agonists stems from TLR5-dependent activation of nuclear factor-κB (NF-κB) that mediates innate and adaptive antitumor immune responses. To extend application of TLR5-targeted anticancer immunotherapy to tumors that do not naturally express TLR5, we created an adenovirus-based vector for intratumor delivery, named Mobilan that drives expression of self-activating TLR5 signaling cassette comprising of human TLR5 and a secreted derivative of Salmonella flagellin structurally analogous to a clinical stage TLR5 agonist, entolimod. Co-expression of TLR5 receptor and agonist in Mobilan-infected cells established an autocrine/paracrine TLR5 signaling loop resulting in constitutive activation of NF-κB both in vitro and in vivo. Injection of Mobilan into primary tumors of the prostate cancer-prone transgenic adenocarcinoma of the mouse prostate (TRAMP) mice resulted in a strong induction of multiple genes involved in inflammatory responses and mobilization of innate immune cells into the tumors including neutrophils and NK cells and suppressed tumor progression. Intratumoral injection of Mobilan into subcutaneously growing syngeneic prostate tumors in immunocompetent hosts improved animal survival after surgical resection of the tumors, by suppression of tumor metastasis. In addition, vaccination of mice with irradiated Mobilan-transduced prostate tumor cells protected mice against subsequent tumor challenge. These results provide proof-of-concept for Mobilan as a tool for antitumor vaccination that directs TLR5-mediated immune response toward cancer cells and does not require identification of tumor antigens.

Metabolic rewiring in melanoma.

Oncogene-driven metabolic rewiring is an adaptation to low nutrient and oxygen conditions in the tumor microenvironment that enables cancer cells of diverse origin to hyperproliferate. Aerobic glycolysis and enhanced reliance on glutamine utilization are prime examples of such rewiring. However, tissue of origin as well as specific genetic and epigenetic changes determines gene expression profiles underlying these metabolic alterations in specific cancers. In melanoma, activation of the mitogen-activated protein kinase (MAPK) pathway driven by mutant BRAF or NRAS is a primary cause of malignant transformation. Activity of the MAPK pathway, as well as other factors, such as HIF1α, Myc and MITF, are among those that control the balance between non-oxidative and oxidative branches of central carbon metabolism. Here, we discuss the nature of metabolic alterations that underlie melanoma development and affect its response to therapy.

Functional genetics-directed identification of novel pharmacological inhibitors of FAS- and TNF-dependent apoptosis that protect mice from acute liver failure.

shRNA-mediated gene-silencing technology paired with cell-based functional readouts reveals potential targets directly, providing an opportunity to identify drugs against the target without knowing the precise role of the target in the pathophysiological processes of interest. By screening a lentiviral shRNA library targeting for major components of human signaling pathways and known drug targets, we identified and validated both canonical as well as 52 novel mediators of FAS and TNF ligand-induced apoptosis. Presence of potential therapeutic targets among these mediators was confirmed by demonstration of in vivo activity of siRNAs against four identified target candidates that protected mice from acute liver failure (ALF), a life-threatening disease with known involvement of death receptor (DR)-mediated apoptosis. Network-based modeling was used to predict small-molecule inhibitors for several candidate apoptosis mediators, including somatostatin receptor 5 (SSTR5) and a regulatory subunit of PP2A phosphatase, PPP2R5A. Remarkably, pharmacological inhibition of either SSTR5 or PPP2R5A reduced apoptosis induced by either FASL or TNF in cultured cells and dramatically improved survival in several mouse models of ALF. These results demonstrate the utility of loss-of-function genetic screens and network-based drug-repositioning methods for expedited identification of targeted drug candidates and revealed pharmacological agents potentially suitable for treatment of DR-mediated pathologies.

Experimental determination and system level analysis of essential genes in Escherichia coli MG1655.

Defining the gene products that play an essential role in an organism's functional repertoire is vital to understanding the system level organization of living cells. We used a genetic footprinting technique for a genome-wide assessment of genes required for robust aerobic growth of Escherichia coli in rich media. We identified 620 genes as essential and 3,126 genes as dispensable for growth under these conditions. Functional context analysis of these data allows individual functional assignments to be refined. Evolutionary context analysis demonstrates a significant tendency of essential E. coli genes to be preserved throughout the bacterial kingdom. Projection of these data over metabolic subsystems reveals topologic modules with essential and evolutionarily preserved enzymes with reduced capacity for error tolerance.

Partial interosseous ligament tears of the wrist: difficulty in utilizing either primary or secondary MRI signs.

PURPOSE: Prior reports on scapholunate ligament (SLL) and lunotriquetral ligament (LTL) tears have evaluated complete tears. As these complete tears have markedly different biomechanical manifestations and surgical considerations than do partial tears, we evaluated the accuracy of MR and the usefulness of secondary MR signs to diagnose partial interosseous ligament tears. METHOD: Fifty wrists in 50 patients underwent arthroscopy following 1.5 T MR. Images were evaluated by two independent blinded observers for normal or partially torn SLL and LTL and for three secondary signs potentially seen as mechanical sequelae of tears: osseous offset, arc disruption, or focal osteoarthritis. RESULTS: Arthroscopically, there were 16 SLL and 14 LTL partial tears. Accuracy of primary MR signs of partial tears was lower than that described in the literature for complete tears [sensitivity/specificity (kappa) = 0.56/0.56 (0.12)-SLL, 0.31/0.76 (0.13)-LTL]. Secondary signs showed low sensitivity but high specificity, particularly for LTL tears: arc disruption [0.17/0.83 (0.43)-SLL, 0.0/1.00 (1.0)- LTL], focal osteoarthritis [0.32/0.78 (0.18)-SLL, 0.11/0.91 (0.12)-LTL], and focal osseous offset [0.39/0.75 (0.10)-SLL, 0.26/0.93 (0.39)-LTL]. Additionally, there was poor interobserver consistency for both primary and secondary signs. CONCLUSION: The sensitivity of morphologic evaluation for diagnosing partial intercarpal ligament tears, particularly those of the LTL, is limited. Secondary signs increase specificity but have low sensitivity, and with the exception of arc disruption, all signs had poor interobserver agreement.

Wrist arthroscopy: principles and clinical applications.

With the development of better and smaller equipment, arthroscopy of the wrist offers the same benefits achievable with arthroscopy of the knee, shoulder, or elbow - not only diagnostic information but also a therapeutic option. Standardized techniques of performing wrist arthroscopy have been developed to evaluate the treat various wrist disorders, such as lesions of the triangular fibrocartilage complex, intra-articular distal radius fractures, and scaphoid fractures. Arthroscopy is now performed in the treatment of dorsal-wrist ganglion cysts and interosseous ligament disruptions, as well as for bone incisions, such as radial styloidectomy, distal ulnar excision (wafer procedure), and proximal-row carpectomy. Compared with other techniques, arthroscopic procedures, such as repair of the triangular fibrocartilage complex, demonstrate better results and improved localization of the injury with a low complication rate. In addition, arthroscopic procedures involve lesssurgical dissection, less postoperative pain, a shorter recovery time, and an earlier return to work for the patient.

Smoking and bony union after ulna-shortening osteotomy.

We examined the relation between cigarette use and occurrence of delayed union and nonunion after ulna-shortening osteotomy for ulnar impaction syndrome. After obtaining the smoking history of 39 patients (40 wrists), we found that, compared with nonsmokers, smokers experienced longer healing times and more of them experienced healing delay and nonunion. Mean union rates were 7.1 months in smokers and 4.1 months in nonsmokers. Six smokers (30%) and no nonsmokers experienced delayed union or nonunion. Given the adverse effects of smoking on bony union, we recommend that smoking history be considered when selecting patients for ulna-shortening procedures.

Scapholunate instability in athletes.

Sports medicine practitioners must be sensitive to even the smallest injuries that affect athletes. Often, less severe ligament injuries go undetected. Scapholunate dissociation is often overlooked in this manner. The authors provide an overview of presentation, diagnosis, and nonoperative and operative treatments of this condition.

Altering the reaction specificity of eukaryotic ornithine decarboxylase.

Ornithine decarboxylase (ODC) catalyzes the first committed step in the biosynthesis of polyamines, and it has been identified as a drug target for the treatment of African sleeping sickness, caused by Trypanosoma brucei. ODC is a pyridoxal 5'-phosphate (PLP) dependent enzyme and an obligate homodimer. X-ray structural analysis of the complex of the T. brucei wild-type enzyme with the product putrescine reveals two structural changes that occur upon ligand binding: Lys-69 is displaced by putrescine and forms new interactions with Glu-94 and Asp-88, and the side chain of Cys-360 rotates into the active site to within 3.4 A of the imine bond. Mutation of Cys-360 to Ala or Ser reduces the k(cat) of the decarboxylation reaction by 50- and 1000-fold, respectively. However, HPLC analysis of the products demonstrates that the mutant enzymes almost exclusively catalyze a decarboxylation-dependent transamination reaction to form pyridoxamine 5-phosphate (PMP) and gamma-aminobutyraldehyde, instead of PLP and putrescine. This side reaction arises when the decarboxylated substrate intermediate is protonated at C4' of PLP instead of at the C(alpha) of substrate. For the reaction catalyzed by the wild-type enzyme, this side reaction occurs infrequently (<0.01% of the turnovers). Single turnover analysis and multiwavelength stopped-flow spectroscopic studies suggest that for the mutant ODCs protonation at C4' occurs either very rapidly or in a concerted reaction with decarboxylation and that the rate-limiting step in the steady-state reaction is Schiff base hydrolysis/product release. These studies demonstrate a role for Cys-360 in the control of the C(alpha) protonation step that catalyzes the formation of the physiological product putrescine. The results further provide insight into the mechanism by which this class of PLP-dependent enzymes controls reaction specificity.

Lunotriquetral injuries in the athlete.

The athlete with an LT injury typically presents with ulnar-sided wrist pain after a high-energy impaction of the wrist. Reagan's LT ballottement test and Kleinman's shear test help the examiner identify these injuries. A thorough radiographic examination includes standard PA and lateral radiographs. Magnetic resonance imaging or arthrography can be performed, but the sensitivity of these imaging studies varies. The palmar portion of the LT interosseous ligament, dorsal radiocarpal ligament, and dorsal intercarpal ligament play the most significant roles in LT stability. Lunotriquetral injuries without instability respond well to immobilization. Arthroscopy is valuable in staging and determining treatment but requires a thorough radiocarpal and midcarpal examination. Acute LT injuries with instability are treated with arthroscopic-assisted reduction and pinning. If desired, this procedure can be incorporated with an open ligament repair through a volar approach. Chronic LT tears without instability can also be treated arthroscopically. Treatment of the chronic LT tear with instability depends on the degree of collapse. Treatment in the athlete includes ligament reconstruction with capsulodesis or, rarely, intercarpal LT arthrodesis.

Structure and mechanism of homoserine kinase: prototype for the GHMP kinase superfamily.

BACKGROUND: Homoserine kinase (HSK) catalyzes an important step in the threonine biosynthesis pathway. It belongs to a large yet unique class of small metabolite kinases, the GHMP kinase superfamily. Members in the GHMP superfamily participate in several essential metabolic pathways, such as amino acid biosynthesis, galactose metabolism, and the mevalonate pathway. RESULTS: The crystal structure of HSK and its complex with ADP reveal a novel nucleotide binding fold. The N-terminal domain contains an unusual left-handed betaalphabeta unit, while the C-terminal domain has a central alpha-beta plait fold with an insertion of four helices. The phosphate binding loop in HSK is distinct from the classical P loops found in many ATP/GTP binding proteins. The bound ADP molecule adopts a rare syn conformation and is in the opposite orientation from those bound to the P loop-containing proteins. Inspection of the substrate binding cavity indicates several amino acid residues that are likely to be involved in substrate binding and catalysis. CONCLUSIONS: The crystal structure of HSK is the first representative in the GHMP superfamily to have determined structure. It provides insight into the structure and nucleotide binding mechanism of not only the HSK family but also a variety of enzymes in the GHMP superfamily. Such enzymes include galactokinases, mevalonate kinases, phosphomevalonate kinases, mevalonate pyrophosphate decarboxylases, and several proteins of yet unknown functions.

X-ray structure of ornithine decarboxylase from Trypanosoma brucei: the native structure and the structure in complex with alpha-difluoromethylornithine.

Ornithine decarboxylase (ODC) is a pyridoxal 5'-phosphate (PLP) dependent homodimeric enzyme. It is a recognized drug target against African sleeping sickness, caused by Trypanosoma brucei. One of the currently used drugs, alpha-difluoromethylornithine (DFMO), is a suicide inhibitor of ODC. The structure of the T. brucei ODC (TbODC) mutant K69A bound to DFMO has been determined by X-ray crystallography to 2.0 A resolution. The protein crystallizes in the space group P2(1) (a = 66.8 A, b = 154.5 A, c = 77.1 A, beta = 90.58 degrees ), with two dimers per asymmetric unit. The initial phasing was done by molecular replacement with the mouse ODC structure. The structure of wild-type uncomplexed TbODC was also determined to 2.9 A resolution by molecular replacement using the TbODC DFMO-bound structure as the search model. The N-terminal domain of ODC is a beta/alpha-barrel, and the C-terminal domain of ODC is a modified Greek key beta-barrel. In comparison to structurally related alanine racemase, the two domains are rotated 27 degrees relative to each other. In addition, two of the beta-strands in the C-terminal domain have exchanged positions in order to maintain the location of essential active site residues in the context of the domain rotation. In ODC, the contacts in the dimer interface are formed primarily by the C-terminal domains, which interact through six aromatic rings that form stacking interactions across the domain boundary. The PLP binding site is formed by the C-termini of beta-strands and loops in the beta/alpha-barrel. In the native structure Lys69 forms a Schiff base with PLP. In both structures, the phosphate of PLP is bound between the seventh and eighth strands forming interactions with Arg277 and a Gly loop (residues 235-237). The pyridine nitrogen of PLP interacts with Glu274. DFMO forms a Schiff base with PLP and is covalently attached to Cys360. It is bound at the dimer interface and the delta-carbon amino group of DFMO is positioned between Asp361 of one subunit and Asp332 of the other. In comparison to the wild-type uncomplexed structure, Cys-360 has rotated 145 degrees toward the active site in the DFMO-bound structure. No domain, subunit rotations, or other significant structural changes are observed upon ligand binding. The structure offers insight into the enzyme mechanism by providing details of the enzyme/inhibitor binding site and allows for a detailed comparison between the enzymes from the host and parasite which will aid in selective inhibitor design.

Lysine-69 plays a key role in catalysis by ornithine decarboxylase through acceleration of the Schiff base formation, decarboxylation, and product release steps.

Ornithine decarboxylase (ODC) is a pyridoxal-5'-phosphate-dependent (PLP) enzyme that catalyzes the biosynthesis of the polyamine putrescine. Similar to other PLP-dependent enzymes, an active site Lys residue forms a Schiff base with PLP in the absence of substrate. The mechanistic role of this residue (Lys-69) in catalysis by Trypanosoma brucei ODC has been studied by analysis of the mutant enzymes, in which Lys-69 has been replaced by Arg (K69R ODC) and Ala (K69A ODC). Analysis of K69A ODC demonstrated that the enzyme copurified with amines (e.g. putrescine) that were tightly bound to the active site through a Schiff base with PLP. In contrast, on the basis of an absorption spectrum of K69R ODC, PLP is likely to be bound to this mutant enzyme in the aldehyde form. Pre-steady-state kinetic analysis of the reaction of K69R ODC with L-Orn and putrescine demonstrated that the rates of both the product release (k(off.Put) = 0.0041 s(-)(1)) and the decarboxylation (k(decarb) = 0.016 s(-)(1)) steps were decreased by10(4)-fold in comparison to wild-type ODC. Further, the rates of Schiff base formation between K69R ODC and either substrate or product have decreased by at least 10(3)-fold. Product release remains as the dominant rate-limiting step in the reaction (the steady-state parameters for K69R ODC are k(cat) = 0.0031 s(-)(1) and K(m) = 0.18 mM). The effect of mutating Lys-69 on the decarboxylation step suggests that Lys-69 may play a role in the proper positioning of the alpha-carboxylate for efficient decarboxylation. K69R ODC binds diamines and amino acids with higher affinity than the wild-type enzyme; however, Lys-69 does not mediate substrate specificity. Wild-type and K69R ODC have similar ligand specificity preferring to bind putrescine over longer and shorter diamines. Kinetic analysis of the binding of a series of diamines and amino acids to K69R ODC suggests that noncovalent interactions in the active site of K69R ODC promote selective ligand binding during Schiff base formation.

Revision of the ununited one-bone forearm.

Between 1975 and 1995, 7 patients were surgically treated for persistent forearm pain following previously unsuccessful attempts of constructing a radioulnar synostosis using interosseous bone grafting with either cross screw or pin fixation. These prior reconstructive procedures were salvage operations to address symptomatic radioulnar instability. The time interval between index operation and revision surgery was a mean of 12.6 months (range, 4-36 months). The postoperative follow-up period averaged 29.7 months (range, 11-61 months). To address these failed radioulnar arthrodeses, plate osteosynthesis and aggressive bone grafting were used in 5 of 7 patients (group 1) (4 with autologous graft and 1 with demineralized bone matrix). Union was achieved in all 5 patients after a single revision operation. Radiographic evidence of solid union was seen at approximately 4 months. In the remaining 2 patients (group 2), revision synostosis procedures were performed; these involved local bone grafting and repeat transverse screw fixation in 1 patient and iliac crest bone grafting alone in the other. One of these 2 patients progressed to union; the other had a persistent symptomatic fibrous union. The 5 patients in group 1 reported symptomatic relief, while the 2 patients in group 2 were dissatisfied. There were no postoperative complications in our series. Based on our findings, we advocate abundant bone grafting and plating for rigid internal fixation in failed radioulnar synostosis procedures.

Carbon-13 isotope effect studies of Trypanosoma brucei ornithine decarboxylase.

Carbon isotope effect studies were undertaken with the wild-type pyridoxal 5'-phosphate (PLP)-dependent enzyme ornithine decarboxylase (ODC) from Trypanosoma brucei and with several active site mutants of the enzyme. For the decarboxylation of the optimal substrate, L-ornithine, by wild-type ODC, the observed carbon isotope effect (k12/k13) is 1.033 at pH 7.3. In comparison to the expected intrinsic isotope effect (k12/k13 = 1.06) for decarboxylation, this value suggests that both the rate of decarboxylation and the rate of Schiff base interchange with L-ornithine are partially rate-limiting for the reaction steps up to decarboxylation. In contrast, with the alternate substrate L-Lys, which shows lower catalytic efficiency, the carbon isotope effect increased to 1.063, demonstrating that decarboxylation has become the rate-limiting step. For the mutant enzymes, E274A ODC and C360A ODC, with L-ornithine as substrate the carbon isotope effect also approaches the intrinsic limit. Glu-274 was previously demonstrated to play a direct role in carbanion stabilization, and thus the large carbon isotope effect (k12/k13 = 1.055) is consistent with an impaired rate of decarboxylation compared to wild-type ODC. In contrast, for K69A ODC, the isotope effect is almost entirely suppressed, suggesting that Schiff-base formation (which now must occur from enzyme-bound PLP, rather than from an enzyme-bound PLP-Schiff base) has become rate-determining.

Reconstruction of the scapholunate ligament in a cadaver model using a bone-ligament-bone autograft from the foot.

This study is an investigation of a new procedure in which the scapholunate interosseous ligament (SLIL) is reconstructed using a bone-ligament-bone autograft from the foot. After investigation, the dorsal medial portion of the navicular-first cuneiform ligament (NFCL) was chosen for testing as a potential donor since it is similar in length and thickness to the SLIL and it is easily harvested with minimal potential donor site morbidity. Eight SLILs and NFCLs were harvested from fresh-frozen cadavers. Biomechanical extensometry testing was performed using an Instron 1000 machine. A 5-mm-wide central portion of the NFCL was tested since this width was compatible with the technical aspects of reconstructing the SLIL. Both ligaments were tested for elastic properties, including stiffness, load to failure, and deformation to failure. Mean length of the NFCL was 7.6 mm (range, 5.5-8.5 mm). Stiffness of the NFCL was 10.6 x 10(5) Nm (range, 8.0-13.0 Nm) compared with 14.4 x 10(5) Nm for the SLIL (range, 10.0-19.5 Nm). Peak load to failure for the NFCL was 1,980 N (range, 1,530-2,940 N) compared with 2,940 N for the SLIL (range, 1,780-4,050 N). Total elongation to failure for the NFCL was 2.50 mm (range, 1.7-3.2 mm) compared with 3.2 mm for the SLIL (range, 2.1-5.2 mm). Thus, the biomechanical characteristics of the NFCL were found to be very similar to those of the SLIL. Having established the biomechanical similarities of the 2 ligaments, we are currently using the NFCL to reconstruct the sectioned SLIL in a fresh-frozen cadaver model. Early results suggest that this procedure is feasible for restoration of normal kinematics of the wrist.

The effect of shear stress on fibroblasts derived from Dupuytren's tissue and normal palmar fascia.

This study examines the real-time intracellular calcium changes of palmar fascia from normal and Dupuytren's diseased fibroblasts in response to shear stress. The real-time cytosolic calcium changes were measured using fluorescence microscopy image processing. The preconfluent primary cultured cells were exposed to 1 minute of flow at 25 dyne/cm2 after a 2-minute baseline of no flow. Additionally, the cells were exposed to an influx of Hank's buffered saline solution with 2% newborn bovine serum to examine the response to serum-born (chemical) agonists. Cytosolic calcium changes were measured as the percentage change over the 2-minute baseline of the mean [Ca2+]i peak. The mean change of the peak [Ca2+]i response of the normal palmar fascia was significantly greater than that of the cells from the Dupuytren's nodular and perinodular tissue. The response to the chemical agonist showed a robust but not statistically different response between the 3 cell types. Our work supports the hypothesis that palmar fascia responds to mechanical stress, specifically laminar fluid flow. These findings may help to explain that an underlying abnormality in the cells of the palmar fascia may be expressed by exposure to laminar fluid flow, a physical signal, rather than a chemical agonist.

Workers compensation. Effect of state law on treatment cost and work status.

Workers compensation legislation is regulated at a state level resulting in different benefits based on the state of employment. The negative effect of workers compensation on the results of surgical treatment has been established previously. A comparison of the results of treatment of patients receiving workers compensation from different states has not been reported. This study prospectively evaluated the effect of the difference in state workers compensation laws on the number of postoperative visits, amount of postoperative therapy, time off from work, and return to work status. The study group consisted of 275 patients. The results indicated a significant increase in the number of postoperative visits, amount of therapy, time off from work, and number of patients who remained out of work in the compensation versus the noncompensation group. A significant increase in these parameters also was present in the Pennsylvania compensation group as compared with the New Jersey compensation group. This study shows that differences in workers compensation benefits have a significant effect on the results of medical treatment, return to work status, and the cost of medical care.