Imaging changes following surgery for ischiofemoral impingement.

Partial resection of the lesser trochanter (LT plasty) has been increasingly recommended to treat ischiofemoral impingement. However, there is a lack of studies on the imaging findings following LT plasty. The purpose of this study was to assess magnetic resonance imaging (MRI) changes on the lesser trochanter and surrounding musculotendinous structures following LT plasty to treat ischiofemoral impingement. Twenty-one patients (21 hips) were studied. The LT length and cross-sectional area of the iliopsoas muscle were measured on MRI before and after surgery. The MRIs were performed on average 11 months (range, 3 to 25 months) after surgery. The mean ± standard deviation amount of LT resected (difference between pre- and postoperative LT length) was 7.3 mm ± 2.5 mm. The iliopsoas cross-sectional area decreased after the LT plasty in 95% of the hips (20/21) by an average of 35% ± 16%. The reduction in iliopsoas size had no significant correlation with improvement on the modified Harris Hip Score at a mean follow-up of 17 months after surgery (r = -0.13, P = 0.58). The iliopsoas muscle size decreased on average 35% following endoscopic LT plasty. The decrease was not correlated with midterm functional outcomes.

Anterior Electronic Hip Pain Drawings Are Helpful for Diagnosis of Intra-articular Sources of Pain: Lateral or Posterior Drawings Are Unreliable.

Purpose: The purpose of this study was to determine the accuracy of electronic hip pain drawing to diagnose intra-articular source of pain in nonarthritic hips, defined by response to an intra-articular injection. Methods: A retrospective assessment was performed in consecutive patients who had an intra-articular injection completed within a 1-year period. Patients were classified as responders or nonresponders to intra-articular hip injection. A positive injection was defined as greater than 50% hip pain relief within 2 hours after injection. Electronic pain drawings collected before injection were then evaluated according to the hip region marked by the patients. Results: Eighty-three patients were studied after applying inclusion and exclusion criteria. Anterior hip pain on drawing had a sensitivity of 0.69, specificity of 0.68, positive predictive value (PPV) of 0.86, and negative predictive value (NPV) of 0.44 for intraarticular source of pain. Posterior hip pain on drawing had a sensitivity of 0.59, specificity of 0.23, PPV of 0.68, and NPV of 0.17 for intra-articular source of pain. Lateral hip pain on drawing had a sensitivity of 0.62, specificity of 0.50, PPV of 0.78, and NPV of 0.32 for intraarticular source of pain. Conclusion: Anterior hip pain on electronic drawing has a sensitivity of 0.69 and specificity of 0.68 for intra-articular source of pain in nonarthritic hips. Lateral and posterior hip pain on electronic pain drawings are not reliable to rule out intra-articular hip disease. Level of Evidence: Level III, case-control study.

Three-year safety observation of subcutaneous administration of epoetin-zeta in patients with chronic renal anemia: Results from PASCO II study.

Epoetin has been used to treat patients with renal anemia since 1988. -Anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA) has been associated with epoetin usage, and a PRCA incidence of 4.5 per 10,000 patient-years was observed for epoetin-α (Eprex) in 2002. The PASCO II study (post-authorization safety cohort observation of Retacrit and Silapo (epoetin-ζ) administered subcutaneously for the treatment of renal anemia) followed 6,346 patients (4,501 Retacrit (group R); 1,845 Silapo (group S)) for up to 3 years of subcutaneous treatment with the biosimilar epoetin-ζ. One PRCA in 1 (0.02%) patient in group R who tested positive for neutralizing antibodies was reported. Overall, 527 adverse events of special interest (AESI) including PRCA occurred in 418 (6.60%) patients, lack of efficacy occurred in 34 (0.54%), and thromboembolic events in 389 (6.14%) patients. 41 adverse drug reactions other than AESIs were reported in 28 (0.44%) patients. The exposure-adjusted incident rate of PRCA was 0.84 per 10,000 patient-years. This real-world study showed that among patients with renal anemia receiving subcutaneous administration of the biosimilar product epoetin-ζ, the incidence rate of PRCA was substantially below the risk observed in 2002 for Eprex and that there was no immunogenicity concern or other new safety concern.

IgG-cleavage protein allows therapeutic AAV gene delivery in passively immunized MPS IIIA mice.

The widespread pre-existing αAAV-Abs in humans pose a critical challenge in translation of AAV gene therapy. The IgG degrading enzyme of Streptococci (IdeS) is demonstrated to specifically cleave IgG of humans and other species (not mouse). This study developed a modified new modified IdeS protein product (IdeSop). When incubated in vitro, IdeSop was shown to completely cleave human and rabbit IgGs within 6 h. To test IdeSop in a disease setting, we established a rabbitized αAAV9-Ab+ mouse by an IV infusion of purified acute αAAV9-Ab+ rabbit IgG into MPS IIIA mice, resulting in serum αAAV9-IgG at 1:6,400 and αAAV9-nAbs at 1:800. IdeSop-Ab-cleavage was shown to be dose-dependent. An IV IdeSop infusion at the effective doses resulted in rapid IgG depletion and clearance of pre-existing αAAV9-IgG and αAAV9-nAbs in rabbitized αAAV9-Abs+ MPS IIIA mice. Importantly, an IV injection of a high dose AAV9-hSGSHop vector (5 × 1013vg/kg) at 24 h post IdeSop treatment led to transduction as effective in αAAV9-Abs+ MPS IIIA mice, as in αAAV9-Abs-negative controls. We believe that transient IdeSop administration may offer a great tool to address the pre-existing-αAAV-Abs for the translation of rAAV gene therapy to treat diseases in humans, making effective rAAV gene therapy available to all patients in need.

Hip physical examination extension loss and radiographic osseous findings in patients with low back pain and nonarthritic hips.

The association between hip and spine abnormalities is frequent, and limitation in hip extension has been linked with low back pain. The purpose of this study was to assess the radiographic osseous findings in nonarthritic hips of patients with hip pain, low back pain, and limited hip extension. Ninety patients (92 hips) were included in this study. Hip extension was tested in the contralateral decubitus position with the hip in neutral abduction/adduction and neutral rotation. In sequence, hip extension was tested by adding passive abduction, followed by internal/external rotation of the hip. A hip extension limitation was defined as less than zero degrees of extension. Imaging studies were assessed for the following osseous morphologies: decreased ischiofemoral space (≤17 mm), increased femoral torsion (≥30°), decreased femoral torsion (≤5°), and posterior acetabular overcoverage. Fifty-seven out of 92 hips (62%) had at least one osseous imaging finding for limitation in hip extension: decreased ischiofemoral space (38/92, 41%), increased femoral torsion (5/92, 5%), decreased femoral torsion (24/92, 26%), and posterior acetabular overcoverage (21/92, 23%). Decreased ischiofemoral space, femoral torsional abnormalities, and/or posterior acetabular wall overcoverage are observed in imaging studies of most individuals with limitation of hip extension and low back pain.

Transient and Local Expression of Chemokine and Immune Checkpoint Traps To Treat Pancreatic Cancer.

Pancreatic tumors are known to be resistant to immunotherapy due to the extensive immune suppressive tumor microenvironment (TME). We hypothesized that CXCL12 and PD-L1 are two key molecules controlling the immunosuppressive TME. Fusion proteins, called traps, designed to bind with these two molecules with high affinity (Kd = 4.1 and 0.22 nM, respectively) were manufactured and tested for specific binding with the targets. Plasmid DNA encoding for each trap was formulated in nanoparticles and intravenously injected to mice bearing orthotopic pancreatic cancer. Expression of traps was mainly seen in the tumor, and secondarily, accumulations were primarily in the liver. Combination trap therapy shrunk the tumor and significantly prolonged the host survival. Either trap alone only brought in a partial therapeutic effect. We also found that CXCL12 trap allowed T-cell penetration into the tumor, and PD-L1 trap allowed the infiltrated T-cells to kill the tumor cells. Combo trap therapy also significantly reduced metastasis of the tumor cells to other organs. We conclude that the trap therapy significantly modified the immunosuppressive TME to allow the host immune system to kill the tumor cells. This can be an effective therapy in clinical settings.

Liver specific gene immunotherapies resolve immune suppressive ectopic lymphoid structures of liver metastases and prolong survival.

The ability to generate potent immunotherapies locally and transiently for the treatment of cancers is a promising strategy to improve efficacy and decrease off-target toxicities. Here, we explored an alternative approach for the delivery of immunotherapeutic agents, in which we deliver the pDNA of an engineered PD-L1 trap and/or CXCL12 trap to the nucleus of liver hepatocytes via a lipid calcium phosphate nanoparticle. This strategy greatly increased the concentrations of immunotherapeutic agents in the local tissue, allowing the therapy to inhibit the accumulation of immune suppressive cells and liver metastasis. Furthermore, we find that the lipid calcium phosphate nanoparticles containing the pCXCL12 trap resolved the formation of immune suppressive ectopic lymphoid structures, while the pPD-L1 trap promoted T-cell survival and migration into the liver following vaccination against tumor antigens (>180% increase in survival). This approach showed superior efficacy in the treatment of the liver metastasis compared to free protein immunotherapies. This strategy should be considered as an approach to support liver metastasis therapies as well as for future research interested in manipulating the chemokine/cytokine immune factors within the liver. SIGNIFICANCE: Our approach results in transient liver specific expression of gene immunotherapies with improved efficacy and reduced off-target toxicities over traditional systemically administered immunotherapies. This approach would allow clinicians to manipulate the liver and immune microenvironment to resist cancer invasion, improve organ health, and prolong patient survival.