Interferon gamma immunoPET imaging to evaluate response to immune checkpoint inhibitors.

Introduction: We previously developed a 89Zr-labeled antibody-based immuno-positron emission tomography (immunoPET) tracer targeting interferon gamma (IFNγ), a cytokine produced predominantly by activated T and natural killer (NK) cells during pathogen clearance, anti-tumor immunity, and various inflammatory and autoimmune conditions. The current study investigated [89Zr]Zr-DFO-anti-IFNγ PET as a method to monitor response to immune checkpoint inhibitors (ICIs). Methods: BALB/c mice bearing CT26 colorectal tumors were treated with combined ICI (anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1)). The [89Zr]Zr-DFO-anti-IFNγ PET tracer, generated with antibody clone AN18, was administered on the day of the second ICI treatment, with PET imaging 72 hours later. Tumor mRNA was analyzed by quantitative reverse-transcribed PCR (qRT-PCR). Results: We detected significantly higher intratumoral localization of [89Zr]Zr-DFO-anti-IFNγ in ICI-treated mice compared to untreated controls, while uptake of an isotype control tracer remained similar between treated and untreated mice. Interestingly, [89Zr]Zr-DFO-anti-IFNγ uptake was also elevated relative to the isotype control in untreated mice, suggesting that the IFNγ-specific tracer might be able to detect underlying immune activity in situ in this immunogenic model. In an efficacy experiment, a significant inverse correlation between tracer uptake and tumor burden was also observed. Because antibodies to cytokines often exhibit neutralizing effects which might alter cellular communication within the tumor microenvironment, we also evaluated the impact of AN18 on downstream IFNγ signaling and ICI outcomes. Tumor transcript analysis using interferon regulatory factor 1 (IRF1) expression as a readout of IFNγ signaling suggested there may be a marginal disruption of this pathway. However, compared to a 250 µg dose known to neutralize IFNγ, which diminished ICI efficacy, a tracer-equivalent 50 µg dose did not reduce ICI response rates. Discussion: These results support the use of IFNγ PET as a method to monitor immune activity in situ after ICI, which may also extend to additional T cell-activating immunotherapies.

Detection of IL12/23p40 via PET Visualizes Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), which includes both Crohn disease and ulcerative colitis, is a relapsing inflammatory disease of the gastrointestinal tract. Long-term chronic inflammatory conditions elevate the patient's risk of colorectal cancer (CRC). Currently, diagnosis requires endoscopy with biopsy. This procedure is invasive and requires a bowel-preparatory regimen, adding to patient burden. Interleukin 12 (IL12) and interleukin 23 (IL23) play key roles in inflammation, especially in the pathogenesis of IBD, and are established therapeutic targets. We propose that imaging of IL12/23 and its p40 subunit in IBD via immuno-PET potentially provides a new noninvasive diagnostic approach. Methods: Our aim was to investigate the potential of immuno-PET to image inflammation in a chemically induced mouse model of colitis using dextran sodium sulfate by targeting IL12/23p40 with a 89Zr-radiolabeled anti-IL12/23p40 antibody. Results: High uptake of the IL12/23p40 immuno-PET agent was exhibited by dextran sodium sulfate-administered mice, and this uptake correlated with increased IL12/23p40 present in the sera. Competitive binding studies confirmed the specificity of the radiotracer for IL12/23p40 in the gastrointestinal tract. Conclusion: These promising results demonstrate the utility of this radiotracer as an imaging biomarker of IBD. Moreover, IL12/23p40 immuno-PET can potentially guide treatment decisions for IBD management.

Selective ablation of TRA-1-60+ pluripotent stem cells suppresses tumor growth of prostate cancer.

Purpose: TRA-1-60 (TRA) is an established transcription factor of embryonic signaling and a well-known marker of pluripotency. It has been implicated in tumorigenesis and metastases, is not expressed in differentiated cells, which makes it an appealing biomarker for immunopositron emission tomography (immunoPET) imaging and radiopharmaceutical therapy (RPT). Herein, we explored the clinical implications of TRA in prostate cancer (PCa), examined the potential of TRA-targeted PET to specifically image TRA+ cancer stem cells (CSCs) and assessed response to the selective ablation of PCa CSCs using TRA-targeted RPT. Experimental Design: First, we assessed the relationship between TRA (PODXL) copy number alterations (CNA) and survival using publicly available patient databases. The anti-TRA antibody, Bstrongomab, was radiolabeled with Zr-89 or Lu-177 for immunoPET imaging and RPT in PCa xenografts. Radiosensitive tissues were collected to assess radiotoxicity while excised tumors were examined for pathologic treatment response. Results: Patients with tumors having high PODXL CNA exhibited poorer progression-free survival than those with low PODXL, suggesting that it plays an important role in tumor aggressiveness. TRA-targeted immunoPET imaging specifically imaged CSCs in DU-145 xenografts. Tumors treated with TRA RPT exhibited delayed growth and decreased proliferative activity, marked by Ki-67 immunohistochemistry. Aside from minor weight loss in select animals, no significant signs of radiotoxicity were observed in the kidneys or livers. Conclusions: We successfully demonstrated the clinical significance of TRA expression in human PCa, engineered and tested radiotheranostic agents to image and treat TRA+ prostate CSCs. Ablation of TRA+ CSCs blunted PCa growth. Future studies combining CSC ablation with standard treatment will be explored to achieve durable responses.

Evaluation and selection of a lead diabody for interferon-γ PET imaging.

INTRODUCTION: Interferon-γ (IFN-γ) is an appealing target to evaluate immune response in cancer immunotherapy as it is a hallmark of an active immune system. Imaging and detection via immunopositron emission tomography (immunoPET) of this soluble cytokine has been made feasible using a 89Zr-labeled (t 1/2 ~ 3.27 d) monoclonal antibody (mAb). Because of its size, using a full-length mAb as an imaging vector is not ideal for repeat serial imaging because of its prolonged blood pool residency and tumor accumulation resulting in lengthier wait times between administration and imaging. This consequently impacts the potential to image a dynamic immune response in real time. This work compares 89Zr-labeled diabodies (Db) designed with variable linker lengths between the VH and VL regions with the goal of selecting a lead Db for future studies. METHODS AND RESULTS: Four Db fragments with various linker lengths (HL-n, n = 7-13 amino acids) were each conjugated to desferrioxamine (DFO). The number of attached chelates was analyzed via mass spectrometry with all immunoconjugates exhibiting one unit of DFO attached. Db-DFO conjugates were subsequently radiolabeled with zirconium-89. All constructs radiolabeled with high yields. Each radioimmunoconjugate was tested for reactivity to IFN-γ. All tracers except for [89Zr]Zr-DFO-NCS-anti-IFN-γ HL-9 exhibited comparable immunoreactivities (>90 %) to the radiolabeled parent mAb (95.8 %). At 24 h post-labeling, the IRF values were retained except for the HL-13 construct. Imaging scans and tissue distribution studies acquired in mice bearing CT26 syngeneic colorectal tumors between 1 and 24 h post-tracer administration demonstrated variable clearance kinetics and tumor localization of each radiotracer. HL-7 had higher binding in non-tumor tissues compared to HL-11 and HL-13 at 3 h p.i. Competitive binding studies versus unmodified parent mAb (AN-18) demonstrated blocking of radiolabeled HL-11 and HL-13. [89Zr]Zr-DFO-NCS-anti-IFN-γ HL-7 was inadequately blocked. CONCLUSION: Despite nuanced differences in linker lengths, our data demonstrates that [89Zr]Zr-DFO-NCS-anti-IFN-γ HL-11 exhibited the best radiotracer properties for the assessment of IFN-γ production in vivo. Work is currently underway to test the potential of using shorter-lived isotopes, like copper-64 (t1/2 ~ 12.7 h) to match pharmacokinetics and half-lives.

Results of hip arthroscopy in elite level water polo players with femoroacetabular impingement: return to play and patient satisfaction.

Water polo places significant stress on the hip joint requiring repetitive hip flexion and rotation to elevate the body out of water for passing, shooting and blocking. Femoroacetabular impingement (FAI) is common in water polo athletes; however, no study to date has investigated the results of hip arthroscopy in this patient population. The purpose of this study was to determine return to play rates and satisfaction following hip arthroscopy for FAI in a cohort of elite level water polo players. A retrospective review of our surgical database was performed. Collegiate water polo players with clinical and radiographic FAI who underwent hip arthroscopy were identified. Pre- and post-operative modified Harris hip scores (mHHSs) were obtained. Patient surveys were administered to determine return to play rates, level of return to play, timing of return and patient satisfaction. A Wilcoxon ranked sum test was performed to compare pre- and post-operative outcome scores. Ten patients met inclusion criteria. Average age was 19.5 years old (SD ±1.08). All patients were male Division 1 collegiate water polo players. Median mHHS improved from 66.0 (SD ±7.9) pre-operatively to 89.5 (SD ±3.2) at average 1.6 years (range: 0.4-3.6 years) post-operatively. Patient survey responses demonstrated a 100% return to water polo and 100% return to the same level of play (NCAA Division 1) at mean 5.75 months (SD ±1.8). All patients (10/10) reported being satisfied with their surgical result. Our study results, suggest that return to sport rates and patient satisfaction are high in water polo players who undergo hip arthroscopy for FAI.

Noninvasive PET Imaging of CDK4/6 Activation in Breast Cancer.

The cell cycle is a progression of 4 distinct phases (G1, S, G2, and M), with various cycle proteins being essential in regulating this process. We aimed to develop a radiolabeled cyclin-dependent kinase 4/6 (CDK4/6) inhibitor for breast cancer imaging. Our transfluorinated analog (18F-CDKi) was evaluated and validated as a novel PET imaging agent to quantify CDK4/6 expression in estrogen receptor (ER)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Methods:18F-CDKi was synthesized and assayed against CDK4/6 kinases. 18F-CDKi was prepared with a 2-step automated synthetic strategy that yielded the final product with remarkable purity and molar activity. In vitro and in vivo biologic specificity was assessed in a MCF-7 cell line and in mice bearing MCF-7 breast tumors. Nonradioactive palbociclib was used as a blocking agent to investigate the binding specificity and selectivity of 18F-CDKi. Results:18F-CDKi was obtained with an overall radiochemical uncorrected yield of 15% and radiochemical purity higher than 98%. The total time from the start of synthesis to the final injectable formulated tracer is 70 min. The retention time reported for 18F-CDKi and 19F-CDKi is 27.4 min as demonstrated by coinjection with 19F-CDKi in a high-pressure liquid chromatograph. In vivo blood half-life (weighted, 7.03 min) and octanol/water phase partition coefficient (1.91 ± 0.24) showed a mainly lipophilic behavior. 18F-CDKi is stable in vitro and in vivo (>98% at 4 h after injection) and maintained its potent targeting affinity to CDK4/6. Cellular uptake experiments performed on the MCF-7 breast cancer cell line (ER-positive and HER2-negative) demonstrated specific uptake with a maximum intracellular concentration of about 65% as early as 10 min after incubation. The tracer uptake was reduced to less than 5% when cells were coincubated with a molar excess of palbociclib. In vivo imaging and ex vivo biodistribution of ER-positive, HER2-negative MCF-7 breast cancer models showed a specific uptake of approximately 4% injected dose/g of tumor (reduced to ∼0.3% with a 50-fold excess of cold palbociclib). A comprehensive biodistribution analysis also revealed a significantly lower activation of CDK4/6 in nontargeting organs. Conclusion:18F-CDKi represents the first 18F PET CDK4/6 imaging agent and a promising imaging agent for ER-positive, HER2-negative breast cancer.

UCL Injury in the Non-throwing Athlete.

PURPOSE OF REVIEW: Primarily reported in the overhead throwing athlete, ulnar collateral ligament (UCL) injuries have been extensively studied since Dr. Frank Jobe first described his technique for ulnar collateral ligament reconstruction on professional baseball pitcher Tommy John. While the framework for our understanding of UCL injury was initially established studying the repetitive valgus loading of the throwers' elbow, other sport-related activities in non-throwing athletes can impart similar valgus stress on the medial elbow placing the UCL at risk for injury. The purpose of this review is to evaluate the current literature on UCL injury specifically in the non-throwing athlete. RECENT FINDINGS: In the four decades since Dr. Jobe's seminal description of UCL reconstruction, an abundance of literature has been published on UCL injury in the throwing athlete. The evidence evaluating the UCL specifically in the non-throwing athlete, however, is quite scarce. Several small retrospective studies have demonstrated good results with high rates of return to play with focused rehabilitation and non-operative management in non-throwing athletes. Recent evidence has also demonstrated that surgical repair and/or reconstruction of the UCL in this population can produce good outcomes. The level of evidence of these published studies is low and consists primarily of case series without control groups. Further investigation is warranted to determine the optimal treatment algorithm for UCL injury in the non-throwing athlete.

Does Medial-Row Fixation Technique Affect the Retear Rate and Functional Outcomes After Double-Row Transosseous-Equivalent Rotator Cuff Repair?

BACKGROUND: Double-row transosseous-equivalent (TOE) rotator cuff repair techniques have been widely accepted because of their superior biomechanical properties when compared with arthroscopic single-row repair. Concerns regarding repair overtensioning with medial-row knot tying have led to increased interest in knotless repair techniques; however, there is a paucity of clinical data to guide the choice of technique. HYPOTHESIS: Arthroscopic TOE repair techniques using knotless medial-row fixation will demonstrate lower retear rates and greater improvements in the Constant score relative to conventional knot-tying TOE techniques. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review of 3 databases (PubMed, Cochrane, and Embase) was performed using PRISMA (Preferred Reporting Items for Systematic Meta-Analyses) guidelines. Inclusion criteria were English-language studies that examined repair integrity or Constant scores after arthroscopic rotator cuff repair with TOE techniques. Two investigators independently screened results for relevant articles. Data regarding the study design, surgical technique, retear rate, and Constant shoulder score were extracted from eligible studies. A quality assessment of all articles was performed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. RESULTS: The systematic review identified a total of 32 studies (level of evidence, 1-4) that met inclusion and exclusion criteria. Of the 32 studies, 5 reported on knotless TOE techniques, 25 reported on knot-tying TOE techniques, and 2 reported on both. In the knotless group, retear rates ranged from 6% to 36%, and Constant scores ranged from 38-65 (preoperative) to 73-83 (postoperative). In the knot-tying group, retear rates ranged from 0% to 48%, and Constant scores ranged from 42-64 (preoperative) to 55-96 (postoperative). CONCLUSION: Despite several theoretical advantages of knotless TOE repair, both knotless and knot-tying techniques reported considerable improvement in functional outcomes after rotator cuff repair. Although tendon failure rates showed a downward trend in knotless studies, additional prospective studies are warranted to better understand the role of medial-row fixation on tendon repair integrity and postoperative clinical outcomes.

Prior Staphylococcus Aureus Nasal Colonization: A Risk Factor for Surgical Site Infections Following Decolonization.

INTRODUCTION: Staphylococcus aureus (S aureus) decolonization regimens are being used to mitigate the risk of surgical site infection (SSI). However, their efficacy is controversial, with mixed results reported in the literature. METHODS: Before undergoing primary total knee arthroplasty (TKA), total hip arthroplasty (THA), or spinal fusion, 13,828 consecutive patients were screened for nasal S aureus and underwent a preoperative decolonization regimen. Infection rates of colonized and noncolonized patients were compared using unadjusted logistic regression. An adjusted regression analysis was performed to determine independent risk factors for SSI. RESULTS: The rate of SSI in colonized patients was 4.35% compared with only 2.39% in noncolonized patients. In our TKA cohort, unadjusted logistic regression identified S aureus colonization to be a significant risk factor for SSI (odds ratio [OR], 2.9; P < 0.001). After controlling for other potential confounders including age, body mass index, tobacco use, and American Society of Anesthesiologists score, an SSI was 3.8 times more likely to develop in patients colonized with S aureus (OR, 3.8; P = 0.0025). The THA and spine colonized patients trended toward higher risk in both unadjusted and adjusted models; however, the results were not statistically significant. DISCUSSION: The results of our study suggest that decolonization may not be fully protective against SSI. The risk of infection after decolonization is not lowered to the baseline of a noncolonized patient. LEVEL OF EVIDENCE: Level IV.

Synthesis and evaluation of (18)F-labeled ATP competitive inhibitors of topoisomerase II as probes for imaging topoisomerase II expression.

Type II topoisomerase (Topo-II) is an ATP-dependent enzyme that is essential in the transcription, replication, and chromosome segregation processes and, as such, represents an attractive target for cancer therapy. Numerous studies indicate that the response to treatment with Topo-II inhibitors is highly dependent on both the levels and the activity of the enzyme. Consequently, a non-invasive assay to measure tumoral Topo-II levels has the potential to differentiate responders from non-responders. With the ultimate goal of developing a radiofluorinated tracer for positron emission tomography (PET) imaging, we have designed, synthesized, and evaluated a set of fluorinated compounds based on the structure of the ATP-competitive Topo-II inhibitor QAP1. Compounds 18 and 19b showed inhibition of Topo-II in in vitro assays and exhibited moderate, Topo-II level dependent cytotoxicity in SK-BR-3 and MCF-7 cell lines. Based on these results, (18)F-labeled analogs of these two compounds were synthesized and evaluated as PET probes for imaging Topo-II overexpression in mice bearing SK-BR-3 xenografts. [(18)F]-18 and [(18)F]-19b were synthesized from their corresponding protected tosylated derivatives by fluorination and subsequent deprotection. Small animal PET imaging studies indicated that both compounds do not accumulate in tumors and exhibit poor pharmacokinetics, clearing from the blood pool very rapidly and getting metabolized over. The insights gained from the current study will surely aid in the design and construction of future generations of PET agents for the non-invasive delineation of Topo-II expression.

Correlation between physician specific discharge costs, LOS, and 30-day readmission rates: an analysis of 1,831 cases.

There is currently wide variation in the use and cost of post acute care following total joint arthroplasty. Additionally the optimum setting to which patients should be discharged after surgery is controversial. Discharge patterns following joint replacement vary widely between physicians at our institution, however, only weak correlations were found between the cost of discharge and length of stay or readmission rates. The inter-physician variance in discharge cost did not correlate to a difference in quality, as measured by length of stay and readmission rates, but does imply there is significant opportunity to modify physician discharge practices without impacting patient outcomes and the quality of care.

A comparison of the imaging characteristics and microregional distribution of 4 hypoxia PET tracers.

UNLABELLED: We compared the imaging characteristics and hypoxia selectivity of 4 hypoxia PET radiotracers ((18)F-fluoromisonidazole [(18)F-FMISO], (18)F-flortanidazole [(18)F-HX4], (18)F-fluoroazomycin arabinoside [(18)F-FAZA], and (64)Cu-diacetyl-bis(N4-methylsemicarbazone) [(64)Cu-ATSM]) in a single murine xenograft tumor model condition using small-animal PET imaging and combined ex vivo autoradiography and fluorescence immunohistochemistry. METHODS: Nude mice bearing SQ20b xenograft tumors were administered 1 of 4 hypoxia PET tracers and images acquired 80-90 min after injection. Frozen sections from excised tumors were then evaluated for tracer distribution using digital autoradiography and compared with histologic markers of tumor hypoxia (pimonidazole, carbonic anydrase 9 [CA9]) and vascular perfusion (Hoechst 33342). RESULTS: The highest tumor uptake was observed with (64)Cu-ATSM (maximum standardized uptake values [SUV(max)], 1.26 ± 0.13) and the lowest with (18)F-FAZA (SUVmax, 0.41 ± 0.24). (18)F-FMISO and (18)F-HX4 had similar intermediate tumor uptake (SUV(max), 0.76 ± 0.38 and 0.65 ± 0.19, respectively). Digital autoradiographs of hypoxia tracer distribution were compared pixel by pixel with images of immunohistochemistry stains. The fluorinated nitroimidazoles all showed radiotracer uptake increasing with pimonidazole and CA9 staining. (64)Cu-ATSM showed the opposite pattern, with highest radiotracer uptake observed in regions with the lowest pimonidazole and CA9 staining. CONCLUSION: The fluorinated nitroimidazoles showed similar tumor distributions when compared with immunohistochemistry markers of hypoxia. Variations in tumor standardized uptake value and normal tissue distribution may determine the most appropriate clinical setting for each tracer. (64)Cu-ATSM showed the highest tumor accumulation and little renal clearance. However, the lack of correlation between (64)Cu-ATSM distribution and immunohistochemistry hypoxia markers casts some doubt on the hypoxia selectivity of (64)Cu-ATSM.

The effect of discharge disposition on 30-day readmission rates after total joint arthroplasty.

Previous studies have demonstrated no significant difference in overall functional outcomes of patients discharged to a sub acute setting versus home with health services after total joint arthroplasty. These findings coupled with pressure to reduce health care costs and the implementation of a prospective payment system under Medicare have supported the use of home rehabilitation services and the trend towards earlier discharge after hospitalization. While the overall functional outcome of patients discharged to various settings has been studied, there is a relative dearth of investigation comparing postoperative complications and readmission rates between various discharge dispositions. Our study demonstrated patients discharged home with health services had a significantly lower 30 day readmission rate compared to those discharged to inpatient rehab facilities. Patients discharged to rehab facilities have a higher incidence of comorbidity and this association could be responsible for their higher rate of readmission.

H(4)octapa-trastuzumab: versatile acyclic chelate system for 111In and 177Lu imaging and therapy.

A bifunctional derivative of the versatile acyclic chelator H4octapa, p-SCN-Bn-H4octapa, has been synthesized for the first time. The chelator was conjugated to the HER2/neu-targeting antibody trastuzumab and labeled in high radiochemical purity and specific activity with the radioisotopes (111)In and (177)Lu. The in vivo behavior of the resulting radioimmunoconjugates was investigated in mice bearing ovarian cancer xenografts and compared to analogous radioimmunoconjugates employing the ubiquitous chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). The H4octapa-trastuzumab conjugates displayed faster radiolabeling kinetics with more reproducible yields under milder conditions (15 min, RT, ~94-95%) than those based on DOTA-trastuzumab (60 min, 37 °C, ~50-88%). Further, antibody integrity was better preserved in the (111)In- and (177)Lu-octapa-trastuzumab constructs, with immunoreactive fractions of 0.99 for each compared to 0.93-0.95 for (111)In- and (177)Lu-DOTA-trastuzumab. These results translated to improved in vivo biodistribution profiles and SPECT imaging results for (111)In- and (177)Lu-octapa-trastuzumab compared to (111)In- and (177)Lu-DOTA-trastuzumab, with increased tumor uptake and higher tumor-to-tissue activity ratios.

Thirty-day readmission rates as a measure of quality: causes of readmission after orthopedic surgeries and accuracy of administrative data.

The rate of unplanned 30-day readmissions to the hospital after discharge is being used as a marker to compare the quality of care across hospitals and to set reimbursement levels for care. While the readmission rate can be reported using administrative data, the accuracy of these data is variable, and defining which readmissions are unplanned and preventable is often difficult. The purpose of this study was to review readmissions to a single orthopedic hospital to identify the causes for readmission and, in particular, which readmissions are planned versus unplanned. Using that hospital's administrative database of patient records from 2007 to 2009, we identified all patients who were readmitted to the hospital within 30 days of a previous hospitalization for a procedure. Readmissions were broadly categorized as planned (a staged or rescheduled procedure or a direct transfer) or unplanned. Unplanned readmissions were defined as either surgical or nonsurgical complications (medical conditions not directly related to the procedure). Almost 30 percent of readmissions were planned. Of the unplanned readmissions, close to 60 percent were triggered by an infection or a concern for an infection. Nonsurgical complications accounted for 18.2 percent of unplanned readmissions. This study highlights the importance of careful data collection and abstraction when calculating early readmission rates. Preventing surgical site infection and better coordinating care between orthopedic surgeons and primary care and medical subspecialty physicians may significantly reduce readmission rates.

(89)Zr-labeled paramagnetic octreotide-liposomes for PET-MR imaging of cancer.

PURPOSE: Dual-modality PET/MR platforms add a new dimension to patient diagnosis with high resolution, functional, and anatomical imaging. The full potential of this emerging hybrid modality could be realized by using a corresponding dual-modality probe. Here, we report pegylated liposome (LP) formulations, housing a MR T(1) contrast agent (Gd) and the positron-emitting (89)Zr (half-life: 3.27 days), for simultaneous PET and MR tumor imaging capabilities. METHODS: (89)Zr oxophilicity was unexpectedly found advantageous for direct radiolabeling of preformed paramagnetic LPs. LPs were conjugated with octreotide to selectively target neuroendocrine tumors via human somatostatin receptor subtype 2 (SSTr2). (89)Zr-Gd-LPs and octreotide-conjugated homolog were physically, chemically and biologically characterized. RESULTS: (89)Zr-LPs showed reasonable stability over serum proteins and chelator challenges for proof-of-concept in vitro and in vivo investigations. Nuclear and paramagnetic tracking quantified superior SSTr2-recognition of octreotide-LP compared to controls. CONCLUSIONS: This study demonstrated SSTr2-targeting specificity along with direct chelator-free (89)Zr-labeling of LPs and dual PET/MR imaging properties.

An analysis of causes of readmission after spine surgery.

STUDY DESIGN: Retrospective review of medical records. OBJECTIVE: We reviewed all early readmissions after elective spine surgery at a single orthopedic specialty hospital to analyze the causes of unplanned readmissions. SUMMARY OF BACKGROUND DATA: Recent advances in techniques and instrumentation have made more complex spinal surgeries possible, although sometimes with more complications. Early readmission rate is being used as a marker to evaluate quality of care. There is little data available regarding the causes of early readmissions after spine surgery. METHODS: Using the hospital's administrative database of patient records from 2007 to 2009, all patients who underwent spine surgery and were readmitted to the hospital within 30 days were identified and broadly categorized as planned (a staged or rescheduled procedure or a direct transfer) or unplanned. Unplanned readmissions were defined to have occurred as a result of either a surgical or a nonsurgical complication. Analysis was focused on 12 common spine procedures based on the principle procedure International Classification of Diseases, Ninth Revision, Clinical Modification code for the patient's initial admission. The readmission rate was calculated for each procedure. RESULTS: A total of 156 early readmissions were identified, of which 141 were unplanned. Of the unplanned readmissions, the most common causes were infection or a concern for an infection (45 patients, 32% of unplanned readmissions), nonsurgical complications (31 patients, 22% of readmissions), complications requiring surgical revision (21 patients, 15% of readmissions), and wound drainage (12 patients, 9% of readmissions). Fifty-seven percent of unplanned readmissions required a return to the operating room (76% of infections or concern for infection). The average length of stay for the unplanned readmissions was 6.5 days. When using the 12 most common procedures based on the International Classification of Diseases, Ninth Revision, Clinical Modification, the early readmission rate was 3.8% (141 early readmissions in 3673 procedures). CONCLUSION: Infection, medical complications after surgery, and surgical complications requiring revision of implants are the primary causes of unplanned early readmissions and spine surgery. Further studies are necessary to identify patients and procedures most associated with readmission.

The persistence of Staphylococcus aureus decolonization after mupirocin and topical chlorhexidine: implications for patients requiring multiple or delayed procedures.

Preoperative screening and decolonization of methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA, respectively) are advocated to reduce surgical site infections. We determined the rate and duration of decolonization in patients undergoing elective orthopedic surgery. Patients undergoing elective orthopedic surgery were seen in our preoperative testing program (PAT) and had their anterior nares cultured for MRSA and MSSA. All patients were treated with intranasal mupirocin and a topical chlorhexidine solution. A cohort of patients returned to PAT before a subsequent elective procedure and were recultured. All culture results and time between PAT visits were recorded, and the rates of successful initial and persistent decolonization were determined. Six hundred ten patients visited PAT 1290 times. Overall, 94 (70.1%) of 134 patients with initially MRSA- or MSSA-positive cultures remained decolonized at a mean time of 156 days (SD=140), whereas 40 patients (29.9%) were not decolonized by the time of repeat testing at a mean time of 213 days (SD=187). At repeat testing, there were 2 newly MRSA-positive and 35 newly MSSA-positive patients. Staphylococcus aureus decolonization with intranasal mupirocin and topical chlorhexidine was effective but not persistent in a significant proportion of patients. A small number of previously uncolonized patients became colonized. Staphylococcus aureus screening and decolonization protocols must be repeated before any readmission, regardless of prior colonization status.

Surgical site infection prevention initiative - patient attitude and compliance.

BACKGROUND: Although the effect of Staphylococcus aureus (SA) decolonization on surgical site infection (SSI) rates has been studied, patient tolerance and acceptance of these regimens has not been assessed. Surgical patients at our hospital's Pre-Admission Testing Clinic (PAT) receive SA reduction protocols instructing the preoperative use of chlorhexidine gluconate (CHG) soap and intranasal mupirocin ointment (MO). Certain insurers do not cover MO costs resulting in out of pocket (OOP) expenses for some patients. OBJECTIVE: This study assessed patient attitudes and compliance with our hospital's SA decolonization regimen. METHODS: One-hundred-forty-six patients received surveys. Descriptive statistics were used for analysis. RESULTS: Of respondents fitting inclusion criteria, 81% followed the MO protocol (MO users) while 89% followed the CHG protocol (CHG users). Fifty-four percent of MO users reported OOP expenses and 13% reported a hard or very hard financial burden. Ninety-three percent of CHG users reported the protocol was easy or very easy to follow. CONCLUSION: Eighty-one percent of patients receiving the SA protocol were fully compliant despite cost or difficulty obtaining MO. Given these barriers and some difficulty with CHG application, we hypothesize compliance may be improved if MO is provided to patients without OOP expenses and if the CHG application method is simplified.