Citations

The Case Study Interpretation (CSI) cases presented at the 2014 International Clinical Cytometry Society (ICCS) meeting in Seattle illustrate the utility of state‐of‐the art multiparameter flow cytometry in the diagnosis of hematolymphoid neoplasms. Download the listmode files (Supporting Information) and test your analysis skills before reading the case reports, keeping in mind the following questions. How many separate abnormal mature B‐cell populations can you identify, and how many of these represent different subtypes of B‐cell neoplasm? How many separate abnormal mature T‐cell populations can you identify, and do these represent different subtypes of T‐cell neoplasm or phenotypic heterogeneity in one neoplasm? How many separate immature/blastic cell populations can you identify, and do they meet criteria for mixed phenotype leukemia? Is there a population of blasts that lacks T‐cell, B‐cell, and myeloid lineage defining antigens and if so, what entities should you consider and what additional antigens should you assess for? © 2015 International Clinical Cytometry Society

ABSTRACTBACKGROUNDDisability progression in multiple sclerosis (MS) remains incompletely understood. Unlike lesional measures, central nervous system atrophy has a strong correlation with disability. Theiler's murine encephalomyelitis virus infection in SJL/J mice is an established model of progressive MS. We utilized in vivo MRI to quantify brain and spinal cord atrophy in this model and analyzed the temporal relationship between atrophy and disability.METHODSInfected and control mice were followed for 12 months. Disability was assessed periodically using rotarod assay. Volumetric MRI datasets were acquired at 7 Tesla. Ventricular volume and C4‐5 spinal cord cross‐sectional area measurements were performed using Analyze 10.RESULTSAt 3 months, brain atrophy reached statistical significance (P = .005). In contrast, disability did not differ until 4 months post‐infection (P = .0005). Cord atrophy reached significance by 9 months (P = 0.009). By 12 months, brain atrophy resulted in 111.8% increased ventricular volume (P = .00003), while spinal cord cross‐sectional area was 25.6% reduced (P = .001) among cases.CONCLUSIONSOur results suggest that significant brain atrophy precedes and predicts the development of disability, while spinal cord atrophy occurs late and correlates with severe disability. The observed temporal relationship establishes a framework for mechanisms of disability progression and enables further investigations of their underlying substrate.

Objectives: Intra-articular (IA) anesthetic injection is commonly performed as a diagnostic test in the setting of femoroacetabular impingement (FAI). Currently, there is a paucity of data correlating post-injection pain relief and outcomes after hip arthroscopy for FAI. The purpose of this study is to determine whether the amount of pain relief after IA injection predicts clinical and functional outcomes following hip arthroscopy. We hypothesize that increased pain relief (>50%) will correlate with better outcomes after surgery. Methods: The records of patients undergoing hip arthroscopy for FAI at our institution between April 2007 and April 2012 were reviewed. We identified patients who underwent IA injection and subsequent hip arthroscopy. Inclusion criteria were: ultrasound or fluoroscopic guided intra-articular anesthetic injection performed at our institution, prospectively documented pre- and post-injection Numerical Rating Scale (NRS) pain scores, no prior ipsilateral hip surgery, and minimum 1 year follow-up. Pre-operative radiographs were reviewed and degree of osteoarthritis was determined using the Tonnis classification system. Outcomes were assessed with Modified Harris Hip Score (MHHS) and Hip Outcome Score (HOS). Univariate and multivariate models were performed to assess whether percent pain relief correlated with outcome scores. Results: 99 hips in 96 patients met our inclusion criteria and included 71 females (74%) and 25 males (26%) with a mean age of 37.5 ± 14.0 years. 26 patients had Tonnis grade 0, 55 had grade 1, and 18 had grade 2 (0 grade 3). Mean pain relief after IA injection was 73.6 ± 36.1 (range 0-100) percent. 26 patients (26%) had ≤50% pain relief while 73 (74%) had >50% pain relief. Outcome scores were obtained at a mean 14.9 months. Mean MHHS, HOS-ADL, and HOS-Sport scores were 79.2 ± 17.3, 82.6 ± 17.3, and 67.4 ± 28.2, respectively. There was no statistical correlation between percent pain relief and MHHS, HOS-ADL, or HOS-Sport scores. There was no significant difference in outcome scores between those with ≤50% and >50% pain relief. While patients that received >50% pain relief by IA injection were more likely to achieve positive results (MHHS >70) with a likelihood ratio of 1.23 (95% CI 0.92-1.53), this was not significant. Multivariate regression analysis demonstrated no significant predictors of outcome, including age, gender, Tonnis grade, percent relief with IA injection, number of months postoperatively, or type of surgery. Conclusion: In patients undergoing hip arthroscopy for FAI, our data indicates that the amount of pain relief from IA injection is a poor predictor of short term outcome, even when adjusting for chondral degeneration. While anesthetic injections can be an important diagnostic tool in select patients, correlation of the clinical history, physical examination, and imaging findings are fundamental. In addition, outcome following hip arthroscopy remains multifactorial.

Background: Multiligament knee injuries (MLKIs) can also involve the medial patellofemoral ligament (MPFL), but there is a paucity of information regarding prevalence and relevance of MPFL involvement in this setting. Purpose: (1) To identify the prevalence of MPFL injury in MLKIs, (2) to determine whether an MPFL tear results in symptomatic patellar instability, and (3) to report clinical and functional outcomes of patients with and without MPFL tears after MLKI surgical reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: The records of all patients who underwent surgical reconstruction of MLKI (defined as a grade 3 injury of ≥2 ligaments) at a single institution from 2007 to 2010 were reviewed. Age, sex, knee dislocation classification (according to Schenck), and MRI findings were documented. All preoperative MRI scans were reviewed by an experienced musculoskeletal radiologist to determine the presence or absence of MPFL involvement. If an MPFL tear was present, its anatomic location and severity as well as the presence of patellar or lateral femoral condyle bone bruises were documented. Inclusion criteria included (1) MLKI treated at a single institution, (2) presence of MPFL tear on preoperative MRI, and (3) minimum 2-year clinical follow-up. Patellar instability symptoms were assessed with the Kujala Knee Questionnaire. Functional outcomes were measured using the International Knee Documentation Committee (IKDC) score. IKDC scores were compared between patients who sustained MLKIs with and without MPFL tears. There were 21 patients in each group. Results: Over the 4-year study period, 30 of 51 patients (59%) treated surgically for a MLKI had MRI evidence of an MPFL tear. Nine were lost to follow-up, leaving 21 patients for review. There were 13 complete (62%), 5 high-grade partial (24%), and 3 partial (14%) MPFL tears. Sixteen of 21 tears (76%) occurred at the proximal third, with the remainder exhibiting diffuse signal abnormality consistent with tearing throughout the length of the MPFL. The superficial medial collateral ligament was involved in all patients. In no case was the MPFL repaired or reconstructed. At mean follow-up of 3.6 years (range, 2.0-5.7 years), only 1 of 21 patients (5%) complained of patellofemoral instability symptoms whereas 20 of 21 patients (95%) did not experience patellar subluxation or dislocation. No significant difference was found when IKDC scores were compared between patients with and without an MPFL tear (mean ± SD, 65.5 ± 22.9 vs 79.4 ± 16.1; P = .07). Conclusion: MPFL tears occur frequently in patients with MLKI but rarely cause instability. In the majority of cases, MPFL tears do not need to be addressed at the time of surgery.

Abstract A 68-year-old avid deer hunter with ischemic cardiomyopathy underwent left ventricular assist device (LVAD) implantation for destination therapy two years ago. He was living an active lifestyle, tracking deer and fishing in a Midwestern forest in November. His wife removed an engorged tick on his thorax. A few days later, he experienced fever, confusion, and ataxia and was hospitalized with septic shock and ventricular fibrillation. The LVAD site had no signs of trauma, drainage, warmth, or tenderness. A peripheral blood smear revealed intraleukocytic anaplasma microcolony inclusions. After completing 14 days of doxycycline, he recovered. Typical non-device-associated infections in LVAD recipients include pneumonia, urinary tract infection, or Clostridium difficile colitis. Human granulocytic anaplasmosis (HGA) is a very atypical non-LVAD infection, and the incidence of tickborne illnesses in LVAD recipients is unknown.

Abstract Background: Mammographic density (MD) is a strong breast cancer risk factor. We previously reported associations of percent mammographic density (PMD) with larger and node-positive tumors across all ages, and estrogen receptor (ER)–negative status among women ages <55 years. To provide insight into these associations, we examined the components of PMD [dense area (DA) and nondense area (NDA)] with breast cancer subtypes. Methods: Data were pooled from six studies including 4,095 breast cancers and 8,558 controls. DA and NDA were assessed from digitized film-screen mammograms and standardized across studies. Breast cancer odds by density phenotypes and age according to histopathologic characteristics and receptor status were calculated using polytomous logistic regression. Results: DA was associated with increased breast cancer risk [OR for quartiles: 0.65, 1.00 (Ref), 1.22, 1.55; Ptrend <0.001] and NDA was associated with decreased risk [ORs for quartiles: 1.39, 1.00 (Ref), 0.88, 0.72; Ptrend <0.001] across all ages and invasive tumor characteristics. There were significant trends in the magnitude of associations of both DA and NDA with breast cancer by increasing tumor size (Ptrend < 0.001) but no differences by nodal status. Among women <55 years, DA was more strongly associated with increased risk of ER+ versus ER− tumors (Phet = 0.02), while NDA was more strongly associated with decreased risk of ER− versus ER+ tumors (Phet = 0.03). Conclusions: DA and NDA have differential associations with ER+ versus ER− tumors that vary by age. Impact: DA and NDA are important to consider when developing age- and subtype-specific risk models. Cancer Epidemiol Biomarkers Prev; 24(5); 798–809. ©2015 AACR.

Abstract We investigated the influence of PD-1 expression on the systemic antitumor response (abscopal effect) induced by stereotactic ablative radiotherapy (SABR) in preclinical melanoma and renal cell carcinoma models. We compared the SABR-induced antitumor response in PD-1–expressing wild-type (WT) and PD-1–deficient knockout (KO) mice and found that PD-1 expression compromises the survival of tumor-bearing mice treated with SABR. None of the PD-1 WT mice survived beyond 25 days, whereas 20% of the PD-1 KO mice survived beyond 40 days. Similarly, PD-1–blocking antibody in WT mice was able to recapitulate SABR-induced antitumor responses observed in PD-1 KO mice and led to increased survival. The combination of SABR plus PD-1 blockade induced near complete regression of the irradiated primary tumor (synergistic effect), as opposed to SABR alone or SABR plus control antibody. The combination of SABR plus PD-1 blockade therapy elicited a 66% reduction in size of nonirradiated, secondary tumors outside the SABR radiation field (abscopal effect). The observed abscopal effect was tumor specific and was not dependent on tumor histology or host genetic background. The CD11ahigh CD8+ T-cell phenotype identifies a tumor-reactive population, which was associated in frequency and function with a SABR-induced antitumor immune response in PD-1 KO mice. We conclude that SABR induces an abscopal tumor-specific immune response in both the irradiated and nonirradiated tumors, which is potentiated by PD-1 blockade. The combination of SABR and PD-1 blockade has the potential to translate into a potent immunotherapy strategy in the management of patients with metastatic cancer. Cancer Immunol Res; 3(6); 610–9. ©2015 AACR.

Abstract Tibial plateau fractures present a difficult range of fractures to treat. Arthroscopy allows for a less invasive option when compared with arthrotomy. Furthermore, visualization of the articular surface arthroscopically can allow for a precise reduction and assessment of any concomitant injuries to the articular cartilage and meniscus. By use of arthroscopy, unicondylar lateral plateaus were traditionally approached through a laterally based metaphyseal window. However, in carefully selected patients and fracture patterns, a medially based, arthroscopic‐assisted approach can create long bony tunnels for subchondral support and allow for greater ease in fracture reduction. We present our technique using a medial approach for arthroscopic‐assisted fixation of lateral tibial plateau fractures. Technique Video video See video under supplementary data.