Association of Patient-Reported Outcomes Measurement Information System Measures With Injection and Surgical Treatment Response in Patients With De Quervain Tenosynovitis.

PURPOSE: Treatment of de Quervain tenosynovitis is largely empiric. Patient-Reported Outcomes Management Information System (PROMIS) scores at the time of diagnosis might provide insights into the probability of success of nonsurgical management and predict the necessity for surgical treatment. We aimed to identify which, if any, of the PROMIS metrics may be used to identify patients who will opt for surgery or be managed with injection alone. METHODS: Patients presenting to a tertiary academic medical center from 2014 to 2019, with a sole diagnosis of de Quervain tenosynovitis, were identified and separated by initial and most invasive treatment of either injection or surgery. These groups were then dichotomized using cut points of more than one SD from the mean on the PROMIS physical function and pain interference scales, and a logistic regression model was used to determine the odds ratio of surgical intervention. RESULTS: Patients who had low physical function or high pain interference had significantly increased odds of ultimately undergoing surgery. Age ranging from 40 to 60 years and female sex were also associated with increased odds of undergoing surgery. CONCLUSIONS: Patients who scored lower than 40 for physical function or higher than 60 for pain interference had significantly increased odds of eventually undergoing surgical release for de Quervain tenosynovitis. PROMIS scores may identify patients who are likely to fail steroid injections as a sole nonsurgical intervention and inform an individualized discussion about surgical management of this condition. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

ASCL2 induces an immune excluded microenvironment by activating cancer-associated fibroblasts in microsatellite stable colorectal cancer.

Proficient mismatch repair or microsatellite stable (pMMR/MSS) colorectal cancers (CRCs) are vastly outnumbered by deficient mismatch repair or microsatellite instability-high (dMMR/MSI-H) tumors and lack a response to immune checkpoint inhibitors (ICIs). In this study, we reported two distinct expression patterns of ASCL2 in pMMR/MSS and dMMR/MSI-H CRCs. ASCL2 is overexpressed in pMMR/MSS CRCs and maintains a stemness phenotype, accompanied by a lower density of tumor-infiltrating lymphocytes (TILs) than those in dMMR/MSI CRCs. In addition, coadministration of anti-PD-L1 antibodies facilitated T cell infiltration and provoked strong antitumor immunity and tumor regression in the MC38/shASCL2 mouse CRC model. Furthermore, overexpression of ASCL2 was associated with increased TGFB levels, which stimulate local Cancer-associated fibroblasts (CAFs) activation, inducing an immune-excluded microenvironment. Consistently, mice with deletion of Ascl2 specifically in the intestine (Villin-Cre+, Ascl2 flox/flox, named Ascl2 CKO) revealed fewer activated CAFs and higher proportions of infiltrating CD8+ T cells; We further intercrossed Ascl2 CKO with ApcMin/+ model suggesting that Ascl2-deficient expression in intestinal represented an immune infiltrating environment associated with a good prognosis. Together, our findings indicated ASCL2 induces an immune excluded microenvironment by activating CAFs through transcriptionally activating TGFB, and targeting ASCL2 combined with ICIs could present a therapeutic opportunity for MSS CRCs.

Initial PROMIS Scores Correlate With Operative and Nonoperative Management of Lateral Epicondylitis.

BACKGROUND: Lateral epicondylitis (LE) is a common source of elbow pain. Treatment options include physical therapy (PT), corticosteroid injection, or surgery, but the efficacy of each remains unclear. In this study, we compare Patient-Reported Outcomes Measurement Information System (PROMIS) scores between patients treated both operatively and nonoperatively for LE. METHODS: Patients presenting to a tertiary academic medical center from February 2015 to December 2018 with a diagnosis of LE were identified. Those with initial and follow-up PROMIS physical function (PF), pain interference (PI), and Depression scores were included and stratified according to treatment. Single-factor analysis of variance testing was used to compare PROMIS scores between intervention types. RESULTS: In all, 982 patients were initially identified with the diagnosis of LE and documented PROMIS scores. Initial treatment consisted of 266 patients receiving formal PT, 238 patients receiving injections, 20 patients undergoing surgery, and 296 patients receiving no formal treatment. At final follow-up, 235 (44.8%) patients had been treated with isolated PT, 237 (45.1%) with injections, and 52 (9.9%) with surgery. Patients who underwent formal PT had the highest initial PF scores when compared with all other interventions. Patients who underwent operative management had higher initial PI scores than those who pursued nonoperative management. CONCLUSIONS: Patient-Reported Outcomes Measurement Information System PF and PI may be useful for determining which treatment course patients suffering from LE are likely to pursue. Pain as a limiting factor in daily living may be a better indication for operative management as opposed to physical metrics.

Development of a Murine Model of Pyogenic Flexor Tenosynovitis.

BACKGROUND: Pyogenic flexor tenosynovitis is a debilitating infection of the hand flexor tendon sheath with high morbidity despite standard treatments of empiric antibiotics with irrigation and debridement. In vivo studies in the available literature have used avian models, but these models are difficult to scale and maintain. The purpose of this study was to demonstrate the plausibility of a murine model of pyogenic flexor tenosynovitis utilizing bioluminescence imaging and tissue analysis at harvest. METHODS: A 2-µL inoculate of bioluminescent Xen29 Staphylococcus aureus or sterile phosphate-buffered saline solution (sPBS) was administered to the tendon sheath of 36 male C57BL/6J mice. The infectious course was monitored by bioluminescence imaging (BLI) via an in vivo imaging system, gross anatomic deformity, and weight change. The infected hind paws were harvested at 4 time points: 24 hours, 72 hours, 1 week, and 2 weeks for histological analysis using Alcian blue, hematoxylin, and Orange-G staining. Two-way analysis of variance with the Sidak multiple comparison test was used to assess differences in bioluminescence and weight at each time point. RESULTS: The infected cohort displayed significantly elevated bioluminescence values, had reductions in weight, and exhibited swelling of the infected digit throughout the course of infection. By day 4, most infected mice saw a substantial decrease in BLI signal intensity; however, 2 infected mice exhibited persistent BLI intensity through day 14. Histological analysis of the infected cohort showed tissue disorganization and the presence of a cellular infiltrate in and around the flexor tendon sheath. CONCLUSIONS: A murine model of pyogenic flexor tenosynovitis is possible and can serve as an experimental platform for further investigation of the pathophysiology of pyogenic flexor tenosynovitis. CLINICAL RELEVANCE: This animal model can be utilized in elucidating the basic molecular and/or cellular mechanisms of pyogenic flexor tenosynovitis while simultaneously evaluating novel therapeutic strategies.

Learning Latent Spiculated Features for Lung Nodule Characterization.

Computer-aided Diagnosis (CAD) systems have long aimed to be used in clinical practice to help doctors make decisions by providing a second opinion. However, most machine learning based CAD systems make predictions without explicitly showing how their predictions were generated. Since the cognitive process of the diagnostic imaging interpretation involves various visual characteristics of the region of interest, the explainability of the results should leverage those characteristics. We encode visual characteristics of the region of interest based on pairs of similar images rather than the image content by itself. Using a Siamese convolutional neural network (SCNN), we first learn the similarity among nodules, then encode image content using the SCNN similarity-based feature representation, and lastly, we apply the K-nearest neighbor (KNN) approach to make diagnostic characterizations using the Siamese-based image features. We demonstrate the feasibility of our approach on spiculation, a visual characteristic that radiologists consider when interpreting the degree of cancer malignancy, and the NIH/NCI Lung Image Database Consortium (LIDC) dataset that contains both spiculation and malignancy characteristics for lung nodules.Clinical Relevance - This establishes that spiculation can be quantified to automate the diagnostic characterization of lung nodules in Computed Tomography images.

VCAM1 Promotes Tumor Cell Invasion and Metastasis by Inducing EMT and Transendothelial Migration in Colorectal Cancer.

Vascular cell adhesion molecular 1 (VCAM1), an important member of the immunoglobulin superfamily, is related to the development of malignant tumors, such as breast cancer, melanoma, and renal clear cell carcinoma. However, the molecular role and mechanism of VCAM1 in the regulation of the progression of colorectal cancer (CRC) has rarely been studied. The results of IHC and RT-PCR analyses proved that VCAM1 was upregulated in human CRC tissues compared with matched adjacent normal intestinal epithelial tissues. Moreover, analysis of data from the TCGA and Gene Expression Omnibus (GEO) databases revealed that a higher level of VCAM1 was strongly correlated with poor differentiation, metastasis, and short survival in CRC patients. Furthermore, VCAM1 significantly influenced the invasion and metastasis of CRC cells in vitro and in vivo and activated the EMT program, by which cancer cells adhere to the endothelium and cross the vessel wall by forming pseudopodia and invadopodia. The current findings demonstrate that VCAM1 promotes tumor progression in CRC.

Surgical management of aggressive hemangiomas of the spine.

Our objective is to describe the surgical management and outcomes following surgical intervention for aggressive spine hemangiomas. Patients from 2005 to 2018 with an aggressive hemangioma of the cervical, thoracic, lumbar spine and sacrum treated surgically at a tertiary referral academic medical center were included in this study. The hospital pathology department database was used to identify patients with a diagnosis of aggressive hemangioma. Patient demographics, medical history, operative procedure, adjunct treatment, early and late complications, and recurrence were analyzed using the Fischer exact test with significance set at p < 0.05 Ten patients met inclusion criteria for the study. The average follow up was 11 months. Eight out of ten patients had aggressive hemangioma of the thoracic spine. Seven of the ten patients presented with back or leg pain. The most common surgery was laminectomy at the site of the lesion (70%). 40% of patients underwent a spinal fusion, with two of these patients receiving concurrent intra-operative vertebroplasty. Three patients underwent post-operative radiation therapy. Five complications were noted among three individuals. There were three perioperative complications, deep venous thrombosis, renal insufficiency, one surgical site infection, and two postoperative complications, both revisions. There were no recurrences. Surgical intervention for aggressive spine hemangiomas is an effective treatment with relatively low complication and recurrence rates.

What Is the Association Between Hospital Volume and Complications After Revision Total Joint Arthroplasty: A Large-database Study.

BACKGROUND: Studies of primary total joint arthroplasty (TJA) show a correlation between hospital volume and outcomes; however, the relationship of volume to outcomes in revision TJA is not well studied. QUESTIONS/PURPOSES: We therefore asked: (1) Are 90-day readmissions more likely at low-volume hospitals relative to high-volume hospitals after revision THA and TKA? (2) Are in-hospital and 90-day complications more likely at low-volume hospitals relative to high-volume hospitals after revision THA and TKA? (3) Are 30-day mortality rates higher at low-volume hospitals relative to high-volume hospitals after revision THA and TKA? METHODS: Using 29,948 inpatient stays undergoing revision TJA from 2008 to 2014 in the Statewide Planning and Research Cooperative System (SPARCS) database for New York State, we examined the relationship of hospital revision volume by quartile and outcomes. The top 5 percentile of hospitals was included as a separate cohort. Advantages of the SPARCS database include comprehensive catchment of all cases regardless of payer, and the ability to track each patient across hospital admissions at different institutions within the state. The outcomes of interest included 90-day all-cause readmission rates and 30- and 90-day reoperation rates, postoperative complication rates, and 30-day mortality rates. The initial cohort that met the MS-DRG and ICD-9 criteria consisted of 30,354 inpatient stays for revision hip or knee replacements. Exclusions included patients with a missing patient identifier (n = 221), missing admission or discharge dates (n = 5), and stays from hospitals that were closed during the study period (n = 180). Our final analytic cohort comprised 29,948 inpatient stays for revision hip and knee replacements from 25,977 patients who had nonmissing data points for the variables of interest. Outcomes were adjusted for underlying hospital, surgeon, and patient confounding variables. The analytic cohort included observations from 25,977 patients, 138 hospitals, 929 surgeons, 14,130 revision THAs, 11,847 revision TKAs, 15,341 female patients (59% of cohort). RESULTS: Patients had lower all-cause 90-day readmission rates in the highest 5th percentile by volume hospitals relative to all other lower hospital volume categories. Reoperation rates within the first 90 days, however, were not different among volume categories. All-cause 90-day readmissions were higher in the quartile 4 hospitals excluding the top 5th percentile (17%) versus the top 5th percentile by volume hospitals (12%) (odds ratio [OR]: 1.3; 95% confidence interval [CI], 1.0-1.5; p = 0.030). All-cause 90-day readmissions were higher in the quartile 3 hospitals (18%) relative to the top 5 percentile by volume hospitals (12%) (OR: 1.5; 95% CI, 1.2-1.9; p < 0.001). All-cause 90-day readmissions were higher in quartile 2 hospitals (18%) relative to the top 5 percentile by volume hospitals (12%) (OR: 1.4; 95% CI, 1.1-1.8; p = 0.010). All-cause 90-day readmissions were higher in quartile 1 hospitals (21%) versus the top 5 percentile by volume hospitals (12%) (OR: 1.6; 95% CI, 1.1-2.3; p = 0.010). Postoperative complication rates were higher among only the quartile 1 hospitals compared with institutions in each higher-volume category after revision TJA. The odds of 90-day complications compared with quartile 1 hospitals were 0.49 (95% CI, 0.33-0.72; p = 0.010) for quartile 2, 0.60 (95% CI, 0.40-0.88; p = 0.010) for quartile 3, 0.43 (95% CI, 0.28-0.64; p = 0.010) for quartile 4 excluding top 5 percentile, and 0.36 (95% CI, 0.22-0.59; p = 0.010) for the top 5 percentile of hospitals. There does not appear to be an association between 30-day mortality rates and hospital volume in revision TJA. The odds of 30-day mortality compared with quartile 1 hospitals were 0.54 (95% CI, 0.20-1.46; p = 0.220) for quartile 2, 0.75 (95% CI, 0.30-1.91; p = 0.550) for quartile 3, 0.57 (95% CI, 0.22-1.49; p = 0.250) for quartile 4 excluding top 5 percentile, and 0.61 (95% CI, 0.20-1.81; p = 0.370) for the top 5 percentile of hospitals. CONCLUSIONS: These findings suggest that regionalizing revision TJA services, or concentrating surgical procedures in higher-volume hospitals, may reduce early complications rates and 90-day readmission rates. Disadvantages of regionalization include reduced access to care, increased patient travel distances, and possible capacity issues at receiving centers. Further studies are needed to evaluate the benefits and negative consequences of regionalizing revision TJA services to higher-volume revision TJA institutions. LEVEL OF EVIDENCE: Level III, therapeutic study.

Indications and Guidelines for Debridement and Implant Retention for Periprosthetic Hip and Knee Infection.

PURPOSE OF REVIEW: Prosthetic joint infection is one the most common causes of revision surgery after hip or knee replacement. Debridement and implant retention (DAIR) is one method of treating these infections; however, significant controversy exists. The purpose of our review was to describe current knowledge about indications, intraoperative/postoperative patient management, and outcomes of DAIR. RECENT FINDINGS: Patient selection affects the success of DAIR. Medical comorbidities, duration of symptoms, and nature of infectious organism all influence outcomes. Intraoperative techniques such as open arthrotomy, extensive debridement, copious irrigation, and exchange of modular parts remain current standards for DAIR. Postoperative administration of antibiotics tailored to operative cultures remains critical. Antibiotic suppression may increase the success of DAIR. DAIR provides reasonable infection eradication between 50 and 80% with improved outcomes in appropriately selected patients. More research is needed on the use of adjuvant therapies intraoperatively and the role of postoperative antibiotic suppression.