Tumor hyaluronan as a novel biomarker in non-small cell lung cancer: A retrospective study.

INTRODUCTION: Hyaluronan (HA) accumulation is associated with tumorigenesis and aggressive tumor behavior. AIMS: We investigated the biomarker potential of HA in non-small cell lung cancer (NSCLC). METHODS: HA levels were scored using affinity histochemistry in 137 NSCLC samples stratified by HA score ≤10, 11-20, 21-30, and >30 with HA-high defined as ≥25% expression in the extracellular matrix (ECM) of the tumor surface area. Overall survival (OS) and time to progression from initiation of taxane therapy (TTP) were compared using log-rank tests based on HA score. RESULTS: Of 122 patients with recurrent/metastatic NSCLC, 93 had mean HA scores that were not significantly different across clinicopathologic variables. Frequency of HA-high tumors did not differ by histology (34/68 adenocarcinomas vs. 12/25 squamous tumors, Fisher's p = 1.0000). Median OS for recurrent/metastatic adenocarcinoma was 35.5 months (95%, 23.6-50.3) vs. 17.9 months for squamous (95%, 12.7-37.0, log-rank test, p = 0.0165). OS was not significantly different by HA quartiles, high or low (<25) HA score and tumor histology, and HA biopsy site (all p > 0.05). Median TTP (n = 98) significantly differed by HA quartile (2.8 months for HA score ≤10; 5.0 months for 11-20; 7.9 months for 21-30; 3.9 months for >30, p = 0.0265). Improved TTP trended in HA-high over HA-low tumors (n = 98, p = 0.0911). CONCLUSION: In this NSCLC cohort, tumor HA level represents a potential biomarker for TTP, which remains a cornerstone of NSCLC therapy. Further validation is warranted to identify the HA accumulation threshold associated with clinical benefit.

Evaluation of International Normalized Ratio Thresholds for Complications in Hip Fractures Treated With Intramedullary Nailing: Analysis of 15,323 Cases.

INTRODUCTION: In hip fracture patients with elevated international normalized ratios (INRs), the risks of delaying surgery for correction of INR are controversial. We examined the association of (1) preoperative INR values and (2) surgical delay with postoperative complications after intramedullary nailing of hip fractures. METHODS: Using the National Surgical Quality Improvement Program database, we retrospectively identified patients that underwent intramedullary nailing for hip fractures from 2005 to 2016. Patients aged older than 55 years with preoperative INR recorded ≤1 day before surgery were included. Patients were stratified into five cohorts-(1) INR ≤ 1.0, (2) 1 < INR ≤ 1.25 (INR [1 to 1.25]), (3) 1.25 < INR ≤ 1.5 (INR [1.25 to 1.5]), (4) 1.5 < INR ≤ 2.0 (INR [1.5 to 2.0]), and (5) INR > 2.0. The primary outcomes of interest were postoperative bleeding requiring transfusion, surgical site infection, and 30-day mortality. Multivariate regression analysis was done to adjust for potential confounding variables. RESULTS: In total, 15,323 patients were included in this analysis. Adjusting for potential confounders, INR [1 to 1.25], INR [1.25 to 1.5], and INR [1.5 to 2.0] were associated with increased mortality (adjusted odds ratio [aOR]: 1.501, P < 0.001; aOR: 2.226, P < 0.001; aOR: 2.524, P < 0.001, respectively) and surgical delay >48 hours (aOR: 1.655, P < 0.001; aOR: 3.434, P < 0.001; aOR: 2.382, P < 0.001, respectively). The INR > 2.0 cohort was not associated with mortality (P = 0.181) or surgical delay (P = 0.529). Surgical delay was associated with mortality (aOR: 1.531, P = 0.004). The INR > 2.0 cohort was associated with increased rate of transfusions (aOR: 1.388, P = 0.039). CONCLUSION: Elevated preoperative INR value within 1 day of surgery between 1.0 and 2.0 was associated with increased risk of 30-day mortality and surgical delay >48 hour, which may represent attempts at INR correction. An INR greater than 2.0 was not associated with mortality or surgical delay but was associated with increased transfusions. Surgical delay was independently associated with increased risk of 30-day mortality. We therefore recommend that INR reversal be attempted but not delay surgical fixation of geriatric hip fractures over 48 hours and counsel patients and their families regarding the risks of surgery with elevated INR. LEVEL OF EVIDENCE: Prognostic-level III/retrospective cohort study.

Comparison of Infrapatellar and Suprapatellar Approaches for Intramedullary Nail Fixation of Tibia Fractures.

OBJECTIVE: To assess clinical, radiographic, and functional outcomes after intramedullary nail (IMN) fixation of tibia fractures with an infrapatellar approach compared to a suprapatellar approach. DESIGN: Retrospective chart review. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: Two hundred four patients with 208 tibia fractures treated with intramedullary nailing between 2008 and 2018. METHODS: A retrospective chart review of tibia fractures was conducted. The clinical and functional outcomes of tibia fractures treated with IMN were compared between groups treated with an infrapatellar approach versus a suprapatellar approach. Multivariate models were created to control for confounding demographic, comorbidity, and injury-related confounders. MAIN OUTCOME MEASUREMENTS: Outcome measures included nonunion, malunion, and infection. Subjective functional patient outcomes were assessed using pain interference and physical function Patient-Reported Outcome Measurements Systems scores. RESULTS: There were 101 patients treated with infrapatellar nailing (49%) and 107 patients treated with suprapatellar nailing (51%). On multivariate analysis, suprapatellar nailing was independently associated with decreased risk of malunion (adjusted odds ratio, 0.165; 95% confidence interval, 0.054-0.501; P = 0.001) and decreased risk of postoperative knee pain (adjusted odds ratio, 0.272; 95% confidence interval, 0.083-0.891; P = 0.032). There was no difference in the rate of nonunion (P = 0.44), infection (P = 0.45), or Patient-Reported Outcome Measurements Systems pain interference or physical function scores. CONCLUSIONS: Suprapatellar IMN fixation of tibial shaft fractures is independently associated with lower risk of malunion and postoperative knee pain compared to the infrapatellar approach. However, there are no functional differences between approaches. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Priority Rankings of Patient-Reported Outcomes for Pancreatic Ductal Adenocarcinoma: A Comparison of Patient and Physician Perspectives.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with high symptom burden. However, treatment decisions currently depend heavily on physician interpretation of clinical parameters and may not consider patients' health preferences. The NIH Patient-Reported Outcomes Measurement Information System (PROMIS) initiative standardized a set of patient-reported outcomes for use in chronic diseases. This study identifies preference rankings among patients with PDAC and physicians for PROMIS domains and compares the priorities of patients and their providers. METHODS: We condensed the 96 NIH PROMIS adult domains into 31 domains and created a Maximum Difference Scaling questionnaire. Domain preference scores were generated from the responses of patients with PDAC and physicians, which were compared using Maximum Difference Scaling software across demographic and clinical variables. RESULTS: Participants included 135 patients with PDAC (53% male; median age, 68 years) and 54 physicians (76% male; median years of experience, 10). Patients selected physical functioning (PF) as their top priority, whereas physicians identified pain as most important. PF, ability to perform activities of daily living, and symptom management were within the top 5 domains for both patients and physicians, and varied only slightly across age, sex, and ethnicity. However, several domains were ranked significantly higher by patients than by physicians, including but not limited to PF; ability to do things for yourself, family, and friends; ability to interact with others to obtain help; and sleep quality. Physicians ranked pain, anxiety, and depression higher than patients did. CONCLUSIONS: Our findings suggest that patients with PDAC value PF and engaging in daily and social activities the most, whereas physicians prioritize symptoms such as pain. Patient-reported outcomes need to become more integrated into PDAC care and research to better identify unmet patient needs, inform treatment decisions, and develop therapies that address outcomes valued by patients.

Diagnosis, treatment, and survival in spinal dissemination of primary intracranial glioblastoma: systematic literature review.

OBJECTIVE: Spinal metastases from primary intracranial glioblastoma (GBM) are infrequently reported, and the disease has yet to be well characterized. A more accurate description of its clinical presentation and patient survival may improve understanding of this pathology, guide patient care, and advocate for increased inclusion in GBM research. The authors sought to describe the clinical presentation, treatment patterns, and survival in patients with drop metastases secondary to primary intracranial GBM. METHODS: A systematic review was performed using the PRISMA guidelines. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane databases were queried for abstracts that included patients with primary intracranial GBM and metastases to the spinal axis. Descriptive statistics were used to evaluate characteristics of the primary brain lesion, timing of spinal metastases, clinical symptoms, anatomical location of the metastases, and survival and treatment parameters. Kaplan-Meier analysis and log-rank analysis of the survival curves were performed for selected subgroups. RESULTS: Of 1225 abstracts that resulted from the search, 51 articles were selected, yielding 86 subjects. The patients' mean age was 46.78 years and 59.74% were male. The most common symptom was lumbago or cervicalgia (90.24%), and this was followed by paraparesis (86.00%). The actuarial median survival after the detection of spinal metastases was 2.8 months and the mean survival was 2.72 months (95% CI 2.59-4.85), with a 1-year cumulative survival probability of 2.7% (95% CI 0.51%-8.33%). A diagnosis of leptomeningeal disease, present in 53.54% of the patients, was correlated, and significantly worse survival was on log-rank analysis in patients with leptomeningeal disease (p = 0.0046; median survival 2.5 months [95% CI 2-3] vs 4.0 months [95% CI 2-6]). CONCLUSIONS: This study established baseline characteristics of GBMs metastatic to the spinal axis. The prognosis is poor, though these results will provide patients and clinicians with more accurate survival estimates. The quality of studies reporting on this disease pathology is still limited. There is significant need for improved reporting methods for spinal metastases, either through enrollment of these patients in clinical trials or through increased granularity of coding for metastatic central nervous system diseases in cancer databases.