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The rate of anterior cruciate ligament (ACL) injuries and reconstruction in pediatric patients is increasing. Perioperative peripheral nerve blocks (PNBs) are widely used for pain management in this population. We used a multi-state administrative claims database to describe the effect of PNB after ACL reconstruction on postoperative opioid consumption. We identified patients 10 to 18 years old undergoing primary ACL reconstruction between 2014 and 2016 in an administrative claims database. Patients filling an outpatient perioperative prescription for opioids with at least 1 year of follow-up were included. We stratified patients based on PNB. Our primary outcome was opioid prescription patterns (in morphine milligram equivalents [MMEs]) and incidence of opioid represcription. Of the 4459 cases, 2432 (54.5%) of the patients were given a PNB during ACL reconstruction while 2027 (45.5%) were not. Patients with PNB were prescribed more MMEs per day (76.1±41.7 vs 62.7±35.7 MMEs, P<.001), more pills (63.6±53.1 vs 54.4±40.6 pills, P<.001), higher MMEs per pill (10.0±9.5 vs 8.3±5.0 MMEs, P<.001), and more total MMEs (460.6±259.4 vs 355.7±215.1 MMEs, P<.001) than patients without PNB. Adjusting for prescription patterns and demographic variables with logistic regression, PNBs were associated with a 60% increase in the odds of opioid represcription within 30 days and a 32% increase in the odds of opioid represcription within 90 days. We demonstrated an increase in postoperative opioid prescription rates with PNB after ACL reconstruction. [Orthopedics. 2024;47(2):83–88.] [ABSTRACT FROM AUTHOR]

Background: A discoid lateral meniscus (DLM) is a congenital anomaly of the knee in which the lateral meniscus has an "O" shape and contains irregular, abnormal collagenous tissue. A DLM can cause mechanical symptoms and pain. Treatment of a symptomatic DLM is arthroscopic saucerization to reshape the meniscus to a more normal contour. Enough tissue must be removed to eliminate mechanical symptoms but not too much to create instability. The residual width of the meniscus is crucial at the popliteus hiatus because here the peripheral rim is unattached at the capsule. Reports in the literature recommend a residual width of 6 to 8 mm. Purpose/Hypothesis: The purpose of this research was to determine the width of the lateral meniscus at the popliteal hiatus in normal specimens. Our null hypothesis was that a residual width of 6 to 8 mm will be sufficient to approximate normal anatomy. Study Design: Cross-sectional study; Level of evidence, 3. Methods: We made direct measurements of the radial width of the lateral meniscus from the outer rim at the popliteal hiatus to the inner edge in 19 specimens (age, 2-120 months.) We measured one 4-year-old specimen with a bilateral complete DLM. We also measured 39 digital images of specimens (age, 1-132 months) using ImageJ. Finally, we made direct arthroscopic measurements of 8 skeletally mature specimens. Results: The average width of specimens <3 years old was 5.5 mm. The average width of the 10-year-old specimens was 12 mm. The average width of the skeletally mature specimens was 16 mm. A 4-year-old DLM specimen measured 19 mm. Conclusion: We rejected our null hypothesis. Direct measurements suggest that a residual width of 6 to 8 mm is insufficient for children ≥8 years old. A width of at least a full centimeter approximates the normal for 8-year-olds and at least 15 mm for adolescents. [ABSTRACT FROM AUTHOR]

Context.-Nasopharyngeal carcinoma (NPC), common in southern China and North Africa, has a complex etiology involving interplay between viral, environmental, and hereditary factors and is almost constantly associated with the Epstein-Barr virus. Since the prognosis of locally advanced and metastatic diseases is poor, increased understanding of the pathogenesis of NPC would be important for discovering novel markers for patients' management. Objectives.-To compare the proteomic expression profile between an Epstein-Barr virus-associated NPC cell line (C666-1) and a normal NP cell line (NP69). The proteins with differential expression were analyzed in 40 undifferentiated NPC paraffin-embedded specimens. Design.-Differentially expressed proteins discovered between the two cell lines were identified by mass spectrometry. After confirmation by immunocytochemical staining, their expression in patient samples was measured using 40 pairs of undifferentiated NPCs together with their adjacent normal epithelia. Results.-Proteomic findings indicated that adenosine triphosphate synthase α chain was up-regulated, whereas annexin II, annexin V, β2-tubulin, and profilin 1 were down-regulated. After confirming the results in agar-processed cell lines, annexin II and β2-tubulin expression were found to be lower in tumor cells than in adjacent normal epithelial cells in 100% and 90% of the patients' specimens, respectively. Finally, annexin II down-regulation was positively associated with lymph node metastasis, suggesting that it may be a prognostic factor in NPC. Conclusions.-The results suggest that annexin II and β2- tubulin down-regulation is important in NPC formation and may represent potential targets for further investigations. [ABSTRACT FROM AUTHOR]

Full article available online at Healio.com/Orthopedics. Search: 20121120-31 Four normal variants of meniscomeniscal ligaments have been previously reported in the anatomy, arthroscopy, and radiology literature. The anterior and posterior transverse meniscal ligaments are the 2 most commonly observed, with a reported frequency of 58% and 1% to 4%, respectively. The last 2 variants include the medial and lateral oblique meniscomeniscal ligaments and account for a combined frequency of 1% to 4%. This article describes 2 patients with unilateral meniscomeniscal ligaments observed on magnetic resonance imaging. One patient had a unilateral lateral meniscomeniscal ligament extending from the anterior horn of the lateral meniscus to the posterior horn of the lateral meniscus and underwent conservative management. The second patient had a unilateral medial meniscomeniscal ligament with a concomitant medial meniscus tear and underwent arthroscopic intervention. The ligament was stable intraoperatively and, therefore, was not resected. Both patients had resolution of their symptoms. These 2 variants are additions to the previously described 4 normal intermeniscal ligament variants. The functions of the 2 new variants described in this article are poorly understood but are thought to involve meniscal stability. Accurate descriptions of normal variants can lead to the proper management of anomalous rare structures and prevent false imaging interpretations because these structures can closely mimic a double posterior cruciate ligament sign. Furthermore, an understanding of the various normal variants of intermeniscal ligaments can prevent unnecessary surgery that could result in further iatrogenic meniscus injury. [ABSTRACT FROM AUTHOR]

Context.-In immunohistochemistry, nonstandardized antigen retrieval protocols and fluids, poor-quality antibodies, and the presence of endogenous biotin frequently lead to incorrect results. Recently, advanced reagents including bifunctional SkipDewax pretreatment solution (BSPS), rabbit monoclonal (RM) antibodies, and biotin-free polymer detection systems (PDSs) have been developed, which, it is claimed, resolve these problems. Objectives.-To determine whether BSPS, RM antibodies, and biotin-free PDSs improve the accuracy of immunohistochemistry; to optimize a new protocol consisting of a combination of BSPS, RM antibodies, and PDSs; and to compare it with a conventional protocol. Design.-The efficacies of BSPS, RM antibodies, and PDSs were compared with those of their respective conventional reagents using multitissue spring-roll sections. The new protocol was compared with a conventional protocol using Ki-67 immunostaining of 49 colorectal carcinoma specimens. Results.-For antigen retrieval, BSPS resulted in similar or better tissue staining than an EDTA solution, but the efficacy of BSPS decreased when it was reused. Most RM antibodies resulted in a greater proportion of positive cells than the corresponding non-RM antibodies, which did not produce satisfactory results in the absence of antigen retrieval. The PDSs Bond, ChemMate, and SuperPicture resulted in a high percentage of positive cells, good staining intensities, and low backgrounds. Other PDSs, except that from Ventana, resulted in high backgrounds and false positivity. The new combined protocol resulted in better Ki-67 staining than the conventional assay. Conclusions.-Bifunctional SkipDewax pretreatment solution, RM antibodies, and PDSs improve staining quality and diagnostic accuracy of immunohistochemistry assays and provide a foundation for standardization. [ABSTRACT FROM AUTHOR]

Purpose: Two Epstein-Barr virus (EBV)-based testing approaches have shown promise for early detection of nasopharyngeal carcinoma (NPC). Neither has been independently validated nor their performance compared. We compared their diagnostic performance in an independent population., Methods: We tested blood samples from 819 incident Taiwanese NPC cases (213 early-stage, American Joint Committee on Cancer version 7 stages I and II) diagnosed from 2010 to 2014 and from 1,768 controls from the same region, frequency matched to cases on age and sex. We compared an EBV antibody score using immunoglobulin A antibodies measured by enzyme-linked immunosorbent assay (EBV antibody score) and plasma EBV DNA load measured by real-time PCR followed by next-generation sequencing (NGS) among EBV DNA-positive individuals (EBV DNA algorithm)., Results: EBV antibodies and DNA load were measured for 2,522 (802 cases; 1,720 controls) and 2,542 (797 cases; 1,745 controls) individuals, respectively. Of the 898 individuals positive for plasma EBV DNA and therefore eligible for NGS, we selected 442 (49%) for NGS testing. The EBV antibody score had a sensitivity of 88.4% (95% CI, 86.1 to 90.6) and a specificity of 94.9% (95% CI, 93.8 to 96.0) for NPC. The EBV DNA algorithm yielded significantly higher sensitivity (93.2%; 95% CI, 91.3 to 94.9; P = 1.33 × 10 -4 ) and specificity (98.1%; 95% CI, 97.3 to 98.8; P = 3.53 × 10 -7 ). For early-stage NPC, the sensitivities were 87.1% (95% CI, 82.7 to 92.4) for the EBV antibody score and 87.0% (95% CI, 81.9 to 91.5) for the EBV DNA algorithm ( P = .514). For regions with a NPC incidence of 20-100/100,000 person-years (eg, residents in southern China and Hong Kong), these two approaches yielded similar numbers needed to screen (EBV antibody score: 5,656-1,131; EBV DNA algorithm: 5,365-1,073); positive predictive values ranged from 0.4% to 1.7% and 1.0% to 4.7%, respectively., Conclusion: We demonstrated high sensitivity and specificity of EBV antibody and plasma EBV DNA for NPC detection, with slightly inferior performance of the EBV antibody score. Cost-effectiveness studies are needed to guide screening implementation.

Objective: We sought to determine prescribing patterns for opioid analgesia following anterior cruciate ligament (ACL) reconstruction among age- and gender-stratified adolescents in a nationally representative database., Design: A retrospective study., Setting: PearlDiver Patient Records., Patients, Participants: Outpatient opioid claims within 30 days of surgery were extracted. The patients were defined into age groups 10-14 ("younger") and 15-19 ("older"). A total of 1,139 patients were included in this study (536 female and 603 males) with 108 patients in the 10-14 age category and 1,034 patients in the 15-19 category., Main Outcome Measure(s): The primary study outcome measures the average number of opioid pills administered, average total morphine milligram equivalents (MMEs) prescribed, and the average prescription strength (MMEs/pill)., Results: No difference was found in the average number of pills (p = 0.26) or normalized total MMEs (p = 0.312) prescribed by age group. Normalized total morphine equivalents per prescription was significantly lower in females than males (p = 0.005). Multivariate linear regression analysis demonstrated that increasing patient age was predictive of fewer total pills (p = 0.017), after accounting for gender., Conclusions: There are age- and gender-based disparities in prescription patterns for adolescent ACL reconstruction. Our findings indicate that patients in the older age group on average received fewer pills than the younger age group, which consequently trended toward receiving higher total MMEs prescribed. This suggests that surgeons may be inadvertently overprescribing in the younger cohort. Additional studies that account for concurrent factors should be conducted to observe potentially similar trends.

Background: Soccer is an increasingly popular sport for children and adolescents in the United States. Little is known about participation patterns related to sport specialization., Purpose: To investigate soccer participation levels and sport specialization characteristics among youth soccer athletes., Study Design: Cross-sectional study., Methods: Adolescent athletes aged between 12 and 18 years completed an online survey addressing participant demographics, sports and soccer participation history, and level of specialization. Descriptive analyses characterized participation, while chi-square and Kruskal-Wallis tests assessed the influence of specialization, sex, and grade on survey variables., Results: Overall, 83.7% of 746 respondents participated in an organized soccer league outside of school, and 37% played in multiple leagues concurrently. Nearly three-quarters of respondents trained in soccer more than 8 months of the year, with those who participated in club soccer being more likely to train more than 8 months of the year. More respondents were classified as high specialization (37.5%), followed by moderate (35.6%) and low (28.6%) specialization. No differences between sexes were noted for level of specialization or quitting other sports to specialize in soccer, but male athletes were more likely to train more than 8 months per year compared with female athletes. Respondents in older grades (9th-10th and 11th-12th grades) were more likely to be highly specialized and quit other sports to focus on soccer. No differences between grade levels were found among respondents training more than 8 months per year., Conclusion: The study findings suggest that many youth soccer athletes participated in multiple teams or leagues at the same time and trained more than 8 months of the year. Characteristics including participation on a club team, level of specialization, and male sex were associated with a greater likelihood of exceeding the 8-month training recommendation., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: M.I. has received educational support from Smith & Nephew and the American Sports Medicine Institute. M.A.C. has received educational support from Stryker, DePuy, DJO, and Smith & Nephew. P.J.L. has received educational support from DePuy, Smith & Nephew, Arthrex, and Kairos Surgical. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Purpose: We hypothesized that axitinib is active with an improved safety profile in nasopharyngeal carcinoma (NPC). Experimental Design: We evaluated axitinib in preclinical models of NPC and studied its efficacy in a phase II clinical trial in recurrent or metastatic NPC patients who progressed after at least one line of prior platinum-based chemotherapy. We excluded patients with local recurrence or vascular invasion. Axitinib was started at 5 mg twice daily in continuous 4-week cycles. Primary endpoint was clinical benefit rate (CBR), defined as the percentage of patients achieving complete response, partial response, or stable disease by RECIST criteria for more than 3 months. Results: We recruited 40 patients, who received a median of 3 lines of prior chemotherapy. Axitinib was administered for a mean of 5.6 cycles, with 16 patients (40%) receiving ≥6 cycles. Of 37 patients evaluable for response, CBR was 78.4% (95% CI, 65.6%-91.2%) at 3 months and 43.2% (30.4%-56.1%) at 6 months. Grade 3/4 toxicities were uncommon, including hypertension (8%), diarrhea (5%), weight loss (5%), and pain (5%). All hemorrhagic events were grade 1 (15%) or grade 2 (3%). Elevated diastolic blood pressure during the first 3 months of axitinib treatment was significantly associated with improved overall survival (HR, 0.29; 95% CI, 0.13-0.64, P = 0.0012). Patient-reported fatigue symptom was associated with hypothyroidism ( P = 0.039). Axitinib PK parameters (C max and AUC (0-t) ) were significantly correlated with tumor response, toxicity, and serum thyroid-stimulating hormone changes. Conclusions: Axitinib achieved durable disease control with a favorable safety profile in heavily pretreated NPC patients. Clin Cancer Res; 24(5); 1030-7. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Backgrounds & Aims: A number of circulating inflammatory factors are implicated in the pathogenesis and prognostication of hepatocellular carcinoma (HCC). We aim to evaluate the prognostication of multiple serum inflammatory factors simultaneously and develop an objective inflammatory score for HCC., Methods: A prospective cohort of 555 patients with HCC with paired serum samples was accrued from 2009 to 2012. The blood levels of conventional inflammatory markers, namely C-reactive protein (CRP), albumin, neutrophils, lymphocytes and platelet, were determined, and 41 other exploratory markers were measured by a multiplex assay. The prognostication and interaction of markers were determined by univariate and multivarite analyses., Results: The cohort was randomly divided into training cohort (n=139) and validation cohort (n=416). There were no differences in baseline characteristics between the two cohorts. In the training cohort, independent prognostic factors for overall survival included CRP (hazard ratio [HR] 1.107; P=.003), albumin (HR 0.953; P=.032) and interleukin-8 (HR=5.816; P<.001). We have modified the existing inflammation-based index (IBI) by adding serum interleukin-8 level. The modified IBI could stratify patients into four groups with distinct overall survival (P<.001). The results were also validated in the validation cohort. When compared with IBI and other conventional inflammatory markers, the modified IBI had better prognostic performance with higher c-index and homogeneity likelihood ratio chi-square., Conclusions: Among the conventional and exploratory circulating inflammatory markers, higher CRP, lower albumin and higher interleukin-8 were independent prognosticators. By combining these factors, a simple and accurate inflammatory index could be constructed., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Context: Nasopharyngeal carcinoma (NPC), common in southern China and North Africa, has a complex etiology involving interplay between viral, environmental, and hereditary factors and is almost constantly associated with the Epstein-Barr virus. Since the prognosis of locally advanced and metastatic diseases is poor, increased understanding of the pathogenesis of NPC would be important for discovering novel markers for patients' management., Objectives: To compare the proteomic expression profile between an Epstein-Barr virus-associated NPC cell line (C666-1) and a normal NP cell line (NP69). The proteins with differential expression were analyzed in 40 undifferentiated NPC paraffin-embedded specimens., Design: Differentially expressed proteins discovered between the two cell lines were identified by mass spectrometry. After confirmation by immunocytochemical staining, their expression in patient samples was measured using 40 pairs of undifferentiated NPCs together with their adjacent normal epithelia., Results: Proteomic findings indicated that adenosine triphosphate synthase alpha chain was up-regulated, whereas annexin II, annexin V, beta(2)-tubulin, and profilin 1 were down-regulated. After confirming the results in agar-processed cell lines, annexin II and beta(2)-tubulin expression were found to be lower in tumor cells than in adjacent normal epithelial cells in 100% and 90% of the patients' specimens, respectively. Finally, annexin II down-regulation was positively associated with lymph node metastasis, suggesting that it may be a prognostic factor in NPC., Conclusions: The results suggest that annexin II and beta(2)-tubulin down-regulation is important in NPC formation and may represent potential targets for further investigations.

Objectives: To investigate the effect of centrifugation in circulating mRNA quantitation and to design a new, consistent protocol for it., Design and Methods: The concentrations of beta-catenin mRNA, P-selectin mRNA, cytokeratin 20 mRNA, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA in the plasma, the mononuclear and red cells (MARC) from metastatic colorectal (CRC) patients whose blood samples were centrifuged with 2 different forces, were measured. A new protocol to measure expression profiles in MARC was studied., Results: When the centrifugal force was increased: (1) the concentrations of all transcripts were dramatically decreased in the plasma samples; (2) only the concentrations of P-selectin mRNA and GAPDH mRNA were significantly increased in the mononuclear cell samples; and (3) their concentrations in the red cells did not change significantly. The new protocol found 9 differential expressed genes., Conclusions: Centrifugal force causes inconsistent mRNA quantitation in the plasma. The new protocol discovered 9 differential expressed genes for metastatic CRC.

Cycloxygenase-2 (COX-2), hypoxia inducible factor 1-alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) can be induced by the Epstein-Barr virus oncoprotein latent membrane protein-1 (LMP-1) in nasopharyngeal cancer (NPC) cell lines. This study examined the prognostic relevance of COX-2 and its relationship with HIF-1alpha and VEGF expression in NPC biopsies. Primary tumor biopsies were obtained from 78 participants of a randomized trial who received radiotherapy (RT) with or without concurrent chemotherapy for locoregionally advanced NPC. These were analyzed for COX-2 expression and then correlated with age, sex, disease stage, treatment arm, survival and disease recurrence, VEGF and HIF-1alpha expression in a regression model. 83% of tumors expressed COX-2, 47% co-expressed COX-2 and VEGF, 38% co-expressed COX-2 and HIF-1alpha. On univariate analysis, COX-2 expression did not correlate with survival and recurrence, but moderate to high COX-2 expression was associated with advanced nodal stage (p=0.03). Although univariate analysis showed that COX-2-HIF-1alpha co-expression was associated with worse progression-free survival (p=0.046), time to local (p=0.004) and regional recurrence (p=0.007), multivariate analysis failed to confirm any correlation between COX-2-HIF-1alpha or COX-2-VEGF co-expression and survival or disease recurrence. Contrary to previous report, this study failed to demonstrate any prognostic significance of COX-2 expression alone or co-expression with HIF-1alpha or VEGF in advanced NPC.

Background: This study prospectively examines the prognostic role of p53 oncoprotein (p53), Ki67-antigen (Ki67), tumor angiogenesis (MVD), epidermal growth factor receptor (EGFR), and HER2 receptor protein (HER2) expression in Chinese with undifferentiated nasopharyngeal carcinoma (NPC)., Methods: Seventy-eight Chinese were recruited from October 1995 to July 1997 at the Prince of Wales Hospital, Hong Kong. Pretreatment immunohistochemical preparations of the primary tumor were made, and clinical data were collected prospectively until October 30, 2000. The markers were correlated with overall survival (OS), disease-free survival (DFS), time to progression (TTP), and UICC stage., Results: On univariate analysis, EGFR expression correlated with poorer OS (p =.0001), DFS (p =.01), shorter TTP (p =.0001), and advanced T stage (p =.036). Strong EGFR expression, when compared with weak or moderate, was associated with poorer OS (p =.04) and shorter TTP in a subgroup of patients with UICC stage III-IV disease. HER2 expression was associated with advanced UICC stage (p =.006). The presence of p53 expression correlated with poorer DFS (p =.01) and a trend toward shorter TTP (p =.06). No correlation was found with Ki67-antigen or MVD. On multivariate analysis, only EGFR expression was significantly linked to shorter OS and TTP., Conclusions: EGFR expression in undifferentiated NPC is associated with a poor clinical outcome. A prognostic role of p53 and HER2 expression is suggestive but not consistently defined in this study. The relatively high prevalence of positive staining for EGFR supports the use of molecular targeted therapy in this disease., (Copyright 2003 Wiley Periodicals, Inc.)

Background: At concentrations <500 microg/L, serum alpha-fetoprotein (AFP) has low specificity in the diagnosis of hepatocellular carcinoma (HCC), but monosialylated AFP (msAFP) is more specific for HCC. We describe two strategies for quantitative analysis of msAFP and explore their diagnostic accuracy in cases of HCC with nondiagnostic serum total AFP concentrations., Methods: We first used isoelectric focusing, Western blot, and densitometry (IEF-Western blot assay). We then developed a second assay, a novel glycosylation immunosorbent assay (GISA), based on the specificity of sialyltransferase and immunosorbent technology. Both assays were used to measure msAFP and msAFP percentage relative to total AFP in sera with nondiagnostic AFP concentrations from 36 patients with newly diagnosed HCC and from 18 patients with liver cirrhosis., Results: The msAFP percentages and concentrations were significantly higher in the HCC patient group regardless of the quantification methods. The msAFP concentrations and msAFP percentages obtained by the two assays were highly correlated (r = 0.70 and 0.49, respectively). For discrimination of HCC with nondiagnostic serum total AFP from liver cirrhosis, the areas under the ROC curves were 0.81 (95% confidence interval, 0.70-0.92) for msAFP by IEF-Western blot assay, 0.73 (0.58-0.87) for msAFP by GISA, 0.89 (0.80-0.97) for msAFP percentage by IEF-Western blot assay, and 0.74 (0.59-0.89) for msAFP percentage by GISA., Conclusions: Both the serum concentration and percentage of msAFP are potential diagnostic markers for HCC with nondiagnostic AFP. GISA can quantify a specific glycoform of a serologic marker.