Effect of Remnant Tissues on Outcomes of Anterior Cruciate Ligament Reconstruction at Follow-up Arthroscopy.

BACKGROUND: Remnant-preserving anterior cruciate ligament reconstruction (ACLR) is sought to enhance vascularization and maturation of a graft and to produce positive clinical outcomes after reconstruction. OBJECTIVE: The purpose of this study was to investigate an effect of remnant anterior cruciate ligament (ACL) tissues on outcomes of ACLR 1 year after reconstruction in younger populations. DESIGN: Retrospective chart review. SETTING: Inpatient orthopedic surgical and rehabilitation clinic. SUBJECTS: The subjects were 644 patients who underwent primary ACLR. INDEPENDENT VARIABLES: The independent variables were age, height, and body weight of the subjects, and the presence of remnant tissue. MAIN OUTCOME MEASURES: The outcome measure was the number of subjects with secondary infra-articular injuries at a follow-up arthroscopy after ACLR. The odds ratio was calculated and compared between the remnant-preserving ACLR (ACLR-P) and remnant-resecting (ACLR-R) groups to investigate the effect of remnant tissues on postoperative outcomes. RESULTS: A total of 416 cases met our inclusion criteria and were included in this study. There were 136 cases (49 males and 87 females) in the ACLR-P group with the mean age (±SD) of 17.86 ± 2.85 years. There were 280 cases (106 males and 174 females) in the ACLR-R group, and the mean age (±SD) was 18.13 ± 2.73 years. Of 136 cases in the ALCR-P group, 54 (39.7%) had abnormal arthroscopic findings that lead to a surgical intervention. Of 280 patients in the ACLR-R group, 128 (45.7%) had abnormal findings. Odds ratio was 0.78 [95% confidence interval (CI), 0.51-1.18; P = 0.24]. Four cases in the ACLR-P group and 8 in the ACLR-R group were diagnosed with ACL retear during follow-up arthroscopy. Odds ratio was 1.03 (95% CI, 0.30-3.48; P = 0.96). CONCLUSIONS: The presence of ACL remnant tissues did not have a significant effect on outcomes 1 year after reconstruction. However, there was a trend that lower percentage of patients with remnant-preserving ALCR had abnormal arthroscopic findings that lead to a surgical treatment at follow-up arthroscopy 1 year after initial reconstruction. The presence of remnant tissues did not have a significant effect on retear rate.

Upper Extremity Range of Motion and Pitching Profile of Baseball Pitchers in Japan.

BACKGROUND: Shoulder range of motion and pitch count in baseball pitchers have been linked to pitching-related upper extremity injury. PURPOSE: To investigate upper extremity range of motion and pitching profiles in baseball pitchers in Japan as well as to make a comparison between injured and noninjured pitchers. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Forty-one Little League to college-level baseball pitchers were measured for bilateral shoulder and elbow range of motion, including shoulder internal rotation (IR), external rotation (ER), shoulder horizontal adduction (HAD), and elbow extension (EXT). They were also asked to answer a simple questionnaire regarding their past pitching-related medical history and pitching profile. Additionally, 28 participants with baseball-related upper extremity injuries (injury group) were compared with 13 participants without injury (no-injury group) for the same parameters. Collected data were analyzed using analysis of variance. RESULTS: Significant limb differences (dominant vs nondominant side) were noted for ER (117.2° vs 109.8°, P = .02), IR (53.5° vs 61.9°, P = .007), HAD (28.3° vs 32.8°, P = .03), and EXT (1.0° vs 4.6°, P = .01). A significant between-group difference (injury vs no-injury group) was observed for IR in both the dominant (55.4° vs 45.6°, P = .03) and nondominant shoulder (65.3° vs 55.0°, P = .01). Participants in the injury group pitched more games in a season and more innings per game started. CONCLUSION: Japanese baseball pitchers displayed adaptive changes in upper extremity range of motion similar to American pitchers when compared bilaterally. Injured pitchers exhibited greater IR range of motion in their pitching arm compared with noninjured pitchers.

Sorafenib Therapy for Pediatric Acute Myeloid Leukemia with FMS-like Tyrosine Kinase 3-internal Tandem Duplication Mutations: 2 Case Reports.

Sorafenib is a promising agent for treating pediatric refractory acute myeloid leukemia (AML) exhibiting FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD); however, its optimal use needs to be established. We report 2 cases of refractory pediatric FLT3-ITD-positive AML treated with sorafenib. Case 1 underwent stem cell transplantation (SCT) without entering remission, despite the use of chemotherapy. This patient relapsed despite receiving post-SCT sorafenib. Chemotherapy combined with sorafenib successfully achieved complete remission in case 2. This patient received post-SCT sorafenib and remains in complete remission. The combination of pre-SCT and post-SCT sorafenib may thus be effective for pediatric refractory FLT3-ITD-positive AML.

Identification of a homozygous JAK3 V674A mutation caused by acquired uniparental disomy in a relapsed early T-cell precursor ALL patient.

Investigation of genetic alterations associated with relapse in acute lymphoblastic leukemia (ALL) may help to identify druggable targets for specific therapies. Early T-cell precursor ALL (ETP-ALL) is a subtype of T-ALL with poor prognosis. Although the genetic landscape of ETP-ALL has been determined, genetic alterations related to the relapse of ETP-ALL have not been fully investigated. Here, we report the first patient with relapsed pediatric ETP-ALL to exhibit a homozygous JAK3 activating mutation, V674A, caused by acquired uniparental disomy (UPD). Single nucleotide polymorphism array analysis revealed acquired UPD (aUPD) at the 19p13.3-p12 locus only in leukemic cells at relapse. Sanger sequence of the JAK3 gene, which was located at 19p13.1 and frequently mutated in ETP-ALL, was performed in paired leukemic samples to determine homozygous JAK3 V674A mutation only in relapsed leukemic cells. In contrast, leukemic cells at initial diagnosis harbored hemizygous JAK3 V674A mutation. Further, whole-exome sequencing revealed mutations in 18 genes only in relapsed samples, although none of these was recurrent in T-ALL. These findings suggest that aUPD at 19p13.1 is partly associated with relapse in this patient. Pharmacological inhibition of JAK3 may be therapeutic in such cases.

Dyskeratosis congenita complicated by hepatic fibrosis with hepatic vein thrombosis.

We describe the case of 2 male siblings with dyskeratosis congenita (DC). Extensive genetic analysis failed to identify a causative genetic abnormality. The elder brother developed hepatic fibrosis accompanied with hepatic vein thrombosis at the age of 9 years. Recent studies have found that patients with DC sometimes develop hepatic complications, including cirrhosis. However, little is known about hepatic complications in patients with DC who lack these mutations. Further genetic studies are required to understand the relationship between DC and hepatic complications. In addition, although danazol can sometimes be effective for treating bone marrow failure, hepatotoxicity can be a major complication. Therefore, when danazol is administered to patients with DC, careful monitoring for hepatic complications is important.

All-trans retinoic acid combined with 5-Aza-2'-deoxycitidine induces C/EBPα expression and growth inhibition in MLL-AF9-positive leukemic cells.

The present study tested whether all-trans retinoic acid (ATRA) and 5-Aza-2'-deoxycitidine (5-Aza) affect AML cell differentiation and growth in vitro by acting on the CCAAT/enhancer binding protein α (C/EBPα) and c-Myc axis. After exposure to a combination of these agents, cell differentiation and growth arrest were significantly higher in human and murine MLL-AF9-expressing cells than in MLL-AF4/AF5q31-expressing cells, which were partly associated with increased expression of C/EBPα, C/EBPε, and PU.1, and decreased expression of c-Myc. These findings indicate that MLL-AF9-expressing cells are more sensitive to ATRA and 5-Aza, indicating that different MLL fusion proteins possess different epigenetic properties associated with retinoic acid pathway inactivation.

Frequency and clinical features of the JAK2 V617F mutation in pediatric patients with sporadic essential thrombocythemia.

BACKGROUND: Pediatric essential thrombocythemia (ET) is a rare and heterogenous disease entity. While several recent studies have focused on the role of the JAK2 V617F mutation in pediatric ET, the frequency of pediatric ET cases with this mutation and the associated clinical features remain unclear. PROCEDURE: We examined six childhood cases who had been diagnosed with ET according to WHO criteria (onset age: 0.2-14 years) for the presence of the JAK2 V617F mutation, MPLW515L mutation and JAK2 exon 12 mutations. Two sensitive PCR-based methods were used for the JAK2 V617F genotyping. We also examined the expression of polycythemia rubra vera-1 (PRV-1), which is a diagnostic marker for clonal ET. RESULTS: We found that three of the six cases had the JAK2 V617F mutation and that all six cases expressed PRV-1 in their peripheral granulocytes. Neither MPL W515L mutation nor JAK2 exon 12 mutations was detected in the patients without JAK2 V617F mutation. The two patients who developed thrombocythemia during infancy were JAK2 V617F-negative. CONCLUSIONS: These findings suggest that the JAK2 V617F mutation is not rare in childhood sporadic ET cases, and that these cases might be older and myeloproliferative features.

Successful management of severe L-asparaginase-associated pancreatitis by continuous regional arterial infusion of protease inhibitor and antibiotic.

BACKGROUND: L-asparaginase is a key drug in the treatment of childhood acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). However, L-asparaginase can cause a fatal complication of pancreatitis, and an effective treatment for L-asparaginase-associated pancreatitis (AAP) has not been developed to date. The authors investigated whether rapidly treating children with AAP by continuous regional arterial infusion (CRAI) of protease inhibitor and antibiotic would quickly resolve AAP. METHODS: Between 2000 and 2007, 104 pediatric patients with ALL or LBL were treated at the authors' affiliated hospitals with intensive regimens that included Escherichia coli-derived L-asparaginase. Six of 104 patients developed severe AAP. One patient was treated with intravenous infusion of protease inhibitor, and the remaining 5 patients received CRAI of protease inhibitor and antibiotic within 48 hours of the onset of AAP. RESULTS: The patient who received intravenous protease inhibitor had pseudocyst formation and developed a subsequent leukemic recurrence after the interruption of chemotherapy for 4.5 months. In the other patients, AAP subsided within 2 to 6 days after the start of CRAI, and serious complications did not emerge. Significantly, chemotherapy could be resumed within 4 weeks (range, 12-23 days) after the onset of AAP, and the patients were in complete remission from 4 months to 44 months with further chemotherapy that excluded L-asparaginase. CONCLUSIONS: The current results indicated that early introduction of CRAI of protease inhibitor and antibiotic is suitable for treating severe AAP.

Successful treatment of congenital systemic juvenile xanthogranuloma with Langerhans cell histiocytosis-based chemotherapy.

Juvenile xanthogranuloma (JXG), one of the most common forms of non-Langerhans cell histiocytosis (LCH), usually presents in young children as spontaneously regressing cutaneous lesions. However, the systemic type of JXG is difficult to treat in newborn infants, and fatal cases have been reported. In the patient described here, solid masses were discovered by fetal sonography during the 38th gestational week. At birth she had multiple tumors on the back, cheek, and hip as well as marked hepatosplenomegaly accompanied by respiratory failure. Laboratory results indicated pancytopenia, obstructive liver dysfunction, and coagulopathy. Brain magnetic resonance imaging revealed a tumor at the left pontine angle, and dysmorphic histiocytes were present in her spinal fluid. She was diagnosed with systemic JXG by histopathologic findings of the hip mass. The LCH-based multiagent chemotherapy including cytarabine, vincristine, methotrexate, and prednisolone ameliorated the symptoms rapidly. She was treated for 12 months and is currently doing well as a normally developing 2-year-old.