Epidemiology of Brachial Plexus Birth Injury and the Impact of Cesarean Section on Its Incidence.

BACKGROUND: While prior research provided thorough analysis of the epidemiology of brachial plexus birth injury (BPBI) from 1997 to 2012, recent trends are unknown. The goal of this study was to update the understanding of the epidemiology and risk factors for BPBI. METHODS: Installments of the Kids' Inpatient Database (1997 to 2019) were used to estimate BPBI incidence in the United States in comparison to several independent variables over time. An interaction between cesarean (C-) section and newborn weight was explored by defining BPBI rates in a stratified manner. A logistic regression model accounting for this interaction was developed to produce odds ratios for independent factors. Lastly, the temporal relationship between BPBI rates and C-section rates was explored using linear regression. RESULTS: BPBI rates were steady around 0.9 to 1.1 per 1000 live births between 2006 and 2019. C-section rates were similarly stable between 32.3% and 34.0% over this period. Stratified analysis indicated C-section delivery was protective against BPBI across newborn weight classes, but the magnitude of this protective value was highest among newborns with macrosomia. Shoulder dystocia was the strongest risk factor for BPBI in the logistic regression model [adjusted odds ratio (AOR): 56.9, P<0.001]. The AOR for a newborn with macrosomia born through C-section (AOR: 0.581, 95% CI: 0.365-0.925) was lower than that for a normal weight newborn born vaginally (AOR: 1.000, P=0.022). Medicaid insurance coverage (AOR: 1.176, 95% CI: 1.124-1.230, P<0.001), female sex (AOR: 1.238, 95% CI: 1.193-1.283, P<0.001), and non-White race (AOR: 1.295, 95% CI: 1.237-1.357, P<0.001) were independent risk factors for BPBI. Over time, the rate of BPBI correlated very strongly with the rate of C-section (R2=0.980). CONCLUSIONS: While BPBI and C-section rates were relatively stable after 2006, BPBI incidence strongly correlated with C-section rates. This highlights the need for close surveillance of BPBI rates as efforts to lower the frequency of C-section evolve. Female, Black, and Hispanic newborns and children with Medicaid insurance experience BPBI at a higher rate, a finding which could direct future research and influence policy. LEVEL OF EVIDENCE: Level IV-case series.

TOX as a new diagnostic marker for T cell large granular lymphocytic leukaemia.

AIMS: T cell large granular lymphocytic leukaemia (T-LGLL) is a rare disorder that may underlie otherwise unexplained cytopenias. The identification of T-LGLL cells in bone marrow biopsies can be a challenge, because a robust immunohistochemistry marker is lacking. The markers currently in use (granzyme B, TIA-1 and CD8) are difficult to interpret or lack specificity. Therefore, we investigated whether immunohistochemistry for thymocyte selection-associated high-mobility group box (TOX), a transcription factor that associates with chronic T cell stimulation, could be a reliable tool for the identification of T-LGLL cells. METHODS AND RESULTS: In this retrospective study, expression of TOX in CD8+ cells in bone marrow biopsies of T-LGLL patients (n = 38) was investigated and compared to bone marrow of controls with reactive T cell lymphocytosis (n = 10). All biopsies were evaluated for TOX staining within the CD8-positive T cell population. The controls were essentially negative for TOX, whereas all T-LGLL cases were positive (median = 80%, range = 10-100%), even when bone marrow involvement was subtle. CONCLUSION: TOX is a highly sensitive marker for the neoplastic cells of T-LGLL and we recommend its use, especially in the diagnostic work-up of patients with unexplained cytopenias.

Pediatric Forearm Malunions.

The aim of this article is to review the evaluation and management of pediatric forearm malunions. Acceptable parameters for nonoperative management of pediatric forearm fractures are reviewed, followed by clinical and imaging workups of malunions and decision-making points for treatment. The landscape of available technology for planning and execution of corrective osteotomy is discussed. Several cases of pediatric forearm malunion are presented, along with surgical and functional outcomes. Recommendations are given regarding the authors' preferred approach for management of pediatric forearm malunions.

Association of Parity and Previous Birth Outcome With Brachial Plexus Birth Injury Risk.

OBJECTIVE: To evaluate the association of maternal delivery history with a brachial plexus birth injury risk in subsequent deliveries and to estimate the effect of subsequent delivery method on brachial plexus birth injury risk. METHODS: We conducted a retrospective cohort study of all live-birth deliveries occurring in California-licensed hospitals from 1996 to 2012. The primary outcome was recurrent brachial plexus birth injury in a subsequent pregnancy. The exposure was delivery history (parity, shoulder dystocia in a previous delivery, or previously delivering a neonate with brachial plexus birth injury). Multiple logistic regression was used to model adjusted associations of delivery history with brachial plexus birth injury in a subsequent pregnancy. The adjusted risk and adjusted risk difference for brachial plexus birth injury between vaginal and cesarean deliveries in subsequent pregnancies were determined, stratified by delivery history, and the number of cesarean deliveries needed to prevent one brachial plexus birth injury was determined. RESULTS: Of 6,286,324 neonates delivered by 4,104,825 individuals, 7,762 (0.12%) were diagnosed with a brachial plexus birth injury. Higher parity was associated with a 5.7% decrease in brachial plexus birth injury risk with each subsequent delivery (adjusted odds ratio [aOR] 0.94, 95% CI 0.92-0.97). Shoulder dystocia or brachial plexus birth injury in a previous delivery was associated with fivefold (0.58% vs 0.11%, aOR 5.39, 95% CI 4.10-7.08) and 17-fold (1.58% vs 0.11%, aOR 17.22, 95% CI 13.31-22.27) increases in brachial plexus birth injury risk, respectively. Among individuals with a history of delivering a neonate with a brachial plexus birth injury, cesarean delivery was associated with a 73.0% decrease in brachial plexus birth injury risk (0.60% vs 2.21%, aOR 0.27, 95% CI 0.13-0.55) compared with an 87.9% decrease in brachial plexus birth injury risk (0.02% vs 0.15%, aOR 0.12, 95% CI 0.10-0.15) in individuals without this history. Among individuals with a history of brachial plexus birth injury, 48.1 cesarean deliveries are needed to prevent one brachial plexus birth injury. CONCLUSIONS: Parity, previous shoulder dystocia, and previously delivering a neonate with brachial plexus birth injury are associated with future brachial plexus birth injury risk. These factors are identifiable prenatally and can inform discussions with pregnant individuals regarding brachial plexus birth injury risk and planned mode of delivery.

Team Approach: The Care of Children with Hand and Upper Limb Differences.

¼ Pediatric hand and upper limb differences include a wide range of conditions that may be genetic, part of a syndrome, or arise from birth trauma or an unknown cause.¼ Because of the variety of conditions and complexity of care requiring professionals from multiple disciplines, the Pediatric Hand Team is similar in purpose to the coordinated multidisciplinary care provided by Craniofacial Panels for children with craniofacial anomalies. Pediatric hand surgeons are trained to lead and coordinate the care of children with these differences, and the Pediatric Hand Team includes occupational and/or certified hand therapists, child life specialists, geneticists and genetic counselors, prosthetists and orthotists, pediatric physical medicine and rehabilitation physicians, pediatric orthopaedic surgeons, pediatric anesthesiologists, and social workers and psychologists. The Team must also have access to pediatric imaging, including ultrasound and magnetic resonance imaging.¼ Treatment of hand differences may include observation, splinting/bracing, therapy, reconstructive surgery, or a combination of these, and indications vary with development, age, associated conditions, and child and family preference. Children who have challenges coping with the stigma of their difference may benefit from programs such as Hand Camp and the Lucky Fin Project.¼ Multiple online and print resources are available to support the Pediatric Hand Team and the child's family and other caregivers.¼ A well-coordinated team-based approach meets the physical and psychosocial needs of the child with hand and upper limb differences from birth to adulthood.

Long-Term Outcomes of Biceps Rerouting for Flexible Supination Contractures in Children With Brachial Plexus Birth Injuries.

PURPOSE: Forearm supination contractures occur in 7% of children with brachial plexus birth injuries (BPBI). Biceps rerouting is proposed when pronation has deteriorated but is passively correctable to at least 0° (neutral). The purpose of this investigation was to evaluate long-term outcomes of biceps rerouting for this indication, including magnitude and maintenance of correction, complications, and subsequent osteotomy. METHODS: We conducted a retrospective review of all children with BPBI and forearm supination contractures treated with biceps rerouting alone, for the above indications, from 1993 to 2017 with at least 2 years follow-up. Demographic information, BPBI characteristics, surgical details, and ranges of motion were obtained from medical records. Pre- and postoperative active pronation (AP) and supination (AS), elbow flexion contracture, and arc of forearm rotation (Arc) were analyzed using linear mixed-effect models. RESULTS: Twenty-five children (13 females; 13 left forearms; 15 global BPBI) underwent biceps rerouting at age 7 ± 3 years and were followed for 6 ± 3 years. Before surgery, the mean AP and AS were 6° ± 29° and 62° ± 27°, respectively. At the final follow-up, the mean AP, AS, and Arc were 39° ± 36°, 18° ± 34°, and 57° ± 42°, respectively. AP was significantly improved and AS was significantly decreased by 2 years after surgery and at the final follow-up. Neither Arc nor elbow flexion contracture changed significantly. Two of 25 (8%) children underwent subsequent forearm osteotomy. CONCLUSIONS: Biceps rerouting in children with BPBI improves the forearm position when pronation is deteriorating by shifting the arc from supination to pronation without decreasing the arc of motion or worsening elbow flexion contractures. There is a low risk of complications and a limited need for subsequent forearm osteotomy. These results are maintained over time. When performed before passive pronation is reduced beyond neutral, this procedure may prevent severe supination contractures and reduce the need for forearm osteotomy. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Prevalence of perinatal factors in infants with brachial plexus birth injuries and their association with injury severity.

OBJECTIVES: To determine the prevalence of perinatal factors associated with brachial plexus birth injury (BPBI) in affected infants and their relationship with BPBI severity. STUDY DESIGN: Retrospective study of BPBI infants prospectively enrolled in a multicenter registry. The prevalence of perinatal factors was calculated. Infants were stratified by injury severity and groups were compared to determine the association of severity and perinatal factors. RESULTS: Seven-hundred-ninety-six BPBI infants had a mean 4.2 ± 1.6 perinatal factors. Nearly all (795/796) reported at least one factor, including shoulder dystocia(96%), no clavicle fracture (91%), difficult delivery(84%), parity >1(61%) and birthweight >4000 g(55%). Ten-percent (74/778) had Horner's syndrome and 28%(222/796) underwent nerve surgery. Birth asphyxia and NICU admission were significantly associated with injury severity. CONCLUSIONS: NICU admission and asphyxia were associated with BPBI severity. An improved understanding of the relationship between perinatal factors and BPBI severity may be used to guide early referral to BPBI providers and support prevention efforts.

Patient-reported Outcomes Measurement Information System (PROMIS) Scores for Children With Brachial Plexus Birth Injury.

BACKGROUND: Patient-reported Outcomes Measurement Information System (PROMIS) for pediatrics is a validated patient-reported or parent-proxy-reported outcomes assessment tool used to evaluate health-related quality of life in children and adolescents with chronic medical conditions. The health-related quality of life of children with brachial plexus birth injury (BPBI) as measured by PROMIS is not well understood. We hypothesized that children with BPBI would report impaired upper extremity (UE) function but normal mobility, pain interference, and peer relationships compared with a reference pediatric population, and that UE function PROMIS scores would be associated with BPBI severity and patient age. METHODS: This is a retrospective cohort study of 180 children with BPBI ages 5 to 17 years old who responded to 4 pediatric PROMIS domains (mobility, pain interference, peer relationships, and UE function) between April 2017 and April 2019. Responses were converted to a T score, which allows comparison with a reference pediatric population (mean reference score=50). Multivariable linear regression was used to quantify the association between PROMIS scores and age, sex, Narakas type, and composite Mallet score. RESULTS: Children with BPBI had normal PROMIS mobility (49.6±8.5), pain interference (44.6±9.7), and peer relationships (52.4±10.6) scores, but reported mild impairment in UE function (40.8±12.1). Age (P<0.0001) and Narakas type (P=0.02) were associated with PROMIS UE function scores, but sex and composite Mallet scores were not. There were no significant associations between the other PROMIS domains and age, sex, Narakas Type, or composite Mallet scores. CONCLUSIONS: Children with BPBI reported PROMIS scores for mobility, pain interference, and peer relationships similar to the reference population but impairment in UE function. Reported UE function decreased with increasing disease severity and increased with age. These PROMIS domains seem to be useful tools for the clinician to evaluate children with BPBI and better understand the challenges they face. Further study is needed to assess their utility in measuring the effects of treatment interventions. LEVEL OF EVIDENCE: Level III.

Outcomes of Botulinum Toxin Injection for Shoulder Internal Rotation Contractures in Infants with Brachial Plexus Birth Injury.

PURPOSE: Shoulder internal rotation contractures (IRC) are common sequela of brachial plexus birth injuries (BPBI). Botulinum toxin A (BTX-A) injection into targeted muscles has been described to facilitate functional improvement at the shoulder joint and prevent glenohumeral dysplasia. The purpose of this study was to assess the outcomes of BTX-A injections on shoulder IRC in children with BPBI. METHODS: We conducted a retrospective analysis of 47 children with shoulder IRC due to BPBI, who were treated with BTX-A. Shoulder passive external rotation in adduction and Active Movement Scale external rotation scores were recorded before and after BTX-A injection. We also recorded the number of children who underwent secondary surgical balancing procedures to improve shoulder motion after BTX-A injection. RESULTS: Mean age at the time of injection was 12 months (range, 5-23 months). Subjects demonstrated a significant increase in passive external rotation of 46° (range, 10° to 90) at 4 months; an average improvement of 18° (range, -30° to 80°) persisted at 11 months after injection. A total of 28 patients (60%) underwent subsequent external rotation tendon transfer. At 5-year follow-up, 7 patients (15%) had adequate functional shoulder range of motion and did not undergo external rotation tendon transfer. CONCLUSIONS: Botulinum toxin A injections result in improvement in IRC due to BPBI, which is sustained beyond the expected half-life of 3 months. As many as 15% of patients who have this treatment avoid external rotation tendon transfer. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.

Posterior Elbow Capsulotomy and Triceps Lengthening for Elbow Extension Contracture in Children with Arthrogryposis Multiplex Congenita.

Posterior elbow capsulotomy plus triceps lengthening facilitates passive elbow flexion in children with arthrogryposis multiplex congenita, allowing independent function for activities of daily living, such as feeding and self-care of the face and hair. DESCRIPTION: The posterior aspect of the distal end of the humerus and the olecranon are identified by palpation and exposed via a curvilinear incision over the posterior aspect of the elbow. Identifying the osseous landmarks can be challenging in some patients. The ulnar nerve is identified and protected. The triceps tendon is isolated, and z-lengthening is performed. Next, the posterior elbow capsule is incised proximal to the tip of the olecranon to expose the joint surface, and the arthrotomy is continued incrementally along the medial and lateral capsule until elbow flexion increases by ≥40°, or past 90° (maximum, 120°), with contact between the lengthened ends of the triceps tendon for repair. The triceps tendon is then repaired in the elongated position. After the wound is closed, the elbow is placed in flexion and immobilized in a cast. ALTERNATIVES: Alternative treatments include passive stretching exercises to increase elbow flexion. RATIONALE: Elbow extension contractures result in substantial limitations in the activities of daily living for children with arthrogryposis multiplex congenita. Those who fail to attain at least 90° of elbow flexion with passive stretching in the first year of life benefit from posterior elbow release and triceps lengthening. In addition, children with <30° of passive elbow flexion are at risk of developing valgus instability of the elbow from passive flexion exercises because the axis of rotation of the elbow is difficult to detect. Once passive elbow flexion is attained, such children may be candidates for tendon transfers allowing active elbow flexion.

Reconstruction of the Suprascapular Nerve in Brachial Plexus Birth Injury: A Comparison of Nerve Grafting and Nerve Transfers.

BACKGROUND: Shoulder external rotation recovery in brachial plexus birth injury is often limited. Nerve grafting to the suprascapular nerve and transfer of the spinal accessory nerve to the suprascapular nerve are commonly performed to restore shoulder external rotation, but the optimal surgical technique has not been clearly demonstrated. We investigated whether there was a difference between nerve grafting and nerve transfer in terms of shoulder external rotation recovery or secondary shoulder procedures. METHODS: This is a multicenter, retrospective cohort study of 145 infants with brachial plexus birth injury who underwent reconstruction with nerve grafting to the suprascapular nerve (n = 59) or spinal accessory nerve to suprascapular nerve transfer (n = 86) with a minimum follow-up of 18 months (median, 25.7 months [interquartile range, 22.0, 31.2 months]). The primary outcome was the Active Movement Scale (AMS) score for shoulder external rotation at 18 to 36 months. The secondary outcome was secondary shoulder surgery. Two-sample Wilcoxon and t tests were used to analyze continuous variables, and the Fisher exact test was used to analyze categorical variables. The Kaplan-Meier method was used to estimate the cumulative risk of subsequent shoulder procedures, and the proportional hazards model was used to estimate hazard ratios (HRs). RESULTS: The grafting and transfer groups were similar in Narakas type, preoperative AMS scores, and shoulder subluxation. The mean postoperative shoulder external rotation AMS scores were 2.70 in the grafting group and 3.21 in the transfer group, with no difference in shoulder external rotation recovery between the groups (difference, 0.51 [95% confidence interval (CI), -0.31 to 1.33]). A greater proportion of the transfer group (24%) achieved an AMS score of >5 for shoulder external rotation compared with the grafting group (5%) (odds ratio, 5.9 [95% CI, 1.3 to 27.4]). Forty percent of the transfer group underwent a secondary shoulder surgical procedure compared with 53% of the grafting group; this was a significantly lower subsequent surgery rate (HR, 0.58 [95% CI, 0.35 to 0.95]). CONCLUSIONS: Shoulder external rotation recovery in brachial plexus birth injury remains disappointing regardless of surgical technique, with a mean postoperative AMS score of 3, 17% of infants achieving an AMS score of >5, and a high frequency of secondary shoulder procedures in this study. Spinal accessory nerve to suprascapular nerve transfers were associated with a higher proportion of infants achieving functional shoulder external rotation (AMS score of >5) and fewer secondary shoulder procedures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Long-Term Outcomes of Brachial Plexus Reconstruction with Sural Nerve Autograft for Brachial Plexus Birth Injury.

BACKGROUND: Infants with brachial plexus birth injury who do not recover motor function spontaneously in a timely manner are candidates for brachial plexus reconstruction with nerve autograft. Outcomes of this intervention are incompletely understood. The authors present the long-term outcomes of brachial plexus reconstruction with sural nerve autograft in infants with brachial plexus birth injury. METHODS: The authors retrospectively reviewed all infants with brachial plexus birth injury who underwent brachial plexus reconstruction with sural nerve autograft between 1992 and 2014 with a minimum 2-year follow-up. The authors used Active Movement Scale scores to determine the presence and timing of shoulder, elbow, and wrist recovery. They assessed recovery of hand function in infants with global brachial plexus birth injury with the Raimondi scale. The number and type of secondary reconstructive procedures were identified. RESULTS: Forty-three infants who underwent brachial plexus reconstruction at age 7 ± 2 months old were followed for 7 ± 5 years. Most infants recovered antigravity elbow flexion (91 percent) and shoulder abduction (67 percent), but fewer recovered antigravity shoulder external rotation (19 percent) and wrist extension (37 percent). Mean postoperative times until observed antigravity motor strength (Active Movement Scale score >5) at the shoulder, elbow, and wrist were all greater than 12 months; evidence of initial motor recovery (Active Movement Scale score >2) was observed earlier. The mean Raimondi score in infants with global brachial plexus birth injury was 2.2 (range, 0 to 5) at final follow-up. Thirty-three children underwent 2 ± 1.2 secondary reconstructive procedures. CONCLUSIONS: Brachial plexus reconstruction with sural nerve autograft reliably results in recovery of shoulder abduction and elbow flexion, but recovery of shoulder external rotation and wrist extension is less predictable, and recovery often takes more than 1 year. Secondary procedures are often performed to optimize function. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

The Quantitative Anatomy of the Dorsal Scapholunate Interosseous Ligament.

BACKGROUND: The anatomy of the scapholunate interosseous ligament (SLIL) has been described qualitatively in great detail, with recognition of the dorsal component's importance for carpal stability. The purpose of this study was to define the quantitative anatomy of the dorsal SLIL and to assess the use of high-frequency ultrasound to image the dorsal SLIL. METHODS: We used high-frequency ultrasound imaging to evaluate 40 wrists in 20 volunteers and recorded the radial-ulnar (length) and dorsal-volar (thickness) dimensions of the dorsal SLIL and the dimensions of the scapholunate interval. We assessed the use of high-frequency ultrasound by comparing the length and thickness of the dorsal SLIL on ultrasound evaluation and open dissection of 12 cadaveric wrists. Student's t test was used to assess the relationship between measurements obtained on cadaver ultrasound and open dissection. RESULTS: In the volunteer wrists, the mean dorsal SLIL length was 7.5 ± 1.4 mm and thickness was 1.8 ± 0.4 mm; the mean scapholunate interval was 5.0 mm dorsally and 2.5 mm centrally. In the cadaver wrists, there was no difference in dorsal SLIL length or thickness between ultrasound and open dissection. CONCLUSIONS: The dorsal SLIL is approximately 7.5 mm long and 1.8 mm thick. These parameters may be useful in treatment of SLIL injuries to restore the native anatomy. High-frequency ultrasound is a useful imaging technique to assess the dorsal SLIL, although further study is needed to assess the use of high-frequency ultrasound in detection of SLIL pathology.

Whole-exome analysis reveals novel somatic genomic alterations associated with outcome in immunochemotherapy-treated diffuse large B-cell lymphoma.

Lack of remission or early relapse remains a major clinical issue in diffuse large B-cell lymphoma (DLBCL), with 30% of patients failing standard of care. Although clinical factors and molecular signatures can partially predict DLBCL outcome, additional information is needed to identify high-risk patients, particularly biologic factors that might ultimately be amenable to intervention. Using whole-exome sequencing data from 51 newly diagnosed and immunochemotherapy-treated DLBCL patients, we evaluated the association of somatic genomic alterations with patient outcome, defined as failure to achieve event-free survival at 24 months after diagnosis (EFS24). We identified 16 genes with mutations, 374 with copy number gains and 151 with copy number losses that were associated with failure to achieve EFS24 (P<0.05). Except for FOXO1 and CIITA, known driver mutations did not correlate with EFS24. Gene losses were localized to 6q21-6q24.2, and gains to 3q13.12-3q29, 11q23.1-11q23.3 and 19q13.12-19q13.43. Globally, the number of gains was highly associated with poor outcome (P=7.4 × 10(-12)) and when combined with FOXO1 mutations identified 77% of cases that failed to achieve EFS24. One gene (SLC22A16) at 6q21, a doxorubicin transporter, was lost in 54% of EFS24 failures and our findings suggest it functions as a doxorubicin transporter in DLBCL cells.

The effect of soft tissue distraction on deformity recurrence after centralization for radial longitudinal deficiency.

PURPOSE: To assess recurrence and complications in children with radial longitudinal deficiency treated with or without external fixator soft tissue distraction prior to centralization. METHODS: Thirteen upper extremities treated with centralization alone were compared with 13 treated with ring fixator distraction followed by centralization. Resting wrist position between the 2 groups was compared before surgery, approximately 2 years after surgery (midterm), and at final follow-up, which was at a mean of 10 years for the centralization-alone group and 6 years for the distraction group. Radiographs were reviewed for hand-forearm angle, hand-forearm position, volar carpal subluxation, ulnar length, and physeal integrity. RESULTS: The clinical resting wrist position was improved significantly after surgery and at final follow-up in both groups, but recurrence was worse at final follow-up in the distraction group patients. Radiographically, in the centralization alone group, the hand-forearm angle improved from 53° before surgery to 13° at midterm but worsened to 27° at final follow-up. In the distraction group, the hand-forearm angle improved from 53° before surgery to 21° at midterm but worsened to 36° at final follow-up. The hand-forearm position improved between preoperative and final assessment in both groups, but at final follow-up, the centralization-alone group had a significantly better position. Volar subluxation was 4 mm improved in the centralization alone group and 2 mm worse in the distraction group at final follow-up. CONCLUSIONS: Centralization, with or without distraction with an external fixator, resulted in improved alignment of the wrist. Distraction facilitated centralization, but it did not prevent deformity recurrence and was associated with a worse final radial deviation and volar subluxation position compared with wrists treated with centralization alone. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

Activation of TAK1 by MYD88 L265P drives malignant B-cell Growth in non-Hodgkin lymphoma.

Massively parallel sequencing analyses have revealed a common mutation within the MYD88 gene (MYD88L265P) occurring at high frequencies in many non-Hodgkin lymphomas (NHLs) including the rare lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia (WM). Using whole-exome sequencing, Sanger sequencing and allele-specific PCR, we validate the initial studies and detect the MYD88L265P mutation in the tumor genome of 97% of WM patients analyzed (n=39). Due to the high frequency of MYD88 mutation in WM and other NHL, and its known effects on malignant B-cell survival, therapeutic targeting of MYD88 signaling pathways may be clinically useful. However, we are lacking a thorough characterization of the role of intermediary signaling proteins on the biology of MYD88L265P-expressing B cells. We report here that MYD88L265P signaling is constitutively active in both WM and diffuse large B-cell lymphoma cells leading to heightened MYD88L265P, IRAK and TRAF6 oligomerization and NF-κB activation. Furthermore, we have identified the signaling protein, TAK1, to be an essential mediator of MYD88L265P-driven signaling, cellular proliferation and cytokine secretion in malignant B cells. Our studies highlight the biological significance of MYD88L265P in NHL and reveal TAK1 inhibition to be a potential therapeutic strategy for the treatment of WM and other diseases characterized by MYD88L265P.

The transverse bone in cleft hand: a case cohort analysis of outcome after surgical reconstruction.

PURPOSE: To evaluate the implications of the transverse bone in cleft hand by assessing outcomes after reconstruction in comparison with a control group. METHODS: This study is a retrospective review of 23 hands in 18 patients following surgical reconstruction of the cleft hand. Eleven hands had a transverse bone component, and 12 hands (control group) did not. Patients and their families were contacted to assess overall satisfaction following reconstruction. Clinical and radiographic records were reviewed to assess aesthetic and functional outcomes, the need for additional surgery, and radiographic divergence angles. RESULTS: There was no difference in aesthetic or functional subjective outcomes. There was no statistically significant difference in any objective outcome measure between the two groups. The use of the cleft for pinch was more dependent on the status of the index finger and the preoperative thumb-index webspace rather than the presence of a transverse bone. Eleven (4 transverse and 7 control) hands required additional surgery to address abnormal function or posture of the index and ring fingers. Preoperative radiographic divergence angles were larger in the transverse bone group than in the control group, whereas postoperative divergence angles were nearly equivalent. CONCLUSIONS: Similar outcomes between the two groups demonstrate that the presence of a transverse bone in cleft hand was not associated with worse outcomes following cleft reconstruction. Preoperative narrowing of the thumb webspace and postoperative index finger metacarpophalangeal joint abnormality are associated with worse functional outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic Level III.

Plasminogen activator inhibitor type 1 in rat spermatozoa: localisation in the tail, in the acrosome and on the surface of the head.

Isolated seminiferous tubules of rat testis contain considerable urokinase-inhibiting activity. An immunohistological analysis revealed the presence of plasminogen activator inhibitor type 1 (PAI-1) in the basement membrane as well as in the interior of the tubules. Distribution and intensity of the intratubular immunoreactivity depends on the stage of the seminiferous cycle. A relatively weak signal is present around elongated nuclei of spermatids at the beginning of chromatin condensation. The signal intensity increases in the course of differentiation until a maximum is reached at stages VII-VIII. In these stages PAI-1 immunoreactivity is localised around the nuclei of the late spermatids as well as along their tails. Spermatozoa in the ductus epididymis also strongly react with the PAI-1-specific antiserum, suggesting that the inhibitor remains associated with the germ cells after spermiation and during maturation in the epididymis. In intact mature spermatozoa isolated from epididymis cauda by "swimming-up' in non-capacitation medium, PAI-1 antigen is localised on the plasma membrane surrounding the head. In addition, in fixed and permeabilised cells the immunoreactivity is detectable in the acrosome and in the tail. Possible functions of PAI-1 in spermatogenesis, sperm motility and sperm-egg interaction are discussed.