Radiographic Features of the Metacarpal in Blauth Type III Thumb Hypoplasia.

PURPOSE: The purpose of this study was to investigate whether radiographs can be used to aid in the determination of Blauth IIIA and IIIB thumbs. METHODS: Six pediatric hand surgeons were asked to evaluate the radiographs of 77 thumbs and classify the thumb as IIIA or IIIB and indicate which morphologic features influenced their decision. Quantitative measurements and ratios of radiographs were obtained and compared between IIIA and IIIB thumbs. RESULTS: The radiographic features selected for type IIIA thumbs include near-normal length and near-normal width and for type IIIB thumbs, abnormally short, tapered proximal end, and round proximal end. The six surveyed surgeons reached consensus in 82% (63/77) of thumbs, and this matched the enrolling surgeon's classification in 77% (59/77) cases. The ratio of the length of the thumb metacarpal compared with the length of the index metacarpal was different between IIIA and IIIB thumbs (66% ± 0.08% and 46% ± 0.18%, respectively). The ratio of the width of the thumb metacarpal shaft at its narrowest aspect to the width of the thumb metacarpal base was notably different between IIIA and IIIB (68% ± 0.13% and 95% ± 0.28%, respectively). CONCLUSIONS: Near-normal length and near-normal width of the metacarpal were used to predict IIIA and abnormally short, abnormally narrow, and a round or tapered base of the metacarpal were used to predict IIIB classification. The length of the thumb metacarpal relative to the index metacarpal is on average 66% of the length of the index metacarpal in IIIA thumbs compared with 46% in IIIB thumbs. The width of the shaft of the thumb metacarpal at its narrowest is 68% of the width of the thumb metacarpal base in IIIA thumbs, indicating a flared base. In IIIB thumbs, the shaft width was on average 95% of the base width, indicating a tapered base. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic level III.

Feasibility of Ultrasound in Infant Wrist and Thumb Imaging.

OBJECTIVES: To determine the feasibility of ultrasound (US) in infant lateral carpal and base-of-the-thumb imaging. We hypothesized that US would be a practical modality for visualizing the unossified structures. METHODS: Institutional review board approval was obtained for this single-center pilot study. Healthy infants aged 12 months or younger were enrolled. Ultrasound examinations of the distal radial epiphysis through the first metacarpal were performed with a high-frequency transducer. RESULTS: Ultrasound evaluations of the base of the thumb were performed in 18 healthy infants (mean age ± SD, 13.8 ± 9.1 weeks; 44% female). Assuming an elliptical shape, the mean areas of the scaphoid and first metacarpal epiphysis measured 0.85 ± 0.19 and 0.44 ± 0.087 cm2 , respectively. The mean areas of the trapezium and ossified first metacarpal as approximate rectangular shapes measured 0.23 ± 0.069 and 0.49 ± 0.16 cm2 . A perimeter tracing was also used as an alternative area calculation. The mean trapezium area-to-scaphoid area ratio (0.28 ± 0.10) showed less variability compared to the first metacarpal epiphysis area-to-scaphoid area ratio (0.55 ± 0.20) or first metacarpal area-to-scaphoid area ratio (0.64 ± 0.31). CONCLUSIONS: Our data suggest that US is well suited for the evaluation of the lateral carpus and base of the thumb in young infants. These data serve as a reference to which wrist and thumb abnormalities can be compared.

Treatment of Madelung Deformity With Vicker Ligament Release and Radial Physiolyses: A Case Series.

PURPOSE: To evaluate the surgical outcomes in a series of Madelung wrists treated with a Vicker ligament release at a young age. We hypothesize that early treatment of Madelung deformity with Vicker ligament release is safe and may minimize progression of deformity. METHODS: A retrospective review was performed at a single large pediatric institution from 2013 to 2016 of patients with a diagnosis of Madelung deformity treated with Vicker ligament release and radial physiolysis. Exclusion criteria included patients who were skeletally mature, who underwent osteotomy procedures, or who had incomplete follow-up. Patient demographics were collected, concomitant surgeries were recorded, and outcomes including range of motion and pain were documented. Measurements of standard anteroposterior and lateral radiographs were calculated before and after surgery to monitor radiographic deformity and progression. RESULTS: Six girls with bilateral Madelung deformity who underwent bilateral Vicker ligament resection and radial physiolysis (12 total wrists) were included. The average age at presentation was 7.5 years (range, 7-9 years), with an average follow-up of 30 months. Reasons for presentation included sports injuries (2), ulnar-sided wrist pain (2), and mild deformity (2). Additional radial and ulnar epiphysiodeses were performed in 2 wrists each. There were no intraoperative complications. Although pain resolved within the first month after surgery for all patients, 2 patients had intermittent unilateral ulnar-sided wrist pain at final follow-up. All patients returned to their presurgery activities. There was no loss of range of motion, and 4 wrists with preoperative supination deficits improved by an average of 17°. Radiographic measurements demonstrated improvement in the radial physeal angle in 10 out of 12 wrists (83%). No patients displayed worsening deformity after surgery. Two patients underwent subsequent procedures. CONCLUSIONS: In patients with early Madelung deformity, Vicker ligament release with radial physiolysis is a safe treatment option that theoretically has the potential to minimize the progression of radiographic deformity. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Treatment of Acute Seymour Fractures.

BACKGROUND: Seymour fractures are distal phalanx fractures in children with a juxta-epiphyseal pattern. The purpose of our study was to investigate the treatments, outcomes, operative ;indications, and antibiotic choice for acute Seymour fractures (presenting within 24 h of injury), to better define optimal management. We hypothesized that: (1) cephalexin provides adequate antibiotic coverage for acute Seymour fractures; (2) most injuries will achieve good outcomes with management in the emergency department (ED) alone; and (3) indication for operative intervention is unsuccessful or unstable reduction in the ED. METHODS: We performed a retrospective study of patients under 18 years old treated at a large pediatric hospital from 2009 to 2017 for an acute Seymour fracture. Study outcomes included management and antibiotic type, infection, fracture healing, malunion, physeal disturbance, nail dystrophy, antibiotic failure, and need for unplanned operative intervention. RESULTS: Mean age of patients was 10 years, with 43 males and 22 females sustaining 65 Seymour fractures. Fifty-eight cases (89%) were initially managed in the emergency department. Seven cases were initially managed with an operative intervention that included I&D, open reduction, and K-wire fixation. The most commonly cited surgical indication was unsuccessful closed reduction. Four patients initially managed in the ED required an unplanned operation, usually because of fracture redisplacement. Complications were rare, with superficial infections being most common. CONCLUSIONS: Most acute Seymour fractures can be successfully managed in the emergency department if stable reduction is achieved. LEVEL OF EVIDENCE: Level IV, therapeutic.

Scientific and Regulatory Policy Committee: Recommended ("Best") Practices for Determining, Communicating, and Using Adverse Effect Data from Nonclinical Studies.

Recommendations (best practices) are provided by the Society of Toxicologic Pathology's Adversity Working Group for making consistent interpretations of test article-related effects as "adverse" and assigning a "no observed adverse effect level" (NOAEL) in nonclinical toxicity studies. Adverse is a term indicating "harm" to the test animal, while nonadverse indicates lack of harm. Adverse findings in the study reports should be defined in relation to effects on the test species used and within the context of the given study. Test article-related effects should be described on their own merits, and decisions to consider them as adverse or nonadverse should be justified. Related effects may be discussed together; in particular, markers of toxicity that are not in and of themselves adverse ideally should be discussed in conjunction with the causal toxicity to determine adversity. Adverse findings should be identified in subreports (clinical data, pathology data, etc.) if sufficient information is available, and/or in the final study report as individual or grouped findings, but study NOAELs should be established at the level of the overall study report. Interpretations such as "not biologically relevant" or "not toxicologically important" should be avoided unless defined and supported by scientific rationale. Decisions defining adverse findings and the NOAEL in final study reports should combine the expertise of all contributing scientific disciplines. Where possible, use of NOAELs in data tables should be linked to explanatory text that places them in context. Ideally, in nonclinical summary documents, NOAELs from multiple studies are considered together in defining the most important adverse responses in the most sensitive species. These responses are then considered along with an understanding of their likely mechanisms, as well as other information such as variability in species sensitivity, comparative pathology, reversibility and progression, kinetics, and metabolism of the test substance to help assess human risk.

Mode of action framework analysis for receptor-mediated toxicity: The peroxisome proliferator-activated receptor alpha (PPARα) as a case study.

Several therapeutic agents and industrial chemicals induce liver tumors in rodents through the activation of the peroxisome proliferator-activated receptor alpha (PPARα). The cellular and molecular events by which PPARα activators induce rodent hepatocarcinogenesis has been extensively studied and elucidated. This review summarizes the weight of evidence relevant to the hypothesized mode of action (MOA) for PPARα activator-induced rodent hepatocarcinogenesis and identifies gaps in our knowledge of this MOA. Chemical-specific and mechanistic data support concordance of temporal and dose-response relationships for the key events associated with many PPARα activators including a phthalate ester plasticizer di(2-ethylhexyl) phthalate (DEHP) and the drug gemfibrozil. While biologically plausible in humans, the hypothesized key events in the rodent MOA, for PPARα activators, are unlikely to induce liver tumors in humans because of toxicodynamic and biological differences in responses. This conclusion is based on minimal or no effects observed on growth pathways, hepatocellular proliferation and liver tumors in humans and/or species (including hamsters, guinea pigs and cynomolgous monkeys) that are more appropriate human surrogates than mice and rats at overlapping dose levels. Overall, the panel concluded that significant quantitative differences in PPARα activator-induced effects related to liver cancer formation exist between rodents and humans. On the basis of these quantitative differences, most of the workgroup felt that the rodent MOA is "not relevant to humans" with the remaining members concluding that the MOA is "unlikely to be relevant to humans". The two groups differed in their level of confidence based on perceived limitations of the quantitative and mechanistic knowledge of the species differences, which for some panel members strongly supports but cannot preclude the absence of effects under unlikely exposure scenarios.

Selective Ulnar Nerve Decompression, Capsular Branch Denervation, and Arthroscopic Debridement as a Unique Technique to Improve Quality of Life for Avascular Necrosis of the Distal Humerus and Radius in a Young Patient With ALL.

Avascular necrosis (AVN), one of the most common therapy-related and debilitating side effects of antileukemic treatment, can adversely affect a patient's long-term quality of life. Our case study presents a young woman with bilateral elbow AVN and hip AVN after acute lymphoblastic leukemia treatment, with a unique treatment strategy for her elbow pain. The treatment strategy included elbow joint denervation with arthroscopic debridement and distal humerus core decompression. The goal of this procedure was to improve symptomatic pain while retaining bone stock in the distal humerus hopefully allowing better function of the patient's elbow. This treatment may not only improve the quality of life in a young patient but also delay the need for future surgery. Our patient had improved pain relief in her elbow postsurgery. This procedure may be used for pain control and may have beneficial future implications in this limited population.

Delayed Presentation of Seymour Fractures: A Single Institution Experience and Management Recommendations.

Background: Seymour fractures in children are prone to complications without prompt and appropriate treatment. This study investigated outcomes of Seymour fractures with delayed presentations; specifically, if deep infection predisposed to operative treatment, if antibiotic administration improved fracture healing, and if oral clindamycin had fewer treatment failures than oral cephalexin. Methods: A single-institution retrospective cohort study was performed of patients with delayed Seymour fracture presentations (defined as greater than 24 hours post-injury) between 2009 and 2017. Data collected included demographics, time to presentation, infection on presentation, operative treatment, antibiotic use and duration, fracture union, and complications. Statistical testing used logistic regression and Fisher's exact test, with results reported as P-values (P), odds ratios (ORs), and 95% confidence intervals (CIs). Results: There were 73 patients with delayed Seymour fracture presentations, with mean age of 11.1 years (standard deviation: 2.9), with 56 (77%) males, and median time to presentation of 7 days (interquartile range: 3-17). Deep infection on presentation was a risk factor for operative intervention (OR = 34.4, P = .0001, CI, 5.5-217.2). Antibiotic administration protected against the development of a nonunion or delayed union (OR = 0.11, P = .008, CI, 0.021-0.57). Time to antibiotics did not protect against nonunion or delayed union (OR = 0.77, P = .306, CI, 0.37-1.3). Clindamycin had fewer treatment failures than cephalexin (P = .039). Conclusions: Deep infection is a risk factor for operative treatment of Seymour fractures with delayed presentations. Clindamycin is a better antibiotic choice for Seymour fractures that present in delayed fashion.

The Development of Trigger Thumb in the Contralateral Thumb in Pediatric Patients Presenting Initially With Unilateral Involvement.

Background: Pediatric trigger thumb is a common condition that can occur bilaterally. There have been reports of a metachronous relationship between trigger thumbs developing in both extremities. Surgeons might consider delaying operative treatment of unilateral trigger thumb due to the concern that contralateral symptoms may develop later in childhood, requiring a second procedure and anesthetic event. Methods: We retrospectively reviewed patients diagnosed with pediatric trigger thumb from 2008 to 2016 at a large pediatric hospital. Data collected included age at presentation and onset, laterality, age and timing of onset of contralateral symptoms, time of index procedure and subsequent procedure (if any), severity of symptoms, previous treatments, range of motion, and birth history. Results: There were 198 patients with pediatric trigger thumb, with 55 patients (28%) presenting with or developing bilateral involvement. Fifty patients (25%) had bilateral involvement upon initial presentation. Five patients (3%) were subsequently diagnosed with contralateral trigger thumb after initial presentation of unilateral trigger thumb. Average time to contralateral trigger thumb development was 12 months after presentation in unilateral patients. Most patients presented with locked flexion contracture with palpable Notta's nodule. Of the 5 patients who developed contralateral trigger thumbs, three required a second surgery after the index procedure. Conclusions: The vast majority of patients with bilateral trigger thumbs had bilateral involvement upon initial presentation to the pediatric hand clinic. Given the rarity of bilateral symptoms after initial unilateral presentation, we do not recommend delayed surgical intervention for patients with unilateral disease in children over 3 years of age.

Completed Ulnar Shaft Stress Fracture in a Fast-Pitch Softball Pitcher.

Stress fractures of the upper extremity have been previously described in the literature, yet reports of isolated injury to the ulna diaphysis or olecranon are rare. The authors describe a case involving an 18-year-old fast-pitch softball pitcher. She presented with a long history of elbow and forearm pain, which was exacerbated during a long weekend of pitching. Her initial physician diagnosed her as having forearm tendinitis. She was treated with nonsurgical means including rest, anti-inflammatory medications, therapy, and kinesiology taping. She resumed pitching when allowed and subsequently had an acute event immediately ceasing pitching. She presented to an urgent care clinic that evening and was diagnosed as having a complete ulnar shaft fracture subsequently needing surgical management. This case illustrates the need for a high degree of suspicion for ulnar stress fractures in fast-pitch soft-ball pitchers with an insidious onset of unilateral forearm pain. Through early identification and intervention, physicians may be able to reduce the risk of injury progression and possibly eliminate the need for surgical management. [Orthopedics. 2017; 40(2):e360-e362.].

A Weight-of-evidence analysis of the cancer dose-response characteristics of 2,3,7,8-tetrachlorodibenzodioxin (TCDD).

Cancer risk assessment for TCDD and other compounds must focus on the cancer dose-response relationship and corresponding potency for the range of human doses before it can have relevance to the human exposure environment. Major differences of opinion exist over whether the dose-response curve for TCDD and other dioxin congeners is non-linear (incorporating a threshold dose region below which tumors are unlikely to be elicited) or linear (implying that any exposure has a statistical likelihood of causing cancer). The World Health Organization and others strongly support a non-linear dose-response relationship for TCDD and cancer, whereas USEPA characterizes the dose-response function as linear. This review critically summarizes the available information on TCDD dose-response relationship for cancer utilizing a weight-of-evidence approach. This assessment concludes that the available data support a non-linear dose-response relationship as being most likely and appropriate for human cancer risk assessment, i.e., the evidence suggests that a biological threshold exists in the dose-response. While proof of a threshold is not absolute, and never can be, the level of certainty for TCDD is substantial because of the concordance of many lines of evidence and the consistency of repeated observations pointing to non-linearity.

The Use of In vivo Hepatic Initiation-Promotion Systems in Understanding the Hepatocarcinogenesis of Technical Grade Dinitrotoluene.

A 2 year bioassay sponsored by the Chemical Industry Institute of Toxicology demonstrated the potent hepatocarcinogenicity of technical grade dinitrotoluene (DNT) which contains 76% 2,4-DNT, 18% 2,6-DNT and less than 3% of each 2,3; 2,5; 3,4 and 3,5-DNT isomers. In contrast, a 2 year bioassay of 2,4-DNT sponsored by the National Cancer Institute did not result in the appearance of hepatic neoplasms above the spontaneous incidence. Using previously described in vivo hepatic initiation-promotion systems, an evaluation of the initiating and promoting activity of individual DNT isomers was undertaken to provide an understanding for the differences between the two bioassays. Weak hepatocyte initiating activity was identified in technical grade DNT and purified 2,6-DNT. In contrast, 2,3; 2,4; 2,5; 3,4 and 3,5 isomers had no detectable initiating activity. When fed following a diethylnitrosamine initiating regimen, technical grade DNT, purified 2,4 and 2,6-DNT isomers had demonstrable promoting activity. Therefore, the hepatic neoplasms resulting from technical grade DNT feeding apparently resulted from the initiating activity of 2,6-DNT followed by the promoting effect of both the 2,4 and 2,6-DNT isomers. The lack of hepatic neoplasms following chronic feeding of 2,4-DNT was apparently due to the lack of hepatic initiating activity.

Intraosseous median nerve entrapment following pediatric posterior elbow dislocation.

Intra-articular entrapment of the median nerve following reduction of a pediatric posterior elbow dislocation is a rare complication but has been reported in the literature.This article describes a case of a 7-year-old girl who sustained a posterior elbow dislocation associated with a medial epicondyle fracture and the subsequent intraosseous entrapment of her median nerve. The entrapment is believed to have resulted from new bone formation over the nerve that went unrecognized for nearly 2 years following injury. Routine imaging studies failed to detect the entrapment prior to exploratory surgery. Intra-articular entrapment of the median nerve must be suspected following pediatric elbow dislocation when concentric reduction fails, postreduction images demonstrate joint widening, or the patient has persistent clinical symptoms. This case demonstrates the potential for delay in diagnosis of the cause for neurological impairment following a relatively common injury in the pediatric population.Objective intraoperative findings and intraoperative micropathology aided in limiting the amount of nerve resected to nonviable portions. Our case demonstrates the potential use of a cable nerve graft to bridge segmental defects in peripheral nerves.

Metabolomics of urine for the assessment of microvesicular lipid accumulation in the liver following isoniazid exposure.

This study was conducted to develop a noninvasive marker of hepatic microvesicular lipid accumulation (MVLA), a histopathological effect currently diagnosed in humans following liver biopsy. MVLA is detected in animal studies of chemicals and drugs and occurs in some humans exposed to chemicals or pharmaceuticals. Because MVLA is a reversible histopathology, early detection of MVLA using a noninvasive method, could aid clinicians in the treatment of patients taking drugs that are known to induce this injury. Isoniazid (INH) was selected as a model compound for this investigation, because MVLA occurs in tuberculosis (TB) patients treated with a combination therapy, which includes INH. This study used male rats dosed daily with INH at 0, 10, or 300 mg/kg/day for up to 8 days. Urine, blood, and liver were obtained following 1 and 8 days. NMR metabolomics of urine revealed markers that correlated (100%) with the findings of MVLA in the right, left, and median liver lobes in 4/9 rats administered the high dose of INH for 8 days. Metabolomics of liver extracts also revealed markers that correlated with the MVLA injury. Serum enzymes that are clinically used to assess liver injury were not consistently correlated to the findings of MVLA. Metabolite changes consistent with the presence of MVLA correlated with interruptions in inositol, carbohydrate, glycerolipid, and glyoxylate metabolism. This study reveals markers that could find pre-clinical use, provides insights into mechanisms involved in MVLA, and demonstrates the need for the validation of noninvasive MVLA markers in human patients.