Pursuit of "endpoint diagnoses" as a cognitive forcing strategy to avoid premature diagnostic closure.

Premature closure is often described as a significant contributor to diagnostic error. Therefore, developing strategies to mitigate premature closure could reduce diagnostic errors and improve patient care. Here we propose the novel concept of pursuit of an "endpoint diagnosis" as a cognitive forcing strategy (CFS) for avoiding premature diagnostic closure. We define an "endpoint diagnosis" as an underlying causative explanation for a patient's signs, symptoms, and laboratory and radiographic data that exhausts additional relevant diagnostic evaluation. We have observed four contexts in which the error of not pursuing an endpoint diagnosis most often occurs: (1) diagnoses that appear to result in the same treatment regardless of etiology, (2) cases that are particularly complex, (3) clinical scenarios that are vulnerable to systems errors, and (4) situations in which patients' problems are attributed to uncontrolled underlying risk factors or an exacerbation of a known condition. Additionally, we address why we believe endpoint diagnoses are not universally pursued, delineate when this approach might be particularly useful, attempt to reconcile the potential conflict between accepting diagnostic ambiguity in certain instances and pursuing endpoint diagnoses, and outline possible concerns that might arise with using this CFS, including the possibility of lengthy evaluations resulting in overdiagnosis and overtreatment. Our overarching goal is for this CFS to help clinicians in their daily clinical practice as they seek to optimize their diagnostic skill and patient care.

Endosteal Biologic Augmentation for Surgical Fixation of Displaced Femoral Neck Fractures.

OBJECTIVES: To report outcomes of a cohort with displaced femoral neck fractures (FNFs) treated with a length/angle-stable construct augmented with an endosteal fibular allograft serving as a biologic dowel. DESIGN: Prospective. SETTING: Level I Trauma Center. PATIENTS: The study group consists of 27 patients with isolated FNF surgically treated by a single surgeon. INTERVENTION: Open reduction of the femoral neck, fixed with a length- and angle-stable construct of 2 fully threaded cannulated screws augmented with an endosteal fibular allograft serving as a biologic dowel. MAIN OUTCOME MEASUREMENTS: Clinical and radiographic outcomes of the fixation construct and the viability of both the femoral head and the fibular allograft, host response to the allograft and osseous union were evaluated using a specialized sequence of contrast-enhanced magnetic resonance imaging (MRI) obtained at 3 and 12 months postoperatively. RESULTS: This construct resulted in high union rates (89%; 24 of 27). Two patients suffered early catastrophic failure and 1 patient developed fracture nonunion, all of wish underwent uneventful conversion to total hip arthroplasty. Three additional patients (11%) had removal of symptomatic implants. The clinical and radiographic outcomes were excellent. Twelve-month MRIs revealed either partial or complete osseous incorporation of 86% the fibular allografts without signs of adverse reaction of the host to the allograft. Femoral head osteonecrosis segments were noted in 76% of patients on MRI; however, radiographically, there were no signs of osteonecrosis or segmental collapse. CONCLUSIONS: The fibular allograft reconstructs the comminuted femoral neck, and the osteointegration overtime increases the strength of the host bone-graft interface. This added strength seems to provide the stability needed to better preserve the intraoperative reduction, obtain good outcomes, and reduce the complications associated with FNF. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Anatomic Fixation of Supination External Rotation Type IV Equivalent Ankle Fractures.

OBJECTIVES: To compare radiographic and clinical outcomes of supination external rotation type IV equivalent (SER IV E) ankle fractures (AO/OTA classification 44-B2.1) treated with transsyndesmotic screw fixation with those treated with deltoid and posterior inferior tibiofibular ligament (PITFL) repair. DESIGN: Case series and single-surgeon retrospective analysis of a prospective database. SETTING: Academic level I trauma center. PATIENTS: Forty-five SER IV E ankle fractures fulfilled all inclusion/exclusion criteria with at least 12 months of radiographic follow-up. INTERVENTION: Deltoid and PITFL repair in addition to lateral malleolus fixation compared with transsyndesmotic screw fixation. MAIN OUTCOME MEASUREMENTS: Syndesmotic reduction compared with contralateral extremity on a postoperative computed tomography scan and maintenance of reduction based on final postoperative radiographs [medial clear space (MCS) and tibiofibular clear space (TCS)]. RESULTS: There was no significant difference in mean postoperative TCS, MCS, or change in TCS or MCS between the cohorts. The anatomic treatment group had significantly better postoperative syndesmotic reduction compared with the transsyndesmotic cohort (7.4% vs. 33.3%; P = 0.02). Fourteen patients in the transsyndesmotic screw cohort underwent removal compared with 3 patients in the anatomic cohort who required secondary procedures. The transsyndesmotic screw cohort had statistically significant better mean dorsiflexion of ankle (mean 20 vs. 17 degrees; P = 0.02). CONCLUSIONS: This comparison of treatment strategies for SER IV E ankle fractures has shown an improvement in immediate postoperative syndesmotic reduction and the elimination of reoperation for removal of transsyndesmotic screws in patients treated with PITFL repair. Previous research has shown a good correlation between functional outcomes and syndesmotic reduction; however, further investigation into the functional outcomes of these patients is necessary to determine the future clinical impact of this anatomic fixation strategy. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

The Axillary View Typically Does Not Contribute to Decision Making in Care for Proximal Humeral Fractures.

BACKGROUND: Convention dictates that an axillary view be obtained when evaluating proximal humerus fractures (PHF). However, the axillary view is frequently omitted because of pain and technical considerations. Furthermore, its diagnostic utility is unclear in this setting. QUESTIONS/PURPOSES: The purpose of this study was to (1) determine the rate of obtaining an adequate axillary X-ray and complete shoulder series at a level I trauma center, (2) understand the cost of ordering and attempting an axillary radiograph, and (3) determine if axillary radiographs influence the management of PHF. PATIENTS AND METHODS: PHF treated between 2009 and 2011 that were ordered for an AP, scapular Y, and axillary view was identified. The types of radiographs actually obtained were recorded. The cost of obtaining three views and a single view of the shoulder with X-ray was determined. Lastly, three surgeons reviewed 42 PHF, both with and without an axillary view (AV), and treatment recommendations were compared. RESULTS: 30% of PHF in this series had an adequate axillary view, and 14% received a complete trauma series. No factors could be identified that were associated with successfully obtaining an axillary view. Reviewers demonstrated substantial intraobserver reliability (κ = 0.759-0.808) regarding treatment recommendations for PHF with and without the axillary view. The addition of the AV had minimal influence on treatment recommendations. CONCLUSION: Considering that the axillary view for PHF is painful, labor-intensive, costly, and does not appear to provide additional diagnostic value, orthopedic surgeons can consider foregoing the use of the axillary view when evaluating and treating PHF, particularly if other advanced imaging is utilized.

Ankle fracture spur sign is pathognomonic for a variant ankle fracture.

BACKGROUND: The hyperplantarflexion variant ankle fracture is composed of a posterior tibial lip fracture with posterolateral and posteromedial fracture fragments separated by a vertical fracture line. This infrequently reported injury pattern often includes an associated "spur sign" or double cortical density at the inferomedial tibial metaphysis. The objective of this study was to quantitatively establish the association of the ankle fracture spur sign with the hyperplantarflexion variant ankle fracture. METHODS: Our clinical database of operative ankle fractures was retrospectively reviewed for the incidence of hyperplantarflexion variant and nonvariant ankle fractures as determined by assessment of injury radiographs, preoperative advanced imaging, and intraoperative observation. Injury radiographs were then evaluated for the presence of the spur sign, and association between the spur sign and variant fractures was analyzed. RESULTS: The incidence of the hyperplantarflexion variant fracture among all ankle fractures was 6.7% (43/640). The spur sign was present in 79% (34/43) of variant fractures and absent in all nonvariant fractures, conferring a specificity of 100% in identifying variant fractures. Positive predictive value and negative predictive value were 100% and 99%, respectively. CONCLUSION: The ankle fracture spur sign was pathognomonic for the hyperplantarflexion variant ankle fracture. It is important to identify variant fractures preoperatively as patient positioning, operative approach, and fixation construct of variant fractures often differ from those employed for osteosynthesis of nonvariant fractures. Identification of the spur sign should prompt acquisition of advanced imaging to formulate an appropriate operative plan to address the variant fracture pattern. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Fetal brain mTOR signaling activation in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is characterized by developmental malformations of the cerebral cortex known as tubers, comprised of cells that exhibit enhanced mammalian target of rapamycin (mTOR) signaling. To date, there are no reports of mTORC1 and mTORC2 activation in fetal tubers or in neural progenitor cells lacking Tsc2. We demonstrate mTORC1 activation by immunohistochemical detection of substrates phospho-p70S6K1 (T389) and phospho-S6 (S235/236), and mTORC2 activation by substrates phospho-PKCα (S657), phospho-Akt (Ser473), and phospho-SGK1 (S422) in fetal tubers. Then, we show that Tsc2 shRNA knockdown (KD) in mouse neural progenitor cells (mNPCs) in vitro results in enhanced mTORC1 (phospho-S6, phospho-4E-BP1) and mTORC2 (phospho-Akt and phospho-NDRG1) signaling, as well as a doubling of cell size that is rescued by rapamycin, an mTORC1 inhibitor. Tsc2 KD in vivo in the fetal mouse brain by in utero electroporation causes disorganized cortical lamination and increased cell volume that is prevented with rapamycin. We demonstrate for the first time that mTORC1 and mTORC2 signaling is activated in fetal tubers and in mNPCs following Tsc2 KD. These results suggest that inhibition of mTOR pathway signaling during embryogenesis could prevent abnormal brain development in TSC.

Rapamycin prevents seizures after depletion of STRADA in a rare neurodevelopmental disorder.

A rare neurodevelopmental disorder in the Old Order Mennonite population called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome; also called Pretzel syndrome) is characterized by infantile-onset epilepsy, neurocognitive delay, craniofacial dysmorphism, and histopathological evidence of heterotopic neurons in subcortical white matter and subependymal regions. PMSE is caused by a homozygous deletion of exons 9 to 13 of the LYK5/STRADA gene, which encodes the pseudokinase STRADA, an upstream inhibitor of mammalian target of rapamycin complex 1 (mTORC1). We show that disrupted pathfinding in migrating mouse neural progenitor cells in vitro caused by STRADA depletion is prevented by mTORC1 inhibition with rapamycin or inhibition of its downstream effector p70 S6 kinase (p70S6K) with the drug PF-4708671 (p70S6Ki). We demonstrate that rapamycin can rescue aberrant cortical lamination and heterotopia associated with STRADA depletion in the mouse cerebral cortex. Constitutive mTORC1 signaling and a migration defect observed in fibroblasts from patients with PMSE were also prevented by mTORC1 inhibition. On the basis of these preclinical findings, we treated five PMSE patients with sirolimus (rapamycin) without complication and observed a reduction in seizure frequency and an improvement in receptive language. Our findings demonstrate a mechanistic link between STRADA loss and mTORC1 hyperactivity in PMSE, and suggest that mTORC1 inhibition may be a potential treatment for PMSE as well as other mTOR-associated neurodevelopmental disorders.