The Continued Misadventures of Intentional C4 Ingestion: A Case Cluster.

Several published case reports describe the intentional ingestion of cyclotrimethylenetrinitramine, more commonly referred to as Composite-4 (C4), by military personnel. This putty-like explosive material, used for breaching operations, can produce euphoric effects through polyisobutylene; however, the additional ingredient of Research Department Explosive (RDX), or "Cyclonite," can cause significant central nervous system disruption resulting in seizures. We report a unique case cluster of active-duty personnel with intentional C4 ingestion and wide-ranging symptoms, including seizures. Unit personnel discovered this cluster after progressive patient presentations. This report illustrates the spectrum of C4 ingestion effects, as well as the need for investigation to ensure prompt medical evaluation and management of those suspected of consumption.

Comparison of Early versus Late Below Knee Amputation After Trauma With Standardized Prosthetic Care.

Background: High energy, lower extremity trauma is associated with longstanding pain and functional limitations. The clinical decision to proceed with early amputation or limb salvage is often controversial. This study was designed to compare differences in complications, costs, and clinical outcomes of below knee amputation (BKA) performed early after injury or after attempted limb salvage in a hospital with standardized prosthetic care following amputation. Methods: This is a retrospective comparative study of subjects who underwent BKA for a traumatic injury at a single level 1 trauma center and received standardized prosthetic care from a single manufacturer from 1999-2016 with minimum 2-year post-amputation follow up. Outcomes collected included demographics, surgical management, unplanned re-operations, and hospital and prosthetic cost data 2 years from time of injury. Results: Overall, 79 subjects met criteria. Early amputation (EA) was defined by median duration between injury and amputation (6 weeks) with 41 subjects in the EA group and 38 subjects in the late amputation (LA) group. Subjects in the EA group were more likely to have open fractures, high energy mechanism, and less likely to have medical comorbidities. Post-amputation infection was common in both groups (17/41 (42%) vs 17/38 (45%), p=0.77). Subjects undergoing EA were more likely to require unplanned post-amputation revision, 22/41 (54%) versus 10/38 (27%), p=0.017. Hospital costs and prosthetics/orthotics costs from the time of injury to two years following amputation were comparable, with mean hospital EA costs $136,044 versus LA costs $125,065, p=0.38. Mean prosthetics/orthotics costs of EA subjects were $33,252 versus LA costs $37,684, p=0.59. Conclusion: Unplanned post-amputation revision surgeries were more common when BKA was performed early after trauma. Otherwise, outcomes and cost were comparable when amputation was performed early versus late. Level of Evidence: IV.

Battlefield pain summit 2022: Expert consensus statements.

BACKGROUND: Battlefield pain occurs in combat casualties who experience multiple severe injuries. The nature of battlefield scenarios requires a distinct approach to battlefield pain research. A battlefield pain summit was thus convened to identify shortcomings in the current understanding of battlefield pain management, review the current state of battlefield pain research, and shape the direction of future research. METHODS: On January 10 to 11, 2022, a hybrid in-person and virtual meeting hosted by the US Army Institute of Surgical Research defined research priorities for the Combat Casualty Care Research Program's Battlefield Pain research portfolio. Summit participants identified the following key focus areas under the umbrella of battlefield pain research: battlefield injury patterns; use of ketamine and nonopioid analgesics; analgesic delivery systems; the impact of analgesia on performance, cognition, and survival; training methods; battlefield regional anesthesia; and research models. Preliminary statements presented during the summit were refined and rank ordered through a Delphi process. RESULTS: Consensus was achieved on 7 statements addressing ideal analgesic properties, delivery systems, operational performance concerns, and pain training. Ketamine was identified as safe and effective for battlefield use, and further research into nonopioid analgesics represented a high priority. CONCLUSION: The 7 consensus statements that emerged from this battlefield pain summit serve as a template to define the near-term research priorities for military-specific battlefield pain research.

Complications of Hardware Removal.

BACKGROUND: While hardware removal may improve patient function, the procedure carries risks of unexpected outcomes. Despite being among the most commonly performed orthopaedic procedures, scant attention has been given to its complication profile. METHODS: We queried the American Board of Orthopaedic Surgery (ABOS) de-identified database of Part II surgical case lists from 2013 through 2019 for American Medical Association Current Procedural Terminology (CPT) implant-removal codes (20680, 20670, 22850, 22852, 22855, 26320). Hardware removal procedures that were performed without any other concurrent procedure ("HR-only procedures") were examined for associated complications. RESULTS: In the 7 years analyzed, 13,089 HR-only procedures were performed, representing 2.1% (95% confidence interval [CI], 2.1% to 2.2%) of the total of 609,150 surgical procedures during that period. A complication was reported to have occurred in association with 1,256 procedures (9.6% [95% CI, 9.1% to 10.1%]), with surgical complications reported in association with 1,151 procedures (8.8% [95% CI, 8.3% to 9.3%]) and medical/anesthetic complications reported in association with 196 procedures (1.5% [95% CI, 1.3% to 1.7%]). Wound-healing delay/failure (2.1% [95% CI, 1.8% to 2.3%]) and infection (1.6% [95% CI, 1.4% to 1.8%]) were among the most commonly reported complications after HR-only procedures, but other serious events were reported as well, including unexpected reoperations (2.5% [95% CI, 2.2% to 2.7%]), unexpected readmissions (1.6% [95% CI, 1.4% to 1.8%]), continuing pain (95% CI, 1.2% [1.0% to 1.4%]), nerve injury (0.6% [95% CI, 0.4% to 0.7%]), bone fracture (0.5% [95% CI, 0.4% to 0.6%]), and life-threatening complications (0.4% [95% CI, 0.3% to 0.5%]). CONCLUSIONS: Hardware removal is one of the most commonly performed orthopaedic procedures and was associated with an overall complication rate of 9.6% (95% CI, 9.1% to 10.1%) in a cohort of recently trained orthopaedic surgeons in the United States. Although specific complications such as infection, refractures, and nerve damage were reported to have relatively low rates of occurrence, and associated life-threatening complications occurred rarely, surgeons and patients should be aware that hardware removal carries a definite risk. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Is load application necessary when using computed tomography scans to diagnose syndesmotic injuries? A cadaver study.

BACKGROUND: Injuries to the distal tibio-fibular ligaments are common. While pronounced injuries can be reliably diagnosed using conventional radiographs, assessment of subtle syndesmotic injuries is challenging. This cadaver study determines the impact of loading on the assessment of incomplete and more complete syndesmotic injuries when using weightbearing computed tomography (CT) scans. METHODS: Fourteen paired male cadavers (tibial plateau to toe-tip) were included. A radiolucent frame held specimens in a plantigrade position while both non-weightbearing and weightbearing computed tomography (CT) scans were taken. The following conditions were tested: First, intact ankles (Native) were scanned. Second, one specimen from each pair underwent anterior inferior tibio-fibular ligament (AITFL) transection (Condition 1A), while the contralateral underwent deltoid transection (Condition 1B). Third, the remaining intact deltoid or AITFL was transected from each specimen (Condition 2). Finally, the distal tibiofibular interosseous membrane (IOM) was transected in all ankles (Condition 3). Eight different measurements were performed to assess the integrity of the distal tibio-fibular syndesmosis on axial CT scans. RESULTS: Load application had no impact on most measurements. While incomplete syndesmotic injuries could not be identified, cadavers with more complete injuries differentiated from native ankles when assessed using axial CT images. No significant difference was evident between discrete AITFL or deltoid ligament transection. CONCLUSIONS: In a cadaver model, load application had no effect on the assessment of the distal tibio-fibular syndesmosis in incomplete and more complete syndesmotic injuries. Only more complete injuries of the distal tibio-fibular syndesmosis could be identified using axial CT images.

Can Weightbearing Computed Tomography Scans Be Used to Diagnose Subtalar Joint Instability? A Cadaver Study.

Chronic hindfoot instability is a frequent problem that includes the ankle and/or the subtalar joint. While ankle joint instability can be diagnosed clinically, accurate assessment of the subtalar joint remains elusive. This study's purpose was to assess the ability of weightbearing computed tomography (CT) scans to detect subtalar joint instability. Seven pairs of fresh frozen male cadavers (tibial plateau to toe-tip) were tested. A radiolucent frame held specimens in a plantigrade position while non-weightbearing and weightbearing CT scans (with and without torque application) were taken. First, intact ankles (Native) were scanned. Second, one specimen from each pair underwent interosseous talo-calcaneal ligament (ITCL) transection, while the contralateral underwent calcaneo-fibular ligament (CFL) transection. Third, the remaining intact ITCL or CFL was transected. Finally, the deltoid ligament was transected in all ankles. Eight radiographic measurements were performed to assess the congruency of the subtalar joint on digitally reconstructed radiographs and single CT images. Axial loading did not impact most measurements, whereas torque did impact most measurements. Radiographic measurements performed at the subtalar joint level were more reliable and better predictors for subtalar joint instability compared with measurements performed at the ankle joint level. While torque application is crucial to identify subtalar joint instability, axial load application should be avoided. Measurements to assess the subtalar joint stability should primarily be performed at the subtalar joint level rather than at the ankle joint level when using weightbearing CT scans. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2457-2465, 2019.

Impact of Torque on Assessment of Syndesmotic Injuries Using Weightbearing Computed Tomography Scans.

BACKGROUND: The diagnosis of subtle injuries to the distal tibiofibular syndesmosis remains elusive. Conventional radiographs miss a large subset of injuries that present without frank diastasis. This study evaluated the impact of torque application on the assessment of syndesmotic injuries when using weightbearing computed tomography (CT) scans. METHODS: Seven pairs of male cadavers (tibia plateau to toe-tip) were included. CT scans with axial load application (85 kg) and with (10 Nm) or without torque to the tibia (corresponding to external rotation of the foot and ankle) were taken during 4 test conditions. First, intact ankles (native) were scanned. Second, 1 specimen from each pair underwent anterior inferior tibiofibular ligament (AITFL) transection (condition 1A), while the contralateral underwent deltoid transection (condition 1B). Third, the lesions were reversed on the same specimens and the remaining intact deltoid or AITFL was transected (condition 2). Finally, the distal tibiofibular interosseous membrane (IOM) was transected in all ankles (condition 3). Measurements were performed to assess the integrity of the distal tibiofibular syndesmosis on digitally reconstructed radiographs (DRRs) and on axial CT scans. RESULTS: Torque impacted DRR and axial CT scan measurements in almost all conditions. The ability to diagnose syndesmotic injuries using axial CT measurements improved when torque was applied. No significant syndesmotic morphological change was observed with or without torque for either isolated AITFL or deltoid ligament transection. DISCUSSION: Torque application had a notable impact on two-dimensional (2-D) measurements used to diagnose syndesmotic injuries for both DRRs and axial CT scans. Because weightbearing conditions allow for standardized positioning of the foot while radiographs or CT scans are taken, the combination of axial load and torque application may be desirable. CLINICAL RELEVANCE: Application of torque to the tibia impacts 2-D measurements and may be useful when diagnosing syndesmotic injuries by DRRs or axial CT images.

Currently used imaging options cannot accurately predict subtalar joint instability.

PURPOSE: To give a systematic overview of current diagnostic imaging options and surgical treatment for chronic subtalar joint instability. METHODS: A systematic literature search across the following sources was performed: PubMed, ScienceDirect, and SpringerLink. Twenty-three imaging studies and 19 outcome studies were included. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2) tool was used to assess the methodologic quality of the imaging articles, while the modified Coleman Score was used to assess the methodologic quality of the outcome studies. RESULTS: Conventional radiographs were most frequently used to assess chronic subtalar joint instability. Talar tilt, anterior talar translation, and subtalar tilt were the three most commonly used measurement methods. Surgery often included calcaneofibular ligament reconstruction. CONCLUSION: Current imaging options do not reliably predict subtalar joint instability. Distinction between chronic lateral ankle instability and subtalar joint instability remains challenging. Recognition of subtalar joint instability as an identifiable and treatable cause of ankle pain requires vigilant clinical investigation. LEVEL OF EVIDENCE: Systematic Review of Level III and Level IV Studies, Level IV.

Biomechanical Comparison of Syndesmotic Repair Techniques During External Rotation Stress.

BACKGROUND: The purpose of this study was to compare mechanical behavior of conventional syndesmosis fixation devices with new anatomic repair techniques incorporating various repair augmentations to determine which approach would return rotational ankle mechanics closer to those of an intact ankle. METHODS: Ten pairs of fresh-frozen through-the-knee cadaveric lower limbs were subjected to 7.5 Nm of external rotation torque while under 750 N of axial compression. After testing specimens intact and with the deltoid and syndesmotic ligament complexes completely destabilized, specimens underwent syndesmotic fixation using a screw, a suture button construct, a prototype structurally augmented flexible trans-syndesmotic fixation device, or the prototype device plus suture repairs of the anterior-inferior tibiofibular ligament and deep deltoid ligament. Syndesmotic repair devices were exchanged between tests so that each specimen was tested with 2 different fixation techniques. Whole-foot rotation angles at 7.5 Nm of applied torque were measured for comparison of the different repair strategies, and reflective markers mounted on the tibia, fibula, and talus were used to track translations and rotations of the talus and the fibula relative to the tibia during testing. RESULTS: Syndesmotic destabilization significantly ( P < .001) increased whole-foot, talus, and fibula rotation in an axial plane and posterior fibula translation under 7.5 Nm of torque. Neither the suture button nor the augmented flexible trans-syndesmotic fixation device reduced those increases. Screw fixation or addition of anatomic ligament repairs to the augmented flexible fixation device successfully reduced axial plane rotations and sagittal plane translations to near intact levels. CONCLUSION: Flexible trans-syndesmotic fixation alone was found to be insufficient for restoring rotational stability to the ankle/talus or preventing sagittal plane displacement of the fibula. CLINICAL RELEVANCE: Repairs to simulate anatomic structures disrupted during a syndesmosis injury were required to restore rotational stability to the foot when using flexible trans-syndesmotic fixation that may have clinical applicability.

Isolated avulsion fracture of the first metatarsal base at the peroneus longus tendon attachment: a case report.

Avulsion fractures of the first metatarsal (MT1) base at the peroneus longus (PL) tendon attachment are rare and may be undiagnosed during an emergency visit. If the injury is not treated properly, chronic pain or persistent impairment for inversion and plantar-flexion of the first ray may occur. This case report presents a 30-year-old woman who presented 10 weeks post trauma to a foot and ankle surgeon due to a swollen right midfoot with diffuse tenderness over the medial Lisfranc joint. Further evaluation showed an isolated avulsion fracture of the first metatarsal, which was undiagnosed during the emergent visit following the accident. In this case, the patient was successfully treated conservatively. The goal of this article is to raise awareness of this rare injury for radiologists and orthopedic surgeons.

Imaging in syndesmotic injury: a systematic literature review.

OBJECTIVES: To give a systematic overview of current diagnostic imaging options for assessment of the distal tibio-fibular syndesmosis. MATERIALS AND METHODS: A systematic literature search across the following sources was performed: PubMed, ScienceDirect, Google Scholar, and SpringerLink. Forty-two articles were included and subdivided into three groups: group one consists of studies using conventional radiographs (22 articles), group two includes studies using computed tomography (CT) scans (15 articles), and group three comprises studies using magnet resonance imaging (MRI, 9 articles).The following data were extracted: imaging modality, measurement method, number of participants and ankles included, average age of participants, sensitivity, specificity, and accuracy of the measurement technique. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was used to assess the methodological quality. RESULTS: The three most common techniques used for assessment of the syndesmosis in conventional radiographs are the tibio-fibular clear space (TFCS), the tibio-fibular overlap (TFO), and the medial clear space (MCS). Regarding CT scans, the tibio-fibular width (axial images) was most commonly used. Most of the MRI studies used direct assessment of syndesmotic integrity. Overall, the included studies show low probability of bias and are applicable in daily practice. CONCLUSIONS: Conventional radiographs cannot predict syndesmotic injuries reliably. CT scans outperform plain radiographs in detecting syndesmotic mal-reduction. Additionally, the syndesmotic interval can be assessed in greater detail by CT. MRI measurements achieve a sensitivity and specificity of nearly 100%; however, correlating MRI findings with patients' complaints is difficult, and utility with subtle syndesmotic instability needs further investigation. Overall, the methodological quality of these studies was satisfactory.

Leukemia/lymphoma-related factor (LRF) exhibits stage- and context-dependent transcriptional controls in the oligodendrocyte lineage and modulates remyelination.

Leukemia/lymphoma-related factor (LRF), a zinc-finger transcription factor encoded by Zbtb7a, is a protooncogene that regulates differentiation in diverse cell lineages, and in the CNS, its function is relatively unexplored. This study is the first to examine the role of LRF in CNS pathology. We first examined LRF expression in a murine viral model of spinal cord demyelination with clinically relevant lesion characteristics. LRF was rarely expressed in oligodendrocyte progenitors (OP) yet, was detected in nuclei of the majority of oligodendrocytes in healthy adult CNS and during remyelination. Plp/CreERT :Zbtb7afl/fl mice were then used with cuprizone demyelination to determine the effect of LRF knockdown on oligodendrocyte repopulation and remyelination. Cuprizone was given for 6 weeks to demyelinate the corpus callosum. Tamoxifen was administered at 4, 5, or 6 weeks after the start of cuprizone. Tamoxifen-induced knockdown of LRF impaired remyelination during 3 or 6-week recovery periods after cuprizone. LRF knockdown earlier within the oligodendrocyte lineage using NG2CreERT :Zbtb7afl/fl mice reduced myelination after 6 weeks of cuprizone. LRF knockdown from either the Plp/CreERT line or the NG2CreERT line did not significantly change OP or oligodendrocyte populations. In vitro promoter assays demonstrated the potential for LRF to regulate transcription of myelin-related genes and the notch target Hes5, which has been implicated in control of myelin formation and repair. In summary, in the oligodendrocyte lineage, LRF is expressed mainly in oligodendrocytes but is not required for oligodendrocyte repopulation of demyelinated lesions. Furthermore, LRF can modulate the extent of remyelination, potentially by contributing to interactions regulating transcription.

Checkpoint kinase 1 expression is an adverse prognostic marker and therapeutic target in MYC-driven medulloblastoma.

Checkpoint kinase 1 (CHK1) is an integral component of the cell cycle as well as the DNA Damage Response (DDR) pathway. Previous work has demonstrated the effectiveness of inhibiting CHK1 with small-molecule inhibitors, but the role of CHK1 mediated DDR in medulloblastoma is unknown. CHK1, both at the mRNA and protein level, is highly expressed in medulloblastoma and elevated CHK1 expression in Group3 medulloblastoma is an adverse prognostic marker. CHK1 inhibition with the small-molecule drug AZD7762, results in decreased cell growth, increased DNA damage and cell apoptosis. Furthermore, AZD7762 acts in synergy with cisplatin in reducing cell proliferation in medulloblastoma. Similar phenotypic changes were observed with another CHK1 inhibitor, PF477736, as well as genetic knockdown using siRNA against CHK1. Treatments with small-molecule inhibitors of CHK1 profoundly modulated the expression of both upstream and downstream target proteins within the CHK1 signaling pathways. This suggests the presence of a feedback loop in activating CHK1. Overall, our results demonstrate that small-molecule inhibition of CHK1 in combination with, cisplatin, is more advantageous than either treatment alone, especially for Group 3 medulloblastoma, and therefore this combined therapeutic approach serves as an avenue for further investigation.

Psoriasis treatment considerations in military patients: unique patients, unique drugs.

Psoriasis is a common dermatologic problem with a chronic and sometimes debilitating course. Psoriasis can impair a service member's ability to perform job-related activities and should certainly be treated; however, use of immunosuppressive treatments can prevent deployment to strategic locations around the world for numerous reasons, such as the need for laboratory monitoring, minimal access to climate-controlled storage, and potential increased risk of exposure to virulent pathogens while on these medications. Similar obstacles can exist for nonmilitary patients who are placed in austere conditions or participate in worldwide travel. Although treatment efficacy, cost, and side-effect profiles are always paramount considerations in deciding on treatment regimens with patients, herein we focus our discussion on a consideration that might be easily overlooked when treating patients in modern society, that being the "logistics" of treatment.

Shooting with sound: optimizing an affordable ballistic gelatin recipe in a graded ultrasound phantom education program.

OBJECTIVES: The goal of this study was to investigate the durability and longevity of gelatin formulas for the production of staged ultrasound phantoms for education. METHODS: Gelatin phantoms were prepared from Knox gelatin (Kraft Foods, Northfield, IL) and a standard 10%-by-mass ordinance gelatin solution. Phantoms were durability tested by compressing to a 2-cm depth until cracking was visible. Additionally, 16 containers with varying combinations of phenol, container type, and storage location were tested for longevity against desiccation and molding. Once formulation was determined, 4 stages of phantoms from novice to clinically relevant were poured, and clinicians with ultrasound training ranked them on a 7-point Likert scale based on task difficulty, phantom suitability, and fidelity. RESULTS: On durability testing, the ballistic gelatin outperformed the Knox gelatin by more than 200 compressions. On longevity testing, gelatin with a 0.5% phenol concentration stored with a lid and refrigeration lasted longest, whereas containers without a lid had desiccation within 1 month, and those without phenol became moldy within 6 weeks. Ballistic gelatin was more expensive when buying in small quantities but was 7.4% less expensive when buying in bulk. The staged phantoms were deemed suitable for training, but clinicians did not consistently rank the phantoms in the intended order of 1 to 4 (44%). CONCLUSIONS: Refrigerated and sealed ballistic gelatin with phenol was a cost-effective method for creating in-house staged ultrasound phantoms suitable for large-scale ultrasound educational training needs. Clinician ranking of phantoms may be influenced by current training methods that favor biological tissue scanning as easier.

The combination of transcriptomics and informatics identifies pathways targeted by miR-204 during neurogenesis and axon guidance.

Vertebrate organogenesis is critically sensitive to gene dosage and even subtle variations in the expression levels of key genes may result in a variety of tissue anomalies. MicroRNAs (miRNAs) are fundamental regulators of gene expression and their role in vertebrate tissue patterning is just beginning to be elucidated. To gain further insight into this issue, we analysed the transcriptomic consequences of manipulating the expression of miR-204 in the Medaka fish model system. We used RNA-Seq and an innovative bioinformatics approach, which combines conventional differential expression analysis with the behavior expected by miR-204 targets after its overexpression and knockdown. With this approach combined with a correlative analysis of the putative targets, we identified a wider set of miR-204 target genes belonging to different pathways. Together, these approaches confirmed that miR-204 has a key role in eye development and further highlighted its putative function in neural differentiation processes, including axon guidance as supported by in vivo functional studies. Together, our results demonstrate the advantage of integrating next-generation sequencing and bioinformatics approaches to investigate miRNA biology and provide new important information on the role of miRNAs in the control of axon guidance and more broadly in nervous system development.

A ß(IV)-spectrin/CaMKII signaling complex is essential for membrane excitability in mice.

Ion channel function is fundamental to the existence of life. In metazoans, the coordinate activities of voltage-gated Na(+) channels underlie cellular excitability and control neuronal communication, cardiac excitation-contraction coupling, and skeletal muscle function. However, despite decades of research and linkage of Na(+) channel dysfunction with arrhythmia, epilepsy, and myotonia, little progress has been made toward understanding the fundamental processes that regulate this family of proteins. Here, we have identified ß(IV)-spectrin as a multifunctional regulatory platform for Na(+) channels in mice. We found that ß(IV)-spectrin targeted critical structural and regulatory proteins to excitable membranes in the heart and brain. Animal models harboring mutant ß(IV)-spectrin alleles displayed aberrant cellular excitability and whole animal physiology. Moreover, we identified a regulatory mechanism for Na(+) channels, via direct phosphorylation by ß(IV)-spectrin-targeted calcium/calmodulin-dependent kinase II (CaMKII). Collectively, our data define an unexpected but indispensable molecular platform that determines membrane excitability in the mouse heart and brain.