Nonoperative Management of Isolated Thoracolumbar Flexion Distraction Injuries: A Single-Center Study.

BACKGROUND: Nonoperative management is an appealing option for purely transosseous thoracolumbar flexion-distraction injuries given the prospects of osseous healing and restoration of the posterior tension band complex. This study seeks to examine differences in outcomes following flexion-distraction injuries after operative and nonoperative management. METHODS: This study reviews all patients at a single Level 1 trauma center from 2004 to 2022 with AO Spine B1 thoracolumbar injuries treated operatively vs nonoperatively. Inclusion criteria were age greater than 16 years, computed tomography-confirmed transosseous flexion-distraction injuries, and at least 3 months of follow-up with available imaging. The primary outcome assessed was a change in local Cobb angles, with secondary outcomes consisting of complications, time to return to work, and need for subsequent operative fixation. RESULTS: Initial Cobb angles in the operative (n = 14) vs nonoperative group (n = 13) were -5° and -13°, respectively (P = 0.225), indicating kyphotic alignment in both cohorts. We noted a significant difference in Cobb angles between cohorts at first follow-up (2.6° and -13.9°, P = 0.015) and within the operative cohort from presentation to first follow-up (P = 0.029). At the second follow-up, there was no significant difference in Cobb angles between cohorts (3.6° and -12.6°, P = 0.07). No significant differences were noted in complication rates (P = 1), time to return to work (P = 0.193), or resolution of subjective back pain (P = 0.193). No crossover was noted. CONCLUSIONS: Nonoperative management of minimally displaced transosseous flexion-distraction injuries is a safe alternative to surgery. Patient factors, such as compliance with follow-up, and location of the injury should be factored into the surgeon's management recommendation. CLINICAL RELEVANCE: Overall, no significant differences in outcomes and complications were noted following nonoperative management of AO Spine B1 injuries, indicating the potential for these injuries to be managed conservatively.

Conofolidine: A Natural Plant Alkaloid That Causes Apoptosis and Senescence in Cancer Cells.

Natural products contribute substantially to anticancer therapy; the plant kingdom provides an important source of molecules. Conofolidine is a novel Aspidosperma-Aspidosperma bisindole alkaloid isolated from the Malayan plant Tabernaemontana corymbosa. Herein, we report conofolidine's broad-spectrum anticancer activity together with that of three other bisindoles-conophylline, leucophyllidine, and bipleiophylline-against human-derived breast, colorectal, pancreatic, and lung carcinoma cell lines. Remarkably, conofolidine was able to induce apoptosis (e.g., in MDA-MB-468 breast) or senescence (e.g., in HT-29 colorectal) in cancer cells. Annexin V-FITC/PI, caspase activation, and PARP cleavage confirmed the former while positive ß-gal staining corroborated the latter. Cell cycle perturbations were evident, comprising S-phase depletion, accompanied by downregulated CDK2, and cyclins (A2, D1) with p21 upregulation. Confocal imaging of HCT-116 cells revealed an induction of aberrant mitotic phenotypes-membrane blebbing, DNA-fragmentation with occasional multi-nucleation. DNA integrity assessment in HCT-116, MDA-MB-468, MIAPaCa-2, and HT-29 cells showed increased fluorescent γ-H2AX during the G1 cell cycle phase; γ-H2AX foci were validated in HCT-116 and MDA-MB-468 cells by confocal microscopy. Conofolidine increased oxidative stress, preceding apoptosis- and senescence-induction in most carcinoma cell lines as seen by enhanced ROS levels accompanied by increased NQO1 expression. Collectively, we present conofolidine as a putative potent anticancer agent capable of inducing heterogeneous modes of cancerous cell death in vitro, encouraging further preclinical evaluations of this natural product.

Anatomical Structures at Risk in Percutaneous Distal Bunionette Correction.

Bunionette deformity is an incredibly pervasive issue in our society with almost a quarter of individuals being affected by it. As it is so common, there are numerous techniques and approaches to correct the deformity. Currently, there is a growing trend that favors percutaneous osteotomy of the bunionette. As there are multiple osteotomy sites, there are anatomical considerations that must be made at each one. The purpose of this study was to investigate the anatomic structures at risk during distal osteotomy of bunionette deformity using a Shannon burr. Using 11 fresh cadaver specimens, the fifth metatarsal was accessed through a carefully marked portal. A Shannon burr was employed for the osteotomy. Dissections were performed to assess potential damage to critical structures, including the lateral dorsal cutaneous nerve (LDCN), abductor digiti minimi (ADM), and extensor digitorum longus (EDL). Measurements were taken from the osteotomy site to each structure. The distal osteotomy site was on average greater than 8 mm from the EDL and ADM, whereas it was 1.64 mm from the LDCN. The Shannon burr made contact with and transected the LDCN on 2 occasions. However, previous studies have highlighted potential anatomical variations of the LDCN that arise distally. The study underscored the challenges posed by minimally invasive approaches to treating bunionette deformity and highlighted the need for cautious consideration when using percutaneous methods.Level of Clinical Evidence: 5.

Ligamentous Augmentation to Prevent Proximal Junctional Kyphosis and Failure: A Biomechanical Cadaveric Study.

STUDY DESIGN: Biomechanical cadaveric study (level V). OBJECTIVE: To evaluate the effectiveness of polyethylene bands looped around the supra-adjacent spinous process (SP) or spinal lamina (SL) in providing strength to the cephalad unfused segment and reducing junctional stress. BACKGROUND: Proximal junctional kyphosis (PJK) is a pathologic kyphotic deformity adjacent to posterior spinal instrumentation after fusion constructs. Recent studies demonstrate a mismatch in stiffness between the instrumented construct and nonfused adjacent levels to be a causative factor in the development of PJK and proximal junction failure. To our knowledge, no biomechanical studies have addressed the effect of different methods of polyethylene band placement at the proximal junction. MATERIALS AND METHODS: Twelve fresh frozen cadavers were divided into 3 groups of 4: pedicle screw-based instrumentation from T10 to L5 ("control"), T10-L5 instrumentation with a polyethylene band to the T9 "SP," T10-L5 instrumentation with 2 polyethylene bands to the T9 "SL." Specimens were tested with an eccentric (10 mm anterior) load at 5 mm/min for 15 mm or until failure occurred. Failure was defined by the inflection point on the load versus deformation curves. Linear regression was utilized to evaluate the effect of augmentation on the load-to-failure. Significance was set at 0.05. RESULTS: Fractures occurred in all specimens tested. The mean peak load to failure was 2148 N (974-3322) for the SP group, and 1248 N (742-1754) for the control group (P > 0.05) and 1390 N (1080-2004) for the SL group. No difference existed between the control group and the SP group in terms of fracture level (P > 0.05). Net kyphotic angulation shows no differences among these 3 groups (P > 0.05). CONCLUSION: Although statistical significance was not achieved, ligament augmentation to the SP increased mean peak load-to-failure in a cadaveric PJK model.

Resilience Improves Patient-Reported Outcomes After Orthopaedic Trauma.

OBJECTIVES: To analyze the relationship between patient resilience and patient-reported outcomes after orthopaedic trauma. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Single Level 1 Trauma Center. PATIENT SELECTION CRITERIA: Patients were selected based on completion of the Patient-Reported Outcomes Measurement Information System (PROMIS) and Brief Resilience Scale (BRS) surveys 6 months after undergoing operative fracture fixation following orthopaedic trauma. Patients were excluded if they did not complete all PROMIS and BRS surveys. OUTCOME MEASURES AND COMPARISONS: Resilience, measured by the BRS, was analyzed for its effect on patient-reported outcomes, measured by PROMIS Global Physical Health, Physical Function, Pain Interference, Global Mental Health, Depression, and Anxiety. Variables collected were demographics (age, gender, race, body mass index), injury severity score, and postoperative complications (nonunion, infection). All variables were analyzed with univariate for effect on all PROMIS scores. Variables with significance were included in multivariate analysis. Patients were then separated into high resilience (BRS >4.3) and low resilience (BRS <3.0) groups for additional analysis. RESULTS: A total of 99 patients were included in the analysis. Most patients were male (53%) with an average age of 47 years. Postoperative BRS scores significantly correlated with PROMIS Global Physical Health, Pain Interference, Physical Function, Global Mental Health, Depression, and Anxiety ( P ≤ 0.001 for all scores) at 6 months after injury on both univariate and multivariate analyses. The high resilience group had significantly higher PROMIS Global Physical Health, Physical Function, and Global Mental Health scores and significantly lower PROMIS Pain Interference, Depression, and Anxiety scores ( P ≤ 0.001 for all scores). CONCLUSIONS: Resilience in orthopaedic trauma has a positive association with patient outcomes at 6 months postoperatively. Patients with higher resilience report higher scores in all PROMIS categories regardless of injury severity. Future studies directed at increasing resilience may improve outcomes in patients who experience orthopaedic trauma. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Limited Intervention in Adult Scoliosis-A Systematic Review.

BACKGROUND/OBJECTIVES: Adult scoliosis is traditionally treated with long-segment fusion, which provides strong radiographic correction and significant improvements in health-related quality of life but comes at a high morbidity cost. This systematic review seeks to examine the literature behind limited interventions in adult scoliosis patients and examine the best approaches to treatment. METHODS: This is a MEDLINE- and PubMed-based literature search that ultimately included 49 articles with a total of 21,836 subjects. RESULTS: Our search found that long-segment interventions had strong radiographic corrections but also resulted in high perioperative morbidity. Limited interventions were best suited to patients with compensated deformity, with decompression best for neurologic symptoms and fusion needed to treat neurological symptoms secondary to up-down stenosis and to provide stability across unstable segments. Decompression can consist of discectomy, laminotomy, and/or foraminotomy, all of which are shown to provide symptomatic relief of neurologic pain. Short-segment fusion has been shown to provide improvements in patient outcomes, albeit with higher rates of adjacent segment disease and concerns for correctional loss. Interbody devices can provide decompression without posterior element manipulation. Future directions include short-segment fusion in uncompensated deformity and dynamic stabilization constructs. CONCLUSIONS: Limited interventions can provide symptomatic relief to adult spine deformity patients, with indications mostly in patients with balanced deformities and neurological pain.

Anatomical Structures at Risk in Percutaneous Preparation Talonavicular Fusion.

BACKGROUND: The stability of the hindfoot greatly relies on the integrity of the talonavicular joint. Pathologies affecting this joint often necessitate fusion. Our study explores the risks posed to neurovascular and tendon structures during simulated percutaneous talonavicular joint preparation for fusion. METHODS: In 9 fresh cadaver specimens, the talonavicular joint was accessed through two portals. A 2-mm Shannon burr was employed for joint surface preparation with distraction provided by a pin-based distractor. Dissections were performed to assess potential damage to critical structures, including the dorsalis pedis artery, superficial and deep peroneal nerves, extensor hallucis longus (EHL), and tibialis anterior (TA) tendons. RESULTS: The dorsal portal site was found to be significantly closer to important structures compared to the medial portal site. The Shannon burr made contact with various structures, with a single transection identified for both deep and superficial peroneal nerve branches. During the dorsal portal site approach, potential injury to the EHL tendon was identified as concern. CONCLUSION: This study sheds light on the potential risks associated with percutaneous dorsal and medial joint preparation approaches using a Shannon burr.Level of Evidence:Level V, mechanism-based reasoning..

The Impact of Smoking on Hospital Course and Postoperative Outcomes in Patients With Fracture-Related Infections.

OBJECTIVES: To assess the relationship between patient smoking status and fracture-related infection (FRI) characteristics including patient symptoms at FRI presentation, bacterial species of FRI, and rates of fracture union. DESIGN: Retrospective cohort study. SETTING: Urban level 1 trauma center. PATIENT SELECTION CRITERIA: All patients undergoing reoperation for FRI from January 2013 to April 2021 were identified through manual review of an institutional database. OUTCOME MEASURES AND COMPARISONS: Data including patient demographics, fracture characteristics, infection presentation, and hospital course were collected through review of the electronic medical record. Patients were grouped based on current smoker versus nonsmoker status. Hospital course and postoperative outcomes of these groups were then compared. Risk factors of methicillin-resistant Staphylococcus aureus (MRSA) infection, Staphylococcus epidermidis infection, and sinus tract development were evaluated using multivariable logistic regression. RESULTS: A total of 301 patients, comprising 155 smokers (51%) and 146 nonsmokers (49%), undergoing FRI reoperation were included. Compared with nonsmokers, smokers were more likely male (69% vs. 56%, P = 0.024), were younger at the time of FRI reoperation (41.7 vs. 49.5 years, P < 0.001), and had lower mean body mass index (27.2 vs. 32.0, P < 0.001). Smokers also had lower prevalence of diabetes mellitus (13% vs. 25%, P = 0.008) and had higher Charlson Comorbidity Index 10-year estimated survival (93% vs. 81%, P < 0.001). Smokers had a lower proportion of S. epidermidis infections (11% vs. 20%, P = 0.037), higher risk of nonunion after index fracture surgery (74% vs. 61%, P = 0.018), and higher risk of sinus tracts at FRI presentation (38% vs. 23%, P = 0.004). On multivariable analysis, smoking was not found to be associated with increased odds of MRSA infection. CONCLUSIONS: Among patients who develop a FRI, smokers seemed to have better baseline health regarding age, body mass index, diabetes mellitus, and Charlson Comorbidity Index 10-year estimated survival compared with nonsmokers. Smoking status was not significantly associated with odds of MRSA infection. However, smoking status was associated with increased risk of sinus tract development and nonunion and lower rates of S. epidermidis infection at the time of FRI reoperation. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Osmosensing by WNK Kinases.

With No Lysine (K) WNK kinases regulate electro-neutral cotransporters that are controlled by osmotic stress and chloride. We showed previously that autophosphorylation of WNK1 is inhibited by chloride, raising the possibility that WNKs are activated by osmotic stress. Here we demonstrate that unphosphorylated WNK isoforms 3 and 1 autophosphorylate in response to osmotic pressure in vitro, applied with the crowding agent polyethylene glycol (PEG)400 or osmolyte ethylene glycol (EG), and that this activation is opposed by chloride. Small angle x-ray scattering of WNK3 in the presence and absence of PEG400, static light scattering in EG, and crystallography of WNK1 were used to understand the mechanism. Osmosensing in WNK3 and WNK1 appears to occur through a conformational equilibrium between an inactive, unphosphorylated, chloride-binding dimer and an autophosphorylation-competent monomer. An improved structure of the inactive kinase domain of WNK1, and a comparison with the structure of a monophosphorylated form of WNK1, suggests that large cavities, greater hydration, and specific bound water may participate in the osmosensing mechanism. Our prior work showed that osmolytes have effects on the structure of phosphorylated WNK1, suggestive of multiple stages of osmotic regulation in WNKs.

A Phosphorylated Intermediate in the Activation of WNK Kinases.

WNK kinases autoactivate by autophosphorylation. Crystallography of the kinase domain of WNK1 phosphorylated on the primary activating site (pWNK1) in the presence of AMP-PNP reveals a well-ordered but inactive configuration. This new pWNK1 structure features specific and unique interactions of the phosphoserine, less hydration, and smaller cavities compared with those of unphosphorylated WNK1 (uWNK1). Because WNKs are activated by osmotic stress in cells, we addressed whether the structure was influenced directly by osmotic pressure. pWNK1 crystals formed in PEG3350 were soaked in the osmolyte sucrose. Suc-WNK1 crystals maintained X-ray diffraction, but the lattice constants and pWNK1 structure changed. Differences were found in the activation loop and helix C, common switch loci in kinase activation. On the basis of these structural changes, we tested for effects on in vitro activity of two WNKs, pWNK1 and pWNK3. The osmolyte PEG400 enhanced ATPase activity. Our data suggest multistage activation of WNKs.

Reducing patient waiting time and length of stay in an Acute Care Pediatric Emergency Department.

Prolonged waiting times and length of stay in Pediatric Emergency Department, are the two of the most challenging patient and clinical outcomes of healthcare institution. These emerged due to various reasons, namely: the use of triaging process and patient flow criteria that eventually lead to bottlenecks and overcrowding in the ED. After realizing the root causes of the prolonged waiting times and length of stay, the KASCH ED instigated a team to study the factors and thereby arrive at a considerable conclusion that will result in an improvement. The quality improvement project was initiated and steps were undertaken to improve the flow, reduce the waiting times, and reduce the overcrowding in Pediatric Emergency Acute Care Unit. The primary cause identified was inadequate team awareness and lack of the ED process flow, thus creating confusion as to where the type of patients based on the triage level will be assessed, managed and treated. Using the Canadian Triage and Acuity Scale (CTAS) as guide in triaging patients, a theory called Pediatric Rapid Assessment and Management (PRAM) was introduced in the Acute Care Unit. This certain model is basically aimed to rapidly assess and managed the patients who were triaged as Level III and Level IV within a period of 30 minutes. Several PDSA cycles were tested and implemented in order to assure that the process fit the criteria and the process flow will be improved. Following the completion of each cycle, significant improvements were noted, such as patients being assessed in Initial Assessment Room on average time less than the target of 15 minutes. In like manner, patients' length of stay on average less than 15 minutes in PRAM bed. The total time for assessment and plan of management is with a target time of less than 30 minutes. The team continuously drive th process and monitored the key performance indicators of the PRAM during the study period and subsequent improvement strategies were likewise implemented.