The Space Omics and Medical Atlas (SOMA) and international astronaut biobank.

Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space1-6. Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools and protocols. Here we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study7, JAXA CFE study8,9, SpaceX Inspiration4 crew10-12, Axiom and Polaris. The SOMA resource represents a more than tenfold increase in publicly available human space omics data, with matched samples available from the Cornell Aerospace Medicine Biobank. The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiome datasets, which reveal some consistent features across missions, including cytokine shifts, telomere elongation and gene expression changes, as well as mission-specific molecular responses and links to orthologous, tissue-specific mouse datasets. Leveraging the datasets, tools and resources in SOMA can help to accelerate precision aerospace medicine, bringing needed health monitoring, risk mitigation and countermeasure data for upcoming lunar, Mars and exploration-class missions.

Using Machine Learning Models to Identify Factors Associated With 30-Day Readmissions After Posterior Cervical Fusions: A Longitudinal Cohort Study.

OBJECTIVE: Readmission rates after posterior cervical fusion (PCF) significantly impact patients and healthcare, with complication rates at 15%-25% and up to 12% 90-day readmission rates. In this study, we aim to test whether machine learning (ML) models that capture interfactorial interactions outperform traditional logistic regression (LR) in identifying readmission-associated factors. METHODS: The Optum Clinformatics Data Mart database was used to identify patients who underwent PCF between 2004-2017. To determine factors associated with 30-day readmissions, 5 ML models were generated and evaluated, including a multivariate LR (MLR) model. Then, the best-performing model, Gradient Boosting Machine (GBM), was compared to the LACE (Length patient stay in the hospital, Acuity of admission of patient in the hospital, Comorbidity, and Emergency visit) index regarding potential cost savings from algorithm implementation. RESULTS: This study included 4,130 patients, 874 of which were readmitted within 30 days. When analyzed and scaled, we found that patient discharge status, comorbidities, and number of procedure codes were factors that influenced MLR, while patient discharge status, billed admission charge, and length of stay influenced the GBM model. The GBM model significantly outperformed MLR in predicting unplanned readmissions (mean area under the receiver operating characteristic curve, 0.846 vs. 0.829; p < 0.001), while also projecting an average cost savings of 50% more than the LACE index. CONCLUSION: Five models (GBM, XGBoost [extreme gradient boosting], RF [random forest], LASSO [least absolute shrinkage and selection operator], and MLR) were evaluated, among which, the GBM model exhibited superior predictive performance, robustness, and accuracy. Factors associated with readmissions impact LR and GBM models differently, suggesting that these models can be used complementarily. When analyzing PCF procedures, the GBM model resulted in greater predictive performance and was associated with higher theoretical cost savings for readmissions associated with PCF complications.

Incidence and Outcomes of Posterior Circulation Involvement in Moyamoya Disease.

BACKGROUND: Moyamoya disease (MMD) is a progressive, occlusive disease of the internal carotid arteries and their proximal branches, with the subsequent development of an abnormal vascular network that is rupture-prone. Steno-occlusive changes in the posterior cerebral arteries (PCAs) may contribute to worsened outcomes in patients with MMD; however, there is little information on the incidence and natural history of posterior circulation MMD (PCMMD). We describe clinical PCMMD characteristics in a large cohort of patients with MMD. METHODS: We retrospectively reviewed patients with MMD treated between 1991 and 2019 at a large academic medical center. Demographics, perioperative outcomes, and radiological phenotypes were recorded for 770 patients. PCA disease was graded as either 0 (no disease), 1 (mild), 2 (moderate), or 3 (severe or occluded) based on cerebral angiography. Patients with angiographically confirmed MMD diagnosis with at least 6 months follow-up and completion of revascularization surgery were included; patients with intracranial atherosclerosis, intracranial dissection, vasculitis, and undefined inflammatory processes were excluded. The presence of stenosis/occlusion was graded radiographically to assess for disease progression and the prevalence of risk factors related to reduced progression-free survival. RESULTS: In all, 686 patients met the inclusion criteria, with PCA disease identified in 282 (41.1%) patients. Of those 282 patients with PCMMD, disease severity ranged from 99 (35.1%) with mild, 72 (25.5%) with moderate, and 111 (39.4%) with severe. The total number of postoperative complications was significantly associated with PCMMD severity (P=0.0067). Additionally, PCMMD severity correlated with worse postoperative modified Rankin Scale scores (P<0.0001). At a mean follow-up of 6.0±3.9 (range, 0.1-25.0) years, a total of 60 (12.6%) patients showed new/worsening PCMMD. The overall postoperative, progression-free survival in patients with PCMMD was 95.4% at 1 year, 82.4% at 3 years, 68.8% at 5 years, and 28.3% at 10 years, with prognostic factors for progression including preoperative PCMMD status, history of tobacco use, and hypertension (P<0.0001, P<0.001, and P<0.0001, respectively). CONCLUSIONS: PCA disease involvement in MMD is associated with higher rates of ischemic perioperative complications and worsened functional outcomes, likely due to reduced collateral flow. Ten-year progression of PCA disease is highly likely and should be monitored throughout follow-up; future studies will assess the impact of PCA disease progression on long-term outcomes.

Interaction of preoperative chemoprophylaxis and tranexamic acid use does not affect transfusion in acetabular fracture surgery.

PURPOSE: While the effects of tranexamic acid (TXA) use on transfusion rates after acetabular fracture surgery are unclear, previous evidence suggests that holding deep vein thrombosis (DVT) chemoprophylaxis may improve TXA efficacy. This study examines whether holding DVT chemoprophylaxis in patients receiving TXA affects intraoperative and postoperative transfusion rates in acetabular fracture surgery. METHODS: We reviewed electronic medical records (EMR) of 305 patients who underwent open reduction and internal fixation of acetabular fractures (AO/OTA 62) and stratified patients per the following perioperative treatment: (1) no intraoperative TXA (noTXA), (2) intraoperative TXA and no preoperative DVT prophylaxis (opTXA/noDVTP), or (3) intraoperative TXA and preoperative DVT prophylaxis (opTXA/opDVTP). The primary outcomes were need for intraoperative or postoperative transfusion. Risk factors for each primary outcome were assessed using multivariable regression. RESULTS: Intraoperative or postoperative transfusion rates did not significantly differ between opTXA/opDVTP and opTXA/noDVTP groups (46.2% vs. 36%, p = 0.463; 15.4% vs. 28%, p = 0.181). Median units transfused did not differ between groups (2 ± 1 vs. 2 ± 1, p = 0.515; 2 ± 1 vs. 2 ± 0, p = 0.099). There was no association between preoperative DVT chemoprophylaxis and TXA with intraoperative or postoperative transfusions. EBL, preoperative hematocrit, and IV fluids were associated with intraoperative transfusions; age and Charlson Comorbidity Index (CCI) were associated with postoperative transfusions. CONCLUSION: Our findings suggest holding DVT prophylaxis did not alter the effect of TXA on blood loss or need for transfusion.

Allometrically scaling tissue forces drive pathological foreign-body responses to implants via Rac2-activated myeloid cells.

Small animals do not replicate the severity of the human foreign-body response (FBR) to implants. Here we show that the FBR can be driven by forces generated at the implant surface that, owing to allometric scaling, increase exponentially with body size. We found that the human FBR is mediated by immune-cell-specific RAC2 mechanotransduction signalling, independently of the chemistry and mechanical properties of the implant, and that a pathological FBR that is human-like at the molecular, cellular and tissue levels can be induced in mice via the application of human-tissue-scale forces through a vibrating silicone implant. FBRs to such elevated extrinsic forces in the mice were also mediated by the activation of Rac2 signalling in a subpopulation of mechanoresponsive myeloid cells, which could be substantially reduced via the pharmacological or genetic inhibition of Rac2. Our findings provide an explanation for the stark differences in FBRs observed in small animals and humans, and have implications for the design and safety of implantable devices.

Outcomes of Biosynthetic and Synthetic Mesh in Ventral Hernia Repair.

The introduction of mesh for reinforcement of ventral hernia repair (VHR) led to a significant reduction in hernia recurrence rates. However, it remains controversial whether synthetic or biologic mesh leads to superior outcomes. Recently, hybrid mesh consisting of reinforced biosynthetic ovine rumen (RBOR) has been developed and aims to combine the advantages of biologic and synthetic mesh; however, outcomes after VHR with RBOR have not yet been compared with the standard of care. Methods: We performed a retrospective analysis on 109 patients, who underwent VHR with RBOR (n = 50) or synthetic polypropylene mesh (n = 59). Demographic characteristics, comorbidities, postoperative complications, and recurrence rates were analyzed and compared between the groups. Multivariate logistic regression models were fit to assess associations of mesh type with overall complications and surgical site occurrence (SSO). Results: Patients who underwent VHR with RBOR were older (mean age 63.7 versus 58.8 years, P = 0.02) and had a higher rate of renal disease (28.0 versus 10.2%, P = 0.01) compared with patients with synthetic mesh. Despite an unfavorable risk profile, patients with RBOR had lower rates of SSO (16.0 versus 30.5%, P = 0.12) and similar hernia recurrence rates (4.0 versus 6.78%, P = 0.68) compared with patients with synthetic mesh. The use of synthetic mesh was significantly associated with higher odds for overall complications (3.78, P < 0.05) and SSO (3.87, P < 0.05). Conclusion: Compared with synthetic polypropylene mesh, the use of RBOR for VHR mitigates SSO while maintaining low hernia recurrence rates at 30-month follow-up.

Augmented Reality Neuronavigation for En Bloc Resection of Spinal Column Lesions.

BACKGROUND: Primary tumors involving the spine are relatively rare but represent surgically challenging procedures with high patient morbidity. En bloc resection of these tumors necessitates large exposures, wide tumor margins, and poses risks to functionally relevant anatomical structures. Augmented reality neuronavigation (ARNV) represents a paradigm shift in neuronavigation, allowing on-demand visualization of 3D navigation data in real-time directly in line with the operative field. METHODS: Here, we describe the first application of ARNV to perform distal sacrococcygectomies for the en bloc removal of sacral and retrorectal lesions involving the coccyx in 2 patients, as well as a thoracic 9-11 laminectomy with costotransversectomy for en bloc removal of a schwannoma in a third patient. RESULTS: In our experience, ARNV allowed our teams to minimize the length of the incision, reduce the extent of bony resection, and enhanced visualization of critical adjacent anatomy. All tumors were resected en bloc, and the patients recovered well postoperatively, with no known complications. Pathologic analysis confirmed the en bloc removal of these lesions with negative margins. CONCLUSIONS: We conclude that ARNV is an effective strategy for the precise, en bloc removal of spinal lesions including both sacrococcygeal tumors involving the retrorectal space and thoracic schwannomas.

Spinal cord injury: a study protocol for a systematic review and meta-analysis of microRNA alterations.

BACKGROUND: Spinal cord injury (SCI) is a devastating condition with no current neurorestorative treatments. Clinical trials have been hampered by a lack of meaningful diagnostic and prognostic markers of injury severity and neurologic recovery. Objective biomarkers and novel therapies for SCI represent urgent unmet clinical needs. Biomarkers of SCI that objectively stratify the severity of cord damage could expand the depth and scope of clinical trials and represent targets for the development of novel therapies for acute SCI. MicroRNAs (miRNAs) represent promising candidates both as informative molecules of injury severity and recovery, and as therapeutic targets. miRNAs are small, regulatory RNA molecules that are tissue-specific and evolutionarily conserved across species. miRNAs have been shown to represent powerful predictors of pathology, particularly with respect to neurologic disorders. METHODS: Studies investigating miRNA alterations in all species of animal models and human studies of acute, traumatic SCI will be identified from PubMed, Embase, and Scopus. We aim to identify whether SCI is associated with a specific pattern of miRNA expression that is conserved across species, and whether SCI is associated with a tissue- or cell type-specific pattern of miRNA expression. The inclusion criteria for this study will include (1) studies published anytime, (2) including all species, and sexes with acute, traumatic SCI, (3) relating to the alteration of miRNA after SCI, using molecular-based detection platforms including qRT-PCR, microarray, and RNA-sequencing, (4) including statistically significant miRNA alterations in tissues, such as spinal cord, serum/plasma, and/or CSF, and (5) studies with a SHAM surgery group. Articles included in the review will have their titles, abstracts, and full texts reviewed by two independent authors. Random effects meta-regression will be performed, which allows for within-study and between-study variability, on the miRNA expression after SCI or SHAM surgery. We will analyze both the cumulative pooled dataset, as well as datasets stratified by species, tissue type, and timepoint to identify miRNA alterations that are specifically related to the injured spinal cord. We aim to identify SCI-related miRNA that are specifically altered both within a species, and those that are evolutionarily conserved across species, including humans. The analyses will provide a description of the evolutionarily conserved miRNA signature of the pathophysiological response to SCI. DISCUSSION: Here, we present a protocol to perform a systematic review and meta-analysis to investigate the conserved inter- and intra-species miRNA changes that occur due to acute, traumatic SCI. This review seeks to serve as a valuable resource for the SCI community by establishing a rigorous and unbiased description of miRNA changes after SCI for the next generation of SCI biomarkers and therapeutic interventions. TRIAL REGISTRATION: The protocol for the systematic review and meta-analysis has been registered through PROSPERO: CRD42021222552 .

Metastatic Pattern of Truncal and Extremity Leiomyosarcoma: Retrospective Analysis of Predictors, Outcomes, and Detection.

Leiomyosarcomas (LMS) are a heterogenous group of malignant mesenchymal neoplasms with smooth muscle origin and are classified as either non-uterine (NULMS) or uterine (ULMS). Metastatic pattern, prognostic factors, and ideal staging/surveillance studies for truncal and extremity LMS have not been defined. A retrospective analysis of patients diagnosed with histopathology-confirmed truncal or extremity LMS between 2009 and 2019 was conducted. Data collected included demographics, tumor characteristics, staging, surveillance, and survival endpoints. The primary site was defined as: (1) extremity, (2) flank/Pelvis, or (3) chest wall/Spine. We identified 73 patients, 23.3% of which had metastatic LMS at primary diagnosis, while 68.5% developed metastatic disease at any point. The mean metastatic-free survival from primary diagnosis of localized LMS was 3.0 ± 2.8 years. Analysis of prognostic factors revealed that greater age (≥50 years) at initial diagnosis (OR = 3.74, p = 0.0003), higher tumor differentiation scores (OR = 12.09, p = 0.002), and higher tumor necrosis scores (OR = 3.65, p = 0.026) were significantly associated with metastases. Older patients (≥50 years, OR = 4.76, p = 0.017), patients with larger tumors (≥5 cm or ≥10 cm, OR = 2.12, p = 0.02, OR = 1.92, p = 0.029, respectively), higher differentiation scores (OR = 15.92, p = 0.013), and higher necrosis scores (OR = 4.68, p = 0.044) show worse survival outcomes. Analysis of imaging modality during initial staging and during surveillance showed greater tumor detection frequency when PET imaging was employed, compared to CT imaging (p < 0.0001). In conclusion, truncal and peripheral extremity LMS is an aggressive tumor with high metastatic potential and mortality. While there is a significant risk of metastases to lungs, extra-pulmonary tumors are relatively frequent, and broad surveillance may be warranted.

Indications for cement augmentation in fixation of geriatric intertrochanteric femur fractures: a systematic review of evidence.

INTRODUCTION: Achieving durable mechanical stability in geriatric intertrochanteric proximal femur fractures remains a challenge. Concomitant poor bone quality, unstable fracture patterns, and suboptimal reduction are additional risk factors for early mechanical failure. Cement augmentation of the proximal locking screw or blade is one proposed method to augment implant anchorage. The purpose of this review is to describe the biomechanical and clinical evidence for cement augmentation of geriatric intertrochanteric fractures, and to elaborate indications for cement augmentation. METHODS: The PubMed database was searched for English language studies up to January 2021. Studies that assessed effect of calcium phosphate or methylmethacrylate cement augmentation during open reduction and internal fixation of intertrochanteric fractures were included. Studies with sample size < 5, nontraumatic or periprosthetic fractures, and nonunion or revision surgery were excluded. Study selection adhered to PRISMA criteria. RESULTS: 801 studies were identified, of which 40 met study criteria. 9 studies assessed effect of cement augmentation on fracture displacement. All but one found that cement decreased fracture displacement. 10 studies assessed effect of cement augmentation on total load or cycles to failure. All but one demonstrated that augmented implants increased this variable. Complication rates of cement augmentation during ORIF of intertrochanteric fractures ranged from 0 to 47%, while non-augmented implants ranged from 0 to 51%. Reoperation rates ranged from 0 to 11% in the cement-augmented group and 0 to 11% in the non-augmented group. Fixation failure ranged from 0 to 11% in the cement-augmented group and 0 to 20% in the non-augmented group. Nonunion ranged from 0 to 3.6% in the cement-augmented group and 0 to 34% in the non-augmented group. CONCLUSIONS: Calcium phosphate or PMMA-augmented CMN fixation of IT fractures increased construct stability and improved outcomes in biomechanical and early clinical studies. The findings of these studies suggest an important role for cement augmentation in patient populations at high risk of mechanical failure.

Tranexamic acid does not affect intraoperative blood loss or in-hospital outcomes after acetabular fracture surgery.

PURPOSE: Tranexamic acid (TXA) reduces need for transfusion in total joint arthroplasty, though findings in acetabular surgery are conflicting. We compared outcomes after acetabular fracture surgery with or without perioperative intravenous (IV) TXA administration. METHODS: We performed a retrospective review of 305 patients with acetabular fractures that underwent open reduction and internal fixation (ORIF). Eighty-nine patients received TXA, and 216 did not. The primary outcome was rates of intraoperative and postoperative allogeneic blood transfusion. RESULTS: Baseline demographics and characteristics were similar. Time from injury to surgery and estimated blood loss were comparable. Operative time (p < 0.01) and intraoperative IV fluids (p < 0.01) were greater in the non-TXA group. The proportion of patients who received blood transfusion and mean units transfused intraoperatively and postoperatively did not differ. Mean differences in preoperative and postoperative hemoglobin and hematocrit, hospital length of stay, and perioperative complications also did not differ. In a multivariable regression model, age 60-70 years, Charlson Comorbidity Index, Injury Severity Score, and fracture patterns likely to bleed were independently associated with intraoperative transfusion. Anterior surgical approaches and intraoperative transfusion requirement were independently associated with postoperative transfusion. CONCLUSION: In this study, perioperative IV TXA did not decrease blood loss, need for transfusion, or improve in-hospital outcomes of acetabular fracture surgery. Age 60-70, CCI, ISS, and fracture patterns likely to bleed were independently associated with intraoperative transfusion. Anterior surgical approach and need for intraoperative transfusion were independently associated with postoperative transfusion. Further prospective trials are warranted to confirm these findings.

Single position lateral decubitus anterior lumbar interbody fusion (ALIF) and posterior fusion reduces complications and improves perioperative outcomes compared with traditional anterior-posterior lumbar fusion.

BACKGROUND CONTEXT: Lateral decubitus single position anterior-posterior (AP) fusion utilizing anterior lumbar interbody fusion and percutaneous posterior fixation is a novel, minimally invasive surgical technique. Single position lumbar surgery (SPLS) with anterior lumbar interbody fusion (ALIF) or lateral lumbar interbody fusion (LLIF) has been shown to be a safe, effective technique. This study directly compares perioperative outcomes of SPLS with lateral ALIF vs. traditional supine ALIF with repositioning (FLIP) for degenerative pathologies. PURPOSE: To determine if SPLS with lateral ALIF improves perioperative outcomes compared to FLIP with supine ALIF. STUDY DESIGN/SETTING: Multicenter retrospective cohort study. PATIENT SAMPLE: Patients undergoing primary AP fusions with ALIF at 5 institutions from 2015 to 2020. OUTCOME MEASURES: Levels fused, inclusion of L4-L5, L5-S1, radiation dosage, operative time, estimated blood loss (EBL), length of stay (LOS), perioperative complications. Radiographic analysis included lumbar lordosis (LL), pelvic incidence (PI), and PI-LL mismatch. METHODS: Retrospective analysis of primary ALIFs with bilateral percutaneous pedicle screw fixation between L4-S1 over 5 years at 5 institutions. Patients were grouped as FLIP or SPLS. Demographic, procedural, perioperative, and radiographic outcome measures were compared using independent samples t-tests and chi-squared analyses with significance set at p <.05. Cohorts were propensity-matched for demographic or procedural differences. RESULTS: A total of 321 patients were included; 124 SPS and 197 Flip patients. Propensity-matching yielded 248 patients: 124 SPLS and 124 FLIP. The SPLS cohort demonstrated significantly reduced operative time (132.95±77.45 vs. 261.79±91.65 min; p <0.001), EBL (120.44±217.08 vs. 224.29±243.99 mL; p <.001), LOS (2.07±1.26 vs. 3.47±1.40 days; p <.001), and rate of perioperative ileus (0.00% vs. 6.45%; p =.005). Radiation dose (39.79±31.66 vs. 37.54±35.85 mGy; p =.719) and perioperative complications including vascular injury (1.61% vs. 1.61%; p =.000), retrograde ejaculation (0.00% vs. 0.81%, p =.328), abdominal wall (0.81% vs. 2.42%; p =.338), neuropraxia (1.61% vs. 0.81%; p =.532), persistent motor deficit (0.00% vs. 1.61%; p =.166), wound complications (1.61% vs. 1.61%; p =.000), or VTE (0.81% vs. 0.81%; p =.972) were similar. No difference was seen in 90-day return to OR. Similar results were noted in sub-analyses of single-level L4-L5 or L5-S1 fusions. On radiographic analysis, the SPLS cohort had greater changes in LL (4.23±11.14 vs. 0.43±8.07 deg; p =.005) and PI-LL mismatch (-4.78±8.77 vs. -0.39±7.51 deg; p =.002). CONCLUSIONS: Single position lateral ALIF with percutaneous posterior fixation improves operative time, EBL, LOS, rate of ileus, and maintains safety compared to supine ALIF with prone percutaneous pedicle screws between L4-S1.

Advanced Age Does Not Impact Outcomes After 1-level or 2-level Lateral Lumbar Interbody Fusion.

STUDY DESIGN: This was a retrospective comparative study. OBJECTIVE: The objective of this study was to assess the effect of increased age on perioperative and postoperative complication rates, reoperation rates, and patient-reported pain and disability scores after lateral lumbar interbody fusion (LLIF). SUMMARY OF BACKGROUND DATA: LLIF was developed to minimize soft tissue trauma and reduce the risk of vascular injury; however, there is little evidence regarding the effect of advanced age on outcomes of LLIF. METHODS: Patients who underwent LLIF from 2009 to 2019 at one institution with a minimum 6-month follow-up were retrospectively reviewed. Patients less than 18 years old with musculoskeletal tumor or trauma were excluded. The primary outcome was the preoperative to postoperative change in the Numeric Pain Rating Scale (NPRS) for back pain. Operative time, estimated blood loss, length of stay, perioperative and 90-day complications, unplanned readmissions, reoperations, and change in Oswestry Disability Index were also evaluated. Relationships with age were assessed both with age as a continuous variable and segmenting by age below 70 versus 70+. RESULTS: In total, 279 patients were included. The median age was 65±13 years and 159 (57%) were female. Age was not related to improvements in back NPRS and Oswestry Disability Index. Operative time, estimated blood loss, length of stay, perioperative and 90-day complications, unplanned readmissions, reoperations, and radiographic fusion rate also were not related to age. After multivariable risk adjustment, increasing age was associated with greater improvements in back NPRS. The decrease in back NPRS was 0.68 (95% confidence interval: 0.14, 1.22; P=0.014) points greater for every 10-year increase in age. Age was not associated with rates of complication, readmission, or reoperation. CONCLUSIONS: LLIF is a safe and effective procedure in the elderly population. Advanced age is associated with larger improvements in preoperative back pain. Surgeons should consider the benefits of LLIF and other minimally invasive techniques when evaluating elderly candidates for lumbar fusion. LEVEL OF EVIDENCE: Level III.

Countersinking the Lag Screw or Blade During Cephalomedullary Nailing of Geriatric Intertrochanteric Femur Fractures: Less Collapse and Implant Prominence Without Increased Cutout Rates.

INTRODUCTION: The lag screw or helical blade of a cephalomedullary nail facilitates controlled collapse of intertrochanteric proximal femur fractures. However, excessive collapse results in decreased hip offset and symptomatic lateral implants. Countersinking the screw or helical blade past the lateral cortex may minimize subsequent prominence, but some surgeons are concerned that this will prevent collapse and result in failure through cutout. We hypothesized that patients with countersunk lag screws or helical blades do not experience higher rates of screw or blade cutout and have less implant prominence after fracture healing. METHODS: A retrospective review of 175 consecutive patients treated with cephalomedullary nails for AO/OTA 31A1-3 proximal femur fractures and a minimum 3-month follow-up and 254 patients with a 6-week follow-up at a single US level I trauma center. Patients were stratified based on countersunk versus noncountersunk lag screw or helical blade in a cephalomedullary nail. The primary outcome was the cutout rate at minimum 3 months, and the secondary outcome was radiographic collapse at minimum 6 weeks. RESULTS: Cutout rates were no different in patients with countersunk and noncountersunk screws and blades, and countersinking was associated with less collapse and less implant prominence at 6 weeks. DISCUSSION: Surgeons can countersink the lag screw or blade when treating intertrochanteric proximal femur fractures with a cephalomedullary nail without increasing failure rates and with the potential benefits of less prominent lateral implants and decreased collapse.

Characterization of the gut microbiome in a porcine model of thoracic spinal cord injury.

BACKGROUND: The gut microbiome is a diverse network of bacteria which inhabit our digestive tract and is crucial for efficient cellular metabolism, nutrient absorption, and immune system development. Spinal cord injury (SCI) disrupts autonomic function below the level of injury and can alter the composition of the gut microbiome. Studies in rodent models have shown that SCI-induced bacterial imbalances in the gut can exacerbate the spinal cord damage and impair recovery. In this study we, for the first time, characterized the composition of the gut microbiome in a Yucatan minipig SCI model. We compared the relative abundance of the most dominant bacterial phyla in control samples to those collected from animals who underwent a contusion-compression SCI at the 2nd or 10th Thoracic level. RESULTS: We identify specific bacterial fluctuations that are unique to SCI animals, which were not found in uninjured animals given the same dietary regimen or antibiotic administration. Further, we identified a specific time-frame, "SCI-acute stage", during which many of these bacterial fluctuations occur before returning to "baseline" levels. CONCLUSION: This work presents a dynamic view of the microbiome changes that accompany SCI, establishes a resource for future studies and to understand the changes that occur to gut microbiota after spinal cord injury and may point to a potential therapeutic target for future treatment.

Proteomic Portraits Reveal Evolutionarily Conserved and Divergent Responses to Spinal Cord Injury.

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of cerebrospinal fluid and serum samples from 111 patients with acute SCI and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at 6 months with an area under the receiver operating characteristic curve of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response and establish the cerebrospinal fluid abundance of glial fibrillary acidic protein as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.

Duraplasty in Traumatic Thoracic Spinal Cord Injury: Impact on Spinal Cord Hemodynamics, Tissue Metabolism, Histology, and Behavioral Recovery Using a Porcine Model.

After acute traumatic spinal cord injury (SCI), the spinal cord can swell to fill the subarachnoid space and become compressed by the surrounding dura. In a porcine model of SCI, we performed a duraplasty to expand the subarachnoid space around the injured spinal cord and evaluated how this influenced acute intraparenchymal hemodynamic and metabolic responses, in addition to histological and behavioral recovery. Female Yucatan pigs underwent a T10 SCI, with or without duraplasty. Using microsensors implanted into the spinal cord parenchyma, changes in blood flow (ΔSCBF), oxygenation (ΔPO2), and spinal cord pressure (ΔSCP) during and after SCI were monitored, alongside metabolic responses. Behavioral recovery was tested weekly using the Porcine Injury Behavior Scale (PTIBS). Thereafter, spinal cords were harvested for tissue sparing analyses. In both duraplasty and non-animals, the ΔSCP increased ∼5 mm Hg in the first 6 h post-injury. After this, the SCP appeared to be slightly reduced in the duraplasty animals, although the group differences were not statistically significant after controlling for injury severity in terms of impact force. During the first seven days post-SCI, the ΔSCBF or ΔPO2 values were not different between the duraplasty and control animals. Over 12 weeks, there was no improvement in hindlimb locomotion as assessed by PTIBS scores and no reduction in tissue damage at the injury site in the duraplasty animals. In our porcine model of SCI, duraplasty did not provide any clear evidence of long-term behavioral or tissue sparing benefit after SCI.

Hypotensive Anesthesia does not reduce Transfusion Rates during and after Acetabular Fracture Surgery.

BACKGROUND: Acetabular fracture open reduction and internal fixation (ORIF) is generally associated with high intraoperative blood loss. Hypotensive anesthesia has been shown to decrease blood loss and intraoperative transfusion in total joint arthroplasty and posterior spinal fusion. In this study, we assessed the effect of reduction in intraoperative mean arterial pressures (MAPs) during acetabular fracture surgery on intraoperative blood loss and need for transfusion. METHODS: Three hundred and one patients with acetabular fractures who underwent ORIF at an academic Level 1 trauma center were retrospectively reviewed. Patients were separated based on mean intraoperative MAPs (<60 mmHg, 60-70 mmHg, >70 mmHg). Thirteen patients had mean intraoperative MAP <60 mmHg, 95 had MAP 60-70 mmHg, and 193 had MAP >70 mmHg. Rates of intraoperative and postoperative allogeneic blood transfusion were compared. RESULTS: Mean intraoperative MAPs were significantly different between groups (p < 0.0001). Time from injury to surgery, estimated blood loss, operative time and intraoperative IV fluids were comparable. The proportion of patients who received blood transfusion and mean units transfused intraoperatively and postoperatively were similar between groups. Mean differences in preoperative and postoperative hemoglobin and hematocrit were also similar. There was no difference in hospital length of stay or perioperative complications between the groups. Multivariate logistic regression analysis demonstrated that body mass index > 30 (p < 0.05) and anterior surgical approach (p < 0.01) were independently associated with intraoperative transfusion and an anterior surgical approach (p < 0.001) was independently associated with postoperative transfusion. CONCLUSION: Decreased intraoperative MAP during acetabular fracture surgery does not reduce blood loss or need for transfusion. On the other hand, no increased end-organ ischemia was seen with hypotensive anesthesia. LEVEL OF EVIDENCE: Therapeutic Level III.