Unique molecular characteristics and microglial origin of Kv1.3 channel-positive brain myeloid cells in Alzheimer's disease.

Kv1.3 potassium channels, expressed by proinflammatory central nervous system mononuclear phagocytes (CNS-MPs), are promising therapeutic targets for modulating neuroinflammation in Alzheimer's disease (AD). The molecular characteristics of Kv1.3-high CNS-MPs and their cellular origin from microglia or CNS-infiltrating monocytes are unclear. While Kv1.3 blockade reduces amyloid beta (Aß) burden in mouse models, the downstream immune effects on molecular profiles of CNS-MPs remain unknown. We show that functional Kv1.3 channels are selectively expressed by a subset of CD11b+CD45+ CNS-MPs acutely isolated from an Aß mouse model (5xFAD) as well as fresh postmortem human AD brain. Transcriptomic profiling of purified CD11b+Kv1.3+ CNS-MPs, CD11b+CD45int Kv1.3neg microglia, and peripheral monocytes from 5xFAD mice revealed that Kv1.3-high CNS-MPs highly express canonical microglial markers (Tmem119, P2ry12) and are distinct from peripheral Ly6chigh/Ly6clow monocytes. Unlike homeostatic microglia, Kv1.3-high CNS-MPs express relatively lower levels of homeostatic genes, higher levels of CD11c, and increased levels of glutamatergic transcripts, potentially representing phagocytic uptake of neuronal elements. Using irradiation bone marrow CD45.1/CD45.2 chimerism in 5xFAD mice, we show that Kv1.3+ CNS-MPs originate from microglia and not blood-derived monocytes. We show that Kv1.3 channels regulate membrane potential and early signaling events in microglia. Finally, in vivo blockade of Kv1.3 channels in 5xFAD mice by ShK-223 reduced Aß burden, increased CD11c+ CNS-MPs, and expression of phagocytic genes while suppressing proinflammatory genes (IL1b). Our results confirm the microglial origin and identify unique molecular features of Kv1.3-expressing CNS-MPs. In addition, we provide evidence for CNS immunomodulation by Kv1.3 blockers in AD mouse models resulting in a prophagocytic phenotype.

Preliminary study on the stabilization of varus proximal femoral osteotomies using pediatric LCP plates in adults undergoing combined correction of proximal femoral and acetabular dysplasia.

PURPOSE: Proximal femoral osteotomy (PFO) with periacetabular osteotomy (PAO) improves femoral head coverage in patients with proximal femoral and acetabular dysplasia. Historically, blade plates used in the PFO cause soft-tissue irritation and often lead to implant removal. Here we present a technique using a lower profile pediatric proximal femoral locking compression plate (LCP) for the PFO in a series of adults. METHODS: The results from 13 hips in 11 patients ≥ 18 years old (age 18-37) with > 10 months of follow-up are presented. RESULTS: All patients had improved radiographic parameters, pain, and total Merle d'Aubigné-Postel scores postoperatively. Eleven hips (85%) had the LCP removed an average of 15.8 ± 8.6 months postoperatively, often due to pain over the greater trochanter. CONCLUSION: The pediatric proximal femoral LCP is effective for PFO in combined PAO PFO procedures but has a high rate of lateral hip discomfort leading to implant removal.

Limb position affects intraoperative assessment of condylar width.

PURPOSE: We sought to define how changes in position and rotation of fluoroscopic imaging may affect the assessment of condylar widening intraoperatively. METHODS: Thirty-three patients with tibial plateau fractures were prospectively identified and included in this study. Fluoroscopic images of the uninjured tibial plateau were obtained in (1) full extension and (2) slight flexion on foam ramp. Beginning with a plateau view, additional views of the tibial plateau were then obtained by rotating the fluoroscope around the knee in 5 degree increments up to 15 degrees in both internal and external rotation. Measurements of distal femoral condylar width (DFW), distal femoral articular width (FAW), proximal tibial articular width (TAW) and lateral plateau width (LPW) were performed. RESULTS: LPW was decreased in flexion compared to extension at all degrees of rotation (p = 0.04-0.00001). There was a trend toward increasing LPW with increasing degrees of internal rotation which reached significance at 15˚ of internal rotation when the knee was flexed. On ANOVA, there was a significant difference of LPW with increasing degree of internal rotation when the knee was in flexion (p = 0.008), but not in extension. There were no differences in DFW, FAW, TAW and DFW/TAW at any point though LPW was decreased in flexion at all degrees of rotation. The FAW/TAW ratio was increased in flexion at all degrees of rotation. DISCUSSION: The knee in flexion will underestimate the measurement of condylar width compared to the knee in full extension, by ~ 2 mm. Rotation of the knee, in comparison, did not have a significant effect on condylar width assessment. LEVEL OF EVIDENCE: Diagnostic II.

Capsular distension in high-energy femoral shaft fractures is associated with occult femoral neck fracture: a preliminary retrospective comparative study.

OBJECTIVES: To determine the association between hip capsular distension, the computed tomography (CT) capsular sign, and lipohemarthrosis as they relate to occult femoral neck fracture (FNF) in the setting of ipsilateral femoral shaft fracture (FSF). DESIGN: Retrospective comparative study. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: Two hundred and forty-two patients with high-energy FSF and no evidence of FNF on preoperative radiographs and pelvis CT. All patients were stabilized with non-reconstruction style nails. INTERVENTION: Pelvis CT scans were examined for hip capsular distension irrespective of the other side, differing side-to-side measurements of capsular distension (i.e., the CT capsular sign), and lipohemarthrosis. MAIN OUTCOME MEASUREMENTS: FNF was observed for on postoperative radiographs. Relative risk (RR), number needed to treat (NNT), sensitivity (SN), and specificity (SP) were determined. RESULTS: Fifty-eight patients (24.0%) had capsular distension. Forty-two patients (17.4%) had differing capsular measurements (i.e., the CT capsular sign), and 16 (6.6%) had symmetrical distension from bilateral hip effusions. Eight patients (3.3%) had lipohemarthrosis. Four FNFs (1.7%) were identified. Three patients had capsular distension, 2 had CT capsular signs, and 1 had lipohemarthrosis. The last patient had no CT abnormalities. Only capsular distension (RR = 10, CI = 1.001-90, P = 0.049; SN = 75%, SP = 77%; NNT = 22) and lipohemarthrosis (RR = 23, CI = 1.6-335, P = 0.022; SN = 50%, SP = 96%; NNT = 8) were associated with occult FNF. CONCLUSIONS: Capsular distension is associated with FNF irrespective of the contralateral hip. Preemptive stabilization using a reconstruction nail could be considered in the setting of capsular distension or lipohemarthrosis to prevent displacement of an occult FNF. LEVEL OF EVIDENCE: Diagnostic Level III.

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.

The Notch1 transcriptional activation domain is required for development and reveals a novel role for Notch1 signaling in fetal hematopoietic stem cells.

Notch1 is required to generate the earliest embryonic hematopoietic stem cells (HSCs); however since Notch-deficient embryos die early in gestation, additional functions for Notch in embryonic HSC biology have not been described. We used two complementary genetic models to address this important biological question. Unlike Notch1-deficient mice, mice lacking the conserved Notch1 transcriptional activation domain (TAD) show attenuated Notch1 function in vivo and survive until late gestation, succumbing to multiple cardiac abnormalities. Notch1 TAD-deficient HSCs emerge and successfully migrate to the fetal liver but are decreased in frequency by embryonic day 14.5. In addition, TAD-deficient fetal liver HSCs fail to compete with wild-type HSCs in bone marrow transplant experiments. This phenotype is independently recapitulated by conditional knockout of Rbpj, a core Notch pathway component. In vitro analysis of Notch1 TAD-deficient cells shows that the Notch1 TAD is important to properly assemble the Notch1/Rbpj/Maml trimolecular transcription complex. Together, these studies reveal an essential role for the Notch1 TAD in fetal development and identify important cell-autonomous functions for Notch1 signaling in fetal HSC homeostasis.

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.

Acetabular labral reconstruction with medial meniscal allograft: preliminary results of a new surgical technique.

PURPOSE: Reconstruction of the acetabular labrum during femoroacetabular impingement (FAI) surgery is accepted when the labrum is deficient and irreparable. Here we describe a novel technique using fresh-frozen medial meniscal allograft for labral reconstruction during surgical hip dislocation for correction of pincer FAI due to acetabular overcoverage. METHODS: The results from seven hips (six patients) that underwent this procedure with 1 year minimum follow-up, and radiographs are presented. RESULTS: Six of the seven hips had improvements in pain, hip flexion, hip abduction, and Merle d'Aubigné-Postel scores. Only one patient with pre-existing osteoarthritis underwent reoperation with conversion to total hip arthroplasty. All digastric trochanteric osteotomies healed, and there were no cases of femoral head osteonecrosis or progression of Tönnis grades. CONCLUSIONS: The medial meniscus is a morphologically and clinically suitable option for labral reconstruction and effectively restores the hip fluid seal.

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.

Extracellular signal-regulated kinase regulates microglial immune responses in Alzheimer's disease.

The importance of mitogen-activated protein kinase (MAPK) pathway signaling in regulating microglia-mediated neuroinflammation in Alzheimer's disease (AD) remains unclear. We examined the role of MAPK signaling in microglia using a preclinical model of AD pathology and quantitative proteomics studies of postmortem human brains. In multiplex immunoassay analyses of MAPK phosphoproteins in acutely isolated microglia and brain tissue from 5xFAD mice, we found phosphorylated extracellular signal-regulated kinase (ERK) was the most strongly upregulated phosphoprotein within the MAPK pathway in acutely isolated microglia, but not whole-brain tissue from 5xFAD mice. The importance of ERK signaling in primary microglia cultures was next investigated using transcriptomic profiling and functional assays of amyloid-ß and neuronal phagocytosis, which confirmed that ERK is a critical regulator of IFNγ-mediated pro-inflammatory activation of microglia, although it was also partly important for constitutive microglial functions. Phospho-ERK was an upstream regulator of disease-associated microglial gene expression (Trem2, Tyrobp), as well as several human AD risk genes (Bin1, Cd33, Trem2, Cnn2), indicative of the importance of microglial ERK signaling in AD pathology. Quantitative proteomic analyses of postmortem human brain showed that ERK1 and ERK2 were the only MAPK proteins with increased protein expression and positive associations with neuropathological grade. In a human brain phosphoproteomic study, we found evidence for increased flux through the ERK signaling pathway in AD. Overall, our analyses strongly suggest that ERK phosphorylation, particularly in microglia in mouse models, is a regulator of pro-inflammatory immune responses in AD pathogenesis.

Using Machine Learning to Evaluate Attending Feedback on Resident Performance.

BACKGROUND: High-quality and high-utility feedback allows for the development of improvement plans for trainees. The current manual assessment of the quality of this feedback is time consuming and subjective. We propose the use of machine learning to rapidly distinguish the quality of attending feedback on resident performance. METHODS: Using a preexisting databank of 1925 manually reviewed feedback comments from 4 anesthesiology residency programs, we trained machine learning models to predict whether comments contained 6 predefined feedback traits (actionable, behavior focused, detailed, negative feedback, professionalism/communication, and specific) and predict the utility score of the comment on a scale of 1-5. Comments with ≥4 feedback traits were classified as high-quality and comments with ≥4 utility scores were classified as high-utility; otherwise comments were considered low-quality or low-utility, respectively. We used RapidMiner Studio (RapidMiner, Inc, Boston, MA), a data science platform, to train, validate, and score performance of models. RESULTS: Models for predicting the presence of feedback traits had accuracies of 74.4%-82.2%. Predictions on utility category were 82.1% accurate, with 89.2% sensitivity, and 89.8% class precision for low-utility predictions. Predictions on quality category were 78.5% accurate, with 86.1% sensitivity, and 85.0% class precision for low-quality predictions. Fifteen to 20 hours were spent by a research assistant with no prior experience in machine learning to become familiar with software, create models, and review performance on predictions made. The program read data, applied models, and generated predictions within minutes. In contrast, a recent manual feedback scoring effort by an author took 15 hours to manually collate and score 200 comments during the course of 2 weeks. CONCLUSIONS: Harnessing the potential of machine learning allows for rapid assessment of attending feedback on resident performance. Using predictive models to rapidly screen for low-quality and low-utility feedback can aid programs in improving feedback provision, both globally and by individual faculty.

Sequential ilioinguinal or anterior intrapelvic approach with anterior approach to the hip during combined internal fixation and total hip arthroplasty for acetabular fractures.

PURPOSE: This study examined the complications and outcomes of geriatric acetabular fractures treated with open reduction internal fixation (ORIF) and total hip arthroplasty (THA) performed via combined ilioinguinal or anterior intrapelvic (AIP) approach to acetabulum and anterior approach to the hip. METHODS: Eight patients with a fracture of the acetabulum were treated at a Level I trauma center between 2010 and 2019 with combined ORIF/THA using an ilioinguinal or AIP approach for the acetabulum and a separate anterior approach to the hip. Wound dehiscence, peri-incisional skin necrosis, surgical site infection, dislocation, fracture union, acetabular component stability, and heterotopic ossification (HO) were utilized as outcome measures. Merle d'Aubigné-Postel scores were collected for the six patients that had one-year minimum follow-up. RESULTS: The mean patient age was 77 years. Four patients had anterior wall fractures, two had associated both column fractures, and two had anterior column-posterior hemitransverse fractures. All fractures healed with stable fixation of the acetabular component by 6 months. There were no instances of skin necrosis, dislocation, infection, or re-operation. One patient had a superficial wound dehiscence that resolved with local wound care. One patient developed radiographic HO but was clinically asymptomatic. The mean Merle d'Aubigné-Postel score was 15.8 (range = 14-16). CONCLUSIONS: Our small series of geriatric patients with fracture of the acetabulum treated with combined ORIF/THA, via the ilioinguinal or AIP approach with a separate anterior approach to the hip, demonstrates satisfactory outcomes with low complications after one-year of follow-up. Further research of these challenging injuries with more patients is warranted in order to determine the subset of fracture types best treated with this method and THA survivorship.

Outcomes after locking plate fixation of distal clavicle fractures with and without coracoclavicular ligament augmentation.

BACKGROUND: The need for coracoclavicular (CC) ligament augmentation when performing locking plate fixation of unstable distal clavicle fractures is controversial. The purpose of this study was to compare the results after locking plate fixation for treatment of Neer type-II and type-V distal clavicle fractures with and without suture suspensory augmentation of the CC ligaments. METHODS: This was a retrospective case series of all Neer type-II and type-V distal clavicle fractures treated with locking plates at a single Level I trauma center. Patients were separated into locking plate-only and locking plate with CC ligament augmentation groups. Postoperative complications and fracture healing rates were recorded. Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores were recorded as functional outcomes during follow-up phone interviews. Standard descriptive statistics were performed. RESULTS: Sixteen patients were treated with locking plate fixation-only, and seven patients were treated with additional CC ligament augmentation. There was a similar distribution of Neer fracture types with each group. All fractures in both groups went onto union without loss of reduction or implant failure. There were no cases of infection or wound complications in either group. QuickDASH scores were comparable between locking plate-only fixation (mean 4.1 ± 3.9) and additional suspensory suture fixation (mean 4.5 ± 3.6). CONCLUSION: This comparative study of Neer type-II and type-V distal clavicle fractures demonstrated comparable outcomes after locking plate fixation with and without CC ligament augmentation. CC ligament augmentation may not be necessary when treating unstable distal clavicle fractures if locking plate fixation is used.

Distal femoral fine wire traction assisted retrograde nailing of the femur.

Here we describe the surgical technique for using distal femoral fine wire traction during retrograde femoral nailing and present case examples. This technique allows for hands-free distraction across the fracture site to restore length and alignment, while not interfering with the preparation and insertion of the retrograde femoral nail. Distal femoral fine wire traction is a useful adjunctive technique to restore length and effect an indirect reduction in femur fractures being stabilized with a retrograde nail.

Trochanteric fixation nail advanced with helical blade and cement augmentation: early experience with a retrospective cohort.

Intra-articular screw cut-out is a potential complication of intertrochanteric femur fracture fixation with a cephalomedullary nail. Cement augmentation of fixation in the proximal segment offers the prospect of increased stability and fewer complications, but clinical experience with non-resorbable cement is limited. To determine the handling properties and efficacy of this new technique, we performed a retrospective propensity-matched cohort of forty-four geriatric intertrochanteric femur fractures treated with a cephalomedullary nail with (n = 11) or without (n = 33) augmentation with non-resorbable cement injected into the proximal segment. In the patients treated with cement augmentation, at minimum 3-month follow-up, there were no instances of intra-articular cut-out, and no increase in re-operation compared to conventional fixation. Cement augmentation appears to be safe and effective in geriatric intertrochanteric femur fractures to mitigate risk of cut-out.

Trochanteric osteotomy for acetabular fracture fixation: a case series and literature review.

PURPOSE: This study examined osteotomy union and heterotopic ossification (HO) after performing digastric trochanteric osteotomies during open reduction and internal fixation (ORIF) of acetabular and combined femoral head fractures. Femoral head osteonecrosis and trochanteric screw removal were secondarily assessed. METHODS: Twenty-six patients treated at a Level I trauma center, from years 2003 to 2019, who received a digastric trochanteric osteotomy during acetabular and combined femoral head fracture ORIF through a posterior surgical approach were retrospectively identified. Osteotomies were fixed with two 3.5 mm cortical lag screws. Rates of osteotomy union, HO, femoral head osteonecrosis, and trochanteric screw removal were determined. RESULTS: All osteotomies went onto union without displacement or failure of fixation. Only three (12%) patients developed severe HO (modified-Brooker class III-IV). There were no instances of femoral head osteonecrosis and only one (7%) patient required trochanteric screw removal. CONCLUSIONS: The digastric trochanteric osteotomy heals reliably with low rates of severe HO, femoral head osteonecrosis, and screw removal for soft-tissue irritation. A review of the literature is presented and found comparable findings.

Management of the posterior wall fracture in associated both column fractures of the acetabulum.

PURPOSE: The primary aim of this study was to compare clinical outcomes in patients with associated both column (ABC) acetabular fractures with fracture of the posterior wall (PW), in which the PW underwent reduction and fragment-specific fixation versus those that were treated with column fixation alone. Secondary aims were to assess PW fracture incidence and morphology, as well as to compare radiographic outcomes including fracture healing and interval displacement of the PW in those that did and did not undergo fragment-specific fixation of the PW. METHODS: This was a retrospective series of ABC acetabular fractures treated at a single Level I trauma center. Separate fractures of the PW were identified, and associated features were assessed. Associated both column fractures that underwent reduction and fragment-specific fixation of the PW where then compared to ABC fractures with PW involvement that underwent column reconstruction alone. Radiographic and clinical outcomes were compared. RESULTS: Fractures of the PW occurred in 55.7% of ABC fractures and were associated with central displacement of the femoral head. The majority of PW fractures were large and involved the acetabular roof. All PW fractures healed without displacement by 3 months, regardless of whether or not reduction and stabilization was performed. Mid-term outcomes at 1-year were similar regardless of whether or not the PW was reduced and stabilized, with regards to Tönnis grade, Merle d'Aubigné-Postel score, and conversion to total hip arthroplasty. CONCLUSION: Reduction and fragment-specific fixation of the PW component of ABC acetabular fractures did not improve outcomes in this small comparative study. Posterior wall fractures associated with ABC patterns are frequently large-sized fragments that involve the acetabular roof and are rendered stable after reconstruction of the columns.

Hook versus locking plate fixation for Neer type-II and type-V distal clavicle fractures: a retrospective cohort study.

PURPOSE: This study examined the outcomes and complications after treatment of unstable distal clavicle fractures with hook or locking plate fixation. METHODS: A retrospective search was performed of all acute distal clavicle fractures treated with open reduction and internal fixation from 2009 to 2019 at a Level I trauma center. Patients were separated into hook and locking plate fixation groups. Rates of union, complications, and reoperation, were extracted. QuickDASH (Disabilities of Arm, Shoulder, and Hand) scores were determined. RESULTS: Thirty-one patients met the inclusion criteria and were included in the study. Of these, 12 patients were treated with hook plates and 19 were treated with locking plates. All fractures healed without loss of reduction, regardless of implant selection. There were no immediate or long-term complications in either group. 83% of hook plate patients underwent planned implant removal, while 37% of locking plate patients requested implant removal secondary to irritation. QuickDASH scores were comparable and excellent in both groups. CONCLUSIONS: Hook and locking plate fixation for Neer type-II and type-V distal clavicle fractures have comparably high rates of union. Hook plates were removed routinely per protocol, while locking plates were removed only if symptomatic and occurred significantly less often.

Inducing chondrogenesis in MSC/chondrocyte co-cultures using exogenous TGF-ß: a mathematical model.

The differentiation of mesenchymal stem cells (MSCs) into chondrocytes (native cartilage cells), or chondrogenesis, is a key step in the tissue engineering of articular cartilage, where the motility and high proliferation rate of MSCs used as seed cells are exploited. Chondrogenesis is regulated by transforming growth factor-beta (TGF-ß), a short-lived cytokine whose effect is prolonged by storage in the extracellular matrix. Tissue engineering applications require the complete differentiation of an initial population of MSCs, and two common strategies used to achieve this in vitro are (1) co-culture the MSCs with chondrocytes, which constitutively produce TGF-ß; or (2) add exogenous TGF-ß. To investigate these strategies we develop an ordinary differential equation model of the interactions between TGF-ß, MSCs and chondrocyte. Here the dynamics of TGF-ß are much faster than those of the cell processes; this difference in time-scales is exploited to simplify subsequent model analysis. Using our model we demonstrate that under strategy 1 complete chondrogenesis will be induced if the initial proportion of chondrocytes exceeds a critical value. Similarly, under strategy 2 we find that there is a critical concentration of exogenous TGF-ß above which all MSCs will ultimately differentiate. Finally, we use the model to demonstrate the potential advantages of adopting a hybrid strategy where exogenous TGF-ß is added to a co-culture of MSCs and chondrocytes, as compared to using either strategy 1 or 2 in isolation.

Practice Patterns of Stereotactic Radiotherapy in Pediatrics: Results From an International Pediatric Research Consortium.

PURPOSE/OBJECTIVES: There is little consensus regarding the application of stereotactic radiotherapy (SRT) in pediatrics. We evaluated patterns of pediatric SRT practice through an international research consortium. MATERIALS AND METHODS: Eight international institutions with pediatric expertise completed a 124-item survey evaluating patterns of SRT use for patients 21 years old and younger. Frequencies of SRT use and median margins applied with and without SRT were evaluated. RESULTS: Across institutions, 75% reported utilizing SRT in pediatrics. SRT was used in 22% of brain, 18% of spine, 16% of other bone, 16% of head and neck, and <1% of abdomen/pelvis, lung, and liver cases across sites. Of the hypofractionated SRT cases, 42% were delivered with definitive intent. Median gross tumor volume to planning target volume margins for SRT versus non-SRT plans were 0.2 versus 1.4 cm for brain, 0.3 versus 1.5 cm for spine/other bone, 0.3 versus 2.0 cm for abdomen/pelvis, 0.7 versus 1.5 cm for head and neck, 0.5 versus 1.7 cm for lung, and 0.5 versus 2.0 cm for liver sites. CONCLUSIONS: SRT is commonly utilized in pediatrics across a range of treatment sites. Margins used for SRT were substantially smaller than for non-SRT planning, highlighting the utility of this approach in reducing treatment volumes.