Precision soft tissue balancing: grid-assisted pie-crusting in total knee arthroplasty.

Introduction: The varus and valgus knee deformities result from imbalance in tension between medial and lateral soft tissue compartments. These conditions need to be addressed during total knee arthroplasty (TKA). However, there is no consensus on optimal soft-tissue release techniques for correcting varus and valgus deformities during TKA. We assessed the efficacy of a novel grid-based pie-crusting technique on soft-tissue release. Methods: Cadaver knees were dissected, leaving only the femur and tibia connected by an isolated MCL or the femur and fibula connected by an isolated LCL. Bone cuts were made as performed during primary TKA. Mechanical testing was performed using an MTS machine. A 3D-printed 12-hole grid was placed directly over the MCL and LCL. Using an 18-gauge needle, horizontal in-out perforations were made 3 mm apart. Deformation and stiffness of the ligaments were collected after every 2 perforations. Means were calculated, and regression analyses were performed. Results: A total of 7 MCL and 6 LCL knees were included in our analysis. The mean medial femorotibial (MFT) space increased from 6.018 ± 1.4 mm-7.078 ± 1.414 mm (R2 = 0.937) following 12 perforations. The mean MCL stiffness decreased from 32.15 N/mm-26.57 N/mm (R2 = 0.965). For the LCL group, the mean gap between the femur and fibula increased from 4.287 mm-4.550 mm following 8 perforations. The mean LCL stiffness decreased from 29.955 N/mm-25.851 N/mm. LCL stiffness displayed a strong inverse relationship with the number of holes performed (R2 = 0.988). Discussion: Our results suggest that using this novel grid for pie-crusting of the MCL and LCL allows for gradual lengthening of the ligaments without sacrificing their structural integrity. Our proposed technique may serve as a valuable piece in the soft-tissue release toolkit for orthopaedic surgeons performing TKA in varus and valgus deformed knees.

Predicting Metacarpal Anatomic Lengths via Adjacent Metacarpals.

Purpose: The purpose of this study is to generate validated prediction rules for metacarpal lengths that can be applied without the need for computation tools to assist with restoration of anatomic length after fracture and utilizes only ipsilateral metacarpals. Methods: The anatomic lengths of all hand bones in 50 hands (25 men, 25 women) were used along with linear regression subset analysis to determine which metacarpals are the most predictive of each other. The most predictive metacarpals were then used to generate simple addition and subtraction prediction rules via simplifying the linear equation generated with linear regression analysis. Those rules were then applied to subsequent test cases, and percent accuracy within various cutoffs were analyzed and compared to the accuracy when using the contralateral side. Results: The prediction rules were generated and were found to be identical for both men and women. When applied to the test cases, the estimated metacarpal lengths were within 3 mm of the actual value in 97.5% of the cases for women and 90% of the cases for men compared to 95% when using the contralateral side. Conclusion: The simple additional and subtraction rules generated in this analysis were as good as or superior to using the contralateral side in all cases for women and were as good as or superior to using the contralateral side in for metacarpals 3-5 for men. Clinical Relevance: Using these simple estimating rules may be superior to using the contralateral side in most cases and provides a secondary method for determining anatomic lengths when contralateral radiographs are not available or when contralateral radiographs were obtained in different enough conditions such that the lengths may not be representative of the hand of interest.

A Transplant or a Patch? A Review of the Biologic Integration of Meniscus Allograft Transplantation.

¼ After transplantation revascularization does occur although data are only available for animal models.¼ The time zero biomechanics, that is, the biomechanical properties at the time of transplant, of a meniscus allograft transplantation appear to appropriately mimic the original so long as the graft is sized correctly within 10% of the original and bone plug fixation is used.¼ Allograft type, that is, fresh vs. frozen, does not appear to affect the integration of the allograft.

A Type IV Extension Supracondylar Fracture With Comminuted Fracture Pattern: A Case Report.

CASE: A three year, 11 month old girl sustained a right displaced extension supracondylar fracture (ESF) of the humerus with comminution of the lateral column after an indoor fall. At surgery, fracture reduction showed multidirectional instability. Adequate reduction was achieved by applying longitudinal traction of the arm with partial elbow flexion and forearm supination. One percutaneous medial pin, followed by one lateral cross pin, was used to immobilize the fracture. Normal posterolateral new periosteal bone formation was seen on radiograph on the lateral side. At 5-year follow-up, she had full range of asymptomatic and symmetrical elbow motion. CONCLUSION: This case report shows a displaced ESF with a comminuted lateral humeral column, which contributed to a lack of adequate lateral pin purchase on bone. A modified pin fixation technique first with a medial pin and followed by a lateral pin with both placed through the medial column was used for stable fracture fixation. In addition, this case showed that fracture comminution was a contributory factor to the rare multidirectional instability of the Gartland Type IV fracture.

Advising Orthopaedic Hopefuls in the Wake of a Pass/Fail US Medical Licensing Examination Step 1: A Proposed Method for Predicting US Medical Licensing Examination Step 2 Clinical Knowledge Outcomes.

INTRODUCTION: Matching into orthopaedic residency has become difficult, and the US Medical Licensing Examination Step 1 transition to pass/fail scoring has complicated the process. Advisors' ability to mentor students has decreased, and program directors may rely on Step 2 Clinical Knowledge (CK) scores in selecting which candidates to interview. This study aims to offer a method to predict Step 2 CK outcomes based on preadmission and preclinical performance. METHODS: The study investigated 486 students from a US medical school who enrolled in 2017 and 2018. Data on demographics, preadmission, and preclinical performance were collected. Before model creation, it was found that sex, Medical College Admission Test scores, Comprehensive Basic Science Examination performance, and preclinical curriculum performance produced optimal models. Multivariate ordinal logistic regression models were built to predict probabilities of four outcome levels of Step 2 CK: <235, 235 to 249, 250 to 265, and >265. Finally, nomograms were created to visualize probability calculations. RESULTS: Each model's odds ratios revealed that female sex, higher MCAT scores, and better Comprehensive Basic Science Examination and preclinical performance were associated with an increased likelihood of being in higher Step 2 CK scoring groups. Preclinical performance had a profound effect, especially for those in the top 1/3. Models were successful in assigning higher probabilities to students in higher Step 2 CK scoring groups in more than 80% of instances. Nomograms presented provide examples of how to apply these models to an individual student. DISCUSSION: This study presents a novel method for predicting probabilities of Step 2 CK outcomes that can be used to mentor students at a time point when Step 1 previously filled this role. It may assist in identifying orthopaedic hopefuls at risk of performing poorly on Step 2 CK and can foster the development of individualized guidance and mitigation strategies.

The Effect of Metacarpal Shortening on Finger Strength and Joint Motion: A Cadaveric Biomechanical Study.

Purpose: Discrepancies exist between previous biomechanical and clinical studies when determining acceptable metacarpal shortening after metacarpal fractures. This study aimed to determine the amount of acceptable shortening after a metacarpal fracture before finger motion and strength is compromised. Methods: We defrosted ten fresh-frozen cadaveric hands. A screw-driven external fixator was placed to stabilize the metacarpal, then a 15.0-mm section of the index metacarpal was excised and replaced with a three dimensional-printed, custom-designed polyethylene insert. The hand was then mounted on a custom testing rig, and the index finger was flexed using the flexor digitorum profundus tendon. Joint angles and fingertip force were recorded as the finger was flexed. Incrementally smaller inserts were placed, and testing was repeated. Results: The average joint angles of the intact condition for the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints were (54 [SD = 13], 79 [SD = 21], and 73 [SD = 10]), respectively. There were no statistically significant changes to any joint angle with any amount of shortening. The maximal fingertip contact pressures were 41 N (17), 31 N (12), 24 N (14), 19 N, (11), and 14 N (8) for the 15 mm, 12.5 mm, 10 mm, 7.5 mm, and 5 mm inserts, respectively. All changes in fingertip force by insert size were statistically significant. Conclusion: Metacarpal shortening does not affect flexion range of motion regardless of the amount of shortening, but it significantly affects finger strength. The loss of strength after shortening was approximately 6.5% per mm of shortening for the fractured metacarpal. Clinical Relevance: When viewed in the context of the hand as a whole and the contribution of the index finger to grip being only 23.5%, it is unlikely that any shortening will significantly affect the average patient regarding grip strength. However, for a patient who requires fine motor strength, any amount of shortening may affect their finger function and needs to be addressed.

Microenvironmental control of hematopoietic stem cell fate via CXCL8 and protein kinase C.

Altered hematopoietic stem cell (HSC) fate underlies primary blood disorders but microenvironmental factors controlling this are poorly understood. Genetically barcoded genome editing of synthetic target arrays for lineage tracing (GESTALT) zebrafish were used to screen for factors expressed by the sinusoidal vascular niche that alter the phylogenetic distribution of the HSC pool under native conditions. Dysregulated expression of protein kinase C delta (PKC-δ, encoded by prkcda) increases the number of HSC clones by up to 80% and expands polyclonal populations of immature neutrophil and erythroid precursors. PKC agonists such as cxcl8 augment HSC competition for residency within the niche and expand defined niche populations. CXCL8 induces association of PKC-δ with the focal adhesion complex, activating extracellular signal-regulated kinase (ERK) signaling and expression of niche factors in human endothelial cells. Our findings demonstrate the existence of reserve capacity within the niche that is controlled by CXCL8 and PKC and has significant impact on HSC phylogenetic and phenotypic fate.

Transcription factor induction of vascular blood stem cell niches in vivo.

The hematopoietic niche is a supportive microenvironment composed of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimensional gene expression and chromatin accessibility analyses in zebrafish, we define a conserved gene expression signature and cis-regulatory landscape that are unique to sinusoidal endothelial cells in the HSPC niche. Using enhancer mutagenesis and transcription factor overexpression, we elucidate a transcriptional code that involves members of the Ets, Sox, and nuclear hormone receptor families and is sufficient to induce ectopic niche endothelial cells that associate with mesenchymal stromal cells and support the recruitment, maintenance, and division of HSPCs in vivo. These studies set forth an approach for generating synthetic HSPC niches, in vitro or in vivo, and for effective therapies to modulate the endogenous niche.

Favourable mid-term outcomes following unicompartmental knee arthroplasty with wider patient selection: A single-centre experience.

OBJECTIVE: The purpose of this study was to determine surgical outcomes of robotic-assisted UKAs utilizing a wider set of indications than traditionally utilized. Additionally, we seek to determine alternate predictive factors as potential surgical indications and contraindications. METHODS: A prospectively maintained institutional joint registry was queried at a single academic centre for all patients that underwent robotic-assisted UKA between January 2010-December 2016. Surgical indication included isolated medial or lateral compartment degenerative disease with a stable knee based on physical exam. In 2013, haemoglobin A1C levels over 7.5% were considered contraindications, which was lowered to 7.0% in 2015. Preoperative alignment, age, activity level and degree of pain were not contraindications for surgery. Preoperative demographics, Oxford scores, radiographic (joint space), comorbidities and operative data were collected and reviewed to determine factors related to conversion to TKA and survivorship of the primary implant. RESULTS: In total, 1878 cases were performed; however, excluding multi-joint knees, there were a total of 1186 knees in 1014 patients with a minimum 4-year follow-up. The mean age was 63.4 â€‹± â€‹10.7 years and mean follow-up was 76.4 â€‹± â€‹17.4 months. Mean BMI was 32.3 â€‹± â€‹6.5 â€‹kg/m2. (52.9% females, 47.1% males). There were 901 patients undergoing medial UKA, 122 patients undergoing lateral UKA and 69 patients undergoing patellofemoral UKA. In total, 85 (7.2%) knees underwent conversion to TKA. Preoperative factors such as the degree of preoperative valgus deformity (p â€‹= â€‹0.01), greater operative joint space (p â€‹= â€‹0.04), previous surgery (p â€‹= â€‹0.01), inlay implant (p â€‹= â€‹0.04) and pain syndrome (p â€‹= â€‹0.01) were associated with increased risk of revision surgery. Factors associated with decreased implant survivorship included patients with history of previous surgery (p â€‹< â€‹0.01), history of pain syndrome (p â€‹< â€‹0.01) and greater preoperative joint space (>2 â€‹mm) (p â€‹< â€‹0.01). There was no association of BMI to conversion to TKA. CONCLUSION: Robotic-assisted UKA with wider patient selection demonstrated favourable outcomes at 4 years with survivorship greater than 92%. The present series agree with emerging indications that do not exclude patients based on age, BMI, or degree of deformity. However, increased operative joint space, inlay design, history of surgery and coexistence of pain syndrome are factors that increase risk of conversion to TKA. LEVEL OF EVIDENCE: Level III.

Gastrointestinal and hepatic manifestations of COVID-19: A systematic review and meta-analysis.

Background and Aim: This review investigates the role of gastrointestinal and hepatic manifestations in COVID-19, particularly with regard to the prevalence of isolated gastrointestinal (GI) symptoms. Methods: We searched PubMed, Embase, and Cochrane library for COVID-19 publications from 1 December 2019 to 18 May 2020. We included any study that reported the presence of GI symptoms in a sample of >5 COVID-19 patients. Data collection and risk of bias assessment were performed independently by two reviewers. Where ≥3 studies reported data sufficiently similar to allow calculation of a pooled prevalence, we performed random effects meta-analysis. Results: This review included 17 776 COVID-19 patients from 108 studies. Isolated GI symptoms only occurred in 1% (95% confidence interval [CI] 0-6%) of patients. GI symptoms were reported in 20% (95% CI 15-24%) of patients. The most common were anorexia (21%, 95% CI 15-27%), diarrhea (13%, 95% CI 11-16%), nausea or vomiting (8%, 95% CI 6-11%), and abdominal pain (4%, 95% CI 2-6%). Transaminase elevations were present in 24% (95% CI 17-31%) of patients. Higher prevalence of GI symptoms were reported in studies published after 1st April, with prevalence of diarrhea 16% (95% CI 13-20), nausea or vomiting 12% (95% CI 8-16%), and any GI symptoms 24% (95% CI 18-34%). GI symptoms were associated with severe COVID-19 disease (odds ratio [OR] 2.1, 95% CI 1.3-3.2), but not mortality (OR 0.90, 95% CI 0.52-1.54). Conclusions: Patients with isolated GI symptoms may represent a small but significant portion of COVID-19 cases. When testing resources are abundant, clinicians should still consider testing patients with isolated GI symptoms or unexplained transaminase elevations for COVID-19. More recent studies estimate higher overall GI involvement in COVID-19 than was previously recognized.

Common variants in signaling transcription-factor-binding sites drive phenotypic variability in red blood cell traits.

Genome-wide association studies identify genomic variants associated with human traits and diseases. Most trait-associated variants are located within cell-type-specific enhancers, but the molecular mechanisms governing phenotypic variation are less well understood. Here, we show that many enhancer variants associated with red blood cell (RBC) traits map to enhancers that are co-bound by lineage-specific master transcription factors (MTFs) and signaling transcription factors (STFs) responsive to extracellular signals. The majority of enhancer variants reside on STF and not MTF motifs, perturbing DNA binding by various STFs (BMP/TGF-ß-directed SMADs or WNT-induced TCFs) and affecting target gene expression. Analyses of engineered human blood cells and expression quantitative trait loci verify that disrupted STF binding leads to altered gene expression. Our results propose that the majority of the RBC-trait-associated variants that reside on transcription-factor-binding sequences fall in STF target sequences, suggesting that the phenotypic variation of RBC traits could stem from altered responsiveness to extracellular stimuli.

RNA helicase DDX21 mediates nucleotide stress responses in neural crest and melanoma cells.

The availability of nucleotides has a direct impact on transcription. The inhibition of dihydroorotate dehydrogenase (DHODH) with leflunomide impacts nucleotide pools by reducing pyrimidine levels. Leflunomide abrogates the effective transcription elongation of genes required for neural crest development and melanoma growth in vivo1. To define the mechanism of action, we undertook an in vivo chemical suppressor screen for restoration of neural crest after leflunomide treatment. Surprisingly, we found that alterations in progesterone and progesterone receptor (Pgr) signalling strongly suppressed leflunomide-mediated neural crest effects in zebrafish. In addition, progesterone bypasses the transcriptional elongation block resulting from Paf complex deficiency, rescuing neural crest defects in ctr9 morphant and paf1(alnz24) mutant embryos. Using proteomics, we found that Pgr binds the RNA helicase protein Ddx21. ddx21-deficient zebrafish show resistance to leflunomide-induced stress. At a molecular level, nucleotide depletion reduced the chromatin occupancy of DDX21 in human A375 melanoma cells. Nucleotide supplementation reversed the gene expression signature and DDX21 occupancy changes prompted by leflunomide. Together, our results show that DDX21 acts as a sensor and mediator of transcription during nucleotide stress.

CXCR1 remodels the vascular niche to promote hematopoietic stem and progenitor cell engraftment.

The microenvironment is an important regulator of hematopoietic stem and progenitor cell (HSPC) biology. Recent advances marking fluorescent HSPCs have allowed exquisite visualization of HSPCs in the caudal hematopoietic tissue (CHT) of the developing zebrafish. Here, we show that the chemokine cxcl8 and its receptor, cxcr1, are expressed by zebrafish endothelial cells, and we identify cxcl8/cxcr1 signaling as a positive regulator of HSPC colonization. Single-cell tracking experiments demonstrated that this is a result of increases in HSPC-endothelial cell "cuddling," HSPC residency time within the CHT, and HSPC mitotic rate. Enhanced cxcl8/cxcr1 signaling was associated with an increase in the volume of the CHT and induction of cxcl12a expression. Finally, using parabiotic zebrafish, we show that cxcr1 acts HSPC nonautonomously to improve the efficiency of donor HSPC engraftment. This work identifies a mechanism by which the hematopoietic niche remodels to promote HSPC engraftment and suggests that cxcl8/cxcr1 signaling is a potential therapeutic target in patients undergoing hematopoietic stem cell transplantation.