The Effect of Acute Aerobic Exercise on Biomarkers of Renal Health and Filtration in Moderate-CKD.

Purpose: Efficacy of exercise to improve renal health and filtration remains understudied in adults with moderate-stages (stages G3a-b) of chronic kidney disease (CKD). Acute exercise may contribute clinically relevant information for exercise-related augmentation of renal health and filtration in CKD. Urine epidermal growth factor (uEGF) and cystatin C (CyC) are proposed to be more direct biomarkers of renal health and filtration. This study aimed to determine the influence of continuous moderate-intensity exercise (CMIE) and high-intensity interval exercise (HIIE) on traditional and novel biomarkers of renal health and filtration in moderate-stages of CKD. Methods: Twenty CKD participants completed 30 minutes of both CMIE and HIIE. Blood and urine samples were obtained pre, 1-hour, and 24-hours post-exercise. Traditional-serum creatinine (sCr) urine creatinine, novel-uEGF, uEGF ratio (uEGFr), and CyC. Estimates of glomerular filtration rate (eGFR)-modification of diet in renal disease (MDRD) and the CKD-Epidemiology (CKD-EPI)-responses were compared pre, 1 hr, and 24 hr post-exercise. Results: Relative to pre-exercise measures, uEGF remained unchanged in both exercise conditions. However, uEGFr was 5.4% greater 24-hours after HIIE (P = .05), while uEGFr remained unchanged with CMIE. sCr decreased 6 to 19% 1-hour post-exercise in both conditions (P = .009). On average renal filtration increased in eGFR-MDRD (7.2 ± 2.0 ml/min/1.73 m2) (P = .007) and eGFR-CKD-EPI (8.6 ± 2.3 ml/min/1.73 m2) 1-hour post-exercise (P = .009). Conclusion: By clinical estimates, renal filtration in CKD was not normalized but transiently improved regardless of exercise condition, with HIIE eliciting transient improvements in renal health.

E-cigarette exposure with or without heating the e-liquid induces differential remodeling in the lungs and right heart of mice.

Various cardiopulmonary pathologies associated with electronic cigarette (EC) vaping have been reported. This study investigated the differential adverse effects of heating-associated by-products versus the intact components of EC aerosol to the lungs and heart of mice. We further dissected the roles of caspase recruitment domain-containing protein 9 (CARD9)-associated innate immune response and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in EC exposure-induced cardiopulmonary injury. C57BL/6 wild type (WT), CARD9-/-, and NLRP3-/- mice were exposed to EC aerosol 3 h/day, 5 days/week for 6 month with or without heating the e-liquid with exposure to ambient air as the control. In WT mice, EC exposure with heating (EwH) significantly increased right ventricle (RV) free wall thickness at systole and diastole. However, EC exposure without heating (EwoH) caused a significant decrease in the wall thickness at systole. RV fractional shortening was also markedly reduced following EwH in WT and NLRP3-/- mice. Further, EwH activated NF-κB and p38 MAPK inflammatory signaling in the lungs, but not in the RV, in a CARD9- and NLRP3-dependent manner. Levels of circulatory inflammatory mediators were also elevated following EwH, indicating systemic inflammation. Moreover, EwoH activated TGF-ß1/SMAD2/3/α-SMA fibrosis signaling in the lungs but not the RV of WT mice. In conclusion, EC aerosol exposure following EwH or EwoH induced differential cardiopulmonary remodeling and CARD9 innate immune response and NLRP3 inflammasome contributed to the adverse effects.

Application of theoretical frameworks on human papillomavirus vaccine interventions in the United States: systematic review and meta-analysis.

PURPOSE: Theoretical frameworks are useful tools to explain the dynamics of behavioral change, develop, and implement intervention studies. The purpose of this systematic review and meta-analysis is to evaluate the application of theoretical frameworks and models to HPV vaccination intervention studies in the United States (US) from January 2006 to December 2019. METHODS: A comprehensive search across databases, including PubMed, EMBASE, ERIC, CINAHL, Academic Search Complete, Scopus, Web of Science, and PsycINFO, was conducted. Articles were included in the systematic analysis if at least one theory was used to develop the intervention phase. All intervention studies targeting populations in the US without restrictions of age, income, sex, and ethnicity were included. Articles were included in the meta-analysis if vaccine uptake and/or vaccine completion was addressed. RESULTS: The Health Belief Model, Motivational Interviewing, Theory of Planned Behavior, and Information-Motivation-Behavioral Skills were the most used theories. Based on theory integrity, theory rationale, and theory operationalization, most of the studies (60%) were rated high for the application of the theoretical frameworks. Our results suggest a preference for theoretical frameworks targeting individual change rather than community change and the existence of gender disparities in the application of theoretical frameworks. The association between theory and increase of likelihood in vaccine uptake and completion was not supported. CONCLUSION: This review spotlights common issues in the application of theoretical frameworks in HPV vaccine interventions in the US. Our results suggest we are still in a developmental phase on several aspects of theory application to HPV vaccination.

Assessing Open-Ended Human-Computer Collaboration Systems: Applying a Hallmarks Approach.

There is a growing desire to create computer systems that can collaborate with humans on complex, open-ended activities. These activities typically have no set completion criteria and frequently involve multimodal communication, extensive world knowledge, creativity, and building structures or compositions through multiple steps. Because these systems differ from question and answer (Q&A) systems, chatbots, and simple task-oriented assistants, new methods for evaluating such collaborative computer systems are needed. Here, we present a set of criteria for evaluating these systems, called Hallmarks of Human-Machine Collaboration. The Hallmarks build on the success of heuristic evaluation used by the user interface community and past evaluation techniques used in the spoken language and chatbot communities. They consist of observable characteristics indicative of successful collaborative communication, grouped into eight high-level properties: robustness; habitability; mutual contribution of meaningful content; context-awareness; consistent human engagement; provision of rationale; use of elementary concepts to teach and learn new concepts; and successful collaboration. We present examples of how we used these Hallmarks in the DARPA Communicating with Computers (CwC) program to evaluate diverse activities, including story and music generation, interactive building with blocks, and exploration of molecular mechanisms in cancer. We used the Hallmarks as guides for developers and as diagnostics, assessing systems with the Hallmarks to identify strengths and opportunities for improvement using logs from user studies, surveying the human partner, third-party review of creative products, and direct tests. Informal feedback from CwC technology developers indicates that the use of the Hallmarks for program evaluation helped guide development. The Hallmarks also made it possible to identify areas of progress and major gaps in developing systems where the machine is an equal, creative partner.

Autologous Stem Cell Transplantation in the Treatment of Pulmonary Light Chain Deposition Disease.

Light chain deposition disease is a rare condition that results in the deposition of light chains in organs and their subsequent dysfunction. It is often the consequence of unchecked light chain production by a plasma cell clone. Rarely does it manifest with solely pulmonary involvement, especially in the young otherwise healthy patient. This article highlights the presentation and diagnosis of pulmonary light chain deposition disease in an active duty solider, the discovery of a plasma cell clone responsible for his symptoms, and the therapy targeted at the plasma cell clone-inducing pulmonary disease. This therapy included a novel successful treatment with an autologous stem cell transplantation. To date, it is among the first such documented successful bone marrow transplantations in treatment of isolated pulmonary light chain deposition disease.

Automatic Segmentation of Kidneys and Kidney Tumors: The KiTS19 International Challenge.

Purpose: Clinicians rely on imaging features to calculate complexity of renal masses based on validated scoring systems. These scoring methods are labor-intensive and are subjected to interobserver variability. Artificial intelligence has been increasingly utilized by the medical community to solve such issues. However, developing reliable algorithms is usually time-consuming and costly. We created an international community-driven competition (KiTS19) to develop and identify the best system for automatic segmentation of kidneys and kidney tumors in contrast CT and report the results. Methods: A training and test set of CT scans that was manually annotated by trained individuals were generated from consecutive patients undergoing renal surgery for whom demographic, clinical and outcome data were available. The KiTS19 Challenge was a machine learning competition hosted on grand-challenge.org in conjunction with an international conference. Teams were given 3 months to develop their algorithm using a full-annotated training set of images and an unannotated test set was released for 2 weeks from which average Sørensen-Dice coefficient between kidney and tumor regions were calculated across all 90 test cases. Results: There were 100 valid submissions that were based on deep neural networks but there were differences in pre-processing strategies, architectural details, and training procedures. The winning team scored a 0.974 kidney Dice and a 0.851 tumor Dice resulting in 0.912 composite score. Automatic segmentation of the kidney by the participating teams performed comparably to expert manual segmentation but was less reliable when segmenting the tumor. Conclusion: Rapid advancement in automated semantic segmentation of kidney lesions is possible with relatively high accuracy when the data is released publicly, and participation is incentivized. We hope that our findings will encourage further research that would enable the potential of adopting AI into the medical field.

The state of the art in kidney and kidney tumor segmentation in contrast-enhanced CT imaging: Results of the KiTS19 challenge.

There is a large body of literature linking anatomic and geometric characteristics of kidney tumors to perioperative and oncologic outcomes. Semantic segmentation of these tumors and their host kidneys is a promising tool for quantitatively characterizing these lesions, but its adoption is limited due to the manual effort required to produce high-quality 3D segmentations of these structures. Recently, methods based on deep learning have shown excellent results in automatic 3D segmentation, but they require large datasets for training, and there remains little consensus on which methods perform best. The 2019 Kidney and Kidney Tumor Segmentation challenge (KiTS19) was a competition held in conjunction with the 2019 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) which sought to address these issues and stimulate progress on this automatic segmentation problem. A training set of 210 cross sectional CT images with kidney tumors was publicly released with corresponding semantic segmentation masks. 106 teams from five continents used this data to develop automated systems to predict the true segmentation masks on a test set of 90 CT images for which the corresponding ground truth segmentations were kept private. These predictions were scored and ranked according to their average Sørensen-Dice coefficient between the kidney and tumor across all 90 cases. The winning team achieved a Dice of 0.974 for kidney and 0.851 for tumor, approaching the inter-annotator performance on kidney (0.983) but falling short on tumor (0.923). This challenge has now entered an "open leaderboard" phase where it serves as a challenging benchmark in 3D semantic segmentation.

TXA (Tranexamic Acid) Risk Evaluation in Combat Casualties (TRECC).

BACKGROUND: The use of tranexamic acid (TXA) has become increasingly prevalent for hemorrhage prevention in military trauma patients due to its known survival benefits. There is concern of increased venous thromboembolism (VTE) subsequent to receiving TXA. The purpose of this retrospective study was to determine the rate of VTE in severely injured military personnel during Operation Enduring Freedom (2009-2014). METHODS: An analysis of 859 military trauma patients from the 2009-2014 Department of Defense Trauma Registry included subjects with an injury severity score (ISS) >10 and a massive transfusion (MT) (>10 units of blood products in the first 24 hours). Outcomes included a documented VTE (eg, deep vein thrombosis (DVT) or pulmonary embolism (PE)) during the patient's hospital course. Comparison between those who did/did not receive TXA was analyzed using three separate multiple regression analyses using listwise deletion, systematic replacement and multiple imputation. RESULTS: Subjects (n=620) met inclusion criteria with 27% (n=169) having a documented VTE. A total of 30% that received TXA had a documented VTE, 26% that did not receive TXA had a documented VTE and 43% (n=264, n=620) of the sample did not have TXA documented as either given or not given. Multiple regression analyses using listwise deletion and systematic replacement of the TXA variable demonstrated no difference in odds of VTE, whereas the multiple imputation analysis demonstrated a 3% increased odds of VTE, a9.4% increased odds of PE and 8.1% decreased odds of DVT with TXA administration. DISCUSSION: TXA use with an ISS >10 and MT resuscitation had a 3% increased odds of VTE and an increased odds of PE, whereas the odds of DVT were found to be decreased after multiple imputation analysis. Further research on the long-term risks and benefits of TXA usage in the military population is recommended. LEVEL OF EVIDENCE: IV-therapeutic.

Salvage extracorporeal membrane oxygenation in induction-associated acute respiratory distress syndrome in acute leukemia patients: A case series.

BACKGROUND:: The prognosis of hematologic malignancies has improved over the past three decades. However, the prognosis in hematologic malignancies with severe acute respiratory distress syndrome has remained poor. Initial reports regarding the utility of extracorporeal membrane oxygenation in hematologic malignancies have been controversial, with limited evaluations of acute leukemia patients supported by extracorporeal membrane oxygenation. METHODS:: We conducted a retrospective review of patients with acute leukemia who developed acute respiratory distress syndrome requiring veno-venous extracorporeal membrane oxygenation support at our facility from July 2015 through August 2017. RESULTS:: Four cases of acute myelogenous leukemia with respiratory failure and acute respiratory distress syndrome treated with veno-venous extracorporeal membrane oxygenation while undergoing induction chemotherapy were identified. All patients completed induction therapy with addition of extracorporeal membrane oxygenation support, with two patients dying secondary to their acute leukemia and the other two surviving to allogeneic hematopoietic stem cell transplant. Overall, 75% (three of four) survived to decannulation with a 1-year survival rate following extracorporeal membrane oxygenation of 50% (two of four). CONCLUSION:: Currently, the use of extracorporeal membrane oxygenation in patients with hematologic malignancies who develop severe acute respiratory distress syndrome remains controversial. Although extracorporeal membrane oxygenation in post-allogeneic hematopoietic stem cell transplant is associated with poorer outcomes, our data suggest that salvage extracorporeal membrane oxygenation support is a viable option to manage moderate to severe acute respiratory distress syndrome while completing therapeutic chemotherapy and following in the peri-induction phase of acute leukemia.

CARD9 as a potential target in cardiovascular disease.

Systemic inflammation and localized macrophage infiltration have been implicated in cardiovascular pathologies, including coronary artery disease, carotid atherosclerosis, heart failure, obesity-associated heart dysfunction, and cardiac fibrosis. Inflammation induces macrophage infiltration and activation and release of cytokines and chemokines, causing tissue dysfunction by instigating a positive feedback loop that further propagates inflammation. Cytosolic adaptor caspase recruitment domain family, member 9 (CARD9) is a protein expressed primarily by dendritic cells, neutrophils, and macrophages, in which it mediates cytokine secretion. The purpose of this review is to highlight the role of CARD9 as a potential target in inflammation-related cardiovascular pathologies.

Nanomedicines: From Bench to Bedside and Beyond.

Advancing nanomedicines from concept to clinic requires integration of new science with traditional pharmaceutical development. The medical and commercial success of nanomedicines is greatly facilitated when those charged with developing nanomedicines are cognizant of the unique opportunities and technical challenges that these products present. These individuals must also be knowledgeable about the processes of clinical and product development, including regulatory considerations, to maximize the odds for successful product registration. This article outlines these topics with a goal to accelerate the combination of academic innovation with collaborative industrial scientists who understand pharmaceutical development and regulatory approval requirements-only together can they realize the full potential of nanomedicines for patients.

Comprehensive Definition of the SigH Regulon of Mycobacterium tuberculosis Reveals Transcriptional Control of Diverse Stress Responses.

Expression of SigH, one of 12 Mycobacterium tuberculosis alternative sigma factors, is induced by heat, oxidative and nitric oxide stresses. SigH activation has been shown to increase expression of several genes, including genes involved in maintaining redox equilibrium and in protein degradation. However, few of these are known to be directly regulated by SigH. The goal of this project is to comprehensively define the Mycobacterium tuberculosis genes and operons that are directly controlled by SigH in order to gain insight into the role of SigH in regulating M. tuberculosis physiology. We used ChIP-Seq to identify in vivo SigH binding sites throughout the M. tuberculosis genome, followed by quantification of SigH-dependent expression of genes linked to these sites and identification of SigH-regulated promoters. We identified 69 SigH binding sites, which are located both in intergenic regions and within annotated coding sequences in the annotated M. tuberculosis genome. 41 binding sites were linked to genes that showed greater expression following heat stress in a SigH-dependent manner. We identified several genes not previously known to be regulated by SigH, including genes involved in DNA repair, cysteine biosynthesis, translation, and genes of unknown function. Experimental and computational analysis of SigH-regulated promoter sequences within these binding sites identified strong consensus -35 and -10 promoter sequences, but with tolerance for non-consensus bases at specific positions. This comprehensive identification and validation of SigH-regulated genes demonstrates an extended SigH regulon that controls an unexpectedly broad range of stress response functions.

Characterization of a cAMP responsive transcription factor, Cmr (Rv1675c), in TB complex mycobacteria reveals overlap with the DosR (DevR) dormancy regulon.

Mycobacterium tuberculosis (Mtb) Cmr (Rv1675c) is a CRP/FNR family transcription factor known to be responsive to cAMP levels and during macrophage infections. However, Cmr's DNA binding properties, cellular targets and overall role in tuberculosis (TB) complex bacteria have not been characterized. In this study, we used experimental and computational approaches to characterize Cmr's DNA binding properties and identify a putative regulon. Cmr binds a 16-bp palindromic site that includes four highly conserved nucleotides that are required for DNA binding. A total of 368 binding sites, distributed in clusters among ~200 binding regions throughout the Mycobacterium bovis BCG genome, were identified using ChIP-seq. One of the most enriched Cmr binding sites was located upstream of the cmr promoter, and we demonstrated that expression of cmr is autoregulated. cAMP affected Cmr binding at a subset of DNA loci in vivo and in vitro, including multiple sites adjacent to members of the DosR (DevR) dormancy regulon. Our findings of cooperative binding of Cmr to these DNA regions and the regulation by Cmr of the DosR-regulated virulence gene Rv2623 demonstrate the complexity of Cmr-mediated gene regulation and suggest a role for Cmr in the biology of persistent TB infection.

A Novel Analytic Technique to Measure Associations Between Circulating Biomarkers and Physical Performance Across the Adult Life Span.

Understanding associations between circulating biomarkers and physical performance across the adult life span could aid in better describing mechanistic pathways leading to disability. We hypothesized that high concentrations of circulating biomarkers would be associated with lower functioning across study populations representing the adult life span. The data were from four intervention and two observational studies with ages ranging 22-89 years. Biomarkers assayed included inflammatory, coagulation, and endothelial function markers. Physical performance was measured either by VO2peak (studies of young and middle-aged adults) or usual gait speed (studies of older adults). Partialled (by age, body mass index, race, and sex) and weighted common correlations were calculated between biomarkers and physical performance. Homogeneity of the associations was also assessed. Interleukin-6 (weighted r = -.22), tumor necrosis factor receptor 2 (weighted r = -.19), D-dimer (weighted r = -.16), tumor necrosis factor receptor 1 (weighted r = -.15), granulocyte colony-stimulating factor (weighted r = -.14), and tumor necrosis factor alpha (weighted r = -.10) were all significantly inversely correlated with physical performance (p < .05). All significant correlations were homogeneous across studies. In summary, we observed consistent inverse associations between six circulating biomarkers and objective measures of physical performance. These results suggest that these serum biomarkers may be broadly applicable for detection, trajectory, and treatment monitoring of physical function across the life span or possibly for midlife predictors of functionally deleterious conditions.

Role of intragenic binding of cAMP responsive protein (CRP) in regulation of the succinate dehydrogenase genes Rv0249c-Rv0247c in TB complex mycobacteria.

Bacterial pathogens adapt to changing environments within their hosts, and the signaling molecule adenosine 3', 5'-cyclic monophosphate (cAMP) facilitates this process. In this study, we characterized in vivo DNA binding and gene regulation by the cAMP-responsive protein CRP in M. bovis BCG as a model for tuberculosis (TB)-complex bacteria. Chromatin immunoprecipitation followed by deep-sequencing (ChIP-seq) showed that CRP associates with ∼900 DNA binding regions, most of which occur within genes. The most highly enriched binding region was upstream of a putative copper transporter gene (ctpB), and crp-deleted bacteria showed increased sensitivity to copper toxicity. Detailed mutational analysis of four CRP binding sites upstream of the virulence-associated Rv0249c-Rv0247c succinate dehydrogenase genes demonstrated that CRP directly regulates Rv0249c-Rv0247c expression from two promoters, one of which requires sequences intragenic to Rv0250c for maximum expression. The high percentage of intragenic CRP binding sites and our demonstration that these intragenic DNA sequences significantly contribute to biologically relevant gene expression greatly expand the genome space that must be considered for gene regulatory analyses in mycobacteria. These findings also have practical implications for an important bacterial pathogen in which identification of mutations that affect expression of drug target-related genes is widely used for rapid drug resistance screening.

Discovery of AMG 232, a potent, selective, and orally bioavailable MDM2-p53 inhibitor in clinical development.

We recently reported the discovery of AM-8553 (1), a potent and selective piperidinone inhibitor of the MDM2-p53 interaction. Continued research investigation of the N-alkyl substituent of this series, focused in particular on a previously underutilized interaction in a shallow cleft on the MDM2 surface, led to the discovery of a one-carbon tethered sulfone which gave rise to substantial improvements in biochemical and cellular potency. Further investigation produced AMG 232 (2), which is currently being evaluated in human clinical trials for the treatment of cancer. Compound 2 is an extremely potent MDM2 inhibitor (SPR KD = 0.045 nM, SJSA-1 EdU IC50 = 9.1 nM), with remarkable pharmacokinetic properties and in vivo antitumor activity in the SJSA-1 osteosarcoma xenograft model (ED50 = 9.1 mg/kg).

Rotational flap closure of first and fifth metatarsal head plantar ulcers: adjunctive procedure when performing first or fifth ray amputation.

Partial ray amputation is a common treatment of diabetes-related neuropathic ulcers located beneath the metatarsal heads. The standard incision for partial first or fifth ray amputation involves a tennis racket incision, with the proximal arm made mid-line along the respective medial or lateral side of the metatarsal head and neck, creating equal dorsal and plantar flaps. This incision works well when the ulcer is located within the excised soft tissue distal to the incision or when the plantar ulcer is superficial and will heal secondarily once the underlying bone has been removed. This standard first or fifth ray amputation incision does not, however, allow excision and closure of plantar ulcers located beneath the first or fifth metatarsal head. Two cases are presented to demonstrate our surgical protocol for partial first or fifth ray amputation using a local rotational flap to cover plantar metatarsal head ulcers. These cases highlight our patient selection criteria, staging protocol when cellulitis or abscess is present, rotational flap design, surgical technique pearls, and the typical postoperative healing progress.

Pathophysiology of primary spinal syringomyelia.

OBJECT: The pathogenesis of syringomyelia in patients with an associated spinal lesion is incompletely understood. The authors hypothesized that in primary spinal syringomyelia, a subarachnoid block effectively shortens the length of the spinal subarachnoid space (SAS), reducing compliance and the ability of the spinal theca to dampen the subarachnoid CSF pressure waves produced by brain expansion during cardiac systole. This creates exaggerated spinal subarachnoid pressure waves during every heartbeat that act on the spinal cord above the block to drive CSF into the spinal cord and create a syrinx. After a syrinx is formed, enlarged subarachnoid pressure waves compress the external surface of the spinal cord, propel the syrinx fluid, and promote syrinx progression. METHODS: To elucidate the pathophysiology, the authors prospectively studied 36 adult patients with spinal lesions obstructing the spinal SAS. Testing before surgery included clinical examination; evaluation of anatomy on T1-weighted MRI; measurement of lumbar and cervical subarachnoid mean and pulse pressures at rest, during Valsalva maneuver, during jugular compression, and after removal of CSF (CSF compliance measurement); and evaluation with CT myelography. During surgery, pressure measurements from the SAS above the level of the lesion and the lumbar intrathecal space below the lesion were obtained, and cardiac-gated ultrasonography was performed. One week after surgery, CT myelography was repeated. Three months after surgery, clinical examination, T1-weighted MRI, and CSF pressure recordings (cervical and lumbar) were repeated. Clinical examination and MRI studies were repeated annually thereafter. Findings in patients were compared with those obtained in a group of 18 healthy individuals who had already undergone T1-weighted MRI, cine MRI, and cervical and lumbar subarachnoid pressure testing. RESULTS: In syringomyelia patients compared with healthy volunteers, cervical subarachnoid pulse pressure was increased (2.7 ± 1.2 vs 1.6 ± 0.6 mm Hg, respectively; p = 0.004), pressure transmission to the thecal sac below the block was reduced, and spinal CSF compliance was decreased. Intraoperative ultrasonography confirmed that pulse pressure waves compressed the outer surface of the spinal cord superior to regions of obstruction of the subarachnoid space. CONCLUSIONS: These findings are consistent with the theory that a spinal subarachnoid block increases spinal subarachnoid pulse pressure above the block, producing a pressure differential across the obstructed segment of the SAS, which results in syrinx formation and progression. These findings are similar to the results of the authors' previous studies that examined the pathophysiology of syringomyelia associated with obstruction of the SAS at the foramen magnum in the Chiari Type I malformation and indicate that a common mechanism, rather than different, separate mechanisms, underlies syrinx formation in these two entities. Clinical trial registration no.: NCT00011245.

The Keck and Kelly wedge calcaneal osteotomy for Haglund's deformity: a technique for reproducible results.

Surgical treatment of Haglund's deformity typically involves either bump removal or a closing wedge calcaneal osteotomy. Although bump removal may initially seem easier to perform and quicker to heal, there are advantages to avoiding bone resection adjacent to the Achilles tendon. Healing of the wedge osteotomy can be faster and more predicable than tendon healing at the Achilles insertion, which is beneficial to the young and active population that tends to have this condition. This article describes a reproducible Keck and Kelly closing wedge osteotomy technique that effectively decompresses the posterior/superior aspect of the calcaneus without need for dissection around the Achilles insertion. Our technique allows for consistent correction of Haglund's deformity, reliable symptom relief, and minimal opportunity for intraoperative or postoperative complications. Technique pearls include patient selection criteria for bump removal versus wedge osteotomy and a preoperative template protocol.