The Effect of the COVID Pandemic on the Rate of Same-Day Discharge in Primary Hip and Knee Arthroplasty.

INTRODUCTION: Same-day discharge (SDD) following primary total hip (THA) and total knee (TKA) arthroplasty started increasing prior to 2020. The purpose of this study was to evaluate the change in the rate of SDD after the pandemic and determine whether those changes became permanent. METHODS: The annual rate of SDD for 15,208 primary THA and TKA cases performed between January 1, 2015, and September 9, 2022, at a single institution was determined. We also examined changes in SDD patient demographics as well as differences in the 90-day complication rates of SDD and overnight patients. RESULTS: In 2015, the rate of SDD for primary arthroplasty was 24%, which grew annually to 29% in 2019. Post-pandemic, the rate of SDD jumped above 50% and continued up to 64% by 2022. The biggest increase was in TKA, which went from under 10% SDD pre-pandemic to 50% by 2022. The average age and BMI of SDD cases pre-pandemic increased significantly to 62 ± 9 years and 29.4 ± 5.3 (P < 0.01). Overnight patients had higher rates of 90-day postoperative complications (8.4 versus 4.2%, P < 0.00001). DISCUSSION: The pandemic caused major changes in the rate of SDD for primary THA and TKA, increasing in subsequent years. The SDD patients became older and heavier due to the expanded criteria for SDD cases. The 90-day postoperative complication rate was lower for SDD patients since higher risk patients were kept overnight. At the pre-pandemic rate, 29% of patients currently being sent home would have stayed overnight.

Identifying tumor type and cell type-specific gene expression alterations in pediatric central nervous system tumors.

Central nervous system (CNS) tumors are the leading cause of pediatric cancer death, and these patients have an increased risk for developing secondary neoplasms. Due to the low prevalence of pediatric CNS tumors, major advances in targeted therapies have been lagging compared to other adult tumors. We collect single nuclei RNA-seq data from 84,700 nuclei of 35 pediatric CNS tumors and three non-tumoral pediatric brain tissues and characterize tumor heterogeneity and transcriptomic alterations. We distinguish cell subpopulations associated with specific tumor types including radial glial cells in ependymomas and oligodendrocyte precursor cells in astrocytomas. In tumors, we observe pathways important in neural stem cell-like populations, a cell type previously associated with therapy resistance. Lastly, we identify transcriptomic alterations among pediatric CNS tumor types compared to non-tumor tissues, while accounting for cell type effects on gene expression. Our results suggest potential tumor type and cell type-specific targets for pediatric CNS tumor treatment. Here we address current gaps in understanding single nuclei gene expression profiles of previously under-investigated tumor types and enhance current knowledge of gene expression profiles of single cells of various pediatric CNS tumors.

OpenPBTA: The Open Pediatric Brain Tumor Atlas.

Pediatric brain and spinal cancers are collectively the leading disease-related cause of death in children; thus, we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, the Children's Brain Tumor Network (CBTN) and Pacific Pediatric Neuro-Oncology Consortium (PNOC) created a systematic process for tumor biobanking, model generation, and sequencing with immediate access to harmonized data. We leverage these data to establish OpenPBTA, an open collaborative project with over 40 scalable analysis modules that genomically characterize 1,074 pediatric brain tumors. Transcriptomic classification reveals universal TP53 dysregulation in mismatch repair-deficient hypermutant high-grade gliomas and TP53 loss as a significant marker for poor overall survival in ependymomas and H3 K28-mutant diffuse midline gliomas. Already being actively applied to other pediatric cancers and PNOC molecular tumor board decision-making, OpenPBTA is an invaluable resource to the pediatric oncology community.

Tumor type and cell type-specific gene expression alterations in diverse pediatric central nervous system tumors identified using single nuclei RNA-seq.

Central nervous system (CNS) tumors are the leading cause of pediatric cancer death, and these patients have an increased risk for developing secondary neoplasms. Due to the low prevalence of pediatric CNS tumors, major advances in targeted therapies have been lagging compared to other adult tumors. We collected single nuclei RNA-seq data from 35 pediatric CNS tumors and three non-tumoral pediatric brain tissues (84,700 nuclei) and characterized tumor heterogeneity and transcriptomic alterations. We distinguished cell subpopulations associated with specific tumor types including radial glial cells in ependymomas and oligodendrocyte precursor cells in astrocytomas. In tumors, we observed pathways important in neural stem cell-like populations, a cell type previously associated with therapy resistance. Lastly, we identified transcriptomic alterations among pediatric CNS tumor types compared to non-tumor tissues, while accounting for cell type effects on gene expression. Our results suggest potential tumor type and cell type-specific targets for pediatric CNS tumor treatment. In this study, we address current gaps in understanding single nuclei gene expression profiles of previously uninvestigated tumor types and enhance current knowledge of gene expression profiles of single cells of various pediatric CNS tumors.

Bicondylar Tibial Plateau Fractures: What Predicts Infection?

OBJECTIVES: The purpose of this study was to identify the patient, injury, and treatment factors associated with infection of bicondylar plateau fractures and to evaluate whether center variation exists. DESIGN: Retrospective review. SETTING: Eighteen academic trauma centers. PATIENTS/PARTICIPANTS: A total of 1,287 patients with 1,297 OTA type 41-C bicondylar tibia plateau fractures who underwent open reduction and internal fixation were included. Exclusion criteria were follow-up less than 120 days, insufficient documentation, and definitive treatment only with external fixation. INTERVENTION: Open reduction and internal fixation. MAIN OUTCOME MEASUREMENTS: Superficial and deep infection. RESULTS: One hundred one patients (7.8%) developed an infection. In multivariate regression analysis, diabetes (DM) (OR [odds ratio] 3.24; P ≤ 0.001), alcohol abuse (EtOH) (OR 1.8; P = 0.040), dual plating (OR 1.8; P ≤ 0.001), and temporary external fixation (OR 2.07; P = 0.013) were associated with infection. In a risk-adjusted model, we found center variation in infection rates (P = 0.030). DISCUSSION: In a large series of patients undergoing open reduction and internal fixation of bicondylar plateau fractures, the infection rate was 7.8%. Infection was associated with DM, EtOH, combined dual plating, and temporary external fixation. Center expertise may also play a role because one center had a statistically lower rate and two trended toward higher rates after adjusting for confounders. LEVEL OF EVIDENCE: Level IV-Therapeutic retrospective cohort study.

Serology and Comorbidities in Patients With Fracture Nonunion: A Multicenter Evaluation of 640 Patients.

INTRODUCTION: This multicenter cohort study investigated the association of serology and comorbid conditions with septic and aseptic nonunion. METHODS: From January 1, 2011, to December 31, 2017, consecutive individuals surgically treated for nonunion were identified from seven centers. Nonunion-type, comorbid conditions and serology were assessed. RESULTS: A total of 640 individuals were included. 57% were male with a mean age of 49 years. Nonunion sites included tibia (35.2%), femur (25.6%), humerus (20.3%), and other less frequent bones (18.9%). The type of nonunion included septic (17.7%) and aseptic (82.3%). Within aseptic, nonvascular (86.5%) and vascular (13.5%) nonunion were seen. Rates of smoking, alcohol abuse, and diabetes mellitus were higher in our nonunion cohort compared with population norms. Coronary artery disease and tobacco use were associated with septic nonunion (P < 0.05). Diphosphonates were associated with vascular nonunion (P < 0.05). Serologically, increased erythrocyte sedimentation rate, C-reactive protein, parathyroid hormone, red cell distribution width, mean platelet volume (MPV), and platelets and decreased absolute lymphocyte count, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and albumin were associated with septic nonunion while lower calcium was associated with nonvascular nonunion (P < 0.05). The presence of four or more of increased erythrocyte sedimentation rate, C-reactive protein, or red cell distribution width; decreased albumin; and age younger than 65 years carried an 89% positive predictive value for infection. Hypovitaminosis D was seen less frequently than reported in the general population, whereas anemia was more common. However, aside from hematologic and inflammatory indices, no other serology was abnormal more than 25% of the time. DISCUSSION: Abnormal serology and comorbid conditions, including smoking, alcohol abuse, and diabetes mellitus, are seen in nonunion; however, serologic abnormalities may be less common than previously thought. Septic nonunion is associated with inflammation, younger age, and malnourishment. Based on the observed frequency of abnormality, routine laboratory work is not recommended for nonunion assessment; however, specific focused serology may help determine the presence of septic nonunion.

Pelvic Fracture Urethral Distraction Defect.

Posterior pelvic fracture urethral distraction defects (PFUDD) can present formidable challenges in genitourinary reconstruction. Once the acuity of trauma subsides, the patient is often faced with chronic, debilitating genitourinary injuries. Treatment requires an astute diagnostic and technical approach, with definitive repair best accomplished in the hands of experts. A delayed, stepwise approach to repair following the resolution of acute injuries remains a time-tested platform for optimal outcomes. The evaluation, relevant anatomy, and approach to surgical repair are described herein.

Risk of Acute Kidney Injury After Hypertensive Disorders of Pregnancy: A Population-Based Cohort Study.

RATIONALE & OBJECTIVE: Even though studies have demonstrated a relationship between hypertensive disorders of pregnancy (HDPs) and chronic kidney disease, there are limited data on the risk of acute kidney injury (AKI) following HDPs. We examined the risk of AKI following the occurrence of HDPs. STUDY DESIGN: Retrospective population-based cohort study. SETTING & PARTICIPANTS: Pregnant women in Ontario, Canada, aged 14-50 years, who delivered at ≥20 weeks' gestation between April 1, 2002, and March 31, 2015. EXPOSURE: Preeclampsia, gestational hypertension, or neither. OUTCOMES: The primary outcome was AKI with receipt of dialysis (AKI-D) ≥90 days after delivery. The main secondary outcome was AKI based on a hospitalization with a diagnostic code for AKI ≥90 days after delivery. ANALYTICAL APPROACH: Time-dependent Cox proportional and cause-specific hazards models were used to evaluate the relationship between HDP and outcomes of interest. Models were adjusted for baseline and time-varying covariates. RESULTS: Our cohort comprised 1,142,656 women and 1,826,235 deliveries, of which 1.7% were associated with gestational hypertension and 4.4% with preeclampsia. After a mean follow-up of 6.7 years, there were 322 episodes of AKI-D (0.41 per 10,000 person-years) and 1,598 episodes of AKI based on diagnostic codes (2.04 per 10,000 person-years). After adjustment, neither preeclampsia nor gestational hypertension was associated with AKI-D. Preeclampsia was associated with AKI (HR, 1.22 [95% CI, 1.03-1.45]), but gestational hypertension was not. LIMITATIONS: Retrospective design and possible unmeasured confounding. Cases of HDPs and AKI may have been undetected. CONCLUSIONS: Preeclampsia was a risk factor for AKI occurring ≥90 days after delivery. Our findings suggest the potential importance of obtaining a pregnancy history as part of a comprehensive risk profile for acute kidney disease and suggest that women with a history of HDP may benefit from monitoring of kidney function.

Pseudo Hyperaldosteronism Secondary to Herbal Medicine Use.

Glycyrrhizic acid, better known as licorice, is commonly found in various food and cosmetic products. Excessive consumption is known to cause a syndrome of apparent mineralocorticoid excess or pseudo hyperaldosteronism. Patients typically present with resistant hypertension and hypokalemia mimicking symptoms of primary hyperaldosteronism however laboratory workup will reveal low or normal levels of plasma renin and aldosterone in the serum. While diagnosis of licorice toxicity is relatively straight forward, the challenge lies in determining the culpable agent. We report the case of a Chinese man who initially presented with resistant hypertension and hypokalemia refractory to therapy and was later diagnosed with pseudo hyperaldosteronism secondary to licorice toxicity.

Macrophages in SHH subgroup medulloblastoma display dynamic heterogeneity that varies with treatment modality.

Tumor-associated macrophages (TAMs) play an important role in tumor immunity and comprise of subsets that have distinct phenotype, function, and ontology. Transcriptomic analyses of human medulloblastoma, the most common malignant pediatric brain cancer, showed that medulloblastomas (MBs) with activated sonic hedgehog signaling (SHH-MB) have significantly more TAMs than other MB subtypes. Therefore, we examined MB-associated TAMs by single-cell RNA sequencing of autochthonous murine SHH-MB at steady state and under two distinct treatment modalities: molecular-targeted inhibitor and radiation. Our analyses reveal significant TAM heterogeneity, identify markers of ontologically distinct TAM subsets, and show the impact of brain microenvironment on the differentiation of tumor-infiltrating monocytes. TAM composition undergoes dramatic changes with treatment and differs significantly between molecular-targeted and radiation therapy. We identify an immunosuppressive monocyte-derived TAM subset that emerges with radiation therapy and demonstrate its role in regulating T cell and neutrophil infiltration in MB.

Reducing Opioid Prescriptions Lowers Consumption Without Detriment to Patient-Reported Pain Interference Scores After Total Hip and Knee Arthroplasties.

BACKGROUND: Opioid addiction is endemic in the United States. We developed a standardized opioid-prescribing schedule (SOPS) after total hip arthroplasty (THA) and total knee arthroplasty (TKA) and evaluated opioid usage alongside Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference scores. We hypothesized that opioid usage would be less than prescribed and reducing prescription would decrease consumption without negatively impacting the PROMIS scores. METHODS: A prospective observational study was performed on all patients undergoing primary THA and TKA from April 7, 2018, to August 10, 2019. Opioid consumption and pain interference were determined 2 weeks after discharge via telephone and email surveys. SOPSs were implemented during the study. Outcomes were compared in patients before and after the SOPS. RESULTS: A total of 715 patients met inclusion criteria; 201 patients completed surveys. Before the SOPS, the mean opioid prescription was 81.2 ± 15.3 tablets for THA and 82.9 ± 10.6 for TKA. The mean usage was 35.1 ± 29.4 tablets and 35.4 ± 33.4, respectively. After the SOPS, the mean usage decreased to 19.4 ± 16.8 (P = .04) and 31.6 ± 20.9 (P = .52), respectively. After implementation of a second SOPS for THA, the mean number of tablets consumed was 21.5 ± 18.6 (P = .05 compared with pre-SOPS). The PROMIS 6B responses in patients who underwent THA demonstrated no significant changes. PROMIS 6B responses for TKA showed an increase in interference with recreational activities (P = .04) and tasks away from home (P = .04), but otherwise had no significant impact on reported scores. CONCLUSIONS: Implementation of the SOPS reduced postoperative opioid prescription and consumption without significantly impacting the reported pain interference, supporting the need to decrease opioid prescription after THA and TKA.

Analysis of Risks and Consequences of Postcatheter Urinary Retention After Primary Total Hip and Knee Arthroplasty.

BACKGROUND: Postoperative urinary retention (POUR) in total joint arthroplasty (TJA) is common. However, risk factors for POUR and its consequences, specifically on postoperative renal function, have not been well defined. METHODS: We performed a review of prospectively collected data on consecutive adult patients undergoing primary total joint arthroplasty from August 2014 to December 2015. Catheters were placed preoperatively and removed on the first or second postoperative day. The exclusion criterion was traumatic catheter insertion or the presence of fracture or neoplasm. Univariate and multiple logistic regression identified associations with POUR and its invasive therapies. Subgroup analysis of renal function by incidence of preoperative bladder outlet obstruction (BOO) and POUR was performed with nonparametric testing. RESULTS: A total of 591 operations met inclusion criteria. The incidence of POUR was 6.4% and was directly related to a positive history of BOO (odds ratio [OR]: 4.15) and increased the duration of urinary catheterization (OR: 1.04). These factors, in addition to preoperative incontinence (OR: 8.36, 28.69) and lengthier hospitalizations (OR: 1.37, 1.30), were significantly associated with intermittent straight catheterization and reinsertion of an indwelling catheter to treat POUR. Serum creatinine increased with combined preoperative BOO and POUR (+0.22 mg/dL) but was preserved in others (+0.02-0.04 mg/dL) (P < 0.01). CONCLUSIONS: Preoperative BOO and longer catheterization increased the risk of POUR and were associated with the use of invasive modalities to treat POUR. POUR was associated with a longer hospitalization and impaired renal function in those with preoperative BOO; therefore, renal function should be monitored closely and nephrotoxic medications used cautiously when using urinary catheters in this patient population. LEVEL OF EVIDENCE: Retrospective Analysis, Level IV.

An Evidence-Based Algorithm for Determining Venous Thromboembolism Prophylaxis After Degenerative Spinal Surgery.

BACKGROUND: Although venous thromboembolism (VTE) is a potentially serious and life-threatening complication, there is no widely accepted protocol to guide VTE prophylaxis in adult degenerative spinal surgery, and pharmacologic overtreatment may result in hemorrhagic complications. Previously, we published the VTE Prophylaxis Risk/Benefit Score, an evidence-based algorithm that balances the risk and consequences of thrombotic versus hemorrhagic complications by taking consideration of patient-related risks, procedure-related risks, and the risk of neurological compromise to guide VTE prophylaxis. To objective of this study was to validate the VTE Prophylaxis Risk/Benefit Score. METHODS: From January 1, 2016, to December 31, 2017, VTE Prophylaxis Risk/Benefit Scores and corresponding prophylaxes were prospectively assigned. When indicated, chemoprophylaxis was dosed 24 to 36 hours postoperatively to allow for adequate surgical hemostasis. Patients were retrospectively evaluated for immediate and short-term complications. The Fisher exact test compared incidence of complications by VTE prophylaxis. Multinomial logistic regression modeled the probability of complication by prophylaxis type, demographics, and comorbidities. Significance was set at P < .05. RESULTS: Of the 266 patients who met inclusion criteria, 79.3% were given mechanical prophylaxis alone and 20.7% were given combined mechanical and chemical prophylaxis. Complications including VTE (0.38%), delayed wound healing or infection (2.26%), and hematoma (0.75%) were observed at rates similar to or lower than previously published studies with increased utilization of chemoprophylaxis. Use of chemoprophylaxis and continuation of perioperative aspirin were significantly associated with the development of a hemorrhagic complication. No patient developed persistent neurologic deficit from hematoma or pulmonary embolism. CONCLUSIONS: The VTE Prophylaxis Risk/Benefit Score comprehensively considers the risk of thrombotic, wound, and bleeding complications and is an effective tool for determining appropriate thromboprophylaxis in adult degenerative spinal surgery. LEVEL OF EVIDENCE: 3.

A Biomechanical Comparison of Modified Radioscapholunate Fusion Constructs for Radiocarpal Arthritis.

PURPOSE: This biomechanical study compared fixation constructs used in radioscapholunate (RSL) arthrodesis. We hypothesized that plates and screws, pin plate, and headless screws would all provide similarly stable fixation constructs. METHODS: We chose 27 fresh-frozen cadaveric extremities, 14 of which were matched pairs and randomized them into 3 groups to match age, body mass index, and sex. An RSL arthrodesis was simulated with plates and screws, pin plates, or headless compression screws via a standard dorsal approach to the wrist. Specimens were mounted into a custom jig and cycled through an arc of 120° for 5,000 cycles to simulate 6 weeks range of motion (ROM). A 9-mm stroke differential variable reluctance transducer recorded continuous displacement, and gross hardware failure in the form of screw or pin cutout was investigated after the simulation. RESULTS: Greater distraction across the RSL articulation was observed in the headless screws compared with the plate-and-screws and pin-plate constructs, with no difference between the plates and screws and pin plates. Greater average displacement was observed in the headless screws compared with the plate-and-screws and pin-plate constructs, with no difference between the pin plates and plates and screws. Gross hardware failure was observed least in plates and screws followed by pin plates. CONCLUSIONS: Plate-and-screw and pin-plate constructs are biomechanically superior in resisting RSL distraction compared with headless compression screws for RSL arthrodesis over 6 weeks of simulated ROM in the absence of healing. CLINICAL RELEVANCE: The results of this study demonstrated negligible arthrodesis site distraction in the plate-and-screws and pin-plate constructs when 6 weeks of ROM was simulated. When translated to a clinical scenario, these findings may allow earlier discontinuation of external immobilization after surgery.

Fate of the Morbidly Obese Patient Who Is Denied Total Joint Arthroplasty.

BACKGROUND: The purpose of this study is to investigate outcomes of patients denied total hip (THA) or knee arthroplasty (TKA) due to morbid obesity. METHODS: We performed an observational study of patients denied arthroplasty due to morbid obesity. A survey including the Harris Hip Score or pain and function components of the original Knee Society Score (KSS) was conducted with minimum 2-year follow-up. Statistical analysis was performed with parametric testing with significance at P < .05. RESULTS: In total, 125 (4.4%) of 2819 patients were denied THA or TKA due to morbid obesity. Twenty-four (19.2%) met target weight and underwent arthroplasty at our institution. Of the remaining 101 (80.8%) patients, 33 (32.7%) agreed to participate in the survey. None received THA and 6 received TKA elsewhere above target body mass index. Harris Hip Score was significantly higher in the successful weight loss cohort at our institution (70.5 ± 13.4 vs 34.6 ± 13.1). KSS Pain (maximum score of 50) and Function (maximum score of 100) were significantly higher in the successful weight loss cohort at our institution (32.9 ± 16.5; 51.1 ± 19.5) compared to the denied nonoperative cohort (7.2 ± 11.5; 33.0 ± 23.1); however, only KSS Pain was higher when compared to the TKA elsewhere cohort (14.2 ± 18.0; 29.2 ± 38.7). KSS Pain and Function were similar for both denial cohorts regardless of undergoing arthroplasty. CONCLUSION: Nearly 80% of patients denied never met target weight for arthroplasty. Those who met target weight prior to arthroplasty often reported better outcomes. Outcomes were similar when target weight was not met regardless of undergoing arthroplasty.

Locally delivered minocycline microspheres do not impair osseointegration of titanium implants in a rat femur model.

BACKGROUND: The purpose of this study was to determine whether intramedullary administration of extended-release minocycline microspheres would affect osseointegration. METHODS: Twenty-two rats were randomized to minocycline or saline femoral intramedullary injection followed by implantation of titanium alloy rods. Following euthanasia at four-weeks, pushout testing was performed and bone-volume-fraction assessed. RESULTS: Pushout strength was marginally greater in minocycline-treated implants (122.5 ± 39.1 N) compared to saline (96.9 ± 26.1 N) (P = 0.098). No difference was observed in energy to maximum load, mean stiffness, or peri-implant bone-volume-fraction (P > 0.05). CONCLUSIONS: Peri-implant minocycline administration did not impair implant fixation strength or peri-implant bone-volume, supporting its potential utility as an adjunct to intramedullary implants.

Interhospital Transfer and Outcomes in Patients with AKI: A Population-Based Cohort Study.

Background: Patients with AKI may require interhospital transfer to receive RRT. Interhospital transfer may lead to delays in therapy, resulting in poor patient outcomes. There is minimal data comparing outcomes among patients undergoing transfer for RRT versus those who receive RRT at the hospital to which they first present. Methods: We conducted a population-based cohort study of all adult patients (≥19 years) who received acute dialysis within 14 days of admission to an acute-care hospital between April 1, 2004 and March 31, 2015. The transferred group included all patients who presented to a hospital without a dialysis program and underwent interhospital transfer (with the start of dialysis ≤3 days of transfer and within 14 days of initial admission). All other patients were considered nontransferred. The primary outcome was time to 90-day all-cause mortality, adjusting for demographics, comorbidities, and measures of acute illness severity. We also assessed chronic dialysis dependence as a secondary outcome, using the Fine and Gray proportional hazards model to account for the competing risks of death. In a secondary post hoc analysis, we assessed these outcomes in a propensity score-matched cohort, matching on age, sex, and prior CKD status. Results: We identified 27,270 individuals initiating acute RRT within 14 days of a hospital admission, of whom 2113 underwent interhospital transfer. Interhospital transfer was associated with lower rate of mortality (adjusted hazard ratio [aHR], 0.90; 95% CI, 0.84 to 0.97). Chronic dialysis dependence was not significantly different between groups (aHR, 0.98; 95% CI, 0.91 to 1.06). In the propensity score-matched analysis, interhospital transfer remained associated with a lower risk of death (HR, 0.88; 95% CI, 0.80 to 0.96). Conclusions: Interhospital transfer for receipt of RRT does not confer higher mortality or worse kidney outcomes.

Understand the genomic diversity and evolution of fungal pathogen Candida glabrata by genome-wide analysis of genetic variations.

The yeast Candida glabrata, an opportunistic human fungal pathogen, is the second most prevalent cause of candidiasis worldwide, with an infection incidence that has been increasing in the past decades. The completion of the C. glabrata reference genome made fundamental contributions to the understanding of the molecular basis of its pathogenic phenotypes. However, knowledge of genome-wide genetic variations among C. glabrata strains is limited. In this study, we present a population genomic study of C. glabrata based on whole genome re-sequencing of 47 clinical strains to an average coverage of ∼63×. Abundant genetic variations were identified in these strains, including single nucleotide polymorphisms (SNPs), small insertion/deletions (indels) and copy number variations (CNVs). The observed patterns of variations revealed clear population structure of these strains. Using population genetic tests, we detected fast evolution of several genes involved in C. glabrata adherence ability, such as EPA9 and EPA10. We also located genome structural variations, including aneuploidies and large fragment CNVs, in regions that are functionally related to virulence. Subtelometric regions were hotspots of CNVs, which may contribute to variation in expression of adhesin genes that are important for virulence. We further conducted a genome-wide association study that identified two SNPs in the 5'UTR region of CST6 that were associated with fluconazole susceptibility. These observations provide convincing evidence for the highly dynamic nature of the C. glabrata genome with potential adaptive evolution to clinical environments, and offer valuable resources for investigating the mechanisms underlying drug resistance and virulence in this fungal pathogen. (249 words).

Systemic cobaltism manifesting as oral mucosal discoloration and metallic gustation after metal-on-metal hip resurfacing.

Systemic cobaltism is a debilitating complication of metal-on-metal (MoM) arthroplasty. In this report, we review a case of a 54-year-old female with metallosis from a MoM hip resurfacing and varying degrees of black discoloration of her tongue and metallic gustation as a result of systemic cobaltism. After explanting the metal components, thorough debridement, and conversion to ceramic-on-polyethylene arthroplasty, the patient's oral mucosal discoloration and metallic gustation resolved. This represents the first documentation of systemic cobaltism from MoM hip resurfacing manifesting as oral mucosal discoloration and metallic gustation with resolution after explant, debridement, and conversion to ceramic-on-polyethylene total hip arthroplasty.