Variable Efficacy of Tranexamic Acid in Geriatric Hip Fractures Treated With Arthroplasty Versus Cephalomedullary Nails.

INTRODUCTION: Geriatric hip fractures are associated with high rates of disability and mortality. Many of these patients require perioperative and postoperative allogeneic blood transfusions, which carry several noteworthy risks. A growing body of literature supports the efficacy of tranexamic acid (TXA) in geriatric hip fractures, without sufficient data examining which subgroups are likely to benefit the most. METHODS: In this study, we sought to evaluate whether TXA was associated with reduced blood loss and transfusions in a geriatric population undergoing hip fracture fixation at our institution during a 2-year period. The first year's data were collected in a retrospective fashion before the introduction of a quality control initiative encouraging TXA administration for all geriatric hip fractures. The second year's data were collected prospectively. A subgroup analysis was conducted for patients who underwent arthroplasties. RESULTS: Among the pooled cohort of patients undergoing surgery, TXA showed no benefit over control subjects for reducing blood loss or transfusion requirements. However, the subgroup of patients undergoing arthroplasty procedures showed a notable decrease in total blood loss and total units transfused during hospitalization. DISCUSSION: These results suggest that TXA may be most beneficial when targeted to arthroplasties performed for geriatric hip fractures.

Bias in Care: Impact of Ethnicity on Time to Emergent Surgery Varies Between Subspecialties.

INTRODUCTION: Disparity in access to emergency care among minority groups continues to exist despite growing awareness of the effect of implicit bias on public health. In this study, we evaluated ethnicity-based differences in time between admission and surgery for patients undergoing emergent procedures at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program. METHODS: We conducted a retrospective review of 249,296 National Surgical Quality Improvement Program cases from 2006 to 2018 involving general, orthopaedic, and vascular surgeries. Analysis of variance was used to compare "time to operating room" (OR) between ethnic groups. RESULTS: Notable differences in time to OR were noted among general and vascular surgeries but not orthopaedic surgery. Post hoc comparison identified notable variation in general surgery between White and Black/African Americans. In vascular surgery, notable variations were identified between White and Black/African Americans and White and Native Hawaiian/Pacific Islanders. DISCUSSION: These findings suggest that certain surgical subspecialties continue to exhibit disparities in care that may manifest as surgical delay, most notably between White and Black/African Americans. Interestingly, variation in time to OR for patients treated by orthopaedic surgery was not notable. Overall, these results highlight the need for additional research into the role of implicit bias in emergent surgical care in the United States.

Evaluating the utility of inflammatory markers in the diagnosis of soft tissue abscesses of the forearm and hand.

Upper extremity abscesses frequently present to the acute care setting with inconclusive physical examination and imaging findings. We sought to investigate the diagnostic accuracy of inflammatory markers including white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). A retrospective cohort study was performed to identify subjects ≥ 18  years treated with surgical debridement of upper extremity abscesses at our institution between January 2012 and December 2015. In this study, 188 patients were screened, and 72 met the inclusion criteria. A confirmed abscess as defined by culture positivity was present in 67 (93.1 %) cases. The sensitivity of WBC, ESR, or CRP individually was 0.45, 0.71, and 0.81. The specificity of WBC, ESR, or CRP individually was 0.80, 0.80, and 0.40. In combination all three markers when positive had a sensitivity of 0.26 and specificity of 1.0. These values were similar among patients with diabetes and those with obesity. With the highest sensitivity and lowest specificity, CRP exhibited the most utility as a screening test (level IV).

Fixation Principles for Pathologic Fractures in Metasatic Disease.

The management of pathologic fractures differs from nonpathologic fractures with respect to preoperative evaluation, surgical strategies, adjuvant therapies, and complication rates. These issues must be understood to provide appropriate musculoskeletal care for patients with metastatic disease.

Discovery of suppressors of CRMP2 phosphorylation reveals compounds that mimic the behavioral effects of lithium on amphetamine-induced hyperlocomotion.

The effective treatment of bipolar disorder (BD) represents a significant unmet medical need. Although lithium remains a mainstay of treatment for BD, limited knowledge regarding how it modulates affective behavior has proven an obstacle to discovering more effective mood stabilizers with fewer adverse side effects. One potential mechanism of action of lithium is through inhibition of the serine/threonine protein kinase GSK3ß, however, relevant substrates whose change in phosphorylation may mediate downstream changes in neuroplasticity remain poorly understood. Here, we used human induced pluripotent stem cell (hiPSC)-derived neuronal cells and stable isotope labeling by amino acids in cell culture (SILAC) along with quantitative mass spectrometry to identify global changes in the phosphoproteome upon inhibition of GSK3α/ß with the highly selective, ATP-competitive inhibitor CHIR-99021. Comparison of phosphorylation changes to those induced by therapeutically relevant doses of lithium treatment led to the identification of collapsin response mediator protein 2 (CRMP2) as being highly sensitive to both treatments as well as an extended panel of structurally distinct GSK3α/ß inhibitors. On this basis, a high-content image-based assay in hiPSC-derived neurons was developed to screen diverse compounds, including FDA-approved drugs, for their ability to mimic lithium's suppression of CRMP2 phosphorylation without directly inhibiting GSK3ß kinase activity. Systemic administration of a subset of these CRMP2-phosphorylation suppressors were found to mimic lithium's attenuation of amphetamine-induced hyperlocomotion in mice. Taken together, these studies not only provide insights into the neural substrates regulated by lithium, but also provide novel human neuronal assays for supporting the development of mechanism-based therapeutics for BD and related neuropsychiatric disorders.

Modularity in Total Hip Arthroplasty: Benefits, Risks, Mechanisms, Diagnosis, and Management.

Modular implants are currently widely used in total hip arthroplasty because they give surgeons versatility during the operation, allow for easier revision surgery, and can be adjusted to better fit the anatomy of the specific patient. However, modular implants, specifically those that have metal-on-metal junctions, are susceptible to crevice and fretting corrosion. This can ultimately cause implant failure, inflammation, and adverse local tissue reaction, among other possible side effects. Surgeons should be aware of the possibility of implant corrosion and should follow a set of recommended guidelines to systematically diagnose and treat patients with corroded implants. Ultimately, surgeons will continue to use modular implants because of their widespread benefits. However, more research is needed to determine how to minimize corrosion and the negative side effects that have been associated with modular junctions in total hip arthroplasty. [Orthopedics. 2017; 40(6):355-366.].

An electronic health records study of long-term weight gain following antidepressant use.

IMPORTANCE: Short-term studies suggest antidepressants are associated with modest weight gain but little is known about longer-term effects and differences between individual medications in general clinical populations. OBJECTIVE: To estimate weight gain associated with specific antidepressants over the 12 months following initial prescription in a large and diverse clinical population. DESIGN, SETTING, AND PARTICIPANTS: We identified 22,610 adult patients who began receiving a medication of interest with available weight data in a large New England health care system, including 2 academic medical centers and affiliated outpatient primary and specialty care clinics. We used electronic health records to extract prescribing data and recorded weights for any patient with an index antidepressant prescription including amitriptyline hydrochloride, bupropion hydrochloride, citalopram hydrobromide, duloxetine hydrochloride, escitalopram oxalate, fluoxetine hydrochloride, mirtazapine, nortriptyline hydrochloride, paroxetine hydrochloride, venlafaxine hydrochloride, and sertraline hydrochloride. As measures of assay sensitivity, additional index prescriptions examined included the antiasthma medication albuterol sulfate and the antiobesity medications orlistat, phentermine hydrochloride, and sibutramine hydrochloride. Mixed-effects models were used to estimate rate of weight change over 12 months in comparison with the reference antidepressant, citalopram. MAIN OUTCOME AND MEASURE: Clinician-recorded weight at 3-month intervals up to 12 months. RESULTS: Compared with citalopram, in models adjusted for sociodemographic and clinical features, significantly decreased rate of weight gain was observed among individuals treated with bupropion (ß [SE]: -0.063 [0.027]; P = .02), amitriptyline (ß [SE]: -0.081 [0.025]; P = .001), and nortriptyline (ß [SE]: -0.147 [0.034]; P < .001). As anticipated, differences were less pronounced among individuals discontinuing treatment prior to 12 months. CONCLUSIONS AND RELEVANCE: Antidepressants differ modestly in their propensity to contribute to weight gain. Short-term investigations may be insufficient to characterize and differentiate this risk.

Rare copy number variation in treatment-resistant major depressive disorder.

BACKGROUND: While antidepressant treatment response appears to be partially heritable, no consistent genetic associations have been identified. Large, rare copy number variants (CNVs) play a role in other neuropsychiatric diseases, so we assessed their association with treatment-resistant depression (TRD). METHODS: We analyzed data from two genome-wide association studies comprising 1263 Caucasian patients with major depressive disorder. One was drawn from a large health system by applying natural language processing to electronic health records (i2b2 cohort). The second consisted of a multicenter study of sequential antidepressant treatments, Sequenced Treatment Alternatives to Relieve Depression. The Birdsuite package was used to identify rare deletions and duplications. Individuals without symptomatic remission, despite two antidepressant treatment trials, were contrasted with those who remitted with a first treatment trial. RESULTS: CNV data were derived for 778 subjects in the i2b2 cohort, including 300 subjects (37%) with TRD, and 485 subjects in Sequenced Treatment Alternatives to Relieve Depression cohort, including 152 (31%) with TRD. CNV burden analyses identified modest enrichment of duplications in cases (empirical p = .04 for duplications of 100-200 kilobase) and a particular deletion region spanning gene PABPC4L (empirical p = .02, 6 cases: 0 controls). Pathway analysis suggested enrichment of CNVs intersecting genes regulating actin cytoskeleton. However, none of these associations survived genome-wide correction. CONCLUSIONS: Contribution of rare CNVs to TRD appears to be modest, individually or in aggregate. The electronic health record-based methodology demonstrated here should facilitate collection of larger TRD cohorts necessary to further characterize these effects.

Pilot investigation of isradipine in the treatment of bipolar depression motivated by genome-wide association.

OBJECTIVES: Motivated by genetic association data implicating L-type calcium channels in bipolar disorder liability, we sought to estimate the tolerability, safety, and efficacy of isradipine in the adjunctive treatment of bipolar depression. METHODS: A total of 12 patients with bipolar I or II depression entered this pilot, proof-of-concept eight-week investigation and 10 returned for at least one post-baseline visit. They were initiated on isradipine at 2.5 mg and titrated up to 10 mg daily, with blinded assessments of depression using the Montgomery-Åsberg Depression Rating Scale (MADRS) as well as adverse effects. RESULTS: Among the 10 patients, three had bipolar II disorder; all but two reported current episode duration longer than six months. In all, four of 10 completed the study; no significant adverse events were observed, although one subject discontinued treatment per protocol because of possible hypomanic symptoms which had resolved prior to study visit. In a mixed-effects model, mean improvement in depression severity, assessed by MADRS, was 2.1 (standard error = 0.36) points/week (p < 0.001). Two of the 10 subjects remitted and four of the 10 subjects experienced 50% or greater symptomatic improvement with treatment. CONCLUSIONS: Isradipine merits further investigation for the treatment of bipolar depression. This preliminary trial illustrates the potential utility of genetic investigation in identifying psychiatric treatment targets.