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OBJECTIVES: Tranexamic acid is proposed as a treatment for gastrointestinal bleeding. The Haemorrhage Alleviation with Tranexamic Acid-Intestinal System trial evaluated extended-use (24 hr) high-dose tranexamic acid, prompting a reappraisal for tranexamic acid in gastrointestinal bleeding. DATA SOURCES: We conducted a systematic review and meta-analysis of randomized controlled trials comparing tranexamic acid with usual care or placebo in adults with gastrointestinal bleeding. We searched MEDLINE, EMBASE, and CENTRAL (inception to September 2019). DATA SELECTION: Two reviewers independently screened citations, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool in duplicate. The main outcomes were mortality, bleeding, and adverse events. DATA EXTRACTION: Studies were analyzed as high-dose IV tranexamic acid versus all other dosing strategies for tranexamic acid using fixed-effects models. We assessed certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: Five randomized controlled trials evaluated extended-use high-dose IV tranexamic acid, seven evaluating low-dose IV or enteral tranexamic acid. Extended-use high-dose IV tranexamic acid did not reduce mortality (relative risk, 0.98%; 95% CI, 0.88-1.09; I2 = 63%; high certainty) or bleeding (relative risk, 0.92; 95% CI, 0.82-1.04; p = 0.17 and absolute risk differences, -0.7%; 95% CI, -1.5 to 0.3; high certainty) but resulted in a small increase in deep venous thrombosis (relative risk, 2.01; 95% CI, 1.08-3.72; I2 = 0%), pulmonary embolism (relative risk, 1.78; 95% CI, 1.06-3.0; I2 = 0%), and seizure (relative risk, 1.73; 95% CI, 1.03-2.93) with high certainty. Low-dose IV/enteral tranexamic acid did not reduce mortality (relative risk, 0.62; 95% CI, 0.36-1.09; I2 = 0%) but did reduce risk of rebleeding (relative risk, 0.5; 95% CI, 0.33-0.75; I2 = 9%) and need for surgery (relative risk, 0.58; 95% CI, 0.38-0.88; I2 = 11%), with moderate certainty. CONCLUSIONS: Extended-use high-dose IV tranexamic acid does not improve mortality or bleeding outcomes and increases adverse events. Low-dose/enteral tranexamic acid may be effective in reducing hemorrhage; more evidence is required to demonstrate its safety.

Background: The evidence base for understanding hospice use among persons with dementia is almost exclusively based on individuals with a primary terminal diagnosis of dementia. Little is known about whether comorbid dementia influences hospice use patterns. Objective: To estimate the prevalence of comorbid dementia among hospice enrollees and its association with hospice use patterns. Design: Pooled cross-sectional analysis of the nationally representative Health and Retirement Study (HRS) linked to Medicare claims. Subjects: Fee-for-service Medicare beneficiaries in the United States who enrolled with hospice and died between 2004 and 2016. Measurements: Dementia was assessed using a validated survey-based algorithm. Hospice use patterns were enrollment less than or equal to three days, enrollment greater than six months, hospice disenrollment, and hospice disenrollment after six months. Results: Of 3123 decedents, 465 (14.9%) had a primary hospice diagnosis of dementia and 943 (30.2%) had comorbid dementia and died of another illness. In fully adjusted models, comorbid dementia was associated with increased odds of hospice enrollment greater than six months (adjusted odds ratio [AOR] = 1.52, 95% confidence interval [CI]: 1.11-2.09) and hospice disenrollment following six months of hospice (AOR = 2.55, 95% CI: 1.43-4.553). Having a primary diagnosis of dementia was associated with increased odds of hospice enrollment greater than six months (AOR = 2.62, 95% CI: 1.86-3.68), hospice disenrollment (AOR = 1.82, 95% CI: 1.32-2.51), and hospice disenrollment following six months of hospice (AOR = 4.31, 95% CI: 2.37-7.82). Conclusion: Approximately 45% of the hospice population has primary or comorbid dementia and are at increased risk for long hospice enrollment periods and hospice disenrollment. Consideration of the high prevalence of comorbid dementia should be inherent in hospice staff training, quality metrics, and Medicare Hospice Benefit policies.

Background Splanchnic vein thrombosis (SVT) is an uncommon manifestation of venous thromboembolism. Historical epidemiological data on SVT-related mortality rate is not available to date. Methods We investigated time trends in SVT-related mortality, 2008–2019, in Veneto, an Italian high-income region of approximatively 5,000,000 inhabitants. SVT-related deaths were identified by the following ICD-10 codes: I81 (portal vein thrombosis), K75.1 (phlebitis of portal vein), K76.3 (liver infarction), K76.5 (hepatic veno-occlusive disease) or I82.0 (Budd-Chiari syndrome). Results During the study period, a total of 557,932 deaths were recorded. SVT was reported in 823 cases; 776 (94%) consisted of portal vein thrombosis. The age-standardized SVT-related mortality rate varied from 1.47 (year 2008) to 1.52 (year 2019) per 100,000 person-years. An increase in the cause-specific annual mortality rate was observed in women (0.56 in 2008 to 1.04 per 100,000 person-years in 2019; average annual percent change +5.7%, 95%CI +3.1; +8.3%). In men, the cause-specific mortality rate moved from 2.53 in 2008 to 2.03 per 100,000 person-years in 2019 (average annual percent change −1.2%, 95%CI -4.0; +1.6%). After conditioning for age and sex, the odds of having a concomitant liver disease were higher for SVT-related deaths (OR 31.6; 95%CI 17.1–37.0) compared with non-SVT-related deaths. This also applies to gastrointestinal cancers (OR 1.28; 95%CI 1.07–1.55), although to a lesser extent. Conclusions We report first epidemiological estimates of SVT-related mortality in a Western country. These values will serve as a reference to weight novel potential factors associated with SVT-related death, putting them into an epidemiological perspective. Summary box What is already known about this subject? Splanchnic vein thrombosis is a rare manifestation of venous thromboembolism, often related to liver diseases. Currently, there is no available data on its impact on the general population in terms of mortality rates. What are the new findings? Splanchnic vein thrombosis-related mortality rate was higher in men than in women and was strongly associated with the presence of liver diseases. In women, the age-standardized splanchnic vein thrombosis-related mortality rate has been increasing since 2008. How might it impact on clinical practice in the foreseeable future? We report first epidemiological estimates of splanchnic vein thrombosis-related mortality rates in a Western country. These values will serve as a reference to weight novel factors or pathologies potentially associated with splanchnic vein thrombosis and interpret them in an epidemiological perspective.

Background: Resistance to antiproliferative chemotherapies remains a significant challenge in the care of patients with solid tumors. Glucocorticoids, including endogenous cortisol, have been shown to induce pro-survival pathways in epithelial tumor cells. While pro-apoptotic effects of glucocorticoid receptor (GR) antagonism have been demonstrated under select conditions, the breadth and nature of these effects have not been fully established. Materials and Methods: To guide studies in cancer patients, relacorilant, an investigational selective GR modulator (SGRM) that antagonizes cortisol activity, was assessed in various tumor types, with multiple cytotoxic combination partners, and in the presence of physiological cortisol concentrations. Results: In the MIA PaCa-2 cell line, paclitaxel-driven apoptosis was blunted by cortisol and restored by relacorilant. In the OVCAR5 cell line, relacorilant improved the efficacy of paclitaxel and the potency of platinum agents. A screen to identify optimal combination partners for relacorilant showed that microtubule-targeted agents consistently benefited from combination with relacorilant. These findings were confirmed in xenograft models, including MIA PaCa-2, HeLa, and a cholangiocarcinoma patient-derived xenograft. In vivo, tumor-cell apoptosis was increased when relacorilant was added to paclitaxel in multiple models. Conclusions: These observations support recently reported findings of clinical benefit when relacorilant is added to paclitaxel-containing therapy in patients with ovarian and pancreatic cancers and provide a new rationale for combining relacorilant with additional cytotoxic agents.

Background Thus, the purpose of the present study was to (1) characterize common postoperative complications and (2) quantify the rates of revision in patients undergoing hemiarthroplasty to reverse total shoulder arthroplasty revisional surgery. We hypothesize that hardware loosenings will be the most common complication to occur in the sample, with the humeral component being the most common loosening. Methods This systematic review adhered to PRISMA reporting guideline. For our inclusion criteria, we included any study that contained intraoperative and/or postoperative complication data, and revision rates on patients who had undergone revision reverse total shoulder arthroplasty due to a failed hemiarthroplasty. Complications include neurologic injury, deep surgical site infections, hardware loosening/prosthetic instability, and postoperative fractures (acromion, glenoid, and humeral fractures). Results The study contained 22 studies that assessed complications from shoulders that had revision reverse total shoulder arthroplasty from a hemiarthroplasty, with a total sample of 925 shoulders. We found that the most common complication to occur was hardware loosenings (5.3%), and of the hardware loosenings, humeral loosenings (3.8%) were the most common. The revision rate was found to be 10.7%. Conclusion This systematic review found that revision reverse total shoulder arthroplasty for failed hemiarthroplasty has a high overall complication and reintervention rates, specifically for hardware loosening and revision rates.

Objectives Cardiopulmonary bypass surgery is complicated by metabolic acidosis, microvascular dysfunction, and capillary leak. The glycocalyx-a layer of proteins and sugars lining the vascular endothelium-is degraded during cardiopulmonary bypass. We aimed to describe the kinetics of glycocalyx degradation during and following cardiopulmonary bypass. We hypothesized that cleavage of negatively charged fragments of the glycocalyx would directly induce metabolic acidosis through changes in the strong ion gap (defined using Stewart's physicochemical approach to acid-base chemistry). We also investigated whether glycocalyx degradation was associated with failure of endothelial function and cardiovascular dysfunction. Design Single-center prospective cohort study. Setting Twenty-two bed surgical/medical PICU. Patients Twenty-seven term infants and children requiring cardiopulmonary bypass surgery for the correction/palliation of congenital heart disease. Interventions None. Measurements and main results We recruited 27 patients, 5 days to 57 months old. We prospectively sampled plasma prior to, during, and following cardiopulmonary bypass at predefined time points. We measured plasma concentrations of interleukin-6 (inflammatory marker), heparan sulfate (negatively charged glycocalyx glycosaminoglycan), and syndecan-1 (neutrally charged glycocalyx protein). We defined the following outcome measures: metabolic acidosis (strong ion gap), renal dysfunction (fold change in creatinine), capillary leak (fluid bolus volume), cardiovascular dysfunction (Vasoactive Inotropic Score), and length of ventilation. In linear regression models, maximum measured heparan sulfate concentration (negatively charged) was associated with metabolic acidosis (p = 0.016), renal dysfunction (p = 0.009), and length of ventilation (p = 0.047). In contrast, maximum measured syndecan-1 concentration (neutrally charged) was not associated with these clinical endpoints (p > 0.30 for all). Conclusions Our data show that metabolic acidosis (increased strong ion gap) is associated with plasma concentration of heparan sulfate, a negatively charged glycosaminoglycan cleaved from the endothelial glycocalyx during cardiopulmonary bypass. In addition, cleavage of heparan sulfate was associated with renal dysfunction, capillary leak, and global markers of cardiovascular dysfunction. These data highlight the importance of designing translational therapies to protect the glycocalyx in cardiopulmonary bypass.

Purpose To investigate the incidence of infection in patients with prior biliary interventions undergoing hepatic embolotherapy following extended antibiotic prophylaxis using moxifloxacin monotherapy or a multidrug regimen. Material and methods Under an Institutional Review Board-approved protocol, retrospective review of a quality assurance database identified all liver-directed therapies (LDTs) at a tertiary care center between 2010 and 2019 with biliary intervention prior to LDT Records were reviewed for infectious complications within 3 months of chemo- or radioembolization. Patients were categorized based on extended antibiotic prophylaxis regimen: oral moxifloxacin monotherapy or multidrug regimen of levofloxacin and metroniodazole plus preprocedural neomycin and erythromycin. Procedures without at least 2 months of clinical follow-up, hepatic ablation, and procedures without extended antibiotic prophylaxis were excluded Regression analysis was used to analyze multivariate data to detect a difference in infection rate. Results Twenty-four chemoembolization and 58 radioembolization procedures were performed on 55 patients with prior biliary interventions. Forty-four used monotherapy and 38 used multidrug regimen. The incidence of infection was 16.7% (4/24) after chemoembolization and 13.8% (8/58) after radioembolization The incidence of infection in patients did not differ between antibiotic prophylaxis regimens (18.2% [8/44] with moxifloxacin monotherapy and 10.5% [4/38] multidrug regimen, P = .3) or between types of biliary interventions (24.1% [7/29] with bilioenteric anastomosis and 23.8% [5/21] biliary stenting, P = .3). Conclusions The types of extended antibiotic prophylaxis (moxifloxacin monotherapy vs multitherapy), prior biliary intervention, and embolotherapy were not found to be associated with differences in the incidence of infectious complications in this population.

OBJECTIVE Infratemporal fossa (ITF) tumors are unique in histological characteristics and difficult to treat. Predictors of patient outcomes in this context are not known. The objective of this study was to identify independent predictors of outcome and to characterize patterns of failure in patients with ITF carcinoma. METHODS All patients who had been surgically treated for anterolateral skull base malignancy between 1999 and 2017 at the authors’ institution were retrospectively reviewed. Patient demographics, preoperative performance status, tumor stage, tumor characteristics, treatment modalities, and pathological data were collected. Primary outcomes were disease-specific survival (DSS) and local progression-free survival (LPFS) rates. Overall survival (OS) and patterns of progression were secondary outcomes. RESULTS Forty ITF malignancies with skull base involvement were classified as carcinoma. Negative margins were achieved in 23 patients (58%). Median DSS and LPFS were 32 and 12 months, respectively. Five-year DSS and OS rates were 55% and 36%, respectively. The 5-year LPFS rate was 69%. The 5-year overall PFS rate was 53%. Disease recurrence was noted in 28% of patients. Age, preoperative performance status, and margin status were statistically significant prognostic factors for DSS. Lower preoperative performance status and positive surgical margins increased the probability of local recurrence. CONCLUSIONS The ability to achieve negative margins was significantly associated with improved tumor control rates and DSS. Cranial base surgical approaches must be considered in multimodal treatment regimens for anterolateral skull base carcinomas.

BACKGROUND: Hospice patients with dementia are at increased risk for live discharge and long lengths of stay (>180 days), causing patient and family caregiver stress and burden. The location and timing of clinician visits are important factors influencing whether someone dies as expected, in hospice, or experiences a live discharge or long length of stay. OBJECTIVE: Examine how home hospice and nurse visit frequency relate to dying in hospice within the Medicare-intended 6-month period. DESIGN: Retrospective cohort study. SETTING: Non-profit hospice agency. PARTICIPANTS: Three thousand eight hundred and thirty seven patients with dementia who received hospice services from 2013 to 2017. METHODS: Multivariable survival analyses examined the effects of receiving home hospice (vs. nursing home) and timing of nurse visits on death within 6 months of hospice enrollment, compared to live discharge or long length of stay. Models adjust for relevant demographic and clinical factors. RESULTS: Thirty-nine percent (39%) of patients experienced live discharge or long length of stay. Home hospice patients were more likely to experience live discharge or long length of stays (HR for death: 0.77, 95%CI: 0.69–0.86, p < 0.001). Frequency of nurse visits was inversely associated with live discharge and long lengths of stay (HR for death: 2.87, 95%CI: 2.47–3.33, p < 0.001). CONCLUSION: Nearly 40% of patients with dementia in our study experienced live discharge or a long length of stay. Additional research is needed to understand why home hospice may result in live discharge or a long length of stay for patients with dementia. Nurse visits were associated with death, suggesting their responsiveness to deteriorating patient health. Hospice guidelines may need to permit longer stays so community-dwelling patients with dementia, a growing segment of hospice patients, can remain continuously enrolled in hospice and avoid burden and costs associated with live discharge.

Endothelial injury and microvascular/macrovascular thrombosis are common pathophysiological features of coronavirus disease-2019 (COVID-19). However, the optimal thromboprophylactic regimens remain unknown across the spectrum of illness severity of COVID-19. A variety of antithrombotic agents, doses, and durations of therapy are being assessed in ongoing randomized controlled trials (RCTs) that focus on outpatients, hospitalized patients in medical wards, and patients critically ill with COVID-19. This paper provides a perspective of the ongoing or completed RCTs related to antithrombotic strategies used in COVID-19, the opportunities and challenges for the clinical trial enterprise, and areas of existing knowledge, as well as data gaps that may motivate the design of future RCTs.

Objective: Characterize hospice staff practices and perspectives on discussing end-of-life care preferences with patients/families, including those desiring intensive treatment and/or full code. Background: Patients in the United States can elect hospice while remaining full code or seeking intensive interventions, for example, blood transfusions, or chemotherapy. These preferences conflict with professional norms, hospice philosophy, and Medicare hospice payment policies. Little is known about how hospice staff manage patient/family preferences for full-code status and intensive treatments. Methods: We recruited employees of four nonprofit US hospices with varying clinical and hospice experience for semi-structured, in-depth interviews. Open-ended questions explored participants' practices and perceptions of discussing end-of-life care preferences in hospice, with specific probes about intensive treatment or remaining full code. Interdisciplinary researchers coded and analyzed data using the constant comparative method. Results: Participants included 25% executive leaders, 14% quality improvement administrative staff, 61% clinicians (23 nurses, 21 social workers, 7 physicians, and 2 chaplains). Participants reported challenges in engaging patients/families about end-of-life care preferences. Preferences for intensive treatment or full-code status presented an ethical dilemma for some participants. Participants described strategies to navigate such preferences, including educating about treatment options, and expressed diverse reactions, including accepting or attempting to shift enrollee preferences. Discussion: This study illuminates a rarely studied aspect of hospice care: how hospice staff engage with enrollees choosing full code and/or intensive treatments. Such patient preferences can produce ethical dilemmas for hospice staff. Enhanced communication training and guidelines, updated organizational and federal policies, and ethics consult services may mitigate these dilemmas.

Thrombophilia testing detects those with a hereditary or acquired prothrombotic states that predispose to venous thromboembolism (VTE). If one considers Virchow's triad, thrombophilia describes the changes in blood constituents that increase the risk of venous thrombosis. Inherited and acquired risk factors for thrombosis are discussed and an algorithm for management of acute deep venous thrombosis (DVT) and pulmonary embolism (PE) presented.

This CIRSE Standards of Practice document is aimed at interventional radiologists and provides best practices for peri-operative anticoagulation management during interventional radiology procedures.

Background Bone grafting during primary reverse shoulder arthroplasty (RSA) is a technique used to restore poor glenoid bone, increase lateralization, and restore abnormal inclination or version. The purpose of this article is to analyze early outcomes of bone grafting during RSA, assessing the influence of technical and patient considerations. Methods In a 4.5-year time period, 137 RSAs with glenoid bone grafting were performed with a minimum 3 months' follow-up. The mean follow-up was 17 months (range, 3-38). The mean age was 71 years (range, 45-89), and body mass index was 28 (range, 19-44). The source of the autografts were humeral head (n = 113) and iliac crest autograft (ICBG; n = 24). The humeral components included 84 onlay and 53 inlay designs. Results Overall, there were 16 complications (12%), of which 6 were major (5%) (3 graft nonunions and 3 infections) and 10 minor (8%) (1 carpal tunnel syndrome and 9 transient axillary neuropraxias). Of the 9 axillary neuropraxias, 8 resolved by the most recent follow-up, whereas 1 patient was lost to follow-up. There were 4 reoperations (3%): 2 for glenoid baseplate loosening, 1 for severe notching associated with severe glenoid bone loss, and 1 for deep periprosthetic infection. One additional patient had a baseplate failure and is undergoing further treatment. There was no difference in the occurrence of graft nonunions, revision surgery, or glenoid component loosening when comparing type of graft or humeral component used. There was an association of revision surgery (P = .02) with ICBG and older age at the time of surgery (P = .02) and an association of transient neuroapraxia with onlay humeral components (P = .01) and workers' compensation cases (P = .04). Conclusions There is a high union rate and low complication rate after bone grafting of the glenoid performed with RSA. Transient neuropraxias are the most frequent complication, but the majority resolve within the first postoperative year. These early findings can serve as the basis for future long-term, comprehensive analysis of complications and outcomes after bone grafting during RSA.

Although the body of literature on syndesmosis injuries is growing with regard to both the biomechanics and clinical outcomes for various fixation constructs, there is little consensus on the optimal treatment and return to sport strategy for these injuries. We endeavoured to assess the current approaches to managing syndesmotic injuries through a Research Electronic Data Capture survey.The survey consisted of 27 questions, including respondent demographics, indications for treatment of syndesmotic injuries, preferred treatment and technique, and postoperative management. Responses were generated through six different athlete scenarios: moderate impact, high impact, and very high impact athletes with/without complete deltoid injury. Frequencies and percentages were calculated for all categorical responses.A total of 742 providers responded to the survey, including 457 American surgeons and 285 members of various international societies. Flexible devices were the preferred fixation construct (47.1%), followed by screws (29.6%), hybrid fixation (e.g. combination of flexible device and screw, 18%), and other (5.3%). Sixty-four percent of respondents noted that their rehabilitation protocols would not change for each athlete scenario. Considerable variability was present in anticipated return to full participation, largely dependent on the presence or absence of a deltoid ligament injury.The most common elements used as surgical indications were syndesmosis widening2 mm on x-ray, an anterior inferior talofibular ligament injury in combination with a posterior inferior talofinular ligament or deltoid ligament involvement on magnetic resonance imaging, and widening of the distal tibiofibular joint during arthroscopic evaluation. Overall, flexible fixation (e.g. suture button) was the preferred device choice for the repair of an injured syndesmosis. Most respondents did not alter their rehab protocol or anticipated return to play timeline based on the injury severity. However, there was considerable variability between respondents on the time to weight-bearing, running, and full participation. Further pragmatic outcomes data are necessary to guide safe return to play protocols for syndesmotic injuries.Level IV.

Received 12th May 2021. Accepted 17th May 2021. Published online 28th May 2021. Issue published 1st August 2021.

European Society for Vascular Surgery (ESVS) 2021 Clinical Practice Guidelines on the Management of Venous Thrombosis

Background: Two common operative fixation techniques for insertional Achilles tendinopathy are the use of all-soft suture anchors vs synthetic anchors with a suture bridge. Despite increasing emphasis on early postoperative mobilization, the biomechanical profile of these repairs is not currently known. We hypothesized that the biomechanical profiles of single-row all-soft suture anchor repairs would differ when compared to double-row suture bridge repairs. Methods: Achilles tendons were detached from their calcaneal insertions on 6 matched-pair, fresh-frozen cadaver through-knee amputation specimens. Group 1 underwent a single-row repair with all-soft suture anchors. Group 2 was repaired with a double-row bridging suture bridge construct. Achilles-calcaneal displacement was tracked while specimens were cyclically loaded from 10 to 100 N for 2000 cycles and then loaded to failure. Linear mixed models were used to analyze the independent effects of age, body mass index, tendon morphology, repair construct, and footprint size on clinical and ultimate failure loads, Achilles-calcaneal displacement, and mode of failure. Results: The suture bridge group was independently associated with an approximately 50-N increase in the load to clinical failure (defined as more than 5 mm tendon displacement). There was no difference in ultimate load to failure or tendon/anchor displacement between the 2 groups. Conclusion: This cadaveric study found that a double-row synthetic bridge construct had less displacement during cyclic loading but was not able to carry more load before clinical failure when compared to a single-row suture anchor construct for the operative repair of insertional Achilles tendinopathy. Clinical Relevance: Our data suggest that double-row suture bridge constructs increase the load to clinical failure for operative repairs of insertional Achilles tendinopathy. It must be noted that these loads are well below what occurs during gait and the repair must be protected postoperatively without early mobilization. This study also identified several clinical factors that may help predict repair strength and inform further research.

Background The homeless patient population is known to have a high occurrence of inappropriate emergency department (ED) utilization. The study hospital initiated a dedicated homeless clinic targeting patients experiencing homelessness with a combination of special features. We aim to determine whether this mode of care can reduce inappropriate ED utilization among homeless patients. Methods We conducted a retrospective observational study from July 1, 2017 to Dec 31, 2017. The study enrolled all homeless patients who visited any hospital regular clinic, dedicated homeless clinic, and ED at least once during the study period. ED homeless patients were divided into four groups (A: no clinic visits; B: those who only visited hospital regular clinic; C: those who only visited dedicated homeless clinic; and D: those who visited both hospital regular clinic and dedicated homeless clinic). The New York University algorithm was used to determine appropriate ED utilization. We compared inappropriate ED utilization among patients from these groups. Multivariate logistic regression was used to determine the risks of different clinical visits in association with inappropriate ED utilization. Results A total of 16,323 clinic and 8511 ED visits occurred among 5022 unique homeless patients, in which 2450 unique patients were seen in hospital regular clinic, 784 patients in dedicated homeless clinic, 688 patients in both hospital regular clinic and dedicated homeless clinic, and 1110 patients with no clinic visits. Twenty‐nine percent (230/784) of patients from dedicated homeless clinic utilized the ED, among which 21% (175/844) of their ED visits were considered inappropriate. In contrast, 40% of patients from hospital regular clinic utilized the ED, among which 29% were inappropriate (P < 0.001). The adjusted odds ratio (OR) was 0.61 (95% confidence interval [CI] = 0.50–0.74, P < 0.001) on dedicated homeless clinic predicting inappropriate ED visits in multivariate logistic regression. Conclusion Implementing a dedicated homeless clinic with these features can reduce ED inappropriate utilization among patients experiencing homelessness.

Objectives Hydroxychloroquine (HCQ) is an anti-malarial and immunomodulatory drug reported to inhibit the Corona virus, SARS-CoV-2, in vitro. At present there is insufficient evidence from clinical trials to determine the safety and efficacy of HCQ as a treatment for COVID-19. However, since the World Health Organisation declared COVID-19 a pandemic in March 2020, the US Food and Drug Administration issued an Emergency Use Authorisation to allow HCQ and Chloroquine (CQ) to be distributed and used for certain hospitalised patients with COVID-19 and numerous clinical trials are underway around the world, including the UK based RECOVERY trial, with over 1000 volunteers. The validation of a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of HCQ and two of its major metabolites, desethylchloroquine (DCQ) and di-desethylchloroquine (DDCQ), in whole blood is described. Methods Blood samples were deproteinised using acetonitrile. HCQ, DCQ and DDCQ were chromatographically separated on a biphenyl column with gradient elution, at a flow rate of 500 μL/min. The analysis time was 8 min. Results For each analyte linear calibration curves were obtained over the concentration range 50-2000 μg/L, the lower limit of quantification (LLOQ) was 13 μg/L, the inter-assay relative standard deviation (RSD) was Conclusion This method has acceptable analytical performance and is applicable to the therapeutic monitoring of HCQ, evaluating the pharmacokinetics of HCQ in COVID-19 patients and supporting clinical trials.

Background Direct oral anticoagulants (DOACs) are prescribed for atrial fibrillation (AF) and venous thromboembolism (VTE) and both occur more frequently in obese patients. Outcomes from DOAC trials included few individuals ≥ 120 kg leading to uncertainty whether high body weight (BW) reduces DOAC concentrations. Objectives This article investigates the relationship between factor Xa (FXa) inhibitor concentrations, BW, and renal function, and compares them in high BW patients with unselected populations. Methods Consecutive patients in two United Kingdom centers, weighing ≥ 120 kg receiving 5 mg twice daily apixaban or 20 mg once daily rivaroxaban for AF or VTE were prospectively included. Peak or trough concentrations were measured using specific chromogenic assays, expressed in mean or median (5th–95th percentiles). On-therapy range was the interval from the 5th percentile trough concentration to the 95th percentile peak concentration. Results One hundred patients were included; age range: 23 to 78 years, 31% were women, 58% had AF, creatinine clearance range: 67 to 474 mL/min. Median BW was 139 kg, and 84% had body mass index (BMI) ≥ 40 kg/m2. DOAC peak and trough concentrations varied from 44 to 727 and 14 to 299 ng/mL, respectively. There was no linear relationship between FXa inhibitor concentrations at peak or trough and BW or BMI, and creatinine clearance. Apixaban troughs in AF and rivaroxaban peaks in VTE were lower than in unselected populations. However, only two trough concentrations were below the expected range, and 109/116 were within the on-therapy range. Conclusion These data indicated that obese or high BW patients generally achieve therapeutic FXa inhibitor concentrations. However, further investigations assessing clinical outcomes are required.

We determined the relationship between plasma kallikrein and cardiovascular disease (CVD) outcomes as well as major adverse cardiovascular events (MACE) in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) cohort of type 1 diabetes (T1D). Plasma kallikrein levels were measured longitudinally in 693 subjects at DCCT baseline (1983–1989), midpoint (1988–1991), and end (1993) and at EDIC years 4–6 (1997–1999), 8–10 (2001–2003), and 11–13 (2004–2006). Cox proportional hazards regression models assessed the association between plasma kallikrein levels and the risk of CVD. In unadjusted models, higher plasma kallikrein levels were associated with higher risk of any CVD during DCCT/EDIC (hazard ratio [HR] = 1.16 per 20 nmol/L higher levels of plasma kallikrein; P = 0.0177) as well as over the EDIC-only period (HR = 1.22; P = 0.0024). The association between plasma kallikrein levels and the risk of any CVD remained significant during the EDIC follow-up after adjustment for age and mean HbA1c (HR = 1.20; P = 0.0082) and in the fully adjusted model for other CVD risk factors (HR = 1.17; P = 0.0330). For MACE, higher plasma kallikrein levels were associated with higher risk in the unadjusted (HR = 1.25; P = 0.0145), minimally adjusted (HR = 1.23; P = 0.0417, and fully adjusted (HR = 1.27; P = 0.0328) models for EDIC only. These novel findings indicate that plasma kallikrein level associates with the risk of any CVD and MACE in T1D individuals.

OBJECTIVEGeographic and racial/ethnic disparities related to diabetes control and treatment have not previously been examined at the national level.RESEARCH DESIGN AND METHODSA retrospective cohort study was conducted in a national cohort of 1,140,634 veterans with diabetes, defined as two or more diabetes ICD-9 codes (250.xx) across inpatient and outpatient records. Main exposures of interest included 125 Veterans Administration Medical Center (VAMC) catchment areas as well as racial/ethnic group. The main outcome measure was HbA1c level dichotomized at ≥8.0% (≥64 mmol/mol).RESULTSAfter adjustment for age, sex, racial/ethnic group, service-connected disability, marital status, and the van Walraven Elixhauser comorbidity score, the prevalence of uncontrolled diabetes varied by VAMC catchment area, with values ranging from 19.1% to 29.2%. Moreover, these differences largely persisted after further adjusting for medication use and adherence as well as utilization and access metrics. Racial/ethnic differences in diabetes control were also noted. In our final models, compared with non-Hispanic Whites, non-Hispanic Blacks (odds ratio 1.11 [95% credible interval 1.09–1.14]) and Hispanics (1.36 [1.09–1.14]) had a higher odds of uncontrolled HBA1c level.CONCLUSIONSIn a national cohort of veterans with diabetes, we found geographic as well as racial/ethnic differences in diabetes control rates that were not explained by adjustment for demographics, comorbidity burden, use or type of diabetes medication, health care utilization, access metrics, or medication adherence. Moreover, disparities in suboptimal control appeared consistent across most, but not all, VAMC catchment areas, with non-Hispanic Black and Hispanic veterans having a higher odds of suboptimal diabetes control than non-Hispanic White veterans.

Those who are infected with Severe Acute Respiratory Syndrome‐related CoronaVirus‐2 are theoretically at increased risk of venous thromboembolism during self‐isolation if they have reduced mobility or are dehydrated. Should patients develop coronavirus disease (COVID‐19) pneumonia requiring hospital admission for treatment of hypoxia, the risk for thromboembolic complications increases greatly. These thromboembolic events are the result of at least two distinct mechanisms – microvascular thrombosis in the pulmonary system (immunothrombosis) and hospital‐associated venous thromboembolism. Since pregnancy is a prothrombotic state, there is concern regarding the potentially increased risk of thrombotic complications among pregnant women with COVID‐19. To date, however, pregnant women do not appear to have a substantially increased risk of thrombotic complications related to COVID‐19. Nevertheless, several organizations have vigilantly issued pregnancy‐specific guidelines for thromboprophylaxis in COVID‐19. Discrepancies between these guidelines reflect the altruistic wish to protect patients and lack of high‐quality evidence available to inform clinical practice. Low molecular weight heparin (LMWH) is the drug of choice for thromboprophylaxis in pregnant women with COVID‐19. However, its utility in non‐pregnant patients is only established against venous thromboembolism, as LMWH may have little or no effect on immunothrombosis. Decisions about initiation and duration of prophylactic anticoagulation in the context of pregnancy and COVID‐19 must take into consideration disease severity, outpatient vs inpatient status, temporal relation between disease occurrence and timing of childbirth, and the underlying prothrombotic risk conferred by additional comorbidities. There is currently no evidence to recommend the use of intermediate or therapeutic doses of LMWH in thromboprophylaxis, which may increase bleeding risk without reducing thrombotic risk in pregnant patients with COVID‐19. Likewise, there is no evidence to comment on the role of low‐dose aspirin in thromboprophylaxis or of anti‐cytokine and antiviral agents in preventing immunothrombosis. These unanswered questions are being studied within the context of clinical trials.

The novel coronavirus disease of 2019 (COVID‐19) pandemic, as declared by the World Health Organization, is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2). Cardiovascular disease and, in particular, venous thromboembolism (VTE) has emerged as an important consideration in the management of hospitalized patients with COVID‐19. The diagnosis of VTE using standardized objective testing is problematic in these patients, given the risk of infecting non‐COVID‐19 hospitalized patients and hospital personnel, coupled with the usual challenges of performing diagnostic testing in critically‐ill patients. Early reports suggest a high incidence of VTE in hospitalized COVID‐19 patients, particularly those with severe illness, that is similar to the high VTE rates observed in patients with other viral pneumonias, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS‐CoV).

Augmented and mixed reality are emerging interactive and display technologies. These technologies are able to merge virtual objects, in either 2 or 3 dimensions, with the real world. Image guidance is the cornerstone of interventional radiology. With augmented or mixed reality, medical imaging can be more readily accessible or displayed in actual 3-dimensional space during procedures to enhance guidance, at times when this information is most needed. In this review, the current state of these technologies is addressed followed by a fundamental overview of their inner workings and challenges with 3-dimensional visualization. Finally, current and potential future applications in interventional radiology are highlighted.

Background: Charcot-Marie-Tooth (CMT) disease is a hereditary motor-sensory neuropathy that is often associated with a cavovarus foot deformity. Limited evidence exists for the orthopedic management of these patients. Our goal was to develop consensus guidelines based upon the clinical experiences and practices of an expert group of foot and ankle surgeons. Methods: Thirteen experienced, board-certified orthopedic foot and ankle surgeons and a neurologist specializing in CMT disease convened at a 1-day meeting. The group discussed clinical and surgical considerations based upon existing literature and individual experience. After extensive debate, conclusion statements were deemed “consensus” if 85% of the group were in agreement and “unanimous” if 100% were in support. Conclusions: The group defined consensus terminology, agreed upon standardized templates for history and physical examination, and recommended a comprehensive approach to surgery. Early in the course of the disease, an orthopedic foot and ankle surgeon should be part of the care team. This consensus statement by a team of experienced orthopedic foot and ankle surgeons provides a comprehensive approach to the management of CMT cavovarus deformity. Level of Evidence: Level V, expert opinion.

Summary This document aims to provide practical guidance for the assessment and management of patients with thrombocytopenia, with a particular focus on immune thrombocytopenia (ITP), during the COVID‐19 pandemic. The intention is to support clinicians and, although recommendations have been provided, it is not a formal guideline. Nor is there sufficient evidence base to conclude that alternative approaches to treatment are incorrect. Instead, it is a consensus written by clinicians with an interest in ITP or coagulation disorders and reviewed by members of the UK ITP forum.

Coagulation changes, thrombosis, and hemorrhage have been described in patients following N‐methyl‐3,4‐methylenedioxymethylamphetamine (MDMA) intoxication who subsequently developed serotonin syndrome and rhabdomyolysis. The clinical features and mechanism of this remain poorly described. We describe 5 sequential cases admitted to critical care due to severe recreational MDMA toxicity where coagulopathy occurred, and discuss key clinical issues. All patients presented with hyperpyrexia then developed subsequent rhabdomyolysis accompanied by a coagulopathy within 24 hours of presentation. This included a severe thrombocytopenia, prolonged coagulation times, grossly elevated D‐dimer levels, and hypofibrogenemia. Multiorgan dysfunction was seen in all patients, including stroke in one patient and major hemorrhage in another. In 2 cases, low‐dose low‐molecular‐weight heparin was used early after presentation, with no significant bleeding complications. Blood products usage was high but variable between the patients with lower use in those who received low‐molecular‐weight heparin early. Other treatments included intravascular therapeutic cooling, renal replacement therapy with large filter pores and cyprohepatidine. Current evidence suggests that in this group, rhabdomyolysis with subsequent myosin release may be a profound activator of coagulation leading to disseminated intravascular coagulation. Myosin‐activated coagulation seems a potential cause of MDMA‐related coagulopathy in the setting of rhabdomyolysis and serotonin syndrome. Further studies are needed to validate this and explore the use of low‐molecular‐weight heparin to reduce the clinical effects of this coagulopathy.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.

Direct oral anticoagulants have become the mainstay of the management of venous thromboembolism and atrial fibrillation, and long-term anticoagulation is indicated for those at high risk of further thrombotic events. This includes patients diagnosed with antiphospholipid syndrome, for whom the ‘triple positive’ laboratory combination of lupus anticoagulant, β2-glycoprotein-1 and anti-cardiolipin antibodies signify those at greatest risk. Data from meta-analysis and randomised control trials have raised the concern that direct oral anticoagulants may be less effective than vitamin K antagonists for the prevention of thrombosis in patients with thrombotic antiphospholipid syndrome, particularly those with the triple positive profile. This article reviews the diagnosis of thrombotic antiphospholipid syndrome, strategies for testing without interruption of anticoagulation, evidence concerning the safety of direct oral anticoagulants in this setting, and the implications for current investigation and management of unprovoked venous thromboembolism.

Purpose Ophthalmologic telemedicine programs help to address the growing demand for eye care and lessen healthcare disparities for patients. One example is Technology-Based Eye Care Services (TECS), implemented in the Veteran Affairs Healthcare System in 2015. Accuracy and quality data for TECS both have been reported, and data suggest that although the TECS examination is comparable with an in-person examination, sensitivity for glaucoma and glaucoma suspect detection is less than that for other diseases, such as macular degeneration. Several articles suggest that OCT can improve disease detection for glaucoma. Therefore, this study was undertaken to test the impact of OCT on the accuracy of the TECS protocol. This article reports the data from part II of the TECS Compare trial; results from part I are discussed in a previous article. Design Prospective comparison between the TECS protocol with OCT versus a face-to-face (FTF) examination for 256 patients. Participants An eligible patient was defined as a patient with no known ocular disease who desired a routine eye examination. Methods Patient underwent the TECS protocol workup and OCT nerve, OCT macula, and FTF examination on the same day. Main Outcome Measures Percent agreement, κ values, sensitivity, and specificity were calculated for nonexpert readers after OCT interpretation of the TECS protocol using the FTF examination as the clinical gold standard. Results OCT did not improve the diagnostic accuracy of the TECS protocol when compared with an FTF examination. In most cases, OCT had no impact, and in the case of reader 2, OCT actually reduced the κ value from moderate agreement to agreement equal to chance while lowering the percent agreement by 10%. OCT also did not impact inter- or intrareader variability parameters. Conclusions In this study, OCT did not seem to improve the accuracy of glaucoma or retinal disease detection when added to the standard TECS protocol. In one case, OCT worsened the agreement of the reader compared with the FTF. Further study is necessary to confirm these findings, and results may change if the readers are glaucoma or retina specialists instead of nonexpert OCT readers, comprehensive and anterior segment specialists.

Background An emerging problem in the treatment of breast cancer is the increasing incidence of metastases to the brain. Metastatic brain tumours are incurable and can cause epileptic seizures and cognitive impairment, so better understanding of this niche, and the cellular mechanisms, is urgently required. Microglia are the resident brain macrophage population, becoming “activated” by neuronal injury, eliciting an inflammatory response. Microglia promote proliferation, angiogenesis and invasion in brain tumours and metastases. However, the mechanisms underlying microglial involvement appear complex and better models are required to improve understanding of function. Methods Here, we sought to address this need by developing a model to study metastatic breast cancer cell-microglial interactions using intravital imaging combined with ex vivo electrophysiology. We implanted an optical window on the parietal bone to facilitate observation of cellular behaviour in situ in the outer cortex of heterozygous Cx3cr1GFP/+ mice. Results We detected GFP-expressing microglia in Cx3cr1GFP/+ mice up to 350 μm below the window without significant loss of resolution. When DsRed-expressing metastatic MDA-MB-231 breast cancer cells were implanted in Matrigel under the optical window, significant accumulation of activated microglia around invading tumour cells could be observed. This inflammatory response resulted in significant cortical disorganisation and aberrant spontaneously-occurring local field potential spike events around the metastatic site. Conclusions These data suggest that peritumoral microglial activation and accumulation may play a critical role in local tissue changes underpinning aberrant cortical activity, which offers a possible mechanism for the disrupted cognitive performance and seizures seen in patients with metastatic breast cancer.

Background and Objectives:Transitioning to a nursing home (NH) is a major life event for 1.4 million NH residents in the United States. Most post-acute NH admissions plan for rehabilitation and discharge home, but with nearly 70% of NH residents being palliative care (PC) eligible, many evolve into long-term placements secondary to poor health and associated decline in function and/or cognition. This article describes the perceptions of NH PC-eligible residents and families transitioning to life in a NH.Methods:Residents at 3 NHs in Northern California (N = 228) were screened for PC eligibility. A convenience sample of PC-eligible residents and their family members (n = 28) participated in qualitative interviews that explored the experience of living as a NH resident with serious illness. Data were analyzed using grounded theory methodology.Results:Our study provides insights into the experiences of transitioning to a NH from the perspectives of PC-eligible residents and their families. These data describe how PC-eligible residents and their families experienced disempowerment as they perceived being left out of decisions to go to a NH, loss of autonomy once at the NH, dealt with the realization that they would not be going home, and described perceived barriers to going home.Discussion and Implications:The inclusive and person-centered model of care that PC provides naturally empowers residents and family members. Adequate provision of PC services, together with changes in policy related to NH culture and benefit management, could improve the experience of transitioning to a nursing home.

The level of venous thrombosis risk in women who experience spontaneous or induced pregnancy loss has previously been uncertain. However, recent data indicate that the risk of venous thrombosis in women undergoing pregnancy termination in the first trimester is increased two-fold compared to non-pregnant women but reduced five-fold compared to women in the 6 weeks following a term birth. The termination procedure itself appears not to influence thrombosis risk. In light of this data, this consensus statement provides recommendations for reducing the risk of venous thrombosis in women undergoing spontaneous or induced pregnancy loss based on Royal College of Obstetricians and Gynaecologists risk stratification guidelines.

Background: Studies suggest breastfeeding lowers obesity risk in childhood, but generalizability of existing evidence is limited. We examined associations of breastfeeding with childhood overweight, obesity, and percentage body fat, in a racially diverse maternal-child cohort. Methods: This cross-sectional study included 823 children, ages 4-8 years, enrolled in the Environmental Exposures and Child Health Outcomes (ECHO) cohort, a subset of the National Institute of Child Health and Human Development Fetal Growth Studies cohort. Logistic regression was used to estimate odds ratios and 95% confidence intervals (CIs) for overweight [BMI (kg/m2) 85th to

Femoral neck stress fractures (FNSFs) are an infrequent condition in athletic and military populations.A high index of suspicion with liberal use of magnetic resonance imaging (MRI) is vital for early recognition and treatment initiation.An associated hip effusion on MRI is a risk factor for an evolving stress injury and requires close assessment and consideration for repeat MRI.Stress reactions and stable, incomplete FNSFs (50% of femoral neck width) can be treated nonsurgically.Surgical intervention is accepted for high-risk, incomplete (≥50% of femoral neck width), and complete FNSFs.Overall, there is a paucity of high-quality literature on the rates of return to activity following FNSF.

The global annual incidence of venous thromboembolism (VTE) is estimated to be 0.75-2.69 per 1,000 population (1). Up to 60% of VTE events occur during or within three months after hospital admission: these are known as hospital-associated VTE and account for an estimated 10 million cases of VTE globally (2). Without preventive measures being used, hospital-associated VTE is the leading preventable cause of hospital death (2). The age-standardized pulmonary embolism (PE)-related mortality rate is similar in magnitude to respiratory infections and obstructive pulmonary disease. Although the impact of PE-related deaths is relatively high among young women (3), its global awareness by the public is low (4).

Background: Ankle fractures are one of the most common orthopedic injuries, and although most patients have a satisfactory outcome following operative fixation, there are patients that have persistent pain despite anatomic reduction. Intra-articular injuries have been suggested as one potential cause of these suboptimal outcomes. Our study assesses the clinical impact of performing an ankle arthroscopy during ankle fracture open reduction and internal fixation (ORIF). Methods: This was a retrospective chart review of all patients who underwent operative fixation of a bimalleolar or trimalleolar ankle fracture at our institution from 2014 through 2018. We extracted all demographic data, fracture pattern, operative procedures performed, tourniquet times, arthroscopic findings and any arthroscopic interventions. We then conducted a phone and e-mail survey. Our study included 213 total patients (142 traditional ORIF, 71 ORIF plus arthroscopy) with an average age of 40 years. The average follow-up was 32.4 months with a survey follow-up rate of 50.7% (110/213). Results: The average tourniquet time for the arthroscopy cohort was 10 minutes longer (89 minutes vs 79 minutes). During the arthroscopy, there was a 28% (20/71) rate of full-thickness osteochondral lesions, 33% (24/71) rate of loose bodies, and a 49% (35/71) rate of partial-thickness cartilage injury. The mean Patient Reported Outcome Information System (PROMIS) physical function score among Weber B fibula fractures was 45.8 and 42.3 in the arthroscopy and nonarthroscopy groups, respectively ( P = .012). In addition, the patient satisfaction rate in Weber B fibula fractures was higher in those patients who underwent arthroscopy compared with ORIF alone (93% vs 75%, P = .05). Patients who had a tibiotalar joint dislocation at the time of the ankle fracture had a significantly higher PROMIS physical function score (46.6 vs 40.2, P = .005) when their surgery included arthroscopy. Conclusion: Ankle arthroscopy at the time of ORIF led to statistically significant improvements in patient-reported outcomes for Weber B fibula fractures and ankle dislocations. There was no increase in complication rates and the arthroscopy took 10 minutes longer on average. Level of Evidence: Level III, retrospective cohort study.

Background: Documenting the healthy articulation of the syndesmosis and talocrural joints, and measurement of 3D medial and lateral clear spaces may improve diagnostic and treatment guidelines for patients suffering from severe syndesmotic injury or chronic instability. This study aimed to define the range of motion (ROM) and displacement of the fibula and talus during static and dynamic activities, and measure the 3D movement in the tibiofibular (syndesmosis) and medial clear space. Methods: Six healthy volunteers performed dynamic weightbearing motions on a single-leg: heel-rise, squat, torso twist, and box jump. Participants posed in a nonweightbearing neutral stance as well as weightbearing neutral standing, plantarflexion, and dorsiflexion. High-speed stereoradiography measured 3D rotation and translation of the fibula and talus throughout each task. Medial clear space and tibiofibular gap distances were measured under each condition. Results: Total ROM for the fibula was greatest in internal-external rotation (9.3 ± 3.5 degrees), and anteroposterior (3.3 ± 2.2 mm) and superior-inferior (2.5 ± 0.9 mm) translation, rather than lateral widening (1.7 ± 1.0 mm). The total rotational ROM of the talus was greatest in dorsiflexion-plantarflexion (34.7 ± 12.9 degrees) and internal-external rotation (15.0 ± 3.4 degrees). Single-leg squatting increased the lateral clear space ( P = .045) and widened the medial tibiofibular joint, whereas single-leg heel-rises decreased the lateral clear space ( P = .001) and widened the tibiotalar space. Gap spaces in the tibiofibular and medial clear spaces did not exceed 2.3 ± 0.9 mm and 2.7 ± 1.2 mm, respectively. Conclusion: These data support a potential shift in the clinical understanding of fibula displacements during dynamic activities and how implant device constructs might be developed to restore physiologic mechanics. Clinical Relevance: Syndesmosis stabilization and rehabilitation should consider restoration of normal physiologic rotation and translation of the fibula and ankle mortise rather than focusing solely on the restriction of lateral translation.

Contains fulltext : 245735.pdf (Publisher’s version ) (Closed access) BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with macro- and micro-thromboses, which are triggered by endothelial cell activation, coagulopathy, and uncontrolled inflammatory response. Conventional antithrombotic agents are under assessment in dozens of randomized controlled trials (RCTs) in patients with COVID-19, with preliminary results not demonstrating benefit in several studies. OBJECTIVES: Given the possibility that more novel agents with antithrombotic effects may have a potential utility for management of patients with COVID-19, we assessed ongoing RCTs including these agents with their potential mechanism of action in this population. METHODS: We searched clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to identify RCTs of novel antithrombotic agents in patients with COVID-19. RESULTS: Based on a systematic literature search, 27 RCTs with 10 novel antithrombotic agents (including nafamostat, dociparstat, rNAPc2, and defibrotide) were identified. The results from these trials have not been disseminated yet. The studied drugs in the ongoing or completed RCTs include agents affecting the coagulation cascade, drugs affecting endothelial activation, and mixed acting agents. Their postulated antithrombotic mechanisms of action and their potential impact on patient management are summarized. CONCLUSION: Some novel antithrombotic agents have pleiotropic anti-inflammatory and antiviral effects, which may help reduce the viral load or fibrosis, and improve oxygenation. Results from ongoing RCTs will elucidate their actual role in the management of patients with COVID-19.