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The Wallstent (WS; Boston Scientific, Malborough, MA) is currently the standard of care for comparisons of clinical efficacy for new stent devices in the treatment of iliac vein outflow disease. Many vein-specific Nitinol-based stents have been now approved by the Food and Drug Administration for use in the iliofemoral venous system. However, few comparisons of these devices to the current standard have been reported. The purpose of this investigation was to compare the complication and reintervention rates between the WS and Venovo stent (VS; BD, Franklin Lakes, NJ).A random sample of 100 WS and 100 VS cases performed from April 2018 through December 2020 were selected for retrospective analysis. The demographics, presenting symptoms, and CEAP (Clinical, Etiology, Anatomy, Pathophysiology) class were assessed. The complication logs and 90-day follow-up data were reviewed for every case to assess the incidence of postoperative deep vein thrombosis, stent thrombosis, in-stent restenosis, bleeding, and transient back pain.WSs had been placed more often in the left common iliac vein segment (52 vs 1), and VSs had been placed more often in the left common iliac vein and external iliac vein segments (36 vs 63; P = .0069). The average diameter and length of the WSs and VSs were 19.7 ± 2.2 mm vs 15 ± 1.4 mm (P = 2.4∗10The complication and reintervention rates between the WS and VS groups were similar. Both stents demonstrated evidence of in-stent stenosis requiring reintervention. Implanted VSs tended to be smaller in diameter and longer in length and covered the common and external iliac veins more often compared with the WSs. Therefore, one VS can be used to cover two territories compared with the WS for which two stents will be required to cover the same vein territory length.

Background The use of iliac vein stenting for the treatment of pelvic pain secondary to pelvic venous insufficiency has significantly increased. In women of childbearing age, the effect of the gravid uterus on stent function and patency is unclear. The purpose of this investigation was to determine the effect of pregnancy on stent patency and reintervention rate in women with iliac vein stents. Methods A retrospective chart review and email survey was performed to identify women treated at the Center for Vascular Medicine who were treated with iliac vein stenting and who had subsequent pregnancies. Medical and surgical comorbidities, stent type, location, length, number of stents, reintervention rates, number of pregnancies after stenting, anticoagulation usage during pregnancy, and type of delivery were assessed. Results From January 2014 to December 2020, 15 women with 16 iliac vein stents and who had 17 subsequent pregnancies were identified. The average age at stenting was 35.3 ± 4.13 years. The average interval between stenting and conception was 350 ± 287 days. Before pregnancy, stent location was in the right common/right external iliac veins in 1 patient and left common/external iliac veins in 14 patients. The average stent diameter and length were 19.6 ± 3 and 79.5 ± 20.3 mm, respectively. Thirteen Boston Scientific Wallstents and three Bard Venovo stents were used before pregnancy. One patient with a Wallstent required a stent extension before pregnancy and one patient had two stents placed at the initial procedure. Two women were pregnant twice after stenting for a total of 17 pregnancies. There were 16 term and 1 premature delivery of single infants. Patients were treated with enoxaparin (Lovenox) for stent-related thrombosis prophylaxis in 11 of 17 pregnancies, 5 had no prophylaxis, and the status of 1 pregnancy is unknown. One asymptomatic patient underwent a stent venoplasty after delivery. Conclusions Iliac vein stents tolerate a gravid uterus well. No stents thrombosed during or after pregnancy and none required reintervention secondary to pregnancy-related compression. Anticoagulation with low-molecular-weight heparin should be considered for stent thrombosis prophylaxis. Potential pregnancy should not be considered a contraindication to iliac vein stenting for the treatment of symptomatic pelvic venous insufficiency.

Fosmanogepix (FMGX), a novel antifungal available in intravenous (IV) and oral formulations, has broad-spectrum activity against pathogenic yeasts and molds, including fungi resistant to standard of care antifungals. This multicenter, open-label, single-arm study evaluated FMGX safety and efficacy for treatment of candidemia and/or invasive candidiasis caused by Candida auris .

Background Venous stenting for iliac vein outflow obstruction is associated with excellent long-term stent patency and symptom resolution. However, the safety of iliac vein stenting performed in an office-based laboratory (OBL) setting is not well-defined. The purpose of our investigation was to determine the safety profile of iliac vein stenting in an OBL setting. Methods Data were prospectively collected in the Center for Vascular Medicine electronic medical record system (NextGen Healthcare Information System, Irvine, Calif) and retrospectively analyzed. Standardized patient safety and sedation protocols were used in accordance with the accreditation standards of the Joint Commission for Accreditation of Hospital Organizations for office-based surgery centers. Patient consultations, interventions, and follow-up at 1 to 6 weeks were included in the present analysis. All the patients had received moderate sedation during their procedure. Complications requiring hospitalization were classified as major complications. Minor complications consisted of bleeding, hematoma, vasovagal response, in-stent thrombosis resulting in complete occlusion of the iliac vein stent, an allergic reaction, hematemesis, hypotension, pelvic discomfort, and pseudoaneurysm. Results Between January 2015 and January 2019, 1223 iliac vein stents were placed in 1104 patients (23.7% male; 76.3% female). A total of 90 minor complications (7.36%) and 5 major complications (0.41%) were observed. The major complications included the following: one allergic reaction, one episode of atrial fibrillation, one episode of supraventricular tachycardia, one episode of chest pain, and one case of acute stent occlusion. The minor complications were primarily insertion site hematomas. No complications were related to sedation or acute renal failure. No patient died. Conclusions Major complications were rare after iliac vein stenting in an OBL setting. Minor complications were primarily insertion site hematomas, which did not require inpatient hospitalization. Our analysis has shown that iliac vein stenting in an OBL setting is a safe and well-tolerated procedure.

Item does not contain fulltext BACKGROUND: Rezafungin is a next-generation, once-a-week echinocandin in development for the treatment of candidaemia and invasive candidiasis and for the prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp after blood and marrow transplantation. We aimed to compare the efficacy and safety of intravenous rezafungin versus intravenous caspofungin in patients with candidaemia and invasive candidiasis. METHODS: ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial done at 66 tertiary care centres in 15 countries. Adults (≥18 years) with systemic signs and mycological confirmation of candidaemia or invasive candidiasis were eligible for inclusion and randomly assigned (1:1) to receive intravenous rezafungin once a week (400 mg in week 1, followed by 200 mg weekly, for a total of two to four doses) or intravenous caspofungin (70 mg loading dose on day 1, followed by 50 mg daily) for no more than 4 weeks. The primary endpoints were global cure (consisting of clinical cure, radiological cure, and mycological eradication) at day 14 for the European Medical Agency (EMA) and 30-day all-cause mortality for the US Food and Drug Administration (FDA), both with a target non-inferiority margin of 20%, assessed in the modified intention-to-treat population (all patients who received one or more doses of study drug and had documented Candida infection based on a culture from blood or another normally sterile site obtained within 96 h before randomisation). Safety was evaluated by the incidence and type of adverse events and deaths in the safety population, defined as all patients who received any amount of study drug. The trial is registered with ClinicalTrials.gov, NCT03667690, and is complete. FINDINGS: Between Oct 12, 2018, and Aug 29, 2021, 222 patients were screened for inclusion, and 199 patients (118 [59%] men; 81 [41%] women; mean age 61 years [SD 15·2]) were randomly assigned (100 [50%] patients to the rezafungin group and 99 [50%] patients to the caspofungin group). 55 (59%) of 93 patients in the rezafungin group and 57 (61%) of 94 patients in the caspofungin group had a global cure at day 14 (weighted treatment difference -1·1% [95% CI -14·9 to 12·7]; EMA primary endpoint). 22 (24%) of 93 patients in the rezafungin group and 20 (21%) of 94 patients in the caspofungin group died or had an unknown survival status at day 30 (treatment difference 2·4% [95% CI -9·7 to 14·4]; FDA primary endpoint). In the safety analysis, 89 (91%) of 98 patients in the rezafungin group and 83 (85%) of 98 patients in the caspofungin group had at least one treatment-emergent adverse event. The most common treatment-emergent adverse events that occurred in at least 5% of patients in either group were pyrexia, hypokalaemia, pneumonia, septic shock, and anaemia. 55 (56%) patients in the rezafungin group and 52 (53%) patients in the caspofungin group had serious adverse events. INTERPRETATION: Our data show that rezafungin was non-inferior to caspofungin for the primary endpoints of day-14 global cure (EMA) and 30-day all-cause mortality (FDA). Efficacy in the initial days of treatment warrants evaluation. There were no concerning trends in treatment-emergent or serious adverse events. These phase 3 results show the efficacy and safety of rezafungin and support its ongoing development. FUNDING: Cidara Therapeutics and Mundipharma.

Background Rezafungin is a next-generation, once-weekly echinocandin in development for treatment of candidemia and invasive candidiasis (IC), and for prevention of invasive fungal diseases caused by Candida, Aspergillus, and Pneumocystis in allogeneic blood and marrow transplant recipients (Fig 1). ReSTORE (NCT03667690) is a global, double-blind, double-dummy, 1:1 randomized, controlled, Phase 3 non-inferiority trial that evaluated the efficacy and safety of rezafungin once weekly (QWk) versus caspofungin once daily (QD) in patients with candidemia and/or IC. This analysis of the completed ReSTORE trial was conducted to evaluate outcomes by baseline pathogen and susceptibility. Methods In ReSTORE, adults (≥18 y) with systemic signs and mycological confirmation of candidemia and/or IC received either rezafungin QWk (400 mg Week 1, then 200 mg QWk) or caspofungin QD for ≥14 days (up to 4 weeks) with optional oral fluconazole step-down in the caspofungin arm. The primary endpoints were global cure at day (D) 14 (per Data Review Committee confirmation of investigator-assessed clinical cure [and radiological cure for IC) + mycological eradication]) and all-cause mortality (ACM) at D30 (Fig 2). Secondary endpoints included mycological eradication at D14. For this analysis, D14 global cure and mycological eradication by treatment group were analyzed by Candida species and in vitro susceptibility at baseline (CLSI broth microdilution MIC values; M27 Ed4) (Fig 3). Results A total of 204 Candida isolates were recovered in 187 patients across both treatment groups. Of the 204 isolates, C. albicans was the most common species, followed by C. glabrata, C. tropicalis, and C. parapsilosis; 61% of all baseline isolates were non-albicans Candida (Fig 3). The rates of D14 global cure and mycological eradication by pathogen are shown in Tables 1 and 2. Overall, outcomes by Candida species and MIC did not appear to be affected by MIC values for either rezafungin or caspofungin (Table 3). Conclusion Rezafungin was efficacious across multiple Candida species in the Phase 3 ReSTORE trial that demonstrated non-inferiority of rezafungin to caspofungin. There was no clear correlation between increased MIC values and clinical outcomes. Disclosures George R. Thompson, III, MD, Amplyx: Advisor/Consultant|Amplyx: Grant/Research Support|Astellas: Advisor/Consultant|Astellas: Grant/Research Support|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Merck: Grant/Research Support|Pfizer: DSMB|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support Alex Soriano, MD, MSD, Pfizer, Shionogi, Angelini, Menarini, Gilead: Honoraria Oliver A. Cornely, Prof. Dr., Abbott: Honoraria|Abbvie: Advisor/Consultant|Actelion: Board Member|Al-Jazeera Pharmaceuticals: Honoraria|Allecra Therapeutics: Board Member|Amplyx: Advisor/Consultant|Amplyx: Grant/Research Support|Astellas: Honoraria|Basilea: Advisor/Consultant|Basilea: Grant/Research Support|Biocon: Advisor/Consultant|Biosys: Advisor/Consultant|BMBF: Grant/Research Support|Cidara: Advisor/Consultant|Cidara: Board Member|Cidara: Expert Testimony|Cidara: Grant/Research Support|CoRe Consulting: Stocks/Bonds|Da Volterra: Advisor/Consultant|DLR: Grant/Research Support|DZIF: Grant/Research Support|Entasis: Board Member|EU Directorate-General for Resarch and Innovation: Grant/Research Support|F2G: Grant/Research Support|German Patent and Trade Mark Office: German patent (DE 10 2021 113 007.7)|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Grupo Biotoscana/United Medical/Knight: Honoraria|Hikma: Honoraria|IQVIA: Board Member|Janssen: Board Member|Matinas: Advisor/Consultant|Matinas: Grant/Research Support|MedPace: Advisor/Consultant|MedPace: Grant/Research Support|MedScape: Honoraria|MedUpdate: Honoraria|Menarini: Advisor/Consultant|Merck/MSD: Grant/Research Support|Merck/MSD: Honoraria|Molecular Partners: Advisor/Consultant|MSG-ERC: Advisor/Consultant|Mundipharma: Grant/Research Support|Mylan: Honoraria|Noxxon: Advisor/Consultant|Octapharma: Advisor/Consultant|Octapharma: Grant/Research Support|Paratek: Board Member|Pardes: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Projektträger Jülich: Grant/Research Support|PSI: Advisor/Consultant|PSI: Board Member|Pulmocide: Board Member|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support|Seres: Advisor/Consultant|Shionogi: Board Member|Wiley (Blackwell): Editor-in-Chief, Mycoses Bart-Jan Kullberg, MD, FRCP, FIDSA, Cidara: Independent Data Review Committee Jeffrey B. Locke, PhD, Cidara Therapeutics: Employee|Cidara Therapeutics: Stocks/Bonds Taylor Sandison, MD, MPH, Cidara Therapeutics: Employee|Cidara Therapeutics: Stocks/Bonds.

Introduction Endovascular stenting is the standard of care for the management of symptomatic chronic venous obstruction. The increased radial resistive force and longer lengths of Nitinol stents have led to questions over persistent post-operative back pain. The purpose of this investigation was to assess the incidence and severity of post-operative back pain of Nitinol stents compared to Wallstents. Methods A retrospective review of data at the Center for Vascular Medicine was performed. Patient demographics, pre-operative, one week, three-, six,- and 12 month visual analog pain scores (VAS) for back pain, stent type, diameter, length, and vein locations were assessed. Results From April 2014 to November 2021, 627 (412 women/215 men) patients were assessed for the presence of post-operative back pain after an initial iliac vein stent placement. Stents utilized were Wallstents ( n = 114), Venovo ( n = 342), and Abre ( n = 171). The most common Nitinol stent diameter and lengths were 14 mm, 16 mm, and 120 mm, respectively ( p ≤ .03). The incidence of back pain at one week was 66% (411/627). VAS scores at one week and one, three, and six months post-operatively were the following: Wallstents-2.6 ± 3 ( n = 66), 1.7 ± 2.6 ( n = 43) 0.7 ± 2 ( n = 51), and 0 ± 0 ( n = 27); Abre-3.5 ± 3 ( n = 130), 3.8 ± 3 ( n = 19), 1.2 ± 2.5 ( n = 12), and 1 ± 2 ( n = 5); and Venovo- 2.5 ± 3 ( n = 216), 2.4 ± 3 ( n = 70), 0.9 ± 2 ( n = 68), and 0.6 ± 1.7 ( n = 49). There was no difference in the severity of back pain at any time point ( p ≥ .99). The development of back pain was unrelated to stent type, diameter, length, or covered vein territory. Conclusions Post-operative back pain was observed in 66% of patients at one week. The average pain score at one week for the entire cohort was three, which declined to less than one at one month. No difference in the severity of back pain between groups was observed at any time point, and the development of back pain is unrelated to stent type, diameter, length, or covered vein territory.

Invasive candidiasis (IC) is a collective term that refers to a group of infectious syndromes caused by a variety of species of Candida, 6 of which cause most cases globally. Candidemia is probably the most commonly recognized syndrome associated with IC; however, Candida can cause invasive infection of any organ, especially visceral organs, vasculature, bones and joints, the eyes and central nervous system. Targeted prevention and empirical therapy are important interventions for patients at high risk for IC, and the current approach should be based on a combination of clinical risk factors and non-culture-based diagnostics, when available.

Cryptococcal antigen (CrAg) detection could direct the timely initiation of antifungal therapy. We searched MEDLINE and Embase for studies where CrAg detection in serum/cerebrospinal fluid (CSF) and CSF fungal culture were done on adults living with human immunodeficiency virus (HIV) who had suspected cryptococcal meningitis (CM). With Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), we evaluated the risk of bias in 11 included studies with 3600 participants, and used a random-effects meta-analysis to obtain summary sensitivity and specificity of serum and CSF CrAg, as well as agreement between CSF CrAg and CSF culture. Summary sensitivity and specificity of serum CrAg were 99.7% (97.4–100) and 94.1% (88.3–98.1), respectively, and summary sensitivity and specificity of CSF CrAg were 98.8% (96.2–99.6) and 99.3% (96.7–99.9), respectively. Agreement between CSF CrAg and CSF culture was 98% (97–99). In adults living with HIV who have CM symptoms, serum CrAg negativity may rule out CM, while positivity should prompt induction antifungal therapy if lumbar puncture is not feasible. In a first episode of CM, CSF CrAg positivity is diagnostic.

Objective To measure patient preferences for attributes associated with thermal ablation and non-thermal, non-tumescent varicose vein treatments. Methods Data were collected from an electronic patient-preference survey taken by 70 adult participants (aged 20 years or older) at 3 Center for Vein Restoration clinics in New Jersey from July 19, 2019, through August 13, 2019. Survey participation was voluntary and anonymous (participation rate of 80.5% [70/87]). Patients were shown 10 consecutive screens that displayed 3 hypothetical treatment scenarios with different combinations of 6 attributes of interest and a “None” option. Choice-based conjoint analysis estimated the relative importance of different aspects of care, trade-offs between these aspects, and total satisfaction that respondents derived from different healthcare procedures. Market simulation analysis compared clusters of attributes mimicking thermal ablation and non-thermal, non-tumescent treatments. Results Of the 6 attributes studied, out-of-pocket expenditures were the most important to patients (37.2%), followed by postoperative discomfort (17.1%), risk of adverse events (16.3%), time to return to normal activity (11.0%), number of injections (10.0%), and number of visits (8.4%). Patients were willing to pay the most to avoid postoperative discomfort ($68.9) and risk of adverse events ($65.8). The market simulation analysis found that, regardless of the level of out-of-pocket spending, 60%-80% of respondents favored attribute combinations corresponding to non-thermal, non-tumescent procedures over thermal ablation, and that less than 1% of participants would forgo either treatment under no cost-sharing. Conclusions Patients are highly sensitive to out-of-pocket costs for minimally-invasive varicose vein treatments. Market simulation analysis favored non-thermal, non-tumescent procedures over thermal ablation.

Background In March 2020, the World Health Organization declared COVID-19, caused by the SARS-CoV-2 virus, a pandemic. Patients with severe cases resulting in hospitalization and mechanical ventilation are at risk for COVID-19–associated pulmonary aspergillosis, an invasive fungal infection, and should be screened for aspergillosis if they have persistent hemodynamic instability and fever. Early detection and treatment of this fungal infection can significantly reduce morbidity and mortality in this population. Objective To develop an evidence-based care step pathway tool to help intensive care unit clinicians assess, diagnose, and treat COVID-19–associated pulmonary aspergillosis. Methods A panel of 18 infectious disease experts, advanced practice registered nurses, pharmacists, and clinical researchers convened in a series of meetings to develop the Care Step Pathway tool, which was modeled on a tool developed by advanced practice nurses to evaluate and manage side effects of therapies for melanoma. The Care Step Pathway tool addresses various aspects of disease management, including assessment, screening, diagnosis, antifungal treatment, pharmacological considerations, and exclusion of other invasive fungal coinfections. Results The Care Step Pathway tool was applied in the care of a patient with COVID-19–associated aspergillosis. The patient was successfully treated. Conclusion The Care Step Pathway is an effective educational tool to help intensive care unit clinicians consider fungal infection when caring for COVID-19 patients receiving mechanical ventilation in the intensive care unit, especially when the clinical course is deteriorating and antibiotics are ineffective.

Invasive fungal infections continue to increase as at-risk populations expand. The high associated morbidity and mortality with fungal diseases mandate the continued investigation of novel antifungal agents and diagnostic strategies that include surrogate biomarkers. Biologic markers of disease are useful prognostic indicators during clinical care, and their use in place of traditional survival end points may allow for more rapid conduct of clinical trials requiring fewer participants, decreased trial expense, and limited need for long-term follow-up. A number of fungal biomarkers have been developed and extensively evaluated in prospective clinical trials and small series. We examine the evidence for these surrogate biomarkers in this review and provide recommendations for clinicians and regulatory authorities.

In this article, the editors of Clinical Infectious Diseases review some of the most important lessons they have learned about the epidemiology, clinical features, diagnosis, treatment and prevention of SARS-CoV-2 infection and identify essential questions about COVID-19 that remain to be answered., This article reviews important lessons learned to this day, October 15, 2020, about the epidemiology, clinical virology, presentation, complications, diagnosis, treatment and prevention of SARS-CoV-2 infection and identifies essential questions about the COVID-19 pandemic that remain to be answered.

Background Assessment of the immediate need for specific blood product transfusions in acutely bleeding patients is challenging. Clinical assessment and commonly used coagulation tests are inaccurate and time-consuming. The goal of this practice management guideline was to evaluate the role of the viscoelasticity tests, which are thromboelastography (TEG) and rotational thromboelastometry (ROTEM), in the management of acutely bleeding trauma, surgical, and critically ill patients. Methods Systematic review and meta-analyses of manuscripts comparing TEG/ROTEM with non-TEG/ROTEM-guided blood products transfusions strategies were performed. The Grading of Recommendations Assessment, Development and Evaluation methodology was applied to assess the level of evidence and create recommendations for TEG/ROTEM-guided blood product transfusions in adult trauma, surgical, and critically ill patients. Results Using TEG/ROTEM-guided blood transfusions in acutely bleeding trauma, surgical, and critically ill patients was associated with a tendency to fewer blood product transfusions in all populations. Thromboelastography/ROTEM-guided transfusions were associated with a reduced number of additional invasive hemostatic interventions (angioembolic, endoscopic, or surgical) in surgical patients. Thromboelastography/ROTEM-guided transfusions were associated with a reduction in mortality in trauma patients. Conclusion In patients with ongoing hemorrhage and concern for coagulopathy, we conditionally recommend using TEG/ROTEM-guided transfusions, compared with traditional coagulation parameters, to guide blood component transfusions in each of the following three groups: adult trauma patients, adult surgical patients, and adult patients with critical illness. Level of evidence Systematic Review/Meta-Analysis, level III.

Background Rezafungin (RZF) is a novel echinocandin exhibiting distinctive pharmacokinetics/pharmacodynamics. STRIVE was a phase 2, double-blind, randomized trial designed to compare the safety and efficacy of RZF once weekly (QWk) to caspofungin (CAS) once daily for treatment of candidemia and/or invasive candidiasis (IC). Methods Adults with systemic signs and mycological confirmation of candidemia and/or IC were randomized to RZF 400 mg QWk (400 mg), RZF 400 mg on week 1 then 200 mg QWk (400/200 mg), or CAS 70 mg as a loading dose followed by 50 mg daily for ≤4 weeks. Efficacy assessments included overall cure (resolution of signs of candidemia/IC + mycological eradication) at day 14 (primary endpoint), investigator-assessed clinical response at day 14, and 30-day all-cause mortality (ACM) (secondary endpoints), and time to negative blood culture. Safety was evaluated by adverse events and ACM through follow-up. Results Of 207 patients enrolled, 183 were in the microbiological intent-to-treat population (~21% IC). Overall cure rates were 60.5% (46/76) for RZF 400 mg, 76.1% (35/46) for RZF 400/200 mg, and 67.2% (41/61) for CAS; investigator-assessed clinical cure rates were 69.7% (53/76), 80.4% (37/46), and 70.5% (43/61), respectively. In total, 30-day ACM was 15.8% for RZF 400 mg, 4.4% for RZF 400/200 mg, and 13.1% for CAS. Candidemia was cleared in 19.5 and 22.8 hours in RZF and CAS patients, respectively. No concerning safety trends were observed; ACM through follow-up was 15.2% (21/138) for RZF and 18.8% (13/69) for CAS. Conclusions RZF was safe and efficacious in the treatment of candidemia and/or IC. Clinical Trials Registration NCT02734862, In a phase 2, randomized, double-blind, multicenter clinical trial conducted to evaluate rezafungin compared with caspofungin followed by fluconazole for primary treatment of patients with proven candidemia or invasive candidiasis, rezafungin demonstrated favorable safety and efficacy.

Background The prevalence and presentation patterns in women with pelvic venous disorders (PeVD) secondary to pelvic venous insufficiency (PVI) at various ages are ill-defined. The purpose of this investigation was to determine if the types of symptoms, interventions, and treatment outcomes of women with PeVD varied with age progression. Methods From January 2015 to December 2019, we retrospectively reviewed prospectively collected data on 1,280 women with PeVD from our electronic medical record at the Center for Vascular Medicine (CVM). Medical and surgical comorbidities, past medical history, presenting pelvic and lower extremity symptoms, Clinical, Etiology, Anatomy, Pathophysiology (CEAP) class, revised Venous Clinical Severity Score (rVCSS), visual analog pain score (VAS) and types of interventions were assessed. Patients were grouped into five categories based on age of initial presentation: 20–29, 30–39, 40–49, 50–59, and greater than or equal to 60. Patients were also subcategorized according to their course of treatment: Iliac venous stenting alone, ovarian vein embolization (OVE) alone, simultaneous iliac vein stenting and ovarian vein embolization, and staged iliac vein stenting and ovarian vein embolization. Differences in groups were analyzed utilizing chi square, analysis of variance and regression analysis with Graphpad Prism 8 (San Diego, CA) and SAS Studio 3.8 (Cary, NC) statistical software. Results From January 2015 through December 2019, 1,280 women were treated for PeVD. The average ages in each group were the following: 26.53 ± 2.90 (n = 57), 35.80 ± 2.84 (n = 238), 44.98 ± 2.78 (n = 345), 54.67 ± 2.90 (n = 324) and 68.39 ± 8.44 (n = 316) respectively. The prevalence of PVI by age group was 4.45%,18.59%, 26.95%, 25.31% and 24.70% respectively (p Conclusion PeVD presents as a spectrum of signs and symptoms, with pelvic and leg symptoms being inversely related according to age. The prevalence of PeVD is lowest in patients in their twenties with differences in presentation observed with increasing age. Venous stenting progressively increases with each decile of age whereas the prevalence of OVE is similar regardless of age. There is overall improvement in symptoms post intervention, although women in their 20 s do not respond as well to intervention as women in other age groups. Future investigations will focus on determining which pelvic venous lesion is the predominant factor that needs correction to achieve maximal pain reduction.

Invasive fungal diseases cause significant morbidity and mortality, in particular affecting immunocompromised patients. Resistant organisms are of increasing importance, yet there are many notable differences in the ability to both perform and interpret antifungal susceptibility testing compared with bacteria. In this review, we will highlight the strengths and limitations of resistance data of pathogenic yeasts and moulds that may be used to guide treatment and predict clinical outcomes.

Antibody immunity has not been studied in organ transplant recipients (OTRs) with cryptococcosis. We determined serum antibody levels in OTRs: 23 cryptococcosis cases and 21 controls. Glucuronoxylomannan immunoglobulin M (IgM) and laminarin IgM were lower in cases than controls, were inversely associated with cryptococcosis status, and may hold promise as markers of cryptococcosis.

Coronavirus disease 2019 (COVID-19) can become complicated by secondary invasive fungal infections (IFIs), stemming primarily from severe lung damage and immunologic deficits associated with the virus or immunomodulatory therapy. Other risk factors include poorly controlled diabetes, structural lung disease and/or other comorbidities, and fungal colonization. Opportunistic IFI following severe respiratory viral illness has been increasingly recognized, most notably with severe influenza. There have been many reports of fungal infections associated with COVID-19, initially predominated by pulmonary aspergillosis, but with recent emergence of mucormycosis, candidiasis, and endemic mycoses. These infections can be challenging to diagnose and are associated with poor outcomes. The reported incidence of IFI has varied, often related to heterogeneity in patient populations, surveillance protocols, and definitions used for classification of fungal infections. Herein, we review IFI complicating COVID-19 and address knowledge gaps related to epidemiology, diagnosis, and management of COVID-19–associated fungal infections.

This chapter covers blastomycosis, which is a systemic pyogranulomatous disease caused by the thermally dimorphic fungus Blastomyces dermatitidis. It mentions B. gilchristii, and B. helices as other pathogenic agents of blastomycosis. It also explains that blastomycosis is endemic to parts of the midwestern and south-central United States and Canada, but there have also been isolated reports of its occurrence in Africa, Asia, and Central and South America. The chapter reviews evidence that indicates that B. dermatitidis exists in warm moist soil enriched by organic debris, including decaying vegetation and wood and that infections occur through inhalation of aerosolized spores. It points out that primary infections from B. dermatitidis are usually asymptomatic or may result in a self-limited flu-like illness.

Background Duplex ultrasound vein mapping (DUVM) may increase autogenous dialysis access procedures but has not been universally adopted by surgeons. Methods We determined reliability and accuracy of arm vein measurements on physical examination (PE) and DUVM, compared to direct measurements in the operating room (OR, gold standard). Operative plans were developed from each set of measurements and we evaluated which approach identified more options for autogenous procedures. Results Vein diameters measured on DUVM correlated well with OR measurements but those made on PE did not. Autogenous access options were identified in 34.8% of patients based on PE and in 96.6% based on their DUVM. The 6-month primary-patency was 86.4%; assisted primary-patency was 89.8%. Conclusions Duplex ultrasound vein mapping is more reliable and accurate for assessing arm vein anatomy than physical examination. It identifies more autogenous options than physical-examination alone. It is essential for the preoperative evaluation for dialysis access.

Objectives To evaluate the safety and efficacy of two dosing regimens of oral ibrexafungerp (formerly SCY-078), a novel orally bioavailable β-glucan synthase inhibitor, in subjects with invasive candidiasis versus the standard of care (SOC) and to identify the dose to achieve target exposure (15.4 μM·h) in >80% of the intended population. Methods In a multinational, open-label study, patients with documented invasive candidiasis were randomized to receive step-down therapy to one of three treatment arms: two dosing regimens of novel oral ibrexafungerp or the SOC treatment following initial echinocandin therapy. Plasma samples were collected to evaluate exposure by population pharmacokinetic (PK) modelling. Safety was assessed throughout the study and global response at the end of treatment. Results Out of 27 subjects enrolled, 7 received ibrexafungerp 500 mg, 7 received ibrexafungerp 750 mg and 8 received the SOC. Five did not meet criteria for randomization. Population PK analysis indicated that an ibrexafungerp 750 mg regimen is predicted to achieve the target exposure in ∼85% of the population. The rate of adverse events was similar among patients receiving ibrexafungerp or fluconazole. Similar favourable response rates were reported among all groups: 86% (n = 6) in the ibrexafungerp 750 mg versus 71% (n = 5) in both the fluconazole and ibrexafungerp 500 mg treatment arms. The one subject treated with continued micafungin had a favourable global response. Conclusions The oral ibrexafungerp dose estimated to achieve the target exposure in subjects with invasive candidiasis is 750 mg daily. This dose was well tolerated and achieved a favourable global response rate, similar to the SOC.

Background Candida species are a major cause of invasive and mucocutaneouls infections. There are limited oral treatment options available for patients with Candida infections who are unresponsive to or who are intolerant of currently available antifungals. Oral ibrexafungerp is an investigational broad-spectrum glucan synthase inhibitor antifungal with activity against Candida and Aspergillus species, including azole- and echinocandin-resistant strains. A Phase 3 open-label, single-arm study of ibrexafungerp (FURI; NCT03059992) is ongoing for the treatment of patients intolerant of or with fungal disease refractory to standard antifungal therapy. We present an analysis of patient outcomes from the FURI study by fungal disease type. Table 1: FURI Outcomes by Fungal Disease Methods FURI patients were eligible for enrollment if they have proven or probable, severe mucocutaneous candidiasis, invasive candidiasis or invasive aspergillosis,other fungal diseases and evidence of failure to, intolerance to, or toxicity related to a currently approved standard-of-care antifungal treatment or can not receive approved oral antifungal options (e.g., susceptibility of the organism) and a continued IV antifungal therapy is clinically undesirable or unfeasible. Results An independent Data Review Committee (DRC) provided an assessment of treatment response for 74 patients enrolled in the FURI study from 22 centers in US, UK and EU treated with ibrexafungerp for mucocutaneous or invasive fungal infections from 2016- 2020. A total of 39 (52.7%) patients had invasive candidiasis, 32 (43.2%) had mucocutaneous candidiasis and 3 (4.5%) patients had invasive aspergillosis. The percent of patients who were determined to have a complete response (CR), partial response (PR), clinical improvement (CI) was 63.5%, stable disease (SD) was 23.0%, patients with progression of disease 6.8% and 4 patients were indeterminate. Additionally, there was 1 death in the FURI study that was not related to fungal disease. Table 1 shows outcomes by fungal disease type as determined by the DRC. Conclusion Analysis of 74 patients from the FURI study indicates that oral ibrexafungerp provides a favorable therapeutic response in patients with challenging fungal disease and limited treatment options. Disclosures Peter G. Pappas, MD, Astellas (Research Grant or Support)Cidara (Research Grant or Support)F2G (Consultant)Matinas (Consultant, Scientific Research Study Investigator)Mayne Pharma (Research Grant or Support)Scynexis (Research Grant or Support) Oliver Cornely, Prof., Actelion (Consultant, Grant/Research Support)Al-Jazeera Pharmaceuticals (Consultant)Allecra Therapeutics (Consultant)Amplyx (Consultant, Grant/Research Support)Astellas (Consultant, Grant/Research Support)Basilea (Consultant, Grant/Research Support)Biocon (Consultant)Biosys (Consultant)Cidara (Consultant, Grant/Research Support)CoRe Consulting (Consultant)Da Volterra (Consultant, Grant/Research Support)DFG (German Research Foundation) (Grant/Research Support)Entasis (Consultant)F2G (Consultant, Grant/Research Support)German Federal Ministry of Research and Education (Grant/Research Support)Gilead (Consultant, Grant/Research Support)Grupo Biotoscana (Consultant)Immunic (Grant/Research Support)IQVIA (Consultant)Janssen (Grant/Research Support)Matinas (Consultant)Medicines Company (Grant/Research Support)MedPace (Consultant, Grant/Research Support)Melinta Therapeutics (Grant/Research Support)Menarini (Consultant)Merck/MSD (Consultant, Grant/Research Support)Molecular Partners (Consultant)MSG-ERC (Consultant)Mylan (Consultant)Nabriva (Consultant)Noxxon (Consultant)Octapharma (Consultant)Paratek (Consultant)Pfizer (Consultant, Grant/Research Support)PSI (Consultant)Roche Diagnostics (Consultant)Scynexis (Consultant, Grant/Research Support)Seres (Consultant)Shionogi (Consultant)Wiley (Blackwell) (Other Financial or Material Support) Philipp Koehler, MD, Ambu GmbH (Consultant, Speaker's Bureau)Astellas Pharma (Speaker's Bureau)Euopean Confederation of Medical Mycology (Speaker's Bureau)German Federal Ministry of Research and Education (Grant/Research Support)Gilead (Consultant, Speaker's Bureau)MSD (Speaker's Bureau)Noxxon N.V. (Consultant)Pfizer (Speaker's Bureau)State of North Rhine-Westphalia, Germany (Grant/Research Support) Todd P. McCarty, MD, Cidara (Grant/Research Support)GenMark (Grant/Research Support, Other Financial or Material Support, Honoraria for Research Presentation)T2 Biosystems (Consultant) Barbara D. Alexander, MD, MHS, SCYNEXIS, Inc. (Consultant) Rachel Miller, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Caryn Morse, MD, Chimerix (Scientific Research Study Investigator)Covis Pharma (Scientific Research Study Investigator)Gilead Sciences Inc. (Scientific Research Study Investigator)Ridgeback Biotherapeutics (Scientific Research Study Investigator)Roche (Scientific Research Study Investigator)SCYNEXIS, Inc. (Scientific Research Study Investigator)Theratechnologies (Advisor or Review Panel member)Viiv (Advisor or Review Panel member) Luis Ostrosky-Zeichner, MD, Amplyx (Consultant)Cidara (Consultant)F2G (Consultant)Gilead (Grant/Research Support, Speaker's Bureau)Pfizer (Scientific Research Study Investigator, Speaker's Bureau)Scynexis (Grant/Research Support, Scientific Research Study Investigator)Viracor (Consultant) Jürgen Prattes, Dr, AbbVie Inc. (Shareholder)Gilead (Speaker's Bureau)MSD (Grant/Research Support)Novo Nordisk (Shareholder)Pfizer (Advisor or Review Panel member)Stryker (Shareholder) Andrej Spec, MD, MSCI, Mayne Pharma (Grant/Research Support) Riina Rautemaa-Richardson, DDS, PhD, FRCPath, SCYNEXIS, Inc. (Scientific Research Study Investigator) Thomas J. Walsh, MD, PhD (hon), Scynexis (Consultant, Grant/Research Support)Shionogi (Consultant, Grant/Research Support) Francisco M. Marty, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Marisa Miceli, MD, SCYNEXIS, Inc. (Advisor or Review Panel member) Martin Hoenigl, MD, Astellas (Grant/Research Support)Gilead (Grant/Research Support)Pfizer (Grant/Research Support) Martin Hoenigl, MD, Astellas (Individual(s) Involved: Self): Grant/Research Support; F2G (Individual(s) Involved: Self): Grant/Research Support; Gilead (Individual(s) Involved: Self): Grant/Research Support; Pfiyer (Individual(s) Involved: Self): Grant/Research Support; Scýnexis (Individual(s) Involved: Self): Grant/Research Support Thomas F. Patterson, MD, SCYNEXIS, Inc. (Advisor or Review Panel member) Nkechi Azie, MD, SCYNEXIS, Inc. (Employee, Shareholder) David A. Angulo, MD, SCYNEXIS, Inc. (Employee, Shareholder)

Objective The purpose of this review was to provide an evidence-based recommendation for community-based programs to mitigate gun violence, from the Eastern Association for the Surgery of Trauma (EAST). Summary background data Firearm Injury leads to >40,000 annual deaths and >115,000 injuries annually in the United States. Communities have adopted culturally relevant strategies to mitigate gun related injury and death. Two such strategies are gun buyback programs and community-based violence prevention programs. Methods The Injury Control and Violence Prevention Committee of EAST developed Population, Intervention, Comparator, Outcomes (PICO) questions and performed a comprehensive literature and gray web literature search. Using GRADE methodology, they reviewed and graded the literature and provided consensus recommendations informed by the literature. Results A total of 19 studies were included for analysis of gun buyback programs. Twenty-six studies were reviewed for analysis for community-based violence prevention programs. Gray literature was added to the discussion of PICO questions from selected websites. A conditional recommendation is made for the implementation of community-based gun buyback programs and a conditional recommendation for community-based violence prevention programs, with special emphasis on cultural appropriateness and community input. Conclusions Gun violence may be mitigated by community-based efforts, such as gun buybacks or violence prevention programs. These programs come with caveats, notably community cultural relevance and proper support and funding from local leadership.Level of Evidence: Review, Decision, level III.

Objective Endovenous therapies are currently the standard of care for the treatment of patients with symptomatic great saphenous vein (GSV) reflux. The effectiveness and long-term outcomes of these therapies for anterior accessory great saphenous veins (AAGSVs) are poorly defined. The objective of this investigation is to determine treatment outcomes in patients with symptomatic AAGSV reflux compared with patients with symptomatic GSV reflux. Methods Data were prospectively collected in the Center for Vein Restoration's electronic medical record system (NexGen Healthcare Information System, Irvine, Calif) and retrospectively analyzed. Treatment outcomes after a standalone ablation and ablation + phlebectomy were compared in patients with isolated AAGSV and GSV reflux. Treatment outcomes were assessed at 1 month and 6 months postprocedure using the revised Venous Clinical Severity Score (rVCSS) and the 20-item Chronic Venous Insufficiency Quality-of-Life Questionnaire (CIVIQ20) survey for quality of life. Medical and surgical comorbidities, Clinical-Etiological-Anatomical-Pathophysiological classification, body mass index, gender, race, and the average number of procedures performed were all analyzed. Results From January 2015 to December 2018, 31,186 patients and 49,193 limbs were assessed. Of these, 91 patients/103 limbs had isolated AAGSV reflux, and 7704 patients/10,371 limbs had isolated GSV reflux. There were 95% and 75% women in the isolated AAGSV and GSV groups, respectively (P ≤ .001). For the ablation-only patients, AAGSV (n = 57 patients/61 limbs) and GSV (n = 5349 patients/7191 limbs), there were no differences in preintervention (7.0 ± 2.0 vs 6.8 ± 2.8, P = .99), 1-month (4.0 ± 2.4 vs 3.9 ± 2.8, P = .99), and 6-month (3.9 ± 2.6 vs 3.9 ± 2.9, P = .55) rVCSS scores. Similar results were observed when ablations and phlebectomies were performed (AAGSV [n = 34 patients/42 limbs] and GSV [n = 1848 patients/2491 limbs]). CIVIQ20 scores for patients with isolated AAGSV and GSV were 53.3 ± 19.6 vs 50.6 ± 18.8 (P = .43) preintervention, 37.2 ± 17.6 vs 35.7 ± 15.9 (P = .91) at 1 month, and 41.3 ± 21.7 vs 35.1 ± 15.7 (P = .36) at 6 months, respectively. Postprocedure scores within groups improved at 1 and 6 months (P ≤ .02); however, 6-month AAGSV CIVIQ20 scores after an ablation increased slightly compared with 1-month scores and were not different to preintervention GSV scores (P = .07). When phlebectomies were performed with ablations, 6-month CIVIQ20 scores were similar between groups (P = .72). There was no difference in the average number of ablations in patients with phlebectomies in the AAGSV or GSV group (1.24 ± 0.44 vs 1.35 ± 0.49, P = .15). Conclusions Endovenous therapies for the treatment of symptomatic AAGSVs demonstrate similar outcomes to patients with symptomatic GSV reflux. For standalone ablations, the rVCSS scores are similar between the groups; however, CIVIQ20 scores increase to preintervention levels in standalone ablation AAGSV patients at 6 months. This increase disappears when phlebectomies are performed with ablations. Based on these data, patients with symptomatic AAGSV treated with ablation also require treatment of the associated tributaries (varicosities) to achieve similar outcomes to patients with GSV, and this calls into question the effectiveness of ablation for isolated AAGSV reflux.

Assessment of the immediate need for specific blood product transfusions in acutely bleeding patients is challenging. Clinical assessment and commonly used coagulation tests are inaccurate and time-consuming. The goal of this practice management guideline was to evaluate the role of the viscoelasticity tests, which are thromboelastography (TEG) and rotational thromboelastometry (ROTEM), in the management of acutely bleeding trauma, surgical, and critically ill patients.Systematic review and meta-analyses of manuscripts comparing TEG/ROTEM with non-TEG/ROTEM-guided blood products transfusions strategies were performed. The Grading of Recommendations Assessment, Development and Evaluation methodology was applied to assess the level of evidence and create recommendations for TEG/ROTEM-guided blood product transfusions in adult trauma, surgical, and critically ill patients.Using TEG/ROTEM-guided blood transfusions in acutely bleeding trauma, surgical, and critically ill patients was associated with a tendency to fewer blood product transfusions in all populations. Thromboelastography/ROTEM-guided transfusions were associated with a reduced number of additional invasive hemostatic interventions (angioembolic, endoscopic, or surgical) in surgical patients. Thromboelastography/ROTEM-guided transfusions were associated with a reduction in mortality in trauma patients.In patients with ongoing hemorrhage and concern for coagulopathy, we conditionally recommend using TEG/ROTEM-guided transfusions, compared with traditional coagulation parameters, to guide blood component transfusions in each of the following three groups: adult trauma patients, adult surgical patients, and adult patients with critical illness.Systematic Review/Meta-Analysis, level III.

Background Traumatic hemothorax poses diagnostic and therapeutic challenges both acutely and chronically. A working group of the Eastern Association for the Surgery of Trauma convened to formulate a practice management guideline for traumatic hemothorax. Methods We formulated four questions: whether tube thoracostomy vs observation be performed, should pigtail catheter versus thoracostomy tube be placed to drain hemothorax, should thrombolytic therapy be attempted versus immediate thoracoscopic assisted drainage (VATS) in retained hemothorax (rHTX), and should early VATS (≤4 days) versus late VATS (>4 days) be performed? A systematic review was undertaken from articles identified in multiple databases. Results A total of 6391 articles were identified, 14 were selected for guideline construction. Most articles were retrospective with very low-quality evidence. We performed meta-analysis for some of the outcomes for three of the questions. Conclusions For traumatic hemothorax we conditionally recommend pigtail catheters, in hemodynamically stable patients. In patients with rHTX, we conditionally recommend VATS rather than attempting thrombolytic therapy and recommend that it should be performed early (≤4 days).

Background Cryptococcosis due to Cryptococcus neoformans and Cryptococcus gattii varies with geographic region, populations affected, disease manifestations, and severity of infection, which impact treatment. Methods We developed a retrospective cohort of patients diagnosed with culture-proven cryptococcosis during 1995–2013 from 5 centers in North America and Australia. We compared underlying diseases, clinical manifestations, treatment, and outcomes in patients with C. gattii or C. neoformans infection. Results A total of 709 patients (452 C. neoformans; 257 C. gattii) were identified. Mean age was 50.2 years; 61.4% were male; and 52.3% were white. Time to diagnosis was prolonged in C. gattii patients compared with C. neoformans (mean, 52.2 vs 36.0 days; P Conclusions This study emphasizes differences in species-specific epidemiology and outcomes of patients with cryptococcosis, including underlying diseases, site of infection, and mortality. Species identification in patients with cryptococcosis is necessary to discern epidemiologic patterns, guide treatment regimens, and predict clinical progression and outcomes.

In recent years, the global public health community has increasingly recognized the importance of antimicrobial stewardship (AMS) in the fight to improve outcomes, decrease costs, and curb increases in antimicrobial resistance around the world. However, the subject of antifungal stewardship (AFS) has received less attention. While the principles of AMS guidelines likely apply to stewarding of antifungal agents, there are additional considerations unique to AFS and the complex field of fungal infections that require specific recommendations. In this article, we review the literature on AMS best practices and discuss AFS through the lens of the global core elements of AMS. We offer recommendations for best practices in AFS based on a synthesis of this evidence by an interdisciplinary expert panel of members of the Mycoses Study Group Education and Research Consortium. We also discuss research directions in this rapidly evolving field. AFS is an emerging and important component of AMS, yet requires special considerations in certain areas such as expertise, education, interventions to optimize utilization, therapeutic drug monitoring, and data analysis and reporting.

Background In patients receiving stents for symptomatic non-thrombotic iliac vein lesions, many clinicians prescribe anti-thrombotic medications. Whether or not anti-coagulation post-venous stenting improves stent patency is unknown. The aim of this investigation is to determine whether prophylactic post-operative anti-thrombotic therapy improves stent patency and/or prevents in-stent restenosis. Methods The medical records and venous ultrasounds for 389 patients stented for non-thrombotic iliac vein lesions were retrospectively reviewed. Patients were categorized into three anti-thrombotic regimens: Clopidogrel, Aspirin and Clopidogrel, and Apixaban or Rivaroxaban. Patients were routinely assessed for restenosis and stent patency at 6, 26, and 52 weeks and treated with anti-thrombotics for 90 days. Results Freedom from in-stent restenosis at 6, 26, and 52 weeks were Clopidogrel (91.50, 82.91, 80.95%), Aspirin and Clopidogrel (88.68, 80.03, 80.03%), and Apixaban or Rivaroxaban (91.03, 85.11, 83.18%). Primary patencies were Clopidogrel (98.77, 98.77, 98.10%), Aspirin and Clopidogrel (100, 95.74, 95.74%), and Apixaban or Rivaroxaban (98.70, 98.70, 96.71%). There were no statistically significant differences. Conclusions The type of post-operative anti-thrombotic therapy for non-thrombotic iliac vein lesions does not appear to improve stent patency or prevent the development of in-stent restenosis.

Disclaimer Due to the evolving field of medicine, new research may, in due course, modify the recommendations presented in this document. At the time of publication, every attempt has been made to ensure that the information provided is up to date and accurate. It is the responsibility of the treating physician to determine the best treatment for the patient. The authors, committee members, editors, and publishers cannot be held responsible for any legal issues that may arise from the citation of this statement. Rules of evidence Management of patients with chronic venous disorders has been traditionally undertaken subjectively among physicians, often resulting in less than optimal strategies. In this document, a systematic approach has been developed with recommendations based upon cumulative evidence from the literature. Levels of evidence and grades of recommendation range from Level I and Grade A to Level III and Grade C. Level I evidence and Grade A recommendations derive from scientifically sound randomized clinical trials in which the results are clear-cut. Level II evidence and Grade B recommendations derive from clinical studies in which the results among trials often point to inconsistencies. Level III evidence and Grade C recommendations result from poorly designed trials or from small case series.1, 2 Meta-analysis Meta-analyses are included in the present document but there should be caution as to their possible abuse. Certain studies may be included in a meta-analysis carelessly without sufficiently understanding of substantive issues, ignoring relevant variables, using heterogenous findings or interpreting results with a bias.3 It has been demonstrated that the outcomes of 12 large randomized controlled trials were not predicted accurately 35% of the time by the meta-analyses published previously on the same topics.4

Background The largest health care–associated infection outbreak in the United States occurred during 2012–2013. Following injection of contaminated methylprednisolone, 753 patients developed infection with a dematiaceous mold, Exserohilum rostratum. The long-term outcomes of these infections have not been described. Methods This retrospective cohort study of 440 of a total of 753 patients with proven or probable Exserohilum infection evaluated clinical and radiographic findings, antifungal therapy and associated adverse effects, and outcomes at 6 weeks, 3, 6, 9, and 12 months after diagnosis. Patients were grouped into 4 disease categories: meningitis with/without stroke, spinal or paraspinal infections, meningitis/stroke plus spinal/paraspinal infections, and osteoarticular infections. Results Among the 440 patients, 223 (51%) had spinal/paraspinal infection, 82 (19%) meningitis/stroke, 123 (28%) both, and 12 (3%) osteoarticular infection. Of 82 patients with meningitis/stroke, 18 (22%) died; among those surviving, 87% were cured at 12 months. Only 7 (3%) of 223 patients with spinal/paraspinal infection died, but at 12 months, 68% had persistent or worsening pain and only 47% were cured. For the 123 patients with both meningitis/stroke and spinal/paraspinal infection, 10 (8%) died, pain persisted in 72%, and 52% were cured at 12 months. Only 37% of those with osteoarticular infection were cured at 12 months. Adverse events from antifungal therapy were noted at 6 weeks in 71% of patients on voriconazole and 81% on amphotericin B. Conclusions Fungal infections related to contaminated methylprednisolone injections culminated in death in 8% of patients. Persistent pain and disability were seen at 12 months in most patients with spinal/paraspinal infections.

Many clinicians will prescribe anticoagulation therapy for patients after iliac vein stenting to prevent early or late stent thrombosis. At present, it is unknown whether therapeutic anticoagulation has any effect on stent patency. Thus, we assessed the role of short-term anticoagulation on iliac vein stent patency in patients with nonthrombotic iliac vein lesions (NIVLs).We performed a retrospective medical record review of all iliac vein stents placed for NIVLs at the Center for Vascular Medicine from January 2018 to December 2019. We compared the stent patency in the two groups. The anticoagulation (AC) group had received rivaroxaban or apixaban postoperatively for a minimum of 90 days and were compared with a group that had received no postoperative anticoagulation (NAC). Stent patency was assessed using transabdominal ultrasound at 3, 6, 12, 18, 24, and 30 months. At the discretion of the treating physician, the patients who demonstrated thrombus layering on surveillance ultrasound scanning continued rivaroxaban or apixaban until thrombus resolution was observed. The demographics and stent location, diameter, and length were assessed. Stent patency was analyzed using life table analyses. Differences in stent patency were analyzed using GraphPad Prism, version 8, statistical software (GraphPad Software Inc, La Jolla, Calif) and the log-rank (Mantel-Cox) test.The number of patients and stents in each group were as follows: AC group, 299 patients and 308 stents; and NAC group, 77 patients and 90 stents. The average age was 52.24 ± 13.44 years and 55.63 ± 14.49 years in the AC and NAC groups, respectively (P ≤ .065). Women constituted 76% of the patients in the AC group and 72% in the NAC group. The average stent diameter and length for the AC group was 20 ± 2 mm and 77 ± 13 mm and for the NAC group was 19 ± 2 mm and 82 ± 9 mm, respectively. The stents had been placed in the right common iliac vein, bilaterally, or left common iliac vein territory in 15%, 3%, and 82% in the AC group and 18%, 2%, and 80% in the NAC group, respectively. The cumulative stent patency at 30 months was 98.7% and 94.6% for the NAC and AC groups, respectively (P ≤ .83). All the stents placed were Wallstents (Boston Scientific, Marlborough, Mass). A total of eight insertion site thromboses occurred that did not affect stent patency: five in the AC group (1.6%) and three in the NAC group (4.5%; P = .15). In addition, 19 patients demonstrated evidence of thrombus layering, with 6 receiving extended anticoagulation.Our data indicate that perioperative stent thrombosis in patients with NIVLs is uncommon. Thus, anticoagulation for perioperative stent thrombosis prophylaxis is not necessary. Anticoagulation should only be used for patients with insertion site thromboses and should be considered if thrombus layering is observed on surveillance scanning.

Background Antibiotic use is a well-known risk factor for acquisition of drug-resistant bacteria and community antibiotic prescribing can drive high rates of resistance within the hospital setting. Owing to concerns over increasing fluoroquinolone (FQ) resistance among Gram-negative organisms at UAB Hospital, our stewardship program implemented a pre-authorization policy. The goal of this study was to assess the relationship between hospital fluoroquinolone use and antibiotic resistance. Methods In 2006, the inpatient formulary was consolidated to only ciprofloxacin and moxifloxacin with implementation of guidelines for use to limit inpatient prescribing. Any use outside of these guidelines required approval from an infectious diseases physician. Organism-specific data were obtained from the clinical microbiology database and FQ use was obtained from the hospital database. Correlations were calculated using Pearson’s coefficient. Results From 1998 to 2004, FQ use peaked at 173 days of therapy (DOT)/1,000 patient-days, but has remained below 60 DOT/1,000 patient-days since restriction implementation (Figure 1). FQ susceptibility was documented for five common Gram-negative isolates, P. aeruginosa, Acinetobacter spp., Enterobacter cloacae, E. coli, and K. pneumoniae, over an 18-year period (1998–2016). Common hospital acquired pathogens, including Pseudomonas aeruginosa, Acinetobacter spp. and Enterobacter cloacae improved in their susceptibilities to fluoroquinolones. Acinetobacter went from 35% to over 50% susceptible in the preceding 10 years after the policy. Pseudomonas improved from 50% susceptible to over 70% and Enterobacter improved from less than 50% to over 90% susceptible. Interestingly this improvement was not seen for E. coli which continued to show a decline in susceptibility from over 90% to near 60% in 2016. Conclusion In a large academic hospital setting, FQ susceptibility for common hospital-acquired GNRS improved significantly with the introduction of a restricted use program. A continued decline in E. coli FQ susceptibility suggests resistance rates may be driven by outpatient and community antibiotic use and thus, outpatient stewardship programs are necessary to prevent further spread of FQ resistance. Disclosures All authors: No reported disclosures.

Background Reflux in the ovarian veins, with or without an obstructive venous outflow component, is reported to be the primary cause of pelvic venous insufficiency (PVI). The degree to which venous outflow obstruction plays a role in PVI is currently ill-defined. Methods We retrospectively reviewed the charts of 227 women with PVI who presented to the Center for Vascular Medicine from January 2012 to September 2015. Assessments and interventions consisted of an evaluation for other causes of chronic pelvic pain by a gynecologist; preintervention and postintervention visual analog scale (VAS) pain score; complete venous duplex ultrasound examination; and Clinical, Etiology, Anatomy, and Pathophysiology classification. All patients underwent diagnostic venography of their pelvic and left ovarian veins as well as intravascular ultrasound of their iliac veins. Patients were treated in one of six ways: ovarian vein embolization (OVE) alone (chemical ± coils), OVE with staged iliac vein stenting, OVE with simultaneous iliac vein stenting, iliac vein stenting alone, OVE with venoplasty, and venoplasty alone. Results Of the 227 women treated, the average age and number of pregnancies was 46.4 ± 10.4 years and 3.36 ± 1.99, respectively. Treatment distribution was the following: OVE, n = 39; OVE with staged stenting, n = 94; OVE with simultaneous stenting, n = 33; stenting alone, n = 50; OVE with venoplasty, n = 8; and venoplasty alone, n = 3. Seven patients in the OVE and stenting groups (staged) and one patient in the OVE + venoplasty group required a second embolization of the left ovarian vein. Eighty percent (181/227) of patients demonstrated an iliac stenosis >50% by intravascular ultrasound. Average VAS scores for the entire cohort before and after intervention were 8.45 ± 1.11 and 1.86 ± 1.61 (P ≤ .001). In the staged group, only 9 of 94 patients reported a decrease in the VAS score with OVE alone. VAS score decreased from 8.6 ± 0.89 before OVE to 7.97 ± 2.10 after OVE. After the planned staged stenting, VAS score decreased to 1.33 ± 2.33 (P ≤ .001). Similarly, in the simultaneous group, preintervention scores were 8.63 ± 1.07 and decreased to 2.36 ± 2.67 after OVE + stenting (P ≤ .001). Conclusions The majority of patients in our series (80%) demonstrated a significant iliac vein stenosis. These observations indicate that the incidence of iliac vein outflow obstruction in PVI is greater than previously reported. In patients with combined ovarian vein reflux and iliac vein outflow obstruction, our data suggest that pelvic venous outflow lesions should be treated first and that ovarian vein reflux should be treated only if symptoms persist. In women with an outflow lesion, ovarian vein reflux, and a large pelvic reservoir, we recommend simultaneous treatment.

Background C-itra is the drug of choice for treatment of most non-CNS, non-life-threatening forms of endemic mycoses (EM), including histoplasmosis, blastomycosis, coccidioidomycosis, sporotrichosis and talaromycosis. SUBA represents a new formulation of itraconazole that utilizes nanotechnology to improve bioavailability when administered orally. SUBA is formulated as nanoparticles allowing for absorption in the small bowel while not relying on gastric acidity for optimal absorption. MSG-15 is an open-label, comparative clinical trial comparing SUBA to c-itra for the treatment of EM. Herein we report the final PK and AE profiles of these two compounds. Methods Subjects with proven and probable EM were eligible this open-label comparative study. The protocol allowed up to 14 d of prior therapy with any antifungal for this episode of EM. Subjects were randomized to receive either SUBA 130 mg po bid or c-itra 200 mg po bid for up to 6 months. Follow up occurred at 7, 14, 28, 42, 84 and 180 d post-enrollment. PK samples were obtained at 7, 14, and 42 d. Clinical assessment, including symptom assessment, AEs, overall drug tolerance, and quality of life were assessed at each visit. We used descriptive statistics for this analysis. Results 89 subjects with EM entered the trial, including 43 on SUBA and 46 on c-itra. We measured PK serum levels of itra and hydroxyl-itra at days 7, 14, and 42 and these data are depicted in Figures 1-3. There were no significant differences in these levels, including combined itra/hydroxyl-itra levels, among the two study arms. AUC for itra and hydroxyl-itra were similar for both arms. AEs as assessed at each study evaluation were also quite similar among the two study arms. Overall, any AE occurred in 74% vs 85% of SUBA and c-itra recipients, respectively (NS). Drug-related AEs occurred in 35% vs 41% of SUBA and itra recipients, respectively (NS). Most common drug-related AEs included cardiovascular (edema and hypertension), nausea and loss of appetite. Combined Itraconazole and Hydroxy-itraconazole Concentration Over Time Conclusion Compared to c-itra, SUBA demonstrates almost identical serum levels despite being dosed at roughly 60% standard dosing for c-itra (130 mg po bid vs 200 mg po bid). SUBA is slightly better tolerated than c-itra, although the specific AEs are similar. Disclosures Peter G. Pappas, MD, Astellas (Research Grant or Support)Cidara (Research Grant or Support)F2G (Consultant)Matinas (Consultant, Scientific Research Study Investigator)Mayne Pharma (Research Grant or Support)Scynexis (Research Grant or Support) Andrej Spec, MD, MSCI, Mayne Pharma (Grant/Research Support) Marisa Miceli, MD, SCYNEXIS, Inc. (Advisor or Review Panel member) George R. R. Thompson III, III, MD, Amplyx (Consultant, Grant/Research Support)Appili (Consultant)Astellas (Consultant, Grant/Research Support)Avir (Grant/Research Support)Cidara (Consultant, Grant/Research Support)F2G (Consultant, Grant/Research Support)Mayne (Consultant, Grant/Research Support)Merck (Scientific Research Study Investigator)Pfizer (Advisor or Review Panel member)

Objectives To identify the frequency of micafungin resistance among clinically significant isolates of Candida stored at our institution from 2005 to 2015. Chart review of patients with resistant isolates then informed the clinical setting and outcomes associated with these infections. Methods Clinical Candida isolates had been stored at -80°C in Brucella broth with 20% glycerol from 2005. Isolates were tested using broth microdilution to determine micafungin MICs. All Candida glabrata isolates and all isolates demonstrating decreased susceptibility to micafungin were screened for FKS mutations using a Luminex assay. Results In total, 3876 Candida isolates were tested for micafungin resistance, including 832 C. glabrata isolates. Of those, 33 isolates from 31 patients were found to have either decreased susceptibility to micafungin and/or an FKS mutation. C. glabrata accounted for the majority of these isolates. While bloodstream infections were found to have a very high mortality rate, isolates from other sites were uncommonly associated with 30-day mortality. Overall resistance rates were very low. Conclusions Echinocandin resistance in C. glabrata has been increasingly reported but rates at our institution remain very low. We hypothesize that a focus on antifungal stewardship may have led to these observations. Knowledge of local resistance patterns is key to appropriate empirical treatment strategies.