Treatment Outcomes Among Patients With a Positive Candida Culture Close to Randomization Receiving Rezafungin or Caspofungin in the ReSTORE Study.

BACKGROUND: Rezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was non-inferior to caspofungin for Day 30 all-cause mortality (ACM) and Day 14 global cure in the Phase 3 ReSTORE trial (NCT03667690). We conducted pre-planned subgroup analyses for patients with a positive culture close to randomization in ReSTORE. METHODS: ReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before and 72 hours after randomization, or a positive culture from another normally sterile site sampled between 48 hours before and 72 hours after randomization. Efficacy endpoints included Day 30 ACM, Day 14 global cure rate, and Day 5 and 14 mycological response. Adverse events were evaluated. RESULTS: This analysis included 38 patients randomized to rezafungin and 46 to caspofungin. In the rezafungin and caspofungin groups, respectively: Day 30 ACM was 26.3% and 21.7% (between-group difference [95% confidence interval] 4.6% [-13.7, 23.5]); Day 14 global response was 55.3% and 50.0% (between-group difference 5.3% [-16.1, 26.0]); and Day 5 mycological eradication was 71.1% and 50.0% (between-group difference 21.1% [-0.2, 40.2]). Safety was comparable between treatments. CONCLUSIONS: These findings support the efficacy and safety of rezafungin compared with caspofungin for the treatment of candidemia and/or IC in patients with a positive culture close to randomization, with potential early treatment benefits for rezafungin.

Outcomes by Candida spp. in the ReSTORE Phase 3 trial of rezafungin versus caspofungin for candidemia and/or invasive candidiasis.

Rezafungin is a long-acting, intravenously administered echinocandin for the treatment of candidemia and invasive candidiasis (IC). Non-inferiority of rezafungin vs caspofungin for the treatment of adults with candidemia and/or IC was demonstrated in the Phase 3 ReSTORE study based on the primary endpoints of day 14 global cure and 30-day all-cause mortality. Here, an analysis of ReSTORE data evaluating efficacy outcomes by baseline Candida species is described. Susceptibility testing was performed for Candida species using the Clinical and Laboratory Standards Institute reference broth microdilution method. There were 93 patients in the modified intent-to-treat population who received rezafungin; 94 received caspofungin. Baseline Candida species distribution was similar in the two treatment groups; C. albicans (occurring in 41.9% and 42.6% of patients in the rezafungin and caspofungin groups, respectively), C. glabrata (25.8% and 26.6%), and C. tropicalis (21.5% and 18.1%) were the most common pathogens. Rates of global cure and mycological eradication at day 14 and day 30 all-cause mortality by Candida species were comparable in the rezafungin and caspofungin treatment groups and did not appear to be impacted by minimal inhibitory concentration (MIC) values for either rezafungin or caspofungin. Two patients had baseline isolates with non-susceptible MIC values (both in the rezafungin group: one non-susceptible to rezafungin and one to caspofungin, classified as intermediate); both were candidemia-only patients in whom rezafungin treatment was successful based on the day 30 all-cause mortality endpoint. This analysis of ReSTORE demonstrated the efficacy of rezafungin for candidemia and IC in patients infected with a variety of Candida species.

Developing Crowdsourced Clinical Registry Studies.

ABSTRACT: Crowdsourced registries have been used to quickly gather information, especially during emerging public health concerns. Registries that began during the COVID-19 pandemic were used to rapidly answer key questions on coinfections, experimental treatments, and morbidity and mortality outcomes. Registries are also used more frequently to support clinical trials and track long-term outcomes in patient populations. This article reviews registry methodology, including the collection of data from crowdsourcing and real-world sources, that can be applied to nurse researcher and clinical research nurse skill sets. The authors illustrate a recently reported crowdsourced COVID-19 and cryptococcal disease registry that followed project management strategies and the Agency for Healthcare Research and Quality registry guidelines for planning, execution, and analysis of registries and other research methods.

Application of the Symptoms-Varices-Pathophysiology classification system in patients with pelvic venous disorders.

Introduction: In 2021, the American Vein and Lymphatic Society convened a multi-disciplinary group to develop a valid and reliable discriminative instrument for the classification of patients suffering from pelvic venous disorders (PeVD) referred to as the Symptoms-Varices-Pathophysiology (SVP) system. Limited data exists regarding the utility of this instrument in the care of patients with PeVD. The goal of this investigation is to apply the SVP classification system to a group of patients treated for PeVDs. Methods: From January 2018 to January 2019, we retrospectively reviewed the records of 70 female patients treated for a PeVD at the Center for Vascular Medicine. Age, race, gender, medical/surgical histories, CEAP classification and intervention types were assessed and patients were categorized according to their SVP classification. The prevalence of each S and V class, their association with gonadal or iliac vein obstructive lesions and the prevalence of lower extremity varicosities was evaluated. Results: The average age of the entire cohort was 47.4 ± 13.4. The race distribution was as follows: African American (6), Hispanic (1), and Caucasian (63). Of the 140 limbs, 57% were C3 or greater with an average rVCSS score of 4.53. At the time of intervention, 54 patients (77%) demonstrated CEAP class 2 disease or greater with 25 patients (35%) demonstrating lower extremity varicosities. Medical co-morbidities included the following: Endometriosis (n = 1), Uterine Fibroids (n = 1), Ovarian cysts (n = 4), history of venous thrombosis (n = 2) and prior lower extremity venous procedures (n = 3). Overall, 47 patients (67.1%) demonstrated S2 disease secondary to dyspareunia, post-coital pain, or dysmenorrhea. S2 alone was observed in 17 patients (24.3%), S2,3a and S2,3a,3b in nine patients each (12.9%), and S2,3b was in 12 patients (17.1%). Thirteen patients presented with isolated extra-pelvic symptoms (19%); four (5.7%) were classified as S3a,3b, and nine (12.9%) were classified as S3b only. Finally, 10 patients (14%) had no pelvic symptoms and thus were classified as S0. V0 disease was observed in 17 patients (24.3%) secondary to a high incidence of iliac vein stenoses (IVS). V1 disease was observed in 1 patient (1.43%). V2 disease was observed in 53 patients (74.3%) secondary to iliac or ovarian vein reflux. Of these, 45 patients (64.3%) presented with reflux in the iliac veins. Sixteen patients had reflux in the common iliac veins, 17 patients exhibited reflux of the external iliac veins, and 41 patients demonstrated reflux of the internal iliac veins. Thirty-two patients (45.7%) presented with V2 disease secondary to reflux of the ovarian veins, 8 of whom presented with isolated ovarian vein reflux without IVS. Bilateral ovarian vein reflux was observed in 6 patients (9%) and unilaterally in 26 (37%) patients with concomitant ovarian vein reflux and IVS observed in 31 patients (44%). In patients with ovarian vein reflux, 89% had a concomitant iliac vein stenosis: (96.9% in the common iliac vein, 81.3% in the external iliac vein and 3.1% in the internal iliac vein). Conclusion: In our patient cohort, 70 women demonstrated 14 different SV classifications. The most common was S2V2, found in 10 patients. Chronic pelvic pain of venous origin, S2 disease, was the most common symptom, present in 47 patients (67.1%); followed by extra-pelvic symptoms as 22 patients demonstrated symptoms of the external genitalia (S3a), and 21 patients had symptoms secondary to the non-saphenous leg veins (S3b). Pelvic varicosities, V2, were also the most common variceal pattern seen in 53 patients, and 17 patients did not have any varices noted by venogram. Non-thrombotic IVS either alone or with ovarian vein reflux was the most common cause of PeVD in this cohort and may reflect referral patterns to our center. To determine the true incidence of these SVP patterns, larger cohort studies are necessary.

The impact of stent protrusion into the inferior vena cava or jailing of the contralateral iliac vein on the incidence of contralateral deep vein thrombosis following venous stenting.

OBJECTIVE: Iliac vein stenting is the standard of care for patients with pelvic venous disorders secondary to symptomatic iliac vein outflow obstruction. Venous stents are often extended proximally into the inferior vena cava (IVC) which may result in partial or complete coverage of the contralateral iliac vein. The purpose of this investigation is to determine if extension of iliac vein stents into the IVC results in increased risk of contralateral deep venous thrombosis (DVT). METHODS: We retrospectively reviewed prospectively collected data from 409 patients who underwent iliac vein stenting at the Center for Vascular Medicine (CVM) from 2019 to 2020. Stent type, covered territories, initial and follow-up consults, ultrasound and operative reports were reviewed to assess for incidence of post-implantation DVT. Patients were stratified into three groups: Iliac vein stents which protruded into the IVC, stents that completely covered the orifice of the contralateral iliac vein and those with no stent protrusion into the IVC. RESULTS: Out of 409 patients, the average age was 53.96 ± 13.40 years with 94 males and 315 females. All stents placed were Venovo stents and all iliac vein lesions were non-thrombotic stenoses. The average follow-up period was 14.35 ± 10.09 months. The most common territories stented were the IVC-LCIV-LEIV (n = , 74%) and the IVC-RCIV-REIV (n = , 26%). Stent protrusion and distance into the IVC in millimeters (mm) was the following: Partial protrusion (n = 314, 77%, 27.6 ± 19.1), jailing of the contralateral iliac vein (n = 78, 19%, 45.9 ± 18.6), no protrusion (n = 16, 4%). The overall DVT rate post-implantation was 0.49% (n = 2). No DVTs ipsilateral to the index stent were identified and both DVTs were contralateral DVTs. A hypercoaguable disorder was reported in 6 patients (1.5%). There were no significant differences in prevalence of contralateral DVT between the three groups. (p = .35). CONCLUSION: The rate of contralateral DVTs post iliac vein stenting with Nitonol based stents is extremely low. Partial or complete coverage of the contralateral iliac vein via stenting does not result in an increased incidence of contralateral DVT in the short-term. Longer follow up is needed to determine if contralateral DVTs occur after long-term implantation.

Clinical Mycology Today: Emerging Challenges and Opportunities.

The Mycoses Study Group Education and Research Consortium is a collective of clinicians, researchers, and educators with the common goal to advance awareness, diagnosis, and management of invasive fungal diseases. Clinical Mycology Today, the Mycoses Study Group Education and Research Consortium's biennial meeting, is dedicated to discussing the most pressing contemporary issues facing the field of clinical mycology, promoting clinical, translational, and basic science collaborations, and mentoring the next generation of clinical mycologists. Here, we review the current opportunities and challenges facing the field of mycology that arose from discussions at the 2022 meeting, with emphasis on novel host risk factors, emerging resistant fungal pathogens, the evolving antifungal pipeline, and critical issues affecting the advancement of mycology research.

MSG-15: Super-Bioavailability Itraconazole Versus Conventional Itraconazole in the Treatment of Endemic Mycoses-A Multicenter, Open-Label, Randomized Comparative Trial.

Background: Invasive fungal disease caused by dimorphic fungi is associated with significant morbidity and mortality. Super-bioavailability itraconazole (SUBA-itra) is a novel antifungal agent with pharmacokinetic advantages over currently available formulations. In this prospective comparative study, we report the outcomes of patients with endemic fungal infections (histoplasmosis, blastomycosis, coccidioidomycosis, and sporotrichosis). Methods: This open-label randomized trial evaluated the efficacy, safety, and pharmacokinetics SUBA-itra compared with conventional itraconazole (c-itra) treatment for endemic fungal infections. An independent data review committee determined responses on treatment days 42 and 180. Results: Eighty-eight patients were enrolled for IFD (SUBA-itra, n = 42; c-itra, n = 46) caused by Histoplasma (n = 51), Blastomyces (n = 18), Coccidioides (n = 13), or Sporothrix (n = 6). On day 42, clinical success was observed with SUBA-itra and c-itra on day 42 (in 69% and 67%, respectively, and on day 180 (in 60% and 65%). Patients treated with SUBA-itra exhibited less drug-level variability at days 7 (P = .03) and 14 (P = .06) of randomized treatment. The concentrations of itraconazole and hydroxyitraconazole were comparable between the 2 medications (P = .77 and P = .80, respectively). There was a trend for fewer adverse events (AEs; 74% vs 87%, respectively; P = .18) and serious AEs (10% vs 26%; P = .06) in the SUBA-itra-treated patients than in those receiving c-itra. Serious treatment-emergent AEs were less common in SUBA-itra-treated patients (12% vs 50%, respectively; P < .001). Conclusions: SUBA-itra was bioequivalent, well tolerated, and efficacious in treating endemic fungi, with a more favorable safety profile than c-itra. Clinical Trials Registration: NCT03572049.

Shared Vision for Improving Outcomes for Serious Fungal Diseases: Report of a Patient, Caregiver, and Clinician Summit.

Background: Recently, increasing focus on patient input into research and healthcare improvements has fostered expanded patient-centered advocacy efforts. This first pan-fungal disease summit, part of the MYCology Advocacy, Research, & Education effort, brought together patients, caregivers, and mycology experts to better document patient experiences with invasive fungal disease (IFD) and establish priorities for mycology education, advocacy, and research. Methods: Patients who had suffered from IFD, their caregivers, clinicians, industry representatives, government officials, and patient advocacy professionals were invited. Patients and caregivers shared their stories and struggles with IFD. Breakout sessions separated mycology experts from patients and caregivers for further discussions to identify commonalities and perceived gaps and to formulate recommendations. The 2 groups then reconvened to develop consensus recommendations. Results: IFD patients and their caregivers shared experiences reflecting the typically lengthy prediagnosis, acute treatment, long-term treatment, and posttreatment recovery stages of IFD. They reported substantial physical, psychological, and financial burdens associated with the IFD experience, particularly related to delayed diagnoses. They reaffirmed a need for coordinated patient-centered education, peer support, and advocacy to document the burden of serious fungal infections. Mycology experts discussed strategies to address gaps in the mycology field, such as insufficient training, inadequate workforce support, and a need to partner more with patient groups. Conclusions: A summit involving patients with IFD, family caregivers, and mycology experts identified a substantial nonclinical burden of disease associated with IFD. Patients and mycology experts prioritized several goals for education, advocacy, and research to raise awareness of IFD and improve outcomes.