Real-world Use of Mold-Active Triazole Prophylaxis in the Prevention of Invasive Fungal Diseases: Results From a Subgroup Analysis of a Multicenter National Registry.

Background: Antifungal prophylaxis can prevent invasive fungal diseases (IFDs) in high-risk, immunocompromised patients. This study assessed the real-world use of mold-active triazoles (MATs) for the prevention of IFDs. Methods: This subgroup analysis of a multicenter, observational, prospective registry in the United States from March 2017 to April 2020 included patients who received MATs for prophylaxis (isavuconazole, posaconazole, and voriconazole) at study index/enrollment. The primary objective was to describe patient characteristics and patterns of MAT use. Exploratory assessments included the frequency of breakthrough IFDs and MAT-related adverse drug reactions (ADRs). Results: A total of 1177 patients (256 isavuconazole, 397 posaconazole, 272 voriconazole, and 252 multiple/sequenced MATs at/after index/enrollment) were included in the prophylaxis subgroup analysis. Patient characteristics were similar across MAT groups, but risk factors varied. Hematological malignancy predominated (76.5%) across all groups. Breakthrough IFDs occurred in 7.1% (73/1030) of patients with an investigator's assessment (5.0% [11/221] isavuconazole; 5.3% [20/374] posaconazole; 4.0% [9/226] voriconazole; and 15.8% [33/209] multiple/sequenced MATs). Aspergillus (29.5% [18/61]) and Candida (36.1% [22/61]) species were the most common breakthrough pathogens recovered. ADRs were reported in 14.1% of patients, and discontinuation of MATs due to ADRs was reported in 11.1% of patients (2.0% [5/245] isavuconazole; 8.2% [30/368] posaconazole; and 10.1% [27/267] voriconazole). Conclusions: Breakthrough IFDs were uncommon in patients who received MATs for prophylaxis. Candida and Aspergillus species were the most commonly reported breakthrough pathogens. The discontinuation of MATs due to ADRs was infrequent. These findings support prophylactic strategies with isavuconazole, posaconazole, and voriconazole in high-risk patients.

Non-Aspergillus Hyaline Molds: A Host-Based Perspective of Emerging Pathogenic Fungi Causing Sinopulmonary Diseases.

The incidence of invasive sino-pulmonary diseases due to non-Aspergillus hyaline molds is increasing due to an enlarging and evolving population of immunosuppressed hosts as well as improvements in the capabilities of molecular-based diagnostics. Herein, we review the following opportunistic pathogens known to cause sinopulmonary disease, the most common manifestation of hyalohyphomycosis: Fusarium spp., Scedosporium spp., Lomentospora prolificans, Scopulariopsis spp., Trichoderma spp., Acremonium spp., Paecilomyces variotii, Purpureocillium lilacinum, Rasamsonia argillacea species complex, Arthrographis kalrae, and Penicillium species. To facilitate an understanding of the epidemiology and clinical features of sino-pulmonary hyalohyphomycoses in the context of host immune impairment, we utilized a host-based approach encompassing the following underlying conditions: neutropenia, hematologic malignancy, hematopoietic and solid organ transplantation, chronic granulomatous disease, acquired immunodeficiency syndrome, cystic fibrosis, and healthy individuals who sustain burns, trauma, or iatrogenic exposures. We further summarize the pre-clinical and clinical data informing antifungal management for each pathogen and consider the role of adjunctive surgery and/or immunomodulatory treatments to optimize patient outcome.

Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases.

Background: Sargramostim (yeast-derived, glycosylated recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) augments innate and adaptive immune responses and accelerates hematopoietic recovery of chemotherapy-induced neutropenia. However, considerably less is known about its efficacy as adjunctive immunotherapy against invasive fungal diseases (IFDs). Methods: The clinical courses of 15 patients with pediatric malignancies and IFDs treated adjunctively with sargramostim at a single institution were analyzed in a retrospective cohort review. Further, a systematic review of published reports of rhu GM-CSF for IFDs was also conducted. Results: Among 65 cases, 15 were newly described pediatric patients and 50 were previously published cases of IFDs treated with rhu GM-CSF. Among the newly reported pediatric patients, IFDs were caused by Candida spp., Trichosporon sp., and molds (Aspergillus spp., Rhizopus sp., Lichtheimia sp., and Scedosporium sp). Twelve (80%) were neutropenic at baseline, and 12 (80%) were refractory to antifungal therapy. Among 12 evaluable patients, the overall response rate was 92% (8 [67%] complete responses, 3 [25%] partial responses, and 1 [8%] stable). Treatment is ongoing in the remaining 3 patients. Among 50 published cases (15 Candida spp., 13 Mucorales, 11 Aspergillus spp., 11 other organisms), 20 (40%) had baseline neutropenia and 36 (72%) were refractory to standard therapy before rhu GM-CSF administration. Consistent with responses in the newly reported patients, the overall response rate in the literature review was 82% (40 [80%] complete responses, 1 [2%] partial response, and 9 [18%] no response). Conclusions: Sargramostim may be a potential adjunctive immunomodulator for selected patients with hematological malignancies and refractory IFDs.

Bloodstream Infections in Hematologic Malignancy Patients With Fever and Neutropenia: Are Empirical Antibiotic Therapies in the United States Still Effective?

Background: Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant. Methods: In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation. Results: Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23%, respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88%, and 96%, respectively, among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor, or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics, or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score ≥2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall. Conclusions: In accordance with US guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high-risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.

Comparison between Perianal Swab and Stool Specimens for Detecting Colonization with Extended-Spectrum Beta-Lactamase-Producing and Fluoroquinolone-Resistant Enterobacterales.

Stool specimens are frequently used to detect gastrointestinal tract colonization with antimicrobial-resistant enteric bacteria, but they cannot be rapidly collected. Perianal swab specimens can be collected more quickly and efficiently, but data evaluating their suitability as a specimen type for this purpose are sparse. We performed selective culture for extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) and fluoroquinolone-resistant Enterobacterales (FQRE) using paired perianal swab and stool specimens that were collected within 1 day of each other from hematopoietic cell transplant recipients and patients with acute leukemia. Nineteen (7.6%) of 251 stool specimens yielded ESBL-E and 64 (26%) of 246 stool specimens yielded FQRE. The positive percent agreement of perianal swab specimens compared to stool specimens was 95% (18/19; 95% confidence interval [CI], 74% to 100%) for detecting ESBL-E and 95% (61/64; 95% CI, 87% to 99%) for detecting FQRE. The concordance between specimen types was 98% (95% CI, 97% to 100%). Perianal swabs are a reliable specimen type for surveillance of the gastrointestinal tract for ESBL-E and FQRE.

Focused multivector ultraviolet (FMUV) technology rapidly eradicates SARS-CoV-2 in-vitro: Implications for hospital disinfection of COVID-19 environments.

Focused Multivector Ultraviolet technology rapidly killed the SARS-CoV-2 coronavirus in-vitro. Plates were inoculated with a mean of greater than 106 plaque forming units of USA-WA1 Washington index patient strain of SARS-CoV-2 and exposed to ultraviolet, resulting in mean reductions of 99.99% within 30 seconds, 99.999% within 60 seconds, and 99.9999% within 90 seconds. These results support the effectiveness of Focused Multivector Ultraviolet technology for SARS-CoV-2 disinfection.

Adenovirus viremia after in vivo T-cell depleted allo-transplant in adults: low lymphocyte counts are associated with uncontrolled viremia and fatal outcomes.

The incidence of adenovirus viremia and the role of screening in preventing adenovirus disease in adult transplant recipients are not well defined. Between January 2017 and May 2020, 262 allogeneic transplants were performed using in vivo T-cell depletion. Adenovirus viremia was found in 59 patients for a cumulative incidence of 10% by one hundred days and 23% (95% CI 20-26%) by one year. There was a higher incidence of viremia associated with cord blood transplant (p = .04). No other patient, donor or transplant characteristics were identified that predicted for viremia. In 47 patients (80%), viremia remained well below 200,000 copies/mL and resolved. Twelve patients developed high level viremia. Treatment with antivirals and in some cases adoptive cell therapy, was often ineffective and only two survived. Low lymphocyte count at initial detection of adenovirus viremia was the best predictor of uncontrolled disease.

Association Between Testosterone Treatment and Risk of Incident Cardiovascular Events Among US Male Veterans With Low Testosterone Levels and Multiple Medical Comorbidities.

Background Testosterone treatment is common in men, although risks for major cardiovascular events are unclear. Methods and Results A study was conducted in US male veterans, aged ≥40 years, with low serum testosterone and multiple medical comorbidities and without history of myocardial infarction, stroke, venous thromboembolism, prostate cancer, or testosterone treatment in the prior year. For the primary outcome, we examined if testosterone treatment was associated with a composite cardiovascular outcome (incident myocardial infarction, ischemic stroke, or venous thromboembolism). Testosterone use was modeled as intramuscular or transdermal and as current use, former use, and no use. Current testosterone users were compared with former users to reduce confounding by indication. The cohort consisted of 204 857 men with a mean (SD) age of 60.9 (9.9) years and 4.7 (3.5) chronic medical conditions. During follow-up of 4.3 (2.8) years, 12 645 composite cardiovascular events occurred. In adjusted Cox regression analyses, current use of transdermal testosterone was not associated with risk for the composite cardiovascular outcome (hazard ratio [HR], 0.89; 95% CI, 0.76-1.05) in those without prevalent cardiovascular disease, and in those with prevalent cardiovascular disease was associated with lower risk (HR, 0.80; 95% CI, 0.70-0.91). In similar analyses, current use of intramuscular testosterone was not associated with risk for the composite cardiovascular outcome in men without or with prevalent cardiovascular disease (HR, 0.91; 95% CI, 0.80-1.04; HR, 0.98; 95% CI, 0.89-1.09, respectively). Conclusions In a large cohort of men without a history of myocardial infarction, stroke, or venous thromboembolism, testosterone treatment was not associated with increased risk for incident composite cardiovascular events.

Efficacy of Non-Testosterone-Based Treatment in Hypogonadal Men: A Review.

INTRODUCTION: Although testosterone replacement therapy is an effective treatment for hypogonadism, there are safety concerns regarding potential cardiovascular risks and fertility preservation. OBJECTIVE: To assess the effect of selective estrogen receptor modulator (SERM), aromatase inhibitor, and human chorionic gonadotropin (hCG) on total testosterone (TT) levels and hypogonadism. METHODS: We performed a systematic literature review from 1987 to 2019 via PubMed, Cochrane review, and Web of Science. Terms used were infertility, hypogonadism, alternative to testosterone therapy, selective estrogen receptor modulator, aromatase inhibitor, and human chorionic gonadotropin. Studies that reported an effect of TT and hypogonadism after treatment of each medication were selected. Hypogonadal symptoms were assessed by the Androgen Deficiency of The Aging Male (ADAM) questionnaire. Aggregated data were analyzed via Chi-squared analysis. RESULTS: From literature, 25 studies were selected; of which, 12 evaluated efficacy of aromatase inhibitor, 8 evaluated SERMs, and 5 evaluated hCG effects. For SERMs, 512 patients with mean age 42.3 ± 1.94 years showed mean TT before treatment vs after treatment (167.9 ± 202.8 [ng/dl] vs 366.2 ± 32.3 [ng/dl], P < .0001 [180.5-216.1 95% confidence interval {CI}]). For aromatase inhibitor, 375 patients with mean age 54.1 ± 0.67 years showed mean TT before treatment vs after treatment (167.9 ± 202.8 [ng/dl] vs 366.2 ± 32.3 [ng/dl], P < .0001 [180.5-216.1 95% CI]). SERMs also showed ADAM before treatment vs after treatment (4.95 ± 0.28 vs 5.50 ± 0.19, P < .0001 [0.523-0.581 95% CI]). For hCG, 196 patients with mean age 41.7 ± 1.5 years showed mean TT before treatment vs after treatment (284.5 ± 13.6 [ng/dl] vs 565.6 ± 39.7 [ng/dl], P < .0001 [275.2-287.0 95% CI]). In addition, hCG also showed ADAM before treatment vs after treatment (28.1 ± 2.0 vs 30.9 ± 2.3, P < .0001 [2.313 95% CI]). CONCLUSIONS: Non-testosterone therapies are efficacious in hypogonadal men. Our results show statistically significant improvement in TT and ADAM scores in all 3 medications after treatment. Future studies are warranted to elucidate the relationship between improved hypogonadism and erectile function in the setting of non-testosterone-based treatment. Raheem OA, Chen TT, Le TV, et al. Efficacy of Non-Testosterone-Based Treatment in Hypogonadal Men: A Review. Sex Med Rev 2021;9:381-392.

Colonization With Fluoroquinolone-Resistant Enterobacterales Decreases the Effectiveness of Fluoroquinolone Prophylaxis in Hematopoietic Cell Transplant Recipients.

BACKGROUND: Levofloxacin prophylaxis is recommended to prevent gram-negative bloodstream infections (BSIs) in patients with prolonged chemotherapy-induced neutropenia. However, increasing fluoroquinolone resistance may decrease the effectiveness of this approach. METHODS: We assessed the prevalence of colonization with fluoroquinolone-resistant Enterobacterales (FQRE) among patients admitted for hematopoietic cell transplantation (HCT) from November 2016 to August 2019 and compared the risk of gram-negative BSI between FQRE-colonized and noncolonized patients. All patients received levofloxacin prophylaxis during neutropenia. Stool samples were collected upon admission for HCT and weekly thereafter until recovery from neutropenia, and underwent selective culture for FQRE. All isolates were identified and underwent antimicrobial susceptibility testing by broth microdilution. FQRE isolates also underwent whole-genome sequencing. RESULTS: Fifty-four of 234 (23%) patients were colonized with FQRE prior to HCT, including 30 of 119 (25%) allogeneic and 24 of 115 (21%) autologous HCT recipients. Recent antibacterial use was associated with FQRE colonization (P = .048). Ninety-one percent of colonizing FQRE isolates were Escherichia coli and 29% produced extended-spectrum ß-lactamases. Seventeen (31%) FQRE-colonized patients developed gram-negative BSI despite levofloxacin prophylaxis, compared to only 2 of 180 (1.1%) patients who were not colonized with FQRE on admission (P < .001). Of the 17 gram-negative BSIs in FQRE-colonized patients, 15 (88%) were caused by FQRE isolates that were genetically identical to the colonizing strain. CONCLUSIONS: Nearly one-third of HCT recipients with pretransplant FQRE colonization developed gram-negative BSI while receiving levofloxacin prophylaxis, and infections were typically caused by their colonizing strains. In contrast, levofloxacin prophylaxis was highly effective in patients not initially colonized with FQRE.

"The Back-up Vasectomy Reversal." Simultaneous Sperm Retrieval and Vasectomy Reversal in the Couple With Advanced Maternal Age: A Cost-Effectiveness Analysis.

OBJECTIVE: To determine the cost-effectiveness of different fertility options in men who have undergone vasectomy in couples with a female of advanced maternal age (AMA). The options include vasectomy reversal (VR), sperm retrieval (SR) with in vitro fertilization (IVF), and the combination of VR and SR with IVF, which is a treatment pathway that has been understudied. MATERIALS AND METHODS: Using TreeAge software, a model-based cost-utility analysis was performed estimating the cost per quality-adjusted life years (QALY) in couples with infertility due to vasectomy and advanced female age over a period of one year. The model stratified for female age (35-37, 38-40, >40) and evaluated four strategies: VR followed by natural conception (NC), SR with IVF, VR and SR followed by failed NC and then IVF, and VR and SR followed by failed IVF and then NC. QALY estimates and outcome probabilities were obtained from the literature and average patient charges were calculated from high-volume centers. RESULTS: The most cost-effective fertility strategy was to undergo VR and try for NC (cost-per-QALY: $7,150 (35-37 y), $7,203 (38-40 y), and $7,367 (>40 y)). The second most cost-effective strategy was the "back-up vasectomy reversal": undergo VR and SR, attempt IVF and switch to NC if IVF fails. CONCLUSION: In couples with a history of vasectomy and female of AMA, it is most cost-effective to undergo a VR. If the couple opts for SR for IVF, it is more cost-effective to undergo a concomitant VR than SR alone.

Recognition of Diagnostic Gaps for Laboratory Diagnosis of Fungal Diseases: Expert Opinion from the Fungal Diagnostics Laboratories Consortium (FDLC).

Fungal infections are a rising threat to our immunocompromised patient population, as well as other nonimmunocompromised patients with various medical conditions. However, little progress has been made in the past decade to improve fungal diagnostics. To jointly address this diagnostic challenge, the Fungal Diagnostics Laboratory Consortium (FDLC) was recently created. The FDLC consists of 26 laboratories from the United States and Canada that routinely provide fungal diagnostic services for patient care. A survey of fungal diagnostic capacity among the 26 members of the FDLC was recently completed, identifying the following diagnostic gaps: lack of molecular detection of mucormycosis; lack of an optimal diagnostic algorithm incorporating fungal biomarkers and molecular tools for early and accurate diagnosis of Pneumocystis pneumonia, aspergillosis, candidemia, and endemic mycoses; lack of a standardized molecular approach to identify fungal pathogens directly in formalin-fixed paraffin-embedded tissues; lack of robust databases to enhance mold identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; suboptimal diagnostic approaches for mold blood cultures, tissue culture processing for Mucorales, and fungal respiratory cultures for cystic fibrosis patients; inadequate capacity for fungal point-of-care testing to detect and identify new, emerging or underrecognized, rare, or uncommon fungal pathogens; and performance of antifungal susceptibility testing. In this commentary, the FDLC delineates the most pressing unmet diagnostic needs and provides expert opinion on how to fulfill them. Most importantly, the FDLC provides a robust laboratory network to tackle these diagnostic gaps and ultimately to improve and enhance the clinical laboratory's capability to rapidly and accurately diagnose fungal infections.

SARS-CoV-2 Viral Load Predicts Mortality in Patients with and without Cancer Who Are Hospitalized with COVID-19.

Patients with cancer may be at increased risk of severe coronavirus disease 2019 (COVID-19), but the role of viral load on this risk is unknown. We measured SARS-CoV-2 viral load using cycle threshold (CT) values from reverse-transcription polymerase chain reaction assays applied to nasopharyngeal swab specimens in 100 patients with cancer and 2,914 without cancer who were admitted to three New York City hospitals. Overall, the in-hospital mortality rate was 38.8% among patients with a high viral load, 24.1% among patients with a medium viral load, and 15.3% among patients with a low viral load (p < 0.001). Similar findings were observed in patients with cancer (high, 45.2% mortality; medium, 28.0%; low, 12.1%; p = 0.008). Patients with hematologic malignancies had higher median viral loads (CT = 25.0) than patients without cancer (CT = 29.2; p = 0.0039). SARS-CoV-2 viral load results may offer vital prognostic information for patients with and without cancer who are hospitalized with COVID-19.

Testicular Mapping: A Roadmap to Sperm Retrieval in Nonobstructive Azoospermia?

Guiding a couple with nonobstructive azoospermia requires an integrated approach to care by the urologist and the reproductive endocrinologist. After informing the couple of the implications of the diagnosis, care must be taken to outline the options of parenthood. Most experts agree that sperm retrieval in men can be challenging. This article describes various options of sperm retrieval, historic and contemporary, and highlights the advantages and disadvantages of each. The authors find that using a testicular map can invariably help guide sperm retrieval and overall fertility care. The right approach is one that involves a shared decision with the couple.

COVID-19 in solid organ transplant recipients: Initial report from the US epicenter.

Solid organ transplant recipients may be at a high risk for SARS-CoV-2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with SARS-CoV-2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty-six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual-organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty-two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non-rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID-19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID-19 has the potential to severely impact solid organ transplant recipients.

Management of osteoarticular fungal infections in the setting of immunodeficiency.

Introduction: Osteoarticular fungal infections (OAFIs) complicate the clinical course of high-risk patients, including immunosuppressed individuals. Their management, however, despite being intricate, is governed by evidence arising from sub-optimal quality research, such as case series. Guidelines are scarce and when present result in recommendations based on low quality evidence. Furthermore, the differences between the management of immunocompromised and immunocompetent patients are not distinct. This is a narrative review after a literature search in PubMed, up to November 2019.Areas covered: The major fungal groups causing osteomyelitis and/or arthritis are Candida spp., Aspergillus spp., non-Aspergillus filamentous fungi, non-Candida yeasts and endemic dimorphic fungi. Their epidemiology is briefly analyzed with emphasis on immunodeficiency and other risk factors. Management of OAFIs includes appropriate antifungal drug therapy (liposomal amphotericin B, triazoles or echinocandins), local surgery and immunotherapy for primary immunodeficiencies. Cessation of immunosuppressive drugs is also mandated.Expert opinion: Management of OAFIs includes affordable and available options and approaches. However, research on therapeutic practices is urgently required to be further improved, due to the rarity of affected patients. Evolution is expected to translate into novel antifungal drugs, less invasive and precise surgical approaches and targeted enhancement of immunoregulatory pathways in defense of challenging fungal pathogens.

Breakthrough Bloodstream Infections Caused by Echinocandin-Resistant Candida tropicalis: An Emerging Threat to Immunocompromised Patients with Hematological Malignancies.

BACKGROUND: Candida tropicalis is a virulent fungal pathogen for which echinocandins are the primary therapy. Emergence of resistance to echinocandins of C. tropicalis carries potentially ominous therapeutic implications. METHODS: We describe herein two patients with breakthrough C. tropicalis fungemia during echinocandin therapy, characterize their molecular mechanism of resistance, and systematically review 13 previously reported cases of echinocandin-resistant C. tropicalis bloodstream infections (BSIs) and other diseases. RESULTS: Among these 15 patients with echinocandin-resistant C. tropicalis infections, the median age was 61 years (ages 28-84 years) and 13 (86%) were immunocompromised. Thirteen (86%) of all patients had a history of pervious or concurrent exposure to echinocandins. Isolates of C. tropicalis from 11 cases, including the two index cases, underwent DNA sequencing of the FKS1 gene for mutations known to confer echinocandin resistance. The amino acid substitution Ser654Pro was shown in four cases, while other FKS1 mutations encoded Ser80S/Pro, Phe641Leu, Phe641Ser, Ser80S/Pro substitutions. These mutational events were not associated with collateral increases in minimum inhibitory concentrations to antifungal triazoles and amphotericin B. Overall mortality in patients with echinocandin-resistant C. tropicalis infections was 40%. Among those six patients who died, two received monotherapy with voriconazole, one was treated with fluconazole, one remained on caspofungin, and two were switched to liposomal amphotericin B. Nine patients (60%) survived after being treated with an antifungal agent other than an echinocandin. CONCLUSIONS: Emergence of resistance to echinocandins by C. tropicalis, occurs during antifungal therapy, is associated with high mortality, is mediated by a diverse range of FKS1 mutations, retains in vitro susceptibility to triazoles and amphotericin B, and constitutes an emerging threat to patients with hematological malignancies.

Injection molded open microfluidic well plate inserts for user-friendly coculture and microscopy.

Open microfluidic cell culture systems are powerful tools for interrogating biological mechanisms. We have previously presented a microscale cell culture system, based on spontaneous capillary flow of biocompatible hydrogels, that is integrated into a standard cell culture well plate, with flexible cell compartment geometries and easy pipet access. Here, we present two new injection molded open microfluidic devices that also easily insert into standard cell culture well plates and standard culture workflows, allowing seamless adoption by biomedical researchers. These platforms allow culture and study of soluble factor communication among multiple cell types, and the microscale dimensions are well-suited for rare primary cells. Unique advances include optimized evaporation control within the well, manufacture with reproducible and cost-effective rapid injection molding, and compatibility with sample preparation workflows for high resolution microscopy (following well-established coverslip mounting procedures). In this work, we present several use cases that highlight the usability and widespread utility of our platform including culture of limited primary testis cells from surgical patients, microscopy readouts including immunocytochemistry and single molecule fluorescence in situ hybridization (smFISH), and coculture to study interactions between adipocytes and prostate cancer cells.

Comparison of clinician and patient users of a mobile phone application to assess penile curvature in Peyronie's disease.

Assessment of Peyronie's disease with penile injection is invasive and uncomfortable. We developed a smartphone application (UWPEN) to assess penile angulation in the home environment. The purpose of this study was to compare clinician and patient measurements and assess the patient experience with UWPEN in a clinical setting. We prospectively enrolled patients with Peyronie's disease undergoing intracavernosal injection of alprostadil. Penile angulation and narrowing were then assessed by patients and clinicians using UWPEN and compared to values obtained via a goniometer and a ruler (gold standard). Measurements were compared using the Pearson correlation test. Upon completion of measurements, patients were surveyed regarding the ease of use, confidence with use, and measurement preferences. Twenty patients were enrolled in the study; two patients were excluded for poor penile turgidity after a maximum dosage of intracavernosal alprostadil. Correlation between UWPEN and gold standard measurements by patients and clinicians was R = 0.55 (p = 0.01) and R = 0.87 (p < 0.01) for dorsal measurements, R = 0.62 (p = 0.01) and R = 0.77 (p < 0.01) for lateral measurements, and R = 0.73 (p < 0.01) and R = 0.64 (p < 0.01) for girth measurements, respectively. Prior evaluation of correlation suggests a strong correlation at R = 0.8, and good correlation at R = 0.5. Overall, patients preferred using UWPEN to traditional measurements, and 75% reported UWPEN as their first preference for measurements. UWPEN enables patients to assess their disease severity with good correlation to gold standard measurements. Patients prefer mobile platforms for disease monitoring, and development of technology for disease monitoring should be a priority within the Peyronie's disease research community.

Impact of a Multiplexed Polymerase Chain Reaction Panel on Identifying Diarrheal Pathogens in Hematopoietic Cell Transplant Recipients.

BACKGROUND: Diarrhea is common and associated with substantial morbidity among hematopoietic cell transplant (HCT) recipients, but the etiology is often not identified. Multiplexed polymerase chain reaction (PCR) assays increase the detection of diarrheal pathogens, but the impact of this technology in this population has not been evaluated. METHODS: Our center replaced stool cultures and other conventional microbiologic methods with the FilmArray Gastrointestinal Panel (GI PCR) in June 2016. We reviewed all adult patients who received an HCT from June 2014-May 2015 (pre-GI PCR, n = 163) and from June 2016-May 2017 (post-GI PCR, n = 182) and followed them for 1 year after transplantation. Clostridioides difficile infection was diagnosed by an independent PCR test in both cohorts. RESULTS: The proportion of patients with ≥1 identified infectious diarrheal pathogen increased from 25% to 37% after implementation of GI PCR (P = .01). Eight patients (5%) in the pre-GI PCR cohort tested positive for a pathogen other than C. difficile versus 49 patients (27%) in the post-GI PCR cohort (P < .001). The most common non-C. difficile diarrheal pathogens in the post-GI PCR cohort were enteropathogenic Escherichia coli (n = 14, 8%), norovirus (n = 14, 8%), and Yersinia enterocolitica (n = 7, 4%). The percentage of diarrheal episodes with an identified infectious etiology increased from 14% to 23% (P = .001). Median total costs of stool testing per patient did not increase (pre: $473; post: $425; P = .25). CONCLUSIONS: Infectious etiologies of diarrhea were identified in a higher proportion of HCT recipients after replacing conventional stool testing with a multiplexed PCR assay, without an increase in testing costs.