Beta-defensin index: A functional biomarker for oral cancer detection.

There is an unmet clinical need for a non-invasive and cost-effective test for oral squamous cell carcinoma (OSCC) that informs clinicians when a biopsy is warranted. Human beta-defensin 3 (hBD-3), an epithelial cell-derived anti-microbial peptide, is pro-tumorigenic and overexpressed in early-stage OSCC compared to hBD-2. We validate this expression dichotomy in carcinoma in situ and OSCC lesions using immunofluorescence microscopy and flow cytometry. The proportion of hBD-3/hBD-2 levels in non-invasively collected lesional cells compared to contralateral normal cells, obtained by ELISA, generates the beta-defensin index (BDI). Proof-of-principle and blinded discovery studies demonstrate that BDI discriminates OSCC from benign lesions. A multi-center validation study shows sensitivity and specificity values of 98.2% (95% confidence interval [CI] 90.3-99.9) and 82.6% (95% CI 68.6-92.2), respectively. A proof-of-principle study shows that BDI is adaptable to a point-of-care assay using microfluidics. We propose that BDI may fulfill a major unmet need in low-socioeconomic countries where pathology services are lacking.

Guideline Compliance and Indications for Inferior Vena Cava Filter Placement at a Quaternary Care Medical Center.

PURPOSE: This study investigated physician compliance with indications for inferior vena cava (IVC) filter placement according to the 2012 American College of Chest Physicians (ACCP) and the 2011 Society of Interventional Radiology (SIR) guidelines. MATERIALS AND METHODS: A retrospective medical record review of 231 retrievable IVC filters placed between August 15, 2016, and December 28, 2017, at a large urban academic medical center. Guideline compliance to the 2012 ACCP and the 2011 SIR guidelines, and indications for IVC filter placements were assessed through an adjudication protocol. Filter retrieval and complication rates were also examined. RESULTS: Compliance to guidelines was low (60.2% for ACCP; 74.0% for SIR), especially for non-intensive care unit (ICU) patients (ICU 74.6% vs non-ICU 54.8%, p=0.007 for ACCP; ICU 82.5% vs non-ICU 70.8%, p=0.092 for SIR). After adjudication, 8.2% (19/231) of filters were considered non-indicated but reasonable, 17.7% (41/231) non-indicated and unreasonable, and 13.9% (32/231) SIR-indicated but not ACCP-indicated. The most common indication was venous thromboembolism with contraindication to anticoagulation. The most common reasons for non-compliance were distal deep venous thrombosis with contraindication to anticoagulation (19/60, 31.6%) and clot burden (19/60, 31.6%). One-year filter retrieval and 90-day complication rates were 32.0% (74/231) and 6.1% (14/231), respectively. CONCLUSION: Compliance to established guidelines was low. Reasons for non-compliance included limitations or discrepancies in guidelines, as well as non-evidence-based filter placements. CLINICAL IMPACT: Despite increasing utilization of inferior vena cava (IVC) filters, guideline compliance for IVC filter placement among providers is unclear. The results of this study indicate that physician compliance to established guidelines is poor, especially in non-intensive-care-unit patients. Noncompliance stems from non-evidence-based filter placement as well as differences and limitations in guidelines. Avoiding non-indicated IVC filter placement and consolidation of guidelines may significantly improve guideline compliance. The critical insights gained from this study can help promote judicious use of IVC filters and highlight the role of venous thromboembolism experts in navigating complex cases and nuances of guidelines.

Impact of Molnupiravir Treatment on Patient-Reported COVID-19 Symptoms in the Phase 3 MOVe-OUT Trial: A Randomized, Placebo-Controlled Trial.

BACKGROUND: Molnupiravir is an orally administered antiviral authorized for COVID-19 treatment in adults at high risk of progression to severe disease. Here, we report secondary and post hoc analyses of participants' self-reported symptoms in the MOVe-OUT trial, which evaluated molnupiravir initiated within 5 days of symptom onset in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed COVID-19. METHODS: Eligible participants completed a 15-item symptom diary daily from day 1 (randomization) through day 29, rating symptom severity as "none," "mild," "moderate," or "severe"; loss of smell and loss of taste were rated as "yes" or "no." Time to sustained symptom resolution/improvement was defined as the number of days from randomization to the first of 3 consecutive days of reduced severity, without subsequent relapse. Time to symptom progression was defined as the number of days from randomization to the first of 2 consecutive days of worsening severity. The Kaplan-Meier method was used to estimate event rates at various time points. The Cox proportional hazards model was used to estimate the hazard ratio between molnupiravir and placebo. RESULTS: For most targeted COVID-19 symptoms, sustained resolution/improvement was more likely, and progression was less likely, in the molnupiravir versus placebo group through day 29. When evaluating 5 distinctive symptoms of COVID-19, molnupiravir participants had a shorter median time to first resolution (18 vs 20 d) and first alleviation (13 vs 15 d) of symptoms compared with placebo. CONCLUSIONS: Molnupiravir treatment in at-risk, unvaccinated patients resulted in improved clinical outcomes for most participant-reported COVID-19 symptoms compared with placebo. Clinical Trials Registration. ClinicalTrials.gov: NCT04575597.

Human ß-Defensin-3 is Associated With Platelet-Derived Extracellular Vesicles and is a Potential Contributor to Endothelial Dysfunction.

While platelets are the essential mediators of hemostasis, they are being increasingly recognized for their potential of contributing to host defenses. Here, using immunofluorescent microscopy, western blot, and ELISA, we found that human ß-defensin 3 (hBD-3), an important antimicrobial peptide produced by epithelial cells, can be detected in human platelets and megakaryocytes. Flow cytometry and immuno-electron microscopy revealed hBD-3 on the surface of thrombin activated platelets. Moreover, hBD-3 was also found in platelet derived extracellular vesicles (p-EVs), isolated from platelet poor plasma and from platelet supernatants following thrombin stimulation. Incubation of platelets with hBD-3 peptide resulted in modest platelet activation and pre-incubation of platelets with synthetic hBD-3 prior to exposure to thrombin appeared to increase hBD-3 content in platelet lysates as well as in p-EVs, suggesting that hBD-3 can be initially taken up by platelets, perhaps via their open canalicular system. Interestingly, in vitro exposure of primary human endothelial cells to either hBD-3 peptide or purified p-EVs, caused significant endothelial dysfunction as documented by diminished levels of phosphorylated endothelial nitric oxide synthase (eNOS), Krüppel like factor-2 (KLF-2), and elevated relative expression of von Willebrand Factor (vWF). Pre-incubation of platelets with hBD-3 appeared to augment endothelial dysfunction caused by p-EVs. Overall, the current study provides evidence that hBD-3 enriched EVs can be released by activated platelets and may play a role in positive feedback of platelet activation as well as in endothelial dysfunction. Theoretically, these effects could contribute to both cellular recruitment to the endothelium creating a pro-thrombotic vascular microenvironment which serve as a bridge between innate immunity and hemostasis.

HBD-2 binds SARS-CoV-2 RBD and blocks viral entry: Strategy to combat COVID-19.

New approaches to complement vaccination are needed to combat the spread of SARS-CoV-2 and stop COVID-19-related deaths and medical complications. Human beta defensin 2 (hBD-2) is a naturally occurring epithelial cell-derived host defense peptide that has anti-viral properties. Our comprehensive in-silico studies demonstrate that hBD-2 binds the site on the CoV-2-RBD that docks with the ACE2 receptor. Biophysical measurements confirm that hBD-2 indeed binds to the CoV-2-receptor-binding domain (RBD) (KD ∼ 2µM by surface plasmon resonance), preventing it from binding to ACE2-expressing cells. Importantly, hBD-2 shows specificity by blocking CoV-2/spike pseudoviral infection, but not VSVG-mediated infection, of ACE2-expressing human cells with an IC50 of 2.8 ± 0.4 µM. These promising findings offer opportunities to develop hBD-2 and/or its derivatives and mimetics to safely and effectively use as agents to prevent SARS-CoV-2 infection.

Ramping Up Antimicrobial Peptides Against Severe Acute Respiratory Syndrome Coronavirus-2.

Human-derived antimicrobial peptides (AMPs), such as defensins and cathelicidin LL-37, are members of the innate immune system and play a crucial role in early pulmonary defense against viruses. These AMPs achieve viral inhibition through a variety of mechanisms including, but not limited to, direct binding to virions, binding to and modulating host cell-surface receptors, blocking viral replication, and aggregation of viral particles and indirectly by functioning as chemokines to enhance or curb adaptive immune responses. Given the fact that we are in a pandemic of unprecedented severity and the urgent need for therapeutic options to combat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), naturally expressed AMPs and their derivatives have the potential to combat coronavirus disease 2019 (COVID-19) and impede viral infectivity in various ways. Provided the fact that development of effective treatments is an urgent public health priority, AMPs and their derivatives are being explored as potential prophylactic and therapeutic candidates. Additionally, cell-based platforms such as human mesenchymal stem cell (hMSC) therapy are showing success in saving the lives of severely ill patients infected with SARS-CoV-2. This could be partially due to AMPs released from hMSCs that also act as immunological rheostats to modulate the host inflammatory response. This review highlights the utilization of AMPs in strategies that could be implemented as novel therapeutics, either alone or in combination with other platforms, to treat CoV-2-infected individuals.

The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging.

An increased accumulation of immune-dysfunction-associated CD4+Foxp3+ regulatory T cells (Tregs) is observed in aging oral mucosa during infection. Here we studied the function of Tregs during oral cancer development in aging mucosa. First, we found heightened proportions of Tregs and myeloid-derived suppressor cells (MDSC) accumulating in mouse and human oral squamous cell carcinoma (OSCC) tissues. Using the mouse 4-Nitroquinoline 1-oxide(4-NQO) oral carcinogenesis model, we found that tongues of aged mice displayed increased propensity for epithelial cell dysplasia, hyperplasia, and accelerated OSCC development, which coincided with significantly increased abundance of IL-1ß, Tregs, and MDSC in tongues. Partial depletion of Tregs reduced tumor burden. Moreover, fungal abundance and dectin-1 signaling were elevated in aged mice suggesting a potential role for dectin-1 in modulating immune environment and tumor development. Confirming this tenet, dectin-1 deficient mice showed diminished IL-1ß, reduced infiltration of Tregs and MDSC in the tongues, as well as slower progression and reduced severity of tumor burden. Taken together, these data identify an important role of dectin-1 signaling in establishing the intra-tumoral immunosuppressive milieu and promoting OSCC tumorigenesis in the context of aging.

Immune-mediated diseases and thromboembolic events: a modified Delphi panel.

INTRODUCTION: A multidisciplinary panel of physicians was convened to gain understanding of the relationship between thromboembolic events (TEs) and immune-mediated diseases (IMDs). The primary objective of the panel was to assess areas of consensus on the IMD most prone to TE as well as modifiable and unmodifiable factors that might exacerbate or mitigate the risk of TEs. METHODS: Thirteen nationally recognized physicians were selected based on their contributions to guidelines, publications and patient care. The modified Delphi panel consisted of four rounds of engagement: (1) a semi-structured interview, (2) an expert panel questionnaire, (3) an in-person panel discussion, and (4) a consensus statement survey. RESULTS: Ulcerative colitis and Crohn's disease were identified as two of four IMDs with the highest TE risk. Consensus was reached on several non-modifiable and modifiable characteristics of high-risk. Approaches to reduce TE incidence were identified such as altering treatment, requiring the monitoring of patients for TEs and modifying patient behaviors. Janus kinase inhibitors and corticosteroids were identified as therapies that required further evaluation given their potential TE risk. DISCUSSION: The panel reached a consensus that several IMDs are at an elevated risk of TEs. Physicians are unable to control most patient level risk factors but can control the therapies being used. Consequently, physicians should consider the specific IMD, be aware of TE risk factors, and take into account risk factors in selecting the therapies to optimally manage their conditions and to reduce the risk of TEs in this population.

Molecular dynamics simulations and functional studies reveal that hBD-2 binds SARS-CoV-2 spike RBD and blocks viral entry into ACE2 expressing cells.

New approaches to complement vaccination are needed to combat the spread of SARS-CoV-2 and stop COVID-19 related deaths and long-term medical complications. Human beta defensin 2 (hBD-2) is a naturally occurring epithelial cell derived host defense peptide that has antiviral properties. Our comprehensive in-silico studies demonstrate that hBD-2 binds the site on the CoV-2-RBD that docks with the ACE2 receptor. Biophysical and biochemical assays confirm that hBD-2 indeed binds to the CoV-2-receptor binding domain (RBD) (KD ~ 300 nM), preventing it from binding to ACE2 expressing cells. Importantly, hBD-2 shows specificity by blocking CoV-2/spike pseudoviral infection, but not VSV-G mediated infection, of ACE2 expressing human cells with an IC50 of 2.4± 0.1 µM. These promising findings offer opportunities to develop hBD-2 and/or its derivatives and mimetics to safely and effectively use as novel agents to prevent SARS-CoV-2 infection.

IL-1ß-MyD88-mTOR Axis Promotes Immune-Protective IL-17A+Foxp3+ Cells During Mucosal Infection and Is Dysregulated With Aging.

CD4+Foxp3+Tregs maintain immune homeostasis, but distinct mechanisms underlying their functional heterogeneity during infections are driven by specific cytokine milieu. Here we show that MyD88 deletion in Foxp3+ cells altered their function and resulted in increased fungal burden and immunopathology during oral Candida albicans (CA) challenge. Excessive inflammation due to the absence of MyD88 in Tregs coincided with a reduction of the unique population of IL-17A expressing Foxp3+ cells (Treg17) and an increase in dysfunctional IFN-γ+/Foxp3+ cells (TregIFN-γ) in infected mice. Failure of MyD88-/- Tregs to regulate effector CD4+ T cell functions correlated with heightened levels of IFN-γ in CD4+ T cells, as well as increased infiltration of inflammatory monocytes and neutrophils in oral mucosa in vivo. Mechanistically, IL-1ß/MyD88 signaling was required for the activation of IRAK-4, Akt, and mTOR, which led to the induction and proliferation of Treg17 cells. In the absence of IL-1 receptor signaling, Treg17 cells were reduced, but IL-6-driven expansion of TregIFN-γ cells was increased. This mechanism was physiologically relevant during Candida infection in aged mice, as they exhibited IL-1 receptor/MyD88 defect in Foxp3+ cells, loss of p-mTORhighTreg17 cells and reduced levels of IL-1ß in oral mucosa, which coincided with persistent tongue inflammation. Concurrent with Treg dysfunction, aging was associated with increased CD4+ T cell hyperactivation and heightened levels of IL-6 in mice and humans in oral mucosa in vivo. Taken together, our data identify IL-1ß/MyD88/Treg axis as a new component that modulates inflammatory responses in oral mucosa. Also, dysregulation of this axis in an aging immune system may skew host defense towards an immunopathological response in mucosal compartments.

Development and External Validation of a Machine Learning Tool to Rule Out COVID-19 Among Adults in the Emergency Department Using Routine Blood Tests: A Large, Multicenter, Real-World Study.

BACKGROUND: Conventional diagnosis of COVID-19 with reverse transcription polymerase chain reaction (RT-PCR) testing (hereafter, PCR) is associated with prolonged time to diagnosis and significant costs to run the test. The SARS-CoV-2 virus might lead to characteristic patterns in the results of widely available, routine blood tests that could be identified with machine learning methodologies. Machine learning modalities integrating findings from these common laboratory test results might accelerate ruling out COVID-19 in emergency department patients. OBJECTIVE: We sought to develop (ie, train and internally validate with cross-validation techniques) and externally validate a machine learning model to rule out COVID 19 using only routine blood tests among adults in emergency departments. METHODS: Using clinical data from emergency departments (EDs) from 66 US hospitals before the pandemic (before the end of December 2019) or during the pandemic (March-July 2020), we included patients aged ≥20 years in the study time frame. We excluded those with missing laboratory results. Model training used 2183 PCR-confirmed cases from 43 hospitals during the pandemic; negative controls were 10,000 prepandemic patients from the same hospitals. External validation used 23 hospitals with 1020 PCR-confirmed cases and 171,734 prepandemic negative controls. The main outcome was COVID 19 status predicted using same-day routine laboratory results. Model performance was assessed with area under the receiver operating characteristic (AUROC) curve as well as sensitivity, specificity, and negative predictive value (NPV). RESULTS: Of 192,779 patients included in the training, external validation, and sensitivity data sets (median age decile 50 [IQR 30-60] years, 40.5% male [78,249/192,779]), AUROC for training and external validation was 0.91 (95% CI 0.90-0.92). Using a risk score cutoff of 1.0 (out of 100) in the external validation data set, the model achieved sensitivity of 95.9% and specificity of 41.7%; with a cutoff of 2.0, sensitivity was 92.6% and specificity was 59.9%. At the cutoff of 2.0, the NPVs at a prevalence of 1%, 10%, and 20% were 99.9%, 98.6%, and 97%, respectively. CONCLUSIONS: A machine learning model developed with multicenter clinical data integrating commonly collected ED laboratory data demonstrated high rule-out accuracy for COVID-19 status, and might inform selective use of PCR-based testing.

Innate immune mechanisms to oral pathogens in oral mucosa of HIV-infected individuals.

A crucial aspect of mucosal HIV transmission is the interaction between HIV, the local environmental milieu and immune cells. The oral mucosa comprises many host cell types including epithelial cells, CD4 + T cells, dendritic cells and monocytes/macrophages, as well as a diverse microbiome predominantly comprising bacterial species. While the oral epithelium is one of the first sites exposed to HIV through oral-genital contact and nursing infants, it is largely thought to be resistant to HIV transmission via mechanisms that are still unclear. HIV-1 infection is also associated with predisposition to secondary infections, such as tuberculosis, and other diseases including cancer. This review addresses the following questions that were discussed at the 8th World Workshop on Oral Health and Disease in AIDS held in Bali, Indonesia, 13 September -15 September 2019: (a) How does HIV infection affect epithelial cell signalling? (b) How does HIV infection affect the production of cytokines and other innate antimicrobial factors, (c) How is the mucosal distribution and function of immune cells altered in HIV infection? (d) How do T cells affect HIV (oral) pathogenesis and cancer? (e) How does HIV infection lead to susceptibility to TB infections?

Diagnosis and Treatment of Pulmonary Embolism During the Coronavirus Disease 2019 Pandemic: A Position Paper From the National PERT Consortium.

The coexistence of coronavirus disease 2019 (COVID-19) and pulmonary embolism (PE), two life-threatening illnesses, in the same patient presents a unique challenge. Guidelines have delineated how best to diagnose and manage patients with PE. However, the unique aspects of COVID-19 confound both the diagnosis and treatment of PE, and therefore require modification of established algorithms. Important considerations include adjustment of diagnostic modalities, incorporation of the prothrombotic contribution of COVID-19, management of two critical cardiorespiratory illnesses in the same patient, and protecting patients and health-care workers while providing optimal care. The benefits of a team-based approach for decision-making and coordination of care, such as that offered by pulmonary embolism response teams (PERTs), have become more evident in this crisis. The importance of careful follow-up care also is underscored for patients with these two diseases with long-term effects. This position paper from the PERT Consortium specifically addresses issues related to the diagnosis and management of PE in patients with COVID-19.

Overview of Management of Intermediate- and High-Risk Pulmonary Embolism.

Anticoagulation is the cornerstone of acute pulmonary embolism (PE) therapy. Intermediate-risk (submassive) or high-risk (massive) PE patients have higher mortality than low-risk patients. It is generally accepted that high-risk PE patients should be considered for more aggressive therapy. Intermediate-risk patients can be subdivided, although more than simply categorizing the patient is required to guide therapy. Therapeutic approaches depend on a prompt, detailed evaluation, and PE response teams may help with rapid assessment and initiation of therapy. More clinical trial data are needed to guide clinicians in the management of acute intermediate- and high-risk PE patients.

Inflatable Penile Prosthesis in the Ambulatory Surgical Setting: Outcomes From a Large Urological Group Practice.

BACKGROUND: The definitive treatment for erectile dysfunction is the surgical implantation of a penile prosthesis, of which the most common type is the 3-piece inflatable penile prosthesis (IPP) device. IPP surgery in outpatient freestanding ambulatory surgical centers (ASC) is becoming more prevalent as payers and health systems alike look to reduce healthcare costs. AIM: To evaluate IPP surgical outcomes in an ASC as compared to contemporaneously-performed hospital surgeries. METHODS: A database of all patients undergoing IPP implantation by practitioners in the largest private community urology group practice in the United States, from January 1, 2013 to August 1, 2019, was prospectively compiled and retrospectively reviewed. Cohorts of patients having IPP implantation performed in the hospital vs ASC setting were compared. MAIN OUTCOME MEASURE: The primary outcome measure was to compare surgical data (procedural and surgical times, need for hospital transfer from ASC) and outcomes (risk for device infection, erosion, and need for surgical revision) between ASC and hospital-based surgery groups. RESULTS: A total of 923 patients were included for this analysis, with 674 (73%) having ASC-based surgery and 249 (27%) hospital-based, by a total of 33 surgeons. Median procedural (99.5 vs 120 minutes, P < .001) and surgical (68 vs 75 minutes, P < .001) times were significantly shorter in the ASC. While the risk for device erosion and need for surgical revision were similar between groups, there was no higher risk for prosthetic infection when surgery was performed in the ASC (1.7% vs 4.4% [hospital], P = .02), corroborated by logistic regression analysis (odds ratio 0.39, P = .03). The risk for postoperative transfer of an ASC patient to the hospital was low (0.45%). The primary reason for mandated hospital-based surgery was medical (51.4%), though requirement as a result of insurance directive (39.7%) was substantial. CLINICAL IMPLICATIONS: IPP implantation in the ASC is safe, has similar outcomes compared to hospital-based surgery with a low risk for need for subsequent hospital transfer. STRENGTHS & LIMITATIONS: The strengths of this study include the large patient population in this analysis as well as the real-world nature of our practice. Limitations include the retrospective nature of the review as well as the potential for residual confounding. CONCLUSION: ASC-based IPP implantation is safe, with shorter surgical and procedural times compared to those cases performed in the hospital setting, with similar functional outcomes. These data suggest no added benefit to hospital-based surgery in terms of prosthetic infection risk. Weinberg AC, Siegelbaum MH, Lerner BD, et al. Inflatable Penile Prosthesis in the Ambulatory Surgical Setting: Outcomes From a Large Urological Group Practice. J Sex Med 2020;17:1025-1032.

Use of the Bedside-Placed Angel Catheter IVC Filter for Venous Thromboembolic Disease in Critically Ill Medical Patients.

Venous thromboembolic disease is a major problem among critically ill patients, with significant associated morbidity and mortality. Many critically ill patients have contraindications to systemic anticoagulation, and inferior vena cava (IVC) filters are an important alternative in preventing pulmonary emboli (PE) in this population. The Angel Catheter (Mermaid, Stenlose, Denmark) is a novel percutaneous and removable IVC filter attached to the end of a triple lumen central venous catheter which has been demonstrated to reduce PE in surgical and trauma patients. This case series describes 18 critically ill medical patients who had an Angel catheter placed either for diagnosed PE or due to high risk for PE; over half had at least submassive PE at the time of Angel catheter placement. None of the patients had a recurrence of PE during Angel catheter use, 29.4% had clot found in the filter via cavogram upon removal, and only one had a minor complication which had no clinical consequence. In 2 patients, the placement of the Angel Catheter resulted in the prevention of PE during catheter-directed thrombolysis of extensive deep vein thrombosis. This case series demonstrates that in a population of critically ill, elderly, and obese medical patients the bedside placement of the Angel IVC filter is feasible, safe, and may be effective for preventing PE.

Role of FAD-I in Fusobacterial Interspecies Interaction and Biofilm Formation.

: RadD, a major adhesin of oral fusobacteria, is part of a four-gene operon encoding the small lipoprotein FAD-I and two currently uncharacterized small proteins encoded by the rapA and rapB genes. Previously, we described a role for FAD-I in the induction of human B-defensin 2 (hBD2) upon contact with oral epithelial cells. Here, we investigated potential roles for fad-I, rapA, and rapB in interspecies interaction and biofilm formation. Gene inactivation mutants were generated for each of these genes in the nucleatum and polymorphum subspecies of Fusobacterium nucleatum and characterized for their adherence to partner species, biofilm formation, and operon transcription. Binding to Streptococcus gordonii was increased in all mutant strains with Δfad-I having the most significant effect. This increased adherence was directly proportional to elevated radD transcript levels and resulted in significantly different architecture and height of the biofilms formed by Δfad-I and S. gordonii compared to the wild-type parent. In conclusion, FAD-I is important for fusobacterial interspecies interaction as its lack leads to increased production of the RadD adhesin suggesting a role of FAD-I in its regulation. This regulatory effect does not require the presence of functional RadD.

Correction: Shokeen, B., et al. Role of FAD-I in Fusobacterial Interspecies Interaction and Biofilm Formation. Microorganisms 2020, 8, 70.

The authors wish to make the following corrections to this paper [...].

Inflatable Penile Prosthesis Implantation in the Ambulatory Setting: A Systematic Review.

INTRODUCTION: Erectile dysfunction is a common problem that may be definitively treated with the implantation of an inflatable penile prosthesis (IPP). The preponderance of available data on IPP surgery derives from institutional studies, most notably from academic centers or large single-surgeon series, where the majority of procedures are performed in a hospital setting. Because insurance companies and health systems look to reduce health care costs, IPP surgery in outpatient freestanding ambulatory surgery centers (ASC) is becoming more prevalent. AIM: To review the utility of surgery in an ASC setting and to explore its role in the modern practice of urology, focusing on IPP implantation. METHODS: A critical review was performed of the literature on ambulatory surgery, with specific focus on IPP surgery, using the PubMed database. Key search terms and phrases included erectile dysfunction, penile prosthesis, ambulatory surgery, ambulatory surgery center, outpatient surgery. MAIN OUTCOME MEASURE: The main outcome measure was the use of IPP implantation in an ASC. RESULTS: In contemporary surgical practice, the implementation of ambulatory surgery in free-standing centers is increasing. The principal benefits include reducing cost and improving efficiency. Studies on the modern use of IPPs support the prospect of implantation in an ambulatory setting, which can achieve similar outcomes to surgeries classically performed in the inpatient hospital setting. Novel approaches to anesthesia, surgical, and nursing care have revolutionized IPP surgery so that it can now be safely and effectively performed in the ambulatory setting. CONCLUSION: The role of ambulatory IPP implantation has increased, with the majority of cases being performed outside the hospital. Although there will always be a need for hospital-based surgery, such as significant medical comorbidities, more studies demonstrating the safety and feasibility of ambulatory surgery are needed. For those men who would otherwise be candidates for ambulatory surgery but whose insurance mandates hospital-based treatment, such studies proving utility, safety, and reduced cost could inspire policy change and broaden the ambulatory practice of IPP surgery. Segal RL, Siegelbaum MH, Lerner BD, et al. Inflatable Penile Prosthesis Implantation in the Ambulatory Setting: A Systematic Review. Sex Med Rev 2020;8:338-347.