Real-world treatment patterns and quality of life among patients with locally advanced or metastatic urothelial carcinoma living in Saudi Arabia, South Korea, Taiwan, and Turkey.

OBJECTIVES: To evaluate demographic and clinical characteristics, treatment patterns, and quality of life in patients with locally advanced or metastatic urothelial carcinoma in Asia. METHODS: Data were drawn from the Adelphi Real World Metastatic Urothelial Carcinoma Disease Specific Programme™, a cross-sectional survey of medical oncologists/urologists and their adult patients in Saudi Arabia, South Korea, Taiwan, and Turkey. Exploratory patient-reported outcomes included the EQ-5D visual analog scale, European Organisation for Research and Treatment of Cancer Quality of Life of Patient Questionnaire global health, and Brief Pain Inventory. Analyses were descriptive. RESULTS: Overall, 175 physicians reported data for 988 patients. Mean (standard deviation) patient age was 66.3 (10.8) years, 77% were men, and 82% had bladder tumors at diagnosis. Of patients receiving first- (n = 988), second- (n = 290), and third-line (n = 87) treatments, 81%, 35%, and 59% received chemotherapy, respectively, and 17%, 63%, and 34% received programmed cell death protein 1/ligand 1 inhibitors, respectively. Patient-reported (n = 319) mean (standard deviation) EQ-5D visual analog scale score was 51.8 (15.6), European Organisation for Research and Treatment of Cancer Quality of Life of Patient Questionnaire global health status score was 44.6 (19.9), and Brief Pain Inventory score was 6.5 (1.9; n = 315). CONCLUSION: The most common first- and second-line treatments for locally advanced or metastatic urothelial carcinoma were chemotherapy and programmed cell death protein 1/ligand inhibitors, respectively. At third line, 10% of patients received best supportive care alone, underscoring an unmet need for effective third-line treatment options. Patients in all regions reported quality-of-life impairment.

Spatially resolved immune exhaustion within the alloreactive microenvironment predicts liver transplant rejection.

Allograft rejection is common following clinical organ transplantation, but defining specific immune subsets mediating alloimmunity has been elusive. Calcineurin inhibitor dose escalation, corticosteroids, and/or lymphocyte depleting antibodies have remained the primary options for treatment of clinical rejection episodes. Here, we developed a highly multiplexed imaging mass cytometry panel to study the immune response in archival biopsies from 79 liver transplant (LT) recipients with either no rejection (NR), acute T cell-mediated rejection (TCMR), or chronic rejection (CR). This approach generated a spatially resolved proteomic atlas of 461,816 cells (42 phenotypes) derived from 96 pathologist-selected regions of interest. Our analysis revealed that regulatory (HLADR+ Treg) and PD1+ T cell phenotypes (CD4+ and CD8+ subsets), combined with variations in M2 macrophage polarization, were a unique signature of active TCMR. These data provide insights into the alloimmune microenvironment in clinical LT, including identification of potential targets for focused immunotherapy during rejection episodes and suggestion of a substantial role for immune exhaustion in TCMR.

Prevalence and impact of vasomotor symptoms due to menopause among women in Brazil, Canada, Mexico, and Nordic Europe: a cross-sectional survey.

OBJECTIVE: This study investigated the prevalence and impact of moderate to severe vasomotor symptoms (VMS), related treatment patterns, and experiences in women. METHODS: The primary objective was to assess the prevalence of moderate to severe menopause-related VMS among postmenopausal women aged 40 to 65 years in Brazil, Canada, Mexico, and four Nordic European countries (Denmark, Finland, Norway, and Sweden) using an online survey. Secondary objectives assessed impact of VMS among perimenopausal and postmenopausal women with moderate to severe VMS using the Menopause-Specific Quality of Life questionnaire, Work Productivity and Activity Impairment questionnaire, Patient-Reported Outcomes Measurement Information System sleep disturbances assessment, and questions regarding treatment patterns and attitudes toward symptoms and available treatments. RESULTS: Among 12,268 postmenopausal women, the prevalence of moderate to severe VMS was about 15.6% and was highest in Brazil (36.2%) and lowest in Nordic Europe (11.6%). Secondary analyses, conducted among 2,176 perimenopausal and postmenopausal women, showed that VMS affected quality of life across all domains measured and impaired work activities by as much as 30%. Greater symptom severity negatively affected sleep. Many women sought medical advice, but most (1,238 [56.9%]) were not receiving treatment for their VMS. The majority (>70%) considered menopause to be a natural part of aging. Those treated with prescription hormone therapy and nonhormone medications reported some safety/efficacy concerns. CONCLUSIONS: Among women from seven countries, moderate to severe menopause-related VMS were widespread, varied by region, and largely impaired quality of life, productivity, and/or sleep.

Spatially resolved immune exhaustion within the alloreactive microenvironment predicts liver transplant rejection.

Allograft rejection is a frequent complication following solid organ transplantation, but defining specific immune subsets mediating alloimmunity has been elusive due to the scarcity of tissue in clinical biopsy specimens. Single cell techniques have emerged as valuable tools for studying mechanisms of disease in complex tissue microenvironments. Here, we developed a highly multiplexed imaging mass cytometry panel, single cell analysis pipeline, and semi-supervised immune cell clustering algorithm to study archival biopsy specimens from 79 liver transplant (LT) recipients with histopathological diagnoses of either no rejection (NR), acute T-cell mediated rejection (TCMR), or chronic rejection (CR). This approach generated a spatially resolved proteomic atlas of 461,816 cells derived from 98 pathologist-selected regions of interest relevant to clinical diagnosis of rejection. We identified 41 distinct cell populations (32 immune and 9 parenchymal cell phenotypes) that defined key elements of the alloimmune microenvironment (AME), identified significant cell-cell interactions, and established higher order cellular neighborhoods. Our analysis revealed that both regulatory (HLA-DR+ Treg) and exhausted T-cell phenotypes (PD1+CD4+ and PD1+CD8+ T-cells), combined with variations in M2 macrophage polarization, were a unique signature of TCMR. TCMR was further characterized by alterations in cell-to-cell interactions among both exhausted immune subsets and inflammatory populations, with expansion of a CD8 enriched cellular neighborhood comprised of Treg, exhausted T-cell subsets, proliferating CD8+ T-cells, and cytotoxic T-cells. These data enabled creation of a predictive model of clinical outcomes using a subset of cell types to differentiate TCMR from NR (AUC = 0.96 ± 0.04) and TCMR from CR (AUC = 0.96 ± 0.06) with high sensitivity and specificity. Collectively, these data provide mechanistic insights into the AME in clinical LT, including a substantial role for immune exhaustion in TCMR with identification of novel targets for more focused immunotherapy in allograft rejection. Our study also offers a conceptual framework for applying spatial proteomics to study immunological diseases in archival clinical specimens.

Practice patterns and perspectives regarding treatment for symptoms of menopause: qualitative interviews with US health care providers.

OBJECTIVE: To document health care providers' views regarding treatments for symptoms associated with menopause and discussions with patients about symptoms and treatment decisions. Results informed development of a data collection form for a retrospective medical record review (reported separately). METHODS: Registered US gynecologists or primary care providers from all US regions were identified from local association directories and an in-house database and were invited to participate in a qualitative interview if they consulted with three or more patients per week presenting with menopausal symptoms. Participants provided demographic data, information about patients' symptoms, and health care provider and patient views on prescription and nonprescription therapies. Key concepts/themes from interviews were identified. RESULTS: Participating health care providers (10 gynecologists, 10 primary care providers) agreed there are effective treatment options for menopausal symptoms, particularly vasomotor symptoms and vaginal dryness and/or atrophy. Health care providers reported that treatment was generally dictated by symptoms that interfered with quality of life and/or daily activities, although patients often had symptoms for months before presentation. All health care providers said they prescribe hormone and/or nonhormone therapies for treatment of menopausal symptoms; half stated that they typically inquire about patients' nonprescription therapy use, and 45% recommend specific nonprescription therapies. The most commonly cited barriers to initiation of any therapy for menopausal symptoms were patient concerns about risks and financial considerations (ie, insurance or cost). CONCLUSIONS: US health care providers reported prescribing therapies for menopausal symptoms and noted that these therapies were perceived as generally effective; however, barriers to initiation of prescription therapy exist, and new treatment options are needed.

Treatment and resource utilization for menopausal symptoms in the United States: a retrospective review of real-world evidence from US electronic health records.

OBJECTIVE: The aim of this study was to generate real-world evidence documenting use of prescription and nonprescription therapies recorded by health care providers for women experiencing vasomotor symptoms (VMS) associated with menopause. METHODS: This noninterventional, retrospective, observational cohort study used data from US patient medical records. Participating health care providers were gynecologists, internal medicine/family physicians, or advanced practice providers who typically saw three or more women per week presenting with menopausal symptoms and could identify eligible medical records; providers were recruited from local medical association directories and from listings from previously conducted research. Eligible women presented January 2016 through December 2019, were 40 to 60 years of age, and reported experiencing bothersome hot flashes at least twice within 24 hours. RESULTS: A total of 283 health care providers provided data for 1,016 women. The most common symptoms at initial presentation were hot flashes (91.2%), sleep problems (49.9%), and vaginal dryness (47.0%). At least one therapy for menopausal symptoms was recorded for 883 women (86.9%), and 611 (60.1%) had documentation of prescription medication, most commonly hormone therapy (70.4%). Nearly 40% of women had no prescription medication documented, and approximately 13% had no therapy documented. Despite experiencing bothersome menopausal symptoms, approximately 50% delayed seeking care for more than 6 months. Women had a mean of 2.1 (SD, 2.0) office visits related to menopause from initial presentation to completion of review, and health care resource utilization did not vary by treatment status. Subgroup analyses indicated nominal differences in treatment use across ethnic groups and varying prescribing patterns for menopausal symptoms by practitioner type and US region. CONCLUSIONS: A high proportion of women with VMS remain untreated even when experiencing bothersome symptoms of menopause. Improved management of VMS is required to provide relief from the symptoms effectively and safely.

ELIGANT: a Phase 4, interventional, safety study of leuprorelin acetate (ELIGARD®) in Asian men with prostate cancer.

Background: The incidence and mortality rate of men with prostate cancer have been increasing in Asia. ELIGARD® is a formulation of leuprorelin acetate whose safety and efficacy have been well-established in Western regions. However, limited safety data are available for Asian populations. Methods: ELIGANT (ELIGard AsiaN sTudy) was a Phase 4, multicenter, prospective, single-arm, interventional study. Men with locally advanced or metastatic prostate cancer without concomitant chemotherapy, or another androgen receptor pathway inhibitor, were enrolled across Asia to receive ELIGARD® (22.5 mg subcutaneous depot injection) every 3 months for 15 months, with a follow-up visit at 18 months. The primary objective was to establish the safety of ELIGARD® in Asian men with hormone-dependent prostate cancer. The secondary objectives were to assess efficacy, via prostate-specific antigen (PSA) progression and testosterone levels, and health-related quality of life (HRQoL). Results: In total, 106 patients were included in the safety analysis set (SAF). The most common treatment-emergent adverse events (TEAEs) included PSA increase, cough, back pain, hot flush, anemia, and upper respiratory tract infection. TEAEs considered related to ELIGARD® were reported in 13.2% of patients (n=14), two of which were serious. In the full analysis set (FAS) (n=105), 81.2% (n=56) and 68.5% (n=61) of patients achieved a PSA reduction of ≥90% from baseline at 12 and 18 months, respectively. At 18 months, the numbers of patients with testosterone levels <20, 20-50, and >50 ng/dL were 65 (61.9%), 17 (16.2%), and two (1.9%), respectively; 20% had missing testosterone measurements. HRQoL remained stable throughout the study with minimal change from baseline at study completion. Conclusions: In conclusion, the safety profile of ELIGARD® (22.5 mg) in Asian men with hormone-dependent prostate cancer is comparable to previous studies in Western regions. Trial Registration: Clinical trial registration number NCT03035032.

Hydroxychloroquine for Primary Progressive Multiple Sclerosis.

OBJECTIVE: Primary progressive multiple sclerosis (PPMS) does not respond well to immunomodulatory or immunosuppressive treatment. Chronic activation of microglia has been implicated in the pathophysiology of PPMS. The antimalarial drug hydroxychloroquine (HCQ) reduces the activity of human microglia and has neuroprotective effects in vitro. METHODS: We conducted a single-arm, phase II futility trial of 200 mg oral HCQ twice daily for 18 months. In an effort to investigate disability worsening in the absence of overt focal inflammation, we excluded participants with contrast enhancing lesions on a screening magnetic resonance imaging (MRI). The primary end point was ≥20% worsening on the timed 25-foot walk measured between 6 and 18 months of follow-up. RESULTS: Based on original trial data, 40% of the cohort were expected to worsen. We used a Simon 2-stage design to compare a null hypothesis of 40% of the cohort worsening against the one-sided alternative of 20%. Using a 5% type 1 error rate and 80% power, HCQ treatment would be deemed successful if fewer than 10 of 35 participants experienced clinically significant worsening. The study met its primary end point, as only 8 of 35 participants worsened between 6 and 18 months. HCQ was overall well-tolerated, with adverse events in 82% and serious adverse events in 12% of participants. All serious adverse events were unlikely related to HCQ use. INTERPRETATION: HCQ treatment was associated with reduced disability worsening in people with PPMS. HCQ is a promising treatment candidate in PPMS and should be investigated further in randomized controlled clinical trials. ANN NEUROL 2021;90:940-948.

Measuring Maximum Head Circumference Within the Picture Archiving and Communication System: A Fully Automatic Approach.

This study describes an automatic technique to accurately determine the maximum head circumference (MHC) measurement from MRI studies within the Picture Archiving and Communications System, and can automatically add this measurement to the final radiology report. Participants were selected through a retrospective chart review of patients referred to the neurosurgery clinic. Forty-nine pediatric patients with ages ranging from 5 months to 11 years were included in the study. We created 14 printed ring structures to mirror the head circumference values at various ages along the x-axis of the Nellhaus chart. The 3D-printed structures were used to create MRI phantoms. Analytical obtainment of circumference values from the 3D objects and phantom images allowed for a fair estimation and correction of errors on the image-based-measuring instrument. Then, standard manual MHC measurements were performed and compared to values obtained from the patients' MRI T1 images using the tuned instrument proposed in this document. A T-test revealed no statistical difference between the manual assessments and the ones obtained by the automation p = 0.357, α = 0.05. This automatic application augments the more error-prone manual MHC measurement, and can add a numerical value to the final radiology report as a standard application.

Comparison of Joint and Landmark Modeling for Predicting Cancer Progression in Men With Castration-Resistant Prostate Cancer: A Secondary Post Hoc Analysis of the PREVAIL Randomized Clinical Trial.

Importance: Dynamic prediction models may help predict radiographic disease progression in advanced prostate cancer. Objective: To assess whether dynamic prediction models aid prognosis of radiographic progression risk, using ongoing longitudinal prostate-specific antigen (PSA) assessments. Design, Setting, and Participants: This prognostic study used data from the PREVAIL study to compare dynamic models for predicting disease progression. The PREVAIL study was a phase 3, multinational, double-blind, placebo-controlled randomized clinical trial of enzalutamide for prostate cancer conducted from September 2010 to September 2012. A total of 773 men with metastatic castration-resistant prostate cancer (CRPC) who had never received chemotherapy and had no baseline visceral disease were treated with enzalutamide. For illustration, 4 patients were selected based on PSA kinetics or PSA response in case studies. Data were analyzed from July 2018 to September 2019. Main Outcomes and Measures: Landmark and joint models were applied to dynamically predict radiographic progression-free survival (PFS) using longitudinal PSA profile, baseline PSA, lactate dehydrogenase, and hemoglobin levels. The main outcome was radiographic PFS as predicted using landmark and joint models. Current PSA and PSA change were considered longitudinal biomarkers possibly associated with radiographic PFS. Predictive performance was evaluated using Brier score for overall prediction errors (PEs) and area under the curve (AUC) for model discriminative capability. Case studies were illustrated using dynamic prediction plots. Results: A total of 763 men with metastatic CRPC treated with enzalutamide (mean [SD] age, 71.2 [8.5] years; mean [SD] body mass index [calculated as weight in kilograms divided by height in meters squared], 28.4 [4.6]) were included in the analysis. Current PSA and PSA change were associated with radiographic PFS in all models. Adding the PSA slope, compared with the landmark models using current PSA alone, improved the prediction of 5-month prospect of radiographic progression, with relative gains of 5.7% in prediction (PE [SE], 0.132 [0.008] vs 0.140 [0.008]) and 7.7% in discrimination (AUC [SE], 0.800 [0.018] vs 0.743 [0.018]) at month 10. In joint models with linear vs nonlinear PSA, prediction of 5-month risk of radiographic progression was improved when PSA trajectories were not assumed to be linear, with 8.0% relative gain in prediction (PE [SE], 0.150 [0.006] vs 0.138 [0.005]) and 19.4% relative gain in discrimination (AUC [SE], 0.653 [0.022] vs 0.780 [0.016]) at month 10. Predictions were affected by amount of marker information accumulated and prespecified assumptions. PSA changes affected progression risk more strongly at later vs earlier follow-up. Conclusions and Relevance: This prognostic study found that prediction of radiographic PFS was improved when longitudinal PSA information was added to baseline variables. In a population of patients with metastatic CRPC, dynamic predictions using landmark or joint models may help identify patients at risk of progression.

Repurposing Domperidone in Secondary Progressive Multiple Sclerosis: A Simon 2-Stage Phase 2 Futility Trial.

OBJECTIVE: To assess whether treatment with the generic drug domperidone can reduce the progression of disability in secondary progressive multiple sclerosis (SPMS), we conducted a phase 2 futility trial following the Simon 2-stage design. METHODS: We enrolled patients in an open-label, Simon 2-stage, single-center, phase 2, single-arm futility trial at the Calgary Multiple Sclerosis Clinic if they met the following criteria: age of 18 to 60 years, SPMS, screening Expanded Disability Status Scale score of 4.0 to 6.5, and screening timed 25-ft walk (T25FW) of ≥9 seconds. Patients received domperidone 10 mg 4 times daily for 1 year. The primary outcome was worsening of disability, defined as worsening of the T25FW performance by ≥20% at 12 months compared to baseline. This trial is registered with ClinicalTrials.gov (NCT02308137). RESULTS: Between February 13, 2015, and January 3, 2020, 110 patients were screened, 81 received treatment, and 64 completed follow-up, of whom 62 were analyzed. The study did not meet its primary endpoint: 22 of 62 (35%) patients experienced significant worsening of disability, which is close to the expected proportion of 40% and above the predefined futility threshold. Patients with higher prolactin levels during the study had a significantly lower risk of disability progression, which may warrant further investigation. Domperidone treatment was reasonably well tolerated, but adverse events occurred in 84% and serious adverse events in 15% of patients. CONCLUSIONS: Domperidone treatment could not reject futility in reducing disability progression in SPMS. The Simon 2-stage trial model may be a useful model for phase 2 studies in progressive MS. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02308137. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in individuals with SPMS participating in a futility trial, domperidone treatment could not reject futility in reducing disability progression at 12 months.

Trends in the choice of a clinician for orthodontic treatment in the United States.

INTRODUCTION: This study evaluated the trends in orthodontic practitioner choice over the past 15 years and explored the lay public's understanding of different orthodontic practitioner options in the U.S., specifically, orthodontists compared with general dentists. METHODS: A survey was distributed to a representative sample of laypersons in the U.S. The response rate was 90.2%, and 727 completed responses were analyzed. RESULTS: A 28.2% shift away from orthodontists toward general dentists over the last 15 years was significant (P <0.001). The 2 most frequently endorsed ways respondents found their orthodontic practitioners were a recommendation from another dentist (54.2%) and their family's general dentist who offered orthodontic treatment in-house (22.9%). Respondents' knowledge of orthodontists was limited; 85.0% believed that dentists who perform orthodontic treatment are also orthodontic specialists. Only 17.1% of respondents disagreed with the statement that "a dentist who advertises orthodontic treatment is an orthodontic specialist." In addition, 89.7% were not aware that a dentist could not be called an orthodontist without separate training from an accredited residency program. Finally, 64.2% of respondents did not know that an orthodontist must complete more education than a general dentist. CONCLUSIONS: Over the past 15 years, the percentage of orthodontic patients treated by general dentists has increased significantly. The public's ability to differentiate between different types of orthodontic practitioners is poor, showing substantial confusion about orthodontists' qualifications. Most respondents believed that orthodontists are best suited for their orthodontic treatment, but they rely heavily on their general dentists for orthodontic practitioner decisions.

Applying Clinical Decision Support Design Best Practices With the Practical Robust Implementation and Sustainability Model Versus Reliance on Commercially Available Clinical Decision Support Tools: Randomized Controlled Trial.

BACKGROUND: Limited consideration of clinical decision support (CDS) design best practices, such as a user-centered design, is often cited as a key barrier to CDS adoption and effectiveness. The application of CDS best practices is resource intensive; thus, institutions often rely on commercially available CDS tools that are created to meet the generalized needs of many institutions and are not user centered. Beyond resource availability, insufficient guidance on how to address key aspects of implementation, such as contextual factors, may also limit the application of CDS best practices. An implementation science (IS) framework could provide needed guidance and increase the reproducibility of CDS implementations. OBJECTIVE: This study aims to compare the effectiveness of an enhanced CDS tool informed by CDS best practices and an IS framework with a generic, commercially available CDS tool. METHODS: We conducted an explanatory sequential mixed methods study. An IS-enhanced and commercial CDS alert were compared in a cluster randomized trial across 28 primary care clinics. Both alerts aimed to improve beta-blocker prescribing for heart failure. The enhanced alert was informed by CDS best practices and the Practical, Robust, Implementation, and Sustainability Model (PRISM) IS framework, whereas the commercial alert followed vendor-supplied specifications. Following PRISM, the enhanced alert was informed by iterative, multilevel stakeholder input and the dynamic interactions of the internal and external environment. Outcomes aligned with PRISM's evaluation measures, including patient reach, clinician adoption, and changes in prescribing behavior. Clinicians exposed to each alert were interviewed to identify design features that might influence adoption. The interviews were analyzed using a thematic approach. RESULTS: Between March 15 and August 23, 2019, the enhanced alert fired for 61 patients (106 alerts, 87 clinicians) and the commercial alert fired for 26 patients (59 alerts, 31 clinicians). The adoption and effectiveness of the enhanced alert were significantly higher than those of the commercial alert (62% vs 29% alerts adopted, P<.001; 14% vs 0% changed prescribing, P=.006). Of the 21 clinicians interviewed, most stated that they preferred the enhanced alert. CONCLUSIONS: The results of this study suggest that applying CDS best practices with an IS framework to create CDS tools improves implementation success compared with a commercially available tool. TRIAL REGISTRATION: ClinicalTrials.gov NCT04028557; http://clinicaltrials.gov/ct2/show/NCT04028557.

Teledentistry Platforms for Orthodontics.

Technology has transformed almost every aspect of our lives. Smartphones enable patients to request, receive, and transmit information irrespective of the time and place. The global pandemic has forced healthcare providers to employ technology to aid in 'flattening the curve. The Novel Coronavirus, which is responsible for COVID-19, is transmitted primarily through person-to-person contact but may also be spread through aerosol generating procedures, so many clinics have severely limited interpersonal interactions. The purpose of this article is to provide helpful information for those orthodontists considering some form of remote practice. Various HIPAA-compliant telecommunication or teledentistry systems that can be used for orthodontic treatment are introduced and discussed. Detailed information about each platform that can potentially be used for orthodontics is provided in Figure 1. The authors do not endorse any of the products listed and the included software is not all inclusive but instead is a glimpse into the options available.

Implementation of teledentistry for orthodontic practices.

Recent advances in technology, growing patient demand, and the need for social distancing due to Coronavirus Disease 2019 has expedited adoption of teledentistry in orthodontics as a means of consulting and monitoring a patient without an in-office visit. However, a lack of computer literacy and knowledge of software choices, and concerns regarding patient safety and potential infringement of regulations can make venturing into this new technology intimidating. In this article, various types of teledentistry systems for orthodontic practices, implementation guidelines, and important regulatory considerations on the use of teledentistry for orthodontic purposes are discussed. A thorough evaluation of the intended use of the software should precede commitment to a service. Selected service should be Health Insurance Portability and Accountability Act compliant at minimum and a Business Associate Agreement should be in place for protection of privacy. Ensuring the compatibility of the designated clinic computer with the system's requirements and installation of all safeguards must follow. Appointments should be documented in the same manner as in-office visits and teledentistry patients must be located within the clinician's statutory license boundary. Informed consent forms should include teledentistry or a supplemental teledentistry consent form should be used. Malpractice insurance covers everything usual and customary under the provider's license but the need for cyber liability insurance increases with teledentistry.

Gloeostereum cimri, a novel shelf fungus isolated from a human pulmonary cyst.

Filamentous basidiomycetes are uncommon agents of human diseases, despite their ubiquitous presence in the environment. We present a case of symptomatic pulmonary infection in a 38-year-old male with cough and fever; a thin-walled cyst in the posterior left upper pulmonary lobe was revealed by radiography. A non-sporulating fungus was isolated from sputum and biopsy material from the cyst. ITS and LSU sequences placed the fungus phylogenetically in Agaricales, family Cyphellaceae, and identified it as a member of shelf fungi in Gloeostereum, but without identity to any known species. The new species is described as Gloeostereum cimri. The clinical strain showed high MIC to voriconazole (>8 µg/ml) but had low MIC to amphotericin B (0.5 µg/ml).

Tumor Membrane Vesicle Vaccine Augments the Efficacy of Anti-PD1 Antibody in Immune Checkpoint Inhibitor-Resistant Squamous Cell Carcinoma Models of Head and Neck Cancer.

Immune checkpoint inhibitor (ICI) immunotherapy improved the survival of head and neck squamous cell carcinoma (HNSCC) patients. However, more than 80% of the patients are still resistant to this therapy. To test whether the efficacy of ICI therapy can be improved by vaccine-induced immunity, we investigated the efficacy of a tumor membrane-based vaccine immunotherapy in murine models of HNSCC. The tumors, grown subcutaneously, are used to prepare tumor membrane vesicles (TMVs). TMVs are then incorporated with glycolipid-anchored immunostimulatory molecules GPI-B7-1 and GPI-IL-12 by protein transfer to generate the TMV vaccine. This TMV vaccine inhibited tumor growth and improved the survival of mice challenged with SCCVII tumor cells. The tumor-free mice survived for several months, remained tumor-free, and were protected following a secondary tumor cell challenge, suggesting that the TMV vaccine induced an anti-tumor immune memory response. However, no synergy with anti-PD1 mAb was observed in this model. In contrast, the TMV vaccine was effective in inhibiting MOC1 and MOC2 murine oral cancer models and synergized with anti-PD1 mAb in extending the survival of tumor-bearing mice. These observations suggest that tumor tissue based TMV vaccines can be harnessed to develop an effective personalized immunotherapy for HNSCC that can enhance the efficacy of immune checkpoint inhibitors.

Exploring Relational Dialogue in Solution-Focused Coaching Sessions: An Analysis of Co-Construction and Reflection.

Purpose: To examine solution-focused coaching (SFC) as a means to enhance clinicians' professional development. Methods: Six pediatric rehabilitation clinicians (three physical, two occupational, and one behavior therapist) each received two SFC sessions targeting clinical listening goals. Conversational intervals were noted in session transcriptions. Frequencies of relational strategies and conversational intervals were calculated. The meaning of intervals > 10 s was examined. Results: The most frequent relational strategies indicated that SFC facilitates reflection and critical thinking, and encourages action. An appreciable number of long intervals (>10 s) occurred, indicating substantial reflection by participants. These were embedded in relational dialogue sequences involving coach questions and formulations, and participant pauses. Conclusions: The findings support the use of SFC as a professional development tool and substantiate the view that SFC 'works' through the coach's use of relational strategies designed to facilitate collaborative conversations that build solutions through an emphasis on reflection and action.