Clinically-observed FOXA1 mutations upregulate SEMA3C through transcriptional derepression in prostate cancer.

FOXA1 is a pioneer transcription factor that is frequently mutated in prostate, breast, bladder, and salivary gland malignancies. Indeed, metastatic castration-resistant prostate cancer (mCRPC) commonly harbour FOXA1 mutations with a prevalence of 35%. However, despite the frequent recurrence of FOXA1 mutations in prostate cancer, the mechanisms by which FOXA1 variants drive its oncogenic effects are still unclear. Semaphorin 3C (SEMA3C) is a secreted autocrine growth factor that drives growth and treatment resistance of prostate and other cancers and is known to be regulated by both AR and FOXA1. In the present study, we characterize FOXA1 alterations with respect to its regulation of SEMA3C. Our findings reveal that FOXA1 alterations lead to elevated levels of SEMA3C both in prostate cancer specimens and in vitro. We further show that FOXA1 negatively regulates SEMA3C via intronic cis elements, and that mutations in FOXA1 forkhead domain attenuate its inhibitory function in reporter assays, presumably by disrupting DNA binding of FOXA1. Our findings underscore the key role of FOXA1 in prostate cancer progression and treatment resistance by regulating SEMA3C expression and suggest that SEMA3C may be a driver of growth and tumor vulnerability of mCRPC harboring FOXA1 alterations.

Establishing a Gold Standard for Noninvasive Identification of Painful Lumbar Discs: Prospective Comparison of Magnetic Resonance Spectroscopy vs Low-Pressure Provocation Discography.

PURPOSE: Verifying lumbar disc pain can present a clinical challenge. Low-pressure provocative discography (PD) has served as the gold standard, although it is invasive and often a challenge to interpret. We reported that magnetic resonance spectroscopy (MRS) biomarkers accurately predict PD results in lumbar discs and improved outcomes for patients with surgery at positive MRS levels versus nonsurgery. To further substantiate MRS for diagnosing painful discs, we report a prospective comparison of 2 MRS-derived measures: NOCISCORE (pain) and SI-SCORE (degeneration severity). METHODS: Lumbar MRS and software-based postprocessing (NOCISCAN-LS, Aclarion Inc.) was performed in 44 discs in 14 patients (prospective cohort [PC]). PC data were compared to prior data used to establish the NOCISCORE (training cohort [TC]). The NOCISCORE was converted to an ordinal value (high/intermediate/low; NOCI+/mild/-) and compared against painful (P) versus nonpainful (NP) control diagnosis (PD) for 19 discs where PD was performed in the PC (12 NP; 7 P). Sensitivity, specificity, and positive and negative predictive values were calculated. The SI-SCORE was compared against MRI Pfirrmann Grades for 465 discs in 126 patients (PC plus TC). RESULTS: For the PC, MRS (NOCI+/-) compared to PD (P/NP) with an accuracy of 87% and sensitivity and specificity of 100%. The positive and negative predictive values of MRS were 100%. NOCISCOREs were significantly higher for PD+ versus PD- discs for PC and TC (P < 0.05), and the NOCISCORE distributions for PD+/- group were not statistically different between the PC and TC (P > 0.05). SI-SCORES differed between Pfirrmann Grades 1 and 2 (less degenerated) versus Grades 3 and 4 (more degenerated; P < 0.05), with a progressively decreasing trend with Pfirrmann Grades 1-5. CONCLUSION: These current data provide prospective confirmation of the predictive value of disc MRS for distinguishing painful discs and for assessing the disc structural integrity. CLINICAL RELEVANCE: NOCISCAN is an adoptable, noninvasive, and objectively quantitative test to improve management of low back pain patients.

Semaphorin 3C promotes de novo steroidogenesis in prostate cancer cells.

Intratumoral androgen biosynthesis contributes to castration-resistant prostate cancer progression in patients treated with androgen deprivation therapy. The molecular mechanisms by which castration-resistant prostate cancer acquires the capacity for androgen biosynthesis to bypass androgen deprivation therapy are not entirely known. Here, we show that semaphorin 3C, a secreted signaling protein that is highly expressed in castration-resistant prostate cancer, can promote steroidogenesis by altering the expression profile of key steroidogenic enzymes. Semaphorin 3C not only upregulates enzymes required for androgen synthesis from dehydroepiandrosterone or de novo from cholesterol but also simultaneously downregulates enzymes involved in the androgen inactivation pathway. These changes in gene expression correlate with increased production of androgens induced by semaphorin 3C in prostate cancer model cells. Moreover, semaphorin 3C upregulates androgen synthesis in LNCaP cell-derived xenograft tumors, likely contributing to the enhanced in vivo tumor growth rate post castration. Furthermore, semaphorin 3C activates sterol regulatory element-binding protein, a transcription factor that upregulates enzymes involved in the synthesis of cholesterol, a sole precursor for de novo steroidogenesis. The ability of semaphorin 3C to promote intratumoral androgen synthesis may be a key mechanism contributing to the reactivation of the androgen receptor pathway in castration-resistant prostate cancer, conferring continued growth under androgen deprivation therapy. These findings identify semaphorin 3C as a potential therapeutic target for suppressing intratumoral steroidogenesis.

Dependency of Tamoxifen Sensitive and Resistant ER+ Breast Cancer Cells on Semaphorin 3C (SEMA3C) for Growth.

Estrogen receptor positive (ER+) breast cancer (BCa) accounts for the highest proportion of breast cancer-related deaths. While endocrine therapy is highly effective for this subpopulation, endocrine resistance remains a major challenge and the identification of novel targets is urgently needed. Previously, we have shown that Semaphorin 3C (SEMA3C) is an autocrine growth factor that drives the growth and treatment resistance of various cancers, but its role in breast cancer progression and endocrine resistance is poorly understood. Here, we report that SEMA3C plays a role in maintaining the growth of ER+ BCa cells and is a novel, tractable therapeutic target for the treatment of ER+ BCa patients. Analyses of publicly available clinical datasets indicate that ER+ BCa patients express significantly higher levels of SEMA3C mRNA than other subtypes. Furthermore, SEMA3C mRNA expression was positively correlated with ESR1 mRNA expression. ER+ BCa cell lines (MCF7 and T47D) expressed higher levels of SEMA3C mRNA and protein than a normal mammary epithelial MCF10A cell line. ER siRNA knockdown was suppressed, while dose-dependent beta-estradiol treatment induced SEMA3C expression in both MCF7 and T47D cells, suggesting that SEMA3C is an ER-regulated gene. The stimulation of ER+ BCa cells with recombinant SEMA3C activated MAPK and AKT signaling in a dose-dependent manner. Conversely, SEMA3C silencing inhibited Estrogen Receptor (ER) expression, MAPK and AKT signaling pathways while simultaneously inducing apoptosis, as monitored by flow cytometry and Western blot analyses. SEMA3C silencing significantly inhibited the growth of ER+ BCa cells, implicating a growth dependency of ER+ BCa cells on SEMA3C. Moreover, the analysis of tamoxifen resistant (TamR) cell models (TamC3 and TamR3) showed that SEMA3C levels remain high despite treatment with tamoxifen. Tamoxifen-resistant cells remained dependent on SEMA3C for growth and survival. Treatment with B1SP Fc fusion protein, a SEMA3C pathway inhibitor, attenuated SEMA3C-induced signaling and growth across a panel of tamoxifen sensitive and resistant ER+ breast cancer cells. Furthermore, SEMA3C silencing and B1SP treatment were associated with decreased EGFR signaling in TamR cells. Here, our study implicates SEMA3C in a functional role in ER+ breast cancer signaling and growth that suggests ER+ BCa patients may benefit from SEMA3C-targeted therapy.

Surveillance of the Initiation of, Participation in, and Completion of Cardiac Rehabilitation in Minnesota, 2017-2018.

INTRODUCTION: Cardiac rehabilitation (CR) is an evidence-based secondary prevention program designed to improve cardiovascular health after a cardiac event. The objective of our study was to identify gaps in CR use among publicly and privately insured people in Minnesota to assist in developing shared goals among public health, cardiac rehabilitation professionals, and program delivery sites to improve CR delivery. METHODS: We applied a published claims-based surveillance methodology to the Minnesota All Payer Claims Database to assess eligibility for, initiation of, participation in, and completion of CR by patients with qualifying events in 2017. We stratified results by sociodemographic and geographic factors and qualifying condition and used adjusted prevalence ratios to make statistical comparisons. RESULTS: Less than half (47.6%) of qualifying patients initiated CR within 1 year of their qualifying event; the rate was higher among men (vs women), adults aged 45 to 64 years (vs ≥65 y), and patients with commercial or Medicaid insurance coverage (vs Medicare). Among those who initiated CR, only 14.0% completed the full series of 36 sessions. Participation in at least 12 sessions and completion of 36 sessions was less likely among adults aged 18 to 64 (vs 65-74 y) and among patients covered by Medicaid (vs Medicare). Patterns of CR initiation, participation, and completion also varied geographically. CONCLUSION: This analysis expands on previous Medicare fee-for-service population CR surveillance and provides a first detailed look at the CR landscape in Minnesota, renewing attention to CR as a key secondary prevention strategy. Collaboration and sharing with partners has established the Minnesota Department of Health as a valuable partner in driving health system change to improve equitable provision of CR in Minnesota.

Magnetic resonance spectroscopy (MRS) identification of chemically painful lumbar discs leads to improved 6-, 12-, and 24-month outcomes for discogenic low back pain surgeries.

PURPOSE: MRS was shown to reliably quantify relative levels of degenerative pain biomarkers, differentiating painful versus non-painful discs in patients with chronic discogenic low back pain (DLBP), and this correlates with surgical success rates. We now report results based on more patients and longer follow-up. METHODS: Disc MRS was performed in DLBP patients who subsequently received lumbar surgery. Custom post-processing (NOCISCAN-LS®; Aclarion Inc.) calculated disc-specific NOCISCORES® that reflect relative differences in degenerative pain biomarkers for diagnosing chemically painful discs. Outcomes in 78 patients were evaluated using Oswestry Disability Index (ODI) scores. Surgical success (≥ 15-point ODI improvement) was compared between surgeries that were "Concordant" (Group C) versus "Discordant" (Group D) with NOCISCORE-based diagnosis for painful discs. RESULTS: Success rates were higher for Group C versus Group D: 6 months (88% vs. 62%; p = 0.01), 12 months (91% vs. 56%; p < 0.001), and 24 months (85% vs. 63%; p = 0.07). Success rates for Group C surgeries were also higher than Group D surgeries in a variety of sub-group comparisons. Group C had a greater reduction in ODI from pre-operative to follow-up than Group D [absolute change (% change), (p)]: 6 months: - 35 (- 61%) versus - 23 (- 39%), (p < 0.05); 12 months: - 39 (- 69%) versus - 22 (- 39%), (p < 0.01); and 24 months: - 38 (- 66%) versus - 26 (- 48%), (p < 0.05). CONCLUSION: More successful, sustained outcomes were obtained when surgically treating chemically painful discs identified by NOCISCAN-LS post-processed disc MRS exams. Results suggest that NOCISCAN-LS provides a valuable new diagnostic tool to help clinicians better select treatment levels.

Anhedonic Depression Is Not Associated With Risk of Recurrent Major Adverse Cardiac Events and All-Cause Mortality in Acute Coronary Syndrome Patients.

BACKGROUND: Depression after acute coronary syndrome (ACS) is common and increases risks of adverse outcomes, but it remains unclear which depression features are most associated with major adverse cardiac events (MACE) and all-cause mortality (ACM). PURPOSE: To examine whether a subtype of depression characterized by anhedonia and major depressive disorder (MDD) predicts 1-year MACE/ACM occurrence in ACS patients compared to no MDD history. We also consider other depression features in the literature as predictors. METHODS: Patients (N = 1,087) presenting to a hospital with ACS completed a self-report measure of current depressive symptoms in-hospital and a diagnostic interview assessing MDD within 1 week post-hospitalization. MACE/ACM events were assessed at 1-, 6-, and 12-month follow-ups. Cox regression models were used to examine the association of the anhedonic depression subtype and MDD without anhedonia with time to MACE/ACM, adjusting for sociodemographic and clinical covariates. RESULTS: There were 142 MACE/ACM events over the 12-month follow-up. The 1-year MACE/ACM in patients with anhedonic depression, compared to those with no MDD, was somewhat higher in an age-adjusted model (hazard ratio [HR] = 1.63, p = .08), but was not significant after further covariate adjustment (HR = 1.24, p = .47). Of the additional depression features, moderate-to-severe self-reported depressive symptoms significantly predicted the risk of MACE/ACM, even in covariate-adjusted models (HR = 1.72, p = .04), but the continuous measure of self-reported depressive symptoms did not. CONCLUSION: The anhedonic depression subtype did not uniquely predict MACE/ACM as hypothesized. Moderate-to-severe levels of total self-reported depressive symptoms, however, may be associated with increased MACE/ACM risk, even after accounting for potential sociodemographic and clinical confounders.

Understanding the effects of ball orientation in Rugby Union place kicking: the preferences of international kickers and the kinematics of the foot-ball impact.

Rugby Union place kicking is influential to match outcome. Previous research has analysed kicker motion prior to ball contact in detail, but ball orientation and the impact phase are typically ignored. This study aims to firstly identify the ball orientations used by international place kickers, and secondly to experimentally analyse the foot-ball interaction in trained kickers using different ball orientations. Overall, 25.5% of the international kickers used an upright ball orientation, 27.5% used a diagonal orientation and 47.1% used a horizontal orientation. However, ball orientation preference was not significant in predicting kick outcome in a binomial logistic regression model. To address the second aim, ball orientation was experimentally manipulated and lower limb and ball kinematics were captured using high-speed (4000 Hz) video. Whilst the impact location on the ball differed significantly between most ball orientation conditions, the impact location relative to the global vertical was largely consistent across all conditions. This was likely due to kickers adopting very consistent lower limb kinematics, although the shank and ankle angles at impact were affected by ball orientation conditions for some kickers. Impact durations also differed between some conditions, although this did not appear to affect the impact efficiency.

An Unusual Etiology of Lemierre-Like Syndrome: Preseptal Cellulitis due to Methicillin-Resistant Staphylococcus aureus.

Lemierre's syndrome (LS) is a rare and potentially fatal condition that predominantly affects young adults with oropharyngeal infection. Fusobacterium necrophorum is the usual etiology and classically causes internal jugular vein septic thrombophlebitis, frequently complicated by septic emboli to several organs (most classically to the lungs). Lemierre-like syndrome (LLS) describes the same constellation of symptoms and pathophysiology as Lemierre's syndrome; however, Fusobacterium spp. are not the cause, and the source of infection may be nonoropharyngeal. We present a case with an unusual etiology of LLS: a patient with untreated preseptal cellulitis and associated methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in the setting of injection drug use. Physical exam revealed tachypnea and rhonchi with severe periorbital and bilateral eyelid edema. Imaging demonstrated bilateral preseptal and orbital cellulitis with thrombosis of both internal jugular veins and bilateral pulmonary cavitary lesions consistent with septic pulmonary emboli. She was managed with anticoagulation and parenteral antibiotics. To our knowledge, this is the first case of LLS originating from preseptal cellulitis without evidence of preceding pharyngitis. While facial and orbital infections are rare etiologies of LLS, the potentially devastating sequelae of LLS warrant its inclusion in differential diagnoses.

International Classification of Diseases (ICD) Codes Fail to Accurately Identify Injection Drug Use Associated Endocarditis Cases.

OBJECTIVES: Infective endocarditis (IE) secondary to injection drug use (IDU-IE) is a disease with high morbidity, cost, and rapid demographic evolution. Studies frequently utilize combinations of International Statistical Classification of Diseases (ICD) codes to identify IDU-IE cases in electronic medical records. This is a validation of this identification strategy in a US cohort. METHODS: Records from January 1, 2004 to September 31, 2015 for those aged ≥18yo with any ICD-coded IE encounter (inpatient or outpatient) were retrieved from the electronic medical record and then manually reviewed and classified as IDU-IE by strict and inclusive criteria. This registry was then used to assess the diagnostic accuracy of 10 identification algorithms that combined substance use, hepatitis C, and IE ICD codes. RESULTS: IE was present in 629 of the 2055 manually reviewed records; 109 reported IDU within 3 months of IE diagnosis and an additional 32 during their lifetime (141 cases). In contrast, no algorithm identified more than 46 (33%) of these cases. Algorithms assessing encounters with both an IE and substance use code had specificities >99% but sensitivities ≤11% with negative predictive values of 83% to 84% and positive predictive values ranging from 75% to 91%. Use of a hepatitis C OR substance use code with an IE-coded encounter resulted in higher sensitivities of 22% to 32% but more false positives and overall positive predictive value of <70%. This algorithm limited to age ≤45yo had the best, but still low, discrimination ability with an area under the receiver operating characteristic curve of 0.62. CONCLUSION: Substance use and hepatitis C codes have poor ability to accurately classify an IE-coded encounter as IDU-IE or routine IE.

Survey of Adherence with COVID-19 Prevention Behaviors During the 2020 Thanksgiving and Winter Holidays Among Members of the COVID-19 Community Research Partnership.

Prevention behaviors represent important public health tools to limit spread of SARS-CoV-2. Adherence with recommended public health prevention behaviors among 20000 + members of a COVID-19 syndromic surveillance cohort from the mid-Atlantic and southeastern United States was assessed via electronic survey following the 2020 Thanksgiving and winter holiday (WH) seasons. Respondents were predominantly non-Hispanic Whites (90%), female (60%), and ≥ 50 years old (59%). Non-household members (NHM) were present at 47.1% of Thanksgiving gatherings and 69.3% of WH gatherings. Women were more likely than men to gather with NHM (p < 0.0001). Attending gatherings with NHM decreased with older age (Thanksgiving: 60.0% of participants aged < 30 years to 36.3% aged ≥ 70 years [p-trend < 0.0001]; WH: 81.6% of those < 30 years to 61.0% of those ≥ 70 years [p-trend < 0.0001]). Non-Hispanic Whites were more likely to gather with NHM than were Hispanics or non-Hispanic Blacks (p < 0.0001). Mask wearing, reported by 37.3% at Thanksgiving and 41.9% during the WH, was more common among older participants, non-Hispanic Blacks, and Hispanics when gatherings included NHM. In this survey, most people did not fully adhere to recommended public health safety behaviors when attending holiday gatherings. It remains unknown to what extent failure to observe these recommendations may have contributed to the COVID-19 surges observed following Thanksgiving and the winter holidays in the United States.

Secondary review reduced inpatient MRI orders and avoidable hospital days.

INTRODUCTION: Medical centers have dramatically increased the use of magnetic resonance imaging (MRI). At 2 large academic tertiary care centers in New York City, nearly half of inpatient MRI orders took more than 12 h to complete, delaying patient discharge and increasing avoidable hospital days. We posited that transitioning inpatient MRIs to outpatient facilities, when safe and appropriate, could reduce inpatient MRI orders and avoidable hospital days. METHODS: We manually reviewed 59 inpatient MRI orders delayed on the estimated date of discharge (EDD). These orders were often delayed due to no standard process to escalate orders for medical reasons or no system to coordinate outpatient orders. We developed a revised workflow involving an automation platform that flagged inpatient MRI orders requested within 24 h of the EDD and emailed the care team to request a second review of the order. The care team reconsidered whether the order was (1) required for discharge, (2) non-urgent and could be converted to an outpatient order, or (3) unnecessary and could be canceled. RESULTS: Over 9 months, the automation platform flagged 618 inpatient MRI orders, of which 53.9% (333/618) were reviewed by the care team. Among the orders, 24.0% (80/333) of reviewed orders and 12.9% (80/618) of all orders were transitioned to either outpatient or canceled orders. These transitioned orders were associated with 267 fewer avoidable hospital days and a cost savings of $199,194. CONCLUSION: A standardized process and second review of inpatient MRI orders on the EDD can reduce inappropriate orders and more effectively use inpatient imaging resources. PRECIS: A standardized workflow and automation platform encouraged a second review of inpatient MRI orders to reduce inappropriate orders, avoidable hospital days, and hospital costs.

Changing Attitudes toward the COVID-19 Vaccine among North Carolina Participants in the COVID-19 Community Research Partnership.

Coronavirus Disease-2019 (COVID-19) vaccine acceptance is variable. We surveyed participants in the COVID-19 Community Research Partnership from 17 December 2020 to 13 January 2021 to assess vaccine receptiveness. Vaccine uptake was then monitored until 15 May 2021; 20,232 participants responded to the receptiveness survey with vaccination status accessed in 18,874 participants via daily follow-up surveys (participants not completing daily surveys ≥30 days to 15 May 2021, were excluded). In the initial survey, 4802 (23.8%) were vaccine hesitant. Hesitancy was most apparent in women (Adjusted RR 0.93, p < 0.001), Black Americans (Adjusted RR 1.39, 1.41, 1.31 to non-Hispanic Whites, Other, and Hispanic or Latino, respectively p < 0.001), healthcare workers (Adjusted RR 0.93, p < 0.001), suburbanites (ref. Urban Adjusted RR 0.85, 0.90 to urban and rural dwellers, respectively, p < 0.01), and those previously diagnosed with COVID-19 (RR 1.20, p < 0.01). Those <50 years were also less accepting of vaccination. Subsequent vaccine uptake was 99% in non-hesitant participants. For those who were unsure, preferred not to answer, or answered "no", vaccination rates were 80% (Adjusted RR 0.86, p < 0.0001), 78% (Adjusted RR 0.83, p < 0.0001), and 52.7% (Adjusted RR 0.65, p < 0.0001), respectively. These findings suggest that initial intent did not correlate with vaccine uptake in our cohort.

Impact of Chronic Hepatitis C virus co-infection on outcomes of infective endocarditis in people who inject drugs.

Injection drug use (IDU) is a risk factor for infective endocarditis (IE) and hepatitis C virus (HCV) infection. This retrospective cohort study assessed HCV's impact on outcomes of adult people who inject drugs (PWID). Those admitted due to IE using modified Duke criteria from January 2012 through May 2018 were identified. The cohort was divided into HCV seropositive and seronegative groups. The seropositive group was further stratified according to HCV viremia. Complications and mortality during the IE hospitalization, at 10 weeks, and 1 year were compared across groups. Clinical factors were similar between the cohorts, except patients without viremia (29, 81%) required more ICU admissions than with viremia (30, 60%) (P < 0.05). There was no difference in mortality at all time periods between the groups. Although several factors affect mortality in PWID with IE, neither HCV antibody positivity nor viremia appear to increase the risk for complications or death.

Vitreous and Chorioretinal Lesions in People Who Inject Drugs and Are Hospitalized with Bloodstream and Related Infections.

PURPOSE: To determine the prevalence of and to characterize vitreous and chorioretinal lesions, to identify causative organisms, and to correlate symptoms with ophthalmic involvement in people who inject drugs and are hospitalized with bloodstream infection (BSI), related metastatic foci of infection (MFI), or both. DESIGN: An academic hospital-based cross-sectional study. PARTICIPANTS: Patients admitted with BSI or MFI related to injection drug use (IDU). METHODS: Patients underwent a complete eye examination within 72 hours of enrollment. Characteristics including gender; age; race; injection drug of choice (DOC); presence of coinfection with hepatitis B, hepatitis C, or human immunodeficiency virus; pathogen causing systemic infection and type of infection; and history of prior infection related to IDU were recorded. MAIN OUTCOME MEASURES: Presence of vitreous or chorioretinal findings, or both. RESULTS: Ninety-one unique patients with 96 separate hospitalizations for systemic infection were enrolled from March 28, 2018, through March 30, 2020. Vitreous or chorioretinal involvement was identified in 16 of 96 patients (16.7%). The most common ocular findings were intraretinal or white-centered hemorrhage in 9 of 96 patients, chorioretinal infiltrate in 8 of 96 patients, endophthalmitis in 5 of 96 patients, and cotton wool spots in 3 of 96 patients. Of the patients with ocular involvement, only 7 of 16 patients (44%) were symptomatic, and 5 of these were patients with endophthalmitis; the others showed chorioretinal infiltrates or intraretinal or white-centered hemorrhage and cotton wool spots. Staphylococcus aureus was the most common causative pathogen in patients with and without ocular findings. Presence of ocular symptoms, worse visual acuity, and injection DOC of methamphetamine were correlated with the presence of ocular findings. CONCLUSIONS: Patients without ocular symptoms with systemic infections related to IDU may have chorioretinal findings. Further study is needed to characterize better the epidemiologic features of these infections and to identify risk factors for ocular involvement in people who inject drugs.

Prostatic abscess: clinical features, management, and outcomes of a "Stealth" infection: retrospective case series and review of the literature.

Prostatic abscess (PA) is uncommon and may be difficult to distinguish from acute prostatitis which often leads to delayed or missed diagnoses. Although gram-negative bacilli are the traditional etiology of PA, Staphylococcus aureus is an emerging cause. The goals of this study were to characterize the current clinical features, microbiology, management, and outcomes of PA at a US academic center. A retrospective review of adult patients hospitalized with an ICD-9/10 diagnosis of PA between January 2013 and July 2018 was conducted. Inclusion criteria included age ≥18 years, a compatible genitourinary (GU) infection syndrome, and imaging consistent with PA. Relevant data were extracted and analyzed by univariate analysis as appropriate. Twenty-two patients with PA were identified with median age 57 years. Five patients (23%) were immunosuppressed and 11 (50%) had diabetes. No patient had prior PA but 3 had past prostatitis. Only 1 patient had recent GU instrumentation and none had indwelling urinary catheters. The most common presenting symptoms were fever (59%), dysuria (45%), and urinary retention (32%). Only 7 out of 18 (39%) patients had prostate tenderness on exam and none had fluctuance. As demonstrated by computed tomography, PAs were multifocal in 8 (36%) patients and 16 (73%) had PAs >2 cm in diameter. The median abscess size was 3.2 cm. S. aureus was isolated in 60% of positive urine cultures and 78% of positive blood cultures; 46% were methicillin-resistant. Nine patients (41%) received antibiotics alone whereas 13 (59%) required antibiotics plus drainage. The median duration of antimicrobial therapy was 34.5 days. Four week mortality was 9%. When comparing S. aureus PA to other causes, S. aureus patients tended to have higher fevers, more often had diabetes, and received longer durations of antibiotic therapy (median 35 days vs 31 days, P = 0.04) but age, abscess size, and mortality did not differ. PA is relatively uncommon and often clinically unsuspected. Imaging may be critical to accurate diagnosis. Optimal management usually requires antibiotics and sometimes drainage depending on abscess size. We found a significant proportion of cases due to S. aureus which might be relevant when deciding empiric antimicrobial therapy.

Infective Endocarditis Guidelines: The Challenges of Adherence-A Survey of Infectious Diseases Clinicians.

BACKGROUND: Guidelines exist to aid clinicians in managing patients with infective endocarditis (IE), but the degree of adherence with guidelines by Infectious Disease (ID) physicians is largely unknown. METHODS: An electronic survey assessing adherence with selected IE guidelines was emailed to 1409 adult ID physician members of the Infectious Diseases Society of America's Emerging Infections Network. RESULTS: Five hundred fifty-seven physicians who managed IE responded. Twenty percent indicated that ID was not consulted on every case of IE at their hospitals, and 13% did not recommend transthoracic echocardiography (TTE) for all IE cases. The duration of antimicrobial therapy was timed from the first day of negative blood cultures by 91% of respondents. Thirty-four percent of clinicians did not utilize an aminoglycoside for staphylococcal prosthetic valve IE (PVE). Double ß-lactam therapy was "usually" or "almost always" employed by 83% of respondents for enterococcal IE. For patients with active IE who underwent valve replacement and manifested positive surgical cultures, 6 weeks of postoperative antibiotics was recommended by 86% of clinicians. CONCLUSIONS: The finding that adherence was <90% with core guideline recommendations that all patients with suspected IE be seen by ID and that all patients undergo TTE is noteworthy. Aminoglycoside therapy of IE appears to be declining, with double ß-lactam regimens emerging as the preferred treatment for enterococcal IE. The duration of postoperative antimicrobial therapy for patients undergoing valve replacement during acute IE is poorly defined and represents an area for which additional evidence is needed.

Transcranial Doppler Emboli Monitoring for Infective Endocarditis.

BACKGROUND AND PURPOSE: Ischemic stroke can occur in 20-55% of patients with infective endocarditis (IE) with 75% occurring during the first 2 weeks of treatment. CT or MRI brain can diagnose the sequelae of stroke but transcranial Doppler (TCD) can document active embolization. We undertook a retrospective review of our patient cohort and a systematic review of literature to assess the role of TCD in early diagnosis and management of ischemic stroke in IE. METHODS: Retrospective chart review and literature review. RESULTS: We found 89 patients with stroke caused by IE at our institution from December 2011 to April 2018. TCDs were obtained on 26 patients; 16 were abnormal for cerebrovascular abnormalities. Only 4 patients had 30-minute emboli monitoring performed, of which one revealed emboli. We found 3 studies investigating the role of TCDs in IE that showed promise in its use as a predictive tool in stroke risk stratification. CONCLUSIONS: Presence of embolization in the form of high-intensity transient signals (HITS) detected on TCDs can be used for early diagnosis of IE, assessing efficacy of antibiotic therapy, and stratification of stroke risk in IE. This can aid further research into testing preventative interventions for reducing stroke burden in IE such as earlier valvular surgery or vacuum-assisted vegetation extraction.

Ehrlichiosis in a recent kidney transplant recipient: The repellent that did not repel! A case report and literature review of ehrlichiosis in solid organ transplant patients.

Ehrlichiosis has been infrequently reported in immunosuppressed patients such as solid organ transplants (SOT). We report a case of Ehrlichia chaffeensis infection in an immunosuppressed woman four months after deceased donor kidney transplantation. The diagnosis was confirmed by PCR testing in serum, and the patient responded promptly to treatment with doxycycline. To supplement our Case Report, a literature review encompassing 1995 to present was also performed using PubMed as the search vehicle. Search terms that were utilized include: ehrlichiosis, HME, E chaffeensis, kidney transplant(ation), renal transplant(ation), solid organ transplant(ation), and immunosuppression. The diagnosis of ehrlichiosis can be challenging in SOT patients since ehrlichiosis is not a classic opportunistic infection in SOT. Transplant physicians must have a high clinical suspicion for the diagnosis in patients with an acute febrile illness accompanied by headache, worsening cytopenias, and transaminitis who live in endemic areas, especially if they have tick exposure.