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Background: Telemedicine (TM) has been widely advocated and used to follow up patients with rheumatic diseases during the COVID-19 outbreak. However, there is no evidence supporting its use in systemic lupus erythematosus. We aimed to evaluate the short-term patient satisfaction, compliance, disease control and infection risk of TM compared with standard in-person follow-up (FU) for patients with lupus nephritis (LN) during the pandemic. Methods: This was a single-center open-label randomized controlled study. Consecutive patients followed at the LN clinic were randomized to either TM or standard FU (SF) group in a 1:1 ratio. Patients in the TM group received FU via videoconferencing. SF group patients continued conventional in-person outpatient care. The 6-month data were compared and presented. Results: From June to December 2020, 122 patients were randomized (TM: 60, SF: 62) and had at least 2 FUs. There were no baseline differences, including SLEDAI-2k and proportion of patients in lupus low disease activity state (LLDAS), between the 2 groups except a higher physician global assessment score (PGA) in the TM group (table). After a mean FU of 19.8 ± 4.5 weeks, the overall patient satisfaction score was higher in the TM group with a significantly shorter waiting time from entering the clinic waiting room (virtual or real) to seeing a rheumatologist (figure). More patients in the TM group had hospitalization (15/60, 25.0% vs 7/62, 11.3%;p=0.049) with higher baseline PGA (OR = 1.15, 95% CI 1.07-1.23) being the independent predictor. The proportions of patients remained in LLDAS were similar in the 2 groups (TM: 75.0% vs SF: 74.2%, p = 0.919). None of the patients had COVID-19. Conclusion: TM FU resulted in better patient satisfaction and similar short-term disease control in patients with LN compared to standard care. However, it was associated with more hospitalizations and might need to be complemented by in-person visits especially in patients with higher PGA. (Table Presented).

Among existing research on social vulnerability, virtually no studies have considered homelessness as a variable in their vulnerability assessments. This study identified the relevance of homelessness as a key index in social vulnerability assessment to inform the public, policymakers and the broader body of literature of its impacts on shaping vulnerability patterns in cities. In this study, the 2018 Homeless data for Austin was disaggregated from the council district level to block group level using dasymetric mapping in Geographic Information System (GIS). Principal Component Analysis (PCA) was used to group highly correlated demographic and socioeconomic variables into factors, which were normalized and summed to model social vulnerability with homeless index (SOVI_H) and without homeless index (SOVI) for each Austin Blockgroup. The result revealed significant differences in geographic patterns between SOVI_H and SOVI. SOVI_H showed hotspots of vulnerabilities in Downtown and East-Austin neighborhoods, depicting a slight shift of social vulnerability westwards of the city. This finding differs from past results of social vulnerabilities in Austin where it used to be predominant in the East. This study showed that incorporating homelessness in identifying social vulnerability can help researchers and other associated organizations identify the most vulnerable groups when conducting social vulnerability assessments.

Soft tissue sarcomas are a heterogenous group of neoplasms without well-validated biomarkers. Cancer-related inflammation is a known driver of tumor growth and progression. Recent studies have implicated a high circulating neutrophil-lymphocyte ratio as a surrogate marker for the inflammatory tumor microenvironment and a poor prognosticator in multiple solid tumors, including colorectal and pancreatic cancers. The impact of circulating neutrophil-lymphocyte ratio in soft tissue sarcomas has yet to be elucidated.We performed a retrospective analysis of patients undergoing curative resection for primary or recurrent extremity soft tissue sarcomas at academic centers within the US Sarcoma Collaborative. Neutrophil-lymphocyte ratio was calculated retrospectively in treatment-naïve patients using blood counts at or near diagnosis.A high neutrophil-lymphocyte ratio (≥4.5) was associated with worse survival on univariable analysis in patients with extremity soft tissue sarcomas (hazard ratio 2.07; 95% confidence interval, 1.54-2.8; P.001). On multivariable analysis, increasing age (hazard ratio 1.03; 95% confidence interval, 1.02-1.04; P.001), American Joint Committee on Cancer T3 (hazard ratio 1.89; 95% confidence interval, 1.16-3.09; P = .011), American Joint Committee on Cancer T4 (hazard ratio 2.36; 95% confidence interval, 1.42-3.92; P = .001), high tumor grade (hazard ratio 4.56; 95% confidence interval, 2.2-9.45; P.001), and radiotherapy (hazard ratio 0.58; 95% confidence interval, 0.41-0.82; P = .002) were independently predictive of overall survival, but a high neutrophil-lymphocyte ratio was not predictive of survival (hazard ratio 1.26; 95% confidence interval, 0.87-1.82; P = .22).Tumor inflammation as measured by high pretreatment neutrophil-lymphocyte ratio was not independently associated with overall survival in patients undergoing resection for extremity soft tissue sarcomas.

Purpose: To report the patterns of use of hypofractionated radiotherapy (HFRT) (≤16 fractions)in breast cancer and ductal carcinoma in situ (DCIS) patients in Ontario, Canada from 2009 to 2015 and identify factors related to HFRT use. Methods: A retrospective cohort study of Ontario women diagnosed with breast cancer or DCIS followed by adjuvant breast or chest wall radiation (RT) from 2009 to 2015 was conducted using data from the Institute for Clinical Evaluative Sciences (ICES). Logistic regression models were used to identify factors associated with HFRT use. Physician was included as a random effect. To calculate the potential amount of time that could be saved if all patients were to receive 16 fractions of HFRT, the number of extra RT treatments after the 16th visit was multiplied by the median amount of time spent to treat one patient at our cancer centre (8.76 minutes). This time was found with Sunnybrook Health Sciences Centre data collected from October 2017 to March 2018 (n=523) and represents the amount of time from when a patient enters the RT unit for treatment setup, until the RT beam is turned off. Results: A total of 42,072 patients were included. Most patients were aged between 50 and 69 years old (56.7%) with stage I or II breast cancer (74.6%) and had breast conserving surgery (BCS) (76.9%). Half previously received chemotherapy and 7.9% were DCIS patients. Use of sequential boost, simultaneous boost, and regional nodal RT was 17.2%, 3.1%, and 31.7% respectively. Institutional variation in HFRT use ranged from 27.5% to 71.6%. HFRT use has increased in all patient populations over the study period. HFRT use was more common in breast cancer and DCIS patients with BCS than in chest wall and nodal RT. Simultaneous boost (OR=0.09), nodal RT (OR=0.08), previous chemotherapy (OR=0.7), stage 0, II, and III breast cancer (OR=0.06 relative to stage I), were correlated with less HFRT use. Older age, later year of diagnosis, sequential boost (OR=0.09), BCS and no surgery (OR=1.2, 1.5 relative to mastectomy) were correlated with higher HFRT use. Institution was significantly correlated to HFRT use. The variance estimate for the physician random effect was 0.33 (p Trends in the use of HFRT (%) from 2009 to 2015 for DCIS and breast cancer patients in Ontario.YearStage I-IV + BCS + Breast RTStage I-IV + BCS + Breast + Nodal RTStage I-IV + Mastectomy + Breast RTStage I-IV + Mastectomy + Breast + Nodal RTDCIS + BCS200962.610.329.09.545.2201062.06.323.76.951.2201162.24.121.34.752.7201263.79.621.711.452.0201365.112.629.315.057.3201469.37.835.415.164.5201573.711.839.217.573.4BCS: breast conserving surgery, RT: radiation treatment Conclusions: HFRT use in Ontario has increased over time for all patient populations, and reflects the current evidence supporting HFRT in different patient populations, with lower HFRT use seen in chest wall and nodal RT and higher HFRT use in early-stage breast cancer patients with BCS. Citation Format: Chow E, Chan S, Yao Z, Sutradhar R, Lee J, Wan BA, Paszat L. Fractionation patterns in adjuvant breast radiotherapy in Ontario, Canada from 2009 to 2015 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-05.

Background Current international guidelines on HIV Pre-Exposure Prophylaxis (PrEP) recommend serological screening for syphilis at routine three-monthly PrEP appointments. The aim of our study was to describe the pattern of clinical presentation of syphilis among men who have sex with men (MSM) taking PrEP. We were interested in whether syphilis is detected through screening at scheduled three-monthly PrEP clinic appointments or whether primary or secondary syphilis presented at unscheduled interval visits. Methods This was a retrospective study of MSM attending the PrEP clinic at the Melbourne Sexual Health Centre between February 2016 and March 2019. Serological screening for syphilis was routinely undertaken at three-monthly PrEP clinic appointments. Diagnoses of early syphilis were identified from PrEP clinic visits and from interim walk-in STI clinic attendances. Results There were 69 cases of early syphilis among 61 MSM taking PrEP during the study period. There were 24 (35%) primary, 16 (23%) secondary and 29 (42%) early latent infections. The incidence of early syphilis was 8.6 per 100 person-years. A substantial proportion of primary (58%) and secondary (44%) syphilis diagnoses were made at interim STI clinic attendances, between PrEP appointments. Conclusions Syphilis screening at routine three-monthly PrEP visits alone fails to detect a proportion of primary and secondary syphilis infections and may be insufficient in preventing onward transmission. Education of MSM taking PrEP regarding the risk of syphilis and symptom recognition is necessary together with access to syphilis testing between PrEP visits.

Background The study aims to examine the trends of syphilis infection in Victoria and the characteristics of notified cases of syphilis among different population groups stratified by risk and in different geographical distributions. Methods We analysed the demographic characteristics, notification trends and geographical distribution of notified cases of syphilis in Victoria between 2015 and 2018. Infectious syphilis cases were categorised into four population groups: men who have sex with men (MSM), men who have sex with women (heterosexual males), females, and men who have sex with men and women (bisexual males). We examined the staging of syphilis, geographic location by residence of cases, HIV status, reasons for testing, and notifying source. Results Of the 4,808 notified infectious syphilis cases, there were 3,801 (64%) MSM, 593 (12%) heterosexual males, 465 (10%) females, and 118 (2%) bisexual males. Females (219% increase, ptrend Conclusion Notified cases of syphilis infection had significantly increased across all population groups but particularly in heterosexual males and females. Campaigns and control measures should be specific for each population group with targeted screening and education in areas with a high number of syphilis cases.

The World Health Organization declared the coronavirus disease 2019 (COVID-19) as a pandemic on 11 March 2020. Since then, many countries have introduced national responses to the COVID-19 pandemic and these include the closure of international borders, stay at home orders, restrictions of movement, curfews, physical distancing and wearing face masks. This talk will discuss how these restrictions have impacted sexual practices among individuals, access to healthcare seeking as well as the diagnoses of sexually transmitted infections globally.

Background Rectal chlamydia is the most commonly diagnosed bacterial sexually transmissible infection among men who have sex with men (MSM) and there is increasing concern about rectal chlamydia in women. The absence of randomised controlled trial (RCT) evidence means there is ongoing debate about the most efficacious treatment. Methods We conducted a double-blind double-dummy RCT to compare the efficacy of azithromycin 1g singledose with 7-days doxycycline 100mg twice daily for the treatment of asymptomatic rectal chlamydia. MSM diagnosed with asymptomatic rectal chlamydia infection at five sexual health clinics in Australia were randomly assigned to receive either doxycycline or azithromycin. Primary outcome was rectal chlamydia microbiological cure defined as a negative nucleic acid amplification test at four weeks. Logistic regression was used to calculate the difference in microbial cure within a modified intention to treat population that excluded L2 serovar diagnoses post-recruitment. Results We enrolled 625 men and randomly assigned 314 to doxycycline and 311 to azithromycin between August 2016 and August 2019. Primary outcome data were available for 290 (92%) assigned to doxycycline and 297 (96%) assigned to azithromycin. In the modified intention to treat population, the observed microbiological cure was 281/290 (96.9%; 95%CI: 94.9, 98.9) for doxycycline and 227/297 (76.4%; 95%CI: 73.8, 79.1) for azithromycin, with an adjusted risk difference of 19.9% (95% CI: 14.6, 25.3; p Conclusions The efficacy of doxycycline was found to be substantially superior to azithromycin in the treatment of asymptomatic rectal chlamydia infection among MSM. Doxycycline must replace azithromycin as firstline treatment for symptomatic rectal chlamydia.

Background The association between meeting partners online and sexual practices has been under-studied in heterosexuals. This study aimed to examine the associations between the methods of meeting partners with sexual practices, as well as sexually transmitted infections (STIs) and human immunodeficiency virus (HIV), in heterosexuals. Methods We conducted a survey among heterosexuals attending the Melbourne Sexual Health Centre between March and April 2019. This survey asked about the methods through which participants had met their sexual partner(s), sexual practices and intravenous drug use (IVDU) over the past 3 months. Participants’ HIV/STI (chlamydia, gonorrhoea, syphilis) status was obtained from clinical testing. A multivariable logistic regression was used to examine the association between each method of meeting partners and the participants’ sexual practices, IVDU, and STI status. Results A total of 698 participants (325 males, 373 females) were included in the study. The majority of participants reported using only one method to meet partners (68.3% males, 65.7% females, p=0.0462). Males most commonly met partners at social-venues (e.g. bar, pub, party) (38.8%, n=126), whilst females most commonly met through friends/family (47.7%, n=178). Paying for sex was associated with males meeting partners at sex-venues (AOR=145.34, 95%CI: 26.13–808.51) and the internet (AOR=10.00, 95%CI: 3.61–27.55). There was no association between IVDU and methods of meeting. Social-venues were associated with condomless vaginal sex in males (AOR=3.31, 95%CI: 1.94–5.71) and females (AOR=2.58, 95%CI: 1.61–4.13) and testing STI positive in males (AOR=3.04, 95%CI: 1.24–7.48) and females (AOR=3.75, 95%CI: 1.58–8.89). Conclusion Heterosexuals that met sexual partners at social-venues had a more than threefold risk of testing positive for STIs, indicating that heterosexuals may benefit from health promotion campaigns that are delivered through a more public setting.

Background Men-who-have-sex-with-men (MSM) living with HIV have a high prevalence of high-risk human papillomavirus (hrHPV) in the anus, and a high incidence of anal cancer. We conducted an open-label, single-arm pilot study to assess the utility of imiquimod cream against hrHPV among MSM living with HIV.[ACTRN12617001355369] Methods The study was conducted at Melbourne Sexual Health Centre between April 2018 and June 2020. MSM aged ≥18 years, living with HIV, who tested positive for any anal hrHPV on clinician-collected swabs were eligible. We instructed men to apply 5% imiquimod cream (6.25 mg) intra-anally and peri-anally 3 doses per-week for 16-weeks (Phase 1), followed by a maintenance period of 1 dose per-week for 48-weeks (Phase 2). We collected adverse events (AE) using text messages and questionnaires. Results Thirty MSM were enrolled to phase 1 and 27 completed the week 16 follow-up(median age 50). Twenty-four MSM (86%) applied at least 50% of imiquimod doses. All men reported AE, with 39.5% reporting grade 1,39.5% grade 2, and 21% grade 3 AEs. Eighteen MSM (67%) required treatment interruption. The reasons for interruption were haemorrhoids (n=3), herpes genitalis reactivation (n=2), and grade 2–3 AEs (n=11) such as irritation, itching and tenderness. 60% of MSM with grade 2(n=6) and 33% with grade 3 AEs (n=2) opted to continue to phase 2. Eighteen MSM were enrolled to phase 2 and 13 completed the week 48 follow-up. All MSM took at least 50% of doses. No treatment-limiting AEs were reported. 10 MSM in phase 1 (37%) and none in phase 2 reported their sex life was negatively impacted from imiquimod use. Conclusion Intra-anal and peri-anal imiquimod at 3 doses per-week was poorly tolerated over 16 weeks and most men required treatment interruption due to AEs. In contrast, once-a-week application was well tolerated with no treatment-limiting AEs reported over 48-weeks.

Background While syphilis transmission is increasing, precisely how Treponema pallidum is transmitted sexually is unclear. This study of MSM with early syphilis determined the frequency of Treponema pallidum shedding from potentially asymptomatic sites and the stage with the most frequent shedding. Methods MSM were recruited between 2015 and 2019, at Melbourne Sexual Health Centre, Australia. Men were eligible if they reported sex with men during the previous year, were aged ≥18 years and had laboratory-confirmed primary, secondary, or early latent syphilis. All syphilis lesions were swabbed. Non-lesion samples collected were oral rinse, oral cavity swab, anal canal swab, urine, and semen. Specimens were tested for T. pallidum using two PCR assays. Results 200 men with serologically-confirmed early syphilis were included: 54 (27%) primary, 93 (46·5%) secondary and 53 (26·5%) early latent cases. T. pallidum DNA was detected orally in 48 (24%; 95% CI: 18.3–30.5%) men by oral rinse and/or oral lesion swab, 24 with no oral lesion. Oral T. pallidum detection was most frequent during secondary syphilis compared to other stages, (44%(41/93) versus 7% (7/107), p Conclusion Unrecognised oral and anal shedding of T. pallidum may be a factor in sustaining syphilis transmission. Secondary syphilis may be the most infectious stage, with oral transmission possibly being important. Earlier detection and treatment for syphilis to prevent progression to the secondary stage may improve syphilis control.

Background Due to the COVID-19 pandemic, sexual health clinics across Australia have switched from clinician-collected to self-collected swabs for oropharyngeal STI screening. The study aimed to determine the acceptability of self-collected throat swabs among 200 gay, bisexual and other men who have sex with men (GBMSM) attending a sexual health service. Methods GBMSM aged ≥16 years old, had a throat swab taken at the Melbourne Sexual Health Centre (MSHC), and provided consent to participate in research, were invited to take this online survey by SMS. The survey collected data on how easy or difficult men found collecting their own throat swab. Results 273 GBMSM completed the survey;218 (79.9%) selfcollected their throat swab and were included in the final analysis. Most participants found collecting their own throat swabs very easy, easy, or were neutral (190;87.2%;95% confidence interval [95%CI]: 82.0% to 91.3%) and 28 (12.8%;95%CI: 8.7% to 18.0%) found it difficult or very difficult. There were 85 (39.0%) who reported taking the swab by themselves was worse than previous experiences of cliniciancollected swabs, compared to 110 (50.5%) who reported it was better taking the swab by themselves or found no difference to previous clinician-collected swabs. The two most commonly reported experiences during self-collection were gagging (155;71.1%) and being worried they had not done it correctly (46 out of 95 who were asked this;48.4%). Almost half of participants preferred to have a clinician take their throat swab (103;47.5%;95%CI: 40.5% to 54.1%);66 (30.4%;CI: 24.3% to 36.8%) did not have a preference and 48 (22.1%;95%CI: 16.7% to 28.1%) preferred to take the swab themselves. Conclusion Most GBMSM did not find self-collecting throat swabs difficult, however almost half of participants preferred to have a clinician take the swab..

Background The residents of Victoria (Australia’s second most populous state), were subject to a hard lockdown for several months as they experienced a second wave of COVID-19. Victorians could only leave their homes for essential activities, were required to wear facemasks, remain within 5km of their homes and were subject to a nightly curfew. Elsewhere in Australia, COVID numbers remained low with no lockdown in place. We examined the impact of the lockdown on the sexual behaviour of Victorians compared with elsewhere in Australia. Methods Our online survey was open for 2.5 weeks during the lockdown (August 13th to 31st). Participants aged 18+ were recruited via social media and asked to report on their current sexual practices. Logistic regression was used to calculate the difference in the proportion of practices between Victorians and non-Victorians. Results 976 people completed the survey: 71% identified as female, 75% were aged 18–29 years, 61% resided in Victoria. Compared with elsewhere in Australia, Victorians were less likely to report sex in the last 4 weeks (54.8% vs 68.0%, diff=-13.3%, 95%CI -19.6, -6.9). Victorians were also less likely to report casual hook-ups (10.6% vs 17.3%; diff=-6.7%, 95%CI -12.5, -0.8) and sex with a fuckbuddy (10.6% vs 16.9%; diff=-6.2%, 95%CI-12.1,-0.4). There was no difference in dating app use in the last 4 weeks between Victorians and others (27.0% vs 26.6%; diff=0.4; 95%CI -5.2,6.1), but Victorians were more likely to report using apps for virtual dates (15.7% vs 2.9%, diff=12.8%, 95%CI 6.2,19.3) and chatting (83.0% vs 72.5%; diff=10.5; 95%CI 0.0,20.9) and less likely to use them for face-to-face dates (15.1% vs 56.9%; diff=-41.8%, 95%CI -52.9,-30.7). Conclusions Hard lockdowns impact sexual behaviour and practices. However, sexual activity did not stop completely, highlighting the importance of ensuring accessibility of sexual and reproductive health services during periods of restriction.

Background Neisseria gonorrhoeae can be cultured from saliva in men with pharyngeal gonorrhoea and could theoretically be transmitted from the pharynx to the urethra when saliva is used as a lubricant for masturbation. To explore this issue, we developed mathematical models for the transmission of Neisseria gonorrhoeae at each of oropharynx, urethra and anorectum among men who have sex with men (MSM). Methods Model 1 included transmission routes (oral sex, anal sex, rimming, kissing, and three sequential sex practices) we have previously validated. In Model 2, we added masturbation to model 1. In Model 3, we included masturbation but excluded the three sequential sex practices. We calibrated our data to six international studies. We evaluated the model performance using the Root Mean Squared Error (RMSE) and Cohen’s d statistic. Results Model 2 has significantly higher RMSE than model 1 (p-value 0.8) compared with Model 1. This suggests performance of Model 1 and Model 2 are similar. In contrast, Model 3 has significantly higher RMSE than both Model 1 and Model 2 (p-value 0.8 for all six datasets) compared with the two models. This suggests performance of Model 3 is significantly worse than Model 1 and Model 2. Conclusion Our findings indicate that masturbation plays a moderate role in the transmission of Neisseria gonorrhoeae. Our model also suggests that sequential sexual practices may be more important than masturbation for explaining the site-specific prevalence in men with multi-site infection. Our model predicted that about 1 in 4 cases of urethral gonorrhoea might arise from masturbation if it transmits gonorrhoea.

Background We aimed to develop machine learning models and evaluate their performance in predicting HIV and sexually transmitted infections (STIs) diagnosis based on a cohort of Australian men who have sex with men (MSM). Methods We collected clinical records of 21,273 Australian MSM during 2011–2017. We compared accuracies for predicting HIV and STIs (syphilis, gonorrhoea, chlamydia) diagnosis using four machine learning approaches against a multivariable logistic regression (MLR) model. Results Machine learning approaches consistently outperformed MLR. Gradient boosting machine (GBM) achieved the highest area under the receiver operator characteristic curve for HIV (76.3%) and STIs (syphilis, 85.8%; gonorrhoea, 75.5%; chlamydia, 68.0%), followed by extreme gradient boosting (71.1%, 82.2%, 70.3%, 66.4%), random forest (72.0%, 81.9%, 67.2%, 64.3%), deep learning (75.8%, 81.0%, 67.5%, 65.4%) and MLR (69.8%, 80.1%, 67.2%, 63.2%). GBM models demonstrated the ten greatest predictors collectively explained 62.7–73.6% of variations in predicting HIV/STIs. STIs symptoms, past syphilis infection, age, time living in Australia, frequency of condom use with casual male sexual partners during receptive anal sex and the number of casual male sexual partners in the past 12 months were most commonly identified predictors. Conclusions Machine learning approaches are advantageous over multivariable logistic regression models in predicting HIV/STIs diagnosis.

SUMMARY Over the past 3 decades, tests of autonomic function have become increasingly standardized across most laboratories, particularly with commercially available equipment similar to other neurophysiologic tests. Most neurologically based laboratories perform four or five tests of autonomic function. Two of these, the sudomotor axon reflex response and the thermoregulatory sweat test (which some laboratories do not perform because it requires extensive equipment), examine sudomotor autonomic function. The remaining three, the cardiovascular response to a tilt table test, the cardiovascular response to the Valsalva maneuver, and the cardiac response to deep breathing examine cardiovascular autonomic function. Tests of sweating typically localize the lesion in the neuraxis, differentiating between central nervous system pathways, the spinal cord, or pre- or postganglionic roots or nerves. Tests of cardiovascular function delineate specific autonomic subsystem involvement, whether vagal parasympathetic as reflected in the deep breathing response and specific phases of the Valsalva maneuver or sympathetic adrenergic as reflected in the tilt table test and the other phases of the Valsalva. This review details the basic performance, analysis, and interpretation of these and a few other tests, with illustrative patient cases.

A 42-year-old man presented with respiratory symptoms, followed by ptosis, ageusia, dysarthria, and left hand weakness. MRI showed a lesion within the splenium of the corpus callosum (figure). Vascular and toxic-metabolic workup was unremarkable. Nasopharyngeal swab revealed Influenza A positivity. Symptoms fully resolved after oseltamivir treatment.

Objective To compare the intrauterine gene expression signatures of women with surgically confirmed ectopic pregnancy (ECT) and those of women with miscarriage to inform the development of a genomic classifier for the reliable delineation of pregnancy location in women with clinically nonviable pregnancies of unknown location (NV-PULs). Design Discovery-based prospective cohort study. Setting Academic medical center. Patient(s) Women with clinically nonviable early pregnancy to include abnormal intrauterine pregnancy (AIUP), ECT, or NV-PUL. Intervention(s) Endometrial (EM) pipelle sampling of the uterus was conducted at the time of scheduled surgery for clinically nonviable early pregnancy (dilation and curettage, manual vacuum aspiration, or laparoscopy). All pregnancy locations were surgically and/or histologically confirmed as intrauterine or ectopic. Main Outcome Measure(s) Gene expression profiles as determined by array hybridization, quantitative real-time polymerase chain reaction, and nCounter technology. Result(s) Intrauterine samples were obtained by EM pipelle from 27 women undergoing surgery for a clinically nonviable early pregnancy. Comparison of array-based global gene expression signatures from women with histologically confirmed ECT versus AIUP revealed 61 differentially expressed genes from which the 5 most informative were included in the pregnancy location classifier. All 5 genes (C20orf85, LRRC46, RSPH4A, WDR49, and ZBBX) were cilia-associated and showed increased expression in pipelle samples from women with ECT relative to expression in samples from women with AIUP. The 5-gene classifier demonstrated an average area under the receiver operator characteristic curve of 0.97 for the detection of ECT. In an external test set composed of publicly available EM pipelle-based gene expression data from a study with similar ECT and AIUP cohorts (n = 19), the classifier revealed an average area under the receiver operator characteristic curve of 0.84. Conclusion(s) Consistently increased expression of cilia-associated genes in the uterine cavity of women with ECT provides a reliable molecular signal for the delineation of pregnancy location in women with clinically assessed NV-PUL. A classifier consisting of the 5 most informative cilia-associated genes demonstrated 91% (42/46) accuracy in predicting the pregnancy location.

Traumatic brain injury (TBI) cause neuroinflammation, exaggerated immune response, and, consequently, neurodegeneration. The gut microbiome is an essential modulator of the immune system, impacting in the brain. There are not effective treatments for TBI, therefore, modulating the gut microbiome may shed novel therapeutics for the damaged brain. Also, in patients with Alzheimer's disease (AD), the microbiota has been associated with a lack of diversity, which negatively modulates the immune system. This study aimed to determine whether the gut microbiota from AD mice exacerbates neurological deficits after TBI in young mice. For this purpose, we performed fecal microbiota transplants from AD (FMT-AD) mice into young C57BL/6 (wild-type, WT) mice following TBI. Thus, FMT-AD and fecal microbiota transplants from healthy controls (FMT-young) were administered orally to young WT mice after the TBI occurred. We first determined the gut microbiota diversity and composition by analyzing full-length 16S rRNA sequences from mouse fecal samples using the Oxford Nanopore MinION technology. We collected the blood, brain, and gut tissues for protein and immunohistochemical analysis. Our results showed that FMT-AD treatment stimulates a higher relative abundance of Muribaculum intestinal and a decrease in Lactobacillus johnsonii compared FMT-young treatment in WT mice. Furthermore, WT mice exhibited larger lesion volumes, increased the number of activated microglia/macrophages cells, and reduced motor recovery after FMT-AD compared to FMT-young one day after TBI. Thus, the gut microbiota from AD mice not only aggravates the neuroinflammatory response and motor recovery, but also increases the lesion size after TBI in young WT mice.

SCOPUS: ar.j, info:eu-repo/semantics/published

Background/Introduction Classic electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH) have been well studied in Western populations, particularly in hypertensive patients. However, their utility in Asian populations is not well studied, and their applicability to young pre-participation cohorts is unclear. We sought to evaluate the performance of classical criteria against that of machine learning models. Aims We sought to evaluate the performance of classical criteria against the performance of novel machine learning models in the identification of LVH. Methodology Between November 2009 and December 2014, pre-participation screening ECG and subsequent echocardiographic data was collected from 13,954 males aged 16 to 22, who reported for medical screening prior to military conscription. Final diagnosis of LVH was made on echocardiography, with LVH defined as a left ventricular mass index >115g/m2. The continuous and binary forms of classical criteria were compared against machine learning models using receiver-operating characteristics (ROC) curve analysis. An 80:20 split was used to divide the data into training and test sets for the machine learning models, and three fold cross validation was used in training the models. We also compared the important variables identified by machine learning models with the input variables of classical criteria. Results Prevalence of echocardiographic LVH in this population was 0.91% (127 cases). Classical ECG criteria had poor performance in predicting LVH, with the best predictions achieved by the continuous Sokolow-Lyon (AUC = 0.63, 95% CI = 0.58–0.68) and the continuous Modified Cornell (AUC = 0.63, 95% CI = 0.58–0.68). Machine learning methods achieved superior performance – Random Forest (AUC = 0.74, 95% CI = 0.66–0.82), Gradient Boosting Machines (AUC = 0.70, 95% CI = 0.61–0.79), GLMNet (AUC = 0.78, 95% CI = 0.70–0.86). Novel and less recognized ECG parameters identified by the machine learning models as being predictive of LVH included mean QT interval, mean QRS interval, R in V4, and R in I. ROC curves of models studies Conclusion The prevalence of LVH in our population is lower than that previously reported in other similar populations. Classical ECG criteria perform poorly in this context. Machine learning methods show superior predictive performance and demonstrate non-traditional predictors of LVH from ECG data. Further research is required to improve the predictive ability of machine learning models, and to understand the underlying pathology of the novel ECG predictors identified.

Background Pre-participation electrocardiogram (ECG) screening is proposed as a means to detect cardiac pathology in asymptomatic individuals, and to select individuals for further cardiac investigation. Isolated ECG finding of Right Ventricular Hypertrophy (RVH) does not require further investigation based on the recent 2017 International Criteria. However, a prominent R wave in V1 has been described in cardiac abnormalities such as Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, cardiomyopathy in Duchenne muscular dystrophy, arrhythmogenic right ventricular cardiomyopathy (ARVC), atrial septal defect and pulmonary hypertension. Purpose We sought to examine the utility of a prominent R wave in V1 as a screening criterion in an asymptomatic young male population of predominantly non-athletes, to detect significant structural cardiac pathology. Methods As part of the Singapore Armed Forces Electrocardiographic and Echocardiographic (SAFE) Protocol Study, pre-military enlistment screening ECG data was collected from 144,346 males between the ages of 16 to 22 from November 2009 to December 2014. Patients with ECGs with a prominent R wave, defined as an R wave ≥0.5mV in lead V1 with an R/S ratio of ≥1, were sent to a tertiary medical facility for a detailed transthoracic echocardiogram and subsequent cardiologist review. Any cardiac pathology identified was deemed significant if it led to the patient being excluded from participation in vigorous physical activity. Results 1,144 patients with an isolated prominent R wave in V1 were studied. The mean age was 18.2±1.09 years and 81% were of Chinese ethnicity. None of the patients had echocardiographic evidence of RVH, 5 patients had a dilated right ventricle and 3 individuals had an elevated pulmonary artery systolic pressure. 11 patients (0.96%) had significant structural heart disease known to be associated with a prominent R wave in V1 that excluded them from participation in physical activity. These included large atrial septal defects (n=8), pulmonary stenosis (n=1), total anomalous pulmonary venous return (n=1) and hypertrophic cardiomyopathy (n=1). The test has a sensitivity of 21.6%, specificity of 93.4%, positive predictive value of 0.96% and negative predictive value of 99.8%, Performance As Screening Criteria Number of Patients With Cardiac Pathology In Those Tested Positive Number of Patients With Cardiac Pathology In Those Tested Negative Positive Predictive Value (%) Negative Predictive Value (%) Sensitivity (%) Specificity (%) 11 40 0.96 99.8 21.6 93.4 Significant Cardiac Pathology Identified Conclusion A prominent R in V1 is not associated with echocardiographic RVH, or ARVC even in a large predominantly non-athletic male population. However, 0.96% of such patients would have other significant cardiac pathologies such as a large atrial septal defect.

Hydrosalpinx, the blockage of fallopian tubes, can result from pelvic inflammatory disease. Hydrosalpinx is a cause of infertility and negatively impacts in vitro fertilization. To better understand the pathobiology of hydrosalpinx, we compared the proteome of lavages from disease vs. healthy fallopian tubes. Results indicate a disruption of redox homeostasis and activation of the complement system, immune cell infiltration, and phagocytosis; pathways that may drive tubal injury. To our surprise among the most prominent proteins with hydrosalpinx was mesothelin (MSLN), which until now has only been associated with epithelial malignancies. Analogous to mesothelioma and ovarian carcinoma, a significant increase of MSLN was detected in plasma from patients with hydrosalpinx. This finding suggests MSLN may provide clinical diagnosis in lieu of the current approaches that require invasive imaging. Importantly, these findings implicate MSLN in a benign disease, indicating that the activation and role of MSLN is not restricted to cancer.

Background Metastatic colorectal cancer (mCRC) with peritoneal carcinomatosis is an increasingly prevalent disease that carries significant mortality if left untreated. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in this patient population is associated with improved outcomes but high morbidity. We sought to study the prognostic significance of the known genomic driver, RAS, in patients with mCRC undergoing CRS/HIPEC to allow for improved assessment of risk-benefit ratio in this patient population. Methods Patients undergoing CRS/HIPEC for mCRC between 2010 and 2017 at our institution were identified. Patient demographics, RAS mutation status, perioperative morbidity, overall survival (OS), and relapse-free survival (RFS) were evaluated. Results Forty-seven patients met inclusion criteria. RAS mutant versus RAS wild-type groups were well matched with no difference in the clinicopathologic factors between groups. RAS mutation was associated with decreased RFS but no difference in OS. Conclusions RAS mutation is an independent marker of early recurrence in patients undergoing CRS/HIPEC for mCRC and may identify patients who do not derive benefit from this high-risk procedure.

Remembering a past event elicits distributed neural patterns that can be distinguished from patterns elicited when encountering novel information. These differing patterns can be decoded with relatively high diagnostic accuracy for individual memories using multivoxel pattern analysis (MVPA) of fMRI data. Brain-based memory detection—if valid and reliable—would have clear utility beyond the domain of cognitive neuroscience, in the realm of law, marketing, and beyond. However, a significant boundary condition on memory decoding validity may be the deployment of “countermeasures”: strategies used to mask memory signals. Here we tested the vulnerability of fMRI-based memory detection to countermeasures, using a paradigm that bears resemblance to eyewitness identification. Participants were scanned while performing two tasks on previously studied and novel faces: (1) a standard recognition memory task; and (2) a task wherein they attempted to conceal their true memory state. Univariate analyses revealed that participants were able to strategically modulate neural responses, averaged across trials, in regions implicated in memory retrieval, including the hippocampus and angular gyrus. Moreover, regions associated with goal-directed shifts of attention and thought substitution supported memory concealment, and those associated with memory generation supported novelty concealment. Critically, whereas MVPA enabled reliable classification of memory states when participants reported memory truthfully, the ability to decode memory on individual trials was compromised, even reversing, during attempts to conceal memory. Together, these findings demonstrate that strategic goal states can be deployed to mask memory-related neural patterns and foil memory decoding technology, placing a significant boundary condition on their real-world utility.

Background Mutations in the androgen receptor (AR) ligand-binding domain (LBD), such as F877L and T878A, have been associated with resistance to next-generation AR-directed therapies. ARN-509-001 was a phase I/II study that evaluated apalutamide activity in castration-resistant prostate cancer (CRPC). Here, we evaluated the type and frequency of 11 relevant AR-LBD mutations in apalutamide-treated CRPC patients. Patients and methods Blood samples from men with nonmetastatic CRPC (nmCRPC) and metastatic CRPC (mCRPC) pre- or post-abiraterone acetate and prednisone (AAP) treatment (≥6 months’ exposure) were evaluated at baseline and disease progression in trial ARN-509-001. Mutations were detected in circulating tumor DNA using a digital polymerase chain reaction-based method known as BEAMing (beads, emulsification, amplification and magnetics) (Sysmex Inostics’ GmbH). Results Of the 97 total patients, 51 had nmCRPC, 25 had AAP-naive mCRPC, and 21 had post-AAP mCRPC. Ninety-three were assessable for the mutation analysis at baseline and 82 of the 93 at progression. The overall frequency of detected AR mutations at baseline was 7/93 (7.5%) and at progression was 6/82 (7.3%). Three of the 82 (3.7%) mCRPC patients (2 AAP-naive and 1 post-AAP) acquired AR F877L during apalutamide treatment. At baseline, 3 of the 93 (3.2%) post-AAP patients had detectable AR T878A, which was lost after apalutamide treatment in 1 patient who continued apalutamide treatment for 12 months. Conclusions The overall frequency of detected mutations at baseline (7.5%) and progression (7.3%) using the sensitive BEAMing assay was low, suggesting that, based on this assay, AR-LBD mutations such as F877L and T878A are not common contributors to de novo or acquired resistance to apalutamide. ClinicalTrials.gov identifier NCT01171898.

To evaluate the utility of pipelle endometrial sampling as a diagnostic tool in the evaluation of abnormal first trimester gestations.Thirty-one women with abnormal first trimester pregnancies defined as gestations with abnormally rising or falling quantitative human chorionic gonadotropin (β-hCG) levels and ultrasound findings consistent with a nonviable or ectopic pregnancy were prospectively evaluated. Endometrial pipelle sampling was performed on each patient in a standardized fashion immediately before curettage and evaluated as a fixed, permanent specimen to assess for the presence of either chorionic villi, trophoblastic or fetal tissue.The sensitivity, specificity, positive predictive value, and negative predictive value for endometrial biopsy were 70.1%, 100%, 100%, and 33.3%, respectively. For curettage, the sensitivity, specificity, positive predictive value, and negative predictive value were 88.9%, 100%, 100%, and 57.1%, respectively.Curettage's overall sensitivity is superior to endometrial biopsy in detecting the presence of intrauterine products of conception in early abnormal pregnancies. However, in some clinical situations where the diagnosis of ectopic pregnancy is in question, particularly if the β-hCG is ≤ 2,000 mIU/mL, endometrial pipelle biopsy could be a useful tool in the evaluation algorithm.

Objectives: To review the literature and examine the accuracy of clinicians’ prediction of survival as well as prognostic factors determined to be predictive of shorter survival in terminal cancer patients. Methods: A literature search was conducted on MEDLINE (1 January 2000 to 29 July 2012), Embase (1 January 2000 to 22 July 2012), and Cochrane Database of Systematic Reviews (1 January 2005 to July 2012). Reference sections of relevant reviews were also examined for relevant articles. All studies examining the accuracy of prediction of survival and prognostic factors indicative of survival in patients with terminal cancer were selected. Descriptive statistics summarised the extracted data. Results: A total of 85 studies published from 1972 to July 2012 with a study cohort of 30 to 6066 patients were identified. Clinicians’ prediction of survival correlated with patient’s actual survival, but the predictions tended to be too optimistic. The ability of varying health care professionals to estimate survival was contradictory among different studies. Some studies noticed those with more experience with terminal cancer patients were better able to predict an accurate estimation, whereas others concluded that there was no difference. The estimations were also more accurate during short-term time ranges such as the ‘horizon effect’. Only a few assessment tools to assist in predicting the remaining duration of survival in patients were validated. A variety of prognostic factors between studies were identified, but the factors were not validated nor any instruments created. Conclusion: Demographic information and clinical symptoms can assist in determining the remaining duration of survival of terminal cancer patients. Assessment tools should be convenient and not a burden for the patient as the goal of palliative care is to maintain or improve the quality of life as much as possible. Even with the application of instruments to formulate a prediction, error cannot be completely eliminated. Physicians should warn the patient and their family of the uncertainty of the predictions.

This phase I study assessed the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, and preliminary antitumor effects of sunitinib combined with modified FOLFOX6 (mFOLFOX6).Patients with advanced solid malignancies received mFOLFOX6 in 2-week cycles with escalating sunitinib doses (25, 37.5, and 50 mg/day) on three schedules: 2 weeks on, 2 weeks off (2/2); 4 weeks on, 2 weeks off (4/2); or continuous daily dosing (CDD). Patients received up to 8 treatment cycles (Schedule 2/2 and CDD schedule) or 6 cycles (Schedule 4/2). An expansion cohort enrolled patients with metastatic colorectal cancer at the Schedule 2/2 MTD.Overall, 53 patients were enrolled, with 43 evaluable for dose-limiting toxicity (DLT). On Schedule 2/2 (n = 18), DLTs occurred in three patients at 50 mg/day (grade 4 neutropenia [n = 1]; grades 3 and 4 thrombocytopenia [n = 2]) and two patients achieved partial responses (PRs). On Schedule 4/2 (n = 13), 37.5 mg/day exceeded the MTD with two DLTs (febrile neutropenia and grade 4 hypokalemia, respectively). On the CDD schedule (n = 12), the MTD was 25 mg/day; one DLT (grade 3 stomatitis) was reported and two patients achieved PRs. The most common adverse events were neutropenia, fatigue, and thrombocytopenia. No clinically significant drug-drug interactions were apparent between sunitinib, its metabolite SU12662, and mFOLFOX6.Sunitinib combined with mFOLFOX6 had acceptable tolerability. The MTDs were sunitinib 50 mg/day on Schedule 2/2 and 25 mg/day on the CDD schedule. A MTD for Schedule 4/2 was not established.

Background Papilloma is the most common finding associated with pathologic nipple discharge. In the absence of breast imaging abnormalities, the incidence of occult malignancy is

SummaryBackground: Clinical trials are widely accepted as a necessary step in evaluating the safety and efficacy of new pharmaceutical products. In order for a sufficiently powered study, a clinical trial depends on the effective and unbiased recruitment of eligible patients. Trials involving seasonal diseases like influenza pose additional challenges.Objective: This is a feasibility study of a mobile real-time alerting system to systematically identify potential study subjects for a randomized controlled trial evaluating the safety and efficacy of early intervention with interferon alfacon-1 for patients hospitalized for influenza virus infection. Methods: The alerting system was setup in a 471-bed acute care teaching hospital, enabled with computerized physician order entry (CPOE) and a rules-based alerting system. Patients were identified from the entire hospital using two alerts types: pharmacy prescription records for antiviral drugs, and positive influenza laboratory results. Email alerts were generated and sent to BlackBerry® devices carried by the study personnel for a 6 month period. The alerts were archived automatically on a secure server and were exported for analysis in Microsoft Access.Results: Over a period of 21 weeks, 779 total alerts were received. The study team was alerted to 241 patients, of whom 85 were potential study subjects. The alert system identified all but one of the patients independently identified by infection control.Conclusions: Real-time identification of potential study subjects is possible with the integration of computerized physician order entry and BlackBerry® technology. It is a viable method for the systematic identification of patients throughout a hospital, particularly for trials investigating time-sensitive disease progression.

Few studies have examined the impact of underlying diagnosis on the functional and oncologic outcomes following endoprosthetic proximal femur replacement (PFR). We performed a retrospective review of 61 consecutive cemented bipolar PFR in 59 patients for treatment neoplastic lesions with a minimum follow-up of 24 months. Twenty-two patients had primary bone tumors and 39 had metastatic disease. Average follow-up for the 30 surviving patients was 55.4 months and the mean postoperative survival for the 29 patients who died was 12.2 months. Patients with primary tumors demonstrated significantly better functional outcomes than those with metastatic disease, with mean Musculoskeletal Tumor Society functional scores of 80.2 and 66.8%, respectively (p=0.0002). Age correlated inversely with functional scores (r=-0.48; p=0.0002), while femoral resection length did not. Preoperative pathologic fracture did not appear to adversely impact final functional outcomes. The Kaplan-Meier 5-year implant survival estimate was 92.5%, with aseptic loosening as the endpoint. Both functional results and survival are increased for primary tumors versus metastatic disease following PFR. However, PFR results in excellent local disease control, reliable pain relief and good functional results in both groups, with prosthesis survival exceeding that of the patient in many cases.

OBJECTIVE: This study was undertaken to estimate the reliability and validity of an objective structured assessment of technical skills (OSATS) for midline episiotomy repair using a lifelike anatomic model. STUDY DESIGN: Eighteen residents were administered an episiotomy OSATS. Two evaluators independently completed an objective score sheet assessing six key components of the repair, seven global surgical skills, and a pass/fail score for each resident. Residents also completed an anonymous self-assessment. RESULTS: Reliability indices were 0.95 for the checklist and global surgical skills rating. Construct validity found significant differences on the checklist, global surgical skills, and pass/fail score sheets by residency level. Residents more often assessed their own global surgical skills performance lower than the independent evaluators. Surprisingly, 61% (11/18) of the residents failed the assessment, including all postgraduate year 1 and postgraduate year 2 residents. CONCLUSION: Episiotomy OSATS that used task-specific and global checklists provide a reliable and valid method of assessing resident skills in this anatomic model, and performance correlates with resident year level of training.

The drive toward miniature photonic devices has been hindered by our inability to tightly control and manipulate light. Moreover, photonics technologies are typically not based on silicon and, until recently, only indirectly benefited from the rapid advances being made in silicon processing technology. In the first part of this article, the successful fabrication of three-dimensional (3D) photonic crystals using silicon processing will be discussed. This advance has been made possible through the use of integrated-circuit (IC) fabrication technologies (e.g., very largescale integration, VLSI) and may enable the penetration of Si processing into photonics. In the second part, we describe the creation of 2D photonic-crystal slabs operating at the λ = 1.55 μm communications wavelength. This class of 2D photonic crystals is particularly promising for planar on-chip guiding, trapping, and switching of light.

This paper presents a simulation of a new dynamic buffer allocation management scheme in ATM networks. To achieve this objective, an algorithm that detects congestion and updates the dynamic buffer allocation scheme was developed for the OPNET simulation package via the creation of a new ATM module.

Although the lithotomy position is frequently used in urologic, gynecologic, and colorectal surgery, the potentially devastating complication of lower extremity compartment syndrome is not widely recognized. The authors report a 50-year-old woman who underwent 8 hours of colorectal surgery in the lithotomy position. After surgery she complained of bilateral calf pain and was noted to have episodes of ventricular tachycardia. After emergency dialysis for hyperkalemia, she required bilateral four-compartment calf fasciotomy. Prevention of compartment syndrome and its sequelae, when using the lithotomy position, requires minimizing the duration of time in lithotomy. If protracted surgery in lithotomy is necessary, the patient should be carefully monitored for compartment syndrome postoperatively. Urgent four-compartment fasciotomy is the treatment of choice if a compartment syndrome is clinically suspected.