bluuebunny/crossref_metadata_2025 huggingface dataset:
THUR 158 Susac’s syndrome: treatment and outcomes in three cases
Authors: Xin Chua Wei , Dan Whittam , Saif Huda , David Rog , Martin Wilson , David Smith , Peter Enevoldson , Anu Jacob
Published: October 2018

Background

Susac’s syndrome (SS) is a rare, autoimmune microangiopathy causing a triad of branch retinal artery occlusions, sensorineural hearing loss and brain lesions. Published data on immunotherapy and outcomes is very limited.

Method

Single centre case note review.

Electronic hospital records between 1996 and 2017 were searched. 277 possible cases were reviewed.

Results

3 cases (2 female, 1 male) with the full SS triad were identified. Median age of disease onset was 35.2 years with headache (n=3), confusion (n=1), hearing loss (n=3), vertigo (n=2) and visual field loss (n=2). Time from onset to diagnosis with the full triad was 3–23 months. MRIs showed characteristic corpus callosum involvement. All patients received high-dose corticosteroids as acute therapy. Case 1 was treated with Mycophenolate Mofetil (MMF) and Prednisolone for 27 months, and followed up for a further 8 months. She remained relapse-free. Case 2 relapsed on steroid-reduction, so received Rituximab followed by MMF and Prednisolone. She has now been stable for 14 months. Case 3 was intolerant to high-dose corticosteroids, Cyclophoshamide and MMF. He relapsed off treatment then commenced Azathioprine. Duration on Azathioprine is 14 months with one further relapse.

Conclusion

SS is rare but causes significant morbidity. Recognition of characteristic findings and early immunotherapy improves outcomes.
WED 162 Cognitive impairment in a greek ms patient cohort using bicams
Authors: T Kalatha , E Koutsouraki , M Arnaoutoglou
Published: October 2018

Introduction

Cognitive impairment (CI) can present in 40%–70% of MS patients and in the early stages of the disease. The Brief International Cognitive assessment for MS (BICAMS) is a brief, practical and potentially universal battery for cognitive assessment in MS.

Aim

To correlate cognitive function with clinical parameters as disease type, EDSS, and disease duration

Methods

The cognitive function was measured with the validated to the Greek population BICAMS tool, which consists of the Symbol Digit Modalities Test (SDMT), the Greek Verbal Learning Test (GVLT) and the Brief Visuospatial Memory Test-Revised (BVMT-R).

Results

36% patients classified as impaired according to the BICAMS battery. Progressive types of disease had worst scores than the relapsing in the SDMT (MD=1.73; 95% CI: 0.46, 3.0; p=0.009), GVLT (MD=1.77; 95% CI: 0.82, 2.72; p=0.001) and BICAMS z-score (MD=1.39; 95% CI: 0.54, 2.24; p=0.002). The two groups were also different in EDSS (p<0.001). EDSS showed correlation with BICAMS test. Disease duration did not correlate with CI. Age was identified as a risk factor of CI.

Discussion

Early management of CI can lead to improvement in the patient’s quality of life. Progressing types of the disease might benefit from early cognitive assessment in the disease course.
WED 170 The utility of brain FDG-PET in a patient with natalizumab associated PML-IRIS
Authors: Aravindhan Baheerathan , Sabrina Kalam , Helen Grote , Cillian Mcnamara , Neil Rane , Richard Nicholas
Published: October 2018

Natalizumab, a highly effective disease modifying drug used in relapsing remitting multiple sclerosis (RRMS), is associated with progressive multifocal leukoencephalopathy (PML), a fatal intracerebral demyelinating disease caused by the JC virus that can be worsened with concurrent use of steorids. Stopping natalizumab in the context of PML can cause immune reconstitution inflammatory syndrome (IRIS) that can be treated with steroids. IRIS can be indistinguishable from PML on MRI - thus causing a clinical conundrum.

We describe a woman with RRMS on Natalizumab who developed dysarthria and right-sided hemiparesis. MRI demonstrated non-enhancing peridentate white matter signal abnormality in the right middle cerebellar peduncle (RMCP). Cerebrospinal fluid JC virus DNA was >1 million copies/ml. PML was diagnosed and Natalizumab withdrawn. Four weeks later she developed bulbar weakness and left-sided hemiparesis despite falling JC virus DNA. Repeat MRI demonstrated new extensive pontine changes consistent with PML-IRIS.

FDG-PET imaging confirmed focal areas of hypometabolism at the original site of PML and multiple areas of hypermetabolism in the left pons and middle cerebellar peduncle, suggestive of IRIS. Her clinical deterioration was attributed to IRIS and Prednisolone was commenced.

In this case FDG-PET scanning helped distinguish between PML and IRIS, guiding patient management.
THUR 172 Phase iv study of cladribine tablets and quality of life: clarify-ms
Authors: Schippling S , Langdon D , Solari A , Brochet B , Hupperts R , Piehl F , Lechner-Scott J , Montalban X , Keller B , Alexandri N
Published: October 2018

Authors Disclaimer: http://medpub-poster.merckgroup.com/ABN2018DISC_CLARIFY.pdf

Background

Relapsing multiple sclerosis (RMS) negatively affects health-related quality of life (HRQoL).

Objective

An open-label, single-arm, exploratory Phase IV study in centres in Europe and Australia will assess HRQoL in RMS patients receiving CT 3.5 mg/kg (CT3.5).

Methods

Eligible patients will receive CT 3.5 (cumulative) over 2 years. HRQoL (Multiple Sclerosis Quality of Life-54 [MSQoL-54]) and other patient-reported outcomes (Fatigue Severity Scale; Hospital Anxiety and Depression Scale; Treatment Satisfaction Questionnaire for Medication v1.4) will be assessed at baseline, and at 6, 12, 24 months.

Other outcomes include AEs, MRI measures (T1 Gd+ lesions, T2 lesions, brain atrophy), number of relapses, and disability/functioning measures (EDSS; 9-Hole Peg Test; Timed 25-Foot Walk and Brief International Cognitive Assessment for Multiple Sclerosis). The sample size estimation is based on the power to detect a mean difference of 5 points in MSQoL-54 composite score at 24 months vs baseline.

Results

The study aims to recruit 356 adults with RMS by 2019. Final data are anticipated in 2022.

Conclusions

This study will explore the effects of CT on HRQoL outcomes, and describe the effects of CT on treatment satisfaction and disability/functioning.

Disclosure statement

The trial is sponsored by Merck KGaA, Darmstadt, Germany.
WED 012 Reversible optic neuritis secondary to metronidazole
Authors: Natalie Anwyll , Paul Gerry , Kevin Gormley
Published: October 2018

Metronidazole is a nitroimidazole antibiotic used to treated anaerobic bacteria and protozoal infections. Neurological side-effects are documented mainly relating to peripheral neuropathy. There are only isolated case reports of optic neuropathy secondary to Metronidazole.

We describe a 36 year old man who presented with reduced central visual loss on a background of a two year history of Metronidazole use for a perianal fistula. Electrophysiology confirmed bilateral optic neuropathy. On cessation of Metronidazole visual acuity and electrophysiological studies returned to normal. This is the reported longest duration of metronidazole at maximal dosing causing an optic neuropathy with complete resolution on cessation.
WED 185 Clarity: mri outcomes in high disease activity relapsing ms
Authors: Giovannoni Gavin , Rammohan Kottil , Cook Stuart , Comi Giancarlo , Rieckmann Peter , Soelberg-Sorensen Per , Vermersch Patrick , Dangond Fernando , Hicking Christine
Published: October 2018

Background

The CLARITY study demonstrated the benefit of cladribine tablets 3.5 mg/kg (CT3.5) for patients with relapsing MS (RMS). Patients with high disease activity (HDA) RMS are at risk of clinical activity and disability progression.

Objective

Post-hoc analysis of MRI outcomes in CLARITY for CT3.5 vs placebo.

Methods

Retrospective analysis using HDA definitions based on relapse history, prior treatment, and MRI characteristics: high relapse activity (HRA) and HRA plus disease activity on treatment (HRA+DAT).

Results

For cumulative new T1 Gd+ lesions, relative risk ratios (RRR) for both subgroups (HRA: 0.087; 95% CI: 0.052 to 0.144; p<0.0001) (HRA+DAT: 0.077; 95% CI: 0.046 to 0.128; p<0.0001) were lower for CT3.5 vs placebo. Risk reductions (RR) (91% and 92%, respectively) were similar to the 90% reduction in the overall CLARITY population (0.097; 95% CI: 0.070 to 0.134; p<0.0001). Cumulative active T2 lesions RRR favoured CT3.5 vs placebo for both subgroups (HRA: 0.263; 95% CI: 0.180 to 0.383, p<0.0001) (HRA+DAT: 0.254; 95% CI: 0.178 to 0.363; p<0.0001): RRs of 74% and 75%, reflecting the 73% overall population reduction (0.272; 95% CI: 0.221 to 0.335; p<0.0001). Cumulative combined unique lesions RRR favoured CT3.5 vs placebo for HRA (0.212; 95% CI: 0.145 to 0.311; p<0.0001) and HRA+DAT (0.203; 95% CI: 0.141 to 0.291; p<0.0001): RRs were 79% and 80%, reflecting the 77% overall population reduction (0.234; 95% CI: 0.190 to 0.290; p<0.0001). There were no significant interactions between HDA and non-HDA subgroups.

Conclusions

The treatment benefit of CT3.5 on MRI outcomes was similar in HDA RMS subgroups and the overall CLARITY study population.

Disclaimer

http://medpub-poster.merckgroup.com/ABN2018DISC_HDAMRI.pdf
WED 187 Infections in ocrelizumab recipients from phase III studies
Authors: Gavin Giovannoni , Hans-Peter Hartung , Giancarlo Comi , Jérôme de Seze , Bernhard Hemmer , Ludwig Kappos , Xavier Montalban , Krzysztof Selmaj , Nicole Mairon , Jerry Wolinsky
Published: October 2018

Background

Ocrelizumab Phase III study safety findings in relapsing (OPERA I/II [NCT01247324/NCT01412333]) and primary progressive multiple sclerosis (ORATORIO [NCT01194570]) were reported; infections and serious infections are reported here. Methods: Ocrelizumab patients received 600 mg intravenously every 24 weeks for 96 weeks (OPERA I/II) or ≥120 weeks (ORATORIO; 2 × 300 mg infusions 14 days apart every 24 weeks). Controls received interferon beta-1a 44 µg thrice weekly (IFNβ−1a; OPERA I/II) or placebo (ORATORIO). Infections were classified by MedDRA system organ class/preferred term.

Results

Non-serious infection rates in ocrelizumab-treated patients in OPERA were 58.4% (pooled analysis) and ORATORIO 69.8%; comparators were IFNβ−1a 52.4% and placebo 67.8%. Most infections were mild-to-moderate. Common infections (≥10% in either group) reported more in ocrelizumab treated patients were upper respiratory tract infections and either nasopharyngitis (OPERA) or influenza (ORATORIO);<1% of ocrelizumab-treated patients withdrew due to non-serious infections. Serious infections occurred in 1.3% (OPERA) and 6.2% (ORATORIO) of ocrelizumab-treated patients; comparators were IFNβ−1a 2.9% and placebo 5.9%. No infection-related deaths occurred in ocrelizumabtreated patients in OPERA; two deaths occurred in ORATORIO (aspiration pneumonia and pneumonia [unrelated per investigator, related per sponsor]). No opportunistic infections were reported.

Conclusion

Serious infection rates with ocrelizumab were numerically lower than with IFNβ−1a and similar compared with placebo.
THUR 193 Alemtuzumab improves disability across functional systems
Authors: Basil Sharrack , Samuel Hunter , Rany Aburashed , Raed Alroughani , Dominique Dive , Giullermo Izquierdo , Jin Kim Ho , Jan Lycke , Richard Macdonell
Published: October 2018

The effect of alemtuzumab on functional systems (FS) scores of the Expanded Disability Status Scale (EDSS) was assessed in CARE-MS II patients over 6 years (y) (CARE-MS II, NCT00548405; extension, NCT00930553). Patients received alemtuzumab (12 mg/day; 2 courses: baseline, 5 days; 12 months later, 3 days), and as-needed alemtuzumab retreatment for relapse/MRI activity in the extension or another disease-modifying therapy per investigator discretion. Assessments: Proportion of patients achieving stable/improved EDSS score (versus core study baseline), FS scores, and 6 month confirmed disability improvement (CDI). In patients who achieved CDI over 6 y (n=126), assessments at 6 months post-CDI onset: EDSS score (<4; ≥4), number of improved FS per patient, and percentage with stable/improved FS scores. At Y6, 77% of patients showed stable/improved EDSS scores; 75%–85% showed stability/improvement in each FS. Through Y6, 43% achieved 6 month CDI. At 6 months post-CDI onset, 96% of CDI patients had an EDSS score <4, and 70% achieved improvements in >1 FS. Improvements were observed in each FS, most frequently Sensory (48%), Pyramidal (44%), and Cerebellar (44%) systems; 21%–25% showed improvements in the Brainstem, Cerebral, Visual, and Bowel/Bladder FS. These findings indicate a broad treatment effect of alemtuzumab on multiple aspects of disability improvements. STUDY SUPPORT: Sanofi and Bayer HealthCare Pharmaceuticals.
THUR 194 Autologous haematopoietic stem cell transplant in ms
Authors: Joyutpal Das , John Snowden , Sona Mistry , Simon Bell , Helen Jessop , Basil Sharrack
Published: October 2018

Introduction

Autologous haematopoietic stem cell transplantation (AHSCT) is a very effective treatment in patients with highly active relapsing remitting multiple sclerosis (RRMS) who failed standard disease modifying therapies (DMTs).

Methods

We retrospectively reviewed the medical records of all patients with RRMS who received AHSCT in Sheffield.

Results

25 patents with RRMS received AHSCT between July 2013 and July 2017. Their median age at diagnosis was 40 (22–56) years. All had highly active disease with gadolinium enhancing lesions on their pre-transplant MRIs. Eighteen patients had previously been treated with various DMTs and seven were treatment naïve. Median pre-AHSCT EDSS was 5.5 (2.5–7.5). Median follow up was 12 (3–42) months. Median post-AHSCT EDSS at the last follow up was 3 (1–6.5), p<0.001. No patient experienced further relapses following transplantation. Three patients had new lesions on their first follow up MRI at 6 months, but none had any new or enhancing lesions on subsequent MRI scans. Only routine transplant related toxicities were observed. One female and the wife of a male patient successfully conceived following AHSCT.

Conclusion

AHSCT is safe and effective in inducing remission in patients with highly active RRMS. Further studies are required to compare its efficacy with standard DMTs.
THUR 198 Safe monitoring of natalizumab therapy in multiple sclerosis
Authors: J Hosty , L Kass-Iliyya , S Bell , L Barker , S Packwood , A Stanislawska , N Hoggard , M Raza , D Paling
Published: October 2018

Natalizumab is one of the most effective therapies for relapsing-remitting Multiple Sclerosis. One complication is Progressive Multifocal Leucoencephalopathy (PML), a viral brain infection in patients already infected with JC virus. Monitoring of neurological symptoms, JC virus serology and regular brain imaging are required to ensure safe use of this therapy. Local audit data from 2015 indicated poor compliance with safety monitoring, with less than 25% of patients undergoing required investigations within the recommended time intervals. Subsequently a protocol was implemented to improve monitoring, with specialist nurses coordinating the requests for MRI scans and arranging JC virus serology, the frequency of which was determined according to the JC virus index. The records of all patients receiving Natalizumab at the centre were audited to assess the impact of this protocol (n=155). 99.2% of patients were appropriately tested for JC virus and 95.3% were imaged within the recommended interval. Additional work with the informatics and virology team ensured serology results became more easily accessible. The use of a standardised nurse-led operating procedure has resulted in marked improvement in the safety monitoring of Natalizumab.
National Standards for Public Involvement in Research: missing the forest for the trees
Authors: McCoy Matthew S , Jongsma Karin Rolanda , Friesen Phoebe , Dunn Michael , Neuhaus Carolyn Plunkett , Rand Leah , Sheehan Mark
Published: October 2018

Biomedical research funding bodies across Europe and North America increasingly encourage—and, in some cases, require—investigators to involve members of the public in funded research. Yet there remains a striking lack of clarity about what ‘good’ or ‘successful’ public involvement looks like. In an effort to provide guidance to investigators and research organisations, representatives of several key research funding bodies in the UK recently came together to develop the National Standards for Public Involvement in Research. The Standards have critical implications for the future of biomedical research in the UK and in other countries as researchers and funders abroad look to the Standards as a model for their own policy development. We assess the Standards and find that despite offering useful suggestions for dealing with practical challenges associated with public involvement, the Standards fail to address fundamental questions about when, why and with whom public involvement should be undertaken in the first place. We show that presented without this justificatory context, many of the recommendations in the Standards are, at best, fragments that require substantial elaboration by those looking to apply the Standards in their own work and, at worst, subject to potentially harmful misapplication by well-meaning investigators. As funding bodies increasingly push for public involvement in research, the key lesson of our analysis is that future recommendations about how public involvement should be conducted cannot be coherently formulated without a clear sense of the underlying goals and rationales for public involvement.
Drug-coated balloons for the treatment of symptomatic intracranial atherosclerosis: initial experience and follow-up outcome
Authors: Han Ju , Zhang Jun , Zhang Xiao , Zhang Jinping , Song Yun , Zhao Wei , Zheng Meimei , Sun Lili , Wang Wei
Published: October 2018

Background

The optimal treatment for patients with symptomatic severe intracranial atherosclerotic disease is not well established. Angioplasty and stenting have been attempted, with controversial results, mainly attributed to perioperative complications and a high incidence of restenosis or in-stent restenosis. Drug-coated balloons (DCBs) have shown encouraging results for coronary and peripheral artery disease, without convincing data for intracranial vasculature.

Objectives

To assess the feasibility, clinical and angiographic outcomes of DCBs for patients with intracranial de novo atherosclerotic disease.

Methods

Between September 2016 and September 2017, details of 30 patients with 31 arteries treated with DCBs for symptomatic severe intracranial atherosclerotic disease (≥70% stenosis or chronic total occlusion) were retrospectively collected in our centre. All lesions were predilated with conventional balloons. Periprocedural complications and clinical and vascular imaging follow-up outcomes were analysed.

Results

All arteries were successfully dilated with DCBs and 29 (93.5%) arteries achieved good antegrade perfusion, with remedial stenting for two arteries. Two patients presented with new ischemic stroke after the procedure. Over a mean follow-up of 9.8±2.6 months, no patient had recurrent ischemic symptoms. Repeat vascular imaging was performed at 7.0±1.1 months, with cerebral angiography in 24 patients (25 arteries) and MR angiography in six patients (six arteries). Only one (3.2%) artery presented with angiographic asymptomatic restenosis.

Conclusions

This study suggests that DCB dilatation may be a safe and effective alternative for intracranial de novo atherosclerotic disease.
Towards the Clinical utility of CFD for assessment of intracranial aneurysm rupture – a systematic review and novel parameter-ranking tool
Authors: Liang Li , Steinman David A , Brina Olivier , Chnafa Christophe , Cancelliere Nicole M , Pereira Vitor M
Published: October 2018

Background

Intracranial aneurysms (IAs) are vascular dilations on cerebral vessels that affect between 1%–5% of the general population, and can cause life-threatening intracranial hemorrhage when ruptured. Computational fluid dynamics (CFD) has emerged as a promising tool to study IAs in recent years, particularly for rupture risk assessment. However, despite dozens of studies, CFD is still far from clinical use due to large variations and frequent contradictions in hemodynamic results between studies.

Purpose

To identify key gaps in the field of CFD for the study of IA rupture, and to devise a novel tool to rank parameters based on potential clinical utility.

Methods

A Pubmed search identified 231 CFD studies for IAs. Forty-six studies fit our inclusion criteria, with a total of 2791 aneurysms. For included studies, study type, boundary conditions, solver resolutions, parameter definitions, geometric and hemodynamic parameters used, and results found were recorded.

Data synthesis

Aspect ratio, aneurysm size, low wall shear stress area, average wall shear stress, and size ratio were the parameters that correlate most strongly with IA rupture.

Limitations

Significant differences in parameter definitions, solver spatial and temporal resolutions, number of cycles between studies as well as frequently missing information such as inlet flow rates were identified. A greater emphasis on prospective studies is also needed.

Conclusions

Our recommendations will help increase standardization and bridge the gaps in the CFD community, and expedite the process of making CFD clinically useful in guiding the treatment of IAs.
Childhood and adult exposure to secondhand tobacco smoke and cardiac structure and function: results from Echo-SOL
Authors: Burroughs Peña Melissa Suzanne , Swett Katrina , Kaplan Robert C , Perreira Krista , Daviglus Martha , Kansal Mayank M , Cai Jianwen , Giachello Aida L , Gellman Marc D , Velazquez Eric J , Rodriguez Carlos J
Published: October 2018

Objective

To describe the relationship of household secondhand smoke (SHS) exposure and cardiac structure and function.

Methods

Participants (n=1069; 68 % female; age 45–74 years) without history of tobacco use, coronary artery disease or severe valvular disease were included. Past childhood (starting at age <13 years), adolescent/adult and current exposure to household SHS was assessed. Survey linear regression analyses were used to model the relationship of SHS exposure and echocardiographic measures of cardiac structure and function, adjusting for covariates (age, sex, study site, alcohol use, physical activity and education).

Results

SHS exposure in childhood only was associated with reduced E/A velocity ratio (β=−0.06 (SE 0.02), p=0.008). SHS exposure in adolescence/adult only was associated with increased left ventricular ejection fraction (LVEF) (1.2 (0.6), p=0.04), left atrial volume index (1.7 (0.8), p=0.04) and decreased isovolumic relaxation time (−0.003 (0.002), p=0.03). SHS exposure in childhood and adolescence/adult was associated with worse left ventricular global longitudinal strain (LVGLS) (two-chamber) (0.8 (0.4), p= 0.049). Compared with individuals who do not live with a tobacco smoker, individuals who currently live with at least one tobacco smoker had reduced LVEF (−1.4 (0.6), p=0.02), LVGLS (average) (0.9 (0.40), p=0.03), medial E′ velocity (−0.5 (0.2), p=0.01), E/A ratio (−0.09 (0.03), p=0.003) and right ventricular fractional area change (−0.02 (0.01), p=0.01) with increased isovolumic relaxation time (0.006 (0.003), p=0.04).

Conclusions

Past and current household exposure to SHS was associated with abnormalities in cardiac systolic and diastolic function. Reducing household SHS exposure may be an opportunity for cardiac dysfunction prevention to reduce the risk of future clinical heart failure.
Effect of sildenafil (Revatio) on postcardiac surgery acute kidney injury: a randomised, placebo-controlled clinical trial: the REVAKI-2 trial protocol
Authors: Aujla Hardeep , Kumar Tracy , Woźniak Marcin , Dott William , Sullo Nikol , Joel-David Lathishia , Morris Thomas , Brookes Cassandra , Barber Shaun , Murphy Gavin James
Published: October 2018

Introduction

Acute kidney injury (AKI) is a common and severe complication of cardiac surgery. The administration of pharmacological renoprotective agents during the perioperative period could prevent or reduce the severity of AKI and improve clinical outcomes. Experimental studies suggest that sildenafil may have therapeutic potential for the prevention of AKI. This trial will test the hypothesis that postoperative AKI will be reduced in cardiac surgery patients if they receive sildenafil compared with placebo.

Methods and analysis

Adult cardiac surgery patients 18 years of age or above undergoing cardiac surgery with cardiopulmonary bypass and cardioplegic arrest at a single tertiary cardiac centre in the UK will be randomised in a 1:1 ratio to receive either sildenafil or placebo. The primary outcome is serum creatinine concentration measured at preoperation and daily for up to 7 days postoperatively. Secondary outcomes will include measures of inflammation, organ injury, volumes of blood transfused and resource use. Allocation concealment, internet-based randomisation stratified by operation type, and blinding of outcome assessors will reduce the risk of bias. A sample size of 112 patients will have a 90% power to detect a mean difference of 10 μmol/L for serum creatinine values between treatment and placebo control groups with an alpha value of 0.05.

Ethics and dissemination

The trial protocol was approved by a UK ethics committee (reference 15/YH/0489). The trial findings will be disseminated in scientific journals and meetings.

Trial registration number

ISRCTN18386427.
Antibiotic therapy for pelvic inflammatory disease: an abridged version of a Cochrane systematic review and meta-analysis of randomised controlled trials
Authors: Savaris Ricardo F , Fuhrich Daniele G , Duarte Rui V , Franik Sebastian , Ross Jonathan D C
Published: October 2018

Objective

To assess the effectiveness and safety of antibiotic regimens used to treat pelvic inflammatory disease (PID).

Design

This is a systematic review and meta-analysis of randomised controlled trials (RCTs). Risk of bias was assessed using the criteria outlined in the Cochrane guidelines. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation.

Data sources

Eight electronic databases were searched from date of inception up to July 2016. Database searches were complemented by screening of reference lists of relevant studies, trial registers, conference proceeding abstracts and grey literature.

Eligibility criteria

RCTs comparing the use of antibiotics with placebo or other antibiotics for the treatment of PID in women of reproductive age, either as inpatient or outpatient treatment.

Results

We included 37 RCTs (6348 women). The quality of evidence ranged from very low to high, the main limitations being serious risk of bias (due to poor reporting of study methods and lack of blinding), serious inconsistency and serious imprecision. There was no clear evidence of a difference in the rates of cure for mild-moderate or for severe PID for the comparisons of azithromycin versus doxycycline, quinolone versus cephalosporin, nitroimidazole versus no use of nitroimidazole, clindamycin plus aminoglycoside versus quinolone, or clindamycin plus aminoglycoside versus cephalosporin. No clear evidence of a difference between regimens in antibiotic-related adverse events leading to discontinuation of therapy was observed.

Conclusions

We found no conclusive evidence that one regimen of antibiotics was safer or more effective than any other for the treatment of PID, and there was no clear evidence for the use of nitroimidazoles (metronidazole) compared with the use of other drugs with activity against anaerobes. More evidence is needed to assess treatments for women with PID, particularly comparing regimens with or without the addition of nitroimidazoles and the efficacy of azithromycin compared with doxycycline.
Trichomonas vaginalis
and HIV infection acquisition: a systematic review and meta-analysis
Authors: Masha Simon Chengo , Cools Piet , Sanders Eduard J , Vaneechoutte Mario , Crucitti Tania
Published: October 2018

Objectives

Trichomoniasis is the most prevalent curable STI globally, with the highest incidence and prevalence in sub-Saharan Africa (sSA). STIs have largely been associated with an increase in HIV acquisition. Our objective was to assess the existing literature available in English regarding the association of Trichomoniasis and HIV-1 acquisition.

Methods

The review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under number CRD42018082702. We searched MEDLINE, Embase and Scopus databases to collect articles measuring the association of
Trichomonas vaginalis
infection and HIV acquisition and performed a meta-analysis and qualitative synthesis of the literature.

Results

We identified 1806 unduplicated citations, of which 18 papers and 1 conference abstract were eligible for inclusion in the review after applying our inclusion and exclusion criteria. All the studies included in the systematic review had been carried out in sSA. The articles reported various measures of effects, namely: HRs, rate ratios, risk ratios and ORs. In a meta-analysis restricted to 11 studies reporting HR, individuals infected with
T. vaginalis
were 1.5 times more likely to acquire HIV compared with individuals not infected with
T. vaginalis
(95% CI 1.3 to 1.7; p<0.001).

Conclusions

T. vaginalis
is an important factor in HIV acquisition especially in sSA where the prevalence
of
both
T. vaginalis
and HIV-1 are high. This systematic review and meta-analysis confirms the evidence that infection with
T. vaginalis
augments HIV acquisition with 50%. Diagnosis and treatment of
T. vaginalis
infection in both high-risk and low-risk individuals may be a potential tool to reduce new HIV infections.

Trial registration number

CRD42018082702
Donald Douglas Lawson
Authors: Clayton‐Jones Gary , Crispin Sheila , Gibbs Christine , Grimes Terry , Renwick Peter
Published: October 2018

With specialisation in its infancy, Professor Donald Lawson was instrumental in the initiation and development of a number of RCVS diplomas as well as the BVA's canine health schemes.
Capacity to adhere to and invade human epithelial cells, as related to the presence of virulence genes in, motility of, and biofilm formation ofCampylobacter jejunistrains isolated from chicken and cattle
Authors: Farfán Mauricio , Lártiga Natalia , Benavides María Belén , Alegría-Morán Raúl , Sáenz Leonardo , Salcedo Cristal , Lapierre Lisette
Published: October 2018

Campylobacter jejuni is a zoonotic pathogen transmitted through the “farm to fork” route. Outbreaks are generally associated with the consumption of chicken meat; however, dairy cows, birds, wild and domestic food animals, and pets are other important sources. Currently, there are not enough data comparing the virulence of strains isolated from these reservoirs. In this study, we compared C. jejuni strains isolated from broiler chickens and dairy cattle by determining their ability to adhere to and invade in vitro human colonic epithelial cells in the T84 cell line with their motility, formation of biofilms, and presence of eight virulence genes. A Wilcoxon Rank Sum test was performed to establish the relationship between presence of the studied genes and cellular invasion and adhesion, as well as differences between the animal species of origin of the isolate. A Spearman correlation was performed to assess the relationship between invasion and motility, along with invasion and biofilm generation. The virB11 gene was positively associated with the adherence capacity of the strains (mean difference = 0.21, p = 0.006), and strains isolated from chickens showed a significant difference for adherence compared with strains isolated from cattle (p = 0.0001). Our results indicate that strains of C. jejuni have a difference in their adherence capacity depending on the animal reservoir from which they came, with chicken isolates displaying higher virulence than dairy cattle isolates.
Adsorption behavior of O2 on vacancy-defected graphene with transition-metal dopants: A theoretical study
Authors: Zhou Qingxiao , Yong Yongliang , Su Xiangying , Ju Weiwei , Fu Zhibing , Li Xiaohong
Published: October 2018

The influence of vacancy and dopants on the adsorption of O2 molecule on graphene was explored by using the density functional theory (DFT) method. The results indicated that the presence of vacancy-defect improved the sensitivity of graphene toward the O2 molecule. Furthermore, the two O atoms of O2 molecule separately formed chemical bonds with C atoms at the defect sites. After introducing the transition-metal (TM) dopants, the O–O bond length of O2 molecule was enlarged by the adsorption on the surface of graphene. Furthermore, the Mn-doped adsorption complexes became magnetic, which was mainly contributed by the O-2p and Mn-3d orbitals.
ACM BCB 2018
Authors: Staff ACM
Published: October 2018

ACM BCB served as the international forum concerned with Bioinformatics, Computational Biology and Health Informatics event. It involves biologist, computer scientists, clinicians and computer engineer researchers to discuss about problems in bioinformatics, healthcare, biological and health related algorithms.
ACM BCB 2018 awards
Authors: Staff ACM
Published: October 2018

The ACM Best Paper Award went to Miya Govek, Camden Sikes,Layla Oesper in recognition of the Best Paper, "A Consensus Approach to Infer Tumor Evolutionary Histories".
SIGCSE launches new conference on a global scale
Authors: Impagliazzo John , Zhang Ming , Wu Xi
Published: October 2018

Hear Ye! Hear Ye! Hear Ye! Did you know that SIGCSE has launched a new conference on a global scale? It's the ACM Global Computing Education Conference, also known as ACM CompEd. This new event is destined to become a leading global conference on computing education. At the intersection of computing and the learning sciences, the CompEd seeks to promote global computing education development. The plan is to hold CompEd every two years in parts of the world not regularly served by SIGCSE conferences.
On the Properties of Neutrinos
Authors: Balantekin A. Baha , Kayser Boris
Published: October 2018

This article reviews our present understanding of neutrino properties with a particular emphasis on observable differences between Majorana and Dirac neutrinos. We summarize current and future experimental efforts toward measuring neutrino properties and describe consequences of the Majorana versus Dirac nature of neutrinos on neutrino masses, neutrino decays, and neutrino electromagnetic properties.
Heavy Ion Collisions: The Big Picture and the Big Questions
Authors: Busza Wit , Rajagopal Krishna , van der Schee Wilke
Published: October 2018

Heavy ion collisions quickly form a droplet of quark–gluon plasma (QGP) with a remarkably small viscosity. We give an accessible introduction to how to study this smallest and hottest droplet of liquid made on Earth and why it is so interesting. The physics of heavy ion collisions ranges from highly energetic quarks and gluons described by perturbative QCD to a bath of strongly interacting gluons at lower energy scales. These gluons quickly thermalize and form QGP, while the energetic partons traverse this plasma and end in a shower of particles called jets. Analyzing the final particles in various ways allows us to study the properties of QGP and the complex dynamics of multiscale processes in QCD that govern its formation and evolution, providing what is perhaps the simplest form of complex quantum matter that we know of. Much remains to be understood, and throughout the review big open questions are encountered.
Diabetes mellitus attenuates the pressure response against hypotensive stress by impairing the sympathetic regulation of the baroreflex afferent arc
Authors: Kamada Kazuhiro , Saku Keita , Tohyama Takeshi , Kawada Toru , Mannoji Hiroshi , Abe Kiyokazu , Nishikawa Takuya , Sunagawa Genya , Kishi Takuya , Sunagawa Kenji , Tsutsui Hiroyuki
Published: October 2018

Patients with diabetes mellitus (DM) often show arterial pressure (AP) lability associated with cardiovascular autonomic neuropathy. Because the arterial baroreflex tightly regulates AP via sympathetic nerve activity (SNA), we investigated the systematic baroreflex function, considering the control theory in DM by open-loop analysis. We used Zucker diabetic fatty (ZDF) rats as a type 2 DM model. Under general anesthesia, we isolated the carotid sinuses from the systemic circulation, changed intracarotid sinus pressure (CSP), and recorded SNA and AP responses. We compared CSP-AP (total loop), CSP-SNA (afferent arc), and SNA-AP (efferent arc) relationships between ZDF lean ( n = 8) and ZDF fatty rats ( n = 6). Although the total loop gain of baroreflex (ΔAP/ΔCSP) at the operating point did not differ between the two groups, the average gain in the lower CSP range was markedly reduced in ZDF fatty rats (0.03 ± 0.01 vs. 0.87 ± 0.10 mmHg/mmHg, P < 0.001). The afferent arc showed the same trend as the total loop, with a response threshold of 139.8 ± 1.0 mmHg in ZDF fatty rats. There were no significant differences in the gain of efferent arc between the two groups. Simulation experiments indicated a markedly higher AP fall and lower total loop gain of baroreflex in ZDF fatty rats than in ZDF lean rats against hypotensive stress because the efferent arc intersected with the afferent arc in the SNA unresponsive range. Thus, we concluded that impaired baroreflex sympathetic regulation in the lower AP range attenuates the pressure response against hypotensive stress and may partially contribute to AP lability in DM.

NEW & NOTEWORTHY In this study, we investigated the open-loop baroreflex function, considering the control theory in type 2 diabetes mellitus model rats to address the systematic mechanism of arterial pressure (AP) lability in diabetes mellitus. The unresponsiveness of baroreflex sympathetic regulation in the lower AP range was observed in type 2 diabetic rats. It may attenuate the baroreflex pressure-stabilizing function and induce greater AP fall against hypotensive stress.
IL-13 promotes in vivo neonatal cardiomyocyte cell cycle activity and heart regeneration
Authors: Wodsedalek Dylan J. , Paddock Samantha J. , Wan Tina C. , Auchampach John A. , Kenarsary Aria , Tsaih Shirng-Wern , Flister Michael J. , O’Meara Caitlin C.
Published: October 2018

There is great interest in identifying signaling mechanisms by which cardiomyocytes (CMs) can enter the cell cycle and promote endogenous cardiac repair. We have previously demonstrated that IL-13 stimulated cell cycle activity of neonatal CMs in vitro. However, the signaling events that occur downstream of IL-13 in CMs and the role of IL-13 in CM proliferation and regeneration in vivo have not been explored. Here, we tested the role of IL-13 in promoting neonatal CM cell cycle activity and heart regeneration in vivo and investigated the signaling pathway(s) downstream of IL-13 specifically in CMs. Compared with control, CMs from neonatal IL-13 knockout (IL-13−/−) mice showed decreased proliferative markers and coincident upregulation of the hypertrophic marker brain natriuretic peptide ( Nppb) and increased CM nuclear size. After apical resection in anesthetized newborn mice, heart regeneration was significantly impaired in IL-13−/− mice compared with wild-type mice. Administration of recombinant IL-13 reversed these phenotypes by increasing CM proliferation markers and decreasing Nppb expression. RNA sequencing on primary neonatal CMs treated with IL-13 revealed activation of gene networks regulated by ERK1/2 and Akt. Western blot confirmed strong phosphorylation of ERK1/2 and Akt in both neonatal and adult cultured CMs in response to IL-13. Our data demonstrated a role for endogenous IL-13 in neonatal CM cell cycle and heart regeneration. ERK1/2 and Akt signaling are important pathways known to promote CM proliferation and protect against apoptosis, respectively; thus, targeting IL-13 transmembrane receptor signaling or administering recombinant IL-13 may be therapeutic approaches for activating proregenerative and survival pathways in the heart.

NEW & NOTEWORTHY Here, we demonstrate, for the first time, that IL-13 is involved in neonatal cardiomyocyte cell cycle activity and heart regeneration in vivo. Prior work has shown that IL-13 promotes cardiomyocyte cell cycle activity in vitro; however, the signaling pathways were unknown. We used RNA sequencing to identify the signaling pathways activated downstream of IL-13 in cardiomyocytes and found that ERK1/2 and Akt signaling was activated in response to IL-13.
Folic Acid and Vitamin B12 Supplementation and the Risk of Cancer: Long-term Follow-up of the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) Trial
Authors: Oliai Araghi Sadaf , Kiefte-de Jong Jessica C. , van Dijk Suzanne C. , Swart Karin M.A. , van Laarhoven Hanneke W. , van Schoor Natasja M. , de Groot Lisette C.P.G.M. , Lemmens Valery , Stricker Bruno H. , Uitterlinden André G. , van der Velde Nathalie
Published: October 2018

Background:

Folic acid and vitamin B12 play key roles in one-carbon metabolism. Disruption of one-carbon metabolism may be involved in the risk of cancer. Our aim was to assess the long-term effect of supplementation with both folic acid and vitamin B12 on the incidence of overall cancer and on colorectal cancer in the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) trial.

Methods:

Long-term follow-up of B-PROOF trial participants (N = 2,524), a multicenter, double-blind randomized placebo-controlled trial designed to assess the effect of 2 to 3 years daily supplementation with folic acid (400 μg) and vitamin B12 (500 μg) versus placebo on fracture incidence. Information on cancer incidence was obtained from the Netherlands cancer registry (Integraal Kankercentrum Nederland), using the International Statistical Classification of Disease (ICD-10) codes C00–C97 for all cancers (except C44 for skin cancer), and C18–C20 for colorectal cancer.

Results:

Allocation to B vitamins was associated with a higher risk of overall cancer [171 (13.6%) vs. 143 (11.3%); HR 1.25; 95% confidence interval (CI), 1.00–1.53, P = 0.05]. B vitamins were significantly associated with a higher risk of colorectal cancer [43(3.4%) vs. 25(2.0%); HR 1.77; 95% CI, 1.08–2.90, P = 0.02].

Conclusions:

Folic acid and vitamin B12 supplementation was associated with an increased risk of colorectal cancer.

Impact:

Our findings suggest that folic acid and vitamin B12 supplementation may increase the risk of colorectal cancer. Further confirmation in larger studies and in meta-analyses combining both folic acid and vitamin B12 are needed to evaluate whether folic acid and vitamin B12 supplementation should be limited to patients with a known indication, such as a proven deficiency.
Accuracy of a Novel Histoplasmosis Enzyme Immunoassay to Evaluate Suspicious Lung Nodules
Authors: Deppen Stephen A. , Massion Pierre P. , Blume Jeffrey , Walker Ronald C. , Antic Sanja , Chen Heidi , Durkin Michele M. , Wheat L. Joseph , Grogan Eric L.
Published: October 2018

Background:

Granulomas caused by infectious lung diseases present as indeterminate pulmonary nodules (IPNs) on radiography. Newly available serum enzyme immunoassay (EIA) for histoplasmosis has not been studied for the evaluation of IPNs. We investigated serum biomarkers of histoplasmosis antibodies as an indication of benign disease in IPNs from a highly endemic region.

Methods:

A total of 152 serum samples from patients presenting with pulmonary nodules ≤30 mm in maximum diameter were analyzed for histoplasmosis antibodies by immunodiffusion and EIA IgG and IgM tests. Serology and FDG-PET/CT scan diagnostic test characteristics were estimated and compared.

Results:

Cancer prevalence was 55% (n = 83). Thirty-nine (26%) individuals were positive for IgG histoplasmosis antibodies. Twelve samples were IgM antibody positive. Immunodiffusion serology was similar to IgM antibody results with 13 positive tests. Diagnostic likelihood ratios for benign disease were 0.62, 0.33, and 0.28 for FDG-PET/CT, IgG, and IgM antibodies, respectively. When both IgG and IgM were positive (n = 8), no nodules were cancerous and six were FDG-PET/CT avid.

Conclusions:

A positive EIA test for both IgM and IgG strongly suggested histoplasmosis etiology and benign granuloma for 12% of benign nodules arising from a highly endemic region. Presence of either IgG or IgM histoplasma antibodies was associated with benign disease. The EIA test was more sensitive in assessing histoplasma exposure than immunodiffusion serology.

Impact:

A new CLIA-certified histoplasmosis antibody EIA test measures histoplasmosis exposure, offers a possible alternative clinical diagnosis for benign IPNs, and may improve IPN evaluation while avoiding harmful invasive biopsies.
STAT3 Inhibition Combined with CpG Immunostimulation Activates Antitumor Immunity to Eradicate Genetically Distinct Castration-Resistant Prostate Cancers
Authors: Moreira Dayson , Adamus Tomasz , Zhao Xingli , Su Yu-Lin , Zhang Zhuoran , White Seok Voon , Swiderski Piotr , Lu Xin , DePinho Ronald A. , Pal Sumanta K. , Kortylewski Marcin
Published: October 2018

Purpose:

Prostate cancers show remarkable resistance to emerging immunotherapies, partly due to tolerogenic STAT3 signaling in tumor-associated myeloid cells. Here, we describe a novel strategy combining STAT3 inhibition with Toll-like Receptor 9 (TLR9) stimulation to unleash immune response against prostate cancers regardless of the genetic background.

Experimental Design:

We developed and validated a conjugate of the STAT3 antisense oligonucleotide (ASO) tethered to immunostimulatory TLR9 agonist (CpG oligonucleotide) to improve targeting of human and mouse prostate cancer and myeloid immune cells, such as myeloid-derived suppressor cells (MDSC).

Results:

CpG-STAT3ASO conjugates showed improved biodistribution and potency of STAT3 knockdown in target cells in vitro and in vivo. Systemic administration of CpG-STAT3ASO (5 mg/kg) eradicated bone-localized, Ras/Myc-driven, and Ptenpc−/−Smad4pc−/−Trp53c−/− prostate tumors in the majority of treated mice. These antitumor effects were primarily immune-mediated and correlated with an increased ratio of CD8+ to regulatory T cells and reduced pSTAT3+/PD-L1+ MDSCs. Both innate and adaptive immunity contributed to systemic antitumor responses as verified by the depletion of Gr1+ myeloid cells and CD8+ and CD4+ T cells, respectively. Importantly, only the bifunctional CpG-STAT3ASO, but not control CpG oligonucleotides, STAT3ASO alone, or the coinjection of both oligonucleotides, succeeded in recruiting neutrophils and CD8+ T cells into tumors. Thus, the concurrence of TLR9 activation with STAT3 inhibition in the same cellular compartment is indispensable for overcoming tumor immune tolerance and effective antitumor immunity against prostate cancer.

Conclusions:

The bifunctional, immunostimulatory, and tolerance-breaking design of CpG-STAT3ASO offers a blueprint for the development of effective and safer oligonucleotide strategies for treatment of immunologically “cold” human cancers.
A Rare Delayed Bladder Migration of a Hem-o-lok Clip 5 Years after Robotic-Assisted Radical Prostatectomy
Authors: Chen Yu-Chen , Chen Hao-Wei , Lee Cheng-Hsueh , Huang Shu-Pin
Published: October 2018

Bladder migration of a Hem-o-lok® clip, due to robotic-assisted radical prostatectomy (RARP), is uncommon, and would form a foreign body in the bladder and present as lower urinary tract symptoms after the early postoperative period. We hereby report a rare, delayed appearance of a secondary bladder stone due to the migration of a Hem-o-lok® clip that occurred 5 years after RARP.