bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility of anorectal chlamydia testing in women: a cross-sectional survey among general practitioners
Authors: Derckx Raissa T , Rinsma Sygriet , Dukers-Muijrers Nicole H T M , AB Elisabeth , van Bergen Jan , de Bont Eefje , Hoebe Christian J P A , Cals Jochen W L
Published: March 2021

Background

Anorectal Chlamydia trachomatis (CT) may be clinically relevant for women in general practice. Although anorectal CT testing in this setting may prevent underdiagnosis and undertreatment, its feasibility is questioned as GPs currently rarely order anorectal CT tests, for yet unknown reasons.

Objective

To explore the feasibility of anorectal CT testing in women in general practice.

Methods

GPs across the Netherlands were invited directly (n = 1481) and by snowball sampling (n = 330) to join an online cross-sectional survey that asked about the acceptability of and barriers for (standard) anorectal testing in women during CT-related consultations. Data were analysed with univariable and multivariable logistic regression models.

Results

The questionnaire was opened by 514 respondents (28%, 514/1811) and 394 fully completed it. GPs’ acceptability of anorectal testing by either self-sampling or provider-sampling was high (86%). Twenty-eight percent of GPs felt neutral, and 43% felt accepting towards standard anorectal testing. Nevertheless, 40% of GPs had never tested for anorectal CT in women, which was associated with a reported difficulty in asking about anal sex (odds ratio [OR]: 3.07, 95% confidence interval [CI]: 1.21–7.80), infrequency of anal sexual history taking (OR: 11.50, 95% CI: 6.39–20.72), low frequency of urogenital CT testing (OR 3.44, 95%-CI: 1.86–6.38) and with practicing in a non-urban area (OR: 2.27, 95% CI: 1.48–3.48). Acceptability of anorectal testing was not associated with the studied factors.

Conclusion

This quantitative survey shows that anorectal CT testing is feasible based on its acceptability, but is likely hindered by a lower awareness of (anorectal) CT in GPs.
A dimensionality reduction technique for unconstrained global optimization of functions with low effective dimensionality
Authors: Cartis Coralia , Otemissov Adilet
Published: March 2021

We investigate the unconstrained global optimization of functions with low effective dimensionality, which are constant along certain (unknown) linear subspaces. Extending the technique of random subspace embeddings in Wang et al. (2016, J. Artificial Intelligence Res., 55, 361–387), we study a generic Random Embeddings for Global Optimization (REGO) framework that is compatible with any global minimization algorithm. Instead of the original, potentially large-scale optimization problem, within REGO, a Gaussian random, low-dimensional problem with bound constraints is formulated and solved in a reduced space. We provide novel probabilistic bounds for the success of REGO in solving the original, low effective-dimensionality problem, which show its independence of the (potentially large) ambient dimension and its precise dependence on the dimensions of the effective and embedding subspaces. These results significantly improve existing theoretical analyses by providing the exact distribution of a reduced minimizer and its Euclidean norm and by the general assumptions required on the problem. We validate our theoretical findings by extensive numerical testing of REGO with three types of global optimization solvers, illustrating the improved scalability of REGO compared with the full-dimensional application of the respective solvers.
Immunoglobulin G Immune Complexes May Contribute to Neutrophil Activation in the Course of Severe Coronavirus Disease 2019
Authors: Mazzitelli Ignacio , Bleichmar Lucia , Ludueña María Guillermina , Pisarevsky Andrea , Labato Mariana , Chiaradia Verónica , Finocchieto Paola , Paulin Francisco , Hormanstorfer Macarena , Baretto María Constanza , Adanza Santiago Piombi , Parodi María Noel , Ragusa Martín , Melucci Claudia , Díaz Fernando Erra , Paletta Ana , Di Diego Facundo , Ceballos Ana , Geffner Jorge
Published: March 2021

Severe coronavirus disease 2019 (COVID-19) is associated with an overactive inflammatory response mediated by macrophages. Here, we analyzed the phenotype and function of neutrophils in patients with COVID-19. We found that neutrophils from patients with severe COVID-19 express high levels of CD11b and CD66b, spontaneously produce CXCL8 and CCL2, and show a strong association with platelets. Production of CXCL8 correlated with plasma concentrations of lactate dehydrogenase and D-dimer. Whole blood assays revealed that neutrophils from patients with severe COVID-19 show a clear association with immunoglobulin G (IgG) immune complexes. Moreover, we found that sera from patients with severe disease contain high levels of immune complexes and activate neutrophils through a mechanism partially dependent on FcγRII (CD32). Interestingly, when integrated in immune complexes, anti–severe acute respiratory syndrome coronavirus 2 IgG antibodies from patients with severe COVID-19 displayed a higher proinflammatory profile compared with antibodies from patients with mild disease. Our study suggests that IgG immune complexes might promote the acquisition of an inflammatory signature by neutrophils, worsening the course of COVID-19.
Differential T-Cell Reactivity to Endemic Coronaviruses and SARS-CoV-2 in Community and Health Care Workers
Authors: da Silva Antunes Ricardo , Pallikkuth Suresh , Williams Erin , Dawen Yu Esther , Mateus Jose , Quiambao Lorenzo , Wang Eric , Rawlings Stephen A , Stadlbauer Daniel , Jiang Kaijun , Amanat Fatima , Arnold David , Andrews David , Fuego Irma , Dan Jennifer M , Grifoni Alba , Weiskopf Daniela , Krammer Florian , Crotty Shane , Hoffer Michael E , Pahwa Savita G , Sette Alessandro
Published: March 2021

Herein we measured CD4+ T-cell responses against common cold coronaviruses (CCC) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in high-risk health care workers (HCW) and community controls. We observed higher levels of CCC-reactive T cells in SARS-CoV-2–seronegative HCW compared to community donors, consistent with potential higher occupational exposure of HCW to CCC. We further show that SARS-CoV-2 T-cell reactivity of seronegative HCW was higher than community controls and correlation between CCC and SARS-CoV-2 responses is consistent with cross-reactivity and not associated with recent in vivo activation. Surprisingly, CCC T-cell reactivity was decreased in SARS-CoV-2–infected HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses, either directly or indirectly. This result was unexpected, but consistently detected in independent cohorts derived from Miami and San Diego.

CD4+ T-cell responses against common cold coronaviruses (CCC) are elevated in SARS-CoV-2 seronegative high-risk health care workers (HCW) compared to COVID-19 convalescent HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses and/or cross-reactivity associated with a protective effect.
Rotavirus Genotype Trends and Gastrointestinal Pathogen Detection in the United States, 2014–2016: Results From the New Vaccine Surveillance Network
Authors: Esona Mathew D , Ward M Leanne , Wikswo Mary E , Rustempasic Slavica M , Gautam Rashi , Perkins Charity , Selvarangan Rangaraj , Harrison Christopher J , Boom Julie A , Englund Janet A , Klein Eileen J , Staat Mary Allen , McNeal Monica M , Halasa Natasha , Chappell James , Weinberg Geoffrey A , Payne Daniel C , Parashar Umesh D , Bowen Michael D
Published: March 2021

Background

Following the implementation of rotavirus vaccination in 2006, severe acute gastroenteritis (AGE) due to group A rotavirus (RVA) has substantially declined in US children. We report the RVA genotype prevalence as well as coinfection data from 7 US New Vaccine Surveillance Network sites during 3 consecutive RVA seasons, 2014–2016

Methods

A total of 1041 stool samples that tested positive for RVA by Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention (CDC) for RVA genotyping and multipathogen testing.

Results

A total of 795 (76%) samples contained detectable RVA when tested at the CDC. Rotavirus disease was highest in children < 3 years of age. Four G types (G1, G2, G9, and G12) accounted for 94.6% of strains while 2 P types (P[4] and P[8]) accounted for 94.7% of the strains. Overall, G12P[8] was the most common genotype detected in all 3 seasons. Stepwise conditional logistic analysis found year and study site were significant predictors of genotype. Twenty-four percent of RVA-positive specimens contained other AGE pathogens.

Conclusions

G12P[8] predominated over 3 seasons, but strain predominance varied by year and study site. Ongoing surveillance provides continuous tracking and monitoring of US genotypes during the postvaccine era.
Bioelectronics in the brain–gut axis: focus on inflammatory bowel disease (IBD)
Authors: Stakenborg Nathalie , Boeckxstaens Guy E
Published: March 2021

Accumulating evidence shows that intestinal homeostasis is mediated by cross-talk between the nervous system, enteric neurons and immune cells, together forming specialized neuroimmune units at distinct anatomical locations within the gut. In this review, we will particularly discuss how the intrinsic and extrinsic neuronal circuitry regulates macrophage function and phenotype in the gut during homeostasis and aberrant inflammation, such as observed in inflammatory bowel disease (IBD). Furthermore, we will provide an overview of basic and translational IBD research using these neuronal circuits as a novel therapeutic tool. Finally, we will highlight the different challenges ahead to make bioelectronic neuromodulation a standard treatment for intestinal immune-mediated diseases.
Presence of HIV-1 G-to-A mutations linked to APOBEC editing is more prevalent in non-B HIV-1 subtypes and is associated with lower HIV-1 reservoir
Authors: Abdi Basma , Lambert-Niclot Sidonie , Wirden Marc , Jary Aude , Teyssou Elisa , Sayon Sophie , Palich Romain , Tubiana Roland , Simon Anne , Valantin Marc-Antoine , Katlama Christine , Morand-Joubert Laurence , Calvez Vincent , Marcelin Anne-Geneviève , Soulie Cathia
Published: March 2021

Objectives

APOBEC3 editing activity contributes to sequences variation and viral diversification. We aimed to characterize virological and clinical factors associated with G-to-A mutations and stop codons in the HIV-1 reservoir, markers of APOBEC3 footprints, in order to better understand HIV-1 diversity among virologically suppressed HIV-1-infected patients.

Methods

Immuno-virological and clinical factors were compared between 92 patients harbouring G-to-A mutations and stop codons (APOBEC+) in the reverse transcriptase gene and 92 patients without G-to-A mutations (APOBEC–) and stop codons in their DNA genotypes.

Results

Patients were predominantly men (74.5%) and were mostly infected by B-subtype (69.0%), with 44.1% and 55.9% in APOBEC+ and APOBEC– groups, respectively. At time of HIV DNA genotypes, the total cell-associated HIV-1 DNA load was 2.34 log10 copies/106 cells (IQR 1.85–2.67) and 33.2% of them had a detectable ultrasensitive plasma viral load. Hypermutated sequences were identified in 28.2% of the APOBEC+ group. The median total cell-associated HIV-1 DNA level was significantly lower in APOBEC+ than APOBEC– group: 2.13 log10 copies/106 cells (IQR 1.60–2.60) versus 2.52 log10 copies/106 cells (IQR 2.19–2.71) (P < 0.001), respectively. Presence of G-to-A mutations and stop codon was independently associated with HIV-1 subtype non-B (P = 0.017).

Conclusions

These results show an independent association between the presence of G-to-A mutations and stop codons with HIV-1 subtype non-B and low proviral DNA that could be explained by the APOBEC3 footprints and restriction of DNA synthesis and integration. However, further investigations are needed to study the contribution of Vif amino acid variability among HIV-1 subtypes.
High level of HIV drug resistance informs dolutegravir roll-out and optimized NRTI backbone strategy in Mozambique
Authors: Carnimeo V , Pulido Tarquino I A , Fuentes S , Vaz D , Molfino L , Tamayo Antabak N , Cuco R M , Couto A , Lobo S , de Amaral Fidelis J , Mulassua J S , Ciglenecki I , Ellman T , Schramm B
Published: March 2021

Background

HIV drug resistance (HIV-DR) is rising in sub-Saharan Africa in both ART-naive and ART-experienced patients.

Objectives

To estimate the level of acquired DR (ADR) and pre-treatment DR (PDR) across selected urban and rural sites in Southern Africa, in Mozambique.

Methods

We conducted two cross-sectional surveys among adult HIV patients (October 2017–18) assessing ADR and PDR. In the (ADR) survey, those on NNRTI-based first-line ART for ≥6 months were recruited (three sites). In the PDR survey, those ART-naive or experienced with ≥3 months of treatment interruption prior were enrolled (eight sites).

Results

Among 1113 ADR survey participants 83% were receiving tenofovir (TDF)/lamivudine (3TC)/efavirenz (EFV). The median time on ART was 4.5 years (Maputo) and 3.2 years (Tete), 8.3% (95% CI 6.2%-10.6%, Maputo) and 15.5% (Tete) had a VL ≥ 1000 copies/mL, among whom 66% and 76.4% had NNRTI+NRTI resistance, and 52.8% and 66.7% had 3TC+TDF-DR. Among those on TDF regimens, 31.1% (Maputo) and 42.2% (Tete) were still TDF susceptible, whereas 24.4% and 11.5% had TDF+zidovudine (ZDV)-DR. Among those on ZDV regimens, 25% and 54.5% had TDF+ZDV-DR. The PDR survey included 735 participants: NNRTI-PDR was 16.8% (12.0–22.6) (Maputo) and 31.2% (26.2–36.6) (Tete), with a higher proportion (≥50%) among those previously on ART affected by PDR.

Conclusions

In Mozambique, viral failure was driven by NNRTI and NRTI resistance, with NRTI DR affecting backbone options. NNRTI-PDR levels surpassed the WHO 10% ‘alert’ threshold. Replacing NNRTI first-line drugs is urgent, as is frequent viral load monitoring and resistance surveillance. Changing NRTI backbones when switching to second-line regimens may need reconsideration.
Dose rate in the highest irradiation area of the rectum correlates with late rectal complications in patients treated with high-dose-rate computed tomography-based image-guided brachytherapy for cervical cancer
Authors: Isohashi Fumiaki , Akino Yuichi , Matsumoto Yuri , Suzuki Osamu , Seo Yuji , Tamari Keisuke , Sumida Iori , Sawada Kenjiro , Ueda Yutaka , Kobayashi Eiji , Tomimatsu Takuji , Nakanishi Erina , Nishi Takahisa , Kimura Tadashi , Ogawa Kazuhiko
Published: March 2021

The purpose of this study was to evaluate the effect of dose rate to the rectum on late rectal complications in patients treated with computed tomography (CT)-based image-guided brachytherapy (IGBT) for cervical cancer. The subjects were 142 patients with cervical cancer who underwent Ir-192 high-dose-rate (HDR)-IGBT between March 2012 and January 2018. The dose rate to the rectum was calculated using in-house software. The minimum, mean and maximum effective dose rate (EDR) was calculated for voxels of the rectal volume covered by cumulative doses >D0.1cc, >D2cc, and > D5cc. The average EDR of three to four brachytherapy sessions was calculated (EDR for patients; EDRp). The total dose of the rectum was calculated as the biologically equivalent dose in 2-Gy fractions (EQD2). The associations between EDRp for D0.1cc, D2cc, and D5cc and the respective rectal EQD2 values with late rectal complications were then analyzed. The median follow-up period was 40 months. Patients with rectal complications of ≥Grade 1 received a significantly higher mean EDRp for D0.1cc–5cc and had a greater EQD2 for D0.1cc–5cc. Multivariate analysis was performed using the mean EDRp for D2cc, EQD2 for D2cc, heavy smoking and BMI. Of these four variables, mean EDRp for D2cc (HR = 3.38, p = 0.004) and EQD2 for D2cc (HR = 2.59, p = 0.045) emerged as independent predictors for late rectal complications. In conclusion, mean EDRp and EQD2 were associated with late rectal complications in patients treated with HDR CT-based IGBT for cervical cancer.
Safeguarding Vulnerable Autonomy? Situational Vulnerability, the Inherent Jurisdiction, and Insights from Feminist Philosophy
Authors: Lewis Jonathan
Published: March 2021

The High Court continues to exercise its inherent jurisdiction to make declarations about interventions into the lives of situationally vulnerable adults with mental capacity. In the light of the protective responses of health care providers and the courts to decision-making situations involving capacitous vulnerable adults, this article has two aims. The first is diagnostic. The second is normative. The first aim is to identify the harms to a capacitous vulnerable adult’s autonomy that arise based on the characterisation of situational vulnerability and autonomy as fundamentally opposed concepts or the failure to adequately acknowledge the conceptual relationship between them at common law. The second (normative) aim is to develop an account of self-authorised, intersubjective autonomy based on insights from analytic feminist philosophy. This approach not only attempts to capture the autonomy of capacitous vulnerable adults and account for the necessary harms to their autonomy that arise from standard common law responses to their situational vulnerability, it is also predicated on the distinctions between mental capacity, informed consent, and autonomy, meaning that it is better placed to fulfil the primary aim of the inherent jurisdiction—to facilitate the autonomy of vulnerable adults with capacity.
Hypermetabolism and impaired cerebrovascular reactivity beyond the standard MRI-identified tumor border indicate diffuse glioma extended tissue infiltration
Authors: Sebök Martina , van Niftrik Christiaan Hendrik Bas , Muscas Giovanni , Pangalu Athina , Seystahl Katharina , Weller Michael , Regli Luca , Fierstra Jorn
Published: March 2021

Background

Diffuse gliomas exhibit diffuse infiltrative growth, often beyond the magnetic resonance imaging (MRI)-detectable tumor lesion. Within this lesion, hypermetabolism and impaired cerebrovascular reactivity (CVR) are found, but its exact distribution pattern into the peritumoral environment is unknown. Our aim was to better characterize the extent of diffuse glioma tissue infiltration, beyond the visible lesion (ie, beyond the T1-contrast-enhancing lesion and/or T2/FLAIR-defined tumor border), with metabolic positron emission tomography (PET), and functional MRI CVR (blood oxygenation-level-dependent CVR [BOLD-CVR]) mapping.

Methods

From a prospective glioma database, 18 subjects (19 datasets) with diffuse glioma (n = 2 with anaplastic astrocytoma, n = 10 with anaplastic oligodendroglioma, and n = 7 with glioblastoma) underwent a BOLD-CVR and metabolic PET study between February 2016 and September 2019, 7 of them at primary diagnosis and 12 at tumor recurrence. In addition, 19 matched healthy controls underwent an identical BOLD-CVR study. The tumor lesion was defined using high-resolution anatomical MRI. Volumes of interest starting from the tumor lesion outward up to 30 mm were created for a detailed peritumoral PET and BOLD-CVR tissue analysis. Student’s t test was used for statistical analysis.

Results

Patients with diffuse glioma exhibit impaired BOLD-CVR 12 mm beyond the tumor lesion (P = .02) with normalization of BOLD-CVR values after 24 mm. Metabolic PET shows a difference between the affected and contralateral hemisphere of 6 mm (P = .05) with PET values normalization after 12 mm.

Conclusion

We demonstrate hypermetabolism and impaired CVR beyond the standard MRI-defined tumor border, suggesting active tumor infiltration in the peritumoral environment.
Soil hydraulics affect the degree of isohydricity
Authors: Javaux Mathieu , Carminati Andrea
Published: March 2021

A soil–plant hydraulic model shows that the degree of isohydricity is constrained by below-ground hydraulic limitations and that the shape of plant water potential (WP) curve depends on soil hydraulics.
Cut-off value to identify a flare using the Flare Assessment in Rheumatoid Arthritis (FLARE-RA) questionnaire: analysis of the TOSCA study
Authors: Aouad Krystel , Gaudin Philippe , Vittecoq Olivier , Morel Jacques , Berthelot Jean-Marie , Senbel Eric , Schaeverbeke Thierry , Lioté Frédéric , Flipo René-Marc , Pinta Alexandrine , Guillemin Francis , Fautrel Bruno
Published: March 2021

Objective

The Flare Assessment in RA (FLARE-RA) self-administered questionnaire aims to identify patients who had flare in the interval between two consultations. This study aimed to establish a threshold for FLARE-RA score to identify RA flare.

Methods

The Tocilizumab SubCutAneous study evaluated the efficacy and safety of s.c. tocilizumab (TCZ) to patients with active RA. Disease activity was assessed with the DAS28ESR at baseline and at week 2 (W2), W4, W12 and W24. The FLARE-RA questionnaire was administered at W12 and W24. Patient satisfaction, assessed at baseline and W24 with the Patient Acceptable Symptom State (PASS), was used as a surrogate marker of no flare. A correlation was sought between the FLARE-RA score at W12 and W24 and the area under the receiver operating characteristic (ROC) curve (AUC) for monthly DAS28ESR. The optimal FLARE-RA cut-off below which patient satisfaction reached the PASS was explored with an ROC curve.

Results

A total of 139 patients were included (mean age 57.3 ± 13.8 years, 74.1% women, mean RA duration 10.8 ± 9.2 years, mean DAS28ESR 5.8 ± 1.1). The correlation between the FLARE-RA score and DAS28ESR AUC was moderate at all times: ρ = 0.41 at W12 (P < 0.0001) and 0.51 at W24 (P < 0.0001). The optimal cut-off for the FLARE-RA score to identify absence of flare (i.e. an acceptable situation based on the PASS) was 2.3 with an AUC of 0.81.

Conclusion

FLARE-RA and DAS28ESR assessment differ; we propose a FLARE-RA cut-off of 2.3, below which the situation (i.e. without flare) is acceptable for patients.
Relevant domains and outcome measurement instruments in neuropsychiatric systemic lupus erythematosus: a systematic literature review
Authors: Silvagni Ettore , Chessa Elisabetta , Bergossi Francesca , D’Amico Maria Ester , Furini Federica , Guerrini Giulio , Cauli Alberto , Scirè Carlo Alberto , Bertsias George , Govoni Marcello , Piga Matteo , Bortoluzzi Alessandra
Published: March 2021

Objectives

Although neuropsychiatric involvement in SLE (NPSLE) is one of the most complex and troubling manifestations of the disease, validated outcome instruments to be used as sensitive endpoints in controlled clinical trials are lacking. We performed a systematic literature review (SLR) to identify outcome measurement instruments and domains used to assess NPSLE.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used. Articles available in English (1967–2020), listed in PubMed, Embase, PsycINFO, Cochrane Library and the EULAR outcome measures library were screened. All domains and outcome measurement instruments were characterized according to the OMERACT Filter 2.1, considering core areas (manifestations/abnormalities, life impact, death/lifespan, societal/resource use) and contextual factors.

Results

Of 3392 abstracts evaluated, 83 studies were included in the SLR (15 974 patients, females 89.9%). Eligible studies included domains and instruments pertinent to all core areas defined by the OMERACT, except for ‘societal/resource use’. The most common core areas were ‘manifestations/abnormalities’, covering 10 domains pertinent to laboratory and instrumental markers, indexes and neuropsychiatric dimension (cognitive, neurologic and psychiatric field), and ‘life impact’, covering 7 domains related to physical function (from both the perspective of the patient and the physician), pain and quality of life.

Conclusion

Our study revealed great heterogeneity in the instruments derived from populations with NPSLE and none of these had high-quality evidence. This supports the need to develop and further validate a core domain set and outcome measurement instruments to promote clinical research in this field, enhancing comparability across studies.
Labor’s Capital and Worker Well-Being: Do US Pension Funds Benefit Labor Interests?
Authors: Liu Larry , Goldstein Adam
Published: March 2021

Since the 1980s, the shareholder value revolution has undermined the position of workers and organized labor within US firms. At the same time, workers have paradoxically become one of the largest classes of shareholders through labor pension funds (LPF), including state public employee funds and private sector union-affiliated funds. Does workers’ concentrated ownership of capital in LPF represent a mechanism to advance worker interests against the prevailing wage, benefit, and jobs squeeze in publicly traded firms? This article links data on US state pension funds’ investments and shareholder activism to firm-level data on work and employment outcomes from 2001–2016. LPF shareholder proposals targeting large firms have declined over time. However, panel regression models show that intra-firm mobilization by LPF in the form of shareholder proposals is associated with modestly improved worker outcomes. There is no evidence that greater ownership share by public pension funds (PPF) is associated with more labor-friendly outcomes. This null association obtains even when focusing only on ownership by the most socially activist funds, or those from Democrat-controlled states. Nor does PPF ownership buffer workers from the negative impact of extractive hedge funds. Together, the results help reconcile contending accounts of pension fund capitalism’s effects on worker well-being. The analysis contributes to the sociological study of financialization, corporate governance, work and employment, and labor movements.
HIV increases sleep-based brain age despite antiretroviral therapy
Authors: Leone Michael J , Sun Haoqi , Boutros Christine L , Liu Lin , Ye Elissa , Sullivan Lee , Thomas Robert J , Robbins Gregory K , Mukerji Shibani S , Westover M Brandon
Published: March 2021

Study Objectives

Age-related comorbidities and immune activation raise concern for advanced brain aging in people living with HIV (PLWH). The brain age index (BAI) is a machine learning model that quantifies deviations in brain activity during sleep relative to healthy individuals of the same age. High BAI was previously found to be associated with neurological, psychiatric, cardiometabolic diseases, and reduced life expectancy among people without HIV. Here, we estimated the effect of HIV infection on BAI by comparing PLWH and HIV− controls.

Methods

Clinical data and sleep EEGs from 43 PLWH on antiretroviral therapy (HIV+) and 3,155 controls (HIV−) were collected from Massachusetts General Hospital. The effect of HIV infection on BAI, and on individual EEG features, was estimated using causal inference.

Results

The average effect of HIV on BAI was estimated to be +3.35 years (p < 0.01, 95% CI = [0.67, 5.92]) using doubly robust estimation. Compared to HIV− controls, HIV+ participants exhibited a reduction in delta band power during deep sleep and rapid eye movement sleep.

Conclusion

We provide causal evidence that HIV contributes to advanced brain aging reflected in sleep EEG. A better understanding is greatly needed of potential therapeutic targets to mitigate the effect of HIV on brain health, potentially including sleep disorders and cardiovascular disease
Clinical Uncertainty and Equipoise in the Management of Recurrent Glioblastoma
Authors: Patel Mukt , Au Karolyn , Davis Faith G. , Easaw Jacob C. , Mehta Vivek , Broad Robert , Chow Michael M.C. , Hockley Aaron , Kaderali Zul , Magro Elsa , Nataraj Andrew , Scholtes Felix , Chagnon Miguel , Gevry Guylaine , Raymond Jean , Darsaut Tim E.
Published: March 2021

Background:

A significant proportion of glioblastoma (GBM) patients are considered for repeat resection, but evidence regarding best management remains elusive. Our aim was to measure the degree of clinical uncertainty regarding reoperation for patients with recurrent GBM.

Methods:

We first performed a systematic review of agreement studies examining the question of repeat resection for recurrent GBM. An electronic portfolio of 37 pathologically confirmed recurrent GBM patients including pertinent magnetic resonance images and clinical information was assembled. To measure clinical uncertainty, 26 neurosurgeons from various countries, training backgrounds, and years’ experience were asked to select best management (repeat surgery, other nonsurgical management, or conservative), confidence in recommended management, and whether they would include the patient in a randomized trial comparing surgery with nonsurgical options. Agreement was evaluated using κ statistics.

Results:

The literature review did not reveal previous agreement studies examining the question. In our study, agreement regarding best management of recurrent GBM was slight, even when management options were dichotomized (repeat surgery vs. other options; κ=0.198 [95% confidence interval: 0.133-0.276]). Country of practice, years’ experience, and training background did not change results. Disagreement and clinical uncertainty were more pronounced within clinicians with (κ=0.167 [0.055-0.314]) than clinicians without neuro-oncology fellowship training (κ=0.601 [0.556-0.646]). A majority (51%) of responders were willing to include the patient in a randomized trial comparing repeat surgery with nonsurgical alternatives in 26/37 (69%) of cases.

Conclusion:

There is sufficient uncertainty and equipoise regarding the question of reoperation for patients with recurrent glioblastoma to support the need for a randomized controlled trial.
Modulation of Metacognitive Confidence Judgments Through Provision of Performance Feedback in Moderate to Severe Traumatic Brain Injury
Authors: Chiou Kathy S. , Klecha Holly , Jones Megan , Dobryakova Ekaterina
Published: March 2021

Objective:

Traumatic brain injury (TBI) may result in metacognitive impairments. Enhancing memory in healthy adults can improve metacognitive accuracy, but it is unclear whether such interventions apply to individuals with TBI. This study examined the effects of manipulating target memory experiences on metacognitive accuracy in TBI.

Participants:

Fourteen community-dwelling adults with TBI and 17 healthy controls.

Main Measures:

Memory was manipulated through performance feedback (monetary, nonmonetary, or none) presented during a word-pair learning task. Recognition of the word pairs was assessed, and metacognition was evaluated by retrospective confidence judgments.

Results:

Both groups demonstrated greater recognition performance for items learned with nonmonetary feedback. Healthy individuals demonstrated improved metacognitive accuracy for items learned with nonmonetary feedback, but this effect was not seen in individuals with TBI. A notable (but statistically nonsignificant) effect was observed whereby adults with TBI overestimated performance for items learned with monetary feedback compared with other feedback conditions.

Conclusion:

Provision of feedback during learning enhances recognition performance. However, target memory experiences may be utilized differently after injury to facilitate confidence judgments. In addition, the type of feedback provided may have different effects on metacognitive accuracy. These results have implications for rehabilitative efforts in the area of memory and metacognition after injury.
Microsporidial Stromal Keratitis: Epidemiological Features, Slit-Lamp Biomicroscopic Characteristics, and Therapy
Authors: Matoba Alice , Goosey John , Chévez-Barrios Patricia
Published: March 2021

Purpose:

Microsporidial stromal keratitis is a rare form of infectious keratitis, with only 7 cases reported in the United States to date. This study was performed to evaluate risk factors, clinical features, and response to therapy.

Methods:

A retrospective review of the medical records of all patients diagnosed with microsporidial stromal keratitis seen in the practices of the authors between 1999 and 2020 was performed. Diagnosis was determined by cytology or histopathology in corneal specimens. Risk factors, presence or absence of distinctive clinical features, and response to medical and surgical therapies were recorded.

Results:

Nine patients—7M:2F, aged 7 to 99 years—with microsporidial stromal keratitis were identified. Exposures to recreational water and hymenopteran insect bites, both epidemiologically linked risk factors for systemic microsporidial infection, were identified in our patients. Presence of stromal edema with features of disciform keratitis and a distinctive granular keratitis were observed in 6 of 9 and 5 of 9 patients, respectively. Poor response to medical therapy was noted. Penetrating keratoplasty was effective in curing the infection. Final visual acuity was 20/40 or better in 6 of 9 patients.

Conclusions:

In patients with slowly progressive keratitis, history of exposure to recreational water or hymenopteran insects should be sought. In patients with corneal edema consistent with disciform keratitis, with evolution to a granular keratitis, microsporidia should be considered in the differential diagnosis. In cases of established microsporidial stromal keratitis, penetrating keratoplasty should be considered if prompt response to medical therapy is not noted.
Ophthalmic Presentation and Outcomes for Malignant Sinonasal Tumors
Authors: Vahdani Kaveh , Rose Geoffrey E.
Published: March 2021

Purpose:

To evaluate the ophthalmic clinical features and functional outcomes for patients with malignant sinonasal tumors who initially presented with orbital symptoms.

Patients and Methods:

Retrospective chart review for patients seen at Moorfields Eye Hospital between 1997 and 2020. Patient demographics and clinical features, radiology, histology, and treatment outcomes were reviewed.

Results:

Forty patients (22 females; 55%) with sinonasal cancers first presented to an ophthalmologist at an average age of 53.9 years (median 56; range 8–92 years), with their having had first symptoms at 53.6 years (median 55.8; range 7.8–91.9 years). The commonest symptoms were persistent periorbital ache (19/40; 48%), periocular swelling (18; 45%), proptosis (16; 40%), and diplopia (15; 38%). All midface tumors affected only 1 orbit, and 13 of 40 (33%) eyes presented with an acuity of 20/60 or worse—5 having no perception of light—and 10 eyes (25%) had a relative afferent pupillary defect. An average of 4.5 mm relative exophthalmos was present (median 4 mm; range 0–9 mm), and a palpable mass in 19 of 40 (48%) orbits. Reduced eye movements and nonaxial displacement were recorded in 29 (73%) and 34 (85%) patients, respectively, and 9 (23%) had an abnormal optic disc or fundus. Bone erosion affected 95% of orbits, and almost a half had involvement of the neighboring extraocular muscles, orbital apex, or intracranially. The commonest tumor groups were sinonasal carcinomas (45%), sarcomas (28%), or lymphomas (11%). Of 37 globe-sparing treatments, 25 (68%) had persistence of previously impaired ophthalmic functions and 6 of 37 (16%) developed new impairment; only 6 of 37 (16%) of affected orbits retained normal function, and 6 patients lost all vision on the affected side.

Conclusions:

Sinonasal malignancies that present with orbital invasion are probably at the more aggressive end of the cancer spectrum, might be expected to carry a worse prognosis, and usually arise from the ethmoid or maxillary sinuses. In our series, carcinomas and sarcomas were the commonest malignancies, with similar 5-year overall survivals (of just over 50%), and over three-quarters of patients developed permanent impairment of orbital function and/or visual loss.
The Contribution of Material, Behavioral, Psychological, and Social-Relational Factors to Income-Related Disparities in Cardiovascular Risk Among Older Adults
Authors: Lee Chiyoung , Yang Qing , Im Eun-Ok , McConnell Eleanor Schildwachter , Jung Sin-Ho , Kim Hyeoneui
Published: March 2021

Background

Understanding the factors underlying health disparities is vital to developing strategies to improve health equity in old age. Such efforts should be encouraged in Korea.

Objective

This study explored how material, behavioral, psychological, and social-relational factors contribute to income-related disparities in cardiovascular risk among Korean adults 65 years and older.

Methods

This was a secondary analysis of Korean National Health and Nutrition Examination Survey data (2013–2017), targeting 7347 older adults (≥65 years). Socioeconomic position, defined as income, was the primary indicator. The outcome was binary for predicted cardiovascular risk (<90 vs ≥90 percentile). Disparities were measured using relative index of inequality (RII). The contributions of material, behavioral, psychological, and social-relational factors were estimated by calculating percentage reduction in RII when adjusted for these factors.

Results

Among men aged 65 to 74 years and women 75 years or older, the largest reductions in RII were achieved after adjusting for social-relational factors. Among men 75 years or older and women aged 65 to 74 years, adjusting for material factors resulted in the largest reductions in RII. Adjustments for behavioral factors also reduced RII for both genders aged 65 to 74 years.

Conclusions

Improving the social, material, and behavioral circumstances of lower-income older adults may help address income-related disparities in cardiovascular risk in old age.
Carotid Web and Ischemic Stroke: A Primer for Nursing
Authors: Sutherly Loretta J. , Wasserman Jessica , Haussen Diogo C.
Published: March 2021

BACKGROUND: Carotid artery web may cause ischemic stroke and affects a vulnerable population of mostly younger patients. Multiple treatment options and lack of diagnostic consensus can cause confusion and reduce the likelihood to follow the recommended follow-up care. METHODS: We reviewed relevant literature using the following keywords: carotid web, CW, risk factors, stroke, treatments, education, incidence, prevalence, diagnostics, and nursing care. RESULTS: CW is commonly missed or misdiagnosed, which has led to scarce prevalence data. It has been reported to potentially represent approximately 0.5% of all ischemic strokes; however, after appropriate workup of patients with no clear stroke etiology, as many as 9.4% to 37% were found to have CW. This fibrotic shelflike lesion in the internal carotid bifurcation leads to flow disruption and possible thrombus formation. Treatment options include dual antiplatelets and anticoagulation or more invasive options such as revascularization with surgical excision or stenting, but research remains limited on which could be most beneficial. CONCLUSION: With multiple options and the uncertainty of which are best, patients can be lost to follow-up because of confusion and stress. Involving neuroscience nurses in the education process of these patients may help facilitate understanding of this disease phenomenon and increase patient understanding and compliance.
Profound Sudden Sensorineural Hearing Loss in Hematologic Malignancy: A Case for Urgent Cochlear Implantation With Discussion and Systematic Review of the Literature
Authors: Dumberger Lukas D. , Hwa Tiffany P. , Panara Kush , Husain Solomon , Yver Christina , Bigelow Douglas C.
Published: March 2021

Objective:

To perform a systematic review of sensorineural hearing loss (SNHL) in hematologic malignancy; to describe an illustrative case of urgent cochlear implantation for bilateral profound SNHL and vestibular hypofunction in hyperviscosity syndrome; to suggest an approach to management of hyperviscosity syndrome-associated deafness with cochlear implantation.

Data Sources:

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, systematic search of PubMed and Embase databases was undertaken for articles detailing clinical information about SNHL caused directly by hematologic malignancies.

Results:

A total of 37 studies from 1989 to 2020 were qualitatively reviewed, the majority of which were case studies or case series. Causes of hearing loss in hematologic malignancy were found to include hyperviscosity syndrome, labyrinthine hemorrhage, infiltration, and infection. Patients with profound SNHL in hematologic malignancies from hyperviscosity syndrome may be candidates for cochlear implantation, and are also at increased risk for cochlear ossification. We review previous cases for their diagnostic approach, treatment paradigm, and outcomes data, and propose an approach to management.

Conclusion:

Bilateral sudden profound SNHL and vestibular hypofunction is a presenting symptom of hyperviscosity syndrome in hematologic malignancy. Although this entity is rare and previous reports have suggested improvement in hearing with oncologic treatment, cases with profound hearing loss are unlikely to recover serviceable hearing. We advocate for early magnetic resonance imaging with attention to fluid signal in the inner ear and serial audiometric follow-up to guide clinical decisions. We advise early consideration for cochlear implantation.
The Mutual Effects of Perceived Spiritual Needs on Quality of Life in Patients With Advanced Cancer and Family Caregivers
Authors: Huang Li-Ting , Tai Chun-Yi , Longcoy Joshua , McMillan Susan C.
Published: March 2021

Perceived spiritual needs may increase when patients with advanced cancer and their family caregivers are confronted with the challenges of physical and psychological distress. Given the intertwined relationships between patients and family caregivers, their interdependence should be considered to understand how perceived spiritual needs affect the quality of life of their own and of their partner. This study used the Actor-Partner Interdependence Model as the conceptual model to investigate the mutual effects of perceived spiritual needs on the quality of life in patients with advanced cancer and their family caregivers after being admitted to hospice. This cross-sectional study used the baseline data of a large clinical trial and identified that patients with cancer and their family caregivers perceived similar spiritual needs associated with the community and outlook needs and had fewer unmet spiritual needs. After controlling for partner effects, perceived outlook needs shown in patients significantly predicted their own functional well-being and social/spiritual well-being. Outlook and community needs perceived by family caregivers also significantly predicted their own mental health. Although partner effects were not shown as expected, the findings provide insight into the mutuality of spirituality and demonstrate the necessity of providing timely and ongoing spiritual assessment and care.
Congenital Syphilis: A Case Report Demonstrating Missed Opportunities for Screening and Inadequate Treatment Despite Multiple Health Care Encounters During Pregnancy
Authors: Fukuda Acasia , Katz Alan R. , Park Ina U. , Komeya Alan Y. , Chang Ann , Ching Natascha , Tomas Juval E. , Wasserman Glenn M.
Published: March 2021

A case of congenital syphilis due to multiple missed opportunities, highlights the challenges of treating syphilis during pregnancy. Although cases are increasing in the United States, congenital syphilis, a disease with devastating consequences, is preventable.
A Comparison of Treponema pallidum Subspecies pallidum Molecular Typing Systems: Multilocus Sequence Typing vs. Enhanced Centers for Disease Control and Prevention Typing
Authors: Sahi Sharon K. , Zahlan Jana M. , Tantalo Lauren C. , Marra Christina M.
Published: March 2021

Background

At least 3 syphilis typing systems are proposed. Recent work suggests that multilocus sequence typing (MLST) may be superior to enhanced Centers for Disease Control and Prevention typing (ECDCT) by yielding a higher discriminatory power. The goal of this study was to compare the 2 systems and identify associations between neurosyphilis and strain types.

Methods

Multilocus sequence typing for tp0136, tp0548, and tp0705 was determined for DNA from 78 Treponema pallidum subspecies pallidum isolates propagated in rabbits, 10 oral and 10 genital or non-genital lesion swabs, and 10 blood samples from patients with syphilis. These samples were chosen because they were completely typeable by ECDCT. Using both systems, association between strain types and neurosyphilis, defined as a reactive cerebrospinal fluid Venereal Disease Research Laboratory test, was determined. Partial and complete ECDCT types were also determined for samples from different anatomical sites in 35 patients, and from blood and blood isolates (rabbit propagated) from 13 patients.

Results

The MLST type could be fully determined for 100 (92.6%) of 108 samples. Although MLST subdivided 3 common ECDCT types, it failed to distinguish among others. Neurosyphilis was more common in individuals infected with type 1.1.2 and tp0705 type 2 using MLST, and tp0548 type f using ECDCT. Enhanced Centers for Disease Control and Prevention typing was stable among anatomical sites and between patient-derived and rabbit propagated organisms.

Conclusions

Compared with ECDCT, MLST was not uniformly more discriminating. Both typing systems demonstrate that specific types may be more neurotropic than others.
Rectal Douching and Anal Human Papillomavirus Among Young Men Who Have Sex With Men in China
Authors: Li Peiyang , Fan Song , Yuan Tanwei , Ouyang Lin , Gong Hui , Ding Yi , Luo Zhenzhou , Yu Maohe , Wu Guohui , Zou Huachun
Published: March 2021

Background

Young men who have sex with men (YMSM) are particularly at increased risk for human papillomavirus (HPV) infection and related malignancies. Rectal douching, commonly practiced among MSM, has been associated with HIV, chlamydia, gonorrhea, and viral hepatitis in cross-sectional studies. We conducted this study to understand the association between self-reported rectal douching and anal HPV among YMSM in China.

Methods

Between September 2018 and March 2019, MSM aged 15 to 24 years who ever engaged in receptive anal intercourse over the last 3 months were recruited via community-based organizations and centers for disease control located in 4 cities in China. Participants were asked to complete an online survey. We performed multivariate logistic regression adjusted for potential confounders to examine the association between self-reported rectal douching and anal HPV.

Results

Among 273 MSM with a median age of 20 years (interquartile range, 19–21 years) included in this study, 130 (47.6%) practiced rectal douching during the preceding 3 months and 96 (36.2%) were infected with anal HPV. Self-reported rectal douching was found to be associated with increased odds of anal HPV infection (odds ratio, 2.16; 95% confidence interval, 1.22–3.82) among YMSM, after adjusting for age, sexual debut, sex with alcohol or drugs, and HIV testing history.

Conclusions

Self-reported rectal douching is associated with higher odds of anal HPV infection independent of sexual behaviors among YMSM. More prospective studies to ascertain this association are needed. Health education materials should inform men of the potential risk of rectal douching. Research on safer rectal douching procedures is warranted.