bluuebunny/crossref_metadata_2025 huggingface dataset:
“You’re Always Jumping Through Hoops”: Journey Mapping the Care Experiences of Individuals With Opioid Use Disorder-associated Endocarditis
Authors: Bearnot Benjamin , Mitton Julian A.
Published: March 2020

Objectives:

Serious infectious complications of opioid use disorder (OUD), and specifically endocarditis, are becoming more common in the US. Individuals with OUD-associated endocarditis require long periods of complex medical care, often face recurrent addiction- and infection-related complications, and have dismal clinical outcomes. The objective of this study was to perform journey mapping analysis to capture common trajectories and patterns of care for people with OUD-associated endocarditis.

Methods:

This was an analysis of qualitative semi-structured interviews of individuals who received care for OUD-associated endocarditis. Interviews were conducted among individuals receiving care at a single academic healthcare system in Boston, Massachusetts. Ten participants meeting DSM-5 criteria for at least mild OUD and a culture-positive diagnosis of endocarditis who had previously completed care for OUD-associated endocarditis were recruited from inpatient and ambulatory settings. Details of participant's care episodes were extracted and visualized in an iterative journey mapping process. A grounded theory approach was then used to identify shared themes and care patterns among participants’ journey maps.

Results:

Common patterns of care included early addiction treatment and intensive outpatient care preceding periods without rehospitalization, while leaving outpatient care and return to drug use often directly preceded rehospitalization. Participants frequently left care by choice and proactively reengaged with care.

Conclusions:

Journey mapping is a novel, patient-centered approach to capturing the care experiences and trajectories of a patient population experiencing significant stigma, who engage with the healthcare system in unexpected and fragmented ways. For individuals with OUD-associated endocarditis, we identified critical moments to support and engage patients to prevent return to drug use and rehospitalization.
A new modular external fixator: A retrospective review
Authors: Khalily Camille , Seligson David , Frangie Robert
Published: March 2020

The Dolphix is a new external fixation system consisting of relatively few components. Its modular nature allows for a variety of possible configurations, making it useful for the treatment of many types of fractures. The fixator can be adjusted after it is placed in order to improve either patient comfort or fracture reduction, and the device can be removed at the bedside under light sedation with no need for additional instrumentation. During the first year of experience with this device at our level I trauma center, fixator times have been relatively short and there have been no equipment failures or pin-tract problems. The Dolphix is a reasonable alternative to some of the more complex and costly external fixation systems currently available.
Skeletal muscle disease in rheumatoid arthritis: the center of cardiometabolic comorbidities?
Authors: Andonian Brian J. , Huffman Kim M.
Published: March 2020

Purpose of review

Despite its critical roles in body movement, structure, and metabolism, skeletal muscle remains underappreciated in the context of rheumatoid arthritis. In rheumatoid arthritis, chronic inflammation, physical inactivity, and medication toxicities impair skeletal muscle. These skeletal muscle alterations contribute to continued rheumatoid arthritis disparities in physical function and cardiometabolic health.

Recent findings

In the prebiologic disease-modifying antirheumatic drug era, rheumatoid arthritis skeletal muscle atrophy was the central feature of ‘rheumatoid cachexia,’ a hypermetabolic state driven by chronic systemic inflammation and muscle protein degradation. In the current era, rheumatoid arthritis muscle deficits are less visible, yet persist as a key component of ‘sarcopenic obesity.’ In rheumatoid arthritis sarcopenic obesity, chronic inflammation, physical inactivity, and medication toxicities contribute to muscle contractile deficits, inflammation, altered metabolism, and intramuscular adiposity, a key predictor of rheumatoid arthritis disability and insulin resistance.

Rheumatoid arthritis skeletal muscle disease in the current era is defined by impaired contractile function (poor strength and endurance) and sarcopenic obesity (decreased muscle mass, increased fat mass, and intramuscular adiposity). These muscle impairments contribute to disability and cardiometabolic disease in rheumatoid arthritis. Management should focus on monitoring of rheumatoid arthritis muscle function and body composition, limiting potentially myotoxic drugs, and prescription of exercise training.
New galaxies in the universe of shared decision-making and rheumatoid arthritis
Authors: Barton Jennifer L. , Décary Simon
Published: March 2020

Purpose of review

Implementing shared decision-making (SDM) is a top international priority to improve care for persons living with rheumatoid arthritis. Using SDM tools, such as decision aids improve patients’ knowledge and support communication with their clinicians on treatment benefits and risks. Despite calls for SDM in treat-to-target, studies demonstrating effective SDM strategies in rheumatology clinical practice are scarce. Our objective was to identify recent and relevant literature on SDM in rheumatoid arthritis.

Recent findings

We found a burgeoning literature on SDM in rheumatoid arthritis that tackles issues of implementation. Studies have evaluated the SDM process within clinical consultations and found that uptake is suboptimal. Trials of newly developed patient decision aids follow high methodological standards, but large-scale implementation is lacking. Innovative SDM strategies, such as shared goals and preference phenotypes may improve implementation of treat-to-target approach. Research and patient engagement are standardizing measures of SDM for clinical uses.

Uptake of SDM in rheumatoid arthritis holds promise in wider clinicians’ and patients’ awareness, availability of decision aids, and broader treat-to-target implementation strategies, such as the learning collaborative. Focused attention is needed on facilitating SDM among diverse populations and those at risk of poorer outcomes and barriers to communication.
Influence of passive smoking on the onset of Legg-Calvè-Perthes disease: a systematic review and meta-analysis
Authors: Gao Huanhuan , Huang Zeqing , Jia Zhaoxu , Ye Hengli , Fu Fanyu , Song Mengge , Zhao Yan , Chen Weiheng
Published: March 2020

The relationship between passive smoking and the onset of Legg-Calvè-Perthes disease is still controversial. Therefore, we conducted the study to systematically evaluate and analyze the relationship. A comprehensive search was conducted. Meta-analysis was performed with RevMan 5.3 software, with the odds ratio as the effect size. Eight English articles with a total of 1379 Legg-Calvè-Perthes disease patients were eventually included. Passive smoking type of family members smoking in indoor (odds ratio = 2.53), paternal smoking (odds ratio = 2.76), maternal smoking (odds ratio = 2.02), maternal smoking during pregnancy (odds ratio = 1.68), using stove indoor (odds ratio = 2.56) are statistically significant (P < 0.05). For the family members smoking indoor, region may be a confounding factor (European group I
2 = 92%, odds ratio = 2.51; USA group I

2
= 5%, odds ratio = 3.26; and Asian group I
2 = 0%, odds ratio = 2.25). In addition, the type of maternal smoking (odds ratio = 0.80, for 1–10 per day; odds ratio = 2.73, for 10–20 per day; odds ratio = 2.78, for >20 per day) and the type of maternal smoking during pregnancy (odds ratio = 1.36, for 1–9 per day; odds ratio = 2.02, for ≥10 per day) may show a dose-effect relationship. Passive smoking is a risk factor for the onset of Legg-Calvè-Perthes disease, but the specific types of passive smoking (haze, etc.), dose, dose-effect relationship, regional confounding, pathological mechanisms, etc. also require clinicians and researchers to continue exploring.
Higher ICU Capacity Strain Is Associated With Increased Acute Mortality in Closed ICUs*
Authors: Wilcox M. Elizabeth , Harrison David A. , Patel Akshay , Rowan Kathryn M.
Published: March 2020

Objectives:

To determine whether patients admitted to an ICU during times of strain, when compared with its own norm (i.e. accommodating a greater number of patients, higher acuity of illness, or frequent turnover), is associated with a higher risk of death in ICUs with closed models of intensivist staffing.

Design:

We conducted a large, multicenter, observational cohort study. Multilevel mixed effects logistic regression was used to examine relationships for three measures of ICU strain (bed census, severity-weighted bed census, and activity-weighted bed census) on the day of admission with risk-adjusted acute hospital mortality.

Setting:

Pooled case mix and outcome database of adult general ICUs participating in the Intensive Care National Audit and Research Centre Case Mix Programme.

Measurements and Main Results:

The analysis included 149,310 patients admitted to 215 adult general ICUs in 213 hospitals in United Kingdom, Wales, and Northern Ireland. A relative lower strain in ICU capacity as measured by bed census on the calendar day (daytime hours) of admission was associated with decreased risk-adjusted acute hospital mortality (odds ratio, 0.94; 95% CI, 0.90–0.99; p = 0.01), whereas a nonsignificant association was seen between higher strain and increased acute hospital mortality (odds ratio, 1.04; 95% CI, 1.00–1.10; p = 0.07). The relationship between periods of high ICU strain and acute hospital mortality was strongest when bed census was composed of higher acuity patients (odds ratio, 1.05; 95% CI, 1.01–1.10; p = 0.03). No relationship was seen between high strain and ICU mortality.

Conclusions:

In closed staffing models of care, variations in bed census within individual ICUs was associated with patient’s predicted risk of acute hospital mortality, particularly when its standardized bed census consisted of sicker patients.
Challenges and opportunities for hepatitis B cure in the setting of HIV--hepatitis B virus co-infection
Authors: Audsley Jennifer , Sasadeusz Joe
Published: March 2020

Purpose of review

To examine issues specific to HIV--HBV co-infection that are relevant to the search for and achieving hepatitis B cure in this the setting

Recent findings

In HIV--HBV co-infection, high rates of hepatitis B surface antigen (HBsAg) loss early after initiation of HBV-active antiretroviral therapy (ART) have previously been reported. Between 2012 and 2016, HBsAg loss from 2.8 to 23% was reported in numerous studies, including those already on suppressive HBV-active ART. Data published in 2018–2019 show that these rates have remained fairly stable (3.0–13.9%). However, it appears that higher HBsAg loss on starting HBV-active ART in co-infection falls within a few years to levels similar to that observed in long-term treated HBV mono-infection. Immune reconstitution and CD4+ T-cell recovery are likely to play a role in high HBsAg loss rates seen in early treated co-infection, although the mechanisms driving this are yet to be fully elucidated.

High rates of HBsAg loss early after HBV-active ART initiation is unique to HIV--HBV co-infection, making it the ideal setting to investigate underlying mechanisms of HBV loss and develop new HBV cure strategies. This phenomenon could be used to enhance HBsAg loss with new therapeutic approaches currently being investigated; however, this is obstructed by excluding co-infection from such studies.
Family history of premature myocardial infarction modifies the associations between bilateral oophorectomy and cardiovascular disease mortality in a US national cohort of postmenopausal women
Authors: Appiah Duke , Nwabuo Chike C. , Owoade Damilola R. , Samad Jaffer , Ebong Imo , Winters Stephen J.
Published: March 2020

Objective:

To test the hypothesis that a family history of premature myocardial infarction (FHPMI) will modify the associations between bilateral salpingo-oophorectomy (BSO) and mortality due to heart disease (HD), cardiovascular disease (CVD), or all-cause mortality with stronger associations observed for BSO occurring before 45 years.

Methods:

We analyzed data from 2,763 postmenopausal women aged 40 years or older who participated in the National Health and Nutrition Examination Survey (1988-1994) and were followed through December 31, 2015. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality outcomes (HD, CVD, and all-cause).

Results:

At baseline, the average age was 62 years. There were 610 women with BSO, 338 women with FHPMI, and 95 women with both BSO and FHPMI. During a median follow-up of 22 years, 1,713 deaths occurred of which 395 and 542 were attributed to HD and CVD, respectively. In models adjusting for CVD risk factors and hormone therapy use, HD mortality was greater among women with both BSO and FHPMI compared to those without either of these conditions (HR: 2.88, 95% CI: 1.72-4.82, P
Interaction = 0.016). HD mortality was higher among women with FHPMI and BSO at an earlier age (<45 y: HR: 4.32, 95% CI: 1.95-9.50 vs ≥45 y: HR: 1.60, 95% CI: 0.63-4.09). Similar observations were seen for CVD and all-cause mortality.

Conclusions:

In this study, the risk of HD, CVD, and all-cause mortality in women with BSO was modified by an FHPMI with the risk limited to women undergoing BSO at younger ages.
Recommendations for blood pressure measurement in large arms in research and clinical practice: position paper of the European society of hypertension working group on blood pressure monitoring and cardiovascular variability
Authors: Palatini Paolo , Asmar Roland , O’Brien Eoin , Padwal Raj , Parati Gianfranco , Sarkis Josh , Stergiou George
Published: March 2020

Blood pressure measurement in obese individuals can be challenging because of the difficulty in properly cuffing large upper arms. Achieving a proper cuff fit can be problematic especially in people with a shorter arm length relative to circumference. This expert statement provides recommendations on blood pressure measurement in large arms for clinical use and research purposes. Tronco-conically shaped cuffs should be used in people with large arms, especially with arm circumferences greater than 42 cm as they better fit on the conical arm shape. Cuffs with frustum of the cone slant angle of 85° should satisfy most conditions. In individuals with short upper-arm that does not allow application of a properly sized cuff, wrist or forearm measurement might be used in clinical practice, but not for validation of automatic devices. Wide-range cuffs coupled to oscillometric devices provided with special software algorithms can also be used as alternatives to standard cuff measurement, provided they are independently validated per AAMI/ISO 81060-2 protocol. For validation studies, the intraarterial measurement is generally considered as the gold standard, yet for possible methodological pitfalls and ethical concerns, it is not recommended as the method of choice. Tronco-conical cuffs with inflatable bladder dimensions of 37–50 × 75–100% arm circumference should be used for reference auscultatory blood pressure measurement wherever the upper arm length allows a proper fit. There is a need for future studies that help identify the optimal shape of cuffs and bladders investigating the influence of sex, age, arm physical properties, and artery characteristics.
Differential impact of psychological and psychophysical stress on low back pain in mice
Authors: La Porta Carmen , Tappe-Theodor Anke
Published: March 2020

Low back pain (LBP) is a highly prevalent and disabling condition whose initiating factors are poorly understood. It is known that psychological and physical stress is associated with LBP but the causal relationship, mechanisms, and mediators have not been elucidated, and a preclinical model enabling the investigation of causality and thereby critically contributing to clinical translation does not exist. In this study, we first established and characterized a myofascial LBP model in mice based on nerve growth factor (NGF) injection into the low back muscles. Second, we investigated the effect of 2 different stress paradigms on this mouse LBP model by applying the chronic unpredictable stress and vertical chronic restraint stress (vCRS) paradigms, to mimic psychological and psychophysical stress, respectively. In these studies, we combined longitudinal behavioral tests with gene and protein expression analysis in the muscle, dorsal root ganglia, and spinal cord. Nerve growth factor-induced LBP was characterized by long-lasting local and plantar mechanical hypersensitivity, cold hyperalgesia, decreased grip strength and wheel running activity, and time-dependent changes of neuropeptide and glial markers in the spinal cord. Interestingly, the exposure to chronic unpredictable stress slightly worsened pain behavior, whereas vCRS primed and highly aggravated pain in this LBP model, by causing per se the intramuscular upregulation of endogenous NGF and increased spinal astrocyte expression. Our mouse model, particularly the combination of NGF injection and vCRS, suggests that similar mechanisms are important in nonspecific LBP and might help to investigate certain aspects of stress-induced exacerbation of pain.
Radiation enteritis: from diagnosis to management
Authors: Hale Melissa Fay
Published: March 2020

Purpose of review

As cancer treatments improve more patients than ever are living for longer with the side effects of these treatments. Radiation enteritis is a heterogenous condition with significant morbidity. The present review aims to provide a broad overview of the condition with particular attention to the diagnosis and management of the condition.

Recent findings

Radiation enteritis appears to be more prevalent than originally thought because of patient underreporting and a lack of clinician awareness. Patient-related and treatment-related risk factors have now been identified and should be modified where possible. Medical and surgical factors have been explored, but manipulation of the gut microbiota offers one of the most exciting recent developments in disease prevention. Diagnosis and treatment are best approached in a systematic fashion with particular attention to the exclusion of recurrent malignancy and other gastrointestinal conditions. Surgery and endoscopy both offer opportunities for management of the complications of radiation enteritis. Experimental therapies offer hope for future management of radiation enteritis but large-scale human trials are needed.

Radiation enteritis is an important clinical problem, but awareness is lacking amongst patients and physicians. Clinical guidelines would allow standardised management which may improve the burden of the disease for patients.
Body Composition Using Air Displacement Plethysmography in Children With Inflammatory Bowel Disease
Authors: Dhaliwal Jasbir , Martincevic Inez , Williams Brock , Frost Karen , Uusoue Krista , Arpino Valerie , Church Peter , Walters Thomas D. , Griffiths Anne M. , Mouzaki Marialena
Published: March 2020

Objective:

The aim of the study was to assess the body composition of children with inflammatory bowel disease (IBD) and to study the accuracy of clinically available tools in predicting excess body fatness. We aimed at also exploring the influence of adiposity on pharmacokinetics during early Infliximab exposure.

Methods:

Prospective cohort study in 5‐ to 17‐year‐old children with IBD initiating Infliximab therapy. Patient demographic, phenotypic, and laboratory data at the time of Infliximab initiation were recorded. Body composition was assessed using air displacement plethysmography (ADP). fat mass index (FMI = fat mass [kg]/(height [m])2) was calculated to determine excess adiposity (defined as FMI ≥75th centile). Anthropometrics (weight, height, mid upper arm circumference [MUAC] and triceps skin fold thickness [TSF]) were obtained and MUAC and TSF measurements were used to calculate arm fat area (AFA) and arm muscle area z‐scores. Statistical analysis was applied as appropriate.

Results:

Fifty‐three (68% male; 55% Crohn disease [CD], 45% ulcerative colitis [UC], median [IQR] age 15 [13–16] years) children with IBD were included. Twenty‐four percentage of children with IBD (21% CD, 29% UC) had excess adiposity. Four children (31%) with FMI ≥75th centile were not identified by body mass index (BMI) alone (kappa of 0.60), and 2 children (15%) were not identified by AFA z‐score alone. The intra‐ and interobserver reliability of MUAC and TSFT measurements was excellent. There was no difference in Infliximab trough levels at the end of induction between those with FMI less than or ≥75th centile.

Conclusions:

Excess adiposity affects approximately 1 in 4 young patients with IBD and can be missed by routine obesity screening. Our exploratory study did not raise concerns of underexposure to infliximab in those children with excess adiposity during early drug exposure.
Rules Are Meant to Be Broken
Authors: Clark Susannah J. , Staffa Steven J. , Ngo Peter D. , Yasuda Jessica L. , Zendejas Benjamin , Hamilton Thomas E. , Jennings Russell W. , Manfredi Michael A.
Published: March 2020

Background and Aims:

The “rule of 3” is a 40‐year‐old expert opinion that suggests dilating an esophageal stricture more than 3 mm is unsafe. Few studies have evaluated this tenet, and do not specify how much larger than 3 mm is reasonable. Our aim was to determine the optimal point for maximum dilation diameter with acceptable risk in a pediatric population.

Methods:

A retrospective review in pediatric patients with esophageal strictures was performed. The number of millimeters the stricture was dilated, defined as delta dilation diameter (ΔDD), was determined by subtracting the initial stricture diameter from the diameter of the largest balloon used. Receiver operating characteristic curve analysis was used to evaluate the discriminatory ability of ΔDD. Youden J index was used to identify optimal cut‐point in predicting perforation.

Results:

Two hundred eighty‐four patients underwent 1384 balloon dilations. Overall perforation rate was 1.66%. There were 8 perforations in 1075 dilations with ΔDD ≤5 mm (0.7%) and 15 perforations in 309 dilations with ΔDD >5 mm (4.9%). Youden J index found an optimal cutoff to be at a ΔDD of ≤5 mm. The cumulative rate of perforation for all dilations ≤5 mm was 0.74% whereas the cumulative risk of perforation for all dilations ≥6 mm was 4.85% (P < 0.001).

Conclusions:

Balloon dilations that expand the initial esophageal anastomosis ≤5 mm in a pediatric population appear to not unduly increase the risk of perforation. Further prospective studies are needed to further investigate the potential for a new rule of 5 for balloon dilation.
Effectivity of Pancreatic Enzyme Replacement Therapy in Malnourished Children
Authors: Güven Burcu , Demir Mis Mevsim , Karaman Kamuran , Şahin Yaşar Akkiz
Published: March 2020

Objective:

Malnutrition is commonly seen in children with exocrine pancreatic insufficiency (EPI). Pancreatic enzyme replacement therapy (PERT) is the mainstay treatment of acute malnutrition in children detected with a disease closely associated with EPI (eg, cystic fibrosis). The effectiveness of PERT in children with malnutrition without any chronic disease, however, remains unclear. The aim of this study was to investigate the effectiveness of PERT on weight gain and EPI in children classified as moderately and severely malnourished according to the World Health Organization (WHO) classification.

Materials and Methods:

The study included a total of 40 children aged 2‐16 years who were classified as moderately and severely malnourished according to the WHO classification. The patients were randomly divided into 2 groups: PERT group (n = 20) received 2000 U lipase/kg/day (in 4 doses) in addition to hypercaloric enteral supplements and control group received hypercaloric enteral supplements only. In both groups, anthropometric measurements and the assessment of fecal elastase‐1 (FE‐1) levels were performed both at first admission and at the end of the 8‐week treatment period.

Results:

On the basis of WHO classification, 10 (25%) children were classified as severely malnourished and 30 (75%) children as moderately malnourished. EPI was detected in all the patients, among whom 24 (60%) patients had severe EPI. At the end of the treatment, body weight, height, and body mass index (BMI) increased significantly in both groups compared to their pre‐treatment values, whereas no significant difference was found with regard to waist circumference (WC) and FE‐1 levels. Similarly, no significant difference was found between pre‐ and posttreatment measurements of PERT and control groups (P > 0.05) and between pre‐ and posttreatment measurements of patients with moderate and severe malnutrition (P > 0.05).

Conclusions:

Malnutrition remains a serious public health problem, and thus, the development of novel treatment methods is highly essential. PERT is one of the most commonly considered alternatives, although there is little documentation of PERT in the literature. In the present study, although PERT resulted in higher weight gain, it established no significant difference between the 2 groups.
Cystic Fibrosis‐related Liver Disease is Associated With Increased Disease Burden and Endocrine Comorbidities
Authors: Singh Harveen , Coffey Michael J. , Ooi Chee Y.
Published: March 2020

Background:

Cystic fibrosis‐related liver disease (CFLD) is the leading nonpulmonary cause of mortality in cystic fibrosis (CF). We evaluated and compared the burden of disease and nonrespiratory comorbidities of those with severe CFLD and those without (noCFLD).

Methods:

A retrospective nationwide (Australia) longitudinal review (from 1998 to 2016) of severe CFLD patients compared with noCFLD controls (matched 1 : 1 for age, genotype, pancreatic insufficiency, and center).

Results:

One hundred sixty‐six patients with severe CFLD and 166 with noCFLD were identified. Forced expiratory volume in 1 second percentage of predicted (FEV1%) was significantly lower in CFLD than noCFLD across all ages (estimate [SE] −6.05% [2.12]; P = 0.004). Median (IQR) hospitalizations per patient per year were higher in CFLD than noCFLD for: respiratory indications (0.6 [0.2–1.3] vs 0.4 [0.1–0.9]; P = 0.002); gastrointestinal indications (0.09 [0–0.2] vs 0 [0–0.05]; P < 0.001); and other indications (0.05 [0–0.2] vs 0 [0–0.1]; P = 0.03). In the CFLD cohort, there was increased use of nasogastric (12.6% vs 5.4%; OR 2.51 [95% CI 1.06–6.46]; P = 0.03) and gastrostomy nutritional supplementation (22.9% vs 13.2%; OR 1.93 [95% CI 1.05–3.63]; P = 0.03). Additionally, the CFLD cohort had a higher frequency of bone diseases, osteopenia (26.5% vs 16.8%; OR 1.77 [95%CI 1.01–3.15]; P = 0.04) and osteoporosis (16.2% vs 8.4%; OR 2.1 [95% CI 1.01–4.52]; P = 0.04), as well as CF‐related diabetes (38.5% vs 19.2%; OR 2.61 [95% CI 1.55–4.47]; P = 0.001).

Conclusions:

Patients with severe CFLD have greater disease burden, with higher number of hospitalizations (both respiratory and nonrespiratory indications), nutritional interventions, and are at higher risk of CF‐related bone disease and diabetes.
A Novel SS18-SSX Fusion-specific Antibody for the Diagnosis of Synovial Sarcoma
Authors: Baranov Esther , McBride Matthew J. , Bellizzi Andrew M. , Ligon Azra H. , Fletcher Christopher D.M. , Kadoch Cigall , Hornick Jason L.
Published: March 2020

Synovial sarcoma (SS), an aggressive soft tissue sarcoma with a predilection for the extremities of young adults, harbors the pathognomonic t(X;18)(p11;q11) translocation, resulting in SS18-SSX rearrangements. SS includes monophasic, biphasic, and poorly differentiated variants, which show considerable histologic overlap with a range of other tumor types, making the diagnosis challenging on limited biopsies. Immunohistochemistry (IHC) is routinely used in the differential diagnosis; however, presently available markers lack specificity. Thus, cytogenetic or molecular genetic techniques are often employed to confirm the diagnosis. Here, we report the development and characterization of 2 novel antibodies: an SS18-SSX fusion-specific antibody (E9X9V, designed to the breakpoint) as well as an SSX-specific antibody (E5A2C, designed to the SSX C-terminus). We validated the selectivity and specificity of the antibodies using immunoblotting, immunoprecipitation, and chromatin immunoprecipitation followed by next-generation sequencing in SS cell lines and demonstrated that both antibodies capture SS18-SSX on chromatin at established target sites (eg, TLE1 and BCL2) genome-wide. Using IHC in whole sections from 400 tumors including 100 genetically confirmed cases of SS and 300 histologic mimics, the SS18-SSX fusion-specific antibody revealed strong diffuse nuclear staining in 95 of 100 (95%) SS cases, whereas none of the 300 control tumors showed any staining. The SSX antibody showed strong diffuse nuclear staining in all 100 (100%) SS cases; 13 (4%) of the 300 other tumors were also positive, 5 of which displayed >50% nuclear staining. In summary, a novel SS18-SSX fusion-specific antibody is highly sensitive (95%) and specific (100%) for SS, and an antibody to the SSX C-terminus is also highly sensitive (100%), but slightly less specific (96%). IHC using the SS18-SSX antibody could replace molecular genetic or cytogenetic testing in most cases, and these reagents together will also provide the research community with valuable tools for further biochemical and genomic interrogation of the SS18-SSX fusion protein.
Understanding the HIV Epidemic Among MSM in Baltimore: A Modeling Study Estimating the Impact of Past HIV Interventions and Who Acquired and Contributed to Infections
Authors: Silhol Romain , Boily Marie-Claude , Dimitrov Dobromir , German Danielle , Flynn Colin , Farley Jason E. , Gelman Marcy , Hughes James P. , Donnell Deborah , Adeyeye Adeola , Remien Robert H. , Beyrer Chris , Paz-Bailey Gabriela , Wejnert Cyprian , Mitchell Kate M.
Published: March 2020

Introduction:

Men who have sex with men (MSM) in the United States are disproportionately affected by HIV. We estimated the impact of past interventions and contribution of different population groups to incident MSM HIV infections.

Setting:

Baltimore, US.

Methods:

We used a deterministic model, parameterized and calibrated to demographic and epidemic Baltimore MSM data, to estimate the fraction of HIV infections among MSM averted by condoms and antiretroviral therapy (ART) over 1984–2017 and the fraction of infections acquired and transmission contributed by MSM from different demographic groups and disease and care continuum stages over 10-year periods from 1988 to 2017, using population attributable fractions.

Results:

Condom use and ART averted 19% (95% uncertainty interval: 14%–25%) and 23% (15%–31%) of HIV infections that would have occurred since 1984 and 1996, respectively. Over 2008–2017, 46% (41%–52%) of incident infections were acquired by and 35% (27%–49%) of transmissions contributed by MSM aged 18–24 years (who constitute 27% of all MSM, 19% of HIV+ MSM). MSM with undiagnosed HIV infection, those with diagnosed infection but not in care, and those on ART contributed to 41% (31%–54%), 46% (25%–56%), and 14% (7%–28%) of transmissions, respectively.

Conclusion:

Condoms and ART have modestly impacted the HIV epidemic among Baltimore MSM to date. Interventions reaching MSM with diagnosed infection who are not in care should be implemented because the largest percentage of HIV transmissions among Baltimore MSM is attributed to this group.
The Efficacy of Over-the-Scope Clip Closure for Gastrointestinal Iatrogenic Perforation During Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography for Pancreaticobiliary Diseases
Authors: Iwasa Yuhei , Iwashita Takuji , Uemura Shinya , Mita Naoki , Iwata Keisuke , Yoshida Kensaku , Mukai Tsuyoshi , Yasuda Ichiro , Shimizu Masahito
Published: March 2020

Background:

Intestinal perforation is a severe adverse event during pancreaticobiliary endoscopy. The use of over-the-scope clip (OTSC) has recently increased; however, the efficacy of OTSC during pancreaticobiliary endoscopy has not been well studied.

Aims:

To evaluate the efficacy of OTSC for the closure of gastrointestinal iatrogenic perforation during pancreaticobiliary endoscopy.

Patients and Methods:

This was a retrospective multicenter cohort study conducted at 3 tertiary care centers. The inclusion criteria were patients who had gastrointestinal perforation during endoscopic procedures for pancreaticobiliary diseases and underwent perforation closure using OTSC. The primary outcome was the clinical success rate. Secondary outcomes were technical success rates, adverse event rates, and the duration until the start of oral intake after OTSC.

Results:

Ten patients were treated by OTSC from January 2013 to December 2017. In 2 out of 10, the perforations could not be closed completely. In the remaining 8, perforations were closed completely, but intestinal obstruction caused by OTSC occurred in 1 patient. The clinical success rate was 80% (8/10). The technical and adverse event rates were 80% (8/10) and 10% (1/10), respectively. A median resumption timing of oral intake was 5 days (range, 3 to 10 d).

Conclusion:

OTSC is considered as effective management for perforations during pancreaticobiliary endoscopy, although careful consideration is required for the indication of OTSC.
Therapeutic Potentials of Localized Blood–Brain Barrier Disruption by Noninvasive Transcranial Focused Ultrasound: A Technical Review
Authors: Cammalleri Amanda , Croce Phillip , Lee Wonhye , Yoon Kyungho , Yoo Seung-Schik
Published: March 2020

The demands for region-specific, noninvasive therapies for neurologic/psychiatric conditions are growing. The rise of transcranial focused ultrasound technology has witnessed temporary and reversible disruptions of the blood–brain barrier in the brain with exceptional control over the spatial precisions and depth, all in a noninvasive manner. Starting with small animal studies about a decade ago, the technique is now being explored in nonhuman primates and humans for the assessment of its efficacy and safety. The ability to transfer exogenous/endogenous therapeutic agents, cells, and biomolecules across the blood–brain barrier opens up new therapeutic avenues for various neurologic conditions, with a possibility to modulate the excitability of regional brain function. This review addresses the technical fundamentals, sonication parameters, experimental protocols, and monitoring techniques to examine the efficacy/safety in focused ultrasound–mediated blood–brain barrier disruption and discuss its potential translations to clinical use.
Nocturnal Rapid Eye Movement Sleep Without Atonia can Be a Diagnostic Parameter in Differentiating Narcolepsy Type 1 From Type 2
Authors: Yon Mehmet Ilker , Azman Filiz , Yon Merve Ecem , Tezer F. Irsel
Published: March 2020

Purpose:

We aimed to compare rapid eye movement sleep without atonia (RSWA), tonic RSWA, and phasic RSWA indices during polysomnography as a potential biomarker between narcolepsy type 1 and type 2.

Methods:

Medical files, polysomnography, and multiple sleep latency tests of patients with narcolepsy were evaluated retrospectively. A total of three adolescents and 31 adult patients were included. We calculated the total number of rapid eye movement (REM) epochs with tonic and phasic activity in accordance with the American Academy of Sleep Medicine manual scoring rules, version 2.4. We defined tonic RSWA index as the ratio of total number of REM sleep stage epochs with only tonic activity to total REM sleep stage epochs, phasic RSWA index as the ratio of total number of REM sleep stage epochs with only phasic activity to total REM sleep stage epochs, and RSWA index as the ratio of total number of REM stage sleep epochs with RSWA to total REM sleep stage epochs on the polysomnography.

Results:

Clinically and polysomnographically diagnosed 25 patients with narcolepsy type 1 and 9 patients with narcolepsy type 2 were included. The median age of the subjects was 30 (10, 61) and 36 (18, 64), respectively. Eleven narcolepsy type 1 patients (44%) and 4 narcolepsy type 2 patients (44.44%) were women. The RSWA index of ≥ 3% yielded a sensitivity of 76% and specificity of 88.9% (AUC = 0.77 (0.09), 95% confidence interval = 0.58 to 0.97, p = 0.01), and the tonic RSWA index of ≥ 2.2% yielded a sensitivity of 72% and specificity of 77.8% (area under the curve = 0.74 (0.1), 95% confidence interval = 0.54–0.94, p = 0.03).

Conclusions:

As an electrophysiological biomarker, RSWA and tonic RSWA indices can be sensitive and specific polysomnography parameters in distinguishing narcolepsy type 1 from narcolepsy type 2.
Vicarious trial-and-error is enhanced during deliberation in human virtual navigation in a translational neuroeconomic task
Authors: Huynh Thach , Alstatt Keanan , Abram Samantha , Schmitzer-Torbert Neil
Published: March 2020

Foraging tasks can provide valuable insights into decision-making, as animals choose how to allocate limited resources (such as time). In the “Restaurant Row” task, rodents move between several sites to obtain food rewards available after a variable delay, while in a translational version (the “Web-Surf”) lacking the navigation component, humans are offered short videos. Both tasks have provided novel insights into decision-making and have been applied to addiction vulnerability and the impact of drug exposure on decision-making. We tested new tasks (the “Movie Row” and “Candy Row”) which use virtual navigation to determine if the behavioral correlates of human decision-making are more broadly similar to those of rodents, and explored the relationship of task performance to smoking and obesity. Humans navigated a virtual maze presented on standard computers to obtain rewards (either short videos or candy) available after a variable delay. Behavior on the tasks replicated previous results for the Restaurant Row and Web-Surf. In conditions promoting deliberation, decision latency was elevated along with measures of vicarious trial-and-error (VTE), supporting VTE as a shared behavioral index of deliberation across species. Smoking status was not well-related to performance, while high BMI (>25) individuals showed reduced sensitivity to a sunk-costs measure and stronger sensitivity to offer value for offers below the preferred delay. These data support the Movie and Candy Row as translational tools to study decision-making during foraging in humans, providing convergent results with a rodent navigation task and demonstrating the potential to provide novel insights relevant to public health.
Polygenic Risk Score Modifies Risk of Coronary Artery Disease Conferred by Low-Density Lipoprotein Cholesterol
Authors: Bolli Alessandro , Di Domenico Paolo , Pastorino Roberta , Busby George , Bottà Giordano
Published: March 2020

Background

An individual’s lifetime risk of Coronary Artery Disease (CAD) is determined by a combination of genetic and lifestyle factors. Whilst adherence to a healthy lifestyle can help individuals with high genetic risk reduce their lifetime risk of CAD, the extent to which blood lipid levels affect CAD risk in individuals with varying genetic risk remains unknown. To explore how genetics, blood lipids and CAD risk interact, we derived a novel genome-wide polygenic risk score (PRS) for CAD. We then applied the PRS to individuals from the UK Biobank and divided them into Low PRS (bottom 10 percentiles of PRS distribution), Intermediate PRS (PRS in the 10th-90th percentiles), and High PRS (top 10 percentiles), and further stratified individuals by blood lipid levels.

Results

We found that the elevated CAD risk conferred by high low-density lipoprotein cholesterol (LDL-C) was modified by the interaction with PRS (P-value interaction: <0.005). Individuals with High PRS and whose LDL-C was Borderline (between 130 and 160 mg/dL) had higher CAD relative risk (HR 3.10; 95% CI, 2.55-3.76) than those at Intermediate PRS whose LDL-C were Very High (>190 mg/dL; HR 2.77; 95% CI, 2.33-3.28). Furthermore, individuals with High PRS but whose lipid levels were below the following thresholds did not have a significantly increased risk for incident CAD: LDL-C <130 mg/dL, total Cholesterol (TC) <200 mg/dL, LDL-C:HDL <2.0 and TC:HDL <3.0. In addition, individuals with Low PRS and Very High LDL-C (>190 mg/dl) did not have increased CAD risk, which was comparable to individuals with Intermediate PRS and Optimal LDL-C (<130 mg/dL).

Conclusions

Our results have important implications for the primary prevention of coronary artery disease. Currently, healthy individuals with Borderline LDL-C (130-159 mg/dL) are not considered to be at high risk of CAD. Here we demonstrate that the combination of Borderline LDL-C and High PRS results in CAD relative risk which is greater than individuals without high polygenic risk, but whose LDL-C levels are high enough for statins to be recommended (>190 mg/dL). This analysis therefore demonstrates that PRS can identify a proportion of the population who are at high-risk of CAD but who are invisible to current approaches for assessing CAD risk. Moreover, of perhaps greater significance is the evidence that individuals who have a combination of High PRS and Optimal blood lipid levels do not have greater risk of CAD than individuals without high polygenic risk and the same Optimal blood lipid levels. Our results suggest that high polygenic risk for CAD could be overcome by controlling blood lipid levels. We propose that incorporating PRS into CAD risk assessment early in life could allow individuals at high polygenic risk to benefit from tailored blood lipid guidelines and avoid lifetime exposure to potentially damaging PRS-dependent LDL-C levels.
The timing of one-shot interventions for epidemic control
Authors: Lauro Francesco Di , Kiss István Z. , Miller Joel C.
Published: March 2020

The apparent early success in China’s large-scale intervention to control the COVID-19 epidemic has led to interest in whether other countries can replicate it as well as concerns about a resurgence of the epidemic if or when China relaxes the interventions. In this paper we look at the impact of a single short-term intervention on an epidemic. We see that if an intervention cannot be sustained long-term, it has the greatest impact if it is imposed once infection levels have become large enough that there is an appreciable number of infections present. For minimising the total number infected it should start close to the peak so that there is no rebound once the intervention is stopped, while to minimise the peak prevalence, it should start earlier, allowing two peaks of comparable size rather than one very large peak. In populations with distinct subgroups, synchronized interventions are less effective than targeting the interventions in each sub-population separately.

We do not attempt to clearly determine what makes an intervention sustainable or not. We believe that is a policy question. If an intervention is sustainable, it should be kept in place. Our intent is to offer insight into how best to time an intervention whose impact on society is too great to maintain.
Validity of Wrist and Forehead Temperature in Temperature Screening in the General Population During the Outbreak of 2019 Novel Coronavirus: a prospective real-world study
Authors: Chen Ge , Xie Jiarong , Dai Guangli , Zheng Peijun , Hu Xiaqing , Lu Hongpeng , Xu Lei , Chen Xueqin , Chen Xiaomin
Published: March 2020

Aims

Temperature screening is important in the population during the outbreak of 2019 Novel Coronavirus (COVID-19). This study aimed to compare the accuracy and precision of wrist and forehead temperature with tympanic temperature under different circumstances.

Methods

We performed a prospective observational study in a real-life population. We consecutively collected wrist and forehead temperatures in Celsius (°C) using a non-contact infrared thermometer (NCIT). We also measured the tympanic temperature using a tympanic thermometers (IRTT) and defined fever as a tympanic temperature ≥37.3°C.

Results

We enrolled a total of 528 participants including 261 indoor and 267 outdoor participants. We divided outdoor participants into four types according to their means of transportation to the hospital as walk, bicycle, electric vehicle, car, and inside the car. Under different circumstance, the mean difference ranged from −1.72 to −0.56°C in different groups for the forehead measurements, and −0.96 to −0.61°C for the wrist measurements. Both measurements had high fever screening abilities in inpatients (wrist: AUC 0.790; 95% CI: 0.725-0.854, P <0.001; forehead: AUC 0.816; 95% CI: 0.757-0.876, P <0.001). The cut-off value of wrist measurement for detecting tympanic temperature ≥37.3°C was 36.2°C with a 86.4% sensitivity and a 67.0% specificity, and the best threshold of forehead measurement was also 36.2°C with a 93.2% sensitivity and a 60.0% specificity.

Conclusions

Wrist measurement is more stable than forehead measurement under different circumstance. Both measurements have great fever screening abilities for indoor patients. The cut-off value of both measurements was 36.2°C. (ClinicalTrials.gov number: NCT04274621)
Estimating the burden of United States workers exposed to infection or disease: a key factor in containing risk of COVID-19 infection
Authors: Baker Marissa G. , Peckham Trevor K. , Seixas Noah S.
Published: March 2020

Introduction

With the global spread of COVID-19, there is a compelling public health interest in quantifying who is at increased risk of disease. Occupational characteristics, such as interfacing with the public and being in close quarters with other workers, not only put workers at high risk for disease, but also make them a nexus of disease transmission to the community. This can further be exacerbated through presenteeism, the term used to describe the act of coming to work despite being symptomatic for disease. Understanding which occupational groups are exposed to infection and disease in the workplace can help to inform public health risk response and management for COVID-19, and subsequent infectious disease outbreaks.

Methods

To estimate the burden of United States workers exposed to infection and disease in the workplace, national employment data (by Standard Occupational Classification) maintained by the Bureau of Labor Statistics (BLS) was merged with BLS O*NET survey data, which ranks occupations with particular physical, ergonomic, and structural exposures. For this analysis, occupations reporting exposure to infection or disease more than once a month was the focus.

Results

Based on our analyses, approximately 10% (14.4 M) of United States workers are employed in occupations where exposure to disease or infection occurs at least once per week. Approximately 18.4% (26.7 M) of all United States workers are employed in occupations where exposure to disease or infection occurs at least once per month. While the majority of exposed workers are employed in healthcare sectors, other occupational sectors also have high proportions of exposed workers. These include protective service occupations (e.g. police officers, correctional officers, firefighters), office and administrative support occupations (e.g. couriers and messengers, patient service representatives), education occupations (e.g. preschool and daycare teachers), community and social services occupations (community health workers, social workers, counselors), and even construction and extraction occupations (e.g. plumbers, septic tank installers, elevator repair).

Conclusions

The large number of persons employed in a wide variety of occupations with frequent exposure to infection and disease underscore the importance of all workplaces developing risk response plans for COVID-19. This work also serves as an important reminder that the workplace is a key locus for public health interventions, which could protect both workers and the communities they serve.