bluuebunny/crossref_metadata_2025 huggingface dataset:
A multi-institutional pilot clinical trial of spectroscopic MRI-guided radiation dose escalation for newly diagnosed glioblastoma
Authors: Ramesh Karthik , Mellon Eric A , Gurbani Saumya S , Weinberg Brent D , Schreibmann Eduard , Sheriff Sulaiman A , Goryawala Mohammed , de le Fuente Macarena , Eaton Bree R , Zhong Jim , Voloschin Alfredo D , Sengupta Soma , Dunbar Erin M , Holdhoff Matthias , Barker Peter B , Maudsley Andrew A , Kleinberg Lawrence R , Shim Hyunsuk , Shu Hui-Kuo G
Published: January 2022

Background

Glioblastomas (GBMs) are aggressive brain tumors despite radiation therapy (RT) to 60 Gy and temozolomide (TMZ). Spectroscopic magnetic resonance imaging (sMRI), which measures levels of specific brain metabolites, can delineate regions at high risk for GBM recurrence not visualized on contrast-enhanced (CE) MRI. We conducted a clinical trial to assess the feasibility, safety, and efficacy of sMRI-guided RT dose escalation to 75 Gy for newly diagnosed GBMs.

Methods

Our pilot trial (NCT03137888) enrolled patients at 3 institutions (Emory University, University of Miami, Johns Hopkins University) from September 2017 to June 2019. For RT, standard tumor volumes based on T2-FLAIR and T1w-CE MRIs with margins were treated in 30 fractions to 50.1 and 60 Gy, respectively. An additional high-risk volume based on residual CE tumor and Cho/NAA (on sMRI) ≥2× normal was treated to 75 Gy. Survival curves were generated by the Kaplan–Meier method. Toxicities were assessed according to CTCAE v4.0.

Results

Thirty patients were treated in the study. The median age was 59 years. 30% were MGMT promoter hypermethylated; 7% harbored IDH1 mutation. With a median follow-up of 21.4 months for censored patients, median overall survival (OS) and progression-free survival were 23.0 and 16.6 months, respectively. This regimen appeared well-tolerated with 70% of grade 3 or greater toxicity ascribed to TMZ and 23% occurring at least 1 year after RT.

Conclusion

Dose-escalated RT to 75 Gy guided by sMRI appears feasible and safe for patients with newly diagnosed GBMs. OS outcome is promising and warrants additional testing. Based on these results, a randomized phase II trial is in development.
Predictive accuracy of T2-FLAIR mismatch sign for the IDH-mutant, 1p/19q noncodeleted low-grade glioma: An updated systematic review and meta-analysis
Authors: Do Yoon Ah , Cho Se Jin , Choi Byung Se , Baik Sung Hyun , Bae Yun Jung , Sunwoo Leonard , Jung Cheolkyu , Kim Jae Hyoung
Published: January 2022

Background

The T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign, has been considered a highly specific imaging biomarker of IDH-mutant, 1p/19q noncodeleted low-grade glioma. This systematic review and meta-analysis aimed to evaluate the diagnostic performance of T2-FLAIR mismatch sign for prediction of a patient with IDH-mutant, 1p/19q noncodeleted low-grade glioma, and identify the causes responsible for the heterogeneity across the included studies.

Methods

A systematic literature search in the Ovid-MEDLINE and EMBASE databases was performed for studies reporting the relevant topic before November 17, 2020. The pooled sensitivity and specificity values with their 95% confidence intervals were calculated using bivariate random-effects modeling. Meta-regression analyses were also performed to determine factors influencing heterogeneity.

Results

For all the 10 included cohorts from 8 studies, the pooled sensitivity was 40% (95% confidence interval [CI] 28–53%), and the pooled specificity was 100% (95% CI 95–100%). In the hierarchic summary receiver operating characteristic curve, the difference between the 95% confidence and prediction regions was relatively large, indicating heterogeneity among the studies. Higgins I2 statistics demonstrated considerable heterogeneity in sensitivity (I2 = 83.5%) and considerable heterogeneity in specificity (I2 = 95.83%). Among the potential covariates, it seemed that none of factors was significantly associated with study heterogeneity in the joint model. However, the specificity was increased in studies with all the factors based on the differences in the composition of the detailed tumors.

Conclusions

The T2-FLAIR mismatch sign is near-perfect specific marker of IDH mutation and 1p/19q noncodeletion.
Management of severe renal disease in anti-neutrophil-cytoplasmic-antibody-associated vasculitis: the place of rituximab and plasma exchange?
Authors: Morel Pauline , Karras Alexandre , Porcher Raphaël , Belenfant Xavier , Audard Vincent , Rafat Cédric , Hanouna Guillaume , Beaudreuil Séverine , Vilain Cédric , Hummel Aurélie , Terrier Benjamin , Pillebout Evangeline , Groh Matthieu , Jouenne Romain , Dhote Robin , Fain Olivier , Ponsoye Matthieu , Noel Nicolas , Limal Nicolas , Puéchal Xavier , Le Jeunne Claire , Guillevin Loïc , Mouthon Luc , Régent Alexis
Published: January 2022

Objective

The optimal induction therapy for severe glomerulonephritis of ANCA-associated vasculitis (AAV) is debated. We compared the efficacy of glucocorticoid and rituximab (RTX) or CYC induction therapy for severe AAV-related glomerulonephritis and evaluated the potential benefit of plasma exchange (PE) as adjunct therapy to CYC.

Methods

This retrospective, multicentre study included AAV patients with severe renal active disease (serum creatinine level ≥350 µmol/l and/or estimated glomerular filtration ratio ≤15 ml/min/1.73 m2). Propensity-score analysis was used to adjust for potential confounders.

Results

Between 2005 and 2017, 153 patients with AAV-related glomerulonephritis were studied (96 [60%] men; mean [s.d.] age 63 [13.1] years): 19 (12%) were treated with RTX and 134 (88%) with CYC. Remission rates did not differ between RTX- and CYC-treated groups. Although more patients with RTX than CYC were dialysis-free at month (M) 12 (79% vs 68%), the difference was not significant after adjustment. Among 134 patients with CYC-treated glomerulonephritis, 76 (57%) also had PE. M3 and M6 remission rates were comparable for weighted CYC groups with or without PE. For weighted groups, the dialysis-free survival rate with CYC was higher with than without PE at M6 (72% vs 64%; odds ratio 2.58) and M12 (74% vs 60%; odds ratio 2.78) reaching statistical significance at M12.

Conclusion

We could not find any difference between RTX and CYC as induction therapy for patients with severe AAV-related glomerulonephritis. In patients receiving CYC induction regimen, the addition of PE conferred short-term benefits with higher dialysis-free rate at M12.
Prospective epidemiological study of juvenile-onset systemic lupus erythematosus in the UK and Republic of Ireland
Authors: Lythgoe Hanna , Smith Eve M D , Killeen Orla G , Murphy Ruth , Pilkington Clarissa , Pain Clare E , Beresford Michael W ,   in association with the British Paediatric Surveillance Unit, Lynn Richard , McDonagh Janet , Tizard Jane , Ioannou Yiannis
Published: January 2022

Objectives

The primary objective was to define the incidence of JSLE in children <16 years of age in the UK and Republic of Ireland (ROI). The secondary objective was to describe presenting features, classification criteria, initial management and disease damage in newly presenting JSLE patients.

Methods

A prospective JSLE epidemiological study was undertaken between September 2017 and September 2019 with support of the British Paediatric Surveillance Unit and other professional groups involved in diagnosis and management of JSLE patients. Treating consultants reported all cases of JSLE seen. A follow-up study at 1 year examined management and progression of disease and treatment.

Results

There were 124 incident cases included in the final analysis. Incidence was estimated using ACR-1997 classification criteria (0.36/100 000), SLICC-2012 classification criteria (0.41/100 000) and clinician expert opinion (0.46/100 000). A high disease burden was seen, with 71.0% of patients requiring ongoing systemic CS treatment at 1 year; 98.2% receiving immunomodulatory treatment; and 20.4% accruing damage in the year following diagnosis (predominantly neuropsychiatric-related), with substantial involvement from multiple speciality teams.

Conclusions

The minimum UK and ROI incidence of JSLE is between 0.36 and 0.46/100 000, depending on the case definition used. Challenges in classification of patients with JSLE are highlighted, but overall this study supports the use of SLICC-2012 classification criteria. The high levels of disease damage and ongoing CS use 1 year after diagnosis is concerning, highlighting the need for further interventions to improve outcomes in JSLE.
ACTIVITY RATIO OF URANIUM IN FUKUSHIMA SOIL SAMPLES USING MULTI-COLLECTOR INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY
Authors: Murugan Rajamanickam , Sahoo Sarata Kumar , Sorimachi Atsuyuki , Omori Yasutaka , Aono Tatsuo
Published: January 2022

The Fukushima soils have been collected from Namie and Futaba areas for the radiocaesium and uranium isotope ratio studies. The 137Cs activity concentration of soil samples ranged from 6 ± 1 to 756 ± 14 kBq/kg. The uranium isotope ratios are measured using multi collector inductively coupled plasma mass spectrometry. The activity ratio (234U/238U) of the Fukushima soils is calculated from the measured 234U/238U isotope ratio. Activity ratio varied from 0.98 to 1.02 which indicates that 234U and 238U are in secular equilibrium. The 235U/238U atomic ratio of the Fukushima soils did not show any heterogeneity compared with the natural terrestrial ratio even with high level of 137Cs in soils.
Primary Nonadherence to Antipsychotic Treatment Among Persons with Schizophrenia
Authors: Lieslehto Johannes , Tiihonen Jari , Lähteenvuo Markku , Tanskanen Antti , Taipale Heidi
Published: January 2022

It has remained unclear what factors relate to primary nonadherence to antipsychotic treatment and whether specific agents and routes of administration differ in how patients adhere to them. We collected electronic prescriptions and their dispensings from the Finnish electronic prescription database for 29 956 patients with schizophrenia prescribed antipsychotics via electronic prescription during 2015–2016. We defined primary nonadherence as being prescribed an antipsychotic, which was not dispensed from the pharmacy within one year from prescription. Using logistic regression, we analyzed whether several sociodemographic and clinical factors related to nonadherence. We found that 31.7% (N = 9506) of the patients demonstrated primary nonadherence to any of their prescribed antipsychotics. We found that young age (OR = 1.77, 95%CI = 1.59–1.96), concomitant benzodiazepines (OR = 1.47, 95%CI = 1.40–1.55) and mood stabilizers (OR = 1.29, 95%CI = 1.21–1.36), substance abuse (OR = 1.26 95%CI = 1.19–1.35), previous suicide attempt (OR = 1.21, 95%CI = 1.11–1.31), diabetes (OR = 1.15, 95%CI = 1.06–1.25), asthma/COPD (OR = 1.14, 95%CI = 1.04–1.25), and cardiovascular disease (OR = 1.12, 95%CI = 1.05–1.19), were related to primary nonadherence to antipsychotic treatment. Patients using clozapine showed the lowest nonadherence (4.77%, 95%CI = 4.66–4.89), and patients using long-acting injectables were more adherent to treatment (7.27%, 95%CI = 6.85–7.71) when compared to respective oral agents (10.26%, 95%CI = 10.02–10.49). These results suggest that selection between different pharmacological agents and routes of administration while taking into account patients’ concomitant medications (benzodiazepines in particular) and comorbidities play a key role in primary nonadherence to antipsychotic treatment.
Experimental methods to study sleep disruption and immune balance in urban children with asthma
Authors: Koinis-Mitchell Daphne , Marshall Gailen D , Kopel Sheryl J , Belanger Nicole M S , Ayala-Figueroa Jesús , Echevarria Sofia , Millman Richard , Zheng Tao , Weathers Jessica , Gredvig Caroline A , Carskadon Mary A
Published: January 2022

Study Objectives

We describe research methods developed to examine effects of sleep disruption on changes in immune balance, lung function, and cognitive performance in a sample of urban, ethnically diverse children with persistent asthma. Two case examples (8- and 10-year-old males) are presented to highlight methods of the current study and illustrate effects of experimentally disrupted sleep on the immune balance profile (Th1/Th2 cytokines), key sleep variables from polysomnography data, and lung function in our sample.

Methods

Children follow an individualized structured sleep schedule consistent with their habitual sleep need (≥9.5 hours’ time in bed) for six days before a laboratory-based experimental sleep protocol. Children then spend two successive nights in the sleep lab monitored by polysomnography: a baseline night consisting of uninterrupted sleep, and a disruption night, during which they are awoken for 2 minutes between 20-minute intervals of uninterrupted sleep. Evening and morning blood draws bracket baseline and disruption nights for immune biomarker assessment.

Results

A shift towards immune imbalance following the sleep disruption protocol was observed in these illustrative cases.

Conclusions

Data from these case examples provide evidence that the experimental protocol caused disruptions in sleep as observed on polysomnography and had the hypothesized downstream effects on immune balance associated with clinical asthma control. Documenting the effects of sleep disruption on immune function in children with persistent asthma is a crucial step towards understanding associations between sleep, immune balance, and asthma outcomes and provides important information for developing novel interventions for youth with asthma and suboptimal sleep.

Clinical Trials

Not applicable.
Understanding Filtering Facepiece Respirators
Authors: Andrews Angela S. , Kiederer Meghan , Casey Megan L.
Published: January 2022

How to ensure adequate protection.
A Plea for Help in Making Nursing Sustainable
Authors: Sato Hui-Wen (Alina)
Published: January 2022

Updated several times a week with posts by a wide variety of authors, AJN's blog Off the Charts allows us to provide more timely—and often more personal—perspectives on professional, policy, and clinical issues. Best of the Blog is a regular column to draw the attention of AJN readers to posts we think deserve a wider audience. To read more, please visit: www.ajnoffthecharts.com.
Suicide risk and prevention in LGBTQ+ youth
Authors: Cottrell Damon B. , Gonzalez John D. , Atchison Phillip T. , Evans Stephanie C. , Stokes Alyssa
Published: January 2022

Lesbian, gay, bisexual, transgender, questioning (or queer), and other sexual and gender minority (LGBTQ+) youth face various forms of bullying and mistreatment that may lead to suicide. Nurses can help recognize, address, and mitigate challenges associated with suicide among LGBTQ+ youth.
Dementia care in the age of COVID-19
Authors: Nelson Andrea , Rosenberg Paul B. , Cotter Valerie T.
Published: January 2022

The COVID-19 pandemic and related measures, such as social distancing, have adversely impacted persons with dementia (PWD) and their caregivers. Nurses must be able to identify the care needs of PWD and their caregivers and intervene with relevant resources.
Association between blood metals mixtures concentrations and cognitive performance, and effect modification by diet in older US adults
Authors: Laouali Nasser , Benmarhnia Tarik , Lanphear Bruce P. , Weuve Jennifer , Mascari Michael , Boutron-Ruault Marie-Christine , Oulhote Youssef
Published: January 2022

Background:

Chronic exposure to heavy metals has been associated with adverse neurological outcomes in older adults. Inflammatory processes are suspected as an underlying pathway by which metals exert their neurotoxicity. In parallel, a diet rich in antioxidant and anti-inflammatory components may protect against chronic inflammation.

Objectives:

We examined the associations of blood concentrations of lead, cadmium, and manganese as a mixture with cognitive performance in older US adults and potential modification of these associations by diet as measured by the Healthy Eating Index 2015 (HEI-2015) and the Adapted Dietary Inflammatory Index (ADII).

Methods:

We used data on 1,777 adults ≥60 years old from the US National Health and Nutrition Examination Survey (NHANES; 2011–2014). We derived the ADII and the HEI-2015 from two nonconsecutive 24-hour diet recalls. Cognitive performance was measured by the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Word Learning subtest, the animal fluency test, and the Digit Symbol Substitution Test (DSST). We also constructed a composite z-score reflecting overall cognitive performance. We used quantile g-computation to evaluate the joint associations of a mixture of metals with cognitive performance test scores. We also evaluated effect modification by sex and diet quality indices using Cochran Q tests.

Results:

The median (interquartile range) of blood metals were 0.38 μg/L (0.35), 14.70 μg/L (11.70), and 8.74 μg/L (4.06) for cadmium, lead, and manganese, respectively. Increasing blood concentrations of all metals by one quartile was associated with a decrease in overall cognitive performance (–0.04; 95% confidence interval [CI] = –0.09, 0.02), CERAD (–0.04; 95% CI = –0.12, 0.03), animal fluency (–0.02; 95% CI, –0.11, 0.06), and DSST (–0.05; 95% CI = –0.11, 0.02) test scores. These associations were more pronounced in adults with high pro-inflammatory or low-diet quality and null or positive though imprecise associations in participants with a high anti-inflammatory. These associations also varied by sex with inverse associations in men and positive associations in women.

Conclusions:

Our findings suggest that adherence to an antioxidant and anti-inflammatory diet may prevent blood metals adverse cognitive effects among older adults. If confirmed, strategies based on diet could provide a potential complementary and efficient approach to counteract effects of environmental pollutants.
Bilateral Finger Morton Neuroma after Primary Fingertip Amputation
Authors: Mogl Adrian Georg , Gualdi Alessandro , Kamolz Lars-Peter , Sarocchi Francesca , Cambiaso-Daniel Janos
Published: January 2022

Morton’s neuroma (MN) is a painful, proliferative fibrosis of perineural tissue caused by pressure or recurrent irritation that was previously thought to affect only the common interdigital nerve of the foot. We present a case of a bilateral MN of both the ulnar and radial proper digital nerves of the fifth finger in a 30-year-old patient, following multiple surgeries on the aforementioned finger. The patient was referred to our center by a peripheral hospital after traumatic fingertip amputation distal the DIP joint, where the fingertip was initially simply sutured. Because of progressive neuropathic pain, he underwent two revision surgeries, in which the distal phalanx was removed, two neuromas were excised, and the nerve stumps were shortened, but both were unsuccessful. A final, more extensive revision surgery was then carried out, in which two club-like enlargements were excised and the nerve stumps coadapted to form a loop. Histopathological examination of the excised specimen revealed perineural fibrosis in the context of a Morton’s neuroma. This is, to our knowledge, the first documented case of a bilateral MN of the hand, which may have resulted from an inadequate primary finger and nerve shortening, resulting in high pressure from the surrounding soft tissue. Finally, this report emphasizes the significance of optimal treatment for finger amputation injuries, as well as the fact that for neuromas, simple nerve resection should be avoided whenever possible, because of the high recurrence rates.
Structured Mammoplasty (Breast Reduction and Mastopexy with Silicone Implants): Standardization of Technique for Predictable Results
Authors: Sakai Rafael L. , Sakai Graciela M.G.A. , Pacheco Lucas C. , Rezende Aline P. , Montenegro Bruno H.
Published: January 2022

Background:

Several methods have been developed for the treatment of ptosis and breast hypertrophy, with good early results but with dissatisfaction in the long term, due to loss of volume and projection of the upper pole and recurrence of ptosis. In the face of this adversity, the purposes of the present study were to describe a surgical technique of breast reduction and mastopexy with silicone implants, named structured mammoplasty, and to present the outcomes of patients who underwent this technique.

Methods:

The structured mammoplasty technique with round silicone prostheses (surgical marking and stages), performed on 100 patients who were operated on between 2017 and 2020 and were followed up for a minimum of 12 months, was described. Postoperative and patient satisfaction assessments were made.

Results:

No major complications were observed in an average of 18 months of follow-up (ranging from 12 to 30 months). The maintenance of the outcome with a projected upper pole and rounded breasts resulted in a high level of satisfaction.

Conclusions:

Structured mammoplasty with silicone implants is a safe and predictable option, ensuring a long-lasting shape. It can be applied to any breast that has surplus skin, making it a more reliable option in the arsenal of the plastic surgeon.
Retinal microvascular abnormalities and risks of incident stroke and its subtypes: The Circulatory Risk in Communities Study
Authors: Li Jiaqi , Imano Hironori , Kitamura Akihiko , Kiyama Masahiko , Yamagishi Kazumasa , Tanaka Mari , Ohira Tetsuya , Sankai Tomoko , Umesawa Mitsumasa , Muraki Isao , Hayama-Terada Mina , Okada Takeo , Cui Renzhe , Tanigawa Takeshi , Iso Hiroyasu
Published: January 2022

Background:

This study aimed to investigate the association between retinal microvascular abnormalities and the risk of incident stroke and its subtypes in the general Japanese population.

Methods:

A total of 12 965 residents aged 40–74 years without a history of stroke and/or coronary heart disease underwent retinal photography during the annual health checkups of four Japanese communities between 1990 and 1999. Retinal microvascular abnormalities, such as the presence or absence of generalized arteriolar narrowing, focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar light reflex, and retinal hemorrhages were graded using standard protocols.

Results:

During a median follow-up of 20 years, 817 patients were diagnosed with incident stroke. Retinal microvascular abnormalities were positively associated with the risk of total stroke; after adjustment for age, sex, community, SBP, antihypertensive medication use, and other cardiovascular risk factors, the multivariable hazard ratio [95% confidence interval (CI)] was 1.68 (1.42–1.98), 1.67 (1.34–2.07), 1.41 (1.17–1.72), 1.54 (1.26–1.87), and 1.57 (1.19–2.07) for generalized arteriolar narrowing, focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar light reflex, and retinal hemorrhages, respectively. Similar positive associations were observed for the risk of stroke subtypes, except for subarachnoid hemorrhage, for which no association was observed. Furthermore, the positive associations were similar in participants with and without hypertension.

Conclusion:

Retinal microvascular abnormalities were positively associated with the risk of incident stroke in the general Japanese population. Routine retinal photography could provide positive clinical insights into stroke risk stratification independent of blood pressure, antihypertensive medication use, and other risk factors.
Beyond Black vs White: racial/ethnic disparities in chronic pain including Hispanic, Asian, Native American, and multiracial US adults
Authors: Zajacova Anna , Grol-Prokopczyk Hanna , Fillingim Roger
Published: January 2022

Previous literature on race/ethnicity and pain has rarely included all major US racial groups or examined the sensitivity of findings to different pain operationalizations. Using data from the 2010 to 2018 National Health Interview Surveys on adults 18 years or older (N = 273,972), we calculated the weighted prevalence of 6 definitions of pain to provide a detailed description of chronic pain in White, Black, Hispanic, Asian, Native American, and multiracial groups. We also estimated modified Poisson models to obtain relative disparities, net of demographic and socioeconomic (SES) factors including educational attainment, family income, and home ownership; finally, we calculated average predicted probabilities to show prevalence disparities in absolute terms. We found that Asian Americans showed the lowest pain prevalence across all pain definitions and model specifications. By contrast, Native American and multiracial adults had the highest pain prevalence. This excess pain was due to the lower SES among Native Americans but remained significant and unexplained among multiracial adults. The pain prevalence in White, Black, and Hispanic adults fell in between the 2 extremes. In this trio, Hispanics showed the lowest prevalence, an advantage not attributable to immigrant status or SES. Although most previous research focuses on Black–White comparisons, these 2 groups differ relatively little. Blacks report lower prevalence of less severe pain definitions than Whites but slightly higher prevalence of severe pain. Net of SES, however, Blacks experienced significantly lower pain across all definitions. Overall, racial disparities are larger than previously recognized once all major racial groups are included, and these disparities are largely consistent across different operationalizations of pain.
Features and methods to discriminate between mechanism-based categories of pain experienced in the musculoskeletal system: a Delphi expert consensus study
Authors: Shraim Muath A. , Sluka Kathleen A. , Sterling Michele , Arendt-Nielsen Lars , Argoff Charles , Bagraith Karl S. , Baron Ralf , Brisby Helena , Carr Daniel B. , Chimenti Ruth L. , Courtney Carol A. , Curatolo Michele , Darnall Beth D. , Ford Jon J. , Graven-Nielsen Thomas , Kolski Melissa C. , Kosek Eva , Liebano Richard E. , Merkle Shannon L. , Parker Romy , Reis Felipe J. J. , Smart Keith , Smeets Rob J. E. M. , Svensson Peter , Thompson Bronwyn L. , Treede Rolf-Detlef , Ushida Takahiro , Williamson Owen D. , Hodges Paul W.
Published: January 2022

Classification of musculoskeletal pain based on underlying pain mechanisms (nociceptive, neuropathic, and nociplastic pain) is challenging. In the absence of a gold standard, verification of features that could aid in discrimination between these mechanisms in clinical practice and research depends on expert consensus. This Delphi expert consensus study aimed to: (1) identify features and assessment findings that are unique to a pain mechanism category or shared between no more than 2 categories and (2) develop a ranked list of candidate features that could potentially discriminate between pain mechanisms. A group of international experts were recruited based on their expertise in the field of pain. The Delphi process involved 2 rounds: round 1 assessed expert opinion on features that are unique to a pain mechanism category or shared between 2 (based on a 40% agreement threshold); and round 2 reviewed features that failed to reach consensus, evaluated additional features, and considered wording changes. Forty-nine international experts representing a wide range of disciplines participated. Consensus was reached for 196 of 292 features presented to the panel (clinical examination—134 features, quantitative sensory testing—34, imaging and diagnostic testing—14, and pain-type questionnaires—14). From the 196 features, consensus was reached for 76 features as unique to nociceptive (17), neuropathic (37), or nociplastic (22) pain mechanisms and 120 features as shared between pairs of pain mechanism categories (78 for neuropathic and nociplastic pain). This consensus study generated a list of potential candidate features that are likely to aid in discrimination between types of musculoskeletal pain.
Pain response to cannabidiol in opioid-induced hyperalgesia, acute nociceptive pain, and allodynia using a model mimicking acute pain in healthy adults in a randomized trial (CANAB II)
Authors: Dieterle Markus , Zurbriggen Laura , Mauermann Eckhard , Mercer-Chalmers-Bender Katja , Frei Priska , Ruppen Wilhelm , Schneider Tobias
Published: January 2022

Opioids in general and remifentanil in particular can induce hyperalgesia. Preclinical data suggest that cannabidiol might have the capacity to reduce opioid-induced hyperalgesia (OIH). Thus, we investigated the effect of oral cannabidiol on OIH in healthy volunteers using an established pain model. Twenty-four healthy participants were included in this randomized, double-blinded, crossover study and received either a 1600-mg single-dose oral cannabidiol or placebo. Hyperalgesia, allodynia, and pain were induced by intracutaneous electrical stimulation. To provoke OIH, participants recieved an infusion of 0.1 µg/kg/min remifentanil over a time frame of 30 minutes, starting 100 minutes after oral cannabidiol ingestion. The primary outcome was the area of hyperalgesia (in square centimetres) up to 60 minutes after remifentanil administration. The area of allodynia (in square centimetres) and pain (numeric rating scale) were also assessed.

Cannabidiol had no significant effect on hyperalgesia, allodynia, or pain at any time point of measurement compared with placebo. The area of hyperalgesia after remifentanil administration significantly increased compared with baseline (17.0 cm2 [8.1-28.7] vs 25.3 cm2 [15.1-39.6]; P = 0.013). Mean cannabidiol blood levels were 4.1 ± 3.0 µg/L (mean ± SD) at 130 minutes after ingestion and were 8.2 μg/L ± 6.9 µg/L (mean ± SD) at 200 minutes. Cannabidiol was well tolerated. We conclude that a high single-oral dose of 1600-mg cannabidiol is not effective in reducing OIH. Before excluding an effect of cannabidiol on OIH, research should focus on drug formulations enabling higher cannabidiol concentrations.
Comparison of Outcomes of Surgical Repair of Spontaneous Temporal Bone CSF Leaks and Encephaloceles Using Bone Cement and Autologous Material
Authors: Hwa Tiffany Peng , Patel Vir , Eliades Steven J. , Brant Jason A. , Bigelow Douglas C. , Ruckenstein Michael J.
Published: January 2022

Objective:

To compare outcomes transmastoid repair of spontaneous middle fossa cerebrospinal fluid (CSF) leak using only bone cement (BC) versus only autologous material (AM) or combined materials (CM) with both bone cement and autologous material.

Study Design:

Retrospective Chart Review.

Setting:

Tertiary Care Hospital.

Patients:

Forty-three adult patients undergoing transmastoid repair of spontaneous middle fossa CSF leak between 2014 and 2020 (BC:12, AM:15, CR:16).

Interventions:

Cortical mastoidectomy, identification of defect, and repair with BC (Cranios® hydroxyapatite), AM (local bone, fascia, fat, and/or cartilage), or CM (Cranios® combined with autologous materials).

Main Outcome Measures:

Successful repair without recurrent CSF leak or encephalocele throughout follow up.

Results:

Fifty-one percent of subjects were female. Mean age at repair was 58.6 years (SD 10.9). Mean BMI was 35.4 (SD 7.6; BC:36.3, AM:36.5, CM:33.6). Forty (93%) patients had successful repair without known recurrent CSF leak or encephalocele since surgery (BC:11, 91.6%; AM:14, 93.3%; CM:15, 93.8%; p = 0.49) over a mean length of follow up of 49.6 months (BC: 37.9, AM: 59.2, CR: 49.5). The difference in mean operative time amongst the groups was faster for patients using bone cement (BC: 100.2 min, AM: 182.8, CM: 133.2; p < 0.00001).

Conclusions:

BC, AM, and CM techniques each demonstrate effective and sustained means of repair for middle fossa CSF leak and encephalocele, even in the presence of multiple defects. Use of isolated BC offers a significant decrease in operative time with a noninferior outcome. Active CSF leak at the time of surgery is associated with increased risk of recurrence.
A Portrait of Menière's Disease Using Contemporary Hearing and Balance Tests
Authors: Hannigan Imelda P. , Rosengren Sally M. , Young Allison S. , Bradshaw Andrew P. , Calic Zeljka , Kwok Belinda , Alraddy Bashayer , Gibson William P. R. , Kong Jonathan , Flanagan Sean , Halmagyi G. Michael , Watson Shaun R. D. , Welgampola Miriam S.
Published: January 2022

Objective:

Menière's disease (MD) is characterized by recurrent vertigo and fluctuating aural symptoms. Diagnosis is straightforward in typical presentations, but a proportion of patients present with atypical symptoms. Our aim is to profile the array of symptoms patients may initially present with and to analyze the vestibular and audiological test results of patients with a diagnosis of MD.

Design:

A retrospective study of patient files.

Setting:

A tertiary, neuro-otology clinic Royal Prince Alfred Hospital, Sydney, Australia.

Method:

We identified 375 patients. Their history, examination, vestibular-evoked myogenic potentials (VEMP), video head-impulse test, canal-paresis on caloric testing, subjective visual horizontal (SVH), electrocochleography, ictal nystagmus, and audiometry were assessed.

Results:

Atypical presenting symptoms were disequilibrium (n = 49), imbalance (n = 13), drop-attacks (n = 12), rocking vertigo (n = 2), and unexplained vomiting (n = 3), nonspontaneous vestibular symptoms in 21.6%, fluctuation of aural symptoms only (46%), and headaches (31.2%). Low velocity, interictal spontaneous-nystagmus in 13.3% and persistent positional-nystagmus in 12.5%. Nystagmus recorded ictally in 90 patients was mostly horizontal (93%) and of high velocity (48 ± 34°/s). Testing yielded abnormal caloric responses in 69.6% and abnormal video head impulse test 12.7%. Air-conducted cervical VEMPs were abnormal in 32.2% (mean asymmetry ratio [AR] 30.2 ± 46.5%) and bone-conducted ocular VEMPs abnormal in 8.8% (AR 11.2 ± 26.8%). Abnormal interictal SVH was in 30.6%, (ipsiversive n = 46 and contraversive n = 19). Mean pure-tone averages 50 dB ± 23.5 and 20 dB ± 13 for affected and unaffected ears.

Conclusion:

Menière's disease has a distinctive history, but atypical presentations with normal vestibular function and hearing are a diagnostic challenge delaying treatment initiation.
Paroxysmal Cold Hemoglobinuria: Diagnosis From the Blood Smear
Authors: Radhakrishnan Kottayam , Downie Peter A. , Earley Ciara M.
Published: January 2022

Phagocytosis of red cells by neutrophils, referred to as neutrophil erythrophagocytosis, on the blood smear as a helpful diagnostic sign of paroxysmal cold hemoglobinuria is underrecognized. We present a child with paroxysmal cold hemoglobinuria and prominent neutrophil erythrophagocytosis to highlight the importance of this finding in the diagnosis of paroxysmal cold hemoglobinuria.
A Randomized Trial of Binocular Dig Rush Game Treatment for Amblyopia in Children Aged 4 to 6 Years
Authors: Manny Ruth E. , Holmes Jonathan M. , Kraker Raymond T. , Li Zhuokai , Waters Amy L. , Kelly Krista R. , Kong Lingkun , Crouch Earl R. , Lorenzana Ingryd J. , Alkharashi Maan S. , Galvin Jennifer A. , Rice Melissa L. , Melia B. Michele , Cotter Susan A. ,   on behalf of the Pediatric Eye Disease Investigator Group
Published: January 2022

SIGNIFICANCE

Binocular treatment for unilateral amblyopia is an emerging treatment that requires evaluation through a randomized clinical trial.

PURPOSE

This study aimed to compare change in amblyopic-eye visual acuity (VA) in children aged 4 to 6 years treated with the dichoptic binocular iPad (Apple, Cupertino, CA) game, Dig Rush (not yet commercially available; Ubisoft, Montreal, Canada), plus continued spectacle correction versus continued spectacle correction alone.

METHODS

Children (mean age, 5.7 years) were randomly assigned to home treatment for 8 weeks with the iPad game (prescribed 1 h/d, 5 d/wk [n = 92], or continued spectacle correction alone [n = 90]) in a multicenter randomized clinical trial. Before enrollment, children wearing spectacles were required to have at least 16 weeks of wear or no improvement in amblyopic-eye VA (<0.1 logMAR) for at least 8 weeks. Outcome was change in amblyopic-eye VA from baseline to 4 weeks (primary) and 8 weeks (secondary) assessed by masked examiner.

RESULTS

A total of 182 children with anisometropic (63%), strabismic (16%; <5∆ near, simultaneous prism and cover test), or combined-mechanism (20%) amblyopia (20/40 to 20/200; mean, 20/63) were enrolled. After 4 weeks, mean amblyopic VA improved by 1.1 logMAR lines with binocular treatment and 0.6 logMAR lines with spectacles alone (adjusted difference, 0.5 lines; 95.1% confidence interval [CI], 0.1 to 0.9). After 8 weeks, results (binocular treatment: mean amblyopic-eye VA improvement, 1.3 vs. 1.0 logMAR lines with spectacles alone; adjusted difference, 0.3 lines; 98.4% CI, −0.2 to 0.8 lines) were inconclusive because the CI included both zero and the pre-defined difference in mean VA change of 0.75 logMAR lines.

CONCLUSIONS

In 4- to 6-year-old children with amblyopia, binocular Dig Rush treatment resulted in greater improvement in amblyopic-eye VA for 4 weeks but not 8 weeks. Future work is required to determine if modifications to the contrast increment algorithm or other aspects of the game or its implementation could enhance the treatment effect.
Long-term Effect of Dual-focus Contact Lenses on Myopia Progression in Children: A 6-year Multicenter Clinical Trial
Authors: Chamberlain Paul , Bradley Arthur , Arumugam Baskar , Hammond David , McNally John , Logan Nicola S. , Jones Deborah , Ngo Cheryl , Peixoto-de-Matos Sofia C. , Hunt Chris , Young Graeme
Published: January 2022

SIGNIFICANCE

Treatment of myopic children with a dual-focus soft contact lens (DFCL; MiSight 1 day) produced sustained slowing of myopia progression over a 6-year period. Significant slowing was also observed in children switched from a single vision control to treatment lenses (3 years in each lens).

PURPOSE

This study aimed to evaluate the effectiveness of DFCLs in sustaining slowed progression of juvenile-onset myopia over a 6-year treatment period and assess myopia progression in children who were switched to a DFCL at the end of year 3.

METHODS

Part 1 was a 3-year clinical trial comparing DFCLs with a control contact lens (Proclear 1 day) at four investigational sites. In part 2, subjects completing part 1 were invited to continue for 3 additional years during which all children were treated with MiSight 1 day DFCLs (52 and 56 from the initially treated [T6] and control [T3] groups, respectively). Eighty-five subjects (45 [T3] and 40 [T6]) completed part 2. Cyclopleged spherical equivalent refractive errors (SEREs) and axial lengths (ALs) were monitored, and a linear mixed model was used to compare their adjusted change annually.

RESULTS

Average ages at part 2 baseline were 13.2 ± 1.3 and 13.0 ± 1.5 years for the T6 and T3 groups, respectively. Slowed myopia progression in the T6 group observed during part 1 was sustained throughout part 2 (mean ± standard error of the mean: change from baseline SERE [in diopters], −0.52 ± 0.076 vs. −0.51 ± 0.076; change in AL [in millimeters], 0.28 ± 0.033 vs. 0.23 ± 0.033; both P > .05). Comparing progression rates in part 2 for the T6 and T3 groups, respectively, indicates that prior treatment does not influence efficacy (SERE, −0.51 ± 0.076 vs. −0.34 ± 0.077; AL, 0.23 ± 0.03 vs. 0.18 ± 0.03; both P > .05). Within-eye comparisons of AL growth revealed a 71% slowing for the T3 group (3 years older than part 1) and further revealed a small subset of eyes (10%) that did not respond to treatment.

CONCLUSIONS

Dual-focus soft contact lenses continue to slow the progression of myopia in children over a 6-year period revealing an accumulation of treatment effect. Eye growth of the initial control cohort with DFCL was slowed by 71% over the subsequent 3-year treatment period.
Impact of 13-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease Among Adults With HIV—United States, 2008–2018
Authors: Kobayashi Miwako , Matanock Almea , Xing Wei , Adih William K. , Li Jianmin , Gierke Ryan , Almendares Olivia , Reingold Arthur , Alden Nisha , Petit Susan , Farley Monica M. , Harrison Lee H. , Holtzman Corinne , Baumbach Joan , Thomas Ann , Schaffner William , McGee Lesley , Pilishvili Tamara
Published: January 2022

Background:

People with HIV (PWH) are at increased risk for invasive pneumococcal disease (IPD). Thirteen-valent pneumococcal conjugate vaccine (PCV13) was recommended for use in US children in 2010 and for PWH aged 19 years or older in 2012. We evaluated the population-level impact of PCV13 on IPD among PWH and non-PWH aged 19 years or older.

Methods:

We identified IPD cases from 2008 to 2018 through the Active Bacterial Core surveillance platform. We estimated IPD incidence using the National HIV Surveillance System and US Census Bureau data. We measured percent changes in IPD incidence from 2008 to 2009 to 2017–2018 by HIV status, age group, and vaccine serotype group, including serotypes in recently licensed 15-valent (PCV15) and 20-valent (PCV20) PCVs.

Results:

In 2008–2009 and 2017–2018, 8.4% (552/6548) and 8.0% (416/5169) of adult IPD cases were among PWH, respectively. Compared with non-PWH, a larger proportion of IPD cases among PWH were in adults aged 19–64 years (94.7%–97.4% vs. 56.0%–60.1%) and non-Hispanic Black people (62.5%–73.0% vs. 16.7%–19.2%). Overall and PCV13-type IPD incidence in PWH declined by 40.3% (95% confidence interval: −47.7 to −32.3) and 72.5% (95% confidence interval: −78.8 to −65.6), respectively. In 2017–2018, IPD incidence was 16.8 (overall) and 12.6 (PCV13 type) times higher in PWH compared with non-PWH; PCV13, PCV15/non-PCV13, and PCV20/non-PCV15 serotypes comprised 21.5%, 11.2%, and 16.5% of IPD in PWH, respectively.

Conclusions:

Despite reductions post-PCV13 introduction, IPD incidence among PWH remained substantially higher than among non-PWH. Higher-valent PCVs provide opportunities to reduce remaining IPD burden in PWH.
Ethnic/Racial Disparities in Longitudinal Neurocognitive Decline in People With HIV
Authors: Wei-Ming Watson Caitlin , Kamalyan Lily , Tang Bin , Hussain Mariam A. , Cherner Mariana , Rivera Mindt Monica , Byrd Desiree A. , Franklin Donald R. , Collier Ann C. , Clifford David B. , Gelman Benjamin , Morgello Susan , McCutchan John Allen , Ellis Ronald J. , Grant Igor , Heaton Robert K. , Marquine María J. ,   for the CHARTER Group
Published: January 2022

Background:

To examine longitudinal neurocognitive decline among Latino, non-Latino Black, and non-Latino White people with HIV (PWH) and factors that may explain ethnic/racial disparities in neurocognitive decline.

Methods:

Four hundred ninety nine PWH (13.8% Latino, 42.7% Black, 43.5% White; baseline age: M = 43.5) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed neurocognitive, neuromedical, and laboratory assessments every 6–12 months with up to 5 years of follow-up. Longitudinal neurocognitive change was determined via published regression-based norms. Survival analyses investigated the relationship between ethnicity/race and neurocognitive change, and baseline and time-dependent variables that may explain ethnic/racial disparities in neurocognitive decline, including socio-demographic, HIV-disease, medical, psychiatric, and substance use characteristics.

Results:

In Cox proportional hazard models, hazard ratios for neurocognitive decline were increased for Latino compared with White PWH (HR = 2.25, 95% CI = 1.35 to 3.73, P = 0.002), and Latino compared with Black PWH (HR = 1.86, 95% CI = 1.14 to 3.04, P = 0.013), with no significant differences between Black and White PWH (P = 0.40). Comorbidities, including cardiometabolic factors and more severe neurocognitive comorbidity classification, accounted for 33.6% of the excess hazard for Latino compared with White PWH, decreasing the hazard ratio associated with Latino ethnicity (HR = 1.83, 95% CI = 1.06 to 3.16, P = 0.03), but did not fully account for elevated risk of decline.

Conclusions:

Latino PWH may be at higher risk of early neurocognitive decline compared with Black and White PWH. Comorbidities accounted for some, but not all, of this increased risk among Latino PWH. Future research examining institutional, sociocultural, and biomedical factors, including structural discrimination and age-related biomarkers, may further explain the observed disparities.
Metallic Artifact Reduction of Multiacquisition With Variable Resonance Image Combination Selective–Short Tau Inversion Recovery for Postoperative Cervical Spine With Artificial Disk Replacement: A Preliminary Study
Authors: Kim Jeong Kyeom , Kim Yeo Ju , Lee Seunghun , Yoon Daehyun , Lee Ro Woon , Hong Jung Ui , Ryu Dal-Sung , Bae Jiyoon
Published: January 2022

Objective

This study aimed to evaluate multiacquisition with variable resonance image combination selective short tau inversion recovery (MAVRIC SL STIR) for metallic artifact reduction in magnetic resonance imaging (MRI) of postoperative cervical spine with artificial disk replacement.

Methods

A porcine cervical spine with artificial disk replacement was subject to 3 T MRI with variable fat-suppressed fluid-sensitive sequences. Five volunteers underwent MRI with MAVRIC SL STIR and STIR. Quantitative and qualitative analyses were performed for metallic artifact reduction.

Results

MAVRIC SL STIR showed the least signal void areas in the tissue phantom and volunteer study. In the tissue phantom study, MAVRIC SL STIR showed the best visualization of anatomic structure, least distortion, and signal pile-up. However, it ranked last for the homogeneity of fat suppression among sequences. In the volunteer study, MAVRIC SL STIR showed better visualization of anatomic structure and lesser distortion, but showed worse image quality of the spinal cord than STIR in the sagittal plane (P < 0.05).

Conclusions

MAVRIC SL STIR might be useful for visualization of anatomy by reduction of signal void areas and distortion in the operated site but should be used as a complement to STIR for evaluation of the spinal cord signal change.
Esophageal Oligometastases of the Foot
Authors: Ricely John M. , Posocco David , Dadparvar Simin
Published: January 2022

Acrometastasis is a rare clinical entity, estimated to represent less than 0.3% of all bone metastases. Here, we present a case of esophageal cancer that was treated with esophagectomy, chemotherapy, and radiation therapy and developed oligometastases of the foot after 8 years in remission. The patient developed pain and swelling in his left ankle and foot as the presenting symptom. He underwent radiography and MRI of the affected area, which revealed the lesion. A 99mTc-MDP whole-body bone scan did not reveal any other sites of metastasis.
Rare “Burned-Out” Testicular Mixed Germ Cell Tumor on 18F-FDG PET/CT
Authors: Wu Yu-Chin , Kao Chia-Hung , Sun Shung-Shung , Hsieh Te-Chun
Published: January 2022

Spontaneous regression of testicular mixed germ cell tumor is rare and is also called burned-out testicular tumor. We herein present the case of a 20-year-old man who was initially diagnosed with metastatic embryonal carcinoma. 18F-FDG PET/CT demonstrated apparent metastases in the lymph node regions and both lungs. A covert right testicular lesion was noted according to the features on the CT component of PET/CT, which was subsequently confirmed as burned-out testicular mixed germ cell tumor.