bluuebunny/crossref_metadata_2025 huggingface dataset:
Framework for opioid stigma in cancer pain
Authors: Bulls Hailey W. , Chu Edward , Goodin Burel R. , Liebschutz Jane M. , Wozniak Antoinette , Schenker Yael , Merlin Jessica S.
Published: May 2021

Millions of patients with cancer pain are treated with prescription opioids each year. However, efforts to mitigate the ongoing opioid crisis result in unintended consequences with opioid pain management, including opioid stigma. Emerging research indicates that opioid stigma is problematic in patients with cancer, but few studies have examined contributors to and impacts of opioid stigma in this population. To guide future research in this area, we propose a conceptual framework—the opioid stigma framework (OSF)—with which to understand and improve opioid stigma in patients with cancer pain. Development of the OSF was guided by a literature review of stigma in health-related conditions, adaptation of the existing Health Stigma and Discrimination Framework, a topical review of challenges related to opioid cancer pain management, and author expertise in cancer, pain, and opioid prescribing. The proposed OSF highlights 5 domains: (1) contributors to opioid stigma, or factors that increase the likelihood that a patient will experience opioid stigma; (2) intersecting stigmas, or the convergence of multiple stigmatized identities within a patient; (3) stigma manifestations, or the ways opioid stigma is manifested in patients, clinicians, and the community; (4) proximal outcomes, or the immediate consequences of opioid stigma in patients; and (5) long-term impacts in patients. The OSF provides 2 main avenues to facilitate future research: (1) providing a framework to explore the mechanisms that underlie opioid stigma and its impact on cancer pain management and (2) supporting the development of targeted, tailored interventions to eliminate opioid stigma.
Rapid On-site Evaluation (ROSE) in Capillary Pull Versus Suction Biopsy Technique With Endobronchial Ultrasound-transbronchial Needle Aspiration (EBUS-TBNA)
Authors: Kassirian Shayan , Mitchell Michael A. , McCormack David G. , Zeman-Pocrnich Cady , Dhaliwal Inderdeep
Published: May 2021

Background:

Suction and capillary pull are 2 biopsy techniques used in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Although these techniques have been shown to perform comparably in terms of overall diagnostic yield, we hypothesized that the capillary pull technique would be associated with improved rapid on-site evaluation (ROSE) adequacy rates thus allowing for a shorter procedure time.

Methods:

One hundred eighteen patients undergoing EBUS-TBNA for any indication were randomized to suction or capillary pull techniques for the first biopsy pass; the technique used for all subsequent passes was based on operator preference and was not recorded. The first pass was subjected to ROSE and an adequacy assessment was given. ROSE slides were also scored for cellularity of diagnostic/lesional cells and blood contamination. The overall procedure time was also recorded.

Results:

There were no significant differences between suction and capillary pull techniques in terms of ROSE adequacy rates. Cellularity of diagnostic/lesional cells and blood contamination scores were also comparable. There was no significant difference in procedure time for the 2 techniques.

Conclusion:

This study suggests no differences in ROSE outcomes between suction and capillary pull techniques in EBUS-TBNA. The technique used should therefore be left to the discretion of the operator.
Clinical characteristics and outcomes of patients with isolated pulmonary embolism
Authors: Lee Yong Hoon , Cha Seung-Ick , Shin Kyung Min , Lim Jae Kwang , Lee Won Kee , Park Ji-Eun , Choi Sun Ha , Seo Hyewon , Yoo Seung-Soo , Lee Shin-Yup , Lee Jaehee , Kim Chang-Ho , Park Jae-Yong
Published: May 2021

The clinical relevance of concomitant deep vein thrombosis (DVT) in patients with pulmonary embolism remains controversial. The aim of the present study was to assess clinical characteristics of patients with isolated pulmonary embolism, thereby investigating isolated pulmonary embolism related clinical factors.

Patients hospitalized for pulmonary embolism who underwent DVT workup within 3 days of pulmonary embolism diagnosis were retrospectively classified into two groups: patients with isolated pulmonary embolism and patients with DVT-associated pulmonary embolism (DVT-PE). The clinical, laboratorial and radiological parameters were compared between the two groups.

Of 1012 patients, 322 (31.8%) presented with isolated pulmonary embolism, and 690 (68.2%) presented with DVT-PE. In a multivariate analysis, female sex was an independent factor for predicting isolated pulmonary embolism [odds ratio (OR) 1.69, 95% confidence interval (CI) 1.26–2.26, P < 0.001], whereas cancer (OR 0.64, 95% CI 0.43–0.96, P = 0.031), leg pain or swelling (OR 0.08, 95% CI 0.04–0.18, P < 0.001), and central pulmonary embolism (OR 0.44, 95% CI 0.32–0.59, P < 0.001) were negatively associated with isolated pulmonary embolism. There were no significant differences between the two groups with regard to risk stratification and short-term prognosis of pulmonary embolism, including adverse outcomes and pulmonary embolism related in-hospital mortality.

Of pulmonary embolism patients who underwent imaging tests for DVT, approximately 32% presented with isolated pulmonary embolism. Isolated pulmonary embolism was positively associated with female sex, whereas it was negatively associated with cancer, leg pain or swelling, and central pulmonary embolism. The presence or absence of concomitant DVT did not influence the severity and short-term prognosis of pulmonary embolism.
Vitamin D in critical care: where are we now and what is next?
Authors: Amrein Karin , Hoffmann Magdalena , Lobmeyr Elisabeth , Martucci Gennaro
Published: May 2021

Purpose of review

To summarize the recent evidence on the role of vitamin D deficiency in critically ill patients and emerging data claiming a role of vitamin D in COVID-19.

Recent findings

Vitamin D is a strong predictor for worse outcomes in critically ill patients, and as well in COVID-19. The vitamin D content in typical nutrition regimes is lower than what is recommended for the general population. Although its supplementation has been shown to reduce respiratory tract infections, asthma exacerbations and mortality risk in noncritically ill patients, its role in the acute setting is not yet clear. Several small intervention trials have shown interesting results in COVID-19, and larger studies are ongoing.

Although research on this topic is still ongoing, it appears reasonable to recommend at least the standard vitamin dose for the healthy population (600--800 IU of native vitamin D3). Many questions remain on the actual role, the best metabolite, regime, and so forth. However, the role for vitamin D in bone health is clear. Elderly ICU survivors have a high risk for osteoporosis/fractures, so at least in this population, an optimal vitamin D status should be targeted.
Higher Medicare Expenditures Are Associated With Better Integrated Care as Perceived by Patients
Authors: Kerrissey Michaela J. , Frean Molly , Traboulsi Abd Al-Rahman , Singer Sara J.
Published: May 2021

Background:

Integrated care that is continuous, coordinated and patient-centered is vital for Medicare beneficiaries, but its relationship to health care expenditures remains unclear.

Research Objective:

This study explores—for the first time—the relationship between integrated care, as measured from the patient’s perspective, and health care expenditures.

Methods:

Subjects include a sample of continuously eligible fee-for-service Medicare beneficiaries (n=8807) in 2015. Analyses draw on 7 previously validated measures of patient-perceived integrated care from the 2015 Medicare Current Beneficiary Survey. These data are combined with 2015 administrative utilization data that measure health care expenditures. Relationships between patient-perceived integrated care and costs are assessed using generalized linear models with comprehensive control measures.

Results:

Patients who perceive more integrated care have higher expenditures for many, but not all, cost categories examined. Aspects of integrated care pertaining to primary provider and specialist care are associated with higher costs in several areas (particularly inpatient costs associated with specialist knowledge of the patient). Office staff members’ knowledge of the patient’s medical history is associated with lower home health costs.

Conclusions:

Patients who experience their care as more integrated may have higher expenditures on average. Thoughtful policy choices, further research, and innovations that enable patients to perceive integrated care at lower or neutral cost are needed.
A Mixed-method Evaluation of the Behavioral Health Integration and Complex Care Initiative Using the Consolidated Framework for Implementation Research
Authors: Siantz Elizabeth , Henwood Benjamin , Rabin Borsika , Center Kimberly , Fenwick Karissa , Gilmer Todd
Published: May 2021

Background:

Integrated behavioral health and primary care can improve the health of persons with complex chronic conditions. The Behavioral Health Integration and Complex Care Initiative (BHICCI) implemented integrated care across a large health system. Whether Behavioral Health Organizations (BHOs) and Federally Qualified Health Centers (FQHCs) implemented the BHICCI differently is unclear.

Objectives:

The objective of this study was to evaluate integration under the BHICCI and to understand implementation differences between BHOs and FQHCs.

Methods:

We used a convergent parallel mixed-method design. Integration was measured quantitatively using the Maine Health Access Site Self-Assessment (SSA), which was completed by clinic teams at baseline and 24 months, and through n=70 qualitative interviews with initiative stakeholders, which were organized using the Consolidated Framework for Implementation Research. Results were compared to understand how qualitative findings explained quantitative results.

Results:

Data were collected in 7 clinics (n=2 FQHC; n=5 BHOs). FQHCs reported greatest improvement in the client centered subscale, with a baseline score of 4.6 (SD=0.64) and 7.8 (SD=0.89) at 24 months. BHOs reported greatest improvement in the organizational supports for integration subscale, with a baseline score of 4.8 (SD=1.07) and 7.9 (SD=1.1) at 24 months. Our Consolidated Framework for Implementation Research analysis illustrates contextual factors, such as insurance plan supports and clinic-level challenges, that explain these scores.

Conclusions:

All clinical settings received support from the health plan, but differences between BHOs and FQHCs affected integration progress. Study results can help identify organizational practices that advance or undermine the delivery of integrated care across multiple clinical settings.
SNF472: mechanism of action and results from clinical trials
Authors: Sinha Smeeta , Raggi Paolo , Chertow Glenn M.
Published: May 2021

Purpose of review

Vascular calcification (VC) is associated with increased cardiovascular event rates, particularly in patients with end-stage kidney disease (ESKD). Dysregulated mineral metabolism and inflammation have been shown to promote VC, however, treatment options targeting VC specifically are not available. This review outlines the pathophysiological mechanisms contributing to VC in ESKD and describes recent studies evaluating the effects of the first-in-class inhibitor of VC, SNF472.

Recent findings

SNF472 directly inhibits calcium phosphate crystal formation and aggregation. SNF472 has completed early phase clinical trials with a favourable safety profile and Phase 2 clinical trial data have shown attenuation of coronary artery and aortic valve calcification in patients receiving hemodialysis.

Therapeutic agents that directly target VC may prevent the multiple complications associated with dystrophic calcification in patients with ESKD.
Recent evidence on the effect of treatment of metabolic acid on the progression of kidney disease
Authors: Hultin Sebastian , Johnson David W. , Badve Sunil V.
Published: May 2021

Purpose of review

Preclinical and epidemiological studies have shown an association between acidosis and progression of chronic kidney disease (CKD) and kidney fibrosis. This review discusses the recent trials evaluating the effect of treatment of metabolic acidosis on kidney outcomes.

Recent findings

The emerging evidence suggests that bicarbonate treatment may slow the progression of CKD and reduce the risk of kidney failure. However, high-certainty evidence on the efficacy and safety of alkali therapy is still lacking. Ongoing studies are evaluating the effect of veverimer, a novel nonabsorbable polymer, on clinical kidney outcomes.

Recent studies indicate a potential benefit from reduction in acid load in patients with CKD. Whilst it is reasonable that clinicians institute acid-lowering interventions in CKD patients with acidosis, adequately powered trials are required to evaluate the benefit of correction of metabolic acidosis to delay kidney disease progression.
Genetic determinants of LDL cholesterol and risk of intracerebral haemorrhage
Authors: Szejko Natalia , Kirsch Elayna , Falcone Guido J.
Published: May 2021

Purpose of review

The role of lipids in spontaneous, nontraumatic intracerebral haemorrhage (ICH) remains controversial, as some studies suggest that lower levels of total and LDL cholesterol could increase the risk of this disease. Because of their random assortment during meiosis, genetic variants known to associate with lipid levels can be used as instruments to evaluate this relationship from a causal perspective. The purpose of this review is to summarize the existing literature related to genetically determined LDL cholesterol levels and risk of ICH.

Recent findings

A number of studies have demonstrated that lower LDL levels are associated with a higher risk of ICH and a higher burden of neuroimaging markers of cerebral small vessel disease, such as microbleeds and white matter hyperintensity volume. As for genetically elevated lipid levels, several studies confirmed an inverse association between LDL levels and ICH. However, a number of observational studies and large meta-analyses of clinical trials of statins have failed to show such association.

Observational studies and clinical trials of statins have yielded inconsistent results regarding a possible link between LDL levels and the risk of ICH. Genetic studies focused on genetically elevated LDL levels and risk of ICH have, for the most, found an inverse association.
Safety and Efficacy of Pegteograstim on Chemotherapy-induced Neutropenia in Children and Adolescents With Solid Tumors
Authors: Cho Hee Won , Lee Ji Won , Ju Hee Young , Hyun Ju Kyung , Yoo Keon Hee , Koo Hong Hoe , Kim Kyunga , Sung Ki Woong
Published: May 2021

Purpose:

Pegteograstim (Neulapeg) is a recombinant human granulocyte colony-stimulating factor conjugated with methoxy-maleimide-polyethylene glycol. We conducted a single-arm study investigating its safety and noninferiority to conventional filgrastim in children and adolescents

Materials and Methods:

Patients younger than 21 years with solid tumors were eligible for the study. Pegteograstim was administered on day 7 of the fourth chemotherapy cycle. Toxicities were monitored, and the change in absolute neutrophil count was compared with that of the historic control (conventional filgrastim). This trial was registered at ClinicalTrials.gov as NCT02787876.

Results:

Thirty-two patients were enrolled. Adverse events possibly related to pegteograstim were musculoskeletal pain (n=3), skin nodule (n=1), paroxysmal cough (n=1), urticaria (n=2), rash (n=1), and itching (n=1). These adverse events were all grade 1 or 2. Duration of neutropenia (ANC<500/µL) was shorter in the pegteograstim group compared with the historic control (median 6.5 vs. 10 d, P=0.004). The time from day 0 to neutrophil recovery (ANC>500/µL) was shorter in the pegteograstim group (median 15 vs. 18 d, P=0.003).

Conclusions:

Pegteograstim is safe and shows comparable efficacy to conventional filgrastim in children and adolescents. Randomized controlled trials are needed to confirm its safety and efficacy.
A Glimpse Into the Magnet® Program Office
Authors: George Nicole
Published: May 2021

The Magnet Recognition Program® has a dedicated team of RNs and non-RNs who are committed to advancing nursing and supporting healthcare organizations on their Magnet® journeys. Healthcare organizations who are either Magnet-designated or applicants for Magnet designation regularly communicate with the various members of the Magnet program office team. This perspective will highlight the roles of the senior Magnet program analysts and the assistant director of Magnet program operations.
Wisdom Shared
Authors: Gruebling Nicole , Beckman Beth P. , Reeves Susan A.
Published: May 2021

With the evolution from single healthcare entities to health systems, the role of the system chief nurse executive (SCNE) has evolved. The SCNE leads at the highest executive level in the system and has continuum of care accountability. To effectively support the scope and breadth of the SCNE role, the organizational structure must contain key elements to ensure success. This article outlines the key elements of a system nursing organization and serves to aid in the development, improvement, and sustainability of successful system nursing structures.
Innovations in Evaluating Nursing Academic Practice Partnerships
Authors: Polancich Shea , Miltner Rebecca , Poe Terri , Harper Doreen , Moneyham Linda , Shirey Maria
Published: May 2021

Academic-practice partnerships are formalized relationships encouraged by the American Association of Colleges of Nursing to meet healthcare and societal needs. While Academic-practice partnerships have existed for decades, the process for evaluating their outcomes often lacks a robust, standardized structure. The purpose of this article is to describe one organization's process for developing and implementing an evaluation blueprint for appraising an Academic-practice partnership.
The Effect of Novel Medical Nonhormonal Treatments on the Angiogenesis of Endometriotic Lesions
Authors: Thanatsis Nikolaos , Filindris Theodoros , Siampalis Antonios , Papageorgiou Evangelia , Panagodimou Evangelia , Adonakis George , Kaponis Apostolos
Published: May 2021

Importance

Irrespective of the precise mechanisms leading to endometriosis, angiogenesis is essential for the establishment and long-term proliferation of the disease. As current surgical and medical management options for women with endometriosis have substantial drawbacks and limitations, novel agents are needed and molecules targeting the angiogenic cascade could serve as potential candidates.

Objective

Our aim was to review current data about the role of angiogenesis in the pathophysiology of endometriosis and summarize the novel antiangiogenic agents that could be potentially used in clinical management of patients with endometriosis.

Evidence Acquisition

Original research and review articles were retrieved through a computerized literature search.

Results

Loss of balance between angiogenic activators and suppressors triggers the nonphysiological angiogenesis observed in endometriotic lesions. Several proangiogenic mediators have been identified and most of them have demonstrated increased concentrations in the peritoneal fluid and/or serum of women with endometriosis. Among the antiangiogenic molecules, anti–vascular endothelial growth factor agents, dopamine agonists, romidepsin, and statins have shown the most promising results so far.

Conclusions and Relevance

Given the limitations of current treatments of endometriosis, there is a need for novel, more efficient agents. Antiangiogenic molecules could be used potentially in clinical management of women with endometriosis; however, their safety and efficiency should be carefully assessed prior to that. Further large prospective trials in humans are needed before any treatment is introduced into daily clinical practice.

Target Audience

Obstetricians and gynecologists, family physicians

Learning Objectives

After participating in this activity, physicians should be better able to summarize current knowledge about the role of proangiogenic and antiangiogenic mediators in the development of endometriosis; outline the main antiangiogenic agents that are under investigation; and describe their effect on the angiogenic mediators of endometriosis.
Levonorgestrel-Releasing Intrauterine System Versus Endometrial Ablation for Heavy Menstrual Bleeding
Authors: Beelen Pleun , van den Brink Marian J. , Herman Malou C. , Geomini Peggy M. A. J. , Dekker Janny H. , Duijnhoven Ruben G. , Mak Nienke , van Meurs Hannah S. , Coppus Sjors F. , van der Steeg Jan Willem , Eising Heleen P. , Massop-Helmink Diana S. , Klinkert Ellen R. , Nieboer Theodoor E. , Timmermans Anne , van der Voet Lucet F. , Veersema Sebastiaan , Smeets Nicol A. C. , Schutte Joke M. , van Baal Marchien , Bossuyt Patrick M. , Mol Ben Willem J. , Berger Marjolein Y. , Bongers Marlies Y.
Published: May 2021

(Abstracted from Am J Obstet Gynecol 2021;224(2):187.e1–187.e10)

Heavy menstrual bleeding (HMB) can negatively influence physical activity, work productivity, and sexual life and therefore has a major impact on women's quality of life (QoL). The National Institute for Health and Care Excellence guidelines recommend the levonorgestrel-releasing intrauterine system (LNG-IUS) as the treatment of first choice for HMB.
Vaginal Estrogen for the Prevention of Recurrent Urinary Tract Infection in Postmenopausal Women: A Randomized Clinical Trial
Authors: Ferrante Kimberly L. , Wasenda Erika J. , Jung Carrie E. , Adams-Piper Emily R. , Lukacz Emily S.
Published: May 2021

(Abstracted from Female Pelvic Med Reconstr Surg 2021;27(2):112–117)

Recurrent urinary tract infection (rUTI) is defined as at least 2 UTIs in a 6-month span or 3 UTIs in a 1-year span. Postmenopausal status is a well-described risk factor for rUTI, with declining levels of systemic estrogen hypothesized as a contributory biological mechanism.
Immunohistochemical Characterization of Bcl-2 in Oral Potentially Malignant Disorders
Authors: Chamorro-Petronacci Cintia M. , Lafuente-Ibanez De Mendoza Irene , Suarez-Peñaranda Jose M. , Padin-Iruegas Elena , Blanco-Carrion Andres , Lorenzo-Pouso Alejandro I. , Ortega Karem L. , Pérez-Sayáns Mario
Published: May 2021

Bcl-2 is a group of apoptotic proteins that play a key role in cellular homeostasis. Overexpression of Bcl-2 has been associated with the poor prognosis of oral squamous cell carcinoma (OSCC). The aim of this study is to analyze the immunohistochemical expression of Bcl-2 in healthy oral mucosa, different oral potentially malignant disorders and OSCC, and to determine its diagnostic value. A retrospective observational study was carried out in the Oral Medicine Unit of the University of Santiago de Compostela. All the clinicopathologic data were collected and paraffin-embedded blocks were available to perform the immunohistochemistry study with Bcl-2. We studied 18 fibromas, 15 OSCC, 29 oral leukoplakia lesions (OL), 59 oral lichen planus (OLP) cases, and 16 healthy controls. OL with epithelial dysplasia (31.2%) showed the highest expression of Bcl-2 and OLP (1.9%) showed the lowest expression of Bcl-2 (P=0.025). Receiver operating characteristics curves showed that the detection of Bcl-2 enables discrimination between OL and OLPs (sensitivity: 58.6%, specificity of 99.32%). Bcl-2 negative expression in the OLP diagnosis obtained an odds ratio of 13.750 (95% confidence interval: 3.354-56.369; P<0.0001) and the positive expression in the OL 4.468 (95% confidence interval: 1.889-10.565; P=0.001). Bcl-2 could be used as a diagnostic biomarker to study their malignant transformation.
Lymphadenopathy Associated With Neutralizing Anti-interferon-gamma Autoantibodies Could Have Monoclonal T-cell Proliferation Indistinguishable From Malignant Lymphoma and Treatable by Antibiotics
Authors: Yuan Chang-Tsu , Wang Jann-Tay , Sheng Wang-Huei , Cheng Pei-Yuan , Kao Chein-Jun , Wang Jann-Yuan , Chen Chien-Yuan , Liau Jau-Yu , Tsai Jia-Huei , Lin Yi-Jyun , Chen Chung-Chung , Chen Yee-Chun , Chang Shan-Chwen , Wu Un-In
Published: May 2021

Early recognition of adult-onset immunodeficiency associated with neutralizing anti-interferon gamma autoantibodies (anti-IFNγ Abs) remains difficult, and misdiagnoses have been reported. Although febrile lymphadenopathy is among the most common initial manifestations of this disorder, no comprehensive clinicopathologic analysis of lymphadenopathy in patients with anti-IFNγ Abs has been reported. Here, we describe 26 lymph node biopsy specimens from 16 patients. All patients exhibited concurrent disseminated nontuberculous mycobacterial infections, and 31% received a tentative diagnosis of lymphoma at initial presentation. We found 3 distinct histomorphologic patterns: well-formed granuloma (46%), suppurative inflammation or loose histiocytic aggregates (31%), and lymphoproliferative disorder (LPD, 23%). The latter shared some of the features of malignant T-cell lymphoma, IgG4-related disease, and multicentric Castleman disease. Half of the specimens with LPD had monoclonal T cells, and 33.3% were indistinguishable from angioimmunoblastic T-cell lymphoma as per current diagnostic criteria. All lymphadenopathy with LPD features regressed with antibiotics without administration of cytotoxic chemotherapy or immunotherapy. The median follow-up time was 4.3 years. Our study highlights the substantial challenge of distinguishing between lymphoma and other benign lymphadenopathy in the setting of neutralizing anti-IFNγ Abs. Increased vigilance and multidisciplinary discussion among clinicians and pathologists are required to achieve the most appropriate diagnosis and management.
Genetic and Clinical Studies of Patients With Increased Multinucleated Megakaryocytes in Bone Marrow as an Isolated Finding
Authors: Zheng Gang , He Rong , Reichard Kaaren K. , Peterson Jess F. , Olteanu Horatiu , Oliveira Jennifer L. , Rangan Aruna , Chen Dong , Shi Min
Published: May 2021

The presence of increased multinucleated megakaryocytes (aka osteoclast-like) is considered a dysplastic feature in myelodysplastic syndrome; however, its clinical significance in isolation is uncertain. Herein, we report the clinicopathologic and genetic features of 18 such cases of 40,539 bone marrow biopsies spanning 10 years. All 18 patients had ≥25% multinucleated megakaryocytes in otherwise normal bone marrow biopsies, which were evaluated for plasma cell neoplasms (n=9), lymphoma (n=4), or anemia/neutropenia (n=5). None of the 17 patients tested showed acquired cytogenetic abnormalities. Sixteen patients underwent targeted gene panel next-generation sequencing: 9 patients had no pathogenic mutations; 3 harbored a single pathogenic mutation with variant allele frequencies of 7.5%, 7.6%, and 10.7%, likely representing clonal hematopoiesis of indeterminate potential; 1 had 2 pathogenic mutations, 1 of which had a variant allele frequency >20%. Fourteen of 18 patients had a follow-up period >6 months (median: 36.5 mo, range: 7 to 110 mo) and no patients developed a new-onset cytopenia, a progressive cytopenia, or a myeloid neoplasm. The patient with 2 mutations had persistent anemia, worrisome for an emerging MDS. However, given the absence of thrombocytopenia, increased multinucleated megakaryocytes in this patient could be an unrelated incidental finding. Our study indicates that increased multinucleated megakaryocytes as an isolated finding is a rare phenomenon, and this sole morphologic finding is not diagnostic of myelodysplastic syndrome. Diagnostic approaches in the presence of increased multinucleated megakaryocytes are proposed based on different clinical and pathologic scenarios.
Morphologic Spectrum of Lymphadenopathy in Adult-onset Immunodeficiency (Anti-interferon-γ Autoantibodies)
Authors: Thingujam Bipin , Syue Ling-Shan , Wang Ren-Ching , Chen Chih-Jung , Yu Shan-Chi , Chen Chien-Chin , Medeiros L.J. , Liao I-Chuang , Tsai Jen-Wei , Chang Kung-Chao
Published: May 2021

Adult-onset immunodeficiency syndrome (AOIS) caused by anti-interferon-γ autoantibodies is an emerging disease. Affected patients present typically with systemic lymphadenopathy, fatigue, and fever. We studied 36 biopsy specimens, 31 lymph nodes, and 5 extranodal sites, of AOIS confirmed by serum autoantibody or QuantiFERON-TB Gold In-Tube assay. We describe the morphologic features and the results of ancillary studies, including special stains, immunohistochemistry, and molecular testing. The overall median age of these patients was 60.5 years (range, 41 to 83 y) with a male-to-female ratio of 20:16. All biopsy specimens showed nontuberculous mycobacterial infection, and most cases showed the following histologic features: capsular thickening with intranodal sclerosing fibrosis, irregularly distributed ill-formed granulomas or histiocytic aggregates with neutrophilic infiltration, interfollicular expansion by a polymorphic infiltrate with some Hodgkin-like cells that commonly effaces most of the nodal architecture and proliferation of high endothelial venules. In situ hybridization analysis for Epstein-Barr virus–encoded RNA showed scattered (<1%) to relatively more common (4% to 5%) positive cells in 29 of 30 (97%) tested specimens, reflecting immune dysregulation due to an interferon-γ defect. In the 31 lymph node specimens, 23 (74%) cases showed increased immunoglobulin G4–positive plasma cells (4 to 145/HPF; mean, 49.7/HPF) with focal areas of sclerosis reminiscent of immunoglobulin G4–related lymphadenopathy, 4 (13%) cases resembled, in part, nodular sclerosis Hodgkin lymphoma, and 9 (29%) cases mimicked T-cell lymphoma. Among 33 patients with available clinical follow-up, 20 (61%) showed persistent or refractory disease despite antimycobacterial therapy, and 1 patient died of the disease. We conclude that the presence of ill-defined granulomas, clusters of neutrophils adjacent to the histiocytic aggregates, and some Epstein-Barr virus–positive cells are features highly suggestive of AOIS. A high index of clinical suspicion and awareness of the morphologic features and differential diagnosis of AOIS are helpful for establishing the diagnosis.
Chimeric Antigen Receptor T-Cell Therapeutics for Multiple Myeloma
Authors: Wang Bo , Rajeeve Sridevi , Madduri Deepu
Published: May 2021

Chimeric antigen receptor (CAR) T-cell therapy has quickly emerged as a highly promising treatment for patients with relapsed and refractory multiple myeloma. There are numerous candidates under development, each with their unique characteristics and points of differentiation. The most recent US Food and Drug Administration approval of the first B-cell maturation antigen–targeted CAR-T cell therapy on March 26, 2021, has paved a path forward for the eventual evaluation of more of these investigational agents undergoing clinical trials. Herein, we highlight, from a clinical development perspective, the CAR-T cell therapies farthest along in development with updated data from the American Society of Hematology 2020 annual meeting. We also discuss potential paths of overcoming resistance to these therapies and the future direction for CAR-T cell therapeutics in multiple myeloma.
Feasibility of Cardiac Computed Tomography for the Evaluation of Ventricular Function in Postoperative Children With Congenital Heart Disease: Comparison With Cardiac Magnetic Resonance Imaging
Authors: Xie Wei-Hui , Guo Chen , Hu Li-Wei , Ouyang Rong-Zhen , Yao Xiao-Fen , Sun Ai-Min , Qiu Hai-Sheng , Yan Qin , Zhu Ya-Xin , Wang Qian , Zhong Yu-Min
Published: May 2021

Objective

We explored the feasibility of cardiac computed tomography (CCT) to evaluate postoperative ventricular function in children with congenital heart disease (CHD) and evaluated the accuracy and reproducibility of CCT using cardiac magnetic resonance (CMR) as a reference.

Methods

Thirty-two postoperative children with CHD (20 boys and 12 girls) who underwent CMR and CCT were enrolled. Left and right ventricular ejection fraction, end-diastolic volume, end-systolic volume, stroke volume, and cardiac index were measured using cardiac function analysis software. Cardiac function data were compared between CMR and CCT. The agreement between the 2 modalities was assessed using a Bland-Altman analysis. Intraclass correlation coefficients were used to assess intraobserver and interobserver reproducibility in CCT functional measurements.

Results

All functional parameters showed no significant difference (P > 0.05) and were well-correlated (r > 0.5, P < 0.05) between CMR and CCT. The mean values of all ventricular function parameters in CCT were higher compared with CMR. As indicated by 95% limits of agreement, left ventricular function parameters showed a better level of agreement compared with right ventricular function parameters between the 2 modalities. Intraobserver and interobserver reproducibility were excellent in CCT measurements for all functional parameters (intraclass correlation coefficient > 0.9).

Conclusions

Compared with the criterion standard of CMR, CCT is feasible for assessing postoperative ventricular function with sufficient diagnostic accuracy and reproducibility in children with CHD. In addition to its important role regarding anatomical characterization, CCT is a suitable alternative and convenient follow-up tool that can be used to functional evaluation in children who are intolerant with CMR or have contraindications to CMR.
Head-to-head Comparison of Qualitative Radiologist Assessment With Automated Quantitative Computed Tomography Analysis for Bronchiolitis Obliterans Syndrome After Hematopoietic Cell Transplantation
Authors: Sharifi Husham , Guenther Zachary D. , Leung Ann N.C. , Johnston Laura , Lai Yu K. , Hsu Joe L. , Guo H. Henry
Published: May 2021

Purpose:

Computed tomography (CT) findings of bronchiolitis obliterans syndrome (BOS) can be nonspecific and variable. This study aims to measure the incremental value of automated quantitative lung CT analysis to clinical CT interpretation. A head-to-head comparison of quantitative CT lung density analysis by parametric response mapping (PRM) with qualitative radiologist performance in BOS diagnosis was performed.

Materials and Methods:

Inspiratory and end-expiratory CTs of 65 patients referred to a post–bone marrow transplant lung graft-versus-host-disease clinic were reviewed by 3 thoracic radiologists for the presence of mosaic attenuation, centrilobular opacities, airways dilation, and bronchial wall thickening. Radiologists’ majority consensus diagnosis of BOS was compared with automated PRM air trapping quantification and to the gold-standard diagnosis of BOS as per National Institutes of Health (NIH) consensus criteria.

Results:

Using a previously established threshold of 28% air trapping on PRM, the diagnostic performance for BOS was as follows: sensitivity 56% and specificity 94% (area under the receiver operator curve [AUC]=0.75). Radiologist review of inspiratory CT images alone resulted in a sensitivity of 80% and a specificity of 69% (AUC=0.74). When radiologists assessed both inspiratory and end-expiratory CT images in combination, the sensitivity was 92% and the specificity was 59% (AUC=0.75). The highest performance was observed when the quantitative PRM report was reviewed alongside inspiratory and end-expiratory CT images, with a sensitivity of 92% and a specificity of 73% (AUC=0.83).

Conclusions:

In the CT diagnosis of BOS, qualitative expert radiologist interpretation was noninferior to quantitative PRM. The highest level of diagnostic performance was achieved by the combination of quantitative PRM measurements with qualitative image feature assessments.
Frailty and Kidney Transplantation: A Systematic Review and Meta-analysis
Authors: Quint Evelien E. , Zogaj Donika , Banning Louise B.D. , Benjamens Stan , Annema Coby , Bakker Stephan J.L. , Nieuwenhuijs-Moeke Gertrude J. , Segev Dorry L. , McAdams-DeMarco Mara A. , Pol Robert A.
Published: May 2021

Background.

Frailty is a multidimensional condition and is the result of the body’s age-associated decline in physical, cognitive, physiological, and immune reserves. The aim of this systematic review is to assess the quality of evidence of the included studies, determine the prevalence of frailty among kidney transplant candidates, and evaluate the relationship between frailty and associated patient characteristics and outcomes after kidney transplantation.

Methods.

A systematic search was performed for relevant literature on frailty and kidney transplantation. This was followed by a meta-analysis for patient characteristics and outcomes reported by a minimum of 2 studies including mean age, gender, mean body mass index, type of kidney transplantation, dialysis, previous kidney transplantation, comorbidities, hypertension, race, preemptive kidney transplantation, delayed graft function, and length of stay.

Results.

A total of 18 studies were included in the systematic review and 14 of those studies were suitable for meta-analysis. The overall pooled prevalence of frailty before transplantation was estimated at 17.1% (95% confidence interval [CI], 15.4-18.7). Frailty was significantly associated with higher age (mean difference, 3.6; 95% CI, 1.4-5.9), lower rate of preemptive transplantation (relative risk, 0.60; 95% CI, 0.4-0.9), longer duration of delayed graft function (relative risk, 1.80; 95% CI, 1.1-3.0), and length of stay longer than 2 wk (odds ratio, 1.64; 95% CI, 1.2-2.3).

Conclusions.

One in 6 kidney transplant recipients is frail before transplantation. The presence of frailty is associated with lower rates of preemptive transplantation, older recipient age, higher rates of delayed graft function, and longer length of stay. Future research is required to explore the association of frailty with other adverse outcomes after kidney transplantation and the effects of intervention programs to improve the different frailty domains.
Personalized, Multisession, Multichannel Transcranial Direct Current Stimulation in Medication-Refractory Focal Epilepsy: An Open-Label Study
Authors: Kaye Harper Lee , San-Juan Daniel , Salvador Ricardo , Biagi Maria Chiara , Dubreuil-Vall Laura , Damar Ugur , Pascual-Leone Alvaro , Ruffini Giulio , Shafi Mouhsin M. , Rotenberg Alexander
Published: May 2021

Purpose:

Animal and proof-of-principle human studies suggest that cathodal transcranial direct current stimulation may suppress seizures in drug-resistant focal epilepsy. The present study tests the safety, tolerability, and effect size of repeated daily cathodal transcranial direct current stimulation in epilepsy have not been established, limiting development of clinically meaningful interventions.

Methods:

We conducted a 2-center, open-label study on 20 participants with medically refractory, focal epilepsy, aged 9 to 56 years (11 women and 9 children younger than18 years). Each participant underwent 10 sessions of 20 minutes of cathodal transcranial direct current stimulation over 2 weeks. Multielectrode montages were designed using a realistic head model–driven approach to conduct an inhibitory electric field to the target cortical seizure foci and surrounding cortex to suppress excitability and reduce seizure rates. Patients recorded daily seizures using a seizure diary 8 weeks prior, 2 weeks during, and 8 to 12 weeks after the stimulation period.

Results:

The median seizure reduction was 44% relative to baseline and did not differ between adult and pediatric patients. Three patients experienced an increase in seizure frequency of >50% during the stimulation period; in one, a 36% increase in seizure frequency persisted through 12 weeks of follow-up. Otherwise, participants experienced only minor adverse events—the most common being scalp discomfort during transcranial direct current stimulation.

Conclusions:

This pilot study supports the safety and efficacy of multifocal, personalized, multichannel, cathodal transcranial direct current stimulation for adult and pediatric patients with medication-refractory focal epilepsy, although identifies a possibility of seizure exacerbation in some. The data also provide insight into the effect size to inform the design of a randomized, sham-stimulation controlled trial.
Interventions targeting non-symptomatic cases can be important to prevent local outbreaks: SARS-CoV-2 as a case study
Authors: Lovell-Read Francesca A. , Funk Sebastian , Obolski Uri , Donnelly Christl A. , Thompson Robin N.
Published: May 2021

During infectious disease epidemics, an important question is whether cases travelling to new locations will trigger local outbreaks. The risk of this occurring depends on the transmissibility of the pathogen, the susceptibility of the host population and, crucially, the effectiveness of surveillance in detecting cases and preventing onward spread. For many pathogens, transmission from pre-symptomatic and/or asymptomatic (together referred to as non-symptomatic) infectious hosts can occur, making effective surveillance challenging. Here, by using SARS-CoV-2 as a case study, we show how the risk of local outbreaks can be assessed when non-symptomatic transmission can occur. We construct a branching process model that includes non-symptomatic transmission and explore the effects of interventions targeting non-symptomatic or symptomatic hosts when surveillance resources are limited. We consider whether the greatest reductions in local outbreak risks are achieved by increasing surveillance and control targeting non-symptomatic or symptomatic cases, or a combination of both. We find that seeking to increase surveillance of symptomatic hosts alone is typically not the optimal strategy for reducing outbreak risks. Adopting a strategy that combines an enhancement of surveillance of symptomatic cases with efforts to find and isolate non-symptomatic infected hosts leads to the largest reduction in the probability that imported cases will initiate a local outbreak.
Extreme lifespan extension in tapeworm-infected ant workers
Authors: Beros Sara , Lenhart Anna , Scharf Inon , Negroni Matteo Antoine , Menzel Florian , Foitzik Susanne
Published: May 2021

Social insects are hosts of diverse parasites, but the influence of these parasites on phenotypic host traits is not yet well understood. Here, we tracked the survival of tapeworm-infected ant workers, their uninfected nest-mates and of ants from unparasitized colonies. Our multi-year study on the antTemnothorax nylanderi,the intermediate host of the tapewormAnomotaenia brevis,revealed a prolonged lifespan of infected workers compared with their uninfected peers. Intriguingly, their survival over 3 years did not differ from those of (uninfected) queens, whose lifespan can reach two decades. By contrast, uninfected workers from parasitized colonies suffered from increased mortality compared with uninfected workers from unparasitized colonies. Infected workers exhibited a metabolic rate and lipid content similar to young workers in this species, and they received more social care than uninfected workers and queens in their colonies. This increased attention could be mediated by their deviant chemical profile, which we determined to elicit more interest from uninfected nest-mates in a separate experiment. In conclusion, our study demonstrates an extreme lifespan extension in a social host following tapeworm infection, which appears to enable host workers to retain traits typical for young workers.
Infrared absorbing nanoparticle impregnated self-heating fabrics for significantly improved moisture management under ambient conditions
Authors: Wijenayaka Lahiru A. , Wijesena Ruchira N. , Tissera Nadeeka D. , Nisansala Bandara W. R. L. , Amaratunga Gehan J. , Nalin De Silva K. M.
Published: May 2021

Propensity of a textile material to evaporate moisture from its surface, commonly referred to as the ‘moisture management’ ability, is an important characteristic that dictates the applicability of a given textile material in the activewear garment industry. Here, an infrared absorbing nanoparticle impregnated self-heating (IRANISH) fabric is developed by impregnating tin-doped indium oxide (ITO) nanoparticles into a polyester fabric through a facile high-pressure dyeing approach. It is observed that under simulated solar radiation, the impregnated ITO nanoparticles can absorb IR radiation, which is effectively transferred as thermal energy to any moisture present on the fabric. This transfer of thermal energy facilitates the enhanced evaporation of moisture from the IRANISH fabric surface and as per experimental findings, a 54 ± 9% increase in the intrinsic drying rate is observed for IRANISH fabrics compared with control polyester fabrics that are treated under identical conditions, but in the absence of nanoparticles. Approach developed here for improved moisture management via the incorporation of IR absorbing nanomaterials into a textile material is novel, facile, efficient and applicable at any stage of garment manufacture. Hence, it allows us to effectively overcome the limitations faced by existing yarn-level and structural strategies for improved moisture management.
Know your foe: synanthropic spiders are deterred by semiochemicals of European fire ants
Authors: Fischer Andreas , Lee Yerin , Dong T'ea , Gries Gerhard
Published: May 2021

Many ants prey on spiders, suggesting that web-building spiders may avoid micro-locations near ant colonies or frequented by foraging ants. Here we tested the hypothesis that ant-derived semiochemicals deter synanthropic spiders. To generate stimuli, we exposed filter paper for 12 h to workers of European fire ants,Myrmica rubra,black garden ants,Lasius niger,or western carpenter ants,Camponotus modoc, and then offered select urban spiders in three-chamber olfactometer bioassays a choice between ant-exposed filter paper and unexposed control filter paper. Semiochemical deposits ofM. rubra, but not ofL. nigerorC. modoc, had a significant deterrent effect on subadults of the false black widow,Steatoda grossa,the black widow,Latrodectus hesperus, and the hobo spider,Eratigena agrestis,as well as a moderate (but statistically not significant) deterrent effect on the cross spider,Araneus diadematus. The deterrent effect caused by semiochemical deposits ofM. rubramay be attributable to the aggressive nature and efficient foraging ofM. rubrain its invaded North American range, exerting selection pressure on community members to recognizeM. rubrasemiochemicals and to avoid micro-locations occupied byM. rubra.
Different trophic positions among social vespid species revealed by stable isotopes
Authors: Torniainen Jyrki , Komonen Atte
Published: May 2021

The social vespid wasps are common insect predators and several species behave in unison in the same biotopes. It is commonly accepted that social wasps are mainly opportunistic generalist predators without differences in prey selection and hence they compete for the same food resources. Trophic positions of six vespid wasp species and their potential prey from four sites in Finland and one in the UK were evaluated using carbon and nitrogen stable isotopes (δ
13
C and δ
15
N). The difference in isotope values indicated different trophic positions among species. In general,
Dolichovespula
spp. showed higher δ
15
N values than
Vespula
spp., which suggests that
Dolichovespula
forage on higher trophic levels.
Dolichovespula media
(Retzius, 1783) showed the highest δ
15
N values, whereas
Vespula vulgaris
showed the lowest.
Dolichovespula media
partly expresses apex predator-like δ
15
N values, whereas
Vespula
species tend to forage on primary consumers. The largest species
Vespa crabro
(Linnaeus, 1758) showed also similar δ
15
N values as
Vespula
spp. However, δ
13
C and δ
15
N values of
V. vulgaris
workers varied slightly during the season. This study offers novel insights about the trophic segregation in the social wasp community, suggesting specialization in diet resource utilization, especially between
Dolichovespula
and
Vespula
.