Is autoimmunology a discipline of its own? A big data-based bibliometric and scientometric analyses

Autoimmunology is a super-specialty of immunology specifically dealing with autoimmune disorders. To assess the extant literature concerning autoimmune disorders, bibliometric and scientometric analyses (namely, research topics/keywords co-occurrence, journal co-citation, citations, and scientific output trends – both crude and normalized, authors network, leading authors, countries, and organizations analysis) were carried out using open-source software, namely, VOSviewer and SciCurve. A corpus of 169,519 articles containing the keyword “autoimmunity” was utilized, selecting PubMed/MEDLINE as bibliographic thesaurus. Journals specifically devoted to autoimmune disorders were six and covered approximately 4.15% of the entire scientific production. Compared with all the corpus (from 1946 on), these specialized journals have been established relatively few decades ago. Top countries were the United States, Japan, Germany, United Kingdom, Italy, China, France, Canada, Australia, and Israel. Trending topics are represented by the role of microRNAs (miRNAs) in the ethiopathogenesis of autoimmune disorders, contributions of genetics and of epigenetic modifications, role of vitamins, management during pregnancy and the impact of gender. New subsets of immune cells have been extensively investigated, with a focus on interleukin production and release and on Th17 cells. Autoimmunology is emerging as a new discipline within immunology, with its own bibliometric properties, an identified scientific community and specifically devoted journals.     

Clinical characteristics and risk factors for low dose methotrexate toxicity: A cohort of 28 patients

Objective

Low dose (10–25 mg/week) methotrexate is widely used for the management of systemic inflammatory diseases, and is considered to be relatively safe. Toxicity due to low dose MTX has been reported but is poorly characterized. We describe the clinical features, risk factors, and outcomes of low dose MTX toxicity in a large case series at our center.

Patients and methods

We conducted a retrospective case series of all adult (> 18 years) patients hospitalized at Sheba Medical Center, between 2005 and 2012 for low dose MTX toxicity.

Results

We identified 28 patients (age: 70.4 ± 13.7 years, range: 33–88; 20 (71%) females) hospitalized for low dose MTX toxicity. Indications for MTX therapy included: rheumatoid arthritis (39.2%), psoriasis ± arthritis (21.5%), polymyalgia rheumatica (10.8%) and other inflammatory conditions (28.5%). Pancytopenia was the most common manifestation of low dose MTX toxicity detected in 78.5% of the patients. Potential risk factors included acute renal failure, hypoalbuminemia, concurrent use of drugs known to interact with MTX, and dose errors. Serum MTX concentrations (n = 20, mean 0.04 ± 0.07 μg/mL range: 0–0.3) did not correlate with the degree of either neutropenia (r = − 0.36; p = 0.18) or thrombocytopenia (r = 0.44; p = 0.10). Seven (25%) patients died, all from pancytopenia followed by sepsis. Serum MTX concentrations did not differ between the patients who died from MTX toxicity (n = 6; mean: 0.05 ± 0.04 μg/mL) and those who survived the toxicity (n = 14 mean 0.04 ± 0.08; p = 0.45).

Conclusions

Low-dose MTX toxicity can be life threatening, mainly due to myelosuppression. There is no rationale for MTX therapeutic drug monitoring in the setting of low-dose toxicity.     

Benign angiopathy of the central nervous system presenting with intracerebral hemorrhage

BACKGROUND: Primary central nervous system vasculitis has traditionally been described as an aggressive condition, with significant morbidity and mortality. A subgroup of patients has been identified who have a similar clinical presentation, but with a benign course. This syndrome of BACNS is successfully treated with low-dose steroids and calcium-channel blockers. Histologic confirmation, when performed, is normal. METHODS: Intracerebral hemorrhage is a rare presenting finding in the setting of BACNS. We present 2 patients with acute onset of headache and neurologic impairment secondary to an ICH. RESULTS: Cerebral angiography showed characteristic findings of diffuse vasculitis. Both patients were subjected to biopsy and both failed to reveal evidence of vasculitis. CONCLUSION: This report is the first to document the normal histologic features of BACNS in the setting of an ICH. Although these angiographic changes are similar to vasculitis, these processes can be differentiated on clinical grounds, which is of vital importance as the treatment and clinical course of BACNS is more benign. Furthermore, the presence of an ICH in the setting of vasoconstriction seen on angiography may represent a novel feature in some patients with BACNS and is not necessarily a harbinger of the more malignant PCNSV.     

Comparison of PET Imaging with 64Cu-Liposomes and 18F-FDG in the 7,12-Dimethylbenz[a]anthracene (DMBA)-Induced Hamster Buccal Pouch Model of Oral Dysplasia and Squamous Cell Carcinoma

Purpose

Currently, 2-deoxy-2-[¹⁸F]fluoro-d-glucose (¹⁸F-FDG) is the gold standard radiotracer for staging of head and neck cancer; however, the low sensitivity of this tracer can impede detection of early lesions. ⁶⁴Cu-liposomes accumulate in various cancers and provide both a sensitive tracer and an indication of the biodistribution of nanotherapeutics. Here, the accumulation of ⁶⁴Cu-liposomes in early and established cancers is assessed and compared with ¹⁸F-FDG in a head and neck cancer model.

Methods

Lesions ranging from mild dysplasia to squamous cell carcinoma were induced in a hamster model of head and neck cancer by topical application of 7,12-dimethylbenz[a]anthracene to the buccal pouch. The hamsters were imaged with micro-positron emission tomography using ¹⁸F-FDG and ⁶⁴Cu-liposomes.

Results

At 24 h postinjection, ⁶⁴Cu-liposome accumulation exceeded the accumulation of ¹⁸F-FDG in every pathologic grade. The lesion-to-cheek pouch (background) ratio and lesion-to-brain ratio were also higher for ⁶⁴Cu-liposomes than for ¹⁸F-FDG.

Conclusion

Imaging of a nanotracer such as ⁶⁴Cu-liposomes can improve the visualization of head and neck tumors. Accumulation of liposomal particles in head and neck tumors over various pathologic grades averaged 3.5 %ID/cc demonstrating the potential for liposomal therapy with targeted chemotherapeutic agents.     

Role of MIB1 in Predicting Survival in Patients with Glioblastomas

Summary Background: Histologic immunomarkers of cell cycle proteins have been utilized for prognosis in high-grade astrocytic tumors. One such marker, MIB1, an antibody immunoreactive throughout the cell cycle, is predictive of more aggressive disease and poorer prognosis in astrocytomas. An independent role of MIB1 analysis for survival prediction and clinical management within histologic grades has not been clearly proven. Methods: This study retrospectively evaluated MIB1 reactivity in tissue samples from 116 patients with glioblastomas on initial medical presentation. Clinical variables considered included gender, age, Karnofsky Performance Scores (KPS), extent of surgical resection, adjuvant radiation and survival. Results: Univariate and multivariate analyses were used to correlate these variables with MIB1 staining. MIB1 staining does not predict overall survival or response to adjuvant therapy as an independent risk factor. Conclusion: MIB1 labeling does not predict patient survival as an independent variable and does not predict response to additional therapies. Patient survival with glioblastoma was predicted by KPS, age, extent of resection and use of adjuvant radiotherapy.