First description of blaNDM-1, blaOXA-48, blaOXA-181 producing Enterobacteriaceae strains in Romania

We report the first isolation and characterization of several Enterobacteriaceae strains harboring bla_NDM-1, bla_OXA-48 and/or bla_OXA-181 genes in a Romanian emergency teaching hospital. Between January 2010 and September 2012 nine carbapenemase-producing Enterobacteriaceae strains were identified. The bla_NDM-1 gene was present in two Enterobacter cloacae strains, an Escherichia coli and two Klebsiella pneumoniae strains. One of these K. pneumoniae strains also harbored the bla_OXA-181 gene. Three other K. pneumoniae strains and one Serratia marcescens carried bla_OXA-48.     

Cutaneous histoplasmosis with prominent parasitization of epidermal keratinocytes: report of a case

Disseminated histoplasmosis most commonly occurs in immunosuppressed individuals and involves the skin in approximately 6% of patients. Cutaneous histoplasmosis with an intraepithelial‐predominant distribution has not been described. A 47‐year‐old man was admitted to our institution with fever and vancomycin‐resistant enterococcal bacteremia. He had been diagnosed with T‐cell prolymphocytic leukemia 4 years earlier and had undergone matched‐unrelated‐donor stem cell transplant 2 years earlier; on admission, he had relapsed disease. His medical history was significant for disseminated histoplasmosis 6 months before admission, controlled with multiple antifungal regimens. During this final hospitalization, the patient developed multiple 2–5 mm erythematous papules, a hemorrhagic crust across the chest, shoulders, forearms, dorsal aspect of the fingers, abdomen and thighs. Skin biopsy revealed clusters of oval yeast forms mostly confined to the cytoplasm of keratinocytes and within the stratum corneum; scattered organisms were present in the underlying superficial dermis without any significant associated inflammatory infiltrate. Special stains and immunohistochemical studies confirmed these to be Histoplasma organisms. We highlight this previously unrecognized pattern of cutaneous histoplasmosis to ensure its prompt recognition and appropriate antifungal therapy.     

Association of sense of coherence and supernatural beliefs with death anxiety and death depression among Romanian cancer patients

The aim of this cross-sectional study was to examine the association of supernatural beliefs and sense of coherence with death anxiety and death depression in a Romanian sample of cancer patients. We found support for the terror management theory worldview defence hypothesis postulating the presence of a curvilinear relation between death anxiety and supernatural beliefs among cancer patients. Results conformed to an inverted U-shape quadratic regression, indicating that cancer patients who scored moderately on supernatural beliefs were afraid of death the most, while death anxiety was lowest for the extreme atheists and extreme believers in supernatural entities.     

Metastatic melanoma with balloon/histiocytoid cytomorphology after treatment with immunotherapy: A histologic mimic and diagnostic pitfall

Epithelioid cells with foamy cytoplasm (histiocytoid features) are typical histopathologic findings among benign and malignant histiocytic neoplasms such as xanthoma and atypical fibroxanthoma. However, these changes are unusual in melanoma, which is typically composed of nested and variably pigmented atypical epithelioid cells. Here, we report a patient with metastatic melanoma in lymph nodes presenting with prominent balloon cell/histiocytoid features expressing melanocytic markers, after treatment with nivolumab. This report suggests that the spectrum of neoplasms with histiocytoid features should be expanded to include melanoma, a pattern that, to the best of our knowledge, is uncommon, especially in the setting of post‐neoadjuvant therapy.     

Analysis of immune reconstitution after autologous bone marrow transplantation in systemic sclerosis

OBJECTIVE: To analyze hematopoietic and immune reconstitution after autologous hematopoietic stem cell transplantation (HSCT) in 7 patients with systemic sclerosis (SSc). METHODS: Two groups of patients were retrospectively constituted according to whether they had a favorable clinical response (group A; n = 4) or no response or a relapse of disease (group B; n = 3) after HSCT. Immune reconstitution was analyzed every 3 months using lymphocyte immunophenotyping, alpha/beta T cell receptor (TCR) diversity analysis, and ex vivo thymic function analysis by quantification of TCR rearrangement excision circles (TRECs). RESULTS: Patients had similar characteristics at study entry, except for a lower modified Rodnan skin thickness score (P = 0.03) and a lower Health Assessment Questionnaire score (P = 0.05) in group A than in group B. The number of reinjected cells and the time to hematopoietic reconstitution were similar in both groups. The absolute numbers of CD19+ and CD20+ B cells were lower in group A than in normal controls (P < 0.05) and within the normal range in group B. Absolute numbers of T and natural killer lymphocytes were normal before HSCT. Numbers of CD3+ cells remained low thereafter. Numbers of CD8+ cells were back to normal 3 months after HSCT in both groups. B cell counts were low until 6 months after HSCT in group A and stayed in the normal range in group B. The CD3+ defect was sustained in group A, with an opposite trend and a faster CD4+ reconstitution profile in group B. The T cell repertoire was skewed before and until 1 year after HSCT, with shared expansions before and after transplant in a given individual. TREC values correlated negatively with C-reactive protein levels (r(s) = -0.41, P = 0.001) and positively with CD19+ (r(s) = 0.35, P = 0.001) and CD20+ (r(s) = 0.34, P = 0.002) lymphocyte counts. CONCLUSION: B and T lymphocyte populations remained disturbed for at least 1 year after HSCT in SSc patients, which may reflect the persistence of an underlying disease mechanism.     

Thyroid cancer in children: a 20-year study at a Romanian oncology institute

Thyroid carcinoma (TC) has an increasing incidence in the last decade and continues to represent the most frequent form of endocrine tumor. The aim of the study was to analyze the pediatric files of TC from the registry of "Prof. Dr. Ion Chiricuta" Institute of Oncology Cluj-Napoca, Romania (IOCN) and to provide the data related to the impact of nuclear fallout of Chernobyl on this pathology. We studied 72 children with TC treated between 1991 and 2010. The mean age was 15.3 years; the ratio female/male was 6.2:1. Twenty-nine children (40.2%) revealed metastasis in regional lymph nodes or lungs at the initial diagnostic. There were 63 differentiated thyroid carcinoma (DTC), 6 cases with medullary cancer (MC), 1 case with anaplastic carcinoma (AC), and 2 mixed cases. All patients underwent total thyroidectomy and the radioiodine was administered in 64 cases (activities between 1.1 - 28.1 GBq I-131). Fifty-two children (80.5%) are free of disease, 8 are in partial remission and 4 children are in evolution of the disease at minimum 12 months of follow-up. The incidence of TC was significantly increased 10 years after the accident. In the years after, the increasing trendline was stopped and at 25 years, the number of cases is stationary. The diagnosis of pediatric TC is made frequently in metastatic disease and the therapies must be conducted for many years till complete remission. A more clear strategy adapted to children is needed in the future.     

Understanding Pancreas Development for β-Cell Repair and Replacement Therapies

The lack or dysfunction of insulin-producing β-cells is the cause of all forms of diabetes. In vitro generation of β-cells from pluripotent stem cells for cell-replacement therapy or triggering endogenous mechanisms of β-cell repair have great potential in the field of regenerative medicine. Both approaches rely on a thorough understanding of β-cell development and homeostasis. Here, we briefly summarize the current knowledge of β-cell differentiation during pancreas development in the mouse. Furthermore, we describe how this knowledge is translated to instruct differentiation of both mouse and human pluripotent stem cells towards the β-cell lineage. Finally, we shortly summarize the current efforts to identify stem or progenitor cells in the adult pancreatic organ and to harness the endogenous regenerative potential. Understanding development and regeneration of β-cells already led to identification of molecular targets for therapy and informed on pathomechanisms of diabetes. In the future might lead to β-cell repair and replacement therapies.