Saint Francis University

About: Saint Francis University is a education organization based out in Loretto, Pennsylvania, United States. It is known for research contribution in the topics: Population & Osteoblast. The organization has 1694 authors who have published 2038 publications receiving 87149 citations.

Retroperitoneal fibrosis due to B-cell non-Hodgkin lymphoma: Responding to rituximab!

Abstract: Retroperitoneal fibrosis is a rare disease manifesting as chronic soft tissue fibrosis in the retroperitoneum, with potential anatomic and/or functional compromise of adjacent organs. It can be primary (idiopathic) or secondary to other conditions such as cancers, autoimmune disorders, or drugs. We report herein a 66-year-old patient with symptomatic retroperitoneal fibrosis leading to bilateral hydronephrosis and renal failure, in whom, after a complex diagnostic work-up and protracted clinical course, a B-cell non-Hodgkin lymphoma in the retroperitoneal space and several vertebral bodies was identified. The patient was treated with radiation therapy and weekly rituximab infusions, with resolution of hydronephrosis and lower back pain. We include a thorough literature review on etiopathogenesis, diagnosis, therapy, and prognosis of retroperitoneal fibrosis. A meticulous search for malignancy is necessary in this rare condition that, if positive, may have significant therapeutic and prognostic implications.

Immune alterations in untreated and treated myelodysplastic syndrome

Abstract: Introduction: Current literature suggests a variety of immune abnormalities are present in myelodysplastic syndrome (MDS) patients. However, they have not been comprehensively characterized or systematized to date. As a result, their clinical implications remain largely unknown. In addition, an increased incidence of various autoimmune conditions has been documented in MDS patients. Areas covered: The authors offer a comprehensive review of the existing literature on immune mechanisms involved in the pathogenesis of MDS, various immune abnormalities documented in its course, their link with the clonal evolution of MDS as well as immune alterations induced by the existing MDS therapies. Expert opinion: The course of MDS is accompanied by complex immune alterations, including T-cell and NK-cell defects, decreased functional abilities of neutrophils and antigen-presenting cells, altered antibody and cytokine production. While contemporary MDS therapies are shown to possess some immunomodulatory properties, a...

Isolated thrombocytopenia: should we routinely screen for antiphospholipid antibodies?

Abstract: BACKGROUND Antiphospholipid (aPL) antibodies are thought to be present in at least 25% of immune thrombocytopenia patients. Conversely, more than 25% of patients with aPL antibody syndrome (APLAS) present with thrombocytopenia. AIMS To identify the rate of a PL antibody positivity in patients with isolated thrombocytopenia and correlate this finding with the occurrence ofthromboembolic (TE) events or equivalents. MATERIALS AND METHODS By performing prospective andretrospective analysis of a series of 64 consecutive patients with moderate persistent thrombocytopenia, we established the serologic evidence of APLAS and performed the existing clinico-laboratory correlations. The presence of aPL antibodies in patients with thromocytopenia was tested for statistical significance using chi2 test of independence for categorical variables (one degree of freedom, 95% confidence) as well as Fisher's exact test for small numbers of observations. RESULTS We detected the presence of aPL antibodies in nine of 64 (14%) of patients with isolated thrombocytopenia and four of nine APLAS patients (approximately 44%) also tested positive for antiplatelet antibodies. Five of nine APLAS patients (approximately 56%) had a consistently increased mean platelet volume (MPV). Although the numbers are small, the values proved statistically significant. Two of nine APLAS patients (approximately 22%) developed TE events or equivalents, and two patients were subsequently diagnosed with systemic lupus erythematosus. CONCLUSIONS We believe that patients with isolated thrombocytopenia should be tested for the presence of aPL antibodies, as our findings have shown a correlation between the presence of aPL antibodies and occurrence of TE events. Identification of an APLAS subset in this context appears justified in terms of early institution of antiplatelet therapy, especially in patients with additional cardiovascular risk factors.

Subclinical Hypothyroidism and Its Association with Increased Cardiovascular Mortality

Abstract: Thyroid hormones play an important role in regulating different metabolism functions and multiple organs' performance Changes in the thyroid hormone axis can lead to profound effects on the stability of vital organs and systems, especially the cardiovascular system Hypothyroidism is classified according to the clinical presentation as overt and subclinical There is some evidence supporting the benefits of thyroxine hormone replacement for subclinical hypothyroidism on cardiovascular mortality outcomes However, the clinical relevance of measuring and treating high thyroid-stimulating hormone (TSH) levels in newly diagnosed heart failure patients with preserved ejection fraction requires further study In this report, we review the current evidence regarding the prognostic significance of subclinical hypothyroidism in heart failure patients with preserved ejection fraction

Phase I Study of Docetaxel and Temsirolimus in Refractory Solid Tumors.

Abstract: Introduction The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphatidylinositol 3-kinase/Akt signaling pathway, and plays a central role in cell proliferation, growth, differentiation, migration, and survival. Temsirolimus (CCI-779), a selective inhibitor of the mTOR, is an ester analog of rapamycin (sirolimus) with improved aqueous solubility and pharmacokinetic (PK) properties. Preclinical studies have confirmed additive and synergistic antitumor activity in cancer cell lines (breast, prostate cancer) with combinations of taxanes and mTOR inhibitors. We conducted a phase I open-label, dose-escalation study to determine the maximal tolerated dose (MTD) of docetaxel in combination with temsirolimus in patients with refractory solid tumors. Patients and methods Eligible patients had a diagnosis of a refractory solid malignancy, measurable disease, and adequate organ function. Patients were sequentially enrolled in 4 dose level intravenous combinations of docetaxel and temsirolimus. Temsirolimus was administered weekly with docetaxel administered every 3 weeks. Laboratory data for tumor markers and radiologic imaging were conducted prestudy and then after every 2 cycles of the treatment. Radiologic response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Blood samples for PK and pharmacodynamic analysis were planned to be drawn at MTD. Apart from the traditional 3+3 design, we also implemented Bayesian Optimal Interval design which uses isotonic regression method to select MTD. We proceeded with isotonic regression analysis by using 20% dose-limiting toxicity (DLT) rate as target. Results Twenty-six patients were treated in this study in 4 cohorts and dose levels. Fourteen males and 12 females were enrolled with a median age of 50 years (range of 27 to 72 y) and median Eastern Cooperative Oncology Group performance score of 1. Tumor histologies included pancreas (6), colon (5), rectum (3), gallbladder (2), non-small cell lung (2), endometrium (1), neuroendocrine (1), esophagus (1), stomach (1), pharynx (1), small intestine (1), and duodenum (1). Stable disease was observed in 2/4 (50%), 3/7 (43%), 4/10 (40%), and 3/5 (60%) patients in cohorts 1, 2, 3, and 4, respectively. Dose escalation in cohorts 2, 3, and 4 was complicated by DLTs such as grade 4 neutropenia and grade 3 diarrhea and an inability for patients to tolerate treatments during and beyond cycle 1 without dose reductions. Therefore, we could not determine an MTD or recommended phase II dose using the traditional 3+3 study analysis. Blood samples for PK and pharmacodynamic analysis were not collected since MTD was not determined. By using 20% DLT rate closest to the target, isotonic regression analysis showed identical estimated DLT rates in dose -1 (docetaxel 50 mg/m2 and temsirolimus 15 mg/m2) and dose level 1 (docetaxel 60mg/m2 and temsirolimus 15 mg/m2). Conclusions Dose escalation of docetaxel and temsirolimus was limited by severe myelosuppressive toxicity in this phase I study. Most of the DLTs occurred after cycle 1 of therapy hence, we were unable to determine MTD or collect blood samples for PK and pharmacodynamic analysis. Our trial did not meet its objectives due to significant DLTs with this chemotherapy combination. Although our novel use of Bayesian Optimal Interval design using isotonic regression method to select MTD showed identical estimated DLT rates in dose levels 1 and -1, clinically our patients were not able to complete 2 cycles of this regimen without dose reductions due to myelosuppressive toxicity in either of these dose levels, and hence, escaped clinical validity. This combination regimen should not be studied further at the dose levels and schedules tested in our study.