Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma.

Background: Bortezomib, lenalidomide, and dexamethasone (VRd) is a preferred first-line treatment option for patients with newly diagnosed multiple myeloma. Whether the addition of the anti-CD38 monoclonal antibody isatuximab to the VRd regimen would reduce the risk of disease progression or death among patients ineligible to undergo transplantation is unclear.

Methods: In an international, open-label, phase 3 trial, we randomly assigned, in a 3:2 ratio, patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation to receive either isatuximab plus VRd or VRd alone.

Inhaled Technosphere Insulin Compared With Injected Prandial Insulin in Type 1 Diabetes: A Randomized 24-Week Trial.

Objective: To compare the efficacy and safety of Technosphere insulin (TI) and insulin aspart in patients with type 1 diabetes.

Research Design And Methods: This open-label noninferiority trial compared the change in HbA1c from baseline to week 24 of prandial TI (n = 174) with that of subcutaneous aspart (n = 171), both with basal insulin, in patients with type 1 diabetes and HbA1c 7.5-10.

Experience with intravenous ferric carboxymaltose in patients with iron deficiency anemia.

Erythropoiesis may be limited by absolute or functional iron deficiency or when chronic inflammatory conditions lead to iron sequestration. Intravenous iron may be indicated when oral iron cannot address the deficiency. Ferric carboxymaltose (FCM) is a nondextran iron preparation recently approved in the United States for intravenous treatment of iron deficiency anemia (IDA) in adult patients with intolerance or unsatisfactory response to oral iron or with nondialysis-dependent chronic kidney disease.

Direct Comparison of the Safety and Efficacy of Ferric Carboxymaltose versus Iron Dextran in Patients with Iron Deficiency Anemia.

Several intravenous iron complexes are available for the treatment of iron deficiency anemia (IDA). Iron dextran (DEX) is associated with an elevated risk of potentially serious anaphylactic reactions, whereas others must be administered in several small infusions to avoid labile iron reactions. Ferric carboxymaltose (FCM) is a nondextran intravenous iron which can be administered in high single doses.

Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal function: the REPAIR-IDA trial.

Background: Iron-deficiency anemia in non-dialysis-dependent chronic kidney disease (NDD-CKD) frequently requires parenteral iron replacement, but existing therapies often require multiple administrations. We evaluated the efficacy and cardiovascular safety of ferric carboxymaltose (FCM), a non-dextran parenteral iron permitting large single-dose infusions, versus iron sucrose in patients with iron-deficiency anemia and NDD-CKD.

Methods: A total of 2584 participants were randomized to two doses of FCM 750 mg in one week, or iron sucrose 200 mg administered in up to five infusions in 14 days.

A multicenter, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia.

Background: Many patients receiving oral iron for iron deficiency anemia (IDA) cannot tolerate or fail to respond to therapy, and existing intravenous (IV) iron formulations often require repeated administrations. Ferric carboxymaltose (FCM), a nondextran IV formulation, permits larger single doses.

Study Design And Methods: We evaluated FCM versus oral iron in IDA patients.

Comparative review of the safety and efficacy of ferric carboxymaltose versus standard medical care for the treatment of iron deficiency anemia in bariatric and gastric surgery patients.

Background: Iron deficiency anemia (IDA) is a common finding in patients after bariatric surgery. The cause is multifactorial including reduced oral iron intake and malabsorption. While many patients can be managed with oral supplements, parenteral iron may be needed to restore and maintain iron stores.

Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women.

Fibroblast growth factor 23 (FGF23) is an osteocyte-derived hormone that regulates phosphate and vitamin D homeostasis. Through unknown mechanisms, certain intravenous iron preparations induce acute, reversible increases in circulating FGF23 levels that lower serum phosphate in association with inappropriately low levels of calcitriol, similar to genetic diseases of primary FGF23 excess. In contrast, studies in wild-type mice suggest that iron deficiency stimulates fgf23 transcription but does not result in hypophosphatemia because FGF23 is cleaved within osteocytes by an unknown catabolic system.

Hepcidin levels predict nonresponsiveness to oral iron therapy in patients with iron deficiency anemia.

Levels of hepcidin, a major regulator of iron homeostasis, may identify patients with iron deficiency anemia (IDA) who will not respond to oral iron therapy. In this study, IDA patients underwent a 14-day trial (run-in) course of ferrous sulfate therapy. Nonresponders (Hgb increase <1 g/dL with 67% compliance rate) were randomized to IV ferric carboxymaltose (FCM; two injections of 750 mg) or further oral iron for 14 days.

Intravenous ferric carboxymaltose versus standard medical care in the treatment of iron deficiency anemia in patients with chronic kidney disease: a randomized, active-controlled, multi-center study.

Background: Currently available intravenous (IV) iron agents vary in indication, dosing regimens and safety profiles. Ferric carboxymaltose (FCM) is a stable, non-dextran-containing iron formulation developed for rapid IV administration in high doses with controlled delivery of iron into target tissues. The objective of the present study was to evaluate the safety of FCM compared with standard medical care (SMC) in dialysis (HD) and non-dialysis-dependent (NDD) chronic kidney disease (CKD) patients.

Safety and Efficacy of Intravenous Ferric Carboxymaltose (750 mg) in the Treatment of Iron Deficiency Anemia: Two Randomized, Controlled Trials.

Background. Iron deficiency anemia (IDA) is a common hematological complication with potentially serious clinical consequences that may require intravenous iron therapy. Ferric carboxymaltose (FCM) is a stable, nondextran iron formulation administered intravenously in large single doses to treat IDA.

Clinical efficacy and safety of IV ferric carboxymaltose (FCM) treatment of RLS: a multi-centred, placebo-controlled preliminary clinical trial.

Objective: Intravenous (IV) iron has been used as a treatment to reduce Restless Legs Syndrome (RLS) symptoms, but two double-blinded trials of a frequently prescribed IV iron formulation, iron sucrose, failed to show lasting efficacy. This study evaluates efficacy and safety of a new IV iron formulation (ferric carboxymaltose, FCM) with molecular properties that may make iron more available for uptake to the brain than iron sucrose does.

Methods: In this 28-day, multi-centre, randomised, placebo-controlled trial 46 RLS patients were discontinued from all RLS treatment.

Randomized evaluation of efficacy and safety of ferric carboxymaltose in patients with iron deficiency anaemia and impaired renal function (REPAIR-IDA): rationale and study design.

Background: Patients with iron deficiency anaemia (IDA) in the setting of non-dialysis-dependent chronic kidney disease (NDD-CKD) may benefit from treatment with intravenous (IV) iron. Ferric carboxymaltose (FCM) is a novel IV iron formulation designed to permit larger infusions compared to currently available IV standards such as Venofer(R) (iron sucrose).

Methods: The primary objective of REPAIR-IDA is to estimate the cardiovascular safety and efficacy of FCM (two doses at 15 mg/kg to a maximum of 750 mg per dose) compared to Venofer(R) (1000 mg administered as five infusions of 200 mg) in subjects who have IDA and NDD-CKD.

Efficacy of cholesterol uptake inhibition added to statin therapy among subjects following a low-carbohydrate diet: a randomized controlled trial.

Background: Low-carbohydrate diets are frequently used as part of weight-loss programs. These are typically associated with increased fat intake. Therefore, cholesterol absorption inhibition is a logical therapeutic strategy to lower low-density lipoprotein cholesterol (LDL-C) in subjects following a low-carbohydrate diet.

An internet-based simulation system for training and development of regional-healthcare-centers managers.

RHCMS (Regional Healthcare Center Management System) is an Internet-based simulation training system for Regional Healthcare-Centers (RHCs) managers. The system is based on an integrative model, designed and developed by an interdisciplinary team of experts, for the purpose of training and developing RHCs' managers. This model involves the study of the following fields: healthcare management, business administration, organizational behavior, health economics, management science, and information technologies.

The inhibitor of cyclin-dependent kinase 4a/alternative reading frame (INK4a/ARF) locus encoded proteins p16INK4a and p19ARF repress cyclin D1 transcription through distinct cis elements.

The Ink4a/Arf locus encodes two structurally unrelated tumor suppressor proteins, p16(INK4a) and p14(ARF) (murine p19(ARF)). Invariant inactivation of either the p16(INK4a)-cyclin D/CDK-pRb pathway and/or p53-p14(ARF) pathway occurs in most human tumors. Cyclin D1 is frequently overexpressed in breast cancer cells contributing an alternate mechanism inactivating the p16(INK4a)/pRb pathway.

Simulation and management games for training command and control in emergencies.

The aim of our project was to introduce and implement simulation techniques in a problematic field of increasing health care system preparedness for disasters. This field was chosen as knowledge is gained by few experienced staff members who need to disperse it to others during the busy routine work of the system personnel. Knowledge management techniques ranging from classifying the current data, centralized organizational knowledge storage and using it for decision making and dispersing it through the organization--were used in this project.

National strategy for mass casualty situations and its effects on the hospital.

A mass-casualty situation (MCS) usually is short in duration and resolves itself. To minimize the risks to patients during MCS, planning is essential. This article summarizes the preparations needed at the hospital level, for a local MCS involving numerous trauma victims arriving to the Emergency Department at a short notice.

RNA polymerase II large subunit is cleaved by caspases during DNA damage-induced apoptosis.

UV radiation induces DNA lesions that are repaired by the nucleotide excision repair (NER) pathway. Cells that are NER deficient such as those derived from xeroderma pigmentosum (XP) patients are susceptible to apoptosis after 10J/m(2) UV radiation, a dose largely survivable by repair proficient cells. Herein, we report that RNA polymerase II large subunit (RNAP II-LS) undergoes caspase-mediated cleavage, yielding a 140kDa C-terminal fragment in XP lymphoblasts but not NER proficient lymphoblasts after 10J/m(2) UV irradiation.

The current status of cardiovascular surgery in the People's Republic of China.

Dr. David Bregman was invited to participate in a thirteen-physician American Teaching Delegation led by Dr. Tsung O.