Management of newly diagnosed high‐risk and intermediate‐risk follicular lymphoma with 90Y ibritumomab tiuxetan in a phase II study

Five‐year overall survival for high‐risk Follicular Lymphoma International Prognostic Index follicular lymphoma is only approximately 50% compared with 90% for low risk. To evaluate an approach to improve upon this poor outcome, we completed an exploratory phase II trial of intensified treatment for patients with intermediate and high‐risk follicular lymphoma. Front‐line treatment with chemo‐immunotherapy consisting of rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone was followed by radio‐ immunotherapy with 90‐Yttrium ibritumomab tiuxetan consolidation, and 2 years of rituximab maintenance. The 5‐year overall survival for intermediate and high‐risk patients was 88% and 83%, respectively. Of 33 enrolled patients, 3 were off study before receiving radio‐immunotherapy. Three months post radio‐immunotherapy, 28/33 (85%) patients had achieved complete response including 6 patients who had only a partial response to chemo‐immunotherapy and converted to complete response after radio‐immunotherapy. The 5‐year progression‐free survival for intermediate and high risk was 79% and 58%, respectively. Nine of 19 patients with molecular markers patients remain in molecular and clinical complete remission with a median follow‐up of 48 months (range 3‐84 months). Post radio‐immunotherapy, hematologic toxicities were mostly grade 1 and 2. However, asymptomatic grade 3 or 4 thrombocytopenia and neutropenia occurred in 11%‐36% and 10%‐24% of patients, respectively. Myelodysplastic syndrome occurred in 1 patient 4 years post treatment. Whereas many patients had prolonged B‐cell reduction and low immunoglobulin levels post treatment, previous immunities to rubella were maintained. More aggressive upfront approaches such as this may benefit higher risk follicular lymphoma, but confirmatory trials are required. http://www.clinicaltrials.gov : NCT01446562.     

Extended infusion of beta-lactam antibiotics: optimizing therapy in critically-ill patients in the era of antimicrobial resistance

Introduction: Beta-lactams are at the cornerstone of therapy in critical care settings, but their clinical efficacy is challenged by the rise in bacterial resistance. Infections with multi-drug resistant organisms are frequent in intensive care units, posing significant therapeutic challenges. The problem is compounded by a dearth in the development of new antibiotics. In addition, critically-ill patients have unique physiologic characteristics that alter the drugs pharmacokinetics and pharmacodynamics.

Areas covered: The prolonged infusion of antibiotics (extended infusion [EI] and continuous infusion [CI]) has been the focus of research in the last decade. As beta-lactams have time-dependent killing characteristics that are altered in critically-ill patients, prolonged infusion is an attractive approach to maximize their drug delivery and efficacy. Several studies have compared traditional dosing to EI/CI of beta-lactams with regard to clinical efficacy. Clinical data are primarily composed of retrospective studies and some randomized controlled trials. Several reports show promising results.

Expert commentary: Reviewing the currently available evidence, we conclude that EI/CI is probably beneficial in the treatment of critically-ill patients in whom an organism has been identified, particularly those with respiratory infections. Further studies are needed to evaluate the efficacy of EI/CI in the management of infections with resistant organisms.     

An in vitro evaluation of ZiReal abutments with hexagonal connection: in original state and following abutment preparation

PURPOSE: Laboratory processing of implant-supported prostheses may alter the surface of the abutment in contact with the implant head, with potential repercussions for the interface fit. The purpose of this study was to assess changes at the implant interface of high-strength zirconia ceramic esthetic abutments with a hexagonal connection (ZiReal; 3i/Iimplant Innovations, Palm Beach Gardens, FL) following abutment preparation for single-tooth restorations. MATERIALS AND METHODS: The depth (d) and width (w) of the titanium hexagonal portion of the abutment, the apical diameter of the abutment (D), and the rotational freedom (R) of the abutment were assessed for 20 ZiReal abutments prior to preparation (time 0) and following abutment preparation (time 1) to detect any eventual change of fit of the abutment on the top of the implant hexagon. RESULTS: No significant differences relative to any study parameter (d, w, D, and R) were observed between time 0 and time 1 (P = .9542). DISCUSSION AND CONCLUSIONS: The hexagonal misfit of the titanium machined ZiReal abutment on the implant hexagon may be implicated in screw joint loosening. The results of this report suggest that if all laboratory steps are carefully observed, changes at the implant/ZiReal abutment do not occur. The maintenance of the original features of the ZiReal abutment may reduce the risk of screw loosening.     

Care Coordination Associated with Improved Timing of Newborn Primary Care Visits

Objective Despite practice recommendations that all newborns be examined within 3–5 days after discharge, many are not seen within this timeframe. Our objective was to determine the association between care coordination and timing of newborn follow-up. Methods This retrospective study evaluated 6251 newborns from eight maternity hospitals who scheduled a primary care appointment at one of two academic pediatric practices over 3.5 years. Two programs were sequentially implemented: (1) newborn discharge coordination, and (2) primary care intake coordination. Primary outcome was days between discharge and follow-up, dichotomized as ≤ or >5 days. Number of rescheduled appointments and loss to follow-up were also assessed. Adjusted relative risks (RR) and odds ratios (OR) were determined by piecewise generalized linear and logistic regression. Results Among 5943 newborns with a completed visit, 52.9 % were seen within 5 days of discharge (mean 6.7 days). After multivariable adjustment, the pre-exposure period (8 months) demonstrated a downward monthly trend in completing early follow-up (RR 0.93, p < 0.001). After initial program implementation, we observed a 3 % monthly increase (RR 1.03, p < 0.001 for test of slope change from pre-exposure to post-exposure), such that likelihood of recommended follow-up increased by roughly 72 % after discharge coordinator implementation and roughly 33 % after primary care coordinator implementation. The latter was also associated with a 13 % monthly decrease in odds of loss to follow-up (OR 0.87, p < 0.001). Conclusions for Practice Care coordination increases adherence among low income families to recommended newborn follow-up after birth hospitalization.     

Neurogenesis in the adult hippocampus: history,regulation, and prospective roles

Background: The hippocampus is one of the sites in the mammalian brain that is capable of continuously generating controversy. Adult neurogenesis is a remarkable process, and yet an intensely debatable topic in contemporary neuroscience due to its distinctiveness and conceivable impact on neural activity. The belief that neurogenesis continues through adulthood has provoked remarkable efforts to describe how newborn neurons differentiate and incorporate into the adult brain. It has also encouraged studies that investigate the consequences of inadequate neurogenesis in neuropsychiatric and neurodegenerative diseases and explore the potential role of neural progenitor cells in brain repair. The adult nervous system is not static; it is subjected to morphological and physiological alterations at various levels. This plastic mechanism guarantees that the behavioral regulation of the adult nervous system is adaptable in response to varying environmental stimuli. Three regions of the adult brain, the olfactory bulb, the hypothalamus, and the hippocampal dentate gyrus, contain new-born neurons that exhibit an essential role in the natural functional circuitry of the adult brain. Purpose/Aim: This article explores current advancements in adult hippocampal neurogenesis by presenting its history and evolution and studying its association with neural plasticity. The article also discusses the prospective roles of adult hippocampal neurogenesis and describes the intracellular, extracellular, pathological, and environmental factors involved in its regulation. Abbreviations AHN Adult hippocampal neurogenesis

AKT Protein kinase B

BMP Bone Morphogenic Protein

BrdU Bromodeoxyuridine

CNS Central nervous system

DG Dentate gyrus

DISC1 Disrupted-in-schizophrenia 1

FGF-2 Fibroblast Growth Factor 2

GABA Gamma-aminobutyric acid

Mbd1 Methyl-CpG-binding domain protein 1

Mecp2 Methyl-CpG-binding protein 2

mTOR Mammalian target of rapamycin

NSCs Neural stem cells

OB Olfactory bulb; P21: cyclin-dependent kinase inhibitor 1

RBPj Recombination Signal Binding protein for Immunoglobulin Kappa J Region

RMS Rostral migratory Stream

SGZ Subgranular zone

Shh Sonic hedgehog

SOX2 SRY (sex determining region Y)-box 2

SVZ Subventricular zone

Wnt3 Wingless-type mouse mammary tumor virus

     

Walk-in Model for Ill Care in an Urban Academic Pediatric Clinic

Objectives

Since the Institute of Medicine's 2001 charge to reform health care, there has been a focus on the role of the medical home. Access to care in the proper setting and at the proper time is central to health care reform. We aimed to increase the volume of patients receiving care for acute illnesses within the medical home rather than the emergency department or urgent care center from 41% to 60%.