Suicidality Over the First 5 Years of Psychosis: Does Extending Early Intervention Have Benefits?

Objective:We aimed to investigate whether individuals with first-episode psychosis (FEP) receiving extended early intervention (EI) were less likely to experience suicidal ideation and behaviors than those transferred to regular care after 2 years of EI. Another objective was to examine the 5-year course of suicidality in FEP.Methods:We conducted a secondary analysis of a randomized controlled trial where 220 patients were randomized after 2 years of EI to receive extended EI or regular care for the subsequent 3 years. Suicidality was rated using the Brief Psychiatric Rating Scale. Linear mixed model analysis was used to study time and group effects on suicidality.Results:Extended EI and regular care groups did not differ on suicidality. There was a small decrease in suicidality over time, F(7, 1038) = 1.84, P = 0.077, with an immediate sharp decline within a month of treatment, followed by stability over the remaining 5 years. Patients who endorsed suicidality at entry (46.6%) had higher baseline positive, negative, and depressive symptoms. The 5-year course fell in 3 groups: never endorsed suicidality (33.9%), endorsed suicidality at low-risk levels (43.1%), and endorsed high-risk levels (23.0%). The high-risk group had a higher proportion of affective versus nonaffective psychosis diagnosis; higher baseline positive and depressive symptoms; higher 5-year mean depression scores, and fewer weeks of positive symptom remission over the 5-year course.Conclusions:The first month of treatment is a critical period for suicide risk in FEP. Although early reductions in suicidality are often maintained, our findings make the case for sustained monitoring for suicide risk management.     

Diagnostic imaging in gynecologic malignancy

Advances in imaging techniques over the past few decades have continued at an astounding pace and now physicians have various modalities to examine the human body. These imaging techniques may be used to assist in diagnosis, staging, and follow-up of oncology patients. The increasing complexity of diagnostic radiology provides a challenge to radiologists and oncologists to use these tools in a clinically efficient and cost-effective manner. The ultimate goal is to offer a safe and effective examination that provides clinically relevant information for the management of an individual patient. Currently ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) are being used to evaluate patients with gynecological malignancies. Goal of this review is to provide an overview of clinically available imaging techniques and discuss relative strengths and weaknesses. This article summarizes the diagnostic performance (sensitivity, specificity, positive and negative likelihood ratios) of US, CT, MRI and PET/CT in the diagnosis of various gynecological diseases and tumors. US is the first-line imaging modality of choice and is used to discriminate between benign and malignant adnexal masses and for characterizing adnexal tumors such as dermoid cyst, endometrioma, hemorrhagic corpus luteum, etc., for diagnosing intrauterine pathology in women with dysfunctional uterine bleeding, and for confirming or refuting pelvic pathology in women with pelvic pain. MRI can play a role in detecting the extent of disease and helps in local staging of gynecologic tumors. CT can be used to detect extrapelvic disease and PET/CT can assist in detecting distant metastatic disease in order to select appropriate surgical candidates.     

Randomized Phase II Study of Two Doses of Pixantrone in Patients with Metastatic Breast Cancer (NCCTG N1031, Alliance)

BackgroundAnthracycline use in metastatic breast cancer (MBC) is hindered by cumulative exposure limits and risk of cardiotoxicity. Pixantrone, a novel aza-anthracenedione with structural similarities to mitoxantrone and anthracyclines, is theorized to exhibit less cardiotoxicity, mainly due to lack of iron binding. We conducted a randomized phase II study to evaluate the efficacy and safety of 2 dosing schedules of pixantrone in patients with refractory HER2-negative MBC.MethodsIntravenous pixantrone was administered at 180 mg/m² every 3 weeks (group A) versus 85 mg/m² on days 1, 8, and 15 of a 28-day cycle (group B). Primary endpoint was objective response rate (ORR) and secondary endpoints included progression-free survival (PFS), median 6-month PFS, overall survival (OS), safety, quality of life, and serial assessment of circulating tumor cells. A 20% ORR was targeted as sufficient for further testing of pixantrone in this patient population.ResultsForty-five patients were evaluable, with 2 confirmed partial responses in group A and 1 in group B. The trial was terminated due to insufficient activity. Overall median PFS and OS were 2.8 (95% confidence interval [CI]: 2.0-4.1) and 16.8 (95% CI: 8.9-21.6) months, respectively. Notable overall grade 3-4 adverse events were the following: neutrophil count decrease (62%), fatigue (16%), and decrease in ejection fraction (EF) (4%).ConclusionPixantrone has insufficient activity in the second- and third-line MBC setting. It appears, however, to have limited cardiotoxicity. (ClinicalTrials.gov ID: {"type":"clinical-trial","attrs":{"text":"NCT01086605","term_id":"NCT01086605"}}NCT01086605).     

Rapid Reversal of Parenteral-Nutrition-Associated Cirrhosis Following Isolated Intestinal Transplantation

Introduction  Liver disease and the development of hepatic fibrosis are complications associated with total parenteral nutrition (TPN). Patients developing cirrhosis and portal hypertension in the setting of intestinal failure have a high mortality and may require combined liver and intestinal transplantation which carries much higher morbidity and mortality than isolated intestinal transplantation. Discussion  Recently, regression of hepatic fibrosis in patients with TPN liver disease has been described following intestinal transplantation. To date, there has been no demonstration of the reversal of established cirrhosis due to long-term TPN injury. Herein, we describe a patient with intestinal failure who developed cirrhosis from long-standing TPN injury and underwent isolated intestinal transplantation. He had no overt clinical stigmata of portal hypertension and had preserved liver function. Serial liver biopsies were reviewed and assessed with standard histology and quantitation of fibrosis using image analysis. Dramatic regression of fibrosis and reversal of cirrhosis were observed 17 months posttransplantation. Image analysis demonstrated a 14% total decrease in the percentage area of fibrosis. Conclusions  Cirrhosis related to TPN may be rapidly reversible after isolated intestinal transplantation. Such patients may be able to undergo isolated intestinal transplantation if they do not have hepatic synthetic compromise or clinical stigmata of portal hypertension.     

Spatiotemporal tracking of cells in tissue‐engineered cardiac organoids

Cardiac tissue engineering aims to create myocardial patches for repair of defective or damaged native heart muscle. The inclusion of non‐myocytes in engineered cardiac tissues has been shown to improve the properties of cardiac tissue compared to tissues engineered from enriched populations of myocytes alone. While attempts have been made to mix non‐myocytes (fibroblasts, endothelial cells) with cardiomyocytes, very little is understood about how the tissue properties are affected by varying the respective ratios of the three cell types and how these cells assemble into functional tissues with time. The goal of this study was to investigate the effects of modulating the ratios of the three cell types and to spatially and temporally track cardiac tri‐cultures of cells. Primary neonatal cardiac fibroblasts and D4T endothelial cells were incubated in 5 µM CellTracker^? green dye and CellTracker^? red dye, respectively, while neonatal cardiomyocytes were labelled with 20 µg/mL DAPI. The non‐myocytes were seeded either sequentially (pre‐culture) or simultaneously (tri‐culture) in Matrigel‐coated microchannels and allowed to form organoids, as in our previous studies. We also varied the seeding percentage of cardiomyocytes while keeping the total cell number constant in an attempt to improve the functional properties of the organoids. Organoids were imaged on days 1 and 4. Endothelial cells were seen to aggregate into clusters when simultaneously tri‐cultured with myocytes and fibroblasts, while pre‐cultures contained elongated cells. Functional properties of organoids were improved by increasing the seeding percentage of enriched cardiomyocytes from 40% to 80%. Copyright © 2009 John Wiley & Sons, Ltd.     

Relationship of maternal serum ferritin with foetal serum ferritin, birth weight and gestation

Haemoglobin and ferritin estimations employing the micro-ELISA technique were done in 308 random selected mothers in labour and their newborns. The values of haemoglobin and serum ferritin as well as birth weight and gestation of babies born to iron depleted, and mildly and moderately anaemic mothers were no different from those of newborns of non-anaemic women. However, the values of serum ferritin per se in all these newborns were much lower than what are generally reported from the western countries. Babies born to severely anaemic women, on the other hand, showed elevated levels of haemoglobin and serum ferritin, and lower birth weights and gestation. Thus, mild to moderate iron deficiency in the mother does contribute to lower iron reserves in the foetus, if not frank iron depletion, and severe iron deficiency anaemia to lower birth weight and gestation.     

Evaluation of three 'ready to formulate' oil adjuvants for foot-and-mouth disease vaccine production

Foot-and-mouth disease virus (FMDV) type OR(2)/75, grown on BHK 21 clone 13 cell monolayers, was inactivated with formalin. The virus was clarified and was either concentrated with 8% polyethylene glycol 6000 (PEG) or used in its untreated form for the preparation of oil adjuvant vaccines. The oil adjuvants used in this study were Montanide ISA 206 (which renders a water-in-oil-in-water (w/o/w) type of emulsion), Montanide ISA 57 and Montanide ISA 50V (both of which render water-in-oil (w/o) type of emulsions). The vaccines were tested on guinea pigs and calves. The results indicated that vaccines emulsified using Montanide ISA 57 elicited the best protective immune response in the animals, followed by those emulsified with Montanide ISA 50V and Montanide ISA 206. It was also found that vaccines formulated with virus concentrated using 8% polyethylene glycol (PEG) were more immunogenic than the vaccines formulated with the untreated harvest virus.