Risk of venous thromboembolism during treatment with antipsychotic agents

The evidence to date on the relation between the risk of venous thromboembolic disease (VTE) and antipsychotic agents derives primarily from observational and case history studies. While an increased risk of VTE has been associated with first‐generation low‐potency antipsychotic agents, particularly clozapine, there appears to be a growing number of reports on the occurrence of this adverse reaction during the use of second‐generation antipsychotics, such as risperidone and olanzapine. The highest risk of pathological blood clotting emerges during the first 3 months after initiation of treatment with the product. Potential etiopathogenetic factors leading to VTE during treatment with antipsychotic agents include sedation, obesity, elevation of antiphospholipid antibodies, increased platelet activation and aggregation, hyperhomocysteinemia, and hyperprolactinemia. Diagnoses of schizophrenia and/or bipolar affective disorder, as well as hospitalization or stress with sympathetic activation and elevation of catecholamine levels, have been reported as known prothrombogenic factors. The present article contains the new version of the guideline for the prevention of VTE in psychiatric patients with limited mobility. Further prospective studies are necessary to elucidate the biological mechanisms of the relations between antipsychotic agents and VTE.     

Nurses experiences in chemical emergency departments: Iran–Iraq war, 1980–1988

BackgroundNurses have played a major role in taking care of the wounded across the centuries. One of the most important roles of Iranian nurses in wartime has been working in chemical emergency departments. This study investigated the nature of nursing practice in chemical emergency departments created in the context of the Iran–Iraq War fought during 1980–1988.MethodThis is a history methodology design with oral history and in-depth interview to detect nurses ‘actual experiences in chemical emergency departments while taking care of the chemically injured military forces.FindingsToday’s nurses emphasize finding new ways to fulfill the present nursing needs and to combine theory and practice in an appropriate framework.Having a retrospective approach to utilize nurses’ experience can well clarify the future way to achieve this goal.ConclusionThis study revealed the way the nurses prepared to take care of the chemically injured in miserable situations and their practice in chemical emergency departments. It highlighted their awareness of wartime nursing and the challenging experiences it brings.     

Molecular characterisation of Anisakidae larvae from fish in Adriatic Sea

In the present study, anisakids from: tuna (Thunnus thynnus) fattened in the Croatian farm in middle Adriatic Sea, three different feral fish species caught near tuna farm (Trachurus trachurus, Scomber japonicus and Oblada melanura) and fish marketed in Croatia (T. trachurus) were analysed by morphology and molecular methods. Larvae were identified to the species level by PCR restriction fragment length polymorphism and characterised by sequencing of nuclear (internal transcribed spacer) and mitochondrial (cytochrome c oxidase subunit 2) markers. The results revealed diverse Anisakidae community consisting of: Anisakis pegreffi, Anisakis simplex (s.s.), Anisakis typica and Hysterothylacium aduncum. This is the first report of A. typica in Adriatic Sea, and also the first record of this species in T. thynnus as host in Mediterranean Sea. Molecular identification of H. aduncum found in co-infection with Anisakis larvae type I expands our knowledge of the occurrence of these taxa in the Adriatic Sea. Zoonotic Anisakidae worms found in fish from the Adriatic Sea could represent a risk to acquire parasitic infection/allergies in Croatia.     

Titanium crystal orientation as a tool for the improved and regulated cell attachment

Cell adhesion is a fundamental process that controls cell proliferation, migration, and differentiation and is crucial for biomaterial-tissue integration. Osteoblast attachment on the surfaces of implant materials is, therefore, essential for the proper function of any implant in which osseointegration is required. Although many reports are available on osteoblast attachment using different surface modification, there is no specific report, so far, that investigates the effect of atomic order of specific crystallographic orientation of substrates on cell behavior. A novel coculture system is proposed to show the differential response of preosteoblast and fibroblast cell lines to the titanium single-crystal substrates. Our investigation has shown that surface recognition by the cell is influenced by the atomic structure of the surface leading to cell-type-specific adhesion. The degree of preosteoblast attachment is significantly higher on the Ti-(1120), whereas the fibroblast adhesion is increased on the Ti-(1010). This demonstrates that the three distinct faces of titanium substrates differ greatly in their capacity to serve as cell adhesive substrates. It also provides clear evidence for the role of crystal structure in regulating and improving cell-substrate interactions relevant for the optimal function of bone implant materials.     

Changing patterns of drug utilization in a neonatal intensive care population

Newborns in the neonatal intensive care unit (NICU) typically are exposed to a large number of drugs and are especially vulnerable to adverse drug reactions. It is important to review changes in drug use patterns periodically in the NICU to identify newly introduced drugs as well as drugs with increasing use. The objective of this study was to determine the changes in drug utilization patterns over a 7-year period in an NICU population. Drug utilization of 2332 neonates treated at an intramural NICU between January 1, 1997 and December 31, 1998, and 2691 neonates between January 1, 2001 and June 30, 2004 was analyzed using chi-square tests, T tests, and linear regression. There was an increased utilization of antibiotics, central nervous system drugs, endocrine agents, cardiovascular and gastrointestinal drugs, and a decreased utilization of ophthalmic drugs. No changes in nutritional, biological, renal, and pulmonary drugs were observed. Some individual drug changes include an increased use of vancomycin, cefepime, caffeine, and a decreased use of morphine. Significant changes in drug utilization patterns in an NICU were observed during a 7-year period. These data are useful in monitoring drug resistance patterns, adverse drug reactions, and prioritizing areas of relevant therapeutic research and educational programs.     

Lymphocyte populations and their change during five-year glatiramer acetate treatment

Background

The goal of this study was to determine the characteristics that are affected in patients treated with glatiramer acetate (GA).

The Combination of MEK Inhibitor With Immunomodulatory Antibodies Targeting Programmed Death 1 and Programmed Death Ligand 1 Results in Prolonged Survival in Kras/p53-Driven Lung Cancer

IntroductionThis study aimed to characterize the tumor-infiltrating immune cells population in Kras/tumor protein 53 (Trp53)-driven lung tumors and to evaluate the combinatorial antitumor effect with MEK inhibitor (MEKi), trametinib, and immunomodulatory monoclonal antibodies (mAbs) targeting either programmed death -1 (PD-1) or programmed cell death ligand 1 (PD-L1) in vivo.MethodsTrp53^FloxFlox;Kras^G12D/+;Rosa26^{LSL-Luciferase/LSL-Luciferase} (PKL) genetically engineered mice were used to develop autochthonous lung tumors with intratracheal delivery of adenoviral Cre recombinase. Using these tumor-bearing lungs, tumor-infiltrating immune cells were characterized by both mass cytometry and flow cytometry. PKL-mediated immunocompetent syngeneic and transgenic lung cancer mouse models were treated with MEKi alone as well as in combination with either anti–PD-1 or anti–PD-L1 mAbs. Tumor growth and survival outcome were assessed. Finally, immune cell populations within spleens and tumors were evaluated by flow cytometry and immunohistochemistry.ResultsMyeloid-derived suppressor cells (MDSCs) were significantly augmented in PKL-driven lung tumors compared to normal lungs of tumor-free mice. PD-L1 expression appeared to be highly positive in both lung tumor cells and, particularly MDSCs. The combinatory administration of MEKi with either anti–PD-1 or anti–PD-L1 mAbs synergistically increased antitumor response and survival outcome compared with single-agent therapy in both the PKL-mediated syngeneic and transgenic lung cancer models. Theses combinational treatments resulted in significant increases of tumor-infiltrating CD8⁺ and CD4⁺ T cells, whereas attenuation of CD11b⁺/Gr-1^high MDSCs, in particular, Ly6G^high polymorphonuclear-MDSCs in the syngeneic model.ConclusionsThese findings suggest a potential therapeutic approach for untargetable Kras/p53-driven lung cancers with synergy between targeted therapy using MEKi and immunotherapies.     

The value of 18F-DOPA PET-CT in patients with medullary thyroid carcinoma: comparison with 18F-FDG PET-CT

The purpose of this prospective study was to compare the value of DOPA PET-CT with FDG PET-CT in the detection of malignant lesions in patients with medullary thyroid carcinoma (MTC). Twenty-six consecutive patients (10 men, 16 women, mean age 59 ± 14 years) with elevated calcitonin levels were evaluated in this prospective study. DOPA and FDG PET-CT modalities were performed within a maximum of 4 weeks (median 7 days) in all patients. The data were evaluated on a patient- and lesion-based analysis. The final diagnosis of positive PET lesions was based on histopathological findings and/or imaging follow-up studies (i.e., DOPA and/or FDG PET-CT) for at least 6 months (range 6–24 months). In 21 (21/26) patients at least one malignant lesion was detected by DOPA PET, while only 15 (15/26) patients showed abnormal FDG uptake. DOPA PET provided important additional information in the follow-up assessment in seven (27%) patients which changed the therapeutic management. The patient-based analysis of our data demonstrated a sensitivity of 81% for DOPA PET versus 58% for FDG PET, respectively. In four (4/26) postoperative patients DOPA and FDG PET-CT studies were negative in spite of elevated serum calcitonin and CEA levels as well as abnormal pentagastrin tests. Overall 59 pathological lesions with abnormal tracer uptake were seen on DOPA and/or FDG PET studies. In the final diagnosis 53 lesions proved to be malignant. DOPA PET correctly detected 94% (50/53) of malignant lesions, whereas only 62% (33/53) of malignant lesions were detected with FDG PET. DOPA PET-CT showed superior results to FDG PET-CT in the preoperative and follow-up assessment of MTC patients. Therefore, we recommend DOPA PET-CT as a one-stop diagnostic procedure to provide both functional and morphological data in order to select those patients who may benefit from (re-)operation with curative intent as well as guiding further surgical procedures.     

Emodin inhibits growth and induces apoptosis in an orthotopic hepatocellular carcinoma model by blocking activation of STAT3

BACKGROUND AND PURPOSE

Aberrant activation of STAT3 is frequently encountered and promotes proliferation, survival, metastasis and angiogenesis in hepatocellular carcinoma (HCC). Here, we have investigated whether emodin mediates its effect through interference with the STAT3 activation pathway in HCC.

EXPERIMENTAL APPROACH

The effect of emodin on STAT3 activation, associated protein kinases and apoptosis was investigated using various HCC cell lines. Additionally, we also used a predictive tumour technology to analyse the effects of emodin. The in vivo effects of emodin were assessed in an orthotopic mouse model of HCC.

KEY RESULTS

Emodin suppressed STAT3 activation in a dose- and time-dependent manner in HCC cells, mediated by the modulation of activation of upstream kinases c-Src, JAK1 and JAK2. Vanadate treatment reversed emodin-induced down-regulation of STAT3, suggesting the involvement of a tyrosine phosphatase and emodin induced the expression of the tyrosine phosphatase SHP-1 that correlated with the down-regulation of constitutive STAT3 activation. Interestingly, silencing of the SHP-1 gene by siRNA abolished the ability of emodin to inhibit STAT3 activation. Finally, when administered i.p., emodin inhibited the growth of human HCC orthotopic tumours in male athymic nu/nu mice and STAT3 activation in tumour tissues.

CONCLUSIONS AND IMPLICATIONS

Emodin mediated its effects predominantly through inhibition of the STAT3 signalling cascade and thus has a particular potential for the treatment of cancers expressing constitutively activated STAT3.     

Repair of esophageal atresia with proximal fistula using endoscopic magnetic compression anastomosis (magnamosis) after staged lengthening

We describe the treatment of a patient with long-gap esophageal atresia with an upper pouch fistula, mircogastria and minimal distal esophageal remnant. After 4.5 months of feeding via gastrostomy, a proximal fistula was identified by bronchoscopy and a thoracoscopic modified Foker procedure was performed reducing the gap from approximately 7–5 cm over 2 weeks of traction. A second stage to ligate the fistula and suture approximate the proximal and distal esophagus resulted in a gap of 1.5 cm. IRB and FDA approval was then obtained for endoscopic placement of 10-French catheter mounted magnets in the proximal and distal pouches promoting a magnetic compression anastomosis (magnamosis). Magnetic coupling occurred at 4 days and after magnet removal at 13 days an esophagram demonstrated a 10 French channel without leak. Serial endoscopic balloon dilation has allowed drainage of swallowed secretions as the baby learns bottling behavior at home.