Outcomes and survival of patients undergoing percutaneous vegetectomy for right heart endocarditis.

Backgrounds: AngioVac is used for the percutaneous removal of vegetations and for debulking of large vegetations in patients who are not surgical candidates.This study aims to identify the demographics, echocardiographic features, indications, improvement of the tricuspid valve regurgitation, and survival outcomes of patients who have undergone AngioVac vegetectomy reported in the literature. Methods: A systematic review was performed to identify articles reporting suction thromectomy or vegetation removal using the AngioVac system for RSIE (right sided infective endocarditis). Survival on discharge was our primary outcome. Additionally, we evaluated indications for suction thrombectomy and TR improvement. Categorical variables were expressed as percentages and ratios. Results: A total of 49 studies were identified. The most common risk factor was intravenous drug abuse seen in 45% (20/49) and cardiovascular implantable electronic device (CIED) in 45% (20/49). Circulatory shock was seen in 35% of patients. The causative organism was gram positive cocci (86%). Moderate to severe TR was present in 74% of cases with documented echocardiograms. Indications for AngioVac were poor surgical candidacy (81%) or to reduce septic emboli risk (19%). Survival at discharge was 93%. TR improvement was reported only in 16% cases and remained unchanged/worsened in 84%. Conclusion: AngioVac procedure is an alternative treatment for critically ill patients who cannot undergo surgery. To understand the survival, safety and candidacy of patients undergoing this procedure, further randomized control studies and literature reviews are needed. The improvement or worsening of tricuspid regurgitation in patients with TR valve involvement is another factor to be investigated.

Ameliorating Effects of TRIM67 against Intestinal Inflammation and Barrier Dysfunction Induced by High Fat Diet in Obese Mice.

Tripartite Motif 67 (TRIM67) is an important member of TRIM family proteins, which participates in different cellular processes including immune response, proliferation, differentiation, carcinogenesis, and apoptosis. In recent years, a high fat diet (HFD) has remained one of the main causes of different metabolic diseases and increases in intestinal permeability as well as inducing intestinal inflammation. The current study investigated the protective effects of TRIM67 in the ileum and colon of obese mice. 4-week-old wild-type (WT) C57BL/6N mice and TRIM67 knockout (KO) C57BL/6N mice were selected and randomly divided into four sub-groups, which were fed with control diet (CTR) or HFD for 14 weeks. Samples were collected at the age of 18 weeks for analysis. To construct an in vitro obesity model, over-expressed IPEC-J2 cells (porcine intestinal cells) with Myc-TRIM67 were stimulated with palmitic acid (PA), and its effects on the expression level of TRM67, inflammatory cytokines, and barrier function were evaluated. The KO mice showed pathological lesions in the ileum and colon and this effect was more obvious in KO mice fed with HFD. In addition, KO mice fed with a HFD or CTR diet had increased intestinal inflammation, intestinal permeability, and oxidative stress compared to that WT mice fed with these diets, respectively. Moreover, IPEC-J2 cells were transfected with TRIM67 plasmid to perform the same experiments after stimulation with PA, and the results were found consistent with the in vivo evaluations. Taken together, our study proved for the first time that HFD and TRIM67 KO mice have synergistic damaging effects on the intestine, while TRIM67 plays an important protective role in HFD-induced intestinal damage.

Publisher Correction: Federated discovery and sharing of genomic data using Beacons.

In the version of this article initially published, Lena Dolman's second affiliation was given as Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. The correct second affiliation is Ontario Institute for Cancer Research, Toronto, Ontario, Canada. The error has been corrected in the HTML and PDF versions of the article.

Risk Factors and Epidemiology of Gastric Cancer in Pakistan.

Gastric cancer is the 2nd most common cause of death among all cancers and is the 4th most common cancer in the world. The number of deaths due to gastric cancer is about 800,000 annually. Gastric cancer is more common in men as compared to women and is 3rd most common cancer after colorectal and breast cancers in women. A progressive rise in the incidence rate has been observed in females over the last 5 years. The highest incidence of stomach cancer is in China, South America and Eastern Europe. The incidence of gastric cancer has 20 fold variation worldwide. Global variation is linked by two factors which play important role in developing gastric cancer. One is infection with Helicobacter pylori and the 2nd is diet. South Asia is a region with low risk, despite a high prevalence of H.pylori. Gastric carcinoma is common in southern region of India. Gastric cancer is more readily treated if diagnosed early. This study aims to provide awareness about gastric cancer as well as an updated knowledge about risk factors and epidemiology of gastric cancer in Pakistan.

Dual endogenous stimuli-responsive polyplex micelles as smart two-step delivery nanocarriers for deep tumor tissue penetration and combating drug resistance of cisplatin.

Massive delivery of therapeutics throughout tumors and efficient cellular internalization into tumor cells remain the major obstacles for polymeric drug delivery system in the treatment of drug-resistant cancers. To address these issues, we strategically programmed dual stimuli-responsive polyplex micelles as drug delivery systems from self-assembly of anionic block copolymers, poly(ethylene glycol)-poly[(N'-dimethylmaleoyl-2-aminoethyl)aspartamide] (PEG-PAsp(EDA-DM)), and platinum(iv)-conjugated cationic poly(amidoamine) (PAMAM-Pt(iv)) dendrimer prodrugs. It is noteworthy that the chemical design for anionic block copolymers affords intriguing charge conversional function in response to a mild acidic environment at the tumor site (pH ∼ 6.8), thereby permitting rapid disassembly of polyplex micelle as a result of electrostatic repulsion. Thus, PAMAM-Pt(iv) prodrugs released in the form of individual molecules exert deep penetration and good dispersion activity in the tumor tissue by virtue of their small size and high mobility. Furthermore, the well-dispersed positively charged PAMAM dendrimers owing to their high affinity to the negatively charged cellular membrane are efficiently internalized into the tumor cells, followed by release of active cisplatin drug in the reductive cytosol. Accordingly, the drug resistance of cisplatin can be addressed. This proof-of-concept anticancer drug delivery platform provides a unique two-step delivery of anti-cancer drugs for the pursuit of deep tumor tissue penetration and overcoming drug resistance.

ROCK: a resource for integrative breast cancer data analysis.

Given the steady increase in breast cancer rates in both the developed and developing world, there has been a concerted research effort undertaken worldwide to understand the molecular mechanisms underpinning the disease. The data generated from numerous clinical trials and experimental studies shed light on different aspects of the disease. We present a new version of the ROCK database (rock.icr.ac.uk), which integrates such diverse data types allowing unique analyses of published breast cancer experimental data. We have added several new data types and analysis modules to ROCK, which allow the user to interactively query and research the huge amounts of available experimental data and perform complex correlations across studies and data types such as gene expression, genomic copy number aberrations, micro RNA expression, RNA interference, survival analysis, clinical annotation and signalling protein networks. We present the recent and major functional updates and enhancements to the ROCK resource, including new analysis modules and microRNA and NGS data integration, and illustrate how ROCK can be used to confirm known experimental results as well as generate novel leads and new experimental hypotheses using the Wnt signalling cell surface receptor FZD7 and the Myc oncogene. ROCK provides a unique breast cancer analysis platform of integrated experimental datasets at the genomic, transcriptomic and proteomic level. This paper presents how ROCK has transitioned from being simply a database to an interactive resource useful to the broader breast cancer research community in our effort to facilitate research into the underlying molecular mechanisms of breast cancer.

An audit of length of bone marrow trephine biopsies at a tertiary care hospital.

BACKGROUND: Bone marrow trephine biopsy is a well established minor surgical procedure for the inspection of bone marrow usually done along with bone marrow aspiration. The objective of this study was to evaluate the length of trephine biopsies and the rate of positivity for diagnosis as well as unfit biopsies in various length ranges. METHODS: This retrospective study was conducted at Fauji Foundation Hospital and Foundation University Medical College Rawalpindi from Jan 2007 to Dec 2009. A total of 394 trephine biopsy reports were collected and reviewed. The criterion for adequate trephine biopsy was > or = 1.5 Cm. The biopsies were divided into four groups according to length, i.e., group-1: > or = 1.5 Cm, group-2: 1-1.4 Cm, group-3: 0.5-0.9 Cm, and group-4: < 0.5 Cm. The adequacy of trephine biopsy length and rate of positive diagnosis as well as unfit biopsies were compared. RESULTS: Total 394 trephine biopsies were reviewed. Group-1 included 88 biopsies and 87 (98.9%) had positive diagnosis. Group-2 included 137 biopsies and 133 (97.1%) had positive diagnosis. Group-3 included 99 biopsies and 91 (92%) had positive diagnosis. Group-4 included 70 biopsies and 57 (81.4%) had positive diagnosis. There was no significant difference between group-1 and group-2 for the rate of positivity of diagnosis (p = 0.65). In group-1, 1 (1.1%) was unfit for evaluation, in group-2, 4 (2.9%) were unfit, in group-3, 8 (8%) were unfit, and in group-4, 13 (18.5%) were unfit for evaluation. Total 26 trephine biopsies were unfit for evaluation, out of which 13 (50%) belonged to group-4. Trephine biopsies that were unfit for evaluation were 4 (4.9%) in 2007, 17 (10.5%) in 2008, and 5 (3.3%) in 2009. CONCLUSION: Although 22.3% biopsies were of recommended length there was no significant difference in rate of positive diagnosis between biopsies of > or = 1.5 Cm and 1-1.4 Cm.

Infection in orthopedic implant surgery, its risk factors and outcome.

BACKGROUND: Infection in orthopedic surgery is a disaster both for the patient and surgeon. Although its incidence has been reduced due to modern theatre facilities and aseptic measures but in developing countries its prevalence is still high. It is better to prevent infection rather than to treat it. The objective of this study is to know the frequency of infection in orthopedic implant surgery in a public hospital and to evaluate the risk factors, causative organism, complications and treatment. METHODS: This prospective study was conducted in orthopedic unit-B Ayub Teaching Hospital, Abbottabad, from 1st April 2007 to 30th October 2007. Close fracture cases admitted for internal fixation devices were included. The exclusion criteria were soft tissue surgery, wounds and open fractures needing external fixation devices. The follow up was done for six months. RESULTS: Infection developed in 6 patients (5.76%), out of which superficial and deep infections were 2 (1.92%) and 4 (3.84%) respectively. There were 2 infection cases in each stage of the infection i.e. early, delayed and late. The staphylococcus aureus was the commonest organism, i.e., 3 (50%) out of 6. The age of the patients was more than 60 years in 3 (2.88%) patients, 30 to 60 years in 2 (1.92%) patients and below 30 year in 1 (0.96%) patient. The smoking history was in 2 (1.92%) patients. CONCLUSION: Infection rate in our study was quite high and needs proper measures to control it because it had great financial burden on patient and on hospital resources and could lead to morbidity and mortality in patients. We could not find significant risk factors in our small sample size study although the infection was relatively more common in patients with advanced age, prolonged surgery time, smoking and skin abrasion at fracture site. Commonest organism was Staphylococcus aureus.

Skin metastasis from prostate adenocarcinoma.

We are presenting an interesting case of skin metastasis from adenocarcinoma prostate. Interestingly bone metastasis were absent as documented on radioisotope bone scan and PSA levels were normal. As it was a hormone refractory disease, he was started on mitoxantrone and prednisolone chemotherapy. Lung metastatis appeared after 2 cycles of chemotherapy. He died of progressive disease 4 months later.