An old problem with a new therapy: GI bleeding in VAD patients and deep bowel enteroscopy (Double balloon. Spiral enteroscopy).

An old problem with a new therapy: GI Bleeding in VAD patients and deep bowel enteroscopy (Spiral and Double Balloon Enteroscopy) Purpose: Evidence suggests that patients treated with non-pulsatile ventricular assist devices (VAD) are at an increased risk for gastrointestinal bleeding (GIB) beyond what is expected from routine anticoagulation. Diagnostic and treatment algorithms are currently undefined. We reviewed our experience of GIB in VAD patients and propose a new algorithm utilizing deep bowel enteroscopy (DBE) aimed to speed diagnosis and limit transfusions. (471) Methods & Procedures From 2004 to 2011, we studied 62 patients who received a non-pulsatile VAD at our center for episodes of GIB. GIB was defined as heme-positive stool, hematemeisis, or drop in Hgb\u3e1gm. All patients were anticoagulated and no patient had any previous bleeding history. The diagnostic and treatment modalities utilized consisted of standard GIB tests but evolved into an algorithm based primarily on DBE. DBE consists of double-balloon and spiral enteroscopy that allow us to see and treat pathology in the small bowel upt o 400 cm beyond the Ligament of Treitz. (723) Results: There were 41 individual episodes of GIB in 14 patients. Separating the episodes into two groups based on days to diagnosis and days to treatment, we found that when the diagnosis was made and treated within 2 hospital days, patients received half (3.53 v. 7.33 with

Prevalence and antimicrobial susceptibility pattern of coagulase-negative staphylococci (CoNS) isolated from clinical specimens in northern of Jordan

BACKGROUND: Coagulase negative Staphylococci (CoNS) are one of the most common bacteria found on human skin and on mucous membranes as a component of normal flora. The presence of CoNS in clinical specimens is frequently associated with an infectious aetiology or contamination. OBJECTIVES: We aimed to evaluate CoNS species distribution and susceptibility patterns in specimens obtained from clinics and hospitals in the Northern area of Jordan. METHODS: Standard identification methods showed the presence of CoNS in 223 specimens at different local hospitals. Susceptibility testing was performed using 18 antibiotics in accordance with the Clinical and Laboratory Standards Institute (CLSI) recommendations. RESULTS: Staphylococcus epidermidis and S. haemolyticus were found to be the most common species isolated from all specimens representing 122 (54.7%) and 52 (23.4%) of all CoNS species, respectively. Antibiotic susceptibility testing of CoNS species revealed their sensitivity to vancomycin, linozolid, rifampin and nitrofurantin, while showing a highly resistant pattern to ampicillin, penicillin, ceftriaxone, cefazolin, amoxicillin-clavulanic acid and erythromycin. Some variation of the susceptibility pattern of CoNS species were identified in specimens isolated from the ICU and paediatric hospital wards as well as from clinical specimens of urine, blood and catheter tips. CONCLUSION: The most common CoNS isolates were found to be S. epidermidis and S. haemolyticus with variable percentages according to the specimen source. Moreover, a high susceptibility CoNS to vancomycin, rifampin, and linezolid showed resistance to amoxicillin and penicillin

Adult ECMO and gastrointestinal bleeding from small bowel arteriovenous malformations: A novel treatment using spiral enteroscopy.

Hemorrhagic complications on extracorporeal membrane oxygenation (ECMO) are common because of the need for anticoagulation to maintain the oxygenator and circuitry. Gastrointestinal bleeding (GIB) is reported to occur in 3-6% of ECMO patients, 1 requiring frequent transfusions as well as multiple diagnostic and therapeutic interventions. Multiple transfusions can result in volume overload, coagulopathies and infections leading to significant morbidity and mortality. We present the first published case of GIB from an arteriovenous malformation (AVM) treated with a novel therapy termed spiral enteroscopy while the patient remained on venoarterial (VA) ECMO

An old problem with a new therapy: gastrointestinal bleeding in ventricular assist device patients and deep overtube-assisted enteroscopy.

Conventional algorithms for diagnosis and treatment of gastrointestinal bleeding (GIB) in patients with nonpulsatile ventricular assist devices (VADs) may take days to perform while patients require transfusions. We developed a new algorithm based on deep overtube-assisted enteroscopy (DOAE) to facilitate a rapid diagnosis and treatment. From 2004 to 2012, 84 patients who underwent VAD placement in our institution, were evaluated for episodes of GIB. Our new algorithm for the management of GIB using DOAE was evaluated by dividing the episodes into three groups: group A (traditional management without enteroscopy), group B (traditional management with enteroscopy performed \u3e24 hours after presentation), and group C (new management algorithm with enteroscopy performedpresentation). Gastrointestinal bleeding was observed in 14 (17%) of our study patients for a total of 45 individual episodes of which 28 met our criteria for subanalysis. Forty-one (84%) lesions were confined to the upper gastrointestinal tract with more than 91% of these lesions being arteriovenous malformations. Average number of transfusions in groups A, B, and C were 4.1, 6.3, and 1.3, respectively (p = 0.001). The number of days to treatment was significantly shorter in group C than group B (0.4 vs. 5.3 days, p = 0.0002). Our new algorithm for the management of GIB using DOAE targets the most common locations of bleeding found in this patient population. When performed early, DOAE has the potential to decrease the need for transfusions and allow for an early diagnosis of GIB in VAD recipients

Efficacy of miniaturized imacor trans-esophageal echocardiografm (TEE) prove in mechanical circulatory support.

Application of the miniaturized ImaCor Trans-Esophageal Echocardiogram (TEE) probe in Heart Transplant/Mechanical Cardiac Support Patients In the surgical cardiac care unit (SCCU), therapeutic interventions often need to be done at the bedside, necessitating the need for a rapidly employable diagnostic tool for the cardiac intensivist. We report the clinical utility of the miniature ImaCor TEE-probe in guiding management of post heart transplant (H-Txp) and mechanical cardiac support patients (MCS) and describe the economic benefit of such a device. This is an IRB approved retrospective review of MCS/H-Txp patients who had ImaCor TEE monitoring in the SCCU of our institution in 2011. The effect on management was stratified into 3 categories; Major (tamponade/device selection/RV failure), Moderate (weaning support device guidance/ inotrope management/fluid management/hemodynamic instability) and Minor (line placement/useful data). The ImaCor TEE-Probe was utilized in a total of 34 patients, of which 21 were either supported by MCS or were post H-Txp. Of these, 13 were on ECMO, 9 were post-VAD, 3 supported by the Impella device and 4 were post-H-Txp. 6 patients were placed on more than 1 method of MCS and 1 patient was supported by ECMO after a H-Txp. The device had a Major effect on management in 4 patients (19%), Moderate effect in 13 (62%) and a Minor effect in 4 (19%). The cost difference between this new device and the traditional TEE is also significant (900 USD vs 4000 USD). Our institution saved in excess of 150,000 USD with the use of this device instead of traditional TEE. This figure did not include the ability of this probe to be used repeatedly within a 72-hour time frame, and the potential cost of going to the operating theatre for further management. This device has proven to be an invaluable new adjunct in the SCCU by allowing previously unobtainable continuous real time monitoring of the MCS/H-Txp patient. Use of the ImaCor TEE-probe provides the cardiac intensivist with timely important clinical data that improves patient care and is economically advantageous

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Hypothyroidism in Pancreatic Cancer: Role of Exogenous Thyroid Hormone in Tumor Invasion-Preliminary Observations.

According to the epidemiological studies, about 4.4% of American general elderly population has a pronounced hypothyroidism and relies on thyroid hormone supplements daily. The prevalence of hypothyroidism in our patients with pancreatic cancer was much higher, 14.1%. A retrospective analysis was performed on patients who underwent pancreaticoduodenectomy (Whipple procedure) or distal pancreatectomy and splenectomy (DPS) at Thomas Jefferson University Hospital, Philadelphia, from 2005 to 2012. The diagnosis of hypothyroidism was correlated with clinicopathologic parameters including tumor stage, grade, and survival. To further understand how thyroid hormone affects pancreatic cancer behavior, functional studies including wound-induced cell migration, proliferation, and invasion were performed on pancreatic cancer cell lines, MiaPaCa-2 and AsPC-1. We found that hypothyroid patients taking exogenous thyroid hormone were more than three times likely to have perineural invasion, and about twice as likely to have higher T stage, nodal spread, and overall poorer prognostic stage (P \u3c 0.05). Pancreatic cancer cell line studies demonstrated that exogenous thyroid hormone treatment increased cell proliferation, migration, and invasion (P \u3c 0.05). We conclude that exogenous thyroid hormone may contribute to the progression of pancreatic cancer

RAN GTPase and Osteopontin in Pancreatic Cancer.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDA) has the worst prognosis among cancers, mainly due to the high incidence of early metastases. RAN small GTPase (RAN) is a protein that plays physiological roles in the regulation of nuclear transport and microtubule spindle assembly. RAN was recently shown to mediate the invasive functions of the prometastatic protein osteopontin (OPN) in breast cancer cells. We and others have shown previously that high levels of OPN are present in PDA. In this study, we analyzed the expression and correlation of RAN with OPN in human pancreatic lesions, and explored their regulation in PDA cell lines. METHODS: Real time PCR was used to analyze RAN and OPN mRNA levels in PDA, adjacent non-malignant, and benign pancreatic tissues. Expression levels were correlated with survival and different clinicopathological parameters using different statistical methods. Transient transfection studies using OPN and RAN plasmids, and knockdown experiments using siRNA were used to examine their mutual regulation. RESULTS: OPN and RAN levels highly correlated with each other (p CONCLUSIONS: The high levels of RAN in PDA and its correlation with OPN and with perineural invasion suggest that RAN may contribute to PDA metastasis and progression through the induction of OPN. RAN\u27s role in the regulation of OPN in PDA is unique and could provide potential novel therapeutic strategies to combat PDA aggressiveness