Improving Catheter Associated Urinary Tract Infection Rates in the Medical Units.

Sheikh Khalifa Medical City (SKMC) in Abu Dhabi is the main tertiary care referral hospital in the United Arab Emirates (UAE) with 560 bed capacity with a high occupancy rate. SKMC senior management has made a commitment to make quality and patient safety a top priority. Preventing health care associated infections, including Catheter Associated Urinary Tract Infection (CAUTI), is a high priority for our hospital. In order to improve CAUTI rates a multidisciplinary task force team was formed and led this performance improvement project. The purpose of this publication is to indicate the quality improvement interventions implemented to reduce CAUTI rates and the outcome of those interventions. We chose to conduct the pilot study in General Medicine as it is the busiest department in the hospital, with an average of 390 patients admitted per month during the study period. The study period was from March 2015 till April 2016. Our aim was to reduce CAUTI rates per 1000 device days in the medical units. Implemented interventions resulted in a reduction of CAUTI from 6.8 per 1000 device days in March 2015 to zero CAUTI in February through April 2016.

Improving venous thromboembolism risk assessment compliance using the electronic tool in admitted medical patients.

Sheikh Khalifa Medical City (SKMC) in Abu Dhabi is the main tertiary care referral hospital in the United Arab Emirates (UAE) with 560 bed capacity that is fully occupied most of the time. SKMC senior management has made a commitment to make quality and patient safety a top priority. Venous thromboembolism (VTE) risk assessment has been identified as a critical patient safety measure and key performance indicator. The electronic VTE risk assessment form a computerized decision support tool was introduced to improve adherence with deep venous thrombosis (DVT) prophylaxis recommendations. A multidisciplinary task force team was formed and led this quality improvement project. The purpose of this publication is to indicate the quality improvement interventions implemented to enhance compliance with VTE risk assessment and the outcomes of those interventions. We chose to conduct the pilot study in General Medicine as it is the busiest department in the hospital. The study period was from April 2014 till August 2015.The lessons learned were disseminated throughout the hospital. Our aim was to improve VTE risk assessment compliance by using the electronic form in order to ensure patient safety and reduce preventable harm. VTE risk assessment compliance improved in general medicine from 4% to 98%, and overall SKMC compliance from 21% to above 90%.

A phase I dose escalation study of Ad GV.EGR.TNF.11D (TNFerade™ Biologic) with concurrent chemoradiotherapy in patients with recurrent head and neck cancer undergoing reirradiation.

BACKGROUND: AdGV.EGR.TNF.11D (TNFerade™ Biologic) is a replication-deficient adenoviral vector expressing human tumor necrosis factor alpha (TNF-α) under the control of the chemoradiation-inducible EGR-1 promoter. TNF-α has been shown to function as a radiation sensitizer. We conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of TNFerade™ Biologic, when added to chemoradiotherapy in poor prognosis patients with recurrent, previously irradiated head and neck cancer (HNC). METHODS: TNFerade™ Biologic was injected intratumorally on day 1 of each 14-day cycle and dose-escalated in log increments from 4 × 10(9) to 4 × 10(11) PU. Daily radiation, infusional 5-fluorouracil (5-FU), and hydroxyurea were given on days 1-5 for seven cycles (FHX). Tumor biopsies were obtained before, during, and after treatment. RESULTS: Fourteen patients were treated. DLT was reached at a dose level of 3 (4 × 10(11) PU) with three thrombotic events. The response rate was 83.3%. The median survival was 9.6 months. One patient (7.1%) remained alive 3 years after treatment. Biopsies were obtained in 90% of patients. Nearly all tumors expressed adenovirus receptors, TNF-α, and TNF-α receptors. Adenoviral DNA was detected in three biopsies from one patient. CONCLUSIONS: TNFerade™ Biologic can be safely integrated with FHX chemoradiotherapy at an MTD of 4 × 10(10) PU. Monitoring for thrombotic events is indicated.

SU-E-J-23: Prostate Bed Motion Study Using Surgical Clips Based on Daily CBCT.

PURPOSE: To study prostate-bed motion after prostatectomy using the surgical clips as a surrogate. METHODS: On the treatment planning CT, surgical clips within the PTV are identified and contoured. They are also identified and contoured in each daily CBCT. The center of mass (COM) coordinates for each clip within the native reference frame of each image set of CT and CBCT are recorded. Each CBCT (for daily image guidance) is registered to the planning CT based on the pelvic bony structure. The resulted 3D transformation matrix is used to convert the clip coordinates in the CBCT to the planning CT reference frame. Difference between the converted COM coordinates and the one in planning CT is taken as the rigid motion of the prostate bed relative to the pelvic bony structure during the course of radiation therapy. The motion data are then analyzed using statistical error analysis and quantified by the commonly defined M (average over all fractions and all patients), S (stdev of averages per patient, the systematic motion), and s (root mean square of stdev per patient, the random motion). Among a large pool of patients, seven patients were selected for this retrospective study, each with 3 to 11 identifiable clips and 17 to 26 CBCT sets. The total number of clips is 44 and total daily CBCT sets 160. RESULTS: In the (right-left, anterio-posterior, foot-head) directions, the M values are (0.2 mm, 0.4 mm, -0.6 mm), S (0.2, 2.5, 3.2), and s (1.7, 2.6, 2.1). CONCLUSIONS: Relative to the bony pelvic structure, the prostate bed motion characteristics are similar to that of intact prostate, as summarized in Table 2 of Rasch et al 2005 ('Target Definition in Prostate, Head, and Neck.' Semin Radiat Oncol 15:136-145).

Pathologic response rates following definitive dose image-guided chemoradiotherapy and resection for locally advanced non-small cell lung cancer.

INTRODUCTION: Treatment of technically operable, medically fit locoregionally advanced non-small cell lung cancer (NSCLC) patients is a controversial therapeutic challenge. Our group routinely uses a trimodality approach. Recent advances in radiotherapy allow for improved tumor targeting and daily patient positioning. We hypothesized that these technologies would improve pathologic response rates. We analyzed consecutively treated stage IIIA/IIIB NSCLC patients undergoing chemoradiotherapy before major lung resection, with particular attention paid to the impact of advanced technologies. METHODS: Locoregionally advanced NSCLC patients (N2) staged in a multidisciplinary forum with mediastinoscopy were planned to receive platinum-based chemotherapy and 60Gy and major lung resection. Four-dimensional CT (4DCT) and image-guided radiotherapy (IGRT) were used as available. Survival endpoints were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using Cox proportional hazards models. RESULTS: We identified 53 patients from 2/1999 to 2/2010. Median RT dose was 59Gy. 68% underwent lobectomy. Forty-three patients were downstaged pathologically (81%), 38 experienced mediastinal sterilization (72%), and 21 (40%) had complete pathologic response (pCR). 1 and 2 year OS were 85.5% and 61.6%. Superior OS and DFS were associated with nodal downstaging and mediastinal sterilization (pN0). Treatment with IGRT/4DCT in 10 patients resulted in high rates of nodal downstaging (100% vs 77%, p=0.0452), mediastinal sterilization (90% vs 67%, p=0.0769), and pCR (60% vs 35%, p=0.0728). CONCLUSIONS: In selected patients, definitive dose CRT followed by major lung resection results in promising DFS and OS. The use of advanced radiotherapy techniques (4DCT and IGRT) appears to result in promising pathologic response rates.

Phase II trial of pemetrexed-based induction chemotherapy followed by concomitant chemoradiotherapy in previously irradiated patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Concurrent chemoreirradiation therapy (CRRT) offers a therapeutic option for patients with locoregionally recurrent squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that response to induction chemotherapy (IC) would improve outcome and predict increased survival. PATIENTS AND METHODS: Subjects with recurrent SCCHN not amenable to standard therapy were eligible. IC consisted of two 28-day cycles of gemcitabine and pemetrexed on days 1 and 14, followed by surgical resection, if appropriate, and/or CRRT consisting of carboplatin, pemetrexed, and single daily fractionated radiotherapy. RESULTS: Thirty-five subjects were enrolled, 31 were assessable for response, with 11 responders [response rate = 35%; 95% confidence interval (CI) 19.2-54.6]. Among 24 subjects who started CRRT, 11 were assessable for radiographic response, 4 complete response, 2 partial response, and 5 progressive disease. Median progression-free survival and overall survival (OS) were 5.5 months (95% CI 3.6-8.3) and 9.5 months (95% CI 7.2-15.4), respectively. One-year OS was 43% (95% CI 26% to 58%). Subjects who responded to IC had improved survival (P = 0.02). Toxic effects included mucositis, dermatitis, neutropenia, infection, hemorrhage, dehydration, and pain. CONCLUSIONS: The combination of pemetrexed plus gemcitabine was active and well tolerated in recurrent SCCHN. Response to IC may help stratify prognosis and offer an objective and dynamic metric in recurrent SCCHN patients being considered for CRRT.

A randomized phase II study of 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy compared with bevacizumab plus 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy for intermediate-stage and T4N0-1 head and neck cancers.

INTRODUCTION: We conducted a randomized phase II study to evaluate the impact of adding bevacizumab (B) to 5-fluorouracil (5-FU), hydroxyurea (HU), and radiotherapy (FHX) for intermediate-stage and select T4 head and neck squamous cell cancers (HNSCC). PATIENTS AND METHODS: Eligible patients had newly diagnosed HNSCC. Randomization was 2:1 in favor of BFHX. All patients received 500 mg HU p.o. b.i.d., 600 mg/m(2)/day continuous infusion 5-FU, and b.i.d. radiotherapy with or without bevacizumab 10 mg/kg administered on day 1 of each 14-day cycle. Patients received five cycles consisting of chemoradiotherapy for 5 days followed by 9 days without therapy. RESULTS: Twenty-six patients were enrolled (19 BFHX and 7 FHX). The study was halted following unexpected locoregional progression. Two-year survival was 68%; 89% treated with FHX and 58% (95% confidence interval 33% to 78%) treated with BFHX. Two-year locoregional control was 80% after chemoradiotherapy and 85% after surgical salvage. All locoregional progression occurred in T4 tumors randomized to BFHX. Two patients receiving BFHX died during therapy, and one died shortly after therapy. No catastrophic bleeding events were seen. CONCLUSIONS: Locoregional progression seen in T4N0-1 tumors treated with BFHX was unexpected and led to study termination. The addition of bevacuzimab to chemoradiotherapy for HNSCC should be limited clinical trials.

Induction chemotherapy and concurrent chemoradiotherapy for locoregionally advanced head and neck cancer: a multi-institutional phase II trial investigating three radiotherapy dose levels.

BACKGROUND: We hypothesized induction chemotherapy (IndCT) would improve distant control (DC) without compromising locoregional control (LRC) for locoregionally advanced head and neck cancer patients. Additionally, we systematically lowered radiotherapy (RT) doses attempting to maintain LRC while decreasing toxicity. PATIENTS AND METHODS: Stages III-IV (M0) locoregionally advanced head and neck cancer patients received carboplatin/paclitaxel (Taxol) IndCT followed by four or five cycles consisting of 5 days of paclitaxel, fluorouracil, hydroxyurea, and BID RT followed by a nine day break. RT dose to gross disease (high risk), intermediate, and low-risk volumes were reduced from cohort A (n = 68): 75, 60, and 45 Gy; to cohort B (n = 64): 75, 54, and 39 Gy; then cohort C (n = 90): 72, 51, and 36 Gy. RESULTS: A total of 222 patients accrued from November 1998 to September 2002. Median follow-up is 56 months. In all, 93/96/76% achieved a complete response to concurrent chemoradiotherapy (CRT) in cohort A/B/C. Three- and 5-year overall survivals (OSs) are 68% and 62%, respectively. Five-year LRC and DC are 91% and 87%, respectively. Response to IndCT predicted for OS, LRC, and time to progression (TTP). Cohort C patients had similar OS (P = 0.95), LRC, and DC, but worse (TTP) (P = 0.027). CONCLUSIONS: IndCT before CRT reduces distant progression while maintaining high LRC. The cohort B schedule provides the best therapeutic ratio. A randomized trial investigating IndCT before CRT has been initiated.

Functional organ preservation with definitive chemoradiotherapy for T4 laryngeal squamous cell carcinoma.

BACKGROUND: Randomized trials established chemoradiotherapy as standard treatment for advanced laryngeal cancer. Patients with large-volume T4 disease (LVT4) were excluded from these trials. The purpose of this study was to report T4 laryngeal cancer patient outcome, including those with LVT4 disease, treated with chemoradiotherapy. PATIENTS AND METHODS: This study is a retrospective subset analysis of 32 patients with T4 laryngeal carcinoma including LVT4 tumors treated on three consecutive protocols investigating paclitaxel (Taxol), 5-fluorouracil, hydroxyurea, and 1.5-Gy twice daily (BID) radiotherapy (TFHX). RESULTS: Median follow-up is 43 months. Four-year locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and laryngectomy-free survival (LFS) was 71%, 67%, 53%, and 86%, respectively. Four patients required laryngectomy for recurrent or persistent disease. Of disease-free patients with >or=1 year follow-up, 90% demonstrated normal or understandable speech. None required laryngectomy for complications. Among LVT4 patients, 4-year LRC, DFS, OS, and LFS was 71%, 65%, 56%, and 81%, respectively. Induction chemotherapy improved 4-year LRC (90% versus 46%, P = 0.03) and DFS (84% versus 42%, P = 0.03). CONCLUSIONS: Promising control and functional outcomes are achieved with TFHX for T4 laryngeal patients. LVT4 disease had outcomes similar to patients with less advanced disease treated on Radiation Therapy Oncology Group 91-11. Induction chemotherapy improved outcomes, warranting further investigation.

[Intracranial localization revealing Hodgkin's disease]. / Lésion intracrânienne révélatrice d'une maladie de Hodgkin.

The central nervous system's (CNS) involvement is uncommon in Hodgkin's disease (HD) and usually occurs in patients with relapsing disease many years after the initial diagnosis. An isolated involvement of the CNS is extremely rare and therefore, difficult to diagnosis. We report the case of a 27-year-old woman with seizure and a left cerebrodural mass on the cerebral imaging; secondarily, she developed cervical lymph node swelling; histological examination of the node revealed HD of the nodular sclerosis type. The dural lesion resolved after chemotherapy for HD.

[Listeria monocytogenes encephalitis revealed by left progressive hemiparesis]. / Hémiparésie d'installation progressive révélant une encéphalite à listéria monocytogènes.

INTRODUCTION: Central nervous system listeriosis is a diagnostic and therapeutic challenge for the clinician. CASE REPORT: We report the case of a 66-year-old woman who was admitted for a left progressive hemiparesis associated with headaches. She was treated for one year by immunosuppressive drugs for vulgaris pemphigus. At the time of admission, examination revealed left hemiparesis without fever, and a computed tomography brain scan demonstrated a focal lesion in the right frontal lobe. Blood analyses were normal. Two days after, she suddenly developed fever (40 degrees C), and aggravation of her motor deficit followed by partial motor seizures. The cerebrospinal fluid was normal. Treatment with amoxicillin (3g IV q6h), cefotaxim, gentamycin (120mg IV q12h) and aciclovir was started empirically. The brain MRI without gadolinium displayed infiltrative lesions in the right hemisphere and in the mildbrain. The blood culture grew Listeria monocytogenes. The antimicrobial regimen was changed to amoxicillin for seven weeks and gentamicin for the first ten days. Four days after beginning the antimicrobial regimen, the brain MRI with gadolinium displayed several abscesses measuring less than one cm diameter. The clinical and imaging outcome excellent. CONCLUSION: Meningitis is by far the most central nervous system listeriosis. In our patient, the diagnosis of listeria monocytogenes encephalitis was established on the basis of positive blood cultures, as such patients do not have sterile cerebrospinal fluid.

The value of phase-contrast magnetic resonance angiography of the circle of Willis in predicting cerebral ischemia-hypoxia (shunt need) during carotid endarterectomy.

BACKGROUND: Cerebral perfusion during carotid cross-clamping depends on collateral function of the circle of Willis. The aim of this study was to determine the value of 3D Phase-Contrast (3D PC) MR angiography in predicting pre-operatively the need of shunting. METHODS: 3D PC MR angiography were performed in 121 patients before carotid endarterectomy under locoregional anaesthesia. Based on the MR analysis, the risk of cerebral ischemia-hypoxia during clamping was classified as high, moderate and low. The analysis was then correlated with intraoperative neurological examination. RESULTS: In patients with high risk of cerebral ischemia (n=9), immediate cerebral ischemia developed in all patients within one min of clamping (P<0.001). All nine underwent shunt placement. In six of the patients with moderate risk (n=46), cerebral ischemia occurred between 20 and 25 min after clamping; All occurred during intraoperative hypotension. CONCLUSION: 3D PC MR angiography can significantly determine the need of shunting in patients with important risk of immediate intraoperative cerebral ischemia. It also focuses on the intraoperative blood pressure stability in patients with moderate risk of ischemia.

Clinical callosum syndrome in a case of multiple sclerosis.

This case report confirms that a clinical callosal disconnection could be observed in multiple sclerosis. Moreover, this case describes a new kind of strange manual behavior related to callosal disconnection. This behavior could neither be considered as a diagonistic dyspraxia nor as an alien hand, but they evoke rather a conflict of intentions.

[An ischemic syndrome of the oculumotor nucleus: associated clinical and anatomical variations on a theme]. / Syndrome nucléaire du nerf oculo-moteur commun (III) d'étiologie ischémique: variations cliniques et anatomiques associées.

Nuclear syndrome of the oculomotor nerve was first described in 1981, it is characterized by the association of an ipsilateral third nerve palsy with a paresis of elevation in the contralateral eye. This syndrome can be caused by vascular or tumoral lesions in the upper midbrain. It is rarely due to ischemic unilateral mesencephalic lesions, because ischemic lesions of the midbrain are usually integrated in a diffuse involvement of the brainstem and the thalamo-sub-thalamic region. In case of nuclear syndrome of the third nerve due to isolated upper midbrain infarct in the paramedian territory, dependent on branches of the basilar artery, oculomotor symptoms are frequently isolated. On the contrary, in fascicular syndromes of the third nerve, resulting from stroke in more lateral territories upon branches of the posterior cerebral artery, many neurological symptoms are associated with the oculomotor signs. We describe 3 patients presenting with a characteristic nuclear syndrome of the third nerve, resulting from a unilateral paramedian ischemic stroke in the upper midbrain, confirmed by cerebral CT scan or MRI examination. Clinical presentation differed in each case, and marked contralateral hemiparesia, cerebellar syndrome and focal asterixis were associated in various ways with the stereotyped oculomotor disorders. In the 3 cases, the nuclear syndrome of the third nerve was associated with fascicular involvement of the nerve, in an unusual clinical picture. The theoretical distinction between nuclear and fascicular syndromes is supported by the anatomical description of the arterial segmentation in the upper midbrain, which remains debated since the first description. According to the variability of clinical presentations, it seems that the arterial territories may be more variable than initially described. Therefore, ischemic lesions of the upper midbrain may involve some vascular borderzones with a high inter-individual variability. Upper midbrain strokes may thus lead to variable clinical pictures.

VISTRAJ: exploring protein conformational space.

UNLABELLED: VISTRAJ is an application which allows 3D visualization, manipulation and editing of protein conformational space using probabilistic maps of this space called 'trajectory distributions'. Trajectory distributions serve as input to FOLDTRAJ which samples protein structures based on the represented conformational space. VISTRAJ also allows FOLDTRAJ to be used as a tool for homology model creation, and structures may be generated containing post-translationally modified amino acids. AVAILABILITY: Binaries are freely available for non-profit use as part of the FOLDTRAJ package at ftp://ftp.mshri.on.ca/pub/TraDES/foldtraj/.

Automatic annotation of BIND molecular interactions from three-dimensional structures.

Software to automate the process of extracting molecular interactions from three-dimensional (3D) structures has been developed that records these as Biomolecular Interaction Network Database (BIND) pairwise interaction records. Full annotation of BIND records is provided through a database processing tool called MMDBind, including detailed atom-atom and residue-residue level interaction information. BIND three-dimensional interaction annotation is synthesized by combining information from the Molecular Modeling Database (MMDB), and the HET (heterogen) group dictionary of small molecules in the macromolecular Crystallographic Information Format (mmCIF). Interactions are validated using the Protein Quaternary Structure (PQS) system. A total of 18,166 interactions were removed as being redundant or biologically irrelevant after PQS validation. This first pass MMDBind annotation creates two new divisions of BIND, 3D Biopolymers (BIND-3DBP) comprising 16,737 initial interaction records, and 3D Small Molecules (BIND-3DSM) comprising 48,219 records. Visualization of interacting residues and nucleotides within a macromolecular structure is possible directly from the BIND database owing to added 3D feature annotation within the BIND records that can be conveniently seen using Cn3D ("see-in-3D") after query from the BIND Data Manager. These interaction records provide a further demonstration of the completeness of the BIND data specification and its capabilities as storage and exchange format for all kinds of molecular interactions, including RNA, DNA, protein, and small molecules. Data from the 3DBP and 3DSM sets are available for downloading in Abstract Syntax Notation.1 (ASN.1) or Extensible Markup Language (XML) formats at ftp://ftp.bind.ca/DB/MMDBBind. Data from the 3DBP set is available for interactive query from the BIND Data Manager at www.bind.ca.

[Retraction nystagmus of vascular origin]. / Nystagmus retractorius d'origine vasculaire.

We report a case of a 42-year-old woman who was referred for diplopia. She appeared to have a convergence retraction syndrome and loss of vertical gaze. The clinical course led to a diagnosis of thromboembolic cerebrovascular event in the region of the posterior commissure on the basis of risk factors such as smoking and oral contraceptive use. The final outcome was rapidly favorable.

The morphology of the femur in developmental dysplasia of the hip.

We studied the morphometry of 35 femora from 31 female patients with developmental dysplasia of the hip (DDH) and another 15 from 15 age- and sex-matched control patients using CT and three-dimensional computer reconstruction models. According to the classification of Crowe et al 15 of the dysplastic hips were graded as class I (less than 50% subluxation), ten as class I/III (50% to 100% subluxation) and ten as class IV (more than 100% subluxation). The femora with DDH had 10 to 14 degrees more anteversion than the control group independent of the degree of subluxation of the hip. In even the most mildly dysplastic joints, the femur had a smaller and more anteverted canal than the normal control. With increased subluxation, additional abnormalities were observed in the size and position of the femoral head. Femora from dislocated joints had a short, anteverted neck associated with a smaller, narrower, and straighter canal than femora of classes I and II/III or the normal control group. We suggest that when total hip replacement is performed in the patient with DDH, the femoral prosthesis should be chosen on the basis of the severity of the subluxation and the degree of anteversion of each individual femur.