Analysis of radiation exposure in trauma patients at a level I trauma center

BackgroundTrauma patients are exposed to potentially high levels of low-dose radiation during radiologic studies.ObjectivesTo assess the cumulative effective dose (CED) of radiation exposure (RE) in 177 successive patients admitted to a trauma service from January 1 through February 28, 2006.ResultsPatients received a total of 1505 radiographs and 400 computed tomography (CT) scans in the study period. The CED was 14.56 mSv (0.97 mSv radiographs, 13.59 mSv CT scans) per patient total length of stay (LOS). CED averaged 8.66 mSv in the first hour and 11.76 mSv in the first 24 h after arrival. The most commonly performed CT scan was brain (n = 147), followed by abdomen and pelvis (n = 80), and cervical spine (n = 69). CT scans of the brain and cervical spine were the most commonly performed combined imaging tests (35%). Twelve percent of patients received no radiographs, and 15% received no CT scans. Six or more CT scans were done in 6% of patients. RE increased with longer LOS (> 6 days vs. 3–5 days vs. 1 day, p < 0.05). “Pan-scans” (a combination of CTs of the brain, cervical spine, chest, abdomen, and pelvis) were done in 13% (n = 23) of patients. There was a higher total RE from CT scans (25.09 mSv ± 19.48 mSv vs. 4.93 mSv ± 14.20 mSv) in patients with injury severity score (ISS) > 9 vs. ≤ 9 ( p < 0.0001). First hour and first 24-h RE rates from radiographs were lower in patients younger than 15 years vs. 15–45 years and older-than-45-year age cohorts (p < 0.05).ConclusionsIn this study, CED was 14.56 mSv per patient. CT scans accounted for 21% of radiologic studies and 93% of CED. There was a higher CED rate in patients with ISS > 9 and longer LOS.     

Impact of oxaliplatin-induced neuropathy: a patient perspective

Introduction

Dose-limiting neurotoxicity is a major side effect of oxaliplatin treatment, producing initial acute neurotoxicity and chronic neuropathy with increasing exposure. The improvement in survival for patients with early-stage colorectal cancer treated with oxaliplatin has highlighted the need for valid and reliable assessment of peripheral neuropathy.

Objectives

The objective of this paper was to explore neuropathic symptoms in oxaliplatin-treated patients as assessed using different methods.

Methods

Consecutive symptomatic patients reporting peripheral neuropathy after oxaliplatin chemotherapy for colorectal cancer were interviewed using a semi-structured clinical interview. Neurotoxicity was also assessed using the National Cancer Institute Common Toxicity Criteria scale (clinician-rated), patient ‘self-report’ questionnaires (PNQ), nerve conduction and clinical assessment.

Results

Twenty patients were assessed, 12.6?±?2.8?months after treatment cessation (mean cumulative oxaliplatin dose, 789?mg/m²). In 40% of patients, neurotoxicity necessitated early cessation of treatment. Only 10% of patients were designated by clinicians with severe neurotoxicity, whilst, in contrast, patient interviews and self-report questionnaires described significant physical limitations due to neuropathic symptoms in 60% of patients. The majority (85%) of patients had objective evidence of sensory neuropathy with nerve conduction studies. Reports from clinical interviews were strongly correlated with patient self-assessment (Pearson coefficient?=?0.790, p?Conclusion Given the discrepancies in symptom prevalence highlighted by these findings, the monitoring of oxaliplatin-induced neurotoxicity would benefit from more informative clinical assessment, with inclusion of patient-reported outcome measures. Such an approach would be beneficial in a clinical trial setting to monitor the efficacy of interventions and in prospective studies of survivorship to determine the true burden of peripheral neuropathy in oxaliplatin-treated patients.     

Low-dose whole organ CT perfusion of the pancreas: preliminary study

Objectives

To investigate the feasibility of low-dose whole pancreas CT perfusion in the clinical practice.

Methods

Sixty-one patients suspected pancreatic disease underwent low-dose whole pancreas CT perfusion scan (by body weight, group A: 70 kV, 120 mAs; group B: 80 kV, 100 mAs) and the individualized pancreas scan. Forty-six patients were enrolled. Perfusion characteristics, such as, blood flow, blood volume and permeability, were analyzed. The effective radiation dose of the whole pancreas CT perfusion and the total CT scan protocol were recorded. CT findings were histologically confirmed by surgical intervention or diagnostic puncture.

Results

Of the 46 cases, 33 were pancreatic adenocarcinoma, 5 were solid-pseudo-papillary tumors of pancreas, 8 cases of pancreatic endocrine tumors on the perfusion study. There was significant interobserver agreement on the measurement of normal pancreatic CT perfusion parameters of group A (n = 28)and group B (n = 18), respectively (p > 0.05). For the normal pancreas, there was no significant difference on CT perfusion parameters between group A and group B (p > 0.05). There were significant differences on blood flow as well as blood volume between the pancreatic adenocarcinomas and the normal pancreas (p < 0.001), whereas no difference on the permeability (p > 0.05). The time to peak of the normal pancreas is 28.94 ± 4.37 s (range from 24 to 38 s). Different pancreatic tumors had different types of time attenuation curve (TAC). TACs were different between pancreatic adenocarcinomas and normal pancreas. The effective radiation dose of the whole pancreas CT perfusion of Group A and Group B were 3.60 and 4.88 mSv (DLP 246 and 325 mGy cm), respectively, and the total radiation dose was around 8.01–16.22 mSv.

Conclusions

Low-dose whole pancreatic CT perfusion can effectively reduce radiation dose, and provide the best phase for the individualized pancreas scan, which has great value in the clinical practice.     

Toward computer-assisted image-guided congenital heart defect repair: an initial phantom analysis

Purpose

Radiation exposure in interventional cardiology is an important consideration, due to risk of cancer and other morbidity to the patient and clinical staff. Cardiac catheterizations rely heavily on fluoroscopic imaging exposing both patient and clinician to ionizing radiation. An image-guided surgery system capable of facilitating cardiac catheterizations was developed and tested to evaluate dose reduction.

Methods

Several electromagnetically tracked tools were constructed specifically a 7-Fr catheter with five 5-degree-of-freedom magnetic seeds. Catheter guidance was accomplished using our image guidance system Kit for Navigation by Image-Focused Exploration and fluoroscopy alone. A cardiac phantom was designed and 3D printed to validate the image guidance procedure. In mock procedures, an expert clinician guided and deployed an occluder across the septal defect of the phantom heart.

Results

The image guidance method resulted in a dose of 1.26 mSv of radiation dose per procedure, while traditional guidance resulted in a dose of 3.33 mSv. Average overall dose savings for the image-guided method was nearly 2.07 mSv or 62 %.

Conclusion

The work showed significant (\(p<0.001\)) decrease in radiation dose with use of image guidance methods at the expense of a modest increase in procedure time. This study lays the groundwork for further exploration of image guidance applications in pediatric cardiology.

     

Efficacy and safety of a high loading dose of clopidogrel administered prehospitally to improve primary percutaneous coronary intervention in acute myocardial infarction: the randomized CIPAMI trial

Objectives

To compare a loading dose of 600?mg clopidogrel given in the prehospital phase versus clopidogrel administered only after the diagnostic angiogram in patients with STEMI scheduled for primary PCI.

Background

The optimal time and dose for the initiation of clopidogrel therapy in patients with STEMI scheduled for primary PCI has not been studied in prospective randomized trials.

Methods

The primary efficacy endpoint was the TIMI 2/3 patency of the infarct-related artery in the diagnostic angiography immediately prior to PCI.

Results

We randomized 337 patients to prehospital (n?=?166) loading dose versus standard therapy (n?=?171). The time interval between initiation of clopidogrel therapy and diagnostic angiography was 47?min. TIMI 2/3 patency before PCI was not different between the groups (49.3 vs. 45.1%, P?=?0.5). We observed a trend towards a reduction of the combined endpoint death, re-infarction, and urgent target vessel revascularization in the prehospital-treated patients (3.0 vs. 7.0%, P?=?0.09), this difference was significant if patients were classified as treated (4/161 vs. 13/174; 2.5 vs. 7.5%, P?P?=?0.8).

Conclusions

Early inhibition of the platelet ADP-receptor with a high loading dose of 600?mg clopidogrel given in the prehospital phase in patients with STEMI scheduled for primary PCI is safe, did not increase pre-PCI patency of the infarct vessel, but was associated with a trend towards a reduction in clinical events.     

Safety of gelatin for volume resuscitation—a systematic review and meta-analysis

Purpose

Gelatin is frequently used as a volume expander in critical care. Our goal was to investigate its safety.

Methods

Systematic review of randomized controlled trials (RCT) in patients receiving gelatin for resuscitation in comparison to albumin or crystalloids.

Results

We identified 40 RCTs published between 1976 and 2010 with 3,275 patients. Median sample size in the gelatin groups was 15 patients (range 10–249). Median gelatin dose was 17?ml/kg (range 6–57?ml/kg). In 32 RCTs (n?=?1,946/3,275, 59?% of all patients), the study period was ≤24.0?h. Twenty-nine RCTs (n?=?2,001) investigated elective surgical patients, mostly undergoing cardiac surgery (18 RCTs, n?=?819). Three RCTs (n?=?723) investigated critically ill adults. Two RCTs (n?=?59) were performed in emergency room patients, and six RCTs (n?=?492) were performed in neonates or children. No study was adequately powered to investigate the frequency of patient-important outcomes. Risks were not statistically significantly different for mortality (RR 1.12, 95?% confidence interval, 0.87–1.44) and exposure to allogeneic transfusion (RR 1.28, 0.89–1.83). On account of only few included studies and the small number of patients, subgroup analyses (high vs. low dose, >24?h vs. shorter periods, and critically ill patients vs. others) were uninformative. Only three RCTs reported the occurrence of acute renal failure.

Conclusion

Despite over 60?years of clinical practice, the safety and efficacy of gelatin cannot be reliably assessed in at least some settings in which it is currently used. We suggest the need to investigate and establish such safety.     

Percutaneous lung biopsy: comparison between an augmented reality CT navigation system and standard CT-guided technique

Purpose

Percutaneous lung biopsies (PLBs) performed for the evaluation of pulmonary masses require image guidance to avoid critical structures. A new CT navigation system (SIRIO, “Sistema robotizzato assistito per il puntamento intraoperatorio”) for PLBs was validated.

Methods

The local Institutional Review Board approved this retrospective study. Image-guided PLBs in 197 patients were performed with a CT navigation system (SIRIO). The procedures were reviewed based on the number of CT scans, patients’ radiation exposure and procedural time recorded. Comparison was performed with a group of 72 patients undergoing standard CT-guided PLBs. Sensitivity, specificity and overall diagnostic accuracy were assessed in both groups.

Results

SIRIO-guided PLBs showed a significant reduction in procedure time, number of required CT scans and the radiation dose administered to patients ( $p<0.001$ ). In terms of diagnostic accuracy, SIRIO proved to be more accurate for small-sized lesions ( $<$ 20 mm) than standard CT-guidance.

Conclusion

SIRIO proved to be a reliable and effective tool when performing CT-guided PLBs and was especially useful for sampling small ( $<$ 20 mm) lesions.     

Biodistribution and Radiation Dosimetry of the <Emphasis Type="Italic">Enterobacteriaceae</Emphasis>-Specific Imaging Probe [<Superscript>18</Superscript>F]Fluorodeoxysorbitol Determined by PET/CT in Healthy Human Volunteers

Purpose

[¹⁸F]fluorodeoxysorbitol ([¹⁸F]FDS) is the first radiopharmaceutical specific for a category of bacteria and has the potential to specifically detect Enterobacteriaceae infections. The purpose of this study was to testify the safety and investigate the biodistribution and radiation dosimetry of [¹⁸F]FDS in healthy human bodies.

Procedures

Six healthy subjects were intravenously injected with 320–520 MBq [¹⁸F]FDS. On each subject, 21 whole-body emission scans and a brain scan were conducted at settled time points within the next 4 h. Residence time for each source organ was determined by multi-exponential regression. Absorbed doses for target organs and effective dose were calculated via OLINDA/EXM.

Results

No adverse events due to [¹⁸F]FDS injection were observed in the study. The tracer was cleared rapidly from the blood pool through the urinary system. A small portion was cleared into the gut through the hepatobiliary system. The effective dose (ED) was estimated to be 0.021?±?0.001 mSv/MBq. The organ receiving the highest absorbed dose was the urinary bladder wall (0.25?±?0.03 mSv/MBq).

Conclusions

[¹⁸F]FDS is safe and well tolerated. The effective dose was comparable to that of other F-18 labeled radiotracers. [¹⁸F]FDS is suitable for human use from a radiation dosimetry perspective.

     

Evaluation of Radiation Exposure to Pediatric Trauma Patients

Background

Pediatric trauma patients pose a diagnostic challenge to physicians. Computed tomography (CT) imaging identifies life-threatening injuries quickly and efficiently. CT radiation dose in pediatric trauma patients is a concern.

Study Objectives

We evaluated the cumulative effective dose of radiation received by pediatric blunt trauma patients and assessed characteristics of patients and studies received.

Methods

We retrospectively identified pediatric blunt trauma patients at a Level I trauma center between January 1 and December 31, 2006 utilizing the North Carolina Trauma Registry. We searched the patient radiographic history for images in the 7 days after their trauma event. We calculated cumulative effective radiation dose using dose length product and age coefficients. We collected demographic information including age, sex, mechanism of injury, hospital length of stay, and discharge status.

Results

Seventy-five pediatric blunt trauma patients with available radiographic records were included. The median age was 11.7 years; males comprised 64% of patients; median Injury Severity Score was 13.8; 64% were transfer patients; median number of CT scans during initial evaluation was 3.4 for directly seen patients and two for transferred patients. Mean effective ionizing radiation dose was 11.4 mSv for CT scans performed in the first 24 h. Sixteen percent of admitted patients had CT scans in the subsequent 6 days, with an average additional CT dose of 4 mSv. Average number of plain radiographs was five.

Conclusions

Pediatric blunt trauma patients receive a major radiation burden in their initial evaluation. Patients who are transferred from an outside facility endure an even higher dose of radiation.     

Pharmacokinetics and Exposure–Response Analyses of Daratumumab in Combination Therapy Regimens for Patients with Multiple Myeloma

Introduction

Daratumumab, a human IgG monoclonal antibody targeting CD38, has demonstrated activity as monotherapy and in combination with standard-of-care regimens in multiple myeloma. Population pharmacokinetic analyses were conducted to determine the pharmacokinetics of intravenous daratumumab in combination therapy versus monotherapy, evaluate the effect of patient- and disease-related covariates on drug disposition, and examine the relationships between daratumumab exposure and efficacy/safety outcomes.

Methods

Four clinical studies of daratumumab in combination with lenalidomide/dexamethasone (POLLUX and GEN503); bortezomib/dexamethasone (CASTOR); pomalidomide/dexamethasone, bortezomib/thalidomide/dexamethasone, and bortezomib/melphalan/prednisone (EQUULEUS) were included in the analysis. Using various dosing schedules, the majority of patients (684/694) received daratumumab at a dose of 16 mg/kg. In GEN503, daratumumab was administered at a dose of 2 mg/kg (n?=?3), 4 mg/kg (n?=?3), 8 mg/kg (n?=?4), and 16 mg/kg (n?=?34). A total of 650 patients in EQUULEUS (n?=?128), POLLUX (n?=?282), and CASTOR (n?=?240) received daratumumab 16 mg/kg. The exposure–efficacy and exposure–safety relationships examined progression-free survival (PFS) and selected adverse events (infusion-related reactions; thrombocytopenia, anemia, neutropenia, lymphopenia, and infections), respectively.

Results

Pharmacokinetic profiles of daratumumab were similar between monotherapy and combination therapy. Covariate analysis identified no clinically important effects on daratumumab exposure, and no dose adjustments were recommended on the basis of these factors. Maximal clinical benefit on PFS was achieved for the majority of patients (approximately 75%) at the 16 mg/kg dose. No apparent relationship was observed between daratumumab exposure and selected adverse events.

Conclusion

These data support the recommended 16 mg/kg dose of daratumumab and the respective dosing schedules in the POLLUX and CASTOR pivotal studies.

Funding

Janssen Research & Development.

     

A systematic review on chronic oxaliplatin-induced peripheral neuropathy and the relation with oxaliplatin administration

Purpose

The aim of this study was to systematically review the literature on the influence of oxaliplatin administration (e.g. cumulative dose, dose intensity, number of cycles and combination regimen) on the long-term prevalence of oxaliplatin-induced peripheral neuropathy (O-IPN) at least 12 months after termination of chemotherapy.

Methods

A computerized search of literature on databases PubMed and Cochrane was performed. Published original articles were included if they reported about long-term O-IPN and gave concomitant information about oxaliplatin therapy given to the patients. All articles were assessed for quality.

Results

We included 14 articles (n?=?3,869 patients), and the majority of these studies were of high quality. All included patients who were treated for colorectal cancer, mainly with oxaliplatin in combination with 5-fluorouracil/leucovorin. Median cumulative doses and dose intensity varied between 676 and 1,449 mg/m² and 30.8 and 42.6 mg/m²/week, respectively. Neuropathy assessment differed between studies, and the National Cancer Institute-Common Terminology Criteria (NCI-CTC) was used most often. The degree of neuropathy ranged from grade 0 to 3. Only six studies directly assessed the relationship between oxaliplatin administration and neuropathy. Of these studies, five did find a relation between neuropathy and higher cumulative dose, while one study did not find a relation.

Conclusions

O-IPN is still present in a great amount of patients in ≥12 months after termination of therapy. A higher cumulative dose is likely to have an influence on the development of long-term O-IPN. More studies are needed that assess long-term neuropathy and oxaliplatin administration by means of validated neuropathy assessments.     

Biodistribution and Radiation Dosimetry of the Carbonic Anhydrase IX Imaging Agent [18 F]VM4-037 Determined from PET/CT Scans in Healthy Volunteers

Purpose

[¹⁸?F]VM4-037 has been developed as a positron emission tomography (PET) imaging marker to detect carbonic anhydrase IX (CA-IX) overexpression and is being investigated for use as a surrogate marker for tissue hypoxia. The purpose of this study was to determine the biodistribution and estimate the radiation dose from [¹⁸?F]VM4-037 using whole-body PET/CT scans in healthy human volunteers.

Procedures

Successive whole-body PET/CT scans were performed after intravenous injection of [¹⁸?F]VM4-037 in four healthy humans. The radiotracer uptakes in different organs were determined from the analysis of the PET scans. Human radiation doses were estimated using OLINDA/EXM software.

Results

High uptake of [¹⁸?F]VM4-037 was observed in the liver and kidneys, with little clearance of activity during the study period, with mean standardized uptake values of ~35 in liver and ~22 in kidneys at ~1 h after injection. The estimated effective dose was 28?±?1 μSv/MBq and the absorbed doses for the kidneys and liver were 273?±?31 and 240?±?68 μGy/MBq, respectively, for the adult male phantom. Hence, the effective dose would be 10?±?0.5 mSv for the anticipated injected activity of 370 MBq, and the kidney and liver doses would be 101?±?11 and 89?±?25 mGy, respectively.

Conclusions

[¹⁸?F]VM4-037 displayed very high uptake in the liver and kidneys with little clearance of activity during the study period, resulting in these organs receiving the highest radiation doses among all bodily organs. Though the effective dose and the organ doses are within the limits considered as safe, the enhanced uptake of [¹⁸?F]VM4-037 in the kidneys and liver will make the compound unsuitable for imaging overexpression of CA-IX in those two organs. However, the tracer may be suitable for imaging overexpression of CA-IX in lesions in other regions of the body such as in the lungs or head and neck region.     

Marker-less intra-fraction organ motion tracking using hybrid ASM

Aim

External beam radiation therapy attempts to deliver a high dose of ionizing radiation to destroy cancerous tissue, while sparing healthy tissues and organs at risk (OAR). Recent advances in intensity modulated radiotherapy treatment call for a greater understanding of uncertainties in the treatment process and more rigorous protocols leading to greater precision in treatment delivery. The degree to which this can be achieved depends largely on the cancer site. The treatment of organs comprises soft tissue (e.g. in the abdomen) and those subject to rhythmic movements (e.g. lungs) causing inter and intra-fraction motion artifacts that are particularly problematic. Various methods have been developed to tackle the problems caused by organ motion during radiotherapy treatment, e.g. Real-time position management respiratory gating (Varian) and synchronized moving aperture radiation therapy, developed by researchers at Harvard Medical School.

Objective

The majority of the work focuses on tracking the position of the pathologic region, with the intra-fraction shape variation of the region being largely ignored.

Materials and Methods

This paper proposes a novel method that addresses both the position and shape variation caused by the intra-fraction movement.

Conclusion

We believe this approach is able to reduce the clinical target volume margin, hence, sparing yet more of the surrounding healthy tissues from radiation exposure and limiting irradiation of OAR.     

[<Superscript>89</Superscript>Zr]Trastuzumab: Evaluation of Radiation Dosimetry,Safety, and Optimal Imaging Parameters in Women with HER2-Positive Breast Cancer

Purpose

The purpose of the present study is to evaluate safety, human radiation dosimetry, and optimal imaging time of [⁸⁹Zr]trastuzumab in patients with HER2-positive breast cancer.

Procedures

Twelve women with HER2-positive breast cancer underwent [⁸⁹Zr]trastuzumab positron emission tomography (PET)/X-ray computed tomography (CT) twice within 7 days post-injection. Biodistribution data from whole-torso PET/CT images and organ time-activity curves were created using data from all patients. Human dosimetry was calculated using OLINDA with the adult female model.

Results

High-quality images and the greatest tumor-to-nontumor contrast were achieved with images performed 5?±?1 day post-injection. Increased [⁸⁹Zr]trastuzumab uptake was seen in at least one known lesion in ten patients. The liver was the dose-limiting organ (retention of ～12 % of the injected dose and average dose of 1.54 mSv/MBq). The effective dose was 0.47 mSv/MBq. No adverse effects of [⁸⁹Zr]trastuzumab were encountered.

Conclusion

[⁸⁹Zr]trastuzumab was safe and optimally imaged at least 4 days post-injection. The liver was the dose-limiting organ.

     

Single-dose intravenous casopitant in combination with ondansetron and dexamethasone for the prevention of oxaliplatin-induced nausea and vomiting: a multicenter, randomized, double-blind, active-controlled, two arm, parallel group study

Purpose

The primary objective was to determine if a single dose of casopitant 90?mg added to ondansetron and dexamethasone would improve the control of chemotherapy-induced nausea and vomiting (CINV) over 0–120?h following initiation of oxaliplatin-based moderately emetic chemotherapy (MEC) compared to ondansetron and dexamethasone alone.

Methods

Patients with colorectal cancer received either casopitant or placebo intravenously (IV) added to ondansetron 8?mg bid oral on study days?1 to 3 and one dose of dexamethasone 8?mg IV given prior to starting the oxaliplatin on day?1. The primary endpoint was the percentage of subjects achieving complete response (CR; no vomiting/retching or use of rescue medication) during 120?h after initiation of chemotherapy in cycle 1.

Results

No difference in the rate of CR was noted in the casopitant group compared to the placebo group for the overall (placebo 85%, casopitant 86%, p?=?0.7273), acute (placebo 96%, casopitant 97%), or delayed phases (placebo 85%, casopitant 86%). The average area under curve (0–∞) of casopitant after a single 90-mg IV dose was 8,390?ng?h/mL. At 24?h after casopitant 90-mg IV dosing, the plasma casopitant concentration was 24% lower than the values noted in prior studies with 150?mg oral administration, and the plasma exposure of the major metabolite (GSK525060) was 18% lower.

Conclusions

Addition of single-dose casopitant 90?mg IV did not improve the control of CINV at any time during 120?h following initiation of oxaliplatin-based MEC. Excellent control of CINV was achieved in this study population with the combination of ondansetron and dexamethasone alone.     

Lung deposition of continuous and intermittent intravenous ceftazidime in experimental Pseudomonas aeruginosa bronchopneumonia

Objective

Lung tissue deposition of intravenous ceftazidime administered either continuously or intermittently was compared in ventilated piglets with experimental bronchopneumonia.

Design

Prospective experimental study

Animals

Eighteen anesthetized and ventilated piglets

Interventions

Bronchopneumonia was produced by the intrabronchial inoculation of Pseudomonas aeruginosa characterized by an impaired sensitivity to ceftazidime (MIC 16?mg/l). Ceftazidime was administered either through a continuous infusion of 90?mg/kg per 24?h after a bolus of 30?mg/kg or by an intermittent infusion of 30?mg/kg per 8?h.

Measurements and results

Piglets were killed 24?h after the initiation of continuous ceftazidime (n?=?6), and 1?h (peak, n?=?6) and 8?h (trough, n?=?6) after the third dose following intermittent administration. Lung tissue concentrations of ceftazidime, measured by HPLC, and lung bacterial burden were assessed on multiple postmortem lung specimens. During continuous administration ceftazidime lung tissue concentrations were 9.7?±?3.8?μg/g. Following intermittent administration peak and trough lung tissue concentrations were, respectively, 7.1?±?2.4?μg/g and 0.6?±?1?μg/g. Lung bacterial burden was different after continuous and intermittent administration (median 7.10³ vs. 4.10²?cfu/g).

Conclusions

Continuous infusion of ceftazidime maintained higher tissue concentrations than intermittent administration.     

Efficacy of Amlodipine/Olmesartan ± Hydrochlorothiazide in Patients Uncontrolled on Prior Calcium Channel Blocker or Angiotensin II Receptor Blocker Monotherapy

Introduction

While monotherapy is often recommended as initial treatment, most patients require dose escalation and add-on agents to achieve their blood pressure (BP) goal. This secondary analysis evaluated the efficacy and safety of initiating patients on a regimen of fixed-dose amlodipine (AML)/olmesartan medoxomil (OM) ± hydrochlorothiazide (HCTZ) who were uncontrolled on prior monotherapy with a calcium channel blocker (CCB) or angiotensin II receptor blocker (ARB).

Methods

Patients uncontrolled on prior monotherapy with CCB or ARB therapy were initiated on AML/OM 5/20 mg and up-titrated every 4 weeks to AML/OM 5/40 mg, AML/OM 10/40 mg, AML/OM 10/40 + HCTZ 12.5 mg, and AML/OM 10/40 + HCTZ 25 mg. Patients were up-titrated to a higher AML/OM dose if mean seated cuff BP (SeBP) was ??120/70 mmHg, and up-titrated to any HCTZ dose if mean SeBP was ??125/75 mmHg. The primary efficacy endpoint was the cumulative proportion of patients achieving a seated cuff systolic BP (SeSBP) goal of <140 mmHg (<130 mmHg for patients with diabetes) after 12 weeks. Secondary endpoints included mean change from baseline in SeBP and ambulatory BP, ambulatory BP target achievement, and safety.

Results

For the prior CCB (n = 118; baseline SeBP: 153.4/91.5 mmHg) and ARB (n = 237; 154.6/92.6 mmHg) groups, SeSBP goal achievement after 12 weeks was 72.7% and 76.9%, respectively. Mean changes (± SE) from baseline in SeBP were dose proportional for prior CCB and ARB patients, ranging from ?9.9 (± 1.25)/?5.8 (± 0.83) mmHg and ?13.9 (± 0.79)/?7.6 (± 0.47) mmHg at the AML/OM 5/20 mg dose, respectively, to ?21.8 (± 1.68)/?11.6 (±.12) mmHg and ?26.2 (± 1.31)/?15.0 (± 0.86) mmHg at the AML/OM 10/40 mg + HCTZ 25 mg dose (P < 0.0001 for all).

Conclusion

An AML/OM-based titration regimen was efficacious in achieving BP goal in patients uncontrolled on prior monotherapy with a CCB or ARB.     

Risk factors for radiation exposure in newly diagnosed IBD patients

Purpose

Patients with inflammatory bowel disease (IBD) may be exposed to high doses of diagnostic radiation. The purpose of this study is to identify subsets of this population at risk for significant radiation exposure.

Methods

This HIPAA compliant, IRB approved study consists of 336 patients (237 adult and 99 pediatric) within the Ocean State Crohn’s & Colitis Area Registry (OSCCAR). All were newly diagnosed with IBD and prospectively enrolled between 1/2008 and 12/2012. Comprehensive chart review was performed.

Results

207 (61.6%) patients were diagnosed with Crohn’s disease (CD), 120 (35.7%) with ulcerative colitis (UC), and 9 (2.7%) with inflammatory bowel disease, type unspecified (IBDU). 192 (57.1%) patients were exposed to GI-specific radiation. Average GI-specific radiation dose for adult IBD patients was 14.1 mSV and was significantly greater among adult CD than adult UC patients (p = 0.01). Pediatric patients underwent fewer CT scans (p < 0.0001). Risk factors for increased radiation exposure include: GI surgery (p = 0.003), biologic therapy (p = 0.01), pain-predominant symptoms (as compared to diarrhea-predominant symptoms; p < 0.05), and isolated ileal disease (p = 0.02). Patients with stricturing or penetrating disease received higher radiation doses than patients with non-stricturing, non-penetrating disease (p < 0.0001).

Conclusions

A variety of risk factors are associated with increased exposure to ionizing radiation after diagnosis of IBD. Knowledge of these risk factors can help physicians prospectively identify patients at risk for elevated radiation exposure and consider low-dose or radiation-free imaging.

     

In Vivo Whole Animal Body Imaging Reveals Colonization of Chlamydia muridarum to the Lower Genital Tract at Early Stages of Infection

Purpose

The leading cause of sexually transmitted bacterial infection is Chlamydia trachomatis. The aim of this study is to investigate the early events in colonization of this bacterium within the murine genital tract.

Procedures

An in vivo animal body imaging technology was used to track fluorophore labeled C. muridarum elementary bodies (EBs) inoculated intravaginally in C57BL/6 mice during the first 24 h of infection.

Results

Ascension of viable EBs was observed (1) to be localized to the lower regions of the murine genital tract within the first 24 h post challenge and (2) was dose independent during this early exposure period. Molecular detection revealed enhanced bacterial load in lower regions of the genital tract with increasing bacterial load in the upper region beginning 12 h post inoculation.

Conclusion

This study provides additional insight into chlamydial colonization in the murine genital tract during the first 12–24 h following inoculation.