Hospital-based antimicrobial stewardship in Denmark, Greenland and the Faroe Islands - current landscape and barriers.

OBJECTIVES: To describe the current organization and implementation of formalized, multi-disciplinary hospital-based antimicrobial stewardship (AMS) structures in Denmark, the Faroe Islands and Greenland. METHODS: A structured electronic questionnaire was sent to all trainees and specialists in clinical microbiology (N=207) and infectious diseases (N=260), as well as clinical pharmacists (N=20) and paediatricians (N=10) with expertise in infectious diseases. The survey had 30 multiple-choice, rating-scale, and open-ended questions based on an international consensus checklist for hospital AMS, adapted to a Danish context. RESULTS: Overall, 145 individual responses representing 20 hospitals were received. Nine hospitals (45%) reported a formal AMS strategy, eight (40%) a formal organizational multi-disciplinary structure and a multi-disciplinary AMS team, and six (30%) a designated professional as a leader of the AMS team. A majority of hospitals reported access to updated guidelines (80%) and regularly monitored and reported the quantity of antibiotics prescribed (70% and 65%, respectively). Only one hospital (5%) reported a dedicated, sustainable and sufficient AMS budget, three hospitals (15%) audited courses of therapy for specific agents/clinical conditions and four hospitals (20%) had a document clearly defining roles, procedures of collaboration and responsibilities for AMS. A total of 42% of all individual respondents had received formal AMS training. Main barriers were a lack of financial resources (52%), a lack of mandate from the hospital management (30%) and AMS not being a priority (18%). CONCLUSIONS: Core elements important for multi-disciplinary hospital-based AMS can be strengthened in Danish hospitals. Funding, clear mandates, prioritization from the hospital management and the implementation of multi-disciplinary AMS structures may help close the identified gaps.

Superconductivity in a uranium containing high entropy alloy.

High entropy alloys (HEA) are an unusual class of materials where mixtures of elements are stochastically arrayed on a simple crystalline lattice. These systems exhibit remarkable functionality, often along several distinct axes: e.g., the examples [TaNb]1-x(TiZrHf)x are high strength and damage resistant refractory metals that also exhibit superconductivity with large upper critical fields. Here we report the discovery of an f-electron containing HEA, [TaNb]0.31(TiUHf)0.69, which is the first to include an actinide ion. Similar to the Zr-analogue, this material crystallizes in a body-centered cubic lattice with the lattice constant a = 3.41(1) Å and exhibits phonon mediated superconductivity with a transition temperatures Tc ≈ 3.2 K and upper critical fields Hc2 ≈ 6.4 T. These results expand this class of materials to include actinide elements, shows that superconductivity is robust in this sub-group, and opens the path towards leveraging HEAs as functional waste forms for a variety of radioisotopes.

Broader Geographic Sharing of Pediatric Donor Lungs Improves Pediatric Access to Transplant.

US pediatric transplant candidates have limited access to lung transplant due to the small number of donors within current geographic boundaries, leading to assertions that the current lung allocation system does not adequately serve pediatric patients. We hypothesized that broader geographic sharing of pediatric (adolescent, 12-17 years; child, <12 years) donor lungs would increase pediatric candidate access to transplant. We used the thoracic simulated allocation model to simulate broader geographic sharing. Simulation 1 used current allocation rules. Simulation 2 offered adolescent donor lungs across a wider geographic area to adolescents. Simulation 3 offered child donor lungs across a wider geographic area to adolescents. Simulation 4 combined simulations 2 and 3. Simulation 5 prioritized adolescent donor lungs to children across a wider geographic area. Simulation 4 resulted in 461 adolescent transplants per 100 patient-years on the waiting list (range 417-542), compared with 206 (range 180-228) under current rules. Simulation 5 resulted in 388 adolescent transplants per 100 patient-years on the waiting list (range 348-418) and likely increased transplant rates for children. Adult transplant rates, waitlist mortality, and 1-year posttransplant mortality were not adversely affected. Broader geographic sharing of pediatric donor lungs may increase pediatric candidate access to lung transplant.

OPTN/SRTR 2013 Annual Data Report: lung.

Lungs are allocated to adult and adolescent transplant candidates (aged ⩾ 12 years) on the basis of age, geography, blood type compatibility, and the lung allocation score (LAS), which reflects risk of waitlist mortality and probability of posttransplant survival. In 2013, the most adult candidates, 2394, of any year were added to the list. Overall median waiting time for candidates listed in 2013 was 4.0 months. The preferred procedure remained bilateral lung transplant, representing approximately 70% of lung transplants in 2013. Measures of short-term and longterm survival have plateaued since the implementation of the LAS in 2005. The number of new child candidates (aged 0-11 years) added to the lung transplant waiting list increased to 39 in 2013. A total of 28 lung transplants were performed in child recipients, 3 for ages younger than 1 year, 9 for ages 1 to 5 years, and 16 for ages 6 to 11 years. The diagnosis of pulmonary hypertension was associated with higher survival rates than cystic fibrosis or other diagnosis (pulmonary fibrosis, bronchiolitis obliterans, bronchopulmonary dysplasia). For child candidates, infection was the leading cause of death in year 1 posttransplant and graft failure in years 2 to 5.

The equitable allocation of deceased donor lungs for transplant in children in the United States.

On June 5, 2013, a US Federal Court ordered a temporary restraining order to allow two children within the court's jurisdiction to be registered on the adolescent lung transplant waiting list. On June 10, 2013, the Organ Procurement and Transplantation Network's Executive Committee altered lung allocation policy to offer candidates aged younger than 12 years greater access to adult lungs at the discretion of the national Lung Review Board. The Scientific Registry of Transplant Recipients reviewed trends over time in deceased donor lung transplant waitlist mortality and transplant rates, comparing children and adults. Mortality rates of candidates active on the waiting list have been higher for children aged 0-5 years, but have not differed for children aged 6-11 years compared with adolescents aged 12-17 years or adults aged 18 years or older. Transplant rates among active waitlist candidates have been comparable across all age groups. Thus, there is little evidence that the allocation system led to differences in waitlist mortality or transplant rates for children compared with adults. However, these comparisons are difficult to interpret given that current policies likely led to unaccounted differences in the severity of illness at the time of listing.

OPTN/SRTR 2012 Annual Data Report: lung.

Lung transplants are increasingly used as treatment for end-stage lung diseases not amenable to other medical and surgical therapies. Lungs are allocated to adult and adolescent transplant candidates on the basis of age, geography, blood type compatibility, and the Lung Allocation Score, which reflects risk of wait-list mortality and probability of posttransplant survival. The overall median waiting time in 2012 was 4 months, and 65.3% of candidates underwent transplant within 1 year of listing; however, this proportion varied greatly by donation service area. Unadjusted median survival of lung transplant recipients was 5.3 years in 2012, and median survival conditional on living for 1 year posttransplant was 6.7 years. Among pediatric lung candidates in 2012, 32.1% were wait-listed for less than 1 year, 17.9% for 1 to less than 2 years, 16.7% for 2 to less than 4 years, and 33.3% for 4 or more years. Both graft and patient survival have continued to improve; survival rates for recipients aged 6-11 years are better than for younger recipients. Compared with recipients of other solid organ transplants, lung transplant recipients experienced the highest rates of rehospitalization for transplant complications: 43.7 per 100 patients in year 1 and 36.0 in year 2.

OPTN/SRTR 2011 Annual Data Report: lung.

Lungs are allocated in part based on the Lung Allocation Score (LAS), which considers risk of death without transplant and posttransplant. Wait-list additions have been increasing steadily after an initial decline following LAS implementation. In 2011, the largest number of adult candidates were added to the waiting list in a single year since 1998; donation and transplant rates have been unable to keep pace with wait-list additions. Candidates aged 65 years or older have been added faster than candidates in other age groups. After an initial decline following LAS implementation, wait-list mortality increased to 15.7 per 100 wait-list years in 2011. Short- and long-term graft survival improved in 2011; 10-year graft failure fell to an all-time low. Since 1998, the number of new pediatric (aged 0-11 years) candidates added yearly to the waiting list has declined. In 2011, 19 pediatric lung transplants were performed, a transplant rate of 34.7 per 100 wait-list years. The percentage of patients hospitalized before transplant has not changed. Both graft and patient survival have continued to improve over the past decade. Posttransplant complications for pediatric lung transplant recipients, similar to complications for adult recipients, include hypertension, renal dysfunction, diabetes, bronchiolitis obliterans syndrome, and malignancy.

Lung and heart allocation in the United States.

Lung and heart allocation in the United States has evolved over the past 20-30 years to better serve transplant candidates and improve organ utilization. The current lung allocation policy, based on the Lung Allocation Score, attempts to take into account risk of death on the waiting list and chance of survival posttransplant. This policy is flexible and can be adjusted to improve the predictive ability of the score. Similarly, in response to the changing clinical phenotype of heart transplant candidates, heart allocation policies have evolved to a multitiered algorithm that attempts to prioritize organs to the most infirm, a designation that fluctuates with trends in therapy. The Organ Procurement and Transplantation Network and its committees have been responsive, as demonstrated by recent modifications to pediatric heart allocation and mechanical circulatory support policies and by ongoing efforts to ensure that heart allocation policies are equitable and current. Here we examine the development of US lung and heart allocation policy, evaluate the application of the current policy on clinical practice and explore future directions for lung and heart allocation.

Enlargement of the spleen as an incidental finding on CT in post-partum females with fever.

OBJECTIVE: The aim was to evaluate whether enlargement of the spleen on CT in a post-partum female with fever is a common phenomenon. METHODS: In this retrospective institutional review board-approved study, the spleen was measured by CT in 77 females (average age 30.7 years) examined for post-partum fever and a control group of 58 febrile females imaged for suspected appendicitis (average age 29.7 years). The splenic length, width and thickness were measured and used to calculate the splenic index. The measurements of both groups of patients were compared. The size of the spleen was assessed again in 12 of the 77 post-partum female who had a follow-up CT for unrelated reasons. Continuous variables were compared, by groups, using analysis of variance (ANOVA). ANOVA with repeated measures was used to evaluate changes over time. A p-value <0.05 was considered significant. RESULTS: The length, thickness and width of the spleen were significantly larger in the patients imaged after delivery compared with those in the control group (p<0.001 for all three comparisons). The mean splenic index was 686.6 cm(3) in the post-partum group and 408.1 cm(3) in the control group (p<0.001). The splenic dimensions and index were significantly smaller in the 12 post-partum females who had a follow-up study. CONCLUSION: An enlarged spleen in febrile females undergoing CT in the puerperium may reflect physiological changes occurring during pregnancy.

CT in the clinical and prognostic evaluation of acute graft-vs-host disease of the gastrointestinal tract.

OBJECTIVE: To determine the role of abdominal CT in assessment of severity and prognosis of patients with acute gastrointestinal (GI) graft-vs-host disease (GVHD). METHODS: During 2000-2004, 41 patients with a clinical diagnosis of acute GI-GVHD were evaluated. CTs were examined for intestinal and extra-intestinal abnormalities, and correlated with clinical staging and outcome. RESULTS: 20 patients had GVHD clinical Stage I-II and 21 had Stage III-IV. 39 (95%) had abnormal CT appearances. The most consistent finding was bowel wall thickening: small (n=14, 34%) or large (n=5, 12%) bowel, or both (n=20, 49%). Other manifestations included bowel dilatation (n=7, 17%), mucosal enhancement (n=6, 15%) and gastric wall thickening (n=9, 38%). Extra-intestinal findings included mesenteric stranding (n=25, 61%), ascites (n=17, 41%), biliary abnormalities (n=12, 29%) and urinary excretion of orally administered gastrografin (n=12, 44%). Diffuse small-bowel thickening and any involvement of the large bowel were associated with severe clinical presentation. Diffuse small-bowel disease correlated with poor prognosis. 8 of 21 patients responded to therapy, compared with 15 of 20 patients with other patterns (p=0.02), and the cumulative incidence of GVHD-related death was 62% and 24%, respectively (p=0.01). Overall survival was not significantly different between patients with diffuse small-bowel disease and patients with other patterns (p=0.31). Colonic disease correlated with severity of GVHD (p=0.04), but not with response to therapy or prognosis (p=0.45). CONCLUSION: GVHD often presented with abdominal CT abnormalities. Diffuse small-bowel disease was associated with poor therapeutic response. CT may play a role in supporting clinical diagnosis of GI GVHD and determining prognosis.

Differentiation between right tubo-ovarian abscess and appendicitis using CT--a diagnostic challenge.

AIM: To determine CT features that can potentially differentiate right tubo-ovarian abscess (TOA) from acute appendicitis (AA; including abscess formation). MATERIALS AND METHODS: The abdominal computed tomography (CT) images of 48 patients with right-sided TOA (average age 39.3 ± 9.8 years) and 80 patients (average age 53.5 ± 19.9 years) with AA (24 with peri-appendicular abscess) were retrospectively evaluated. Two experienced radiologists evaluated 12 CT signs (including enlarged, thickened wall ovary, appendix diameter and wall thickness, peri-appendicular fluid collection, adjacent bowel wall thickening, fat stranding, free fluid, and extraluminal gas) in consensus to categorize the studies as either TOA or AA. The diagnosis and the frequency of each of the signs were correlated with the surgical and clinical outcome. RESULTS: Reviewers classified 92% cases correctly (TOA=85%, AA=96.3%), 3% incorrectly (TOA=6.3%, AA=1.3%); 5% were equivocal (TOA=8.3%, AA=2.5%). In the peri-appendicular abscess group reviewers were correct in 100%. Frequent findings in the TOA group were an abnormal ovary (87.5%), peri-ovarian fat stranding (58.3%), and recto-sigmoid wall thickening (37.5%). An abnormal appendix was observed in 2% of TOA patients. Frequent findings in the AA group were a thickened wall (32.5%) and distended (80%) appendix. Recto-sigmoid wall thickening was less frequent in AA (12.5%). The appendix was not identified in 45.8% of the TOA patients compared to 15% AA. CONCLUSIONS: In the presence of a right lower quadrant inflammatory mass, peri-ovarian fat stranding, thickened recto-sigmoid wall, and a normal appearing caecum, in young patients favour the diagnosis of TOA. An unidentified appendix does not contribute to the differentiation between TOA and peri-appendicular abscess.

Post-transplant lymphoproliferative disorders in lung transplant recipients: 20-yr experience at the University of Minnesota.

Post-transplant lymphoproliferative disorders (PTLD) are potentially fatal complications of solid organ transplantation. The natural history of PTLD varies considerably among the different types of organs transplanted. While lung transplant recipients are highly susceptible to PTLD, there are only a few small studies that detail PTLD in this setting. We undertook this study to better describe the characteristics and treatment response in PTLD after lung transplantation. We conducted a retrospective chart review of lung and heart/lung-transplant recipients between 1985 and 2008. A total of 32 cases (5%) of PTLD were identified in 639 patients. The median interval after transplantation to the diagnosis was 40 (3-242) months. Eight patients (25%) were diagnosed within one yr of transplantation and had PTLD predominantly within the thorax and allograft. Twenty-four patients (75%) were diagnosed more than one yr after transplantation and their tumors mainly affected the gastrointestinal tract. Monomorphic PTLD, diffuse large B-cell lymphoma, was diagnosed in 91%. Treatment of PTLD varied according to stage and clinical circumstances. Twenty-four patients (75%) have died. The median overall survival was 10 (0-108) months. PTLD after lung transplantation remains a challenge as a result of its frequency, complexity and disappointing outcome.

Sealed rupture of abdominal aortic aneurysms: CT features in 6 patients and a review of the literature.

PURPOSE: To assess the CT features of sealed rupture of abdominal aortic aneurysm. PATIENTS AND METHODS: We reviewed the CT scans of six index cases obtained over a 3 year period with a sealed rupture of an abdominal aortic aneurysm and those reported in the literature over a 21 year period. CT scans were reviewed for aneurysm size, the presence of a draped aorta and adjacent vertebral erosion. A group of consecutive patients with non-ruptured abdominal aortic aneurysm, referred for endovascular aneurysm repair during the same 3 year period constituted the control group. RESULTS: In the study group of 31 patients the mean size of the aneurysm was 6.24 +/- 2.01 cm, compared to 6.01 +/- 0.99 cm in the control group, without statistically significant difference (t = 0.75, df = 97, P = 0.46). A draped aorta was detected in all patients with a sealed rupture. Vertebral erosion was present in all our six, but mentioned in only 14 of the cases reported. CONCLUSION: A sealed rupture of an abdominal aortic aneurysm can occur in relatively small aneurysms. A draped aorta and adjacent vertebral erosion are characteristic CT signs of such a rupture.

Fat halo sign in the bowel wall of patients with Crohn's disease.

AIM: To evaluate the prevalence and localization of the deposition of submucosal fat, the "fat halo sign" (FHS), using computed tomography (CT) in the bowel wall of patients with Crohn's Disease, and to assess its relation to the duration of the disease. MATERIALS AND METHODS: The abdominal CT examinations of 100 consecutive patients were reviewed for the presence of the FHS in the bowel wall. A measurement of less than -10HU was regarded as indicative of fat. CT findings were correlated with the duration of the disease and statistically tested by simple regression analysis. The patients were divided into two groups: group A included 26 patients with a disease duration of less than 1 year and group B included 73 with a longer disease duration. In one patient disease duration was unknown. To test the relationship between disease duration and FHS the cumulative number of FHS positive and negative patients was plotted against disease duration. RESULTS: The FHS was present in 17 of the 100 patients in 20 bowel segments, mainly in the ileum (10) and the ascending colon (8). The FHS was present in 3.8% in group A and in 21.9% in group B (p<0.0375). CONCLUSION: The FHS was present in 17% of patients with CD. Its location was mainly in the terminal ileum and ascending colon, typical sites of the disease. Its prevalence was significantly duration dependent.

Rebound thymic enlargement on CT in adults.

The objective of this study is to report the development of thymic enlargement in adults, mainly associated with chemotherapy for malignancy. The typical CT features of this phenomenon are described. The clinical data and CT studies of 13 adult patients with newly appearing thymic enlargement on CT were reviewed. These patients were followed-up mainly for malignancy. Further follow-up CTs were studied when available. Medical records were reviewed as to the primary disease, its medical treatment and the time of initial appearance of the enlarged thymus in relation to treatment. The study group included 13 adult patients, 12 with malignant disease and one with a slowly resolving pneumonia. The enlarged thymus appeared as a triangular, arrowhead-shaped structure, with a bilobed configuration and convex borders. Density measurements were consistent with homogeneous soft tissue. Location was in the anterior mediastinum, in the normal site of the thymus. In nine patients, follow-up studies were available. The observation period ranged from 5 months to 8 years from the initial appearance of the enlarged thymus. In five of the nine patients, the thymic enlargement resolved after 1-4.5 years. In four of the nine patients, the thymus remained enlarged during a follow-up ranging from 5 months to 2.5 years. Thymic enlargement, while a rare phenomenon in adults, may occur, mainly after chemotherapy. This phenomenon should be included in the differential diagnosis of a soft tissue mass appearing in the anterior mediastinum on follow-up CT in adult patients particularly following treatment for malignancy.

The wandering spleen: CT findings and possible pitfalls in diagnosis.

AIM: To report the CT features of wandering spleen, a rare condition which can be incidentally detected as an abdominal or pelvic mass or can present with torsion, causing an acute abdomen. MATERIALS AND METHODS: The CT studies of seven patients, two children and five adults, with wandering spleen were reviewed. CT was performed urgently in three patients for acute abdomen, and electively in four. RESULTS: CT findings of wandering spleen included absence of the spleen in its normal position and a mass located elsewhere in the abdomen or pelvis, i.e. an ectopic spleen, enhancing homogeneously in four cases and failing partially or completely to enhance in the other three, indicating infarction. A "whirl" appearance representing the twisted splenic pedicle was seen in the three cases with torsion. Urgent splenectomy confirmed infarction secondary to torsion. CONCLUSION: The possible diagnosis of wandering spleen should be kept in mind when CT shows the spleen to be absent from its usual position and a mass is found elsewhere in the abdomen or pelvis. When, in addition, a "whirl" or partial or no enhancement of this mass are seen in a case presenting with acute abdomen, torsion of a wandering spleen is a likely diagnosis.

Congenital anomalies of the spleen.

Various congenital anomalies may affect the spleen, starting with common anomalies, such as an accessory spleen, up to rare conditions such as a wandering spleen and polysplenia. Most of these anatomic variants have no clinical significance; they need, however, to be recognized by the radiologist as such. Awareness of these variants is important for the radiologist to interpret the findings correctly and avoid mistaking them for a clinically significant abnormality. In this review we illustrate the spectrum of congenital anomalies of the spleen and stress pitfalls and possible complications resulting from these anomalies.

Predictors of chronic kidney disease in long-term survivors of lung and heart-lung transplantation.

Renal insufficiency is common after non-renal organ transplants. The predictors of long-term renal outcomes are not well established. A total of 219 lung and heart-lung transplant recipients surviving more than 6 months after transplantation were studied to determine predictors of time to doubling of serum creatinine and end-stage kidney disease (ESKD) with death as a competing risk. Median follow-up was 79 months (range 9-222 months). Baseline estimated glomerular filtration rate (GFR) was 96.3+/-34.5 mL/min/1.73 m2. One hundred twenty-two recipients (55%) doubled their serum creatinine, 16 (7.3%) progressed to ESKD and 143 (65%) died. The majority of recipients who survived >6 years had a GFR<60 mL/min at both 1 and 7 years. Most of the loss of renal function occurred in the first year post-transplant. Older age at transplant, lower GFR at 1 month and cyclosporine use in the first 6 months predicted shorter time to doubling of serum creatinine when death was handled as a competing risk. Based on this prevalence data and using GFR decay and death as study endpoints, we offer sample size estimates for a prospective, interventional trial that is aimed at slowing or preventing the progression of kidney disease.