Hip kinematics and kinetics in patients with femoroacetabular impingement syndrome before and 1 year after hip arthroscopic surgery. Results from the HAFAI cohort.

INTRODUCTION: Patients with femoroacetabular impingement syndrome (FAIS) experience decreased function. Consequently, earlier studies have evaluated gait biomechanics in these patients, but a larger study evaluating gait biomechanics before and after an intervention standardising gait speed is lacking. We aimed at investigating gait kinematics and kinetics in patients with FAIS compared with pain-free controls before and 1 year after hip arthroscopic surgery. Secondary, we aimed at analysing gait pattern separately for the sexes and to investigate associations between peak kinematics and kinetics and the Copenhagen Hip and Groin Outcome Score (HAGOS). MATERIALS AND METHODS: Sixty patients with FAIS and 30 pain-free controls were tested at a standardised gait speed (1.40 m/s ± 10%). Patients were tested twice: before and 1 year after surgery. Kinematics and kinetics were recorded using infrared high-speed cameras and a force plate. Participants answered HAGOS. RESULTS: The largest difference among groups was that gait differed between males and females. Neither before nor after surgery could we demonstrate large alterations in gait pattern between patients and pain-free controls. Male patients demonstrated associations between peak kinematics and kinetics and HAGOS Sports function. CONCLUSIONS: Gait pattern was only vaguely altered in patients with FAIS compared with pain-free controls before and after surgery when using at standardised gait speed. Hence, analysing gait in patients with FAIS does not seem of major importance. Nevertheless, there was an association between HAGOS Sports function and peak kinematics and kinetics in male patients, implying that there could be a clinical importance.

The genetic diversity of multiple sclerosis risk among Hispanic and African American populations living in the United States.

BACKGROUND: Substantial progress has been made toward unraveling the genetic architecture of multiple sclerosis (MS) within populations of European ancestry, but few genetic studies have focused on Hispanic and African American populations within the United States. OBJECTIVE: We sought to test the relevance of common European MS risk variants outside of the major histocompatibility complex (n = 200) within these populations. METHODS: Genotype data were available on 2652 Hispanics (1298 with MS, 1354 controls) and 2435 African Americans (1298 with MS, 1137 controls). We conducted single variant, pathway, and cumulative genetic risk score analyses. RESULTS: We found less replication than statistical power suggested, particularly among African Americans. This could be due to limited correlation between the tested and causal variants within the sample or alternatively could indicate allelic and locus heterogeneity. Differences were observed between pathways enriched among the replicating versus all 200 variants. Although these differences should be examined in larger samples, a potential role exists for gene-environment or gene-gene interactions which alter phenotype differentially across racial and ethnic groups. Cumulative genetic risk scores were associated with MS within each study sample but showed limited diagnostic capability. CONCLUSION: These findings provide a framework for fine-mapping efforts in multi-ethnic populations of MS.

Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies.

BACKGROUND: Selinexor is an oral inhibitor of the nuclear export protein Exportin 1 (XPO1) with demonstrated antitumor activity in solid and hematological malignancies. We evaluated the efficacy and safety of selinexor in heavily pretreated, recurrent gynecological malignancies. METHODS: In this phase 2 trial, patients received selinexor (35 or 50 mg/m2 twice-weekly [BIW] or 50 mg/m2 once-weekly [QW]) in 4-week cycles. Primary endpoint was disease control rate (DCR) including complete response (CR), partial response (PR) or stable disease (SD) ≥12 weeks. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. RESULTS: 114 patients with ovarian (N = 66), endometrial (N = 23) or cervical (N = 25) cancer were enrolled. Median number of prior regimens for ovarian, endometrial and cervical cancer was 6 (1-11), 2 (1-5), and 3 (1-6) respectively. DCR was 30% (ovarian 30%; endometrial 35%; cervical 24%), which included confirmed PRs in 8%, 9%, and 4% of patients with ovarian, endometrial, and cervical cancer respectively. Median PFS and OS for patients with ovarian, endometrial and cervical cancer were 2.6, 2.8 and 1.4 months, and 7.3, 7.0, and 5.0 months, respectively. Common Grade 3/4 adverse events (AEs) were thrombocytopenia (17%), fatigue (14%), anemia (10%), nausea (9%) and hyponatremia (9%). Patients with ovarian cancer receiving 50 mg/m2 QW had fewer high-grade AEs with similar efficacy as BIW treatment. CONCLUSIONS: Selinexor demonstrated single-agent activity and disease control in patients with heavily pretreated ovarian and endometrial cancers. Side effects were a function of dose level and treatment frequency, similar to previous reports, reversible and mitigated with supportive care.

Reduced disease severity following therapeutic treatment with angiotensin 1-7 in a mouse model of multiple sclerosis.

Multiple Sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by autoimmune and neurodegenerative pathologies for which there is no cure and no defined etiology. Although several, modestly effective, disease modifying drugs are available to treat MS, there are presently no treatments that offer neuroprotection and prevent clinical progression. Therapies are needed that control immune homeostasis, prevent disease progression, and stimulate regeneration in the CNS. Components of the renin-angiotensin-system (RAS) have recently been identified as chemical mediators in the CNS and in neurological disease. Here we show the beneficial effect of therapeutic treatment with the Mas receptor agonist and metabolite of the protective arm of RAS, angiotensin 1-7 (A(1-7)), in the experimental autoimmune encephalomyelitis (EAE) animal model of MS. Therapeutic treatment with A(1-7) caused a dose-dependent reduction both in clinical disease severity and progression, and was dependent on Mas receptor activation. Further analysis of the most optimal dose of A(1-7) treatment revealed that the reductions in clinical disease course were associated with decreased immune infiltration and demyelination, axonal loss and oxidative stress in the spinal cord. In addition A(1-7) treatment was also associated with increases in circulating alternatively activated monocytes/macrophages.

The origin of endodontic Enterococcus faecalis explored by comparison of virulence factor patterns and antibiotic resistance to that of isolates from stool samples, blood cultures and food.

AIM: To elucidate the origin of Enterococcus faecalis isolated from secondary root canal infections and the possibility for a foodborne transmission by comparing them to strains recovered from food, blood and stool regarding putative virulence factors and antibiotic susceptibility profiles, where strains from common origin were hypothesized to harbour similar characteristics. METHODOLOGY: A total of 108 E. faecalis strains recovered in the county of Stockholm, Sweden, were screened using PCR for putative virulence factors esp, cylA, gelE/gelatinase-negative phenotype (ef1841/fsrC), efaA, ace and asa1. The minimum inhibitory concentration (MIC) for ampicillin, piperacillin-tazobactam, imipenem, gentamicin, vancomycin, ciprofloxacin and linezolid was determined using the agar dilution method. RESULTS: Next to strains from blood, the food isolates presented the highest average number of virulence determinants and were frequently enriched with asa1 coding for aggregation substance. None of the endodontic strains carried cylA, and the gelatinase-negative phenotype caused by a deletion dominated the group. Altogether, the most prevalent genes were gelE, efaA and ace, and a combination of them was equally present in approximately 80% of the strains from food, stool and root canals in comparison with 43.3% of the blood isolates. High-level resistance to ciprofloxacin and gentamicin was observed in 30% of the blood isolates, whereas the isolates from other origins, with single exceptions, were susceptible to all tested antibiotics. CONCLUSIONS: Evidence for a foodborne transmission, explaining the high reported prevalence of E. faecalis in root filled teeth, could not be determined based on the similarities in virulence factor patterns and antibiotic susceptibility. The only linkage between isolates from food and root canals consisted of a shared common combination of the genes gelE, efaA and ace. The high occurrence of putative virulence traits in food isolates questions the safety of E. faecalis in food products.

Trends in prevalent and incident opioid receipt: an observational study in Veterans Health Administration 2004-2012.

BACKGROUND: Improved understanding of temporal and regional trends may support safe and effective prescribing of opioids. OBJECTIVE: We describe national, regional, and facility-level trends and variations in opioid receipt between fiscal years (FY) 2004 and 2012. DESIGN: Observational cohort study using Veterans Health Administration (VHA) administrative databases. PARTICIPANTS: All patients receiving primary care within 137 VHA healthcare systems during a given study year and receiving medications from VHA one year before and during a given study year. MAIN MEASURES: Prevalent and incident opioid receipt during each year of the study period. KEY RESULTS: The overall prevalence of opioid receipt increased from 18.9% of all veteran outpatients in FY2004 to 33.4% in FY2012, a 76.7% relative increase. In FY2012, women had higher rates of prevalent opioid receipt than men (42.4% vs. 32.9%), and the youngest veterans (18-34 years) had higher prevalent opioid receipt compared to the oldest veterans (≥ 80 years) (47.6% vs. 17.9%). All regions in the United States saw increased rates of prevalent opioid receipt during this time period. Prevalence rates varied widely by facility: in FY2012, the lowest-prescribing facility had a rate of 13.5%, and the highest of 50.8%. Annual incident opioid receipt increased from 8.8% in FY2004 to 10.2% in FY2011, with a decline to 9.8% in FY2012. Incident prescribing increased at some facilities and decreased at others. Facilities with high prevalent prescribing tended to have flat or decreasing incident prescribing rates during the study time frame. CONCLUSIONS: Rates of opioid receipt increased throughout the study time frame, with wide variation in prevalent and incident rates across geographical region, sex, and age groups. Prevalence and incidence rates reflect distinct prescribing practices. Areas with the highest prevalence tended to have lower increases in incident opioid receipt over the study period. This likely reflects facility-level variations in prescribing practices as well as baseline rates of prevalent use. Future work assessing opioid prescribing should employ methodologies to account for and interpret both prevalent and incident opioid receipt.

Potential for nosocomial transmission of Enterococcus faecalis from surfaces in dental operatories.

AIM: To assess the potential for nosocomial transmission of Enterococcus faecalis during root canal treatment by measuring its occurrence on surfaces in dental operatories in relation to the efficacy of disinfection routines. METHODOLOGY: Eight dental clinics (two endodontic specialist clinics and six general dentistry clinics) were included. Bacterial sampling was conducted in duplicate after root canal treatment and collected before and after disinfection from four surfaces expected to be frequently disinfected and six surfaces expected to be occasionally disinfected. RESULTS: A total of 320 samples were collected. Overall, 40.6% (n = 130) exhibited bacterial growth, mostly consisting of environmental bacteria (36.3%) and to a lesser extent of bacteria from salivary contamination (3.4%). Only three surfaces, all of which were probably seldomly disinfected, were positive for E. faecalis (0.9%). Disinfection routines resulted in an increased contamination in the majority of general dentistry clinics: 64% (32/50) of the surfaces were contaminated prior to and 70% (35/50) after disinfection. Conversely, disinfection of surfaces in the specialist clinics reduced contamination levels by 10%. CONCLUSIONS: The origin of E. faecalis in secondary root canal infections remains unclear, as the potential for nosocomial transmission of enterococci from environmental surfaces in dental surgeries appears to be very small. The incorrect or ineffective disinfection procedures in general dentistry clinics needs to be addressed to counteract the risk for bacterial transmission in dental operatories.

A computerised third molar surgery simulator--results of supervision by different professionals.

The purpose of the study was to investigate which supervisory approach afforded the most efficient learning method for undergraduate students in oral and maxillofacial surgery (OMS) using a computerised third molar surgery simulator. Fifth year dental students participated voluntarily in a randomised experimental study using the simulator. The amount of time required and the number of trials used by each student were evaluated as a measure of skills development. Students had the opportunity to practise the procedure until no further visible improvements were achieved. The study assessed four different types of supervision to guide the students. The first group was where they were supported by a teacher/specialist in OMS, the second by a teaching assistant, the third group practised without any supervision and the fourth received help from a simulator technician/engineer. A protocol describing assessment criteria was designed for this purpose, and a questionnaire was completed by all participating students after the study. The average number of attempts required to virtually remove a third molar tooth in the simulator was 1.44 times for the group supervised by an OMS teacher; 1.5 times for those supervised by a teaching assistant; 2.8 times for those who had no supervision; and 3.6 times when support was provided only by a simulator technician. The results showed that the most efficient experience of the students was when they were helped by an OMS teacher or a teaching assistant. In a time and cost-effective perspective, supervision by a teaching assistant for a third molar surgery simulator would be the optimal choice.

Cost analysis of orthognathic surgery: outpatient care versus inpatient care.

With limited healthcare resources, it is important to provide the right level and form of care. The aim of this study was to determine whether selected single-jaw orthognathic surgery in outpatient care (OPC) generates lower healthcare costs than in inpatient care (IPC). The costs of surgically assisted rapid maxillary expansion (SARME), Le Fort I osteotomy (LFI), and bilateral sagittal split osteotomy (BSSO) were calculated for 165 patients, 107 treated in OPC and 58 in IPC. Additionally, costs for revisits, emergency visits, emergency phone calls, re-operations, and plate removal during the first 12 months postoperatively were recorded. The total mean costs of the different operations including revisits, emergency visits, and phone calls were 34.2-48.8% lower in OPC than in IPC at 12 months postoperatively. Operation costs were lower for LFI in OPC (P = 0.009) and for SARME in IPC (P = 0.007). Anaesthesia costs were lower for LFI (P < 0.001) and BSSO (P < 0.001) in OPC, and there were fewer revisits (P = 0.001) and lower costs (P = 0.002) after LFI in OPC compared to IPC. This study showed that selected single-jaw orthognathic surgeries in outpatient care are associated with lower healthcare costs compared to inpatient care.

Impact of overweight and obesity on cardiac benefit of antihypertensive treatment.

BACKGROUND AND AIMS: Increased body mass index (BMI) has been associated with increased cardiovascular morbidity and mortality in hypertension. Less is known about the impact of BMI on improvement in left ventricular (LV) structure and function during antihypertensive treatment. METHODS AND RESULTS: Annual BMI, echocardiograms and cardiovascular events were recorded in 875 hypertensive patients with LV hypertrophy during 4.8 years randomized treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy. Patients were grouped by baseline BMI into normal (n = 282), overweight (n = 405), obese (n = 150) and severely obese groups (n = 38) (BMI ≤24.9, 25.0-29.9, 30.0-34.9, and ≥35.0 kg/m(2), respectively). At study end, residual LV hypertrophy was present in 54% of obese and 79% of severely obese patients compared to 31% of normal weight patients (both p < 0.01). In regression analyses, adjusting for initial LV mass/height(2.7), higher BMI predicted less LV hypertrophy reduction and more reduction in LV ejection fraction (both p < 0.05), independent of blood pressure reduction, diabetes and in-study weight change. During follow-up, 91 patients suffered cardiovascular death, myocardial infarction or stroke. In Cox regression analysis 1 kg/m(2) higher baseline BMI predicted a 5% higher rate of cardiovascular events and 10% higher cardiovascular mortality over 4.8 years (both p < 0.05). CONCLUSIONS: In hypertensive patients in the LIFE study, increased BMI was associated with less reduction of LV hypertrophy and less improvement in LV systolic function which may contribute to the observed higher cardiovascular event rate of treated hypertensive patients.

Patient safety with orthognathic surgery in an outpatient setting.

Orthognathic surgery is traditionally performed in inpatient care. The question is whether patient safety is maintained when orthognathic surgery is performed in outpatient care. This retrospective cohort study was conducted to investigate patient safety in selected single-jaw orthognathic surgeries performed in outpatient care compared to inpatient care. Postoperative infection, postoperative bleeding, postoperative pain, plate removal, and re-operation, as well as emergency visits/phone calls and postoperative admission during the first 12 months after surgery were recorded. Predictor variables were sex, age, smoking, general disease, antibiotics, operation type, and operation time. Of the 165 patients included, 58 were treated in inpatient care and 107 in outpatient care. No significant difference was found between the groups regarding postoperative bleeding, pain, plate removal, re-operation, or emergency visits/phone calls. Ninety-four percent of outpatients (n = 101) were able to leave the hospital on the day of surgery as planned. There was an increased risk of postoperative infection in the outpatient care group (odds ratio 2.46, P = 0.049). Selected single-jaw orthognathic surgery can be performed in the outpatient setting, with maintained patient safety. The reason for the increased risk of postoperative infection among patients operated in outpatient care should be investigated in further studies.

Health-related quality of life in recurrent platinum-sensitive ovarian cancer--results from the CALYPSO trial.

BACKGROUND: In the CALYPSO trial, carboplatin-pegylated liposomal doxorubicin (CD) demonstrated superior therapeutic index versus carboplatin-paclitaxel (CP) in patients with recurrent ovarian cancer. This paper reports the health-related quality of life (HRQoL) findings. MATERIALS AND METHODS: HRQoL was measured with the EORTC QoL-QC30 questionnaire and OV28 ovarian cancer module. Mean change scores from baseline in HRQoL subscales (five functional scales and global health status) in each arm and the proportion of patients improved or worsened were calculated every 3 months until 12 months. RESULTS: Compliance was 90% at baseline and 76%, 64%, 57% at 3, 6, and 9 months, respectively. Baseline HRQoL showed already impaired global scores (mean 62/100) and considerable symptom burden (90% of patients reporting nonzero scores). Global QoL and abdominal symptom scores improved over time in both arms; at 6 months, 36% of patients met criteria for improved symptoms. Treatment with CD resulted in less peripheral neuropathy (9.8 versus 24.2), fewer other chemotherapy side-effects (9.5 versus 16.2), and less impact on body image (3.8 versus 10.4) versus CP (all P<0.02) at 6 months. CONCLUSIONS: These patient-reported outcomes confirm the overall lower toxicity of CD versus CP. The improved disease-related outcomes achieved with CD were not at the expense of QoL.

Multiple sclerosis in Hispanics: a study of clinical disease expression.

BACKGROUND: Hispanics living with multiple sclerosis (MS) in the United States are not well defined. OBJECTIVE: To describe the clinical characteristics of MS among Hispanic Whites (HW) in Southern California with those of non-Hispanic Whites (NHW). METHODS: We performed a medical chart review to identify all cases of HW with MS (n = 125) who were treated at our institution during a 1-year period. We also identified cases of NHW with MS (100 NHW) treated at those clinics. All HW patients were interviewed to ascertain ancestry including detailed migration history. Disease progression was assessed by ambulatory disability and defined as Expanded Disability Status Scale (EDSS) score ≥6. RESULTS: Compared with NHW, HW were more likely to have a relapsing-remitting form of MS and a younger age of onset (28.4 ± 0.97 years) with presenting symptoms of optic neuritis and transverse myelitis. However, overall ambulatory disability did not differ between HW and NHW. Migration to the US at age >15 years was associated with increased risk of disability in HW. CONCLUSIONS: HW living in the USA may be at risk of developing MS at an earlier age compared with NHW. Migration history can play an important role in the management of HW with MS.

Enterococcus faecalis infection in root canals - host-derived or exogenous source?

AIMS: Enterococcus faecalis is associated with a significant number of refractory endodontic infections. Previous studies report a prevalence of Ent. faecalis ranging from 24% up to 77% in teeth with failed endodontic treatment. The origin of the micro-organism remains unclear, as enterococci do not belong to the normal oral microflora. The aim of this study was to determine whether these enterococci were of endogenous or exogenous origin. METHODS AND RESULTS: Fifty consecutive patients with apical periodontitis in need of endodontic orthograde re-treatment were included. Samples were collected from root canals, saliva and faeces and subjected to microbiological culturing. The genetic relationship between Ent. faecalis from root canals and isolates from the different host sources was determined using pulsed-field gel electrophoresis. In 16% (8/50) of the patients, enterococci were collected from the root canal samples. The genetic analysis showed that the isolates from the root canals were not related to those from the normal gastrointestinal microflora. None of these patients had enterococci in their saliva samples. CONCLUSIONS: Endodontic infections with Ent. faecalis are probably not derived from the patient's own normal microflora, which indicates that these infections ent. faecalis are of exogenous origin. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to genetically compare endodontic infectious Ent. faecalis isolates with isolates from the hosts' own normal microflora.

Serial dilation reduces graft slippage compared to extraction drilling in anterior cruciate ligament reconstruction: a randomized controlled trial using radiostereometric analysis.

PURPOSE: This study tested the hypothesis that serial dilation of the tibial tunnel could provide a stronger anchorage of the graft-fixation-device complex compared to traditional extraction drilling. METHODS: Forty patients (22 men and 18 women) undergoing ACL reconstruction were randomized to either extraction drilling (group ED) or compaction by serial dilation (group SD) of the tibial tunnel. Tantalum beads were placed in the tibia, femur, and in the hamstring graft. Radiostereometric analysis (RSA) was performed postoperatively and again after 6, 12, and 24 weeks. Migration of graft in the bone tunnels as well as knee laxity was assessed using RSA and a TELOS stress device. RESULTS: Six patients (three men and three women) were excluded during follow-up, which resulted in 17 patients in group ED [median age 30 years (range 20-50)] and 17 patients in group SD [median age 32 years (range 20-49)]. The mean migration of the graft in the tibial bone canal after 3 months was 1.3 (SD 0.6) mm in group ED and 0.8 (SD 0.5) mm in group SD (P = 0.02). The overall knee laxity after 3 months was 13.0 (SD 4.0) mm in group ED and 10.9 (SD 3.1) mm in group SD. CONCLUSION: This study found less slippage of the hamstring graft in the tibial bone canal in the serial dilated group compared to the extraction drilling group. The clinical relevance of the difference is unknown. No difference in stress radiographic knee laxity was found between the two groups.

A systematic approach to improve oral and maxillofacial surgery education.

To improve teaching quality and student satisfaction, a new curriculum in Oral Surgery was implemented at Karolinska Institutet in 2007. This paper describes the curriculum change as well as the results regarding quality, satisfaction, cost-effectiveness and workload for teachers and staff. To design the new curriculum, all members of the teaching staff participated in a series of group discussions where problems with the previous curriculum were identified and ideas on how to improve the curriculum were discussed. Cost-effectiveness was evaluated by comparing the number of teaching sessions between the new and the old curriculum. A questionnaire was used to investigate the staffs' perceived change in workload and teaching quality. The students' satisfaction and attitudes to learning was screened for by on-line questionnaires. The large amount of passive observational teaching was considered as the main problem with the old curriculum. Half of these sessions were replaced by either clinical seminars or demonstrations performed in an interactive form. Students rated the new curriculum as a clear improvement. Analyses of time and cost-effectiveness showed a decrease in teaching sessions by almost 50%. Generally, the teachers were more positive towards the changes compared to the non-teaching staff. The students rated the new type of learning activities relatively high, whilst the traditional observational teaching was seen as less satisfactory. They preferred to learn in a practical way and few indicated analytic or emotional preferences. The majority of the students reported a good alignment between the new course curriculum and the final exam.

The agreement between magnetic resonance imaging and arthroscopic findings in temporomandibular joint disorders.

The aim of this retrospective observational study was to assess the potential agreement between independent magnetic resonance imaging (MRI) and arthroscopic findings and their respective contributions to a final diagnosis in patients with refractory temporomandibular joint disorders. Two dentomaxillofacial radiologists and two oral and maxillofacial surgeons scored 50 joints. All observers, who were blinded to additional clinical information, used a specific scoring form and selected one or more diagnostic labels. Agreement between MRI and arthroscopy and their contributions to the final diagnosis were assessed as primary outcomes using Fleiss' kappa. Intra-modality agreement and the correlation between signal intensity ratio (SIR) measurements on MRI and synovitis grading on arthroscopy were assessed as secondary outcomes. Agreement between MRI and arthroscopy was poor. A fair level of agreement was only reached for reduction capacity of the disc and disc perforation. Arthroscopic diagnostic labels matched better with the final diagnosis, suggesting a bigger contribution to that diagnosis. Higher SIR measurements correlated with higher synovitis grading scores for the retrodiscal tissue and the posterior band of the disc. Intra-modality agreement was better in arthroscopy. When blinded to clinical information, arthroscopy and MRI observations can lead to different conclusions. The diagnostic outcomes of both examinations should be considered and integrated into a final diagnosis.

Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting.

PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse (CIR5y) of 9.5%. FCM-MRD levels on days 15 (HzR 4.0, p < 0.0001), 29 (HzR 2.7, p < 0.0001), and 79 (HzR 3.5, p < 0.0001) associated with hazard of relapse adjusted for age, cytogenetics, and WBC. The early (day 15) response associated with CIR5y adjusted for day 29 FCM-MRD, with higher levels in adults (median 2.4 × 10-2 versus 5.2 × 10-3, p < 0.0001). Undetectable FCM- and/or PCR-MRD on day 29 identified patients with a very good outcome (CIR5y = 3.2%). For patients who did not undergo transplantation, day 79 FCM-MRD > 10-4 associated with a CIR5y = 22.1%. In conclusion, FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.

Frequent occurrence of multidrug-resistant CC17 Enterococcus faecium among clinical isolates in Sweden.

AIMS: To screen for the globally spread cluster of Enterococcus faecium, clonal complex 17 (CC17) and characterize the genetic profile of Swedish clinical Ent. faecium isolates. METHODS: A total of 203 consecutive isolates collected from 2004 to 2007 from patients with bacteraemia in Sweden. All isolates were genotyped using multiple-locus variable-number tandem repeat analysis (MLVA) and 20 isolates representing different MLVA types (MT) were chosen for multilocus sequence typing (MLST). Minimal inhibitory concentrations against clinically relevant antibiotics were determined with agar dilution. Presence of the virulence genes esp and hyl was investigated using PCR. RESULTS: A total of 65% (n = 109) of all isolates belonged to MT-1, and the second most common MLVA type was MT-159 (13%, n = 21). MLST analysis confirmed the presence of CC17 during the entire study period. The number of isolates resistant to gentamicin and vancomycin, as well as the presence of hyl, increased significantly during the investigation period. CONCLUSIONS: The present study demonstrates that nosocomial infections caused by Ent. faecium CC17 are commonly occurring in Sweden. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of CC17 Ent. faecium in Sweden. The increase of antibiotic resistance and virulence indicates that these strains are further adapting to the hospital environment.

Bacillus licheniformis prevents necrotic enteritis in broiler chickens.

Three studies were conducted using Clostridium perfringens as an intestinal challenge to produce necrotic enteritis (NE). The studies consisted of two battery screening studies and one production study in floor pens, which were used to test the effect of the addition of Bacillus licheniformis (DSM 17236) spores at different doses and feeding periods in comparison to birds fed diets with subtherapeutic levels of virginiamycin (15 g/ton feed). In all three studies the use of B. licheniformis (1.6 x 10(6) - 8 x 10(7) CFUs/g) or virginiamycin (15 g/ton feed) showed no difference in effect with regard to feed conversion ratio, weight gain, NE lesion score, and NE mortality. In the two battery studies, both treatments showed a significantly decreased feed conversion ratio, increased weight gain, reduced NE lesion score, and NE-reduced mortality compared to the nonmedicated C. perfringens-challenged group. In general, none of the treatments performed as well as the no-challenge group. The present data indicate that the use of B. licheniformis spores as a probiotic or direct-fed microbial could be an alternative to adding medication to the feed to overcome NE under commercial-like conditions and could therefore be of direct use in preventing antibiotic-resistant pathogens in chickens.