Meta-analysis of diagnostic accuracy studies with multiple thresholds: Comparison of different approaches.

Methods for standard meta-analysis of diagnostic test accuracy studies are well established and understood. For the more complex case in which studies report test accuracy across multiple thresholds, several approaches have recently been proposed. These are based on similar ideas, but make different assumptions. In this article, we apply four different approaches to data from a recent systematic review in the area of nephrology and compare the results. The four approaches use: a linear mixed effects model, a Bayesian multinomial random effects model, a time-to-event model and a nonparametric model, respectively. In the case study data, the accuracy of neutrophil gelatinase-associated lipocalin for the diagnosis of acute kidney injury was assessed in different scenarios, with sensitivity and specificity estimates available for three thresholds in each primary study. All approaches led to plausible and mostly similar summary results. However, we found considerable differences in results for some scenarios, for example, differences in the area under the receiver operating characteristic curve (AUC) of up to 0.13. The Bayesian approach tended to lead to the highest values of the AUC, and the nonparametric approach tended to produce the lowest values across the different scenarios. Though we recommend using these approaches, our findings motivate the need for a simulation study to explore optimal choice of method in various scenarios.

Case-control study on factors associated with a decreased milk yield and a depressed health status of dairy herds in northern Germany.

BACKGROUND: In the past years, it became apparent that health status and performance differ considerably within dairy farms in Northern Germany. In order to obtain clues with respect to possible causes of these differences, a case-control study was performed. Case farms, which showed signs of health and performance problems, and control farms, which had none of these signs, were compared. Risk factors from different areas such as health management, housing, hygiene and nutrition were investigated as these are known to be highly influential. The aim of this study was to identify major factors within these areas that have the strongest association with health and performance problems of dairy herds in Northern Germany. RESULTS: In the final model, a lower energy density in the roughage fraction of the diet, more pens with dirty lying areas and a low ratio of cows per watering spaces were associated with a higher risk for herd health problems. Moreover, case farms were affected by infections with intestinal parasites, lungworms, liver flukes and Johne's Disease numerically more often than control farms. Case farms more often had pens with raised cubicles compared to the deep bedded stalls or straw yards found in control farms. In general, the hygiene of the floors and beddings was worse in case farms. Concerning nutrition, the microbiological and sensory quality of the provided silages was often insufficient, even in control farms. Less roughage was provided to early lactating cows and the feed was pushed to the feeding fence less frequently in case farms than in control farms. CONCLUSIONS: The results show that milk yield and health status were associated with various factors from different areas stressing the importance of all aspects of management for good animal health and performance. Moreover, this study confirmed well-known risk factors for health problems and performance losses. These should better be taken heed of in herd health management.

[Ethical consideration of studies involving human subjects outside the regulatory framework: not mandatory, but of high relevance]. / Ethische Bewertung von Studien am Menschen außerhalb des regulatorischen Rahmens: nicht bindend, aber von großer Wichtigkeit.

According to the Declaration of Helsinki, ethics committees are obliged to evaluate any type of medical research involving human subjects in order to ensure an objective view on ethical considerations. This does not only mean considering whether the risks to study participants are ethically justifiable or not, but also checking whether the scientific quality of a study is sufficient. However, the role of ethics committees differs depending on whether the study to be considered is, for example, an approval study according to the German Medicines Act (AMG) or whether the study is outside the regulatory framework. For these so-called unregulated studies it is not always mandatory to obtain approval from an ethics committee or an institutional review board.In this paper, we first explain the term "unregulated studies" in detail and elaborate for which types of unregulated studies an application for ethical approval is required before we deal with the application for ethical approval as such and in particular with the study protocol as one of its major components. Registry studies, postmarketing surveillance studies, analyses of secondary data, surveys, intervention, and prognostic studies serve as examples to illustrate the broad range of unregulated studies.Finally, we discuss crucial aspects of the role of ethics committees with respect to the consideration of unregulated studies. In our conclusion, we point out the necessity of having ethics committees at each university in Germany that are also responsible for unregulated studies. In addition, the German legislature should define a stricter regulation such that unregulated studies also have to adhere to the vote of the ethics committee.

Antimicrobial susceptibility testing of Arcobacter butzleri: development and application of a new protocol for broth microdilution.

Objectives: To develop a standard reference broth microdilution method for antimicrobial susceptibility testing (AST) of Arcobacter butzleri. The protocol was subsequently applied to a collection of A. butzleri isolates from different sources. Methods: Broth microdilution susceptibility testing was performed on eight A. butzleri isolates in three media: non-supplemented CAMHB, CAMHB + 2% FBS and CAMHB + 5% FBS. The MIC values were read after 24 and 48 h of incubation at 35 ±âŸ2 °C in ambient air. A logistic regression model was used to determine the combination of medium and incubation time yielding the most homogeneous results. Subsequently, the protocol was applied to 65 A. butzleri isolates to determine their MICs of 31 antimicrobial agents. Results: The statistical analysis revealed that the most homogeneous MIC values were obtained with CAMHB + 5% FBS and reading of MIC values after 24 h of incubation. The standardized method was successful for AST of all 65 A. butzleri isolates. MIC values were distributed unimodally for most antimicrobial agents. However, one field isolate showed elevated MIC values of gentamicin, streptomycin, tetracycline and trimethoprim/sulfamethoxazole. Conclusions: This study presents a new protocol for AST of A. butzleri by broth microdilution and shows the distribution of MIC values of 31 antimicrobial agents for a collection of A. butzleri isolates from different origins.

Inflation of the type I error: investigations on regulatory recommendations for bioequivalence of highly variable drugs.

PURPOSE: We investigated different evaluation strategies for bioequivalence trials with highly variable drugs on their resulting empirical type I error and empirical power. The classical 'unscaled' crossover design with average bioequivalence evaluation, the Add-on concept of the Japanese guideline, and the current 'scaling' approach of EMA were compared. METHODS: Simulation studies were performed based on the assumption of a single dose drug administration while changing the underlying intra-individual variability. RESULTS: Inclusion of Add-on subjects following the Japanese concept led to slight increases of the empirical α-error (≈7.5%). For the approach of EMA we noted an unexpected tremendous increase of the rejection rate at a geometric mean ratio of 1.25. Moreover, we detected error rates slightly above the pre-set limit of 5% even at the proposed 'scaled' bioequivalence limits. CONCLUSIONS: With the classical 'unscaled' approach and the Japanese guideline concept the goal of reduced subject numbers in bioequivalence trials of HVDs cannot be achieved. On the other hand, widening the acceptance range comes at the price that quite a number of products will be accepted bioequivalent that had not been accepted in the past. A two-stage design with control of the global α therefore seems the better alternative.

Identification of a lineage specific zinc responsive genomic island in Mycobacterium avium ssp. paratuberculosis.

BACKGROUND: Maintenance of metal homeostasis is crucial in bacterial pathogenicity as metal starvation is the most important mechanism in the nutritional immunity strategy of host cells. Thus, pathogenic bacteria have evolved sensitive metal scavenging systems to overcome this particular host defence mechanism. The ruminant pathogen Mycobacterium avium ssp. paratuberculosis (MAP) displays a unique gut tropism and causes a chronic progressive intestinal inflammation. MAP possesses eight conserved lineage specific large sequence polymorphisms (LSP), which distinguish MAP from its ancestral M. avium ssp. hominissuis or other M. avium subspecies. LSP14 and LSP15 harbour many genes proposed to be involved in metal homeostasis and have been suggested to substitute for a MAP specific, impaired mycobactin synthesis. RESULTS: In the present study, we found that a LSP14 located putative IrtAB-like iron transporter encoded by mptABC was induced by zinc but not by iron starvation. Heterologous reporter gene assays with the lacZ gene under control of the mptABC promoter in M. smegmatis (MSMEG) and in a MSMEG∆furB deletion mutant revealed a zinc dependent, metalloregulator FurB mediated expression of mptABC via a conserved mycobacterial FurB recognition site. Deep sequencing of RNA from MAP cultures treated with the zinc chelator TPEN revealed that 70 genes responded to zinc limitation. Remarkably, 45 of these genes were located on a large genomic island of approximately 90 kb which harboured LSP14 and LSP15. Thirty-five of these genes were predicted to be controlled by FurB, due to the presence of putative binding sites. This clustering of zinc responsive genes was exclusively found in MAP and not in other mycobacteria. CONCLUSIONS: Our data revealed a particular genomic signature for MAP given by a unique zinc specific locus, thereby suggesting an exceptional relevance of zinc for the metabolism of MAP. MAP seems to be well adapted to maintain zinc homeostasis which might contribute to the peculiarity of MAP pathogenicity.

Effects of ultrafine particles on the allergic inflammation in the lung of asthmatics: results of a double-blinded randomized cross-over clinical pilot study.

BACKGROUND: Epidemiological and experimental studies suggest that exposure to ultrafine particles (UFP) might aggravate the allergic inflammation of the lung in asthmatics. METHODS: We exposed 12 allergic asthmatics in two subgroups in a double-blinded randomized cross-over design, first to freshly generated ultrafine carbon particles (64 µg/m³; 6.1 ± 0.4 × 105 particles/cm³ for 2 h) and then to filtered air or vice versa with a 28-day recovery period in-between. Eighteen hours after each exposure, grass pollen was instilled into a lung lobe via bronchoscopy. Another 24 hours later, inflammatory cells were collected by means of bronchoalveolar lavage (BAL). ( TRIAL REGISTRATION: NCT00527462) RESULTS: For the entire study group, inhalation of UFP by itself had no significant effect on the allergen induced inflammatory response measured with total cell count as compared to exposure with filtered air (p = 0.188). However, the subgroup of subjects, which inhaled UFP during the first exposure, exhibited a significant increase in total BAL cells (p = 0.021), eosinophils (p = 0.031) and monocytes (p = 0.013) after filtered air exposure and subsequent allergen challenge 28 days later. Additionally, the potential of BAL cells to generate oxidant radicals was significantly elevated at that time point. The subgroup that was exposed first to filtered air and 28 days later to UFP did not reveal differences between sessions. CONCLUSIONS: Our data demonstrate that pre-allergen exposure to UFP had no acute effect on the allergic inflammation. However, the subgroup analysis lead to the speculation that inhaled UFP particles might have a long-term effect on the inflammatory course in asthmatic patients. This should be reconfirmed in further studies with an appropriate study design and sufficient number of subjects.

The timing of amniotomy, oxytocin and neuraxial analgesia and its association with labour duration and mode of birth.

PURPOSE: The objective was to study the association of different timings of intrapartum interventions with labour duration and mode of birth. METHODS: A longitudinal cohort study of 2,090 nulliparae and 1,873 multiparae with a singleton in cephalic presentation was conducted. We assessed the association between, on the one hand, the timing of augmentation with oxytocin, neuraxial analgesia and amniotomy, and, on the other hand, the time to complete dilatation, spontaneous or operative vaginal delivery or caesarean delivery, using a Cox regression model accounting for standard confounders. RESULTS: From amniotomy onwards labour was accelerated. In multiparae, amniotomy was associated with an initial 6.6-fold acceleration, decreasing first stage duration until the hazard ratio reached around 3.5, where the intervention was performed 5 h after labour onset; thereafter, acceleration continued with a hazard ratio of around 3. In nulliparae, neuraxial analgesia was associated with a shorter first stage when administered between 7 and 11 h after labour onset; the later it was performed, the less likely was spontaneous birth and the more likely an operative vaginal birth in nulliparae or a caesarean section in multiparae. The start of oxytocin augmentation was associated with acceleration towards both full dilatation and caesarean section during first stage and an increased risk of operative vaginal birth during second stage. The later oxytocin augmentation started, the more likely it was that spontaneous birth would be retarded in multiparous women. CONCLUSIONS: Applying amniotomy, oxytocin and neuraxial analgesia at their optimal timing may improve the progress and outcome of labour.

Referring physicians' intention to use hospital report cards for hospital referral purposes in the presence or absence of patient-reported outcomes: a randomized trial.

PURPOSE: This study aims to determine the intention to use hospital report cards (HRCs) for hospital referral purposes in the presence or absence of patient-reported outcomes (PROs) as well as to explore the relevance of publicly available hospital performance information from the perspective of referring physicians. METHODS: We identified the most relevant information for hospital referral purposes based on a literature review and qualitative research. Primary survey data were collected (May-June 2021) on a sample of 591 referring orthopedists in Germany and analyzed using structural equation modeling. Participating orthopedists were recruited using a sequential mixed-mode strategy and randomly allocated to work with HRCs in the presence (intervention) or absence (control) of PROs. RESULTS: Overall, 420 orthopedists (mean age 53.48, SD 8.04) were included in the analysis. The presence of PROs on HRCs was not associated with an increased intention to use HRCs (p = 0.316). Performance expectancy was shown to be the most important determinant for using HRCs (path coefficient: 0.387, p < .001). However, referring physicians have doubts as to whether HRCs can help them. We identified "complication rate" and "the number of cases treated" as most important for the hospital referral decision making; PROs were rated slightly less important. CONCLUSIONS: This study underpins the purpose of HRCs, namely to support referring physicians in searching for a hospital. Nevertheless, only a minority would support the use of HRCs for the next hospital search in its current form. We showed that presenting relevant information on HRCs did not increase their use intention.

Favorable acceptance of mini-tablets compared with syrup: a randomized controlled trial in infants and preschool children.

OBJECTIVE: To evaluate acceptability of 2 mm solid dosage forms (mini-tablets) as an alternative administration modality in young children in comparison with syrup. STUDY DESIGN: Three hundred six pediatric in- and outpatients aged 6 months-5 years (51 in each of 6 age groups) were recruited. An open, randomized cross-over study was conducted to compare acceptability and capability to swallow 2 mm uncoated or coated mini-tablets vs 3 mL syrup. RESULTS: In the overall patient population of 306 children, the acceptability of uncoated mini-tablets was superior to syrup (difference in proportions 14.8%, 95% CI 10.2-19.4; P < .0001). In line with this finding, the level of capability to swallow was higher for uncoated mini-tablets compared with syrup as well (difference in proportions 12.3%, 95% CI 5.4-19.3; P = .0008). All 3 pharmaceutical formulations were well tolerated, and none of the 306 children inhaled or coughed because of the syrup or the uncoated mini-tablet; only 2 of the 306 children (both in age group 0.5-1 year) coughed because of the coated mini-tablet, in both cases without clinical relevance. CONCLUSIONS: Mini-tablets are a valuable alternative to syrup for children 6 months-6 years of age and are more acceptable compared with liquid formulation. Regulatory bodies such as Food and Drug Administration and European Medicine Agency are encouraged to take our data into account for guideline updates and future drug approval processes.

Suitability and user acceptance of the eResearch system "Prospective Monitoring and Management App (PIA)"-The example of an epidemiological study on infectious diseases.

BACKGROUND: The eResearch system "Prospective Monitoring and Management App (PIA)" allows researchers to implement questionnaires on any topic and to manage biosamples. Currently, we use PIA in the longitudinal study ZIFCO (Integrated DZIF Infection Cohort within the German National Cohort) in Hannover (Germany) to investigate e.g. associations of risk factors and infectious diseases. Our aim was to assess user acceptance and compliance to determine suitability of PIA for epidemiological research on transient infectious diseases. METHODS: ZIFCO participants used PIA to answer weekly questionnaires on health status and report spontaneous onset of symptoms. In case of symptoms of a respiratory infection, the app requested participants to self-sample a nasal swab for viral analysis. To assess user acceptance, we implemented the System Usability Scale (SUS) and fitted a linear regression model on the resulting score. For investigation of compliance with submitting the weekly health questionnaires, we used a logistic regression model with binomial response. RESULTS: We analyzed data of 313 participants (median age 52.5 years, 52.4% women). An average SUS of 72.0 reveals good acceptance of PIA. Participants with a higher technology readiness score at the beginning of study participation also reported higher user acceptance. Overall compliance with submitting the weekly health questionnaires showed a median of 55.7%. Being female, of younger age and being enrolled for a longer time decreased the odds to respond. However, women over 60 had a higher chance to respond than women under 60, while men under 40 had the highest chance to respond. Compliance with nasal swab self-sampling was 77.2%. DISCUSSION: Our findings show that PIA is suitable for the use in epidemiologic studies with regular short questionnaires. Still, we will focus on user engagement and gamification for the further development of PIA to help incentivize regular and long-term participation.

The elicitation of patient and physician preferences for calculating consumer-based composite measures on hospital report cards: results of two discrete choice experiments.

PURPOSE: The calculation of aggregated composite measures is a widely used strategy to reduce the amount of data on hospital report cards. Therefore, this study aims to elicit and compare preferences of both patients as well as referring physicians regarding publicly available hospital quality information METHODS: Based on systematic literature reviews as well as qualitative analysis, two discrete choice experiments (DCEs) were applied to elicit patients' and referring physicians' preferences. The DCEs were conducted using a fractional factorial design. Statistical data analysis was performed using multinomial logit models RESULTS: Apart from five identical attributes, one specific attribute was identified for each study group, respectively. Overall, 322 patients (mean age 68.99) and 187 referring physicians (mean age 53.60) were included. Our models displayed significant coefficients for all attributes (p < 0.001 each). Among patients, "Postoperative complication rate" (20.6%; level range of 1.164) was rated highest, followed by "Mobility at hospital discharge" (19.9%; level range of 1.127), and ''The number of cases treated" (18.5%; level range of 1.045). In contrast, referring physicians valued most the ''One-year revision surgery rate'' (30.4%; level range of 1.989), followed by "The number of cases treated" (21.0%; level range of 1.372), and "Postoperative complication rate" (17.2%; level range of 1.123) CONCLUSION: We determined considerable differences between both study groups when calculating the relative value of publicly available hospital quality information. This may have an impact when calculating aggregated composite measures based on consumer-based weighting.

Comparison of different thoracic trauma scoring systems in regards to prediction of post-traumatic complications and outcome in blunt chest trauma.

BACKGROUND: As accurate assessment of thoracic injury severity in the early phase after trauma is difficult, we compared different thoracic trauma scores regarding their predictive ability for the development of post-traumatic complications and mortality. MATERIALS AND METHODS: Two hundred seventy-eight multiple trauma patients (ISS ≥ 16) age > 16 y with severe blunt chest trauma (AIS(chest) ≥ 3) admitted between 2000 and 2009 to Level I Trauma center were included. Exclusion criteria were severe traumatic brain injury (AIS(head) ≥ 3) and penetrating thoracic trauma. The association between AIS(chest), Pulmonary Contusion score (PCS), Wagner-score and Thoracic Trauma Severity score (TTS), and duration of ventilation, length of ICU stay, development of post-traumatic complications, and mortality was investigated. Statistical analysis was performed with χ(2)-test, ANOVA, logistic regression, and receiver operating characteristic (ROC) curve. RESULTS: Patients' mean age was 42.7 ± 17.0 y, the mean injury severity score was 28.7 ± 9.3 points. Overall, 60 patients (21.6%) developed ARDS, 143 patients (51.4%) SIRS, 110 patients (39.6%) sepsis, and 36 patients (13.0%) MODS. Twenty-two patients (7.9%) died. Among the examined thoracic trauma scores only the TTS was an independent predictor of mortality. With the TTS showing the best prediction power, the TTS, PCS, and Wagner-score were independent predictors of ventilation time, length of ICU stay, and the development of post-traumatic ARDS and MODS. CONCLUSIONS: Thoracic trauma scores combining anatomical and physiologic parameters like the TTS seem to be most suitable for severity assessment and prediction of outcome in multiple trauma patients with concomitant blunt chest trauma.

Tip apex distance, hip screw placement, and neck shaft angle as potential risk factors for cut-out failure of hip screws after surgical treatment of intertrochanteric fractures.

PURPOSE: To describe the quality of osteosynthesis after intertrochanteric fractures evaluation of tip apex distance (TAD) and position of the hip screw have been established. Furthermore, a slightly valgus fracture reduction has been suggested to reduce the risk of cut-out failure. However, uniform recommendations for optimal screw positioning and fracture reduction are still missing. The purpose of our study was to confirm potential risk factors for cut-out of hip screws of intertrochanteric fractures and to provide recommendations for practical clinical use. METHODS: A retrospective analysis of all patients with intertrochanteric fractures treated with a DHS or a gamma nail between January of 2007 and May of 2010 was performed at a level I trauma center. RESULTS: Two hundred thirty-five patients with intertrochanteric fractures after intra- and extramedullary stabilization were analyzed. A TAD of more than 25 mm was demonstrated to be the most important factor for cut-out in stable and unstable fractures. Fracture reduction with a valgus NSA of 5-10° was associated with a trend towards a lower rate of screw cut-out while an anterior placement of the screw (Parker's ratio index of <40) significantly increased cut-out incidence. CONCLUSIONS: According to our results, the TAD should not exceed 25 mm in stable (AO/OTA A1) as well as unstable (AO/OTA A2) fractures. An increased anterior hip screw placement should be avoided while fracture reduction with a slight valgus Neck Shaft seems favorable.

A semiparametric approach for meta-analysis of diagnostic accuracy studies with multiple cut-offs.

The accuracy of a diagnostic test is often expressed using a pair of measures: sensitivity (proportion of test positives among all individuals with target condition) and specificity (proportion of test negatives among all individuals without target condition). If the outcome of a diagnostic test is binary, results from different studies can easily be summarized in a meta-analysis. However, if the diagnostic test is based on a discrete or continuous measure (e.g., a biomarker), several cut-offs within one study as well as among different studies are published. Instead of taking all information of the cut-offs into account in the meta-analysis, a single cut-off per study is often selected arbitrarily for the analysis, even though there are statistical methods for the incorporation of several cut-offs. For these methods, distributional assumptions have to be met and/or the models may not converge when specific data structures occur. We propose a semiparametric approach to overcome both problems. Our simulation study shows that the diagnostic accuracy is under-estimated, although this underestimation in sensitivity and specificity is relatively small. The comparative approach of Steinhauser et al. is better in terms of coverage probability, but may lead to convergence problems. In addition to the simulation results, we illustrate the application of the semiparametric approach using a published meta-analysis for a diagnostic test differentiating between bacterial and viral meningitis in children.

The use intention of hospital report cards among patients in the presence or absence of patient-reported outcomes.

BACKGROUND: So far, the adoption of hospital report cards (HRCs) falls short of expectations. One promising strategy is to modify the content of HRCs by presenting patient-reported outcomes (PROs). OBJECTIVE: To identify the key determinants influencing patients to use HRCs for hospital decision making and determine the effect of presenting PROs on HRCs on their use intention. METHODS: Primary survey data were collected (5/6-2021) on a sample of 2000 randomly selected insurees from a German statutory health insurance who have undergone elective hip arthroplasty surgery. RESULTS: Overall, 447 participants (mean age 66.56) completed the survey and were included in the analysis. Respondents rated "PROs" as most important for the hospital choice followed by "Mobility at hospital discharge" and "Confirmed diagnosis rate". Patients generally perceive HRCs to be a good idea that makes searching for a hospital more interesting. We identified attitude and social influence as the most important determinants for using HRCs (p<.001 each). The presence of PROs on HRCs was not associated with an increased intention to use HRCs neither in our descriptive analysis (p=.593), nor in our research model (p=.763). CONCLUSIONS: Patients value PROs to be an important information for choosing a hospital. Nevertheless, health policy makers should note that presenting PROs on HRCs as a single approach is not likely to increase the use of HRCs.

In vitro experimental (211)At-anti-CD33 antibody therapy of leukaemia cells overcomes cellular resistance seen in vivo against gemtuzumab ozogamicin.

PURPOSE: Monoclonal anti-CD33 antibodies conjugated with toxic calicheamicin derivative (gemtuzumab ozogamicin, GO) are a novel therapy option for acute myeloid leukaemia (AML). Key prognostic factors for patients with AML are high CD33 expression on the leukaemic cells and the ability to overcome mechanisms of resistance to cytotoxic chemotherapies, including drug efflux or other mechanisms decreasing apoptosis. Alpha particle-emitting radionuclides overwhelm such anti-apoptotic mechanisms by producing numerous DNA double-stranded breaks (DSBs) accompanied by decreased DNA repair. METHODS: We labelled anti-CD33 antibodies with the alpha-emitter (211)At and compared survival of leukaemic HL-60 and K-562 cells treated with the (211)At-labelled antibodies, GO or unlabelled antibodies as controls. We also measured caspase-3/7 activity, DNA fragmentation and necrosis in HL-60 cells after treatment with the different antibodies or with free (211)At. RESULTS: The mean labelling ratio of (211)At-labelled antibodies was 1:1,090 +/- 364 (range: 1:738-1:1,722) in comparison to 2-3:1 for GO. Tumour cell binding of (211)At-anti-CD33 was high in the presence of abundant CD33 expression and could be specifically blocked by unlabelled anti-CD33. (211)At-anti-CD33 decreased survival significantly more than did GO at comparable dilution (1:1,000). No significant differences in induction of apoptosis or necrosis or DNA DSB or in decreased survival were observed after (211)At-anti-CD33 (1:1,090) versus GO (1:1) treatment. CONCLUSION: Our results suggest that (211)At is a promising, highly cytotoxic radioimmunotherapy in CD33-positive leukaemia and kills tumour cells more efficiently than does calicheamicin-conjugated antibody. Labelling techniques leading to higher chemical yield and specific activities must be developed to increase (211)At-anti-CD33 therapeutic effects.

Lesion dose in differentiated thyroid carcinoma metastases after rhTSH or thyroid hormone withdrawal: 124I PET/CT dosimetric comparisons.

PURPOSE: Renal radioiodine excretion is ~50% faster during euthyroidism versus hypothyroidism. We therefore sought to assess lesion dose/GBq of administered 131I activity (LDpA) in iodine-avid metastases (IAM) of differentiated thyroid carcinoma (DTC) in athyreotic patients after recombinant human thyroid-stimulating hormone (rhTSH) versus after thyroid hormone withdrawal (THW). METHODS: We retrospectively compared mean LDpA between groups of consecutive patients (N=63) receiving 124I positron emission tomography/computed tomography (124I PET/CT) aided by rhTSH (n=27) or THW (n=36); we prospectively compared LDpA after these stimulation methods within another individual. Data derived from serial PET scans and one CT scan performed 2-96 h post-124I ingestion. A mixed model analysis of covariance (ANCOVA) calculated the treatment groups' mean LDpAs adjusting for statistically significant baseline intergroup differences: non-IAM were more prevalent, median IAM count/patient lower in cervical lymph nodes and higher in distant sites, median stimulated thyroglobulin higher, mean cumulative radioiodine activity greater and prior diagnostic scintigraphy more frequent in the rhTSH patients. RESULTS: Mean LDpAs were: rhTSH group (n=71 IAM), 30.6 Gy/GBq; THW group (n=66 IAM), 51.8 Gy/GBq. The difference in group means (rhTSH less THW), -21.2 Gy/GBq, was statistically non-significant (p=0.1667). However, the 95% confidence interval of that difference (-51.4 to +9 Gy/GBq) suggested a trend favouring THW. The within-patient comparison found 2.9- to 10-fold higher LDpAs under THW. CONCLUSION: We found some suggestions, but no statistically significant evidence, that rhTSH administration results in a lower radiation dose to DTC metastases than does THW. A large, well-controlled, prospective within-patient study should resolve this issue.

The diagnostic value of erythrocyte sedimentation rate in management of brain tumors.

OBJECTIVE: Erythrocyte sedimentation rate (ESR) is considered as an indicator of inflammatory processes, and it has a prognostic value in the management of specific neoplastic diseases. It also responds to surgical intervention. There is very little data about the alteration of ESR in patients with brain tumors and information on its course after intracranial tumor surgery is completely lacking. METHODS: ESR was measured for 10 days in 46 patients (19 women and 27 men; mean age: 49.7 years; range: 13-70 years) who underwent elective craniotomy for tumor microsurgery (70-425 minutes with a mean of 230 minutes) under general anaesthesia. Blood samples were taken on the day before surgery and on each consecutive day after surgery for 10 days. The standard method of measuring ESR was based on the technique first described by Westergren. RESULTS: The mean ESR level on the day before surgery was 8.26 +/- 7.27 mm/h after 1 hour and 14.80 +/- 10.36 mm/h after 2 hours. After tumor surgery, ESR increased stepwise. The mean peak value of 22.89 +/- 13.41 mm/h after the first hour was reached on the third post-operative day. Whereas mean values varied over time, ESR remained increased and did not decline to normal values until the tenth post-operative day. The mean ESR peak value was higher in patients having undergone surgery for intra-axial lesions (31.36 +/- 30.43 mm/h on the post-operative day 6) as compared to patients with extra-axial lesions (21.31 +/- 12.20 mm/h on the post-operative day 3). CONCLUSION: ESR is not relevantly increased in patients harboring brain tumors. Because it remains elevated until the tenth post-operative day after uneventful craniotomy and generally responds more slowly than other indicators like C-reactive protein, it is also not suitable for the detection of post-operative infective complications.