Imaging for local recurrence of breast cancer.

PURPOSE: Isolated locoregional recurrence of breast cancer (ILRR) and contralateral breast cancer (CBC) affect up to 20% of all breast cancer (BC) patients in the first 20 years after primary diagnosis. Treatment options comprise surgical interventions and further systemic therapies depending on the histological subtype. Patients with hereditary breast or ovarian cancer (HBOC) undergo MRI, mammography, and ultrasound in the aftercare of BC, while non-HBOC (nHBOC) patients do not regularly receive MRI. Since early detection is crucial for morbidity and mortality, the evaluation and constant improvement of imaging methods of the breast is necessary. METHODS: We retrospectively analyzed the data of 1499 former BC patients that received imaging of the breast at a tertiary-care university hospital between 2015 and 2020. The analysis comprised various patient characteristics, such as breast density, age, tumor size and subtype, and their influence on BC detection rates by the different imaging methods. RESULTS: Within the patient sample, 176 individuals (11.7% of former BC patients) were diagnosed with either ILRR or CBC. CBC was observed in 32.4% of patients, while both ILRR and secondary breast cancer occurred in 20.5% and 23.9% of all patients. Sensitivity of MRI, mammography, and ultrasound for recurrent malignancy was 97.9%, 66.3%, and 67.8%, respectively. ILRR and CBC detection rates were similar for patients with and without HBOC history. Lower breast density and larger tumor size increased the detection rates of all imaging modalities. CONCLUSION: In breast cancer survivors, MRI might improve the early detection of ILRR and CBC in both HBOC and nHBOC patients.

Origin-Independent Dynamic Polarizability Density from Coupled Cluster Response Theory.

The calculation of the origin-independent density of the dynamic electric dipole polarizability, previously presented for uncorrelated and density functional theory (DFT)-based methods, has been developed and implemented at the coupled cluster singles and doubles (CCSD) level of theory. A pointwise analysis of polarizability densities calculated for a number of molecules at Hartree-Fock (HF) and CCSD clearly shows that the electron correlation effect is much larger than one would argue considering the integrated dipole electric polarizability alone. Large error compensations occur during the integration process, which hide fairly large deviations mainly located in the internuclear regions. The same is observed when calculated CCSD and B3LYP polarizability densities are compared, with the remarkable feature that positive/negative deviations between CCSD and HF reverse sign, becoming negative/positive when comparing CCSD to B3LYP.

Potential of employing a quantum iterative reconstruction algorithm for ultra-high-resolution photon-counting detector CT of the hip.

INTRODUCTION: This study investigated the image quality of a new quantum iterative reconstruction algorithm (QIR) for high resolution photon-counting CT of the hip. METHODS: Using a first-generation photon-counting CT scanner, five cadaveric specimens were examined with ultra-high-resolution protocols matched for radiation dose. Images were post-processed with a sharp convolution kernel and five different strength levels of iterative reconstruction (QIR 0 - QIR 4). Subjective image quality was rated independently by three radiologists on a five-point scale. Intraclass correlation coefficients (ICC) were computed for assessing interrater agreement. Objective image quality was evaluated by means of contrast-to-noise-ratios (CNR) in bone and muscle tissue. RESULTS: For osseous tissue, subjective image quality was rated best for QIR 2 reformatting (median 5 [interquartile range 5-5]). Contrarily, for soft tissue, QIR 4 received the highest ratings among compared strength levels (3 [3-4]). Both ICCbone (0.805; 95% confidence interval 0.711-0.877; p < 0.001) and ICCmuscle (0.885; 0.824-0.929; p < 0.001) suggested good interrater agreement. CNR in bone and muscle tissue increased with ascending strength levels of iterative reconstruction with the highest results recorded for QIR 4 (CNRbone 29.43 ± 2.61; CNRmuscle 8.09 ± 0.77) and lowest results without QIR (CNRbone 3.90 ± 0.29; CNRmuscle 1.07 ± 0.07) (all p < 0.001). CONCLUSION: Reconstructing photon-counting CT data with an intermediate QIR strength level appears optimal for assessment of osseous tissue, whereas soft tissue analysis benefitted from applying the highest strength level available. IMPLICATIONS FOR PRACTICE: Quantum iterative reconstruction technique can enhance image quality by significantly reducing noise and improving CNR in ultra-high resolution CT imaging of the hip.

Orodispersible films - Recent developments and new applications in drug delivery and therapy.

Orodispersible films (ODF) are innovative drug formulations that introduce a promising approach to pharmacotherapy. They represent single- or multi-layer polymer films that show sufficient stability but disintegrate easily. Often no water is needed for ingestion. Therefore, ODF are suitable for patients with swallowing difficulties such as elderly people, children, or patients with restricted transport in the gastrointestinal tract. Also, to avoid the first-pass effect when the drug is already absorbed via the mucosa. Initially developed as niche products ODFs are currently the subject of industrial and university research as dosage forms for improved application and compliance for medical treatment of a multitude of different diseases. An interesting aspect is that ODF can also be produced in an individualized way. This can support the trend toward personalized medicine. Here, we provide at first an overview of the historical background, characterization, and composition of ODFs. Subsequently, technical aspects of the manufacturing process, including three-dimensional printing technology and inkjet printing will be reviewed. As ODFs are promising drug delivery systems for customized small-scale pharmacy preparations, we place particular emphasis on product examples giving the possibility for individualization for their consumers. Finally, we summarize formulations, applications in development, limitations, and the current patent situation.

Quantitative and qualitative assessment of plasma cell dyscrasias in dual-layer spectral CT.

OBJECTIVES: Virtual non-calcium (VNCa) images could improve assessment of plasma cell dyscrasias by enhancing visibility of bone marrow. Thus, VNCa images from dual-layer spectral CT (DLCT) were evaluated at different calcium suppression (CaSupp) indices, correlating results with apparent diffusion coefficient (ADC) values from MRI. METHODS: Thirty-two patients with initial clinical diagnosis of a plasma cell dyscrasia before any chemotherapeutic treatment, who had undergone whole-body low-dose DLCT and MRI within 2 months, were retrospectively enrolled. VNCa images with CaSupp indices ranging from 25 to 95 in steps of 10, conventional CT images, and ADC maps were quantitatively analyzed using region-of-interests in the vertebral bodies C7, T12, L1-L5, and the iliac bone. Independent two-sample t-test, Wilcoxon-signed-rank test, Pearson's correlation, and ROC analysis were performed. RESULTS: Eighteen patients had a non-diffuse, 14 a diffuse infiltration in conventional MRI. A significant difference between diffuse and non-diffuse infiltration was shown for VNCa-CT with CaSupp indices from 55 to 95, for conventional CT, and for ADC (each p < 0.0001). Significant quantitative correlation between VNCa-CT and MRI could be found with strongest correlation at CaSupp index 65 for L3 (r = 0.68, p < 0.0001) and averaged L1-L5 (r = 0.66, p < 0.0001). The optimum CT number cut-off point for differentiation between diffuse and non-diffuse infiltration at CaSupp index 65 for averaged L1-L5 was -1.6 HU (sensitivity 78.6%, specificity 75.0%). CONCLUSION: Measurements in VNCa-CT showed the highest correlation with ADC at CaSupp index 65. VNCa technique may prove useful for evaluation of bone marrow infiltration if MRI is not feasible. KEY POINTS: • VNCa-CT images can support the evaluation of bone marrow infiltration in plasma cell dyscrasias. • VNCa measurements of vertebral bodies show significant correlation with ADC in MRI. • Averaging L1-L5 at CaSupp index 65 allowed quantitative detection of infiltration comparable to MRI ADC.

Pedestrian hit by a car impacted metal pole: reconstructing the head load.

Fatal head injuries are frequently seen in pedestrians hit by motorized vehicles. In our case, the pedestrian sustained a devastating head injury with skull splitting in the mediosagittal plane. A car collided with a traffic sign causing a bending of the pole. The metal pole hit a man standing close beside it; the man had a head injury severity that is more commonly due to falling objects than due to traffic accidents. Assuming a head mass of 5 kg, simplified calculations yield maximum contact forces of ca. 36 kN exceeding mean parietal fracture forces which are in the order of magnitude of 12.5 kN. The influences of the effective body mass and the horizontal distance between the pole and the pedestrian on maximum contact forces are investigated. High contact forces in our case can be mainly explained by the comparably high impact velocity and by a partial mass transfer of the total car mass to the pole.

Reliability and main findings of the flexible endoscopic evaluation of swallowing-Tensilon test in patients with myasthenia gravis and dysphagia.

BACKGROUND AND PURPOSE: Diagnosis of pharyngeal dysphagia caused by myasthenia gravis (MG) based on clinical examination alone is often challenging. Flexible endoscopic evaluation of swallowing (FEES) combined with Tensilon (edrophonium) application, referred to as the FEES-Tensilon test, was developed to improve diagnostic accuracy and to detect the main symptoms of pharyngeal dysphagia in MG. Here we investigated inter- and intra-rater reliability of the FEES-Tensilon test and analyzed the main endoscopic findings. METHODS: Four experienced raters reviewed a total of 20 FEES-Tensilon test videos in randomized order. Residue severity was graded at four different pharyngeal spaces before and after Tensilon administration. All interpretations were performed twice per rater, 4 weeks apart (a total of 160 scorings). Intra-rater test-retest reliability and inter-rater reliability levels were calculated. RESULTS: The most frequent FEES findings in patients with MG before Tensilon application were prominent residues of semi-solids spread all over the hypopharynx in varying locations. The reliability level of the interpretation of the FEES-Tensilon test was excellent regardless of the rater's profession or years of experience with FEES. All four raters showed high inter- and intra-reliability levels in interpreting the FEES-Tensilon test based on residue clearance (kappa = 0.922, 0.981). The degree of residue normalization in the vallecular space after Tensilon application showed the highest inter- and intra-rater reliability level (kappa = 0.863, 0.957) followed by the epiglottis (kappa = 0.813, 0.946) and pyriform sinuses (kappa = 0.836, 0.929). CONCLUSION: Interpretation of the FEES-Tensilon test based on residue severity and degree of Tensilon clearance, especially in the vallecular space, is consistent and reliable.

The bioequivalence of a single intravenous administration of the anesthetic alfaxalone in cyclodextrin versus alfaxalone in cyclodextrin plus preservatives in cats.

To demonstrate the bioequivalence of alfaxalone in cyclodextrin (Reference Product) to a formulation of alfaxalone in cyclodextrin also containing the preservatives ethanol, chlorocresol, and benzethonium chloride (Test Product) when administered for the purpose of inducing anesthesia in the cat. Blinded, single-dose, randomized, two-period, two-sequence, cross-over bioequivalence study with a 7-day washout period between treatments. Twenty-four (12 neutered males and 12 intact females), healthy, adult cats weighing 4.1±0.9 kg. Cats were administered 5 mg/kg IV of alfaxalone in the Reference or Test Product using a randomized cross-over design. One-milliliter venous blood samples were collected at predetermined time points to 12 hr after drug administration to determine alfaxalone plasma concentration over time. Alfaxalone concentrations were determined by a validated analytical testing method using HPLC-MS/MS. Plasma profiles of alfaxalone concentration against time were analyzed by noncompartmental analysis. The pivotal variables for bioequivalence were AUClast and Cmax . Equivalence was achieved if the 90% confidence interval for AUClast and Cmax fell into the asymmetric ±20% interval (0.80-1.25). Physiological variables, quality of anesthesia visual analog scale (VAS) scoring and anesthetic event times were recorded. ANOVA or ANCOVA (single time point), RMANOVA or RMANCOVA (multiple time point) was used for normally distributed data. GLIMMIX was used for nonnormally distributed data. VAS scores were analyzed as for blood bioequivalence data. Variables were evaluated for safety and assessed at alpha = 0.10. Cmax and AUClast for Reference and Test Products were statistically bioequivalent. No physiological variables except for a drug by time interaction for respiratory rate differed between treatment groups, and this difference was not clinically relevant. No anesthetic event times or VAS scores for quality of anesthesia were different between treatment groups. Neither formulation caused pain upon injection. The Reference and Test Products are pharmaceutically bioequivalent formulations when administered as a single intravenous administration for the purpose of induction of anesthesia in cats.

X-linked inhibitor of apoptosis protein mediates tumor cell resistance to antibody-dependent cellular cytotoxicity.

Inflammatory breast cancer (IBC) is the deadliest, distinct subtype of breast cancer. High expression of epidermal growth factor receptors [EGFR or human epidermal growth factor receptor 2 (HER2)] in IBC tumors has prompted trials of anti-EGFR/HER2 monoclonal antibodies to inhibit oncogenic signaling; however, de novo and acquired therapeutic resistance is common. Another critical function of these antibodies is to mediate antibody-dependent cellular cytotoxicity (ADCC), which enables immune effector cells to engage tumors and deliver granzymes, activating executioner caspases. We hypothesized that high expression of anti-apoptotic molecules in tumors would render them resistant to ADCC. Herein, we demonstrate that the most potent caspase inhibitor, X-linked inhibitor of apoptosis protein (XIAP), overexpressed in IBC, drives resistance to ADCC mediated by cetuximab (anti-EGFR) and trastuzumab (anti-HER2). Overexpression of XIAP in parental IBC cell lines enhances resistance to ADCC; conversely, targeted downregulation of XIAP in ADCC-resistant IBC cells renders them sensitive. As hypothesized, this ADCC resistance is in part a result of the ability of XIAP to inhibit caspase activity; however, we also unexpectedly found that resistance was dependent on XIAP-mediated, caspase-independent suppression of reactive oxygen species (ROS) accumulation, which otherwise occurs during ADCC. Transcriptome analysis supported these observations by revealing modulation of genes involved in immunosuppression and oxidative stress response in XIAP-overexpressing, ADCC-resistant cells. We conclude that XIAP is a critical modulator of ADCC responsiveness, operating through both caspase-dependent and -independent mechanisms. These results suggest that strategies targeting the effects of XIAP on caspase activation and ROS suppression have the potential to enhance the activity of monoclonal antibody-based immunotherapy.

Towards a Mg Lattice Clock: Observation of the

We optically excite the electronic state 3s3p ^{3}P_{0} in ^{24}Mg atoms, laser cooled and trapped in a magic-wavelength lattice. An applied magnetic field enhances the coupling of the light to the otherwise strictly forbidden transition. We determine the magic wavelength, the quadratic magnetic Zeeman shift, and the transition frequency to be 468.46(21) nm, -206.6(2.0) MHz/T^{2}, and 655 058 646 691(101) kHz, respectively. These are compared with theoretical predictions and results from complementary experiments. We also develop a high-precision relativistic structure model for magnesium, give an improved theoretical value for the blackbody radiation shift, and discuss a clock based on bosonic magnesium.

Molecular and biochemical alterations in tubular epithelial cells of patients with isolated methylmalonic aciduria.

Methylmalonic acidurias (MMAurias) are a group of inherited disorders in the catabolism of branched-chain amino acids, odd-chain fatty acids and cholesterol caused by complete or partial deficiency of methylmalonyl-CoA mutase (mut(0) and mut(-) subtype respectively) and by defects in the metabolism of its cofactor 5'-deoxyadenosylcobalamin (cblA, cblB or cblD variant 2 type). A long-term complication found in patients with mut(0) and cblB variant is chronic tubulointerstitial nephritis. The underlying pathomechanism has remained unknown. We established an in vitro model of tubular epithelial cells from patient urine (hTEC; 9 controls, 5 mut(0), 1 cblB). In all human tubular epithelial cell (hTEC) lines we found specific tubular markers (AQP1, UMOD, AQP2). Patient cells showed disturbance of energy metabolism in glycolysis, mitochondrial respiratory chain and Krebs cycle in concert with increased reactive oxygen species (ROS) formation. Electron micrographs indicated increased autophagosome production and endoplasmic reticulum stress, which was supported by positive acridine orange staining and elevated levels of LC3 II, P62 and pIRE1. Screening mTOR signaling revealed a release of inhibition of autophagy. Patient hTEC produced and secreted elevated amounts of the pro-inflammatory cytokine IL8, which was highly correlated with the acridine orange staining. Summarizing, hTEC of MMAuria patients are characterized by disturbed energy metabolism and ROS production that lead to increased autophagy and IL8 secretion.

Melissa officinalis extract induces apoptosis and inhibits proliferation in colon cancer cells through formation of reactive oxygen species.

PURPOSE: Efficient strategies for the prevention of colon cancer are extensively being explored, including dietary intervention and the development of novel phytopharmaceuticals. Safe extracts of edible plants contain structurally diverse molecules that can effectively interfere with multi-factorial diseases such as colon cancer. In this study, we describe the antiproliferative and proapoptotic effects of ethanolic lemon balm (Melissa officinalis) leaves extract in human colon carcinoma cells. We further investigated the role of extra- and intracellular reactive oxygen species (ROS). METHODS: Antitumor effects of lemon balm extract (LBE) were investigated in HT-29 and T84 human colon carcinoma cells. Inhibition of proliferation was analyzed by DNA quantification. The causal cell cycle arrest was determined by flow cytometry of propidium iodide-stained cells and by immunoblotting of cell cycle regulator proteins. To investigate apoptosis, cleavage of caspases 3 and 7 was detected by immunoblotting and fluorescence microscopy. Phosphatidylserine externalization was measured by Annexin V assays. Mechanistic insights were gained by measurement of ROS using the indicator dyes CM-H2DCFDA and Cell ROX Green. RESULTS: After 3 and 4 days of treatment, LBE inhibited the proliferation of HT-29 and T84 colon carcinoma cells with an inhibitory concentration (IC50) of 346 and 120 µg/ml, respectively. Antiproliferative effects were associated with a G2/M cell cycle arrest and reduced protein expression of cyclin dependent kinases (CDK) 2, 4, 6, cyclin D3, and induced expression of cyclin-dependent kinase inhibitor 2C (p18) and 1A (p21). LBE (600 µg/ml) induced cleavage of caspases 3 and 7 and phosphatidylserine externalization. LBE-induced apoptosis was further associated with formation of ROS, whereas quenching of ROS by antioxidants completely rescued the colon carcinoma cells from LBE-induced apoptosis. CONCLUSIONS: Lemon balm (Melissa officinalis) extract inhibits the proliferation of colon carcinoma cells and induces apoptosis through formation of ROS. Taken together, LBE or subfractions thereof could be used for the prevention of colon cancer.

[Institutionalised dying in Germany. Trends in place of death distribution: home, hospitals and nursing homes]. / Institutionalisiertes Sterben in Deutschland. Trends in der Sterbeortverteilung: zu Hause, Krankenhaus und Pflegeheim.

BACKGROUND: The aim of this study is to identify the degree of institutionalised dying and to assess the differentiation between place of death, be it at a hospital, in a nursing home or at home (with/or without home care), as well as to illustrate trends in the place of death distribution. DATA AND METHODS: Process-produced routine data of the deaths of patients insured with the statutory health insurance "Gmünder Ersatzkasse" (GEK, n = 59,922) are used to calculate distributions of the deceased population (≥ 30 years old) from 2000-2009. RESULTS: In 2009, about 248,000 (29 %) and 598,000 (71 %) people in Germany died at home and in an institution, respectively. During the last 10 years the degree of institutionalised dying has increased by 6 percentage points. Women die more frequently in institutions than men (74 % compared to 67 %). For older age groups, dying in nursing homes becomes more prominent than dying in hospitals. CONCLUSION: The discrepancy between the preferred (at home) and empirically ascertained (institutions) place of death could increase even further as a result of the demographic as well as disease-specific developments in Germany.

A new paradigm to understand and treat diabetic neuropathy.

The clinical symptoms of diabetic neuropathy (DN) manifest in a time dependent manner as a positive symptoms (i. e. pain, hypersensitivity, tingling, cramps, cold feet etc.) during its early stages and by a loss of function (i. e. loss of sensory perception, delayed wound healing etc.) predominating in the later stages. Elevated blood glucose alone cannot explain the development and progression of DN and the lowering of blood glucose is insufficient in preventing and/or reversing neuropathy in patients with type 2 diabetes. Recently it has been shown that the endogenous reactive metabolite methylglyoxal (MG) can contribute to the gain of function via post-translational modification in DN of neuronal ion channels involved in chemosensing and action potential generation in nociceptive nerve endings. Dicarbonyls, such as MG, that are elevated in diabetic patients, modify DNA as well as extra- and intracellular proteins, leading to the formation of advanced glycation endproducts (AGEs). Increased formation of AGEs leads to increased cellular stress, dysfunction and ultimately cell death. The interaction of AGE-modified proteins through cell surface receptors, such as RAGE, can lead to increased cellular activation and sustained inflammatory responses, which are the molecular hallmarks of the later, degenerative, stages of DN. The direct and indirect effects of dicarbonyls on nerves or neuronal microvascular network provides a unifying mechanism for the development and progression of DN. Targeting the accumulation of MG and/or prevention of RAGE interactions may therefore provide new, more effective, therapeutic approaches for the treatment of DN.

Predictive value of longitudinal whole-body magnetic resonance imaging in patients with smoldering multiple myeloma.

Previous studies demonstrated the relevance of focal lesions (FL) in whole-body magnetic resonance imaging (wb-MRI) at the initial workup of patients with smoldering multiple myeloma (SMM). The aim of this study was to assess the effects of longitudinal wb-MRIs on progression into multiple myeloma (MM). Sixty-three patients with SMM were analyzed who received at least two wb-MRIs for follow-up before progression into MM. Radiological progressive disease (MRI-PD) was defined as detection of new FL or increase in diameter of existing FL and a novel or progressive diffuse infiltration. Radiological stable disease (MRI-SD) was defined by no change compared with the prior MRI. Patients were followed-up every 3-6 months, including a serological and clinical evaluation. One Hundred and eighty-two wb-MRIs were analyzed. MRI-PD occurred in 31 patients (49%), and 25 (40%) patients developed MM. MRI-PD was highly significantly associated with progression into MM, regardless of findings at the initial MRI. In multivariate analysis, MRI-PD remained a risk factor, independent of relevant baseline parameters like serum monoclonal protein or ⩾95% aberrant plasma cells in the bone marrow. Patients with MRI-SD had no higher risk of progression, even when FL were present at the initial MRI. Therefore, MRI is suitable for the follow-up of patients with SMM.

Therapeutic safety of high myocardial expression levels of the molecular inotrope S100A1 in a preclinical heart failure model.

Low levels of the molecular inotrope S100A1 are sufficient to rescue post-ischemic heart failure (HF). As a prerequisite to clinical application and to determine the safety of myocardial S100A1 DNA-based therapy, we investigated the effects of high myocardial S100A1 expression levels on the cardiac contractile function and occurrence of arrhythmia in a preclinical large animal HF model. At 2 weeks after myocardial infarction domestic pigs presented significant left ventricular (LV) contractile dysfunction. Retrograde application of AAV6-S100A1 (1.5 × 10(13) tvp) via the anterior cardiac vein (ACV) resulted in high-level myocardial S100A1 protein peak expression of up to 95-fold above control. At 14 weeks, pigs with high-level myocardial S100A1 protein overexpression did not show abnormalities in the electrocardiogram. Electrophysiological right ventricular stimulation ruled out an increased susceptibility to monomorphic ventricular arrhythmia. High-level S100A1 protein overexpression in the LV myocardium resulted in a significant increase in LV ejection fraction (LVEF), albeit to a lesser extent than previously reported with low S100A1 protein overexpression. Cardiac remodeling was, however, equally reversed. High myocardial S100A1 protein overexpression neither increases the occurrence of cardiac arrhythmia nor causes detrimental effects on myocardial contractile function in vivo. In contrast, this study demonstrates a broad therapeutic range of S100A1 gene therapy in post-ischemic HF using a preclinical large animal model.

Autologous stem cell transplantation for elderly patients with newly diagnosed multiple myeloma in the era of novel agents.

BACKGROUND: High-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is considered the standard of care for multiple myeloma (MM) patients <65 years. Safety and outcome of ASCT for patients >65 years is currently uncertain, especially since the introduction of novel agents for induction and maintenance therapy. Furthermore, there are no conclusive data available on risk assessment in elderly patients treated with HDT. PATIENTS AND METHODS: We retrospectively analyzed 202 patients ≥60 years with newly diagnosed MM who underwent ASCT at our institution. Patients were stratified by age into three groups (60-64, 65-69 and 70-75 years). For safety assessment, we compared data about hospitalization, hematopoetic reconstitution and early mortality. Remission before and after ASCT was analyzed according to age and application of novel agents. Event-free (EFS) and overall survival (OS) were analyzed to identify impact of age, remission before/after ASCT and maintenance therapy as well as ISS score and cytogenetic aberrations on outcome in elderly patients. RESULTS: The assessment of safety, remission before/after ASCT as well as EFS and OS showed no significant differences between the three groups (median EFS: 60-64 years: 27 months; 65-69 years: 23 months; 70-75 years: 23 months; median OS: not reached). Patients receiving novel agents as part of induction therapy achieved significantly higher nCR + CR rates than patients treated without novel agents. In Cox regression analysis, ISS and cytogenetics as well as remission after ASCT had the highest prognostic impact on EFS and OS. Maintenance therapy was associated with longer EFS in uni- and multivariate analyses. CONCLUSION: ASCT is feasible for selected patients >65 and >70 years without increased mortality. Age at transplantation has no prognostic significance on outcome after ASCT. Novel agents during induction therapy and maintenance therapy improves outcome of older patients eligible for ASCT. ISS and cytogenetic analysis should be carried out routinely for risk assessment.

Contractures with special reference in elderly: definition and risk factors - a systematic review with practical implications.

PURPOSE: Contractures are common problems for the elderly with far reaching functional and medical consequences. The aim of this systematic literature review was to give an overview of contracture and to identify potential risk factors associated with contractures. METHODS: A systematic literature search with two objectives limited to the last 10 years was performed to identify studies dealing with definition of contracture (objective 1 = O1) and with risk factors (objective 2 = O2). Predefined information including age, sample size, study design, setting, condition, joint, definition of contracture, mode of measurement, and whether inter- and/or intra-rater reliability were assessed, as well as risk factors of contracture were extracted. RESULTS: One hundred and sixty one and 25 studies were retrieved. After applying exclusion criteria 47 studies (O1) and 3 studies (O2) remained. Only 9 studies (O1) provided a definition of contracture. In 3 studies (O2) several potential risk factors were identified. CONCLUSIONS: In most of the studies it seems that the presence of a contracture is equivalent with the presence of restriction in the range of motion (ROM) of a joint. Very little is known about risk factors for contractures. But it seems that immobility may play a pivotal role in the development of this condition. IMPLICATION FOR REHABILITATION: The prevalence of contractures in nursing home residents is estimated at 55% with significant functional and medical consequences. In most studies, which were published in the last 10 years, the presence of a contracture is equivalent with the presence of restriction in the range of motion of a joint. Immobility seems to play a role in the development of contractures. Potential avenues to prevention of contractures and subsequent functional limitations are exercise programmes for and maintenance of mobility of the elderly.