Motor, cognitive and mobility deficits in 1000 geriatric patients: protocol of a quantitative observational study before and after routine clinical geriatric treatment - the ComOn-study.

BACKGROUND: Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany). METHODS: This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week's inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters. DISCUSSION: This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.

Gait Event Detection for Stroke Patients during Robot-Assisted Gait Training.

Functional electrical stimulation and robot-assisted gait training are techniques which are used in a clinical routine to enhance the rehabilitation process of stroke patients. By combining these technologies, therapy effects could be further improved and the rehabilitation process can be supported. In order to combine these technologies, a novel algorithm was developed, which aims to extract gait events based on movement data recorded with inertial measurement units. In perspective, the extracted gait events can be used to trigger functional electrical stimulation during robot-assisted gait training. This approach offers the possibility of equipping a broad range of potential robot-assisted gait trainers with functional electrical stimulation. In particular, the aim of this study was to test the robustness of the previously developed algorithm in a clinical setting with patients who suffered a stroke. A total amount of N = 10 stroke patients participated in the study, with written consent. The patients were assigned to two different robot-assisted gait trainers (Lyra and Lokomat) according to their performance level, resulting in five recording sessions for each gait-trainer. A previously developed algorithm was applied and further optimized in order to extract the gait events. A mean detection rate across all patients of 95.8% ± 7.5% for the Lyra and 98.7% ± 2.6% for the Lokomat was achieved. The mean type 1 error across all patients was 1.0% ± 2.0% for the Lyra and 0.9% ± 2.3% for the Lokomat. As a result, the developed algorithm was robust against patient specific movements, and provided promising results for the further development of a technique that can detect gait events during robot-assisted gait training, with the future aim to trigger functional electrical stimulation.

Feasibility of a Sensor-Based Gait Event Detection Algorithm for Triggering Functional Electrical Stimulation during Robot-Assisted Gait Training.

Technologies such as robot-assisted gait trainers or functional electrical stimulation can improve the rehabilitation process of people affected with gait disorders due to stroke or other neurological defects. By combining both technologies, the potential disadvantages of each technology could be compensated and simultaneously, therapy effects could be improved. Thus, an algorithm was designed that aims to detect the gait cycle of a robot-assisted gait trainer. Based on movement data recorded with inertial measurement units, gait events can be detected. These events can further be used to trigger functional electrical stimulation. This novel setup offers the possibility of equipping a broad range of potential robot-assisted gait trainers with functional electrical stimulation. The aim of this paper in particular was to test the feasibility of a system using inertial measurement units for gait event detection during robot-assisted gait training. Thus, a 39-year-old healthy male adult executed a total of six training sessions with two robot-assisted gait trainers (Lokomat and Lyra). The measured data from the sensors were analyzed by a custom-made gait event detection algorithm. An overall detection rate of 98.1% ± 5.2% for the Lokomat and 94.1% ± 6.8% for the Lyra was achieved. The mean type-1 error was 0.3% ± 1.2% for the Lokomat and 1.9% ± 4.3% for the Lyra. As a result, the setup provides promising results for further research and a technique that can enhance robot-assisted gait trainers by adding functional electrical stimulation to the rehabilitation process.

Prognostic Role of Preoperative Serum Lipid Levels in Patients Undergoing Radical Prostatectomy for Clinically Localized Prostate Cancer.

BACKGROUND: The prognostic role of preoperative serum lipid levels in patients undergoing radical prostatectomy (RP) for clinically localized prostate cancer (PCa) is unclear. The aim of the present study was to investigate preoperative serum lipid levels in patients with clinically localized PCa undergoing RP and their association with clinicopathological features and oncological outcome. METHODS: Preoperative lipid levels (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides) and statin use from consecutive patients with clinically localized PCa undergoing RP in a tertiary referral center between 2008 and 2015 were recorded and patients were followed prospectively. Logistic regression analysis was used to test the association between lipid levels and clinicopathological parameters. Lipid values were analyzed both as continuous and dichotomized variables. Univariable and multivariable Cox regression analyses were performed to identify predictors for recurrence-free survival (RFS). Recurrence was defined as rising and verified PSA levels >0.1 ng/ml. RESULTS: Our cohort consisted of 371 men with a median age of 63 years (range 41-78 years) and a median preoperative PSA value of 6.79 ng/ml (0.43-81.4 ng/ml). Median follow-up was 28 months (1-64). No association was found between lipid levels and adverse pathological characteristics such as ≥pT3, Gleason score ≥8, positive nodal status and positive surgical margins. Recurrence occurred in 49 patients (15.4%) at a median time of 18 months (2-51 month). Compared to low LDL cholesterol, high LDL cholesterol was associated with longer RFS in univariable analysis (continuous: Hazard Ratio (HR): 0.67, 95%-Confidence Interval (CI): 0.47-0.96, P = 0.03; 3 mM cut-point: HR: 0.44, 95%-CI: 0.24-0.79, P = 0.006). Neither levels of other lipids, nor statin use were associated with RFS. Preoperative LDL cholesterol remained an independent predictor for PCa recurrence in a multivariable model adjusted for age, preoperative PSA, statin use, tumor stage, Gleason score, nodal status and surgical margin status (continuous: HR: 0.66, 95%-CI: 0.44-0.99, P = 0.04; 3 mM cut-point: HR: 0.41, 95%-CI: 0.21-0.78, P = 0.007). CONCLUSIONS: This is the first prospective study showing the potential adverse and independent prognostic role of low preoperative LDL cholesterol levels in patients with localized PCa undergoing RP. Prostate 77:549-556, 2017. © 2017 Wiley Periodicals, Inc.

Two Decades of Active Surveillance for Prostate Cancer in a Single-Center Cohort: Favorable Outcomes after Transurethral Resection of the Prostate.

OBJECTIVE: To report the outcomes of active surveillance (AS) for low-risk prostate cancer (PCa) in a single-center cohort. PATIENTS AND METHODS: This is a prospective, single-center, observational study. The cohort included all patients who underwent AS for PCa between December 1999 and December 2020 at our institution. Follow-up appointments (FU) ended in February 2021. RESULTS: A total of 413 men were enrolled in the study, and 391 had at least one FU. Of those who followed up, 267 had PCa diagnosed by transrectal ultrasound (TRUS)-guided biopsy (T1c: 68.3%), while 124 were diagnosed after transurethral resection of the prostate (TURP) (T1a/b: 31.7%). Median FU was 46 months (IQR 25-90). Cancer specific survival was 99.7% and overall survival was 92.3%. Median reclassification time was 11.2 years. After 20 years, 25% of patients were reclassified within 4.58 years, 6.6% opted to switch to watchful waiting, 4.1% died, 17.4% were lost to FU, and 46.8% remained on AS. Those diagnosed by TRUS had a significantly higher reclassification rate than those diagnosed by TURP (p < 0.0001). Men diagnosed by targeted MRI/TRUS fusion biopsy tended to have a higher reclassification probability than those diagnosed by conventional template biopsies (p = 0.083). CONCLUSIONS: Our single-center cohort spanning over two decades revealed that AS remains a safe option for low-risk PCa even in the long term. Approximately half of AS enrollees will eventually require definitive treatment due to disease progression. Men with incidental prostate cancer were significantly less likely to have disease progression.

The Role of New Technologies in the Diagnosis and Surveillance of Non-Muscle Invasive Bladder Carcinoma: A Prospective, Double-Blinded, Monocentric Study of the XPERT© Bladder Cancer Monitor and Narrow Band Imaging© Cystoscopy.

Follow-up is essential for the early detection of recurrent non-muscle invasive bladder cancers (NMIBC). This study investigates the clinical relevance of new diagnostic tools such as an mRNA-based urine test (XPERT© Bladder Cancer Monitor, XBCM) and Narrow Band Imaging© (NBI) and compares them with the established follow-up diagnostics (white-light cystoscopy (WLC) and urine cytology). This was a prospective, double-blind, single-center study that involved patients undergoing NMIBC screening at a tertiary care center. Enrollment occurred between January 2018 and March 2020. In addition to standard care (WLC, cytology, and ultrasound), patients underwent XBCM urine testing and NBI cystoscopy. In total, 301 WLCs were performed; through this, 49 patients demonstrated NMIBC recurrence. NBI cystoscopy was congruent with WLC in all patients. Cytology showed a sensitivity (SE) and specificity (SP) of 27% and 97% (PPV: 65%; NPV 87%), respectively, whereas XBCM showed SE and SP of 58% and 89%, respectively (PPV: 51%; NPV: 92%; AUC: 0.79 (0.716-0.871)). Subgroup analysis showed improved SE and similar SP (PPV, NPV) for high grade (HG) recurrence, with a SE of 74% and SP of 89% (39%, 97%). NBI cystoscopy does not necessarily provide additional benefit over standard WLC. However, the XBCM may provide better SE and a diagnostic advantage in instances of HG disease recurrence.

On the Formation of Black Silicon Features by Plasma-Less Etching of Silicon in Molecular Fluorine Gas.

In this paper, we study the plasma-less etching of crystalline silicon (c-Si) by F2/N2 gas mixture at moderately elevated temperatures. The etching is performed in an inline etching tool, which is specifically developed to lower costs for products needing a high volume manufacturing etching platform such as silicon photovoltaics. Specifically, the current study focuses on developing an effective front-side texturing process on Si(100) wafers. Statistical variation of the tool parameters is performed to achieve high etching rates and low surface reflection of the textured silicon surface. It is observed that the rate and anisotropy of the etching process are strongly defined by the interaction effects between process parameters such as substrate temperature, F2 concentration, and process duration. The etching forms features of sub-micron dimensions on c-Si surface. By maintaining the anisotropic nature of etching, weighted surface reflection (Rw) as low as Rw < 2% in Si(100) is achievable. The lowering of Rw is mainly due to the formation of deep, density grade nanostructures, so-called black silicon, with lateral dimensions that are smaller to the major wavelength ranges of interest in silicon photovoltaics.

Antibodies against beta-amyloid slow cognitive decline in Alzheimer's disease.

To test whether antibodies against beta-amyloid are effective in slowing progression of Alzheimer's disease, we assessed cognitive functions in 30 patients who received a prime and a booster immunization of aggregated Abeta(42) over a 1 year period in a placebo-controlled, randomized trial. Twenty patients generated antibodies against beta-amyloid, as determined by tissue amyloid plaque immunoreactivity assay. Patients who generated such antibodies showed significantly slower rates of decline of cognitive functions and activities of daily living, as indicated by the Mini Mental State Examination, the Disability Assessment for Dementia, and the Visual Paired Associates Test of delayed recall from the Wechsler Memory Scale, as compared to patients without such antibodies. These beneficial clinical effects were also present in two of three patients who had experienced transient episodes of immunization-related aseptic meningoencephalitis. Our results establish that antibodies against beta-amyloid plaques can slow cognitive decline in patients with Alzheimer's disease.

No relevant association of kinematic gait parameters with Health-related Quality of Life in Parkinson's disease.

BACKGROUND: Health-related Quality of Life (HrQoL) is probably the most important outcome parameter for the evaluation and management of chronic diseases. As this parameter is subjective and prone to bias, there is an urgent need to identify objective surrogate markers. Gait velocity has been shown to be associated with HrQoL in numerous chronic diseases, such as Parkinson's disease (PD). With the development and wide availability of simple-to-use wearable sensors and sophisticated gait algorithms, kinematic gait parameters may soon be implemented in clinical routine management. However, the association of such kinematic gait parameters with HrQoL in PD has not been assessed to date. METHODS: Kinematic gait parameters from a 20-meter walk from 43 PD patients were extracted using a validated wearable sensor system. They were compared with the Visual Analogue Scale of the Euro-Qol-5D (EQ-5D VAS) by performing a multiple regression analysis, with the International Classification of Functioning, Disability and Health (ICF) model as a framework. RESULTS: Use of assistive gait equipment, but no kinematic gait parameter, was significantly associated with HrQoL. CONCLUSION: The widely accepted concept of a positive association between gait velocity and HrQoL may, at least in PD, be driven by relatively independent parameters, such as assistive gait equipment.

White Matter Changes-Related Gait and Executive Function Deficits: Associations with Age and Parkinson's Disease.

Background: White matter changes (WMC) are a common finding among older adults and patients with Parkinson's disease (PD), and have been associated with, e.g., gait deficits and executive dysfunction. How the factors age and PD influence WMC-related deficits is, to our best knowledge, not investigated to date. We hypothesized that advanced age and presence of PD leads to WMC-related symptoms while practicing tasks with a low complexity level, and low age and absence of PD leads to WMC-related symptoms while practicing tasks with a high complexity level. Methods: Hundred and thirty-eight participants [65 young persons without PD (50-69 years, yPn), 22 young PD patients (50-69 years, yPD), 36 old persons without PD (70-89 years, oPn) and 15 old PD patients (70-89 years, oPD)] were included. Presence and severity of WMC were determined with the modified Fazekas score. Velocity of walking under single and dual tasking conditions and the Trail Making Test (TMT) were used as gait and executive function parameters. Correlations between presence and severity of WMC, and gait and executive function parameters were tested in yPn, yPD, oPn, and oPD using Spearman's rank correlation, and significance between groups was evaluated with Fisher's z-transformed correlation coefficient. Results: yPn and yPD, as well as oPn and oPD did not differ regarding demographic and clinical parameters. Severity of WMC was not significantly different between groups. yPn and yPD displayed significant correlations of WMC with executive function parameters at low levels of task complexity, oPn at intermediate, and oPD at high complexity levels. Conclusion: This study argues for a relevant association of age and PD-related brain pathology with WMC-related gait and executive function deficits.

Corrigendum: White Matter Changes-Related Gait and Executive Function Deficits: Associations with Age and Parkinson's Disease.

[This corrects the article on p. 213 in vol. 9, PMID: 28713264.].

Evidence of a genetic basis of Morgagni-Stewart-Morel syndrome. A case report of identical twins.

We report two 71-year-old female monozygotic twins presenting with advanced hyperostosis frontalis interna, obesity, shortness and cognitive impairment. They both have suffered from generalized seizures since their early adulthood. Moreover, the patients showed some additional conditions only occurring in one individual or the other such as migraine, marked recurrent depressive disorder or polyarthrosis. The symptoms common to both twins appear to correspond to the Morgagni-Stewart-Morel syndrome and indicate a genetic basis of this disorder as these features occur in genetically identical patients.

Esophageal dysfunction on psychotropic medication. A case report and literature review.

We report the association of long-term clozapine and clomipramine therapy with severe esophageal dilation and hypomotility in a patient with chronic schizophrenia leading to life threatening aspiration pneumonia. Severe aspiration pneumonia manifested suddenly and required intubation and intensive care. Gross impairment of swallowing function with esophageal dilation and hypomotility was detected on videofluoroscopy and manometry. The patient recovered well following a reduction in the dose of clozapine and the withdrawal of clomipramine. The restoration of esophageal function was documented by manometry. The reported side effects and possible pharmacological actions of clozapine, an atypical neuroleptic, and clomipramine, a tricyclic antidepressant, on esophageal motility are discussed.

Interactive computer-training as a therapeutic tool in Alzheimer's disease.

The current study sought to evaluate a novel kind of interactive computer-based cognitive training (ICT) in Alzheimer's disease (AD). AD patients (N = 9), age- and gender-matched patients with a major depressive episode (N = 9), and healthy control subjects (N = 10) were trained to use an ICT program that relates to activities of daily living (ADL). Digital photographs of a shopping route were implemented in a close-to-reality simulation on a computer touch-screen. The task was to find a predefined shopping route, to buy three items, and to answer correctly 10 multiple-choice questions addressing knowledge related to the virtual tasks. Training performance was rated using the number of mistakes (wrong way), time needed for the tasks, number of correct multiple-choice answers, and of repeat of instruction. Compared to normal controls and depressed patients, AD patients performed significantly worse with regard to all variables. Within a 4-week training period including 12 sessions, however, substantial training gains were observed, including a significant reduction of mistakes. Training effects were sustained until follow-up 3 weeks later. The performance of the depressed patients and the normal controls improved as well, with no difference between the two groups. Self-reported effects revealed that the training was well perceived. Thus, the task performance of AD patients improved substantially and subjects appeared to have liked this approach to ICT. New interactive media, therefore, may yield interesting opportunities for rehabilitation and (psycho)therapeutic interventions.

Skill learning in patients with moderate Alzheimer's disease: a prospective pilot-study of waltz-lessons.

The authors report the effect of a 12-day prospective, blinded dance-learning trial in 5 patients with moderate Alzheimer's disease (AD) and 5 age-matched depressed patients. Patients with AD showed a significant effect in procedural learning whereas depressed patients did not. These findings suggest potential implications for therapeutic interventions in patients with moderate AD.