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Light's Timed-Functional-Movements (TFMs) battery is a timed functional mobility assessment for older persons. The purpose of the current study was to investigate the concurrent validity of on-site to videotape timing of the TFMs, followed by interrater, intrarater, and test-retest reliability of the TFMs battery with a frail, elderly population. Twenty frail, elderly subjects participated in two test sessions. Test movements were timed and videotaped on-site by a primary examiner. After establishing the high concurrent validity of videotape timing, the interrater, intrarater, and test-retest reliability of the TFMs were examined by videotape timed measure. This methodology was chosen to allow the test-retest reliability of the client's performance to be separated from the therapist's intrarater reliability. Reliability measures were calculated using intraclass correlation coefficients (ICCs; 2, 1). The concurrent validity of videotape timing to on-site timing ranged from ICC = .90-1.0. Interrater ICCs for both self-selected and maximum speeds were .97 or greater. Exceptions were self-selected-speed lie to sit (.87) and maximum-speed stand to sit (.88). All intrarater ICCs were .98 or greater. Test-retest ICCs varied by movement. In conclusion, the TFMs Battery is easily administered, has high interrater and intrarater reliability, moderate to high test-retest reliability, and high concurrent validity of the on-site to videotape analysis. When close guarding of the client is required during the on-site assessment, the therapist may videotape the TFMs and later complete the analysis. [ABSTRACT FROM AUTHOR]

Background and Objective: Urothelial bladder cancer (UCB) care requires frequent follow-up cystoscopy and surgery. Confocal laser endomicroscopy (CLE), a probe-based optical technique for real-time microscopic evaluation, has shown promising accuracy for grading of UCB. We investigated the diagnostic accuracy of CLE-based assessment of the surgical radicality of the bladder resection bed (RB)., Methods: We prospectively included 40 participants scheduled for transurethral resection of bladder tumors (TURBT) in two academic hospitals. Exclusion criteria were flat lesions, fluorescein allergy, and pregnancy. We performed CLE of the RB during TURBT. Histopathology of an RB biopsy was the reference test. Results at first cystoscopy 3 mo after TURBT are reported. A panel of two blinded observers evaluated the CLE images. The diagnostic accuracy of CLE for detection of detrusor muscle (DM) and residual tumor (rT) was calculated using 2 × 2 tables., Key Findings and Limitations: Histopathology for 22 CLE-matched RB biopsies revealed rT in four cases (18%) and DM in 13 (59%). The quality of CLE imaging was low in four (18%), moderate in 16 (73%), and good in two (9%) cases. CLE was able to correctly predict rT in two of the four cases (50%) identified on histopathology. The sensitivity, specificity, positive predictive value, and negative predictive value were 0.5 (95% confidence interval [CI] 0.07-0.93), 0.83 (95% CI 0.59-0.96), 0.4 (95% CI 0.05-0.85), and 0.88 (95% CI 0.64-0.99) for CLE prediction of rT, and 0.69 (95% CI 0.39-0.91), 0.33 (95% CI 0.07-0.7), 0.6 (95% CI 0.32-0.84), and 0.43 (95% CI 0.1-0.82) for prediction of DM, respectively. Five patients (23%) had rT at 3-mo follow-up; CLE had predicted rT in three, and histopathology had revealed rT in two cases at TURBT., Conclusions and Clinical Implications: CLE does not appear to be a reliable tool for detecting rT or DM in the RB after TURBT., Patient Summary: We investigated a special imaging technique called confocal laser endomicroscopy (CLE) for checking the bladder after surgery for bladder cancer in a group of 40 patients. CLE results were compared to traditional biopsy results and the patients were checked after 3 months. CLE was not very reliable in detecting any remaining cancer (only 50% accurate) or important muscle tissue in the surgical area, and the quality of the images varied. While CLE shows some promise, it is not currently a dependable method for evaluating the bladder after bladder cancer surgery., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology.)

Introduction: Multimodal therapy has become the standard treatment for curable upper gastrointestinal cancers. However, it remains unclear which 8th edition AJCC post-neoadjuvant therapy pathological classification system, esophageal (ypTNM-EC) or gastric (ypTNM-GC), can predict the overall survival (OS) of patients with Siewert II adenocarcinomas better., Methods: Patients diagnosed with Siewert II adenocarcinomas receiving neoadjuvant therapy plus curative resection at the University Medical Center Utrecht (UMC Utrecht) and the Peking University Cancer Hospital (PUCH) between the 2001 and 2022 were included in this study. The patients from two institutions were analyzed separately. Predictive univariable and multivariable Cox models based on ypTNM-EC and ypTNM-GC were constructed. The C-index and calibration curves were used to compare the predictive abilities of ypTNM-EC and ypTNM-GC Cox models., Results: A total of 125 patients from UMCU and 145 from PUCH were included. There was no significant difference in the C-index between the ypTNM-EC and the ypTNM-GC univariable and multivariable Cox models in the UMC Utrecht (p-value = 0.883; p-value=0.681) and PUCH (p-value = 0.808; p-value=0.548) cohorts, and no significant difference was observed between their calibration curves in the two cohorts., Conclusion: The AJCC 8th edition ypTNM prognostic classification systems for esophageal and gastric cancer demonstrated no difference in predicting OS for patients with Siewert II adenocarcinomas both in the Western and Eastern data. The ypTNM-GC, with fewer stage groups, may offer greater convenience for clinical application., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Focal laser ablation (FLA) serves as a targeted therapy for prostate cancer (PCa). Clinical studies have demonstrated significant variations in ablation volumes with consistent fiber configurations. Consequently, a prediction model is needed for the safe application of FLA in treating PCa., Objective: This study aimed to evaluate the reproducibility of FLA-induced temperature profiles in controlled ex vivo experiments using clinical laser treatment protocols. Additionally, it sought to examine the effectiveness of the CEM43 model in predicting the zone of irreversible damage (ZID) and to compare these findings with outcomes derived from the Arrhenius model., Methods: Freshly excised postmortem human prostate and porcine liver specimens were used for controlled ex vivo ablation. Tissues were secured in a Perspex sample holder for precise placement of the laser fiber and thermocouples. FLA was conducted with a 1064-nm Nd:YAG laser at 3 W in continuous-wave mode for 10 min. Pre- and post-FLA 3D T1-weighted 7 T MRI scans were obtained to assess the treatment area. Whole-mount hematoxylin and eosin histological slides were prepared and digitized. On histology, the ZID was defined as the total of vaporized, carbonized, and coagulated tissue. A 2D thermal development map was created from temperature data, using bi-cubic interpolation. The cumulative equivalent thermal isoeffect dose at 43°C in minutes (CEM43) model was applied to predict the ZID, with 240 equivalent minutes (240-CEM43) used as the damage threshold. Additionally, the Arrhenius thermal model was used for comparison of CEM43 results. Predicted ZIDs were compared to MRI and histology., Results: FLA treatment was performed on ex vivo human prostate samples (n = 2) and porcine liver specimens (n = 5). For human prostate tissue, FLA did not result in an identifiable ZID upon histological macroscopic examination or a lesion on MRI. Ex vivo porcine liver samples showed a clearly demarcated oval-shaped hyperintense lesion surrounding the laser fiber tip on post-FLA MRI. The MRI lesion (range 1.6-2.1 cm 2 ) corresponded with the shape and location of the ZID on histology, but was smaller (median 1.7 vs. 3.2, p = 0.02). Histological examination of porcine liver samples revealed ZIDs ranging from 2.1 to 4.1 cm 2 , whereas 240-CEM43-predicted ZIDs ranged from 3.3 to 3.8 cm 2 . Although the median 240-CEM43-predicted ZID was not significantly larger than the histology ZID (3.8 vs. 3.2 cm 2 , p = 0.22), it tended to overpredict the histological results in most experiments. The median Arrhenius-predicted ZID was similar to the histological ZID (3.2 vs. 3.2 cm 2 , p = 0.56), but varied in size when comparing individual experiments (range 2.5-3.2 cm 2 )., Conclusion: FLA on ex vivo human prostate showed no thermal damage on histopathology or MRI. Ex vivo porcine liver FLA resulted in identifiable ZID on histology and lesions on MRI. 240-CEM43 generally overestimated the ZID and had less variability compared to histology. Results from the Arrhenius model were in better agreement with the histology findings, but still did not predict the individual FLA-induced histological thermal damage. Inter-experiment ZID variability underlines the need for developing a more comprehensive predictive dosimetry model for FLA in PCa treatment., (© 2024 The Author(s). Lasers in Surgery and Medicine published by Wiley Periodicals LLC.)

Pathologists' assessment of sentinel lymph nodes (SNs) for breast cancer (BC) metastases is a treatment-guiding yet labor-intensive and costly task because of the performance of immunohistochemistry (IHC) in morphologically negative cases. This non-randomized, single-center clinical trial (International Standard Randomized Controlled Trial Number:14323711) assessed the efficacy of an artificial intelligence (AI)-assisted workflow for detecting BC metastases in SNs while maintaining diagnostic safety standards. From September 2022 to May 2023, 190 SN specimens were consecutively enrolled and allocated biweekly to the intervention arm (n = 100) or control arm (n = 90). In both arms, digital whole-slide images of hematoxylin-eosin sections of SN specimens were assessed by an expert pathologist, who was assisted by the 'Metastasis Detection' app (Visiopharm) in the intervention arm. Our primary endpoint showed a significantly reduced adjusted relative risk of IHC use (0.680, 95% confidence interval: 0.347-0.878) for AI-assisted pathologists, with subsequent cost savings of ~3,000 €. Secondary endpoints showed significant time reductions and up to 30% improved sensitivity for AI-assisted pathologists. This trial demonstrates the safety and potential for cost and time savings of AI assistance., (© 2024. The Author(s).)

Purpose: Urothelial bladder cancer (UCB) care requires frequent follow-up cystoscopy and surgery. Confocal laser endomicroscopy (CLE) is a probe-based optical technique that can provide real-time microscopic evaluation with the potential for outpatient grading of UCB. This study aims to investigate the diagnostic accuracy and interobserver variability for the grading of UCB with CLE during flexible cystoscopy (fCLE)., Methods: Participants scheduled for transurethral resection of papillary bladder tumors were prospectively included for intra-operative fCLE. Exclusion criteria were flat lesions, fluorescein allergy or pregnancy. Two independent observers evaluated fCLE, classifying tumors as low- or high-grade urothelial carcinoma (LGUC/HGUC) or benign. Interobserver agreement was calculated with Cohens kappa (κ) and diagnostic accuracy with 2 × 2 tables. Histopathology was the reference test., Results: Histopathology of 34 lesions revealed 14 HGUC, 14 LGUC and 6 benign tumors. Diagnostic yield for fCLE was 80-85% with a κ of 0.75. Respectively, sensitivity, specificity, NPV and PPV were: for benign tumors 0-20%, 96-100%, unmeasureable-50% and 87%, for LGUC 57-64%, 41-58%, 44-53% and 54-69% and for HGUC 38-57%, 56-68%, 38-57% and 56-68%, with an interobserver agreement of κ 0.61., Conclusion: fCLE is currently insufficient to grade UCB., (© 2024. The Author(s).)

Background: Transperineal focal laser ablation (TPLA) treatment for prostate cancer (PCa) is an experimental focal ablative therapy modality with low morbidity. However, a dosimetry model for TPLA is lacking., Objective: To determine (1) the three-dimensional (3D) histologically defined ablation zone of single- and multifiber TPLA treatment for PCa correlated with magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) and (2) a reliable imaging modality of ablation zone volumetry., Design Setting and Participants: This was a prospective, multicenter, and interventional phase I/II pilot study with an ablate-and-resect design. TPLA was performed in 12 patients with localized prostate cancer divided over four treatment regimens to evaluate potential variation in outcomes., Intervention: TPLA was performed approximately 4 wk prior to robot-assisted radical prostatectomy (RARP) in a daycare setting using local anesthesia., Outcome Measurements and Statistical Analysis: Four weeks after TPLA, ablation zone volumetry was determined on prostate MRI and CEUS by delineation and segmentation into 3D models and correlated with whole-mount RARP histology using the Pearson correlation index., Results and Limitations: Twelve office-based TPLA procedures were performed successfully under continuous transrectal ultrasound guidance using local perineal anesthesia. No serious adverse events occurred. A qualitative analysis showed a clear demarcation of the ablation zone on T2-weighted MRI, dynamic contrast-enhanced MRI, and CEUS. On pathological evaluation, no remnant cancer was observed within the ablation zone. Ablation zone volumetry on CEUS and T2-weighted MRI compared with histology had a Pearson correlation index of r  = 0.94 (95% confidence interval [CI] 0.74-0.99, p  < 0.001) and r  = 0.93 (95% CI 0.73-0.98, p  < 0.001), respectively., Conclusions: CEUS and prostate MRI could reliably visualize TPLA ablative effects after minimally invasive PCa treatment with a high concordance with histopathological findings and showed no remnant cancer., Patient Summary: The treatment effects of a novel minimally invasive ablation therapy device can reliably be visualized with radiological examinations. These results will improve planning and performance of future procedures., (© 2023 The Author(s).)

Objective: To assess the diagnostic accuracy and intra-observer agreement of endoscopic stone recognition (ESR) compared with formal stone analysis. Introduction: Stone analysis is a corner stone in the prevention of stone recurrence. Although X-ray diffraction (XRD) and infrared spectroscopy are the recommended techniques for reliable formal stone analysis, this is not always possible, and the process takes time and is costly. ESR could be an alternative, as it would give immediate information on stone composition. Materials and Methods: Fifteen endourologists predicted stone composition based on 100 videos from ureterorenoscopy. Diagnostic accuracy was evaluated by comparing the prediction from visual assessment with stone analysis by XRD. After 30 days, the videos were reviewed again in a random order to assess intra-observer agreement. Results: The median diagnostic accuracy for calcium oxalate monohydrate was 54% in questionnaire 1 (Q1) and 59% in questionnaire 2 (Q2), whereas calcium oxalate dihydrate had a median diagnostic accuracy of 75% in Q1 and 50% in Q2. The diagnostic accuracy for calcium hydroxyphosphate was 10% in Q1 and 13% in Q2. The median diagnostic accuracy for calcium hydrogen phosphate dihydrate and calcium magnesium phosphate was 0% in both questionnaires. The median diagnostic accuracy for magnesium ammonium phosphate was 20% in Q1 and 40% in Q2. The median diagnostic accuracy for uric acid was 22% in both questionnaires. Finally, there was a diagnostic accuracy of 60% in Q1 and 80% in Q2 for cystine. The intra-observer agreement ranged between 45% and 72%. Conclusion: Diagnostic accuracy of ESR is limited and intra-observer agreement is below the threshold of acceptable agreement.

The acoustic parameter of non-linearity B/A has been found capable of discriminating some types of pathological tissue from healthy tissue. The literature on the utility of B/A for cancer diagnostics is very limited, with measurements on the human breast and liver. This work expands the current research on cancer diagnostics by B/A assessment of eight slices of human clear cell renal cell carcinoma (ccRCC) from two patients and four slices of healthy kidney tissue from two healthy kidney samples. The Wilcoxon test identified the B/A distribution of malignant tissue as not significantly different from that of healthy tissue. An alternative way of defining outliers resulted in median B/A values of 8.1 for ccRCC and 6.8 for healthy tissue (p < 0.05). Acoustic attenuation at 2.1 MHz was significantly greater (p < 0.05) for ccRCC (1.7 dB/cm) than for healthy tissue (1.0 dB/cm). The observed differences in the measured values suggest that B/A and acoustic attenuation may represent potential diagnostic markers of ccRCC. More data and an improved experimental design are required to provide a definitive conclusion on the utility of B/A for cancer diagnostics., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the safety and technical feasibility of in-vivo needle-based forward-looking confocal laser endomicroscopy in prostate tissue. Methods: For this feasibility study, 2 patients with a suspicion of prostate cancer underwent transperineal needle-based confocal laser endomicroscopy during ultrasound-guided transperineal template mapping biopsies. After intravenous administration of fluorescein, needle-based confocal laser endomicroscopy imaging was performed with a forward-looking probe (outer diameter 0.9 mm) in 2 trajectories during a manual push-forward and pullback motion. A biopsy was taken in a coregistered parallel adjacent trajectory to the confocal laser endomicroscopy trajectory for histopathologic comparison. Peri- and postprocedural adverse events, confocal laser endomicroscopy device malfunction and procedural failures were recorded. Needle-based confocal laser endomicroscopy image quality assessment, image interpretation, and histology were performed by an experienced confocal laser endomicroscopy rater and uro-pathologist, blinded to any additional information. Results: In both patients, no peri- and post-procedural adverse events were reported following needle-based confocal laser endomicroscopy. No confocal laser endomicroscopy device malfunction nor procedural failures were reported. Within 1.5 min after intravenous administration of fluorescein, needle-based confocal laser endomicroscopy image quality was sufficient for interpretation for at least 14 min, yielding more than 5000 confocal laser endomicroscopy frames per patient. The pullback confocal laser endomicroscopy recordings and most of the push-forward recordings almost only visualized erythrocytes, being classified as non-representative. During the push-forward recordings, prostate tissue was occasionally visualized in single frames, insufficient for histopathologic comparison. Prostate carcinoma was identified by biopsy in one patient (Gleason score 4 + 3 = 7, >50%), while the biopsy from the other patient showed no malignancy. Conclusion: Needle-based confocal laser endomicroscopy imaging of in-vivo prostate tissue with a forward-looking confocal laser endomicroscopy probe is safe without device malfunctions or procedural failures. Needle-based confocal laser endomicroscopy is technically feasible, but the acquired confocal laser endomicroscopy datasets are non-representative. The confocal laser endomicroscopy images' non-representative nature is possibly caused by bleeding artifacts, movement artifacts and a lack of contact time with the tissue of interest. A different confocal laser endomicroscopy probe or procedure might yield representative images of prostatic tissue.

Background: Pulmonary embolism (PE) is a potentially fatal disease, but data on the incidence of fatal PE in cancer patients are scant., Objective: We sought to estimate the proportion of cancer patients with PE at autopsy., Methods: For this retrospective cohort study, all autopsy reports of cancer patients were retrieved from PALGA: Dutch Pathology Registry and used for data extraction. The primary outcome was PE at time of autopsy, defined as any clot obstructing a pulmonary artery. The secondary outcome was venous thromboembolism, defined as the composite of thrombotic PE, deep vein thrombosis, splanchnic vein thrombosis, or internal jugular vein thrombosis., Results: A total of 9571 cancer patients were included. In 1191 (12.4%; 95% confidence interval [CI], 11.8-13.1) patients, one or more PE events were observed at autopsy, of whom 1074 (90.2%) had a thrombotic embolism, 168 (14.1%) a tumor embolism, 9 (0.8%) a septic embolism, 7 (0.6%) a fat tissue embolism, and 3 (0.3%) a bone marrow embolism. Among patients with PE for whom the cause of death was specified in the autopsy report, death was considered PE-related in 642 patients (66.7%), which was 6.7% of the total study population. Venous thromboembolism was observed in 1223 (12.8%; 95% CI, 12.1-13.5) patients., Conclusion: The proportion of PE in cancer patients at autopsy is substantial. Although the study population is not representative for the total cancer population, it suggests that PE is an important disease complication in cancer patients., (© 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

The neurocognitive impairments associated with mild traumatic brain injury (TBI) often resolve within 1-2 weeks; however, a subset of people exhibit persistent cognitive dysfunction for weeks to months after injury. The factors that contribute to these persistent deficits are unknown. One potential risk factor for worsened outcome after TBI is a history of stress experienced by a person early in life. Early life stress (ELS) includes maltreatment such as neglect, and interferes with the normal construction of cortical and hippocampal circuits. We hypothesized that a history of ELS contributes to persistent learning and memory dysfunction following a TBI. To explore this interaction, we modeled ELS by separating Sprague Dawley pups from their nursing mothers from post-natal days 2-14 for 3 h daily. At 2 months of age, male rats received sham surgery or mild to moderate parasagittal fluid-percussion brain injury. We found that the combination of ELS with TBI in adulthood impaired hippocampal-dependent learning, as assessed with contextual fear conditioning, the water maze task, and spatial working memory. Cortical atrophy was significantly exacerbated in TBI animals exposed to ELS compared with normal-reared TBI animals. Changes in corticosterone in response to restraint stress were prolonged in TBI animals that received ELS compared with TBI animals that were normally reared or sham animals that received ELS. Our findings indicate that ELS is a risk factor for worsened outcome after TBI, and results in persistent learning and memory deficits, worsened cortical pathology, and an exacerbation of the hormonal stress response.

Background : Motor imagery (MI) is a mental technique, absent of physical movement, to foster movement patterns and relieve pain via a training model enacting the brain before the body. This case study assessed MI's efficacy in decreasing phantom limb pain and attaining functional gait and balance after lower extremity amputation. Description : The participant was a 71-year-old female with a transfemoral amputation seven years prior. She required a standard walker for ambulation. The participant underwent three sessions per week for four weeks of MI intervention, with immediate, post-test, and 1-week retention testing involving subjective and functional assessments. Intervention sessions involved quiet sitting with eyes closed while listening to the MI script. The scripts focused on functional movement patterns and tasks that were relevant to the participant, such as walking, balancing, and reaching. Each session's script focused on a different task. These scripts guided her through proper action and biomechanics of the skills to imagine herself moving safely and functionally. Outcomes : Short Form Berg Balance Scale and Tinetti Performance Oriented Mobility Assessment scores demonstrated clinically important and sustained improvement. Further, the participant reported decreased phantom limb pain and could walk a short distance independently for the first time in seven years. Discussion : MI is a time- and cost-effective, low-risk treatment option that decreased phantom pain and improved balance and functional gait in an individual with an amputation. The use of MI as an intervention for the rehabilitation of persons with amputation must be further examined.

Objectives: To evaluate the diagnostic yield and concordance of upper tract urothelial carcinoma (UTUC) grading between ureterorenoscopic biopsies and surgical resections. Materials and Methods: The nationwide Dutch Pathology Registry (nationwide network and registry of histo- and cytopathology in the Netherlands [PALGA]) was searched for UTUC-positive renal units (RUs) with histopathology excerpts from ureterorenoscopic biopsies and surgical resections, matched for laterality and localization of the tumor, from 2011 until 2018. The positive predictive value (concordance) of the biopsy grade with regard to the final grade according to the World Health Organization (WHO) 2004 classification was calculated. Results: A total of 1002 UTUC-positive rental units were included, of which 776 UTUC-positive RUs were graded according to the WHO 2004 classification in the ureterorenoscopic biopsy, the localization-matched surgical resection, or in both. The diagnostic yield of biopsies for a classifying diagnosis was 89% with a sensitivity for UTUC of 84%. In case of UTUC, the diagnostic yield for biopsy-based grading and staging was 97% and 72%, respectively. The concordance of high-grade biopsies with regard to the final histopathology was 97% and 62% for low-grade biopsies. Upgrading to final high grade occurred in 33% of the low-grade biopsies. Downgrading to final low grade occurred in 2% of high-grade biopsies. Conclusions: This is the first study to portray the limitations of ureterorenoscopic biopsies for UTUC in a nationwide cohort. The diagnostic yield of ureterorenoscopic biopsies for a classifying diagnosis is suboptimal, but the diagnostic yield for grading according to the WHO 2004 classification is high. Yet, a worrisome amount of ureterorenoscopic biopsies are upgraded with regard to the surgical resection. Consequently, one-third of patients, who qualify for kidney-sparing treatment according to one of the criteria recommended for risk stratification, might be stratified incorrectly. These findings stress the importance of a timely and stringent ureterorenoscopic follow-up after kidney-sparing surgery and highlight the need for improvements in the diagnostic approach to optimize the risk stratification.

NK cells are innate immune cells characterized by their ability to spontaneously lyse tumor and virally infected cells. We have recently demonstrated that IL-15-sufficient DC regulate NK cell effector functions in mice. Here, we established that among ITAM-proximal signaling molecules, the expression levels of the scaffold molecule Linker for Activation of T cells (LAT) and its transcription factor ELF-1 were reduced 4 days after in vivo depletion of DC. Addition of IL-15, a cytokine presented by DC to NK cells, regulates LAT expression in NK cells with a significant effect on the DNAM1 + subset compared to DNAM1 - cells. We also found that LAT expression is regulated via interaction of the DNAM1 receptor with its ligand CD155 in both immature and mature NK cells, independently of NK cell education. Finally, we found that LAT expression within DNAM1 + NK cells might be responsible for enhanced calcium mobilization following the triggering of activating receptors on NK cells. Altogether, we found that LAT expression is tightly regulated in DNAM1 + NK cells, via interaction(s) with DC, which express CD155 and IL-15, resulting in rapid activation of the DNAM1 + subset during activating receptor triggering., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Cystoscopy enables the visualisation of suspicious bladder lesions but lacks the ability to provide real-time histopathologic information. Confocal laser endomicroscopy (CLE) is a probe-based optical technique that can provide real-time microscopic images. This high-resolution optical imaging technique may enable real-time tumour grading during cystoscopy., Objective: To validate and adapt CLE criteria for bladder cancer diagnosis and grading., Design, Setting, and Participants: Prospectively, 73 patients scheduled for transurethral resection of bladder tumour(s) were included. CLE imaging was performed intraoperatively prior to en bloc resection. Histopathology was the reference standard for comparison., Intervention: Cystoscopic CLE imaging., Outcome Measurements and Statistical Analysis: Three independent observers evaluated the CLE images to classify tumours as low- or high-grade urothelial carcinoma (UC), or benign lesions. Interobserver agreement was calculated with Fleiss kappa analysis and diagnostic accuracy with 2×2 tables., Results and Limitations: Histopathology of 66 lesions (53 patients) revealed 25 low-grade UCs, 27 high-grade UCs, and 14 benign lesions. For low-grade UC, most common features were papillary configuration (100%), distinct cell borders (81%), presence of fibrovascular stalks (79%), cohesiveness of cells (77%), organised cell pattern (76%), and monomorphic cells (67%). A concordance between CLE-based classification and histopathology was found in 19 cases (76%). For high-grade UC, pleomorphic cells (77%), indistinct cell borders (77%), papillary configuration (67%), and disorganised cell pattern (60%) were the most common features. A concordance with histopathology was found in 19 cases (70%). In benign lesions, the most prevalent features were disorganised cell pattern (57%) and pleomorphic cells (52%), and a concordance with histopathology was found in four cases (29%)., Conclusions: The CLE criteria enable identification of UC. CLE features correlate to histopathologic features that may enable real-time tumour grading. However, flat lesions remain difficult to classify., Patient Summary: Confocal laser endomicroscopy may enable real-time cancer differentiation during cystoscopy, which is important for prognosis and disease management., (Copyright © 2018. Published by Elsevier B.V.)

Background: Flexible ureteroscopy is an established treatment modality for evaluating and treating abnormalities in the upper urinary tract. Reusable ureteroscope (USC) durability is a significant concern., Objective: To evaluate the durability of the latest generation of digital and fiber optic reusable flexible USCs and the factors affecting it., Design, Setting, Participants: Six new flexible USCs from Olympus and Karl Storz were included. The primary endpoint for each USC was its first repair. Data on patient and treatment characteristics, accessory device use, ureteroscopy time, image quality, USC handling, disinfection cycles, type of damage, and deflection loss were collected prospectively., Intervention: Ureteroscopy., Outcome Measurements and Statistical Analysis: USC durability was measured as the total number of uses and ureteroscopy time before repair. USC handling and image quality were scored. After every procedure, maximal ventral and dorsal USC deflection were documented on digital images., Results and Limitations: A total of 198 procedures were performed. The median number of procedures was 27 (IQR 16-48; 14h) for the six USCs overall, 27 (IQR 20-56; 14h) for the digital USCs, and 24 (range 10-37; 14h) for the fiber optic USCs. Image quality remained high throughout the study for all six USCs. USC handling and the range of deflection remained good under incremental use. Damage to the distal part of the shaft and shaft coating was the most frequent reason for repair, and was related to intraoperative manual forcing. A limitation of this study is its single-center design., Conclusions: The durability of the latest reusable flexible USCs in the current study was limited to 27 uses (14h). Damage to the flexible shaft was the most important limitation to the durability of the USCs evaluated. Prevention of intraoperative manual forcing of flexible USCs maximizes their overall durability., Patient Summary: Current flexible ureteroscopes proved to be durable. Shaft vulnerability was the most important limiting factor affecting durability., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The Lower Quarter Y-Balance Test (LQ-YBT), a measure of dynamic balance used in young adults, has not been adequately studied in older women. We determined the reliability, normative values, and relationships to other balance measures for LQ-YBT in women aged 50-79 years. Interrater reliability was strong, and test-retest reliability was moderate to strong. Results by decade showed women 50-59 years had significantly better scores than both older groups. There were moderate positive correlations between single leg stance, gait speed, and LQ-YBT composite score. LQ-YBT may be used as a dynamic balance assessment in healthy older women.

Purpose: Urothelial carcinoma of the bladder (UCB) is the most common urinary cancer. White-light cystoscopy (WLC) forms the corner stone for the diagnosis of UCB. However, histopathological assessment is required for adjuvant treatment selection. Probe-based confocal laser endomicroscopy (pCLE) enables visualization of the microarchitecture of bladder lesions during WLC, which allows for real-time tissue differentiation and grading of UCB. To improve the diagnostic process of UCB, computer-aided classification of pCLE videos of in vivo bladder lesions were evaluated in this study. Materials and Methods: We implemented preprocessing methods to optimize contrast and to reduce striping artifacts in each individual pCLE frame. Subsequently, a semiautomatic frame selection was performed. The selected frames were used to train a feature extractor based on pretrained ImageNet networks. A recurrent neural network, in specific long short-term memory (LSTM), was used to predict the grade of bladder lesions. Differentiation of lesions was performed at two levels, namely (i) healthy and benign vs malignant tissue and (ii) low-grade vs high-grade papillary UCB. A total of 53 patients with 72 lesions were included in this study, resulting in ∼140,000 pCLE frames. Results: The semiautomated frame selection reduced the number of frames to ∼66,500 informative frames. The accuracy for differentiation of (i) healthy and benign vs malignant urothelium was 79% and (ii) high-grade and low-grade papillary UCB was 82%. Conclusions: A feature extractor in combination with LSTM results in proper stratification of pCLE videos of in vivo bladder lesions.

Purpose: Confocal laser endomicroscopy (CLE) is a fluorescence-based fiber-optic imaging technique with the potential for intraoperative grading of upper tract urothelial carcinoma (UTUC). This study aims to (1) investigate the prevalence of the previously proposed CLE criteria for bladder cancer in papillary UTUC, (2) estimate the diagnostic value of CLE for UTUC grading and (3) propose a scoring system for a more quantifiable approach of CLE-based grading of UTUC., Materials and Methods: Ureteroscopic CLE was performed in patients with UTUC. Following CLE imaging, co-localized biopsies were taken for histopathologic comparison. Postoperatively, two blinded raters assessed the CLE images., Results: Fifty-three papillary UTUCs (34 low grade and 19 high grade) were imaged with CLE in 36 patients. All the previously described CLE criteria were identifiable in varying proportions. After excluding 10 non-diagnostic recordings (5 low grade and 5 high grade) due to insufficient image quality, the histopathologic grade was correctly identified with CLE in 26 low-grade UTUCs (90%) and in 12 high-grade UTUCs (86%). The most prevalent CLE criteria with the highest diagnostic potential were cellular organization, morphology and cohesiveness of cells. A scoring system was proposed with these criteria, which yielded similar diagnostic accuracies., Conclusions: Based on the previously proposed criteria, CLE enables accurate grading of papillary UTUC at a non-diagnostic rate of 19%. The most prevalent CLE criteria with the highest diagnostic potential for grading of papillary UTUC are cellular organization, morphology and cohesiveness of cells. The proposed scoring system may simplify the assessment of CLE images for UTUC grading but external validation is required.

Objectives: To investigate the diagnostic accuracy, inter-rater and intrarater agreement of grade predictions based on the visual appearance of papillary upper tract urothelial carcinoma (UTUC) during digital ureteroscopy., Methods: Nine urologists predicted the histopathologic grade of 64 papillary UTUC (low-grade vs high-grade) by assessing the visual appearance of the tumors in videos from digital ureteroscopy. The diagnostic accuracy was estimated by comparing the grade predictions with the histopathology from colocalized biopsies. Inter-rater agreement was assessed by pairwise inter-rater percentage agreement and Fleiss Kappa analysis. The videos were rated in a random order again 30 days after the first assessment to evaluate the intrarater percentage agreement., Results: Low-grade tumors were predicted correctly in 37%-85% of the cases with a median concordance of 59% for questionnaire 1 and 66% for questionnaire 2. High-grade tumors were predicted correctly in 26%-91% of the cases with a median concordance of 52% and 61% for each questionnaire. The median pairwise inter-rater percentage agreement was 66% for both questionnaires with a Fleiss Kappa of 0.29 and 0.38, respectively. The median intrarater percentage agreement was 81%., Conclusion: The histopathologic grade of UTUC is essential to the risk-stratification for treatment selection. Predictions of the histopathologic grade based on the visual appearance of papillary UTUC with digital ureteroscopy are often incorrect in comparison with biopsy results and yield low inter-rater agreement. Urologists must be aware of these limitations in the assessment of the tumor grade during digital ureteroscopy to warrant good clinical practice., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose: Previous studies have shown that older adults at high fall risk exhibit altered spatiotemporal gait parameters such as lesser gait speed, shorter step length, and greater step width compared with their healthy counterparts. Measurement of these gait parameters for older adults can play a pivotal role in clinical evaluation. While the GAITRite walkway has been previously validated and used extensively for research purposes, the Zeno walkway validity has not been established. Although both walkways use pressure sensor-based technology, comparison of the spatiotemporal gait measurements between the systems for older adults is unknown. Our purpose was to determine the concurrent validity of the Zeno walkway with the gold-standard GAITRite walkway among healthy older adults and those at high fall risk using a cross-sectional study design., Methods: Thirty healthy older adults and 17 older adults at high fall risk performed 5 walking trials barefoot on a 16´ × 4´ Zeno walkway and a 14´ × 2´ GAITRite walkway in a quasi-randomized order. Testing on the Zeno walkway was performed in a continuous manner while testing on the GAITRite walkway was performed using 5 discrete trials. Walking trials were done at self-selected comfortable and fast pace conditions. Data from the Zeno walkway were processed using the PKMAS software. Data from the GAITRite were processed using the GAITRite software. For each group and condition, spatiotemporal gait parameters common to both walkways' footfall processing software were compared using a Wilcoxon signed rank test. Concurrent validity was estimated using intraclass correlation coefficient (ICC(2,5)) and Bland-Altman plots., Results and Discussion: Both groups had significantly greater stride width on the GAITRite walkway during both conditions. During the fast pace condition, both groups walked with greater gait speed, cadence, and stride velocity, lesser step time, stance time, and double-support time, greater percentage of gait cycle spent in single-support phase, and lesser percentage of gait cycle spent in double-support phase on the GAITRite walkway. Differences observed could be attributed to surface textures, software used to process the footfalls, dimensions of the walkways, or the continuous versus discrete protocols used in the current study. The ranges of ICC(2,5) values for healthy older adults and adults at high fall risk walking at a comfortable pace were 0.449 to 0.918 and 0.854 to 0.969 and at a fast pace were 0.784 to 0.964 and 0.850 to 0.976, respectively. These values imply that the concurrent validity was moderate for most temporal parameters when healthy older adults walked at comfortable pace and excellent otherwise. Overall, the concurrent validity between both walkways was acceptable., Conclusion: Concurrent validity for spatiotemporal parameters between the GAITRite walkway and the Zeno walkway was moderate to excellent for older adults dependent on the specific parameter (spatial vs temporal), population (healthy or fall risk), and walking pace (comfortable or fast).

Introduction: With catheter based optical coherence tomography (OCT), high resolution images of the upper urinary tract can be obtained, thereby facilitating the detection of upper tract urothelial carcinomas (UTUC). We hypothesized that the attenuation coefficient of the OCT signal (μ OCT ) is related to the histopathologic grade of the tumor., Objectives: In this study, we aimed to define the μ OCT cut-off for discriminating high grade and low grade papillary UTUC., Methods: For this post-hoc analysis, data from OCT imaging of papillary UTUC was obtained from patients during ureterorenoscopy. OCT images and raw data were simultaneously analyzed with in-house developed software. The μ OCT determined in papillary UTUCs and corresponding histopathologic grading from either biopsies or radical resection specimens were compared., Results: Thirty-five papillary UTUC from 35 patients were included. μ OCT analysis was feasible in all cases. The median μ OCT was 3.3 mm -1 (IQR 2.7-3.7 mm -1 ) for low-grade UTUC and 4.9 mm -1 (IQR 4.3-6.1 mm -1 ) for high-grade UTUC (P = 0.004). ROC analysis yielded a μ OCT cut-off value of >4.0 mm -1 (AUC = 0.85, P < 0.001) with a sensitivity of 83% and a specificity of 94% for high-grade papillary UTUC., Conclusions: This study proposes a μ OCT cut-off of 4.0 mm -1 for quantitative grading of UTUC with ureterorenoscopic OCT imaging. The promising diagnostic accuracy calculations justify further studies to validate the proposed cut-off value. Implementation of the software for the μ OCT analysis in OCT systems may allow for μ OCT assessment at real time during ureterorenoscopy. Lasers Surg. Med. 51:399-406, 2019. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

Purpose: We assessed the frequency of preoperative and persistent microbial contamination of flexible ureteroscopes after reprocessing and the relation of contamination to cumulative ureteroscope use., Materials and Methods: We evaluated the effectiveness of high level disinfection with peracetic acid as well as data on ureteroscope use for 20 new flexible ureteroscopes from December 2015 to December 2017 at a single center. In the operating room pre-use and postuse microbial samples of the ureteroscope shaft and working channel were collected to evaluate microbial contamination after reprocessing. Positive cultures were defined as 30 cfu/ml or greater of skin flora, or 10 cfu/ml or greater of uropathogenic microorganisms. A generalized estimating equation model was used to analyze whether cumulative ureteroscope use was associated with positive pre-use cultures., Results: Microbial samples were collected during 389 procedures. Pre-use ureteroscope cultures were positive in 47 of 389 procedures (12.1%), of which uropathogens were found in 9 of 389 (2.3%) and skin flora in 38 of 389 (9.8%). Urinary tract infection symptoms did not develop in any of the patients who underwent surgery with a uropathogen contaminated ureteroscope. In 1 case the pre-use culture contained the same bacteria type as the prior postuse culture. Cumulative ureteroscope use was not associated with a higher probability of positive cultures., Conclusions: Microbial contamination of reprocessed ureteroscopes was found in an eighth of all procedures. Notably uropathogenic microorganisms were discovered in a small proportion of all procedures. Persistent ureteroscope contamination with uropathogens was only rarely encountered. Cumulative ureteroscope use was not associated with a higher probability of microbial contamination.

Kidney-sparing surgery of upper tract urothelial carcinoma (UTUC) requires a stringent follow-up with frequent ureteroscopies. Triage testing could reduce the number of follow-up ureteroscopies and hence minimize the invasiveness of follow-up. The use of urine-based markers for triage seems appealing but should be feasible with selective urine from outpatient cystoscopy to maximize the reduction of invasiveness. In this study, the feasibility of UroVysion ® fluorescence in situ hybridization (FISH) for the detection of UTUC in 1 mL of selective urine is investigated. Ten consecutive patients with biopsy-proven UTUC and five patients with negative diagnostic ureteroscopy findings were included in this case-control study. During ureteroscopy, 1 mL of selective urine was collected passively with a ureteral splint for Urovysion® FISH. The FISH rater was blinded to any clinical information. The results of FISH were compared to the findings of concomitantly collected selective urine cytology and the patients' UTUC status. FISH was feasible in all samples with a sensitivity of 90% and a specificity of 80% for UTUC. In comparison, selective cytology resulted in a diagnostic yield of 87% with a sensitivity of 80% and a specificity of 67%. In conclusion, UTUC detection is feasible with FISH in 1 mL of passively collected selective urine. Thus from a technical point of view, FISH could be used as an outpatient triage test to decide if follow-up ureteroscopy is necessary after kidney-sparing surgery of UTUC. Evaluation of the diagnostic accuracy of FISH for the suggested pathway deserves further attention.

Purpose: To evaluate the opinion of urologists and their audience regarding patient safety and educational value of live surgical demonstrations (LSD) and semi-live surgical demonstrations (semi-LSD)., Methods: Following the '2017 Challenges in Endourology' meeting, a survey addressing patient safety and the educational value of LSD and semi-LSD was disseminated online to all participants. Survey outcomes of LSD and semi-LSD were compared., Results: All 279 respondents attended both LSD and semi-LSD. Overall, 53% of said respondents stated that patient safety was always the highest priority for LSD, while 74% noted the same for semi-LSD. The complication risk in LSD was perceived equal by 57% of the respondents when compared to cases of similar difficulty in routine practice, while 38% perceived it as a greater risk. For semi-LSD, the complication risk was perceived equal by 84%, while 5% perceived it to be a greater risk in comparison to general practice. On a scale from 0 (no value) to 10 (highly valuable), the average educational value of LSD and semi-LSD was rated 8.4 and 8.3, respectively. A substantial percentage of the surgeons who perform LSD express concerns that live surgery is not the optimal setting to ensure patient safety., Conclusions: LSD remains a popular tool for surgical education among urologists and their audience. However, patient safety remains a concern and is perceived less of a concern for semi-LSD. The educational value of LSD and semi-LSD was scored equally high. Therefore, we should consider to advocate the use of semi-LSD more often.

Purpose: Expansion of clinical pharmacist positions through sustainable funding is described., Summary: The University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences was awarded a 2-year program grant to establish an integrated clinical pharmacy program for underserved residents in family health centers in northeastern Colorado. The grant enabled the hiring of 2 bilingual, full-time, board-certified, postgraduate year 2-trained clinical pharmacists to initiate comprehensive clinical pharmacy services. Clinical pharmacy services for diabetes, hypertension, and dyslipidemia management were provided during direct patient care visits using collaborative drug therapy management protocols to facilitate comprehensive medication management. Initial visits lasted 1 hour, and follow-up visits lasted 30 minutes. In addition, clinical pharmacists provided point-of-care consultations for patients seeing other healthcare providers. All patient encounters and consultations were documented in the electronic health record. Success of the clinical pharmacy program was evaluated based on the achievement of goal blood pressure values, glycosylated hemoglobin values, and low-density-lipoprotein cholesterol levels. Pharmacists' involvement in patient care activities led to improvements in all of these clinical outcomes. This coincided with unique funding opportunities with regional accountable care organizations that sought to demonstrate improved patient care in an expansion population. As a result, 2 grant-funded clinical pharmacist positions in 2 community health clinics were converted into 4 faculty positions in 5 community health centers funded by regional accountable care organizations., Conclusion: Collaboration with accountable care organizations resulted in the successful funding of ambulatory care clinical pharmacy services. These services resulted in improved chronic disease control and provider satisfaction., (Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Background: Aging and Parkinson's disease are often associated with impaired postural control. Providing extrinsic feedback via vibrotactile sensation could supplement intrinsic feedback to maintain postural control., Research Question: We investigated the postural control response to vibrotactile feedback provided at the trunk during challenging stance conditions in older adults at high fall risk and individuals with Parkinson's disease compared to healthy older adults., Methods: Nine older adults at high fall risk, 9 persons with Parkinson's disease and 10 healthy older adults performed 30s quiet standing on a force platform under five challenging stance conditions with eyes open/closed and standing on firm/foam surface with feet together, each with and without vibrotactile feedback. During vibrotactile feedback trials, feedback was provided when participants swayed >10% over the center of their base of support. Participants were instructed vibrations would be in response to their movement. Magnitude of postural sway was estimated using center of pressure path length, velocity, and sway area. Dynamics of individuals' postural control was evaluated using detrended fluctuation analysis., Results: Results showed that vibrotactile feedback induced a change in postural control dynamics among persons with Parkinson's disease when standing with intact intrinsic visual input and altered intrinsic somatosensory input, but there was no change in sway magnitude. However, use of vibrotactile feedback did not significantly alter dynamics of postural control in older adults with high risk of falling or reduce the magnitude of sway., Significance: Considering the effects of vibrotactile feedback were dependent on the population and stance condition, designing an optimal therapeutic regimen for balance training should be carefully considered and be specific to a target population. Furthermore, our results suggest that explicit instructions on how to respond to the vibrotactile feedback could affect training outcome., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Visual confirmation of a suspicious lesion in the urinary tract is a major corner stone in diagnosing urothelial carcinoma. However, during cystoscopy (for bladder tumors) and ureterorenoscopy (for tumors of the upper urinary tract) no real-time histopathologic information can be obtained. Confocal laser endomicroscopy (CLE) is an optical imaging technique that allows for in vivo high-resolution imaging and may allow real-time tumor grading of urothelial lesions., Objective: The primary objective of both studies is to develop descriptive criteria for in vivo CLE images of urothelial carcinoma (low-grade, high-grade, carcinoma in situ) and normal urothelium by comparing CLE images with corresponding histopathology., Methods: In these two prospective clinical trials, CLE imaging will be performed of suspicious lesions and normal tissue in the urinary tract during surgery, prior to resection or biopsy. In the bladder study, CLE will be performed in 60 patients using the Cystoflex UHD-R probe. In the upper urinary tract study, CLE will be performed in 25 patients during ureterorenoscopy, who will undergo radical treatment (nephroureterectomy or segmental ureter resection) thereafter. All CLE images will be analyzed frame by frame by three independent, blinded observers. Histopathology and CLE-based diagnosis of the lesions will be evaluated. Both studies comply with the IDEAL stage 2b recommendations., Results: Presently, recruitment of patients is ongoing in both studies. Results and outcomes are expected in 2018., Conclusions: For development of CLE-based diagnosis of urothelial carcinoma in the bladder and the upper urinary tract, a structured conduct of research is required. This study will provide more insight in tissue-specific CLE criteria for real-time tumor grading of urothelial carcinoma., Trial Registration: Confocal Laser Endomicroscopy: ClinicalTrials.gov NCT03013894; https://clinicaltrials.gov /ct2/show/NCT03013894?term=NCT03013894&rank=1 (Archived by WebCite at http://www.webcitation.org/6wiPZ378I); and Dutch Central Committee on Research Involving Human Subjects NL55537.018.15; https://www.toetsingonline.nl /to/ccmo&#95;search.nsf/fABRpop?readform&unids=6B72AE6EB0FC3C2FC125821F001B45C6 (Archived by WebCite at http://www.webcitation.org/6wwJQvqWh). Confocal Laser Endomicroscopy in the upper urinary tract: ClinicalTrials.gov NCT03013920; https://clinicaltrials.gov/ct2/show/NCT03013920? term=NCT03013920&rank=1 (Archived by WebCite at http://www.webcitation.org/6wiPkjyt0); and Dutch Central Committee on Research Involving Human Subjects NL52989.018.16; https://www.toetsingonline.nl/to/ccmo&#95;search.nsf/fABRpop?readform&unids=D27C9C3E5755CFECC12581690016779F (Archived by WebCite at http://www.webcitation.org/6wvy8R44C)., (©Esmee IML Liem, Jan Erik Freund, Joyce Baard, D Martijn de Bruin, M Pilar Laguna Pes, C Dilara Savci-Heijink, Ton G van Leeuwen, Theo M de Reijke, Jean JMCH de la Rosette. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 07.02.2018.)

Background: Parkinson's disease (PD) commonly impairs posture, gait, and cognition. Exercise in the form of aerobic activity as well as exergaming may improve motor ability and cognition in persons with PD. Exergaming and treadmill training can be a practical form of exercise within the home; however, there is minimal research on this combined multimodal intervention for persons with PD., Objective: We investigated the effects of this combined intervention on cognition, balance, and gait in a person with PD through supervised lab sessions augmented by home-based sessions., Methods: This case study utilized an ABA single subject experimental design with 4 weeks of pre-intervention, followed by 8 weeks of intervention, and 4 weeks of post-intervention. The intervention consisted of treadmill walking and Xbox Kinect exergaming, 30 minutes each, performed unsupervised at home and at supervised lab sessions. The two standard deviation band method was used to determine significance., Results: MiniBEST test, 2-minute walk distance, sway area, endurance test, and a few parameters of gait initiation and gait improved significantly throughout the intervention period. Only a few measures sustained the improvement 4 weeks after completion of intervention., Conclusion: Eight weeks of treadmill and exergaming intervention with a person with PD improved static and dynamic postural control measures, but not gait, cognition, endurance, and clinical measures of balance. Longer and more intense multimodal intervention may be warranted.

Purpose of Review: Image enhancement techniques and optical diagnostic tools have emerged in the quest to improve diagnostics and treatment in patients with upper urinary tract carcinoma (UTUC). The aim of the present report is to describe their mechanisms of action and to assess the current evidence on applicability and utility in UTUC., Recent Findings: Image enhancement techniques including narrow band imaging, Image1 S, and photodynamic diagnosis aim at better visualization of malignant urothelium and especially flat tumours or carcinoma in situ which are often difficult to see with white light endoscopy. Conducted studies in the upper tract are scarce but first results show that tumour detection seems to be better for narrow band imaging and photodynamic diagnosis-guided inspection.Optical diagnostic tools as confocal laser endomicroscopy and optical coherence tomography aim at providing real time optical biopsies giving pathologic information. A pilot study of optical coherence tomography proved its feasibility to visualize, grade and stage low and high-grade UTUC., Summary: Better visualization of suspect lesions and optical diagnostic techniques providing real time optical biopsies aim to facilitate in higher diagnostic precision and optimal individualized treatment of our patients with UTUC. As the disease is rare, studies are scarce but indispensable for future implication of these techniques.

Unlabelled: Learning and memory impairments are common in traumatic brain injury (TBI) survivors. However, there are no effective treatments to improve TBI-induced learning and memory impairments. TBI results in decreased cAMP signaling and reduced cAMP-response-element binding protein (CREB) activation, a critical pathway involved in learning and memory. TBI also acutely upregulates phosphodiesterase 4B2 (PDE4B2), which terminates cAMP signaling by hydrolyzing cAMP. We hypothesized that a subtype-selective PDE4B inhibitor could reverse the learning deficits induced by TBI. To test this hypothesis, adult male Sprague-Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury. At 3 months postsurgery, animals were administered a selective PDE4B inhibitor or vehicle before cue and contextual fear conditioning, water maze training and a spatial working memory task. Treatment with the PDE4B inhibitor significantly reversed the TBI-induced deficits in cue and contextual fear conditioning and water maze retention. To further understand the underlying mechanisms of these memory impairments, we examined hippocampal long-term potentiation (LTP). TBI resulted in a significant reduction in basal synaptic transmission and impaired expression of LTP. Treatment with the PDE4B inhibitor significantly reduced the deficits in basal synaptic transmission and rescued LTP expression. The PDE4B inhibitor reduced tumor necrosis factor-α levels and increased phosphorylated CREB levels after TBI, suggesting that this drug inhibited molecular pathways in the brain known to be regulated by PDE4B. These results suggest that a subtype-selective PDE4B inhibitor is a potential therapeutic to reverse chronic learning and memory dysfunction and deficits in hippocampal synaptic plasticity following TBI., Significance Statement: Currently, there are an estimated 3.2-5.3 million individuals living with disabilities from traumatic brain injury (TBI) in the United States, and 8 of 10 of these individuals report cognitive disabilities (Thurman et al., 1999; Lew et al., 2006; Zaloshnja et al., 2008). One of the molecular mechanisms associated with chronic cognitive disabilities is impaired cAMP signaling in the hippocampus. In this study, we report that a selective phosphodiesterase 4B (PDE4B) inhibitor reduces chronic cognitive deficits after TBI and rescues deficits in hippocampal long-term potentiation. These results suggest that PDE4B inhibition has the potential to improve learning and memory ability and overall functioning for people living with TBI., (Copyright © 2016 the authors 0270-6474/16/367095-14$15.00/0.)

Background: Multiple sclerosis (MS) is a chronic progressive disease of the central nervous system. Compared to healthy individuals, persons with multiple sclerosis (PwMS) have increased postural sway in quiet stance, decreased gait speed and increased fall incidence. Trunk performance has been implicated in postural control, gait dysfunction, and fall prevention in older adults. However, the relationship of trunk performance to postural control and gait has not been adequately studied in PwMS., Objective: To compare trunk muscle structure and performance in PwMS to healthy age and gendered-matched controls (HC); to determine the effects of isometric trunk endurance testing on postural control in both populations; and to determine the relationship of trunk performance with postural control, gait and step activity in PwMS., Methods: Fifteen PwMS and HC completed ultrasound imaging of trunk muscles, 10 m walk test, isometric trunk endurance tests, and postural sway test. Participants wore a step activity monitor for 7 days., Results: PwMS had worse isometric trunk endurance compared to HC. PwMS trunk flexion endurance negatively correlated to several postural control measures and positively correlated to gait speed and step activity., Conclusions: Clinicians should consider evaluation and interventions directed at impaired trunk endurance in PwMS.

Background: In neonates with hypoplastic left heart complex (HLHC), biventricular repair is considered superior to univentricular repair. The Z-scores of the mitral and the aortic valve annulus are primary factors for the choice of repair. Predictive cutoff values for the feasibility and optimal outcome of biventricular repair are unknown. This study assesses the growth of left side heart structures and the midterm outcome after biventricular repair with an interatrial fenestration in our HLHC population., Methods: Retrospective study of 19 HLHC patients who underwent biventricular repair in a single tertiary referral center between 2004 and 2013. The cardiac dimensions (mitral and aortic valve annulus, left ventricle inlet length, left ventricular internal diastolic dimension) were measured before and at 6, 12, 24, and 48 months after biventricular repair., Results: The follow-up ranged from 2 to 98 months. There was no early mortality, and the midterm survival rate was 95%. One patient died of a noncardiac- and nonintervention-related cause. Seven patients (37%) required a total of 8 reinterventions because of recurring or residual obstructive lesions. After biventricular repair, the left cardiac structures grew significantly., Conclusions: Neonatal biventricular repair is successful and safe in HLHC patients, even with preoperative mitral and aortic valve annulus Z-scores of -4.5 and -5.5, respectively. Residual or restenosis required reintervention in 37% of our HLHC population, but was not significantly correlated with the magnitude of the preoperative Z-scores. Within the first 6 months of follow-up, the Z-scores almost normalized., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A congenital coronary cameral fistula (CCCF) is characterized by left ventricular dysfunction, electrocardiographic changes due to a reduced left coronary blood flow and impaired physical activity. CCCF's with a giant aneurysm are very rarely seen. The presence of a giant aneurysm imposes even greater health risks. We report a case of a CCCF from the left coronary artery to the right ventricle with a large distal aneurysm in a 20-year-old woman that we closed percutaneously with coils for the closure of ventricular septal defects (VSD) and persistent ductus arteriosus (PDA)., (© 2014 Wiley Periodicals, Inc.)

Background and Purpose: The authors previously reported on the functional recovery of an adult with chronic, severe ataxia secondary to traumatic brain injury (TBI) after 28 sessions of trunk stabilization and locomotor training (LT). The purpose of this case report is to describe this individual's functional abilities 3.5 years after the intervention., Case Description: Thirteen months post-TBI and not expected to be a functional ambulator, an adult male participated in a trunk stabilization and LT intervention. After the intervention, he continued to exercise in a hospital-based fitness program and received additional physical therapy. Evaluation of balance, gait, trunk performance, self-reported function, and quality of life was performed at 6 weeks (baseline), 1 year, and 3.5 years after completing the intervention., Outcomes: Balance, gait, and function improved. Resting left transverse abdominis thickness, measured using ultrasound imaging, increased as did left-side bridge and trunk flexion endurance. He increased community participation and expressed general satisfaction with his overall quality of life., Discussion and Conclusion: In the 3.5 years after participation in an intervention of trunk stabilization and LT this adult became an independent limited community ambulator. Persons with severe ataxia secondary to TBI may continue to improve many years after injury.

The purpose of this study is to describe the effects of trunk stabilization training and locomotor training (LT) using body-weight support on a treadmill (BWST) and overground walking on balance, gait, self-reported function, and trunk muscle performance in an adult with severe ataxia secondary to brain injury. There are no studies on the effectiveness of these combined interventions in persons with ataxia. The subject was a 23-year-old male who had a traumatic brain injury 13 months prior. An A-B-A withdrawal single-system design was used. Outcome measures were Berg Balance Test (BBT), timed unsupported stance, Functional Ambulation Category (FAC), 10-meter walk test (10-MWT), Outpatient Physical Therapy Improvement in Movement Assessment Log (OPTIMAL), transverse abdominis (TrA) thickness, and isometric trunk endurance tests. Performance on the BBT, timed unsupported stance, FAC, 10-MWT, and OPTIMAL each improved after 10 weeks of intervention. In additions, TrA symmetry at rest improved as did right side-bridge endurance time. LT, using BWST and overground walking, and trunk stabilization training may be effective in improving balance, gait, function, and trunk performance in individuals with severe ataxia. Further research with additional subjects is indicated.

Investigation showed that in a two-choice correction procedure the probability of an errorless response in those rats which have consistently made errors is not constant, as required by the all-or-none model, but increases with trials. Even an all-or-none model which provides for accidental error and accidental success is inadequate.