Inhibition of the Renin-Angiotensin System Improves Response to Neoadjuvant Therapy in Patients With Liver Metastasis of Colorectal Cancers.

INTRODUCTION: Renin-angiotensin-aldosterone system inhibitors (RAAS-I) have been shown to prolong overall survival in patients with liver metastasized colorectal cancer in combination with antiangiogenic treatment. The effects of RAAS-I combined with neoadjuvant chemotherapy on colorectal cancer liver metastasis remain unexplored. We aimed to study the response of patients undergoing liver resection to RAAS-I in combination with neoadjuvant therapy to elucidate their potential benefits. METHODS: Between February 2005 and May 2012, 62 patients fulfilled the inclusion criteria for distant metastasis (cM1) and comparable computed tomography or magnetic resonance tomography scans in the Picture Archiving Communication System of our center before and after neoadjuvant chemotherapy. Follow-up data and clinicopathological characteristics were collected from a prospective database and retrospectively investigated. The chemotherapeutic response to liver metastasis was evaluated according to the Response Evaluation Criteria in Solid Tumors criteria 1.1. RESULTS: Comparing the average reduction of measured lesions, a significant response to chemotherapy was detected in the patients receiving RAAS-I (n = 24) compared to those who did not (n = 38) (P = 0.031). Interestingly, the effect was more distinctive when the size reduction was compared between high responses with more than 50% size reduction of all measured lesions (P = 0.011). In the subgroup analysis of patients receiving bevacizumab treatment, high responses to chemotherapy were observed only in the RAAS-I cohort (28.6% versus 0%, P = 0.022). CONCLUSIONS: For neoadjuvantly treated patients, concomitant antihypertensive treatment with RAAS-I showed a higher total size reduction of liver metastasis as a sign of treatment response, especially in combination with antiangiogenic treatment with bevacizumab.

The effect of the SARS-CoV-2 pandemic and civil unrest on massive transfusion protocol activations in Minneapolis 2020.

BACKGROUND: The year 2020 presented the transfusion community with unprecedented events and challenges, including the ongoing SARS-CoV-2 (COVID-19) pandemic, and more recently by civil unrest, following the death of George Floyd in late May of 2020. As a level 1 trauma center located in Minneapolis, Minnesota, Hennepin Healthcare (HCMC) offers a unique perspective into the changes in massive transfusion protocol (MTP) activations and usage during this tumultuous period. This may provide insight for addressing similar future events. STUDY DESIGN AND METHODS: MTP logs from March 2020 to August 2020 were compared to logs from March to August 2019. The data were de-identified, and MTP activations and component usage were categorized by activation reason. These categories were compared across the 2-year period to examine the impact of COVID-19, including stay-at-home orders, and civil unrest. RESULTS: For the examined 6 months of the year 2020, there were a total of 140 MTP activations, compared to 143 in 2019. There were more activations for violent trauma (VT) in 2020 than 2019 (44 vs. 32). This increase in activations for VT was offset by a decrease in non-trauma activations (54 vs. 66). There was a significant increase in the number of components used in VT activations. DISCUSSION: During 2020, the initial mild decrease in MTP activations was followed by a dramatic increase in the number of activations and component usage for VT in June and July of that year.

New Polyfluorinated Cyanine Dyes for Selective NIR Staining of Mitochondria.

In this communication, the synthesis of three unknown polyfluorinated cyanine dyes and their application as selective markers for mitochondria are presented. By incorporating fluorous side chains into cyanine dyes, their remarkable photophysical properties were enhanced. To investigate their biological application, several different cell lines were incubated with the synthesized cyanine dyes. It was discovered that the presented dyes can be utilized for selective near-infrared-light (NIR) staining of mitochondria, with very low cytotoxicity determined by MTT assay. This is the first time that polyfluorinated cyanine fluorophores are presented as selective markers for mitochondria. Due to the versatile applications of polyfluorinated fluorophores in bioimaging and materials science, it is expected that the presented fluorophores will be stimulating for the scientific community.

Glutaminase 1 regulates the release of extracellular vesicles during neuroinflammation through key metabolic intermediate alpha-ketoglutarate.

BACKGROUND: Extracellular vesicles (EVs) are important in the intercellular communication of the central nervous system, and their release is increased during neuroinflammation. Our previous data demonstrated an increased release of EVs during HIV-1 infection and immune activation in glial cells. However, the molecular mechanism by which infection and inflammation increase EV release remains unknown. In the current study, we investigated the role of glutaminase 1 (GLS1)-mediated glutaminolysis and the production of a key metabolic intermediate α-ketoglutarate on EV release. METHODS: Human monocyte-derived macrophage primary cultures and a BV2 microglia cell line were used to represent the innate immune cells in the CNS. Transmission electron microscopy, nanoparticle tracking analysis, and Western blots were used to determine the EV regulation. GLS1 overexpression was performed using an adenovirus vector in vitro and transgenic mouse models in vivo. Data were evaluated statistically by ANOVA, followed by the Bonferroni post-test for paired observations. RESULTS: Our data revealed an increased release of EVs in GLS1-overexpressing HeLa cells. In HIV-1-infected macrophages and immune-activated microglia BV2 cells, treatment with bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) or CB839, two specific GLS inhibitors, significantly decreased EV release, suggesting a critical role of GLS1 in EV release. Furthermore, addition of α-ketoglutarate or ceramide rescued EV release during BPTES treatment, implicating α-ketoglutarate and ceramide as critical downstream effectors for GLS inhibitors. These findings were further corroborated with the investigation of brain tissues in GLS1-transgenic mice. The EV levels were significantly higher in GLS1 transgenic mice than those in control mice, suggesting that GLS1 increases EV release in vivo. CONCLUSIONS: These findings suggest that GLS1-mediated glutaminolysis and its downstream production of α-ketoglutarate are essential in regulating EV release during HIV-1 infection and immune activation. These new mechanistic regulations may help understand how glutamine metabolism shapes EV biogenesis and release during neuroinflammation.

The expression of hematopoietic progenitor cell antigen CD34 is regulated by DNA methylation in a site-dependent manner in gastrointestinal stromal tumours.

The anatomic site-dependent expression of hematopoietic progenitor cell antigen CD34 is a feature of gastrointestinal stromal tumours (GISTs). The basis for the differential CD34 expression is only incompletely understood. This study aimed at understanding the regulation of CD34 in GISTs and clarification of its site-dependent expression. Two sample sets of primary GISTs were interrogated including 52 fresh-frozen and 134 paraffin-embedded and formalin-fixed specimens. DNA methylation analysis was performed by HumanMethylation450 BeadChip array in three cell lines derived from gastric and intestinal GISTs, and differentially methylated CpG sites were established upstream of CD34. The methylation degree was further quantified by pyrosequencing, and inverse correlation with CD34 mRNA and protein abundance was revealed. The gene's expression could be activated upon induction of DNA hypomethylation with 5-aza-2'-deoxycytidine in GIST-T1 cells. In patient samples, a strong inverse correlation of DNA methylation degree with immunohistochemically evaluated CD34 expression was documented. Both CD34 expression and DNA methylation levels were specific to the tumours' anatomic location and mutation status. A constant decrease in methylation levels was observed ranging from almost 100% hypermethylation in intestinal GISTs from duodenum to hypomethylation in rectum. CD34 was heavily methylated in gastric PDGFRA-mutant GISTs in comparison to hypomethylated KIT-mutant counterparts. Next to CD34 hypermethylation, miR-665 was predicted and experimentally confirmed to target CD34 mRNA in GIST-T1 cells. Our results suggest that CD34 expression in GISTs may undergo a complex control by DNA methylation and miR-665. Differential methylation and expression of CD34 in GISTs along the gastrointestinal tract axis and in tumours that harbour different gain-of-function mutations suggest the origin from different cell populations in the gastrointestinal tract.

Combined DNA methylation and gene expression profiling in gastrointestinal stromal tumors reveals hypomethylation of SPP1 as an independent prognostic factor.

Gastrointestinal stromal tumors (GISTs) have distinct gene expression patterns according to localization, genotype and aggressiveness. DNA methylation at CpG dinucleotides is an important mechanism for regulation of gene expression. We performed targeted DNA methylation analysis of 1.505 CpG loci in 807 cancer-related genes in a cohort of 76 GISTs, combined with genome-wide mRNA expression analysis in 22 GISTs, to identify signatures associated with clinicopathological parameters and prognosis. Principal component analysis revealed distinct DNA methylation patterns associated with anatomical localization, genotype, mitotic counts and clinical follow-up. Methylation of a single CpG dinucleotide in the non-CpG island promoter of SPP1 was significantly correlated with shorter disease-free survival. Hypomethylation of this CpG was an independent prognostic parameter in a multivariate analysis compared to anatomical localization, genotype, tumor size and mitotic counts in a cohort of 141 GISTs with clinical follow-up. The epigenetic regulation of SPP1 was confirmed in vitro, and the functional impact of SPP1 protein on tumorigenesis-related signaling pathways was demonstrated. In summary, SPP1 promoter methylation is a novel and independent prognostic parameter in GISTs, and might be helpful in estimating the aggressiveness of GISTs from the intermediate-risk category.

Understanding Employee Voice Behavior Through the Use of Digital Voice Channel in Long-Term Care: Protocol for an Embedded Multiple-Case Study.

BACKGROUND: Specific challenges in the health care sector, such as hierarchical structures, shortages of nursing staff, and high turnover of nursing staff, can be addressed by a change process of organizational culture into shared governance. Data from business organizations show that the use of digital voice channels provides employee voice. This approach makes concrete the opportunity for employees to raise their voices by answering surveys and making comments in an anonymous forum, which subsequently positively influences staff turnover and sick leave. Since there is no clear understanding of how a digital voice channel can be used in long-term care to address employee voice, a research gap has been identified. OBJECTIVE: The purpose of ADVICE (Understanding Employee Voice Behavior; the acronym for this study) is to understand how the use of a digital voice channel performs in long-term care (residential long-term care and home care facilities). The aim of this study is to understand how the digital voice channel can support staff in making their voices heard and to see what managers need to use the voice channel to change the work environment. METHODS: An embedded multiple-case study will be used to explore the experiences of 2 health care providers who have already implemented a digital voice channel. ADVICE is organized into two main phases: (1) a scoping review and (2) an embedded multiple-case study. For this purpose, focus group interviews with employees, discursive-dialogical interviews with managers, meeting protocols, and data from the digital voice channel will be analyzed. First, all units of analysis from every embedded unit will be separately analyzed and then comprehensively analyzed to obtain a case vignette from every embedded unit (within-analysis). In the second stage, the analyzed data from the embedded units will be compared with each other in a comparative analysis (cross-analysis). RESULTS: The results will provide insight into how digital voice channels can be used in long-term care to address employee voice. We expect to find how the digital voice channel can empower nurses to speak up and, consequently, create a better work environment. Data collection began in August 2023, and from a current perspective, the first results are expected in summer 2024. CONCLUSIONS: In summary, the results may help to better understand the use of a digital voice channel in the health care sector and its transformative potential for leadership. At the organizational level, research can help to improve the attractiveness of the workplace by understanding how to give employees a voice. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/48601.

Dietary protein content affects isotopic carbon and nitrogen turnover.

RATIONALE: Isotopic turnover quantifies the metabolic renewal process of elements in organs and excreta. Knowledge of the isotopic turnover of animal organs and excreta is necessary for diet reconstruction via stable isotope analysis, as used in animal ecology, palaeontology and food authentication. Effects of dietary protein content on the isotopic carbon and nitrogen turnover (i.e. delay, representing the time between ingestion and start of renewal, and half-life) are unknown for most mammalian organs and excreta. METHODS: To examine the effect of dietary protein content on turnover (delay and turnover rate), we fed 18 rats either a diet at protein maintenance or above protein maintenance, and quantified their isotopic carbon and nitrogen turnover in ten organs and excreta. These included the excreta faeces and urine, the visceral organs blood plasma, liver, kidney, lung and spleen, the cerebral tissue brain, and the muscular tissues heart and muscle. For data analysis, we used piecewise linear/non-linear exponential modelling that allows quantifying delay and turnover rate simultaneously. RESULTS: Delays were ~0.5 days for carbon and nitrogen turnover and were not affected by dietary protein content. Half-lives during the following reaction progress were in the range of 1 to 45 days, increasing from excreta to visceral organs to muscular and cerebral organs. Rats fed the higher protein amount had 30% shorter nitrogen half-lives, and 20% shorter carbon half-lives. CONCLUSIONS: The renewal times of organs and excreta depend on the dietary protein content. Hence, isotopic diet reconstruction is confronted with variation in half-lives within the same organ or excrement, altering the time window through which information can be perceived.

Effects of Arm Dominance and Decision Demands on Change of Direction Performance in Handball Players.

This field study investigated the effect of unilateral dominance (handedness of players) on the change of direction speed in a specific cutting manoeuvre with a ball (in the direction of the throwing arm vs. against the direction of the throwing arm) in team handball. In addition, the effect of a cutting manoeuvre in response to an immediate stimulus compared to one planned in advance on the movement speed was analysed. Forty participants (22 male, 18 female, Mage 23 years) performed change of direction actions to the left and the right side (the direction of the throwing arm vs. against the direction of the throwing arm) under planned and reactive (light as visual stimuli) conditions. Change of direction speed was measured post-hoc by video-analyses. The results showed two effects. First, the decision demand in reaction to a visual stimulus reduced the speed in the change of direction compared to the planned action. Second, participants performed their action faster in the direction of the throwing arm than against it. The results replicate the effects of decision demands of previous studies and regardless of the reaction to the stimuli being unspecific, further studies could investigate if specific training can reduce the speed loss due to decision demands. The lateral speed differences of cutting manoeuvres of handball players have been analysed for the first time in this study. This effect could have several causes (e.g., coordination, power, motivation) which should be investigated in future studies in more detail.

Diaphragmatic pacing for the prevention of sudden unexpected death in epilepsy.

Sudden unexpected death in epilepsy is the leading cause of epilepsy related death. Currently, there are no reliable methods for preventing sudden unexpected death in epilepsy. The precise pathophysiology of sudden unexpected death in epilepsy is unclear; however, convergent lines of evidence suggest that seizure-induced respiratory arrest plays a central role. It is generally agreed that sudden unexpected death in epilepsy could be averted if the patient could be rapidly ventilated following the seizure. The diaphragm is a muscle in the chest which contracts to draw air into the lungs. Diaphragmatic pacing is a surgical intervention which facilitates normal ventilation in situations, such as spinal cord injury and sleep apnoea, in which endogenous respiration would be inadequate or non-existent. In diaphragmatic pacing, electrodes are implanted directly onto diaphragm or adjacent to the phrenic nerves which innervate the diaphragm. These electrodes are then rhythmically stimulated, thereby eliciting contractions of the diaphragm which emulate endogenous breathing. The goal of this study was to test the hypothesis that seizure-induced respiratory arrest and death can be prevented with diaphragmatic pacing. Our approach was to induce respiratory arrest using maximal electroshock seizures in adult, male, C57BL6 mice outfitted with EEG and diaphragmatic electrodes (n = 8 mice). In the experimental group, the diaphragm was stimulated to exogenously induce breathing. In the control group, no stimulation was applied. Breathing and cortical electrographic activity were monitored using whole body plethysmography and EEG, respectively. A majority of the animals that did not receive the diaphragmatic pacing intervention died of seizure-induced respiratory arrest. Conversely, none of the animals that received the diaphragmatic pacing intervention died. Diaphragmatic pacing improved postictal respiratory outcomes (two-way ANOVA, P < 0.001) and reduced the likelyhood of seizure-induced death (Fisher's exact test, P = 0.026). Unexpectedly, diaphragmatic pacing did not instantly restore breathing during the postictal period, potentially indicating peripheral airway occlusion by laryngospasm. All diaphragmatically paced animals breathed at some point during the pacing stimulation. Two animals took their first breath prior to the onset of pacing and some animals had significant apnoeas after the pacing stimulation. Sudden unexpected death in epilepsy results in more years of potential life lost than any other neurological condition with the exception of stroke. By demonstrating that seizure-induced respiratory arrest can be prevented by transient diaphragmatic pacing in animal models we hope to inform the development of closed-loop systems capable of detecting and preventing sudden unexpected death in epilepsy.

Reproducibility of the German and Slovakian Versions of the Dietary Habits and Nutrition Beliefs Questionnaire (KomPAN).

PURPOSE: The aim of this study was to assess the reproducibility and reliability of the KomPAN questionnaire among two groups of university students from Germany and Slovakia. METHODS: A total of 422 individuals (mean age 21.4 years, SD 4.0), including 197 from Slovakia (men 26.2%) and 225 from Germany (men 22.3%), were tested using the self-administered (SA-Q) version of the KomPAN questionnaire and then retested two weeks later. A cross-classification analysis, kappa coefficients, Cronbach's ɑ coefficients, and a test-retest result comparison were conducted separately for each group of students to assess the reproducibility and reliability of the questionnaire. RESULTS: The cross-classification values were higher than 46.2% among the German students and higher than 55.8% among the Slovakian students. The kappa coefficients ranged from 0.21 to 0.90 in the German students and from 0.38 to 0.94 in the Slovakian students. Cronbach's ɑ ranged from 0.58 to 0.78. CONCLUSION: The questionnaire displayed a moderate to very good reproducibility, which was slightly higher in the Slovakian group than in the German group. Therefore, the questionnaire can be recommended for further analysis and comparison of the dietary habits among Germans and Slovakians on a larger scale.

Association genetics in Solanum tuberosum provides new insights into potato tuber bruising and enzymatic tissue discoloration.

BACKGROUND: Most agronomic plant traits result from complex molecular networks involving multiple genes and from environmental factors. One such trait is the enzymatic discoloration of fruit and tuber tissues initiated by mechanical impact (bruising). Tuber susceptibility to bruising is a complex trait of the cultivated potato (Solanum tuberosum) that is crucial for crop quality. As phenotypic evaluation of bruising is cumbersome, the application of diagnostic molecular markers would empower the selection of low bruising potato varieties. The genetic factors and molecular networks underlying enzymatic tissue discoloration are sparsely known. Hitherto there is no association study dealing with tuber bruising and diagnostic markers for enzymatic discoloration are rare. RESULTS: The natural genetic diversity for bruising susceptibility was evaluated in elite middle European potato germplasm in order to elucidate its molecular basis. Association genetics using a candidate gene approach identified allelic variants in genes that function in tuber bruising and enzymatic browning. Two hundred and five tetraploid potato varieties and breeding clones related by descent were evaluated for two years in six environments for tuber bruising susceptibility, specific gravity, yield, shape and plant maturity. Correlations were found between different traits. In total 362 polymorphic DNA fragments, derived from 33 candidate genes and 29 SSR loci, were scored in the population and tested for association with the traits using a mixed model approach, which takes into account population structure and kinship. Twenty one highly significant (p < 0.001) and robust marker-trait associations were identified. CONCLUSIONS: The observed trait correlations and associated marker fragments provide new insight in the molecular basis of bruising susceptibility and its natural variation. The markers diagnostic for increased or decreased bruising susceptibility will facilitate the combination of superior alleles in breeding programs. In addition, this study presents novel candidates that might control enzymatic tissue discoloration and tuber bruising. Their validation and characterization will increase the knowledge about the underlying biological processes.

Small molecule kinase inhibitors enhance aminolevulinic acid-mediated protoporphyrin IX fluorescence and PDT response in triple negative breast cancer cell lines.

SIGNIFICANCE: We demonstrate that clinically used kinase inhibitors such as lapatinib can be used for enhancing aminolevulinic acid (ALA) for tumor fluorescence imaging and photodynamic therapy (PDT). AIM: ALA is used as a prodrug for protoporphyrin IX (PpIX) fluorescence-guided tumor resection and PDT. Our previous studies indicate that tumors with high ABCG2 activity exhibit low PpIX fluorescence, which hampers the application of ALA. We aim to determine whether clinically used ABCG2-interacting kinase inhibitors increase ALA-PpIX fluorescence and PDT. APPROACH: PpIX fluorescence was determined by spectrofluorometry, flow cytometry, and confocal microscopy after ALA alone or in combination with kinase inhibitors in triple negative breast cancer (TNBC) cell lines. Cytotoxicity was examined after ALA-PDT alone or in combination with kinase inhibitors. Effect of single and combination treatments on apoptosis was assessed by Western blot. RESULTS: Four kinase inhibitors (lapatinib, PD169316, sunitinib, gefitinib) significantly increased ALA-PpIX fluorescence and PDT response in TNBC cells with ABCG2 activity, but not in MCF10A nontumor breast epithelial cell line without ABCG2 activity. Confocal microscopic imaging showed that PpIX fluorescence was weak and diffuse after ALA alone, which was greatly enhanced by kinase inhibitors, particularly in the mitochondria. Lapatinib was the only inhibitor that significantly reduced PpIX efflux in cell culture medium and showed stronger enhancement of PDT response than other kinase inhibitors. Lapatinib, in combination with ALA, induced tumor cells to undergo apoptosis, whereas no apoptosis was detected after each individual treatment. CONCLUSIONS: Although all four kinase inhibitors were able to enhance ALA-PpIX fluorescence and PDT, lapatinib exhibited the strongest enhancement effect. As an FDA-approved kinase inhibitor for breast cancer treatment, lapatinib is ready to be used in combination with ALA for therapeutic enhancement in tumors with elevated ABCG2 activity. This rational combination approach warrants further investigation in tumor models.

Speckle Tracking Analysis Reveals Altered Left Atrial and Ventricular Myocardial Deformation in Patients with End-Stage Liver Disease.

BACKGROUND: Cardiac function can be influenced by liver cirrhosis and should be thoroughly evaluated before liver transplantation. We investigated left ventricular (LV) and, for the first time, left atrial (LA) strain and strain rate in end-stage liver cirrhosis patients of different etiologies. METHODS: This retrospective, cross-sectional study evaluated left heart function in 80 cirrhosis patients and 30 controls using standardized echocardiographic techniques and speckle tracking technology (STE) analysis. Serum markers of liver function were used for correlation analysis. RESULTS: While conventional parameters demonstrated no alteration in systolic function, speckle tracking analysis showed a significant increase in LV longitudinal strain throughout all cardiac layers, with significant correlation to model of end-stage liver disease (MELD) score. LA reservoir and conduit strain as well as LA strain rate in all phases were significantly reduced in end-stage liver disease (ESLD) patients compared to control. STE for the evaluation of LA phasic function seemed to be more sensitive than volumetric methods. Kaplan-Meier curves showed a trend towards reduced post-transplant survival in patients with a reduced LA reservoir and conduit strain. CONCLUSION: STE analysis detected increased LV and decreased LA deformation in cirrhosis patients, thus proving to be highly sensitive to cardiac changes and useful for more precise cardiac evaluation.

Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population.

Adipose tissue expansion, as seen in obesity, is often metabolically detrimental causing insulin resistance and the metabolic syndrome. However, white adipose tissue expansion at early ages is essential to establish a functional metabolism. To understand the differences between adolescent and adult adipose tissue expansion, we studied the cellular composition of the stromal vascular fraction of subcutaneous adipose tissue of two and eight weeks old mice using single cell RNA sequencing. We identified a subset of adolescent preadipocytes expressing the mature white adipocyte marker Asc-1 that showed a low ability to differentiate into beige adipocytes compared to Asc-1 negative cells in vitro. Loss of Asc-1 in subcutaneous preadipocytes resulted in spontaneous differentiation of beige adipocytes in vitro and in vivo. Mechanistically, this was mediated by a function of the amino acid transporter ASC-1 specifically in proliferating preadipocytes involving the intracellular accumulation of the ASC-1 cargo D-serine.

Cost of care for persons with dementia: using a discrete-time Markov chain approach with administrative and clinical data from the dementia service Centres in Austria.

BACKGROUND: There is growing evidence that the cost for dementia care will increase rapidly in the coming years. Therefore, the objective of this paper was to determine the economic impact of treating clients with dementia in outpatient Dementia Service Centres (DSCs) and simulate the cost progression with real clinical and cost data. METHODS: To estimate the cost for dementia care, real administrative and clinical data from 1341 clients of the DSCs were used to approximate the total cost of non-pharmaceutical treatment and simulate the cost progression with a discrete-time Markov chain (DTMC) model. The economic simulation model takes severity and progression of dementia into account to display the cost development over a period of up to ten years. RESULTS: Based on the administrative data, the total cost for treating these 1341 clients of the DSCs came to 67,294,910 EUR in the first year. From these costs, 74% occurred as indirect costs. Within a five-year period, these costs will increase by 7.1-fold (16.2-fold over 10 years). Further, the DTMC shows that the greatest share of the cost increase derives from the sharp increase of people with severe dementia and that the cost of severe dementia prevails the cost in later periods. CONCLUSION: The DTMC model has shown that the cost increase of dementia care is mostly driven by the indirect cost and the increase of severity of dementia within any given year. The DTMC reveals also that the cost for mild dementia will decrease steadily over the time period of the simulation, whereas the cost for severe dementia increases sharply after running the simulation for 3 years.

Primary Neuroendocrine Tumor of the Ileostomy Stoma on 68Ga-DOTATATE PET/CT.

A 75-year-old man presented with bleeding ileostomy stoma 20 years after total colectomy and end ileostomy for chronic ulcerative colitis. On physical examination, the stoma was mass-like and firm with friable mucosa. Wedge biopsy of the ileostomy stoma revealed well-differentiated neuroendocrine tumor (intermediate grade). Ga-DOTATATE PET/CT showed mass-like focal radiotracer uptake at the ileostomy site without radiotracer-avid lymphadenopathy or distant metastatic disease. No additional sites of neoplasm in the gastrointestinal tract were further identified by endoscopy. The diagnosis of isolated primary neuroendocrine tumor of the ileostomy stoma was confirmed, an extremely rare entity.

3-T T2 mapping magnetic resonance imaging for biochemical assessment of normal and damaged glenoid cartilage: a prospective arthroscopy-controlled study.

This study evaluated the ability of T2 mapping to assess the glenoid cartilage using arthroscopy as the gold standard. Eighteen consecutive patients (mean age: 52.4 ± 14.72 years, including 12 men) with shoulder pain underwent T2 mapping at 3-T with subsequent shoulder arthroscopy. With correlation to cartilage-sensitive morphologic sequences regions-of-interest were placed in the corresponding T2 maps both in normal-appearing cartilage and focal cartilage lesions using a quadrant-wise approach. Inter-reader and intra-reader correlation coefficients (ICCs) between two independent radiologists as well as cut-off values with their sensitivities/specificities for the detection of cartilage damage were calculated. The mean T2 value for healthy cartilage was 23.0 ± 3 ms with significantly higher values in the superior quadrants compared to the inferior quadrants (p < 0.0001). In 5 patients with focal cartilage damage significantly higher T2 values of 44.7 ± 3.7 ms (P < 0.01) were observed. The maximum T2 value in normal cartilage (27.3 ms) was lower than the minimum value in damaged cartilage (40.8 ms) resulting in perfect sensitivities/specificities of 100% (95% confidence-interval 47.8-100.0) for all cut-off values between 27.3-40.8 ms. ICCs ranged between 0.63 and 0.99. In conclusion, T2 mapping can evaluate biochemical cartilage integrity and discriminates arthroscopy-proven healthy and damaged glenoid cartilage with high diagnostic performance.

Impact of needle positioning on ablation success of irreversible electroporation: a unicentric retrospective analysis.

Irreversible electroporation (IRE) is an ablation procedure in which cell death is induced by ultrashort electrical pulses. In this unicentric retrospective study we investigated the influence of needle positioning on ablation success. 15 IREs with residual tumor after ablation, detected in the first follow-up MRI, were included, and compared with 30 successful ablations. Evaluation of needle geometry revealed significantly higher values for needle divergence (NDiv, 7.0° vs. 3.7°, p = 0.02), tumor-center-to-ablation-center distance (TACD, 11.6 vs. 3.2 mm, p < 0.001), tumor-to-needle distance (4.7 vs. 1.9 mm, p = 0.04), and tumor diameter per needle (7.5 vs. 5.9 mm/needle, p = 0.01) in patients with residual tumor. The average number of needles used was higher in the group without residual tumor after ablation (3.1 vs. 2.4, p = 0.04). In many cases with residual tumor, needle depth was too short (2.1 vs. 6.8 mm tumor overlap beyond the most proximal needle tip, p < 0.01). The use of a stereotactic navigation system in 10 cases resulted in a lower NDiv value (2.1° vs. 5.6°, p < 0.01). Thus, correct needle placement seems to be a crucial factor for success and the assistance of a stereotactic navigation system might be helpful. As most important geometrical parameter TACD could be identified. Main reasons for high TACD were insufficient needle depth and a lesion location out of the needle plane.