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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Diet Quality Compared to the Nutritional Knowledge of Polish, German, and Slovakian University Students-Preliminary Research.

The eating habits of students differ significantly from those recommended by health practitioners. The aim of this study was to find differences related to diet quality and knowledge on nutrition among Polish, German, and Slovakian students as well as to examine which factors differentiate the diet quality of students from these three countries. The study was conducted on a group of 394 university students from Poland, Germany, and Slovakia. The assessment of diet quality and knowledge on food and nutrition was done with the use of the Dietary Habits and Nutrition Beliefs Questionnaire. The diet of German students was characterized by a significantly higher consumption of legume-based foods, vegetables, and fruit compared to Polish students and Slovakian participants (p < 0.001). The diet of the Poles was characterized by a high consumption of cured meat, smoked sausages, hot dogs, white bread and bakery products, butter, fried foods, and energy drinks. The most important factors significantly associated with diet quality involved the country, place of residence, Body Mass Index (BMI), physical activity, and time spent watching TV or using a computer. Polish students were characterized by the highest level of knowledge on food and nutrition (p < 0.001). However, it was not reflected in their diet. The authorities of universities should aim to provide students with access to canteens on campuses which would offer the possibility of consumption of both affordable and healthy meals.

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.

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.

Substrate-dependent CO2 fixation in heterotrophic bacteria revealed by stable isotope labelling.

Virtually all heterotrophs incorporate carbon dioxide by anaplerotic fixation. Little explored, however, is the interdependency of pathways and rates of CO2fixation on the concurrent usage of organic substrate(s). Potentially, this could reveal which substrates out of a pool of dissolved organic carbon are utilised by environmental microorganisms. To explore this possibility, Bacillus subtilis W23 was grown in a minimal medium with normalised amounts of either glucose, lactate or malate as only organic substrates, each together with 1 g/L NaH13CO3. Incorporation of H13CO3- was traced by elemental analysis-isotope ratio mass spectrometry of biomass and gas chromatography-mass spectrometry of protein-derived amino acids. Until the late logarithmic phase, 13C incorporation into the tricarboxylic acid cycle increased with time and occurred via [4-13C]oxaloacetate formed by carboxylation of pyruvate. The levels of 13C incorporation were highest for growth on glucose and lowest on malate. Incorporation of 13C into gluconeogenesis products was mainly detected in the lactate and malate experiment, whereas glucose down-regulated this path. A proof-of-principle study with a natural groundwater community confirmed the ability to determine incorporation from H13CO3- by natural communities leading to specific labelling patterns. This underlines the potential of the labelling approach to characterise carbon sources of heterotrophic microorganisms in their natural environments.

Association between colorectal cancer testing and insurance type: Evidence from the Swiss Health Interview Survey 2012.

Both colonoscopy and fecal occult blood test (FOBT) are commonly used for colorectal cancer (CRC) screening, but colonoscopy costs much more than FOBT. Swiss insurance offers high or low deductibles and choice of basic or private insurance. We hypothesized that high deductibles and basic insurance discourage colonoscopy, but do not change FOBT rates. We determined the proportion of patients tested for CRC in Switzerland (colonoscopy within 10 years, FOBT within 2 years), and determined associations with health insurance type. We extracted data on 50-75-year-olds from the Swiss Health Interview Surveys of 2012 to determine colonoscopy and FOBT testing rates (n = 7335). Multivariate logistic regression models estimated prevalence ratios (PRs) of CRC testing associated with health insurance type (deductible and private insurance), adjusted for socio-demographic factors (age, gender, education, income) and self-rated health. The weighted proportion of individuals tested for CRC within recommended intervals was 39.5%. Testing with colonoscopy was significantly associated with private insurance (PR 1.85, 95% CI: 1.46-2.35) and low deductible (PR 2.00, 95% CI: 1.56-2.57). Testing with FOBT was significantly associated with deductible (PR 1.71, 95%CI:1.09-2.68) but not with private insurance. About 60% of the Swiss population was not current with CRC testing. After adjusting for covariates, private insurance and low deductible was significantly associated with higher prevalence of CRC testing, indicating that waiving the deductible could increase CRC screening uptake and reduce health inequality.

Comparative expression profiling in the intestine of patients with Giardia-induced postinfectious functional gastrointestinal disorders.

BACKGROUND: A Giardia outbreak in Bergen, Norway, caused postinfectious functional gastrointestinal disorders (PI-FGIDs). Despite the devastating effects of this outbreak, it presented a unique chance to investigate the implication on the dysregulation of genetic pathways in PI-FGID. METHODS: We performed the first comparative expression profiling of miRNAs and their potential target genes in microdissected rectal biopsies from 20 Giardia-induced PI-FGID patients vs 18 healthy controls by nCounter analysis. Subsequently, candidates were validated on protein level by immunostaining. KEY RESULTS: miRNA profiling on rectal biopsy samples from 5 diarrhea-predominant PI-IBS cases compared to 10 healthy controls revealed differential expression in the epithelial layer. The top five regulated miRNAs were implicated in GI disease, inflammatory response, and immunological disease. Subsequently, these miRNAs and 100 potential mRNA targets were examined in 20 PI-FGID cases and 18 healthy controls in both the mucosal epithelium and the lamina propria. Although deregulation of the selected miRNAs could not be verified in the larger sample set, mRNAs involved in barrier function were downregulated in the epithelium. Pro-inflammatory genes and genes implicated in epigenetic modifications were upregulated in the lamina propria. Immunostaining for selected candidates on 17 PI-FGID cases and 16 healthy controls revealed increased tryptase levels as well as a decreased and aberrant subcellular expression of occludin. CONCLUSIONS AND INFERENCES: Genes relevant to immune and barrier function as well as stress response and epigenetic modulation are differentially expressed in PI-FGIDs and may contribute to disease manifestation.

Impact of MRI, CT, and Clinical Characteristics on Microbial Pathogen Detection Using CT-Guided Biopsy for Suspected Spondylodiscitis.

Spondylodiscitis accounts for 2-7% of osteomyelitis cases and is characterized by pain, systemic inflammation, and permanent neurological deficits. We aimed to identify imaging characteristics and clinical parameters to successfully predict microbiological pathogens by computed tomography (CT)-guided biopsy in suspected spondylodiscitis cases. Forty consecutive patients (mean age 65.1 years) with suspected spondylodiscitis underwent CT-guided biopsy. CT features (non-sclerotic endplate erosions (NSEs)), magnetic resonance criteria (paravertebral/epidural abscess (PA/EA) formation), and clinical data (C-reactive protein (CRP) > 50 mg/L) were assessed for their predictive potential. NSEs were detected in 6/11 (54.5%) and 1/29(3.4%) patients with positive and negative microbiology, respectively. PA and EA, respectively, were present in 7/11(63.6%) and 3/11 patients with positive microbiology and 7/29 (24.1%) and 2/29 patients with negative microbiology. CRP > 50 was observed in 7/11 (63.6%) and in 7/29 (24.1%) patients with positive and negative microbiology, respectively. Three double combinations possessed near-perfect specificity (PA + NSE, 100%; PA + CRP > 50, 96.6%; NSE + CRP > 50, 96.6%). The top three Youden indices included combinations with NSE. Since CT/magnetic resonance (MR) imaging and CRP are routinely used to evaluate spondylodiscitis, the presented diagnostic criteria and combinations can aid decision-making for biopsy.

Right Heart Remodeling in Patients with End-Stage Alcoholic Liver Cirrhosis: Speckle Tracking Point of View.

BACKGROUND: Data regarding cardiac remodeling in patients with alcoholic liver cirrhosis are scarce. We sought to investigate right atrial (RA) and right ventricular (RV) structure, function, and mechanics in patients with alcoholic liver cirrhosis. METHODS: This retrospective cross-sectional investigation included 67 end-stage cirrhotic patients, who were referred for evaluation for liver transplantation and 36 healthy controls. All participants underwent echocardiographic examination including strain analysis, which was performed offline. RESULTS: RV basal diameter and RV thickness were significantly higher in patients with cirrhosis. Conventional parameters of the RV systolic function were similar between the observed groups. Global, endocardial, and epicardial RV longitudinal strains were significantly lower in patients with cirrhosis. Active RA function was significantly higher in cirrhotic patients than in controls. The RA reservoir and conduit strains were significantly lower in cirrhotic patients, while there was no difference in the RA contractile strain. Early diastolic and systolic RA strain rates were significantly lower in cirrhotic patients than in controls, whereas there was no difference in the RA late diastolic strain rate between the two groups. Transaminases and bilirubin correlated negatively with RV global longitudinal strain and RV-free wall strain in patients with end-stage liver cirrhosis. The Model for End-stage Liver Disease (MELD) score, predictor of 3-month mortality, correlated with parameters of RV structure and systolic function, and RA active function in patients with end-stage liver cirrhosis. CONCLUSIONS: RA and RV remodeling is present in patients with end-stage liver cirrhosis even though RV systolic function is preserved. Liver enzymes, bilirubin, and the MELD score correlated with RV and RA remodeling.

Variation in colorectal cancer testing between primary care physicians: a cross-sectional study in Switzerland.

OBJECTIVES: To determine the proportion of 50-75-year-old patients who visit a primary care physician's (PCP) office and were tested for colorectal cancer (CRC) by either colonoscopy within 10 years or fecal occult blood testing (FOBT) within 2 years. To describe the variation in care between PCPs and factors associated with these proportions. METHODS: Cross-sectional data collected between April and December 2017. PARTICIPANTS: PCPs reporting for the Swiss Sentinel Surveillance Network. Each PCP collected demographic data and CRC testing status from 40 consecutive patients. MEASUREMENTS: proportions of patients up to date with CRC screening and method used (colonoscopy/FOBT/Other); variation in the outcome measures between PCPs; association of physician-level factors with main outcomes. RESULTS: 91/129 PCPs collected data from 3451 patients; 45% had been tested for CRC within recommended intervals (41% colonoscopy, 4% FOBT). The proportions of patients tested and testing with colonoscopy versus FOBT varied widely between PCPs. Language region was associated with PCPs' rate of FOBT prescription. CONCLUSIONS: Less than half of patients who visited PCPs in Switzerland were tested for CRC within recommended intervals. PCPs varied widely in their testing practices.