Colorectal cancer (CRC) is the second most common cause of all cancer deaths in Europe and the Western world with a lifetime risk of approximately 5%. Despite several improvements in the treatment of patients with unresectable CRC prognosis is poor and there is the need of developing new treatment strategies for patients with metastatic chemorefractory disease. The S100 calcium binding protein A4 (S100A4) predicts metastasis formation and reduced CRC patient survival. S100A4 was previously identified as transcriptional target of the Wnt/β-catenin signaling pathway. The Food and Drug Administration (FDA)-approved anti-helminthic drug niclosamide is known to intervene in the Wnt/β-catenin pathway signaling, leading to reduced expression of S100A4 linked to restricted in vivo metastasis formation. Thus, we aim at translation of our findings on restricting S100A4-driven metastasis into clinical practice for treating metastasized CRC patients progressing after standard therapy. NIKOLO is a phase II, single center, one-arm open-label clinical trial to investigate the safety and efficacy of niclosamide tablets in patients with metastasized CRC progressing under standard therapy. Eligible patients will receive 2 g of orally applied niclosamide once a day and will continue with the treatment once daily till disease progression or toxicity. Toxicities will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03. The primary objective of this trial is to assess the progression free survival after 4 months, secondary objectives are overall survival, time to progression, disease control rate (remission + partial remission + stable disease), and safety. Furthermore, pharmacokinetic analysis will be conducted to evaluate niclosamide plasma concentration. This study is expected to provide evidence of the feasibility, toxicity and efficacy of niclosamide in the treatment of patients with metastasized CRC and could help to establish a new treatment option. The study is registered with ClinicalTrials.gov ( NCT02519582 ) and the European Clinical Trials Database (EudraCT 2014-005151-20).

In participants with stable chest pain referred for invasive coronary angiography, those with a coronary artery calcium score of 0 at CT had very low, while higher scores had increasing occurrence ... Background Coronary artery calcium (CAC) has prognostic value for major adverse cardiovascular events (MACE) in asymptomatic individuals, whereas its role in symptomatic patients is less clear. Pur...

The nicotinic system is involved in the pathophysiology of schizophrenia. However, very little is known about its genetic basis and how it relates to clinical symptoms and potentially pharmacological intervention. Here, we investigated five single nucleotide polymorphisms (SNPs) [rs3826029] [rs2337506] [rs982574] [rs904952] [rs2337980] of the cholinergic nicotinic receptor gene, alpha 7 subunit (CHRNA7) and their association to schizophrenia. We found an association with rs904952 (p = 0.009) in a German sample of 224 schizophrenic patients and 224 healthy control subjects. The same trend was shown in an independent Georgian sample of 50 schizophrenic patients, 57 first order unaffected relatives, and 51 healthy controls. In addition, visual backward masking (VBM), a sensitive test for early visual information processing, was assessed in the Georgian sample. In line with prior studies, VBM performance deficits were much more pronounced in schizophrenic patients and their unaffected relatives compared to healthy controls (schizophrenic patients: 156 ms; unaffected relatives: 60 ms; healthy controls: 33 ms). VBM was strongly correlated with SNP rs904952 (H[2] = 7.3, p = 0.026). Our results further support the notion that changes in the nicotinic system are involved in schizophrenia and open the avenue for pharmacological intervention.

The international nine-item Voice Handicap Index (VHI-9i) is a clinically established short-scale version of the original VHI, quantifying the patients’ self-assessed vocal handicap. However, the current vocal impairment classification is based on percentiles. The main goals of this study were to establish test–retest reliability and a sound statistical basis for VHI-9i severity levels. Between 2009 and 2021, 17,660 consecutive cases were documented. A total of 416 test–retest pairs and 3661 unique cases with complete multidimensional voice diagnostics were statistically analyzed. Classification candidates were the overall self-assessed vocal impairment (VHIs) on a four-point Likert scale, the dysphonia severity index (DSI), the vocal extent measure (VEM), and the auditory–perceptual evaluation (GRB scale). The test–retest correlation of VHI-9i total scores was very high (r = 0.919, p < 0.01). Reliability was excellent regardless of gender or professional voice use, with negligible dependency on age. The VHIs correlated best with the VHI-9i, whereas statistical calculations proved that DSI, VEM, and GRB are unsuitable classification criteria. Based on ROC analysis, we suggest modifying the former VHI-9i severity categories as follows: 0 (healthy): 0 ≤ 7; 1 (mild): 8 ≤ 16; 2 (moderate): 17 ≤ 26; and 3 (severe): 27 ≤ 36.

Low dietary K levels have been associated with increasing renal Ca excretion in humans, indicating a higher risk of calcium oxalate (CaOx) urolith formation. Therefore, the present study aimed to investigate whether dietary K also affects the urine composition of cats. A total of eight adult cats were fed diets containing 0·31 % native K and 0·50, 0·75 and 1·00 % K from KCl or KHCO₃and were evaluated for the effects of dietary K. High dietary K levels were found to elevate urinary K concentrations (P< 0·001). Renal Ca excretion was higher in cats fed the KCl diets than in those fed the KHCO₃diets (P= 0·026), while urinary oxalate concentrations were generally lower in cats fed the KCl diets and only dependent on dietary K levels in cats fed the KHCO₃diets (P< 0·05). Fasting urine pH increased with higher dietary K levels (P= 0·022), reaching values of 6·38 (1·00 % KCl) and 7·65 (1·00 % KHCO₃). K retention was markedly negative after feeding the cats with the basal diet ( − 197 mg/d) and the 0·50 % KCl diet ( − 131 mg/d), while the cats tended to maintain their balance on being fed the highest-KCl diet ( − 23·3 mg/d). In contrast, K from KHCO₃was more efficiently retained (P= 0·018), with K retention being between − 82·5 and 52·5 mg/d. In conclusion, the dietary inclusion of KHCO₃instead of KCl as K source could be beneficial for the prevention of CaOx urolith formation in cats, since there is an association between a lower renal Ca excretion and a generally higher urine pH. The utilisation of K is distinctly influenced by the K salt, which may be especially practically relevant when using diets with low K levels.

Purpose: The aim of this retrospective study was to evaluate correlations between parameters of quantitative computed tomography (QCT) analysis, especially the 15th percentile of lung attenuation (P15), and parameters of clinical tests in a large group of patients with pulmonary emphysema. Patients and Methods: One hundred and seventy-two patients with pulmonary emphysema and chronic obstructive pulmonary disease (COPD) global initiative for chronic obstructive lung disease (GOLD) stage 3 or 4 were assessed by nonenhanced thin-section CT scans in full inspiratory and expiratory breath-hold, pulmonary function test (PFT), a 6-minute walk test (6MWT), and quality of life questionnaires (SGRQ and CAT). QCT parameters included total lung volume (TLV), total emphysema score (TES), and P15, all measured at inspiration (IN) and expiration (EX). Differences between inspiration and expiration were calculated for TLV (TLV_Diff), TES (TES_Diff), and P15 (P15_Diff). Spearman correlation analysis was performed. Results: CT-measured lung volume in inspiration (TLV_IN) correlated strongly with spirometry-measured total lung capacity (TLC) (r=0.81, p< 0.001) and moderately to strongly with residual volume (RV), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV₁)/FVC (r=0.60, 0.56, and − 0.49, each p< 0.001). Lung volume in expiration (TLV_EX) correlated moderately to strongly with TLC, RV and FEV₁/FVC ratio (r=0.75, 0.66, and − 0.43, each p< 0.001). TES and P15 showed stronger correlations with the carbon monoxide transfer coefficient (KCO%) (r= − 0.42, 0.44, both p< 0.001), when measured during expiration. P15_Diff correlated moderately with KCO% and carbon monoxide diffusing capacity (DLCO%) (r= 0.41, 0.40, both p< 0.001). The 6MWT and most QCT parameters showed significant differences between COPD GOLD 3 and 4 groups. Conclusion: Our results suggest that QCT can help predict the severity of lung function decrease in patients with pulmonary emphysema and COPD GOLD 3 or 4. Some QCT parameters, including P15_EX and P15_Diff, correlated moderately to strongly with parameters of pulmonary function tests.