Life on the line - Incidence and management of central venous catheter complications in intestinal failure.

BACKGROUND & AIMS: Loss of venous access is threatening for patients with intestinal failure (IF) under long-term parenteral nutrition (PN). We aimed to identify the incidence of central venous catheter (CVC) complications, compare different devices, and analyze interventional recanalizing procedures to restore the patency of occluded CVCs. METHODS: For this retrospective cohort study, patient data from a prospective IF database spanning 16 years was analyzed at a tertiary referral center. Catheter dwell times (CDTs) were distinguished by Kaplan-Meier survival analysis and subgroup analyses were performed for different CVC types (tunneled/port catheters). Specific complications (occlusion, catheter-related infection (CRI), displacement, and material defect) were analyzed. Explantation rates and CDTs were compared. RESULTS: Overall, 193 CVCs in 77 patients with IF under PN could be enrolled (62.524 "CVC-days"). Broviac type "B" was found to be significantly superior to type "A" regarding occlusion, CRI, and material defects (log-rank test: p = 0.05; p = 0.026; p = 0.005 respectively). Port catheters were displaying the highest incidence of CRI (2.13 events/1000 catheter days). Interventional catheter recanalization was performed 91 times and significantly increased the CDT from a median of 131 days (IQR: 62; 258) to 389 days (IQR: 262; 731) (Mann-Whitney-U-test: p= <0.001) without increasing complications. CONCLUSIONS: Different complication rates and CDT were seen depending on CVC type. Tunneled catheters were significantly superior concerning CRI. Interventional catheter recanalization is a viable alternative to fibrinolytics to restore CVC patency, but long-term patency data is scarce.

Workforce strategies during the first wave of the COVID-19 pandemic: a retrospective online survey at intensive care units in Germany.

BACKGROUND: As the COVID-19 pandemic swept across the globe at the beginning of 2020, healthcare systems were forced to rapidly adapt and expand to meet the sudden surge in demand for intensive care services. This study is the first systematic analysis of the strategies employed by German hospitals to recruit personnel and expand bed capacities during the first wave of the pandemic, and to evaluate the effectiveness of those recruitment measures. METHODS: 152 German hospitals with intensive care capacities were selected and invited to participate in an online-based retrospective survey. Factors like the geographic distribution, individual COVID burden and level of care were considered for inclusion in the sample. The data were analyzed descriptively. RESULTS: A total of 41 hospitals participated in the survey. The additional demand for intensive care beds was met primarily by activating intensive care beds that were previously considered as non-operational in existing intensive care units (81% of respondents) and by upgrading recovery rooms (73%). The physician staffing requirements were met at approximately 75%, while the nursing staffing requirements were only met by about 45%. Staffing needs were met through reallocations/transfers (85%), staff recruitment from parental leave or retirement (49%), increased hours worked by internal staff (49%), new staff hiring (44%) and increased use of temporary staff (32%). Staff reallocations/transfers to critical care within a hospital were rated as the most effective measure. In this context, specialized personnel mostly from anesthesiology departments were appointed to intensive care medicine. CONCLUSIONS: Despite multiple recruitment efforts, the pandemic has exacerbated the nursing staff shortage. The reallocation of existing staff within hospitals was a key element in covering the staffing needs. However, additional measures and efforts are required in order to ensure that critically ill patients can be cared for without compromise. The results of this study may have important implications for healthcare providers and policymakers, offering an evidence-based foundation for responding to future public health emergencies with agility, efficiency, and success.

Safety management in times of crisis: Lessons learned from a nationwide status-analysis on German intensive care units during the COVID-19 pandemic.

Background: The status of Safety Management is highly relevant to evaluate an organization's ability to deal with unexpected events or errors, especially in times of crisis. However, it remains unclear to what extent Safety Management was developed and sufficiently implemented within the healthcare system during the COVID-19 pandemic. Providing insights of potential for improvement is expected to be directional for ongoing Safety Management efforts, in times of crisis and beyond. Method: A nationwide survey study was conducted among healthcare professionals and auxiliary staff on German Intensive Care Units (ICUs) evaluating their experiences during the first wave of the COVID-19 pandemic. Error Management and Patient Safety Culture (PSC) measures served to operationalize Safety Management. Data were analyzed descriptively and by using quantitative content analysis (QCA). Results: Results for n = 588 participants from 53 hospitals show that there is a gap between errors occurred, reported, documented, and addressed. QCA revealed that low quality of safety culture (27.8%) was the most mentioned reason for errors not being addressed. Overall, ratings of PSC ranged from 26.7 to 57.9% positive response with Staffing being the worst and Teamwork Within Units being the best rated dimension. While assessments showed a similar pattern, medical staff rated PSC on ICUs more positively in comparison to nursing staff. Conclusion: The status-analysis of Safety Management in times of crisis revealed relevant potential for improvement. Human Factor plays a crucial role in the occurrence and the way errors are dealt with on ICUs, but systemic factors should not be underestimated. Further intensified efforts specifically in the fields of staffing and error reporting, documentation and communication are needed to improve Safety Management on ICUs. These findings might also be applicable across nations and sectors beyond the medical field.

Butyrate modulates antioxidant enzyme expression in malignant and non-malignant human colon tissues.

The induction of antioxidant enzymes is an important mechanism in colon cancer chemoprevention, but the response of human colon tissue to butyrate, a gut fermentation product derived from dietary fiber, remains largely unknown. Therefore, our study investigated the effect of a butyrate treatment on catalase (CAT) and superoxide dismutase (SOD2) in matched human colon tissues of different transformation stages (n = 3-15 in each group) ex vivo. By performing quantitative real-time PCR, Western blot, and spectrophotometric measurements, we found an increase in SOD2 at expression and activity level in colonic adenocarcinomas (mRNA: 1.96-fold; protein: 1.41-fold, activity: 1.8-fold; P < 0.05). No difference was detectable for CAT between normal, adenoma, and carcinoma colon tissues. Treatment of normal colon epithelium (12 h) with a physiologically relevant concentration of butyrate (10 mM) resulted in a significant increase (P < 0.05) in CAT mRNA (1.24-fold) and protein (1.39-fold), without affecting the enzymatic activity. Consequently, preliminary experiments failed to show any protective effect of butyrate against H2 O2 -mediated DNA damage. Despite a significantly lowered SOD2 transcript (0.51-fold, P < 0.01) and, to a lesser extent, protein level (0.86-fold) after butyrate exposure of normal colon cells, the catalytic activity was significantly enhanced (1.19-fold, P < 0.05), suggesting an increased protection against tissue superoxide radicals. In malignant tissues, greater variations in response to butyrate were observed. Furthermore, both enzymes showed an age-dependent decrease in activity in normal colon epithelium (CAT: r = -0.49, P = 0.09; SOD2: r = -0.58, P = 0.049). In conclusion, butyrate exhibited potential antioxidant features ex vivo but cellular consequences need to be investigated more in depth.

Chemopreventive effects of in vitro digested and fermented bread in human colon cells.

PURPOSE: Bread as a staple food product represents an important source for dietary fibre consumption. Effects of wheat bread, wholemeal wheat bread and wholemeal rye bread on mechanisms which could have impact on chemoprevention were analysed in colon cells after in vitro fermentation. METHODS: Effects of fermented bread samples on gene expression, glutathione S-transferase activity and glutathione content, differentiation, growth and apoptosis were investigated using the human colon adenoma cell line LT97. Additionally, apoptosis was studied in normal and tumour colon tissue by determination of caspase activities. RESULTS: The expression of 76 genes (biotransformation, differentiation, apoptosis) was significantly upregulated (1.5-fold) in LT97 cells. The fermented bread samples were able to significantly increase glutathione S-transferase activity (1.8-fold) and glutathione content (1.4-fold) of the cells. Alkaline phosphatase activity as a marker of differentiation was also significantly enhanced (1.7-fold). The fermented bread samples significantly inhibited LT97 cell growth and increased the level of apoptotic cells (1.8-fold). Only marginal effects on apoptosis in tumour compared to normal tissue were observed. CONCLUSIONS: This is the first study which presents chemopreventive effects of different breads after in vitro fermentation. In spite of differences in composition, the results were comparable between the bread types. Nevertheless, they indicate a potential involvement of this staple food product regarding the prevention of colon cancer.

Impact of butyrate on PKM2 and HSP90ß expression in human colon tissues of different transformation stages: a comparison of gene and protein data.

Due to protection of oncogenic proteins from degradation and enhancement of glycolytic phosphometabolites for synthetic processes, respectively, heat shock protein 90 (HSP90) and pyruvate kinase type M2 (PKM2) are important proteins for tumor growth. The present study was undertaken to investigate the susceptibility of both proteins and their encoding genes to the chemopreventive agent butyrate in human colon cells. Matched tissue of different transformation stages derived from 20 individual colon cancer patients was used for the experiments. The results of quantitative real-time PCR revealed a moderate increase of HSP90ß and PKM2 mRNA in colon tumors (P < 0.01) compared to normal tissues without relation to clinical parameters. The expression pattern could be confirmed for PKM2 protein by Western blot but not for HSP90ß. During culturing with butyrate, the amount of PKM2 transcripts decreased in all three tissue types with the strongest effects observed in tumors (median fold decrease 45%, P < 0.05). The protein data have not reflected this influence supposing a more gradual degradation rate due to a longer half-life of PKM2. In contrast, the mRNA expression of HSP90ß in normal tissue was found 1.38-fold increased by butyrate (P < 0.05), but not the corresponding protein level. HSP90ß expression in adenomas and tumors remained generally insensitive. Only in malignant tissue, however, a significant correlation was found between the individual effects observed on gene and protein expression level. In conclusion, the present study identified PKM2 as a potential direct target of butyrate in neoplastic colon tissue, whereas HSP90ß is none of it.

Defensin alpha 6 (DEFA 6) overexpression threshold of over 60 fold can distinguish between adenoma and fully blown colon carcinoma in individual patients.

BACKGROUND: It is known that alpha-defensin expression is enhanced in colon cancer. However, the expression of human alpha defensin 6 (DEFA 6) in earlier stages, such as adenoma, has so far not yet been studied in a patient resolved manner. METHODS: By using quantitative Real Time-PCR, the gene expression pattern of DEFA 1-3 and DEFA 6 was analyzed in tissue of different stages of carcinogenesis, derived from colorectal cancer patients. In addition to paired normal and tumor tissue, matched normal near tumor and adenoma tissue samples were examined. RESULTS: The median gene expression of human defensin alpha 6 (DEFA 6) has been found to be moderately increased (~ 5 fold) in tumor samples derived from individuals with colorectal cancer (CRC) when compared to their normal counterparts. However, when the data were analyzed in a patient-wise manner, a large expression variation among individual patients is found, making the use of DEFA 6 for individual diagnosis of fully blown colon carcinoma difficult. Surprisingly, in adenoma the gene expression analysis revealed a 100 fold increased median expression of DEFA 6 relative to normal colon tissue. 13/18 samples had an individual overexpression of more than 60 fold in adenoma but only 3/17 in carcinoma. In each of the individual patients, at least either the adenoma or the carcinoma showed strong DEFA 6 overexpression. CONCLUSIONS: We suggest that the expression of DEFA 6 preferably can be used as a potential diagnostic marker for adenoma and not as a marker for fully blown carcinoma. This is supported by the fact that DEFA 6 is a downstream target of the Wnt pathway, which is mutational active during the earliest stage of cancer development.

Does an extract of carob (Ceratonia siliqua L.) have chemopreventive potential related to oxidative stress and drug metabolism in human colon cells?

Phenolic ingredients of an aqueous carob extract are well characterized and consist of mainly gallic acid (GA). In order to assess possible chemopreventive mechanisms of carob, which can be used as a cacao substitute, effects on expression of genes related to stress response and drug metabolism were studied using human colon cell lines of different transformation state (LT97 and HT29). Stress-related genes, namely catalase (CAT) and superoxide dismutase (SOD2), were induced by carob extract and GA in LT97 adenoma, but not in HT29 carcinoma cells. Although corresponding protein products and enzyme activities were not elevated, pretreatment with carob extract and GA for 24 h reduced DNA damage in cells challenged with hydrogen peroxide (H(2)O(2)). In conclusion, carob extract and its major phenolic ingredient GA modulate gene expression and protect colon adenoma cells from genotoxic impact of H(2)O(2). Upregulation of stress-response genes could not be related to functional consequences.