[Challenges in visceral medicine during COVID-19]. / Herausforderungen der Viszeralmedizin bei COVID-19: Erfahrungen aus einem Krankenhaus der Grund- und Regelversorgung.

BACKGROUND: The worldwide dissemination of the coronavirus disease 2019 (COVID-19) pandemic has become a relevant problem for the German healthcare system and the whole of society within only a few weeks. Because visceral medicine is at the focal point many adjustments in procedures are necessary. MATERIAL AND METHODS: Necessary organizational structures and challenges in visceral medicine are described for urgent abdominal surgery after screening and for patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, an analysis of the current and relevant literature was performed and changes in the procedures in a hospital for basic and standard healthcare in Lower Rhine are described. RESULTS: This article describes the organizational structures and changes in a German hospital facing the crisis and management during the pandemic. These include establishment of a corona screening center at the hospital's main entrance and a multidisciplinary crisis management team. Specific internal guidelines were formulated for the management, confirmed by international experience and studies and regularly changed due to the requirements of the situation. CONCLUSION: In comparison to other countries the crisis reached hospitals in Germany with a clear delay and a relatively mild course. In order to be prepared for severely ill patients, adequate preparations could be made to meet the challenges on intensive care units, isolation wards, operating theaters and in endoscopy. The primary goal was the safeguarding of patients and employees. In the light of the pandemic medical rituals and habits need to be reconsidered.

Inequalities in education and national income are associated with poorer diet: Pooled analysis of individual participant data across 12 European countries.

BACKGROUND: Malnutrition linked to noncommunicable diseases presents major health problems across Europe. The World Health Organisation encourages countries to conduct national dietary surveys to obtain data to inform public health policies designed to prevent noncommunicable diseases. METHODS: Data on 27334 participants aged 19-64y were harmonised and pooled across national dietary survey datasets from 12 countries across the WHO European Region. Weighted mean nutrient intakes were age-standardised using the Eurostat 2013 European Standard Population. Associations between country-level Gross Domestic Product (GDP) and key nutrients and nutrient densities were investigated using linear regression. The potential mitigating influence of participant-level educational status was explored. FINDINGS: Higher GDP was positively associated with total sugar intake (5·0% energy for each 10% increase in GDP, 95% CI 0·6, 9·3). Scandinavian countries had the highest vitamin D intakes. Participants with higher educational status had better nutritional intakes, particularly within lower GDP countries. A 10% higher GDP was associated with lower total fat intakes (-0·2% energy, 95% CI -0·3, -0·1) and higher daily total folate intakes (14µg, 95% CI 12, 16) in higher educated individuals. INTERPRETATION: Lower income countries and lower education groups had poorer diet, particularly for micronutrients. We demonstrate for the first time that higher educational status appeared to have a mitigating effect on poorer diet in lower income countries. It illustrates the feasibility and value of harmonising national dietary survey data to inform European policy regarding access to healthy diets, particularly in disadvantaged groups. It specifically highlights the need for strong policies supporting nutritional intakes, prioritising lower education groups and lower income countries.

Surgery for colorectal cancer in elderly patients: is there such a thing as being too old?

INTRODUCTION: The overall increase in life expectancy causes a rapid increase in number of elderly patients needing colorectal surgery. It remains unclear if there is a significant risk factor in patients over 80 years of age for postoperative morbidity and mortality. For this reason we investigated the perioperative, outcome and long-term survival after surgery for colorectal cancer in our hospital. MATERIALS AND METHODS: We retrospectively analysed a database containing information about patients who underwent surgery for colorectal cancer from January 2010 to December 2015 at the St. Bernhard Hospital in Kamp-Lintfort, Germany. The last follow-up date was 31th of December 2017. RESULTS: A total of 232 patients were enrolled and analysed in this study. All patients were separated in tow groups depending in age. The first group was ≥80 years old (n=49). The second group was <80 years old (n=183). High ASA-Scores (≥3) were detectable more often in elderly patients (p<0,05). Elderly and young patients had a similar risk for postoperative anastomosic leakages (p=0,047). Likewise there were no significant differences regarding the Dindo-Clavien-Classification (p=0,13). The mortality within the first 30 days after surgery was significant elevated for elderly patients compared to younger patients (p=0,04). Also the overall 1-year survival was 90% for the younger and 73,5% for the older study group (p<0,05) Conclusion. Both the short-term outcome and long-term survival rate after colorectal surgery for cancer are worse for patients older than 80 years of age. After interpretation of all data it remains unclear if the age itself is still the biggest risk factor. When old patients have a good ASA-Score and no severe comorbidities, colorectal surgery remains safe even for patients older than 80 years.

Development and evaluation of a short 24-h food list as part of a blended dietary assessment strategy in large-scale cohort studies.

BACKGROUND/OBJECTIVES: The validity of dietary assessment in large-scale cohort studies has been questioned. Combining data sources for the estimation of usual intake in a blended approach may enhance the validity of dietary measurement. Our objective was to develop a web-based 24-h food list for Germany to identify foods consumed during the previous 24 h and to evaluate the performance of the new questionnaire in a feasibility study. SUBJECTS/METHODS: Available data from the German National Nutrition Survey II were used to develop a finite list of food items. A total of 508 individuals were invited to fill in the 24-h food list via the Internet up to three times during a 3-6-month time period. In addition, participants were asked to evaluate the questionnaire using a brief online evaluation form. RESULTS: In total, 246 food items were identified for the 24-h food list, reflecting >75% variation in intake of 27 nutrients and four major food groups. Among the individuals invited, 64% participated in the feasibility study. Of these, 100%, 85% and 68% of participants completed the 24-h food list one, two or three times, respectively. The average time needed to complete the questionnaire was 9 min, and its acceptability by participants was rated as high. CONCLUSIONS: The 24-h food list represents a promising new dietary assessment tool that can be used as part of a blended approach combining multiple data sources for valid estimation of usual dietary intake in large-scale cohort studies.

Plasma beta-carotene is not a suitable biomarker of fruit and vegetable intake in german subjects with a long-term high consumption of fruits and vegetables.

BACKGROUND/OBJECTIVE: beta-Carotene is often used as a marker for the amount of fruit and vegetables consumed, but little is known about plasma beta-carotene concentrations in subjects whose habitual (long-term) diets are characterized by different amounts of foods of plant origin. We compared dietary beta-carotene intake and plasma concentrations in women on habitual diets differing in the consumed amounts of foods of plant origin. METHODS: A comparison of dietary beta-carotene intakes and plasma beta-carotene concentrations in women adhering to an average Western diet (n = 172), wholesome nutrition (following preventive recommendations) (n = 238) or a raw food diet (n = 104). RESULTS: Dietary beta-carotene intake was 5.5, 9.3, 14.7 mg/day for women adhering to an average Western diet, wholesome nutrition and raw food diet, respectively (p < 0.001). Corresponding multivariate adjusted plasma beta-carotene concentrations were 1.07, 1.65, and 1.16 micromol/l, respectively (p < 0.001). Comparable dietary beta-carotene intake resulted in lower multivariate adjusted plasma beta-carotene in women adhering to a raw food diet and average Western diet compared to those on wholesome nutrition (p < 0.001 for all intake groups up to 20 mg/day). The amount of fruit and vegetable intake did not predict plasma beta-carotene levels in women consuming a raw food diet. CONCLUSIONS: Plasma beta-carotene concentrations differed among the diet groups, with highest plasma levels in women adhering to wholesome nutrition. Plasma beta-carotene concentrations may not reflect beta-carotene intake and the amount of fruit and vegetables consumed.

Continuous complete hematological and cytogenetic remission with molecular minimal residual disease 9 years after discontinuation of interferon-alpha in a patient with Philadelphia chromosome-positive chronic myeloid leukemia.

Interferon-alpha has been used as standard therapy for patients with Philadelphia-positive chronic myeloid leukemia (CML) for more than 20 years. Recently randomized trials have shown a superiority of the tyrosine kinase inhibitor imatinib in respect to its efficacy to induce complete hematological and cytogenetic remissions and more importantly in overall survival. Although follow-up is much shorter for imatinib than for interferon-alpha, this data changed the treatment algorithms in this disease. At the end of the era of interferon-alpha as a single-drug first-line treatment for most patients we present a case report which exemplifies a rare but exciting property of interferon-alpha in CML: the induction of complete hematological and cytogenetic remissions which can persist over years after discontinuation of the drug. Hence, the enrollment of CML patients in clinical trials which explore a combination treatment of imatinib and interferon-alpha is warranted.

Long-term effect of a plant-based diet on magnesium status during pregnancy.

OBJECTIVE: To compare dietary magnesium intake and magnesium concentrations in serum, red blood cells (RBC) and urine during pregnancy of women habitually following a long-term plant-based diet and of women following an average Western (control) diet. DESIGN: Prospective study during pregnancy. SETTING: Giessen, Germany. SUBJECTS: Healthy pregnant women (n=108) in their 9-12th, 20-22nd and 36-38th gestational week habitually following a plant-based diet for more than 3 y or an average Western diet. The vegetarians were subdivided into ovo-lacto vegetarians (n=27) and low-meat eaters (n=43). RESULTS: Significant higher dietary magnesium intakes were observed in pregnant women consuming a plant-based diet (508+/-14 mg/day for ovo-lacto vegetarians, P<0.001 and 504+/-11 mg/day for low-meat eaters, P<0.001) than in pregnant women consuming a control diet (412+/-9 mg/day). Serum magnesium concentrations were similar in all diet groups whereas RBC magnesium was slightly higher in low-meat eaters than in controls (P=0.058). Urinary magnesium excretion was higher in ovo-lacto vegetarians (P=0.023), followed by low-meat eaters (P=0.017) when compared to the control group. During the third trimester of pregnancy, the frequency and the occurrence of calf cramps was lower in the plant-based diet group than in the control group (P=0.004 and 0.008). CONCLUSIONS: Owing to a higher dietary magnesium intake confirmed by higher urinary magnesium excretion, habitual plant-based diets result in a slightly improved magnesium status during pregnancy and reduce the frequency of calf cramps during the third trimester of pregnancy compared to an average Western diet. Therefore, plant-based diets during pregnancy can be recommended with regard to magnesium supply.

[Endoscopic removal of an intraluminal duodenal diverticulum in an adult with upper abdominal pain]. / Endoskopische Spaltung eines intraluminalen Duodenaldivertikels beim Erwachsenen wegen Oberbauchbeschwerden.

We report here on a 44-year-old previously healthy patient with a two-year history of intermittent upper abdominal pain. In the outpatient gastroduodenoscopy and X- ray examinations of the small intestine an intraluminal duodenal diverticulum was suspected. Clinical examination and laboratory tests did not show any abnormal findings. In order to exclude other causes for the patient's complaints coloscopy, ERP and MRCP were performed. The latter was done because the bile duct could not be intubated in the ERCP due to the altered anatomy. By use of endoscopic ultrasound a mucosal duplication was demonstrated and thus the diagnosis confirmed. Subsequently, the diverticulum sac was sliced by argon plasma coagulation. The postinterventional course was without complications and the patient was without symptoms afterwards. The intraluminal duodenal diverticulum is a rare differential diagnosis of pain in the upper abdomen. The diverticulum should be endoscopically removed if other causes for abdominal pain have been ruled out and possibly associated malformations have been excluded.

[Posthepatic icterus caused by a solitary granular cell tumor of the common bile duct]. / Posthepatischer Ikterus durch einen solitären Granularzelltumor des Ductus choledochus.

We report a case of a 26-year-old female patient who was referred to our hospital with a painless jaundice. By means of an ERCP we found a nearly complete occlusion of the common bile duct caused by a tumor. After stenting and normalization of the cholestasis parameters, additional investigations such as endosonography, cholangioscopy and MR angiography no longer showed any manifestation of the tumor. The histological and cytological specimens did not confirm a malignant process. As there was apparently only a solitary tumor a resection according to Whipple was performed. The histological examination showed a granular cell tumor. This case report demonstrates that a posthepatic icterus may rarely be caused by a granular cell tumor. Furthermore, it clearly shows the difficulty to correctly diagnose a tumor in the extrahepatic common bile duct as one may often have to rely solely on imaging procedures.

A genome-wide analysis of immune responses in Drosophila.

Oligonucleotide DNA microarrays were used for a genome-wide analysis of immune-challenged Drosophila infected with Gram-positive or Gram-negative bacteria, or with fungi. Aside from the expression of an established set of immune defense genes, a significant number of previously unseen immune-induced genes were found. Genes of particular interest include corin- and Stubble-like genes, both of which have a type II transmembrane domain; easter- and snake-like genes, which may fulfil the roles of easter and snake in the Toll pathway; and a masquerade-like gene, potentially involved in enzyme regulation. The microarray data has also helped to greatly reduce the number of target genes in large gene groups, such as the proteases, helping to direct the choices for future mutant studies. Many of the up-regulated genes fit into the current conceptual framework of host defense, whereas others, including the substantial number of genes with unknown functions, offer new avenues for research.

The influence of lorazepam on somatosensory-evoked fast frequency (600 Hz) activity in MEG.

The generators of high frequency bursts (600-Hz activity) detected at the parietal scalp over the primary somatosensory cortex after electrical stimulation of peripheral nerves are not yet known. We investigated the influence of benzodiazepine on the somatosensory-evoked 600-Hz activity by means of neuromagnetic measurements and source analysis. After oral administration of lorazepam, the latency of the 600-Hz burst activity was increased; specifically later peaks were delayed more than earlier peaks. In contrast, the latency of the concurrent primary cortical low frequency response (N20m) was not significantly changed. The source strengths of both N20m and 600-Hz bursts were significantly increased. Our results provide evidence for two components of the 600-Hz activity with a different generator structure.

[Toxic liver damage caused by HMG-CoA reductase inhibitor]. / Toxischer Leberschaden durch HMG-CoA-Reduktase-Hemmer.

CASE REPORTS: We report on 4 patients who were referred to the clinic with suspected acute hepatitis and to investigate high transaminase values. After exclusion of specific hepatitis, unspecific virus hepatitis, autoimmune hepatitis, a metabolic disorder damaging the liver and extrahepatic cholestasis, a toxic liver damage remained as the probable cause and was histologically verified. Since other drugs and alcoholics could be eliminated as possible causes of the damage, the toxicity had to be attributed to statin ingestion. CLINICAL COURSE: After discontinuation of the medication with continuation of all other therapeutic agents of the general practitioners, the transaminase values normalized within a few weeks. Renewed administration of statin was not prescribed for ethical reasons. CONCLUSION: Therefore, when prescribing a HMG-CoA-reductase inhibitor, the possibility of liver damage should be mentioned and regular checks of the transaminase values should be performed.

[Transesophageal endosonographically-guided fine needle aspiration biopsy of mediastinal space-occupying lesions of uncertain importance]. / Die transösophageale endosonographisch gesteuerte Feinnadelaspirationsbiopsie mediastinaler Raumforderungen unklarer Dignität.

BACKGROUND AND OBJECTIVE: Endoscope-guided fine-needle biopsy of mediastinal space-occupying lesions is a recently introduced method of low invasiveness. This is a report of the authors' experience. PATIENTS AND METHODS: Between Nov. 1996 and April 1999 endoscope-guided mediastinal biopsies (Pentax FG 32 UA) were performed in 31 patients (eight women, 23 men; aged 27-80 years). The space-occupying lesion had to be less than 1 cm from the oesophagus and not more easily approachable in other ways. RESULTS: The method was successful in 23 of the 31 patients (74%). In ten of the 31 patients (32%) a malignant lesion was histologically proven. In six patients (19%) sarcoidosis was revealed. Of the eight patients with inadequate biopsy material a malignancy was ultimately diagnosed in three, sarcoidosis in one (in three by mediastinoscopy, in one by laparoscopy). Thus the sensitivity of diagnosing a malignancy was 77%, with a specificity of 100%. Follow-up examinations in the remaining four patients excluded a malignancy. CONCLUSION: Endoscope-guided fine-needle biopsy of mediastinal space-occupying lesions is a technically simple method causing little stress to the patient that can frequently elucidate the lesion's benignity or malignancy. Invasive procedures, such as mediastinoscopy, may thus be avoided in some patients.

Photo-cross-linking studies suggest a model for the architecture of an active human immunodeficiency virus type 1 integrase-DNA complex.

The virally encoded integrase protein carries out retroviral integration, which requires specific interactions with the two ends of the viral DNA, and also with host DNA that is the target of integration. We attached a photo-cross-linking agent to specific viral and target DNA sites to identify regions of the integrase polypeptide that are in close proximity to those substrate features in the active integrase-DNA complex. The active form of integrase is a multimer. The higher-order organization of the active integration complex was therefore investigated by determining whether specific cross-links occurred to the active-site containing protomer. Both viral and target DNA cross-links to human immunodeficiency virus type 1 (HIV-1) integrase mapped predominantly to integrase protomers in trans to the active site, in a multimeric integrase complex. The results provide the basis for a model of the protein-DNA architecture of an active HIV-1 integration complex that suggests specific functions for the N-terminal, core, and C-terminal domains of retroviral integrase. One implication of this model is that the integrase multimer that mediates concerted integration of the viral DNA ends is composed of at least eight integrase protomers.

Cloning of prokaryotic genomes in yeast artificial chromosomes: application to the population genetics of Pseudomonas aeruginosa.

Yeast artificial chromosomes (YACs) can accommodate large inserts and hence should be attractive tools for intra- and interspecies comparisons of bacterial genomes. YAC libraries were constructed from size-selected partial digests of human and Pseudomonas aeruginosa PAO DNA and SpeI-restricted PAO DNA. Whereas YACs from human DNA had an average size of 350 kilobase pairs (kbp), a P. aeruginosa sequence larger than 120 kbp was absent or truncated in the eukaryotic host. Coligation occurred for YACs smaller than 40 kbp, but stable YACs with 40-120 kbp large inserts of P. aeruginosa DNA were obtained in high yield. SpeI-restricted chromosomes from 97 P. aeruginosa strains representing 47 genotypes were hybridized with stable YACs from three equidistant regions of the PAO genome. The low complexity of hybridizing bands demonstrated that the analyzed 100 kbp sequence contigs were stably maintained in most P. aeruginosa isolates from both disease and environmental habitats.

Smith/Birnstiel mapping of genome rearrangements in Pseudomonas aeruginosa.

A novel application of the Smith/Birnstiel technique is presented for the analysis of intraspecies genomic diversity in small genomes. Rare-cutter total/N frequent-cutter partial restriction digestions are separated in N separate lanes by pulsed-field gel electrophoresis, blotted and hybridized with rare-cutter fragment ends as probes. The evaluation of the autoradiogram results in high-resolution restriction maps of 10-200 kbp regions. The technique was applied to the analysis of genome rearrangements in Pseudomonas aeruginosa strains. Comparison of the region encoding the tryptophan biosynthesis genes in the PAO and the IATS serotype 5 strains revealed that shared sequence characterized by almost identical restriction fingerprints was interrupted in the serotype 5 strain by small islands displaying strain-specific restriction site signatures. A multistep rearrangement in a hypervariable chromosome region downstream of the phn locus was detected in serial airway isolates from a patient with cystic fibrosis.

Mapping features of HIV-1 integrase near selected sites on viral and target DNA molecules in an active enzyme-DNA complex by photo-cross-linking.

The virally encoded integrase protein carries out retroviral integration, and to do so, it must make specific interactions with both viral and target DNA sequences. The retroviral integrase has three domains: an amino-terminal region of about 50 amino acids that contains a zinc finger-like motif, a tightly folded, phylogenetically conserved core domain that contains the active site, and a carboxy-terminal domain that can bind DNA in a nonspecific manner. The complete roles of the amino- and carboxyl-terminal domains have not yet been determined, but they appear to participate in multimerization and nonspecific or target DNA binding, respectively. The number and identity of integrase's DNA binding sites have been difficult to determine by conventional mutagenesis studies. In this report, we describe a photo-cross-linking approach to address these issues. Our findings suggest that HIV-1 integrase contacts with conserved features of the viral DNA end are likely to be mediated by residues in two peptides within the conserved core domain. Additional cross-links were seen between viral DNA and the carboxy-terminal DNA binding domain. Numerous sites in integrase, including peptides in each of the three domains, could be cross-linked to target DNA features. Integrase is known to function as a multimer, and it remains to be determined which specific contacts are in cis or trans with respect to the active site.

Infections with Pseudomonas aeruginosa in patients with cystic fibrosis.

The lung infection with Pseudomonas aeruginosa is regarded as one of the major causes of health decline in patients with cystic fibrosis (CF). The CF host response to the persistent bacterial antigen load in the endobronchiolar lumen is characterized by a pronounced humoral response, local production of cytokines, influx of neutrophils into the lung and a protease-protease inhibitor imbalance predominantly sustained by released neutrophil elastase. CF is an autosomal recessive disease, and we could demonstrate for our local patient population that the age-dependent risk to become chronically colonized with P. aeruginosa can be differentiated by the disease-causing CFTR mutation genotype. The age-specific colonisation rates were significantly lower in pancreas sufficient than in pancreas insufficient patients. P. aeruginosa is occasionally detected in throat swabs already in infancy or early childhood in most patients although there is a lapse of several years amenable to preventive measures such as vaccination until onset of persistent colonization. The epidemiology of the infection with P. aeruginosa was investigated by quantitative macrorestriction fragment pattern analysis. The distribution and frequency of clones found in CF patients match that found in other clinical and environmental aquatic habitats, but the over-representation of specific clones at a CF clinic indicates a significant impact of nosocomial transmission for the prevalence of P. aeruginosa-positive patients at a particular center. Most patients remain colonized with the initially acquired P. aeruginosa clone. According to direct sputum analysis the majority of patients is carrying a single clonal variant at a concentration of 10(7)-10(9) CFU. Co-colonization with other species or other clones is infrequent. Independent of the underlying genotype, the CF lung habitat triggers a uniform, genetically fixed conversion of bacterial phenotype. Most CFP, aeruginosa strains become non-motile, mucoid, LPS-, pyocin- and phage-deficient, secrete less virulence determinants and shift the production of cytokines evoked in neutrophils. On the other hand, other properties such as antimicrobial susceptibility or adherence to bronchial mucins remain highly variable reflecting the capacity of P. aeruginosa to adapt to ongoing changes in the CF lung habitat.

Genetic diversity of flagellins of Pseudomonas aeruginosa.

Physical genome analysis of the virulence-associated fliC locus in 20 Pseudomonas aeruginosa strains by mapping and sequencing revealed groups of heterologous a-type (1164 bp; 1185 bp) and highly conserved b-type (1467 bp) flagellin genes. Whereas only two synonymous nucleotide substitutions were detected in eight b-type fliC sequences, the 12 a-type sequences exhibited 57 nucleotide substitutions, of which 39 occurred within a variable central region. Although a-type and b-type flagellins differ by 35% in their primary structure, they share strong homology in their predicted features, implying that the polymorphic proteins fold into similar structures during polymerization of the flagella.