Symptoms and Clinical Course of EHEC O104 Infection in Hospitalized Patients: A Prospective Single Center Study

Objectives

Shiga-toxin producing O157:H7 Entero Haemorrhagic E. coli (STEC/EHEC) is one of the most common causes of Haemolytic Uraemic Syndrome (HUS) related to infectious haemorrhagic colitis. Nearly all recommendations on clinical management of EHEC infections refer to this strain. The 2011 outbreak in Northern Europe was the first to be caused by the serotype O104:H4. This EHEC strain was found to carry genetic features of Entero Aggregative E. coli (EAEC) and extended spectrum β lactamase (ESBL). We report symptoms and complications in patients at one of the most affected centres of the 2011 EHEC O104 outbreak in Northern Germany.

Methods

The courses of patients admitted to our hospital due to bloody diarrhoea with suspected EHEC O104 infection were recorded prospectively. These data include the patients’ histories, clinical findings, and complications.

Results

EHEC O104 infection was confirmed in 61 patients (female = 37; mean age: 44±2 years). The frequency of HUS was 59% (36/61) in our cohort. An enteric colonisation with co-pathogens was found in 57%. Thirty-one (51%) patients were treated with plasma-separation/plasmapheresis, 16 (26%) with haemodialysis, and 7 (11%) with Eculizumab. Patients receiving antibiotic treatment (n = 37; 61%) experienced no apparent change in their clinical course. Twenty-six (43%) patients suffered from neurological symptoms. One 83-year-old patient died due to comorbidities after HUS was successfully treated.

Conclusions

EHEC O104:H4 infections differ markedly from earlier reports on O157:H7 induced enterocolitis in regard to epidemiology, symptomatology, and frequency of complications. We recommend a standard of practice for clinical monitoring and support the renaming of EHEC O104:H4 syndrome as “EAHEC disease”.     

Receiving Palliative Treatment Moderates the Effect of Age and Gender on Demoralization in Patients with Cancer

Background

Existential distress is an important factor affecting psychological well-being in cancer patients. We studied occurrence and predictors of demoralization, a syndrome of existential distress, in particular the interaction of age, gender, and curative vs. palliative treatment phase.

Methods

A cross-sectional sample of N = 750 patients with different tumor sites was recruited from in- and outpatient treatment facilities. Patients completed the following self-report questionnaires: Demoralization Scale, Patient Health Questionnaire-9, Illness-Specific Social Support Scale Short Version-8, and physical problems list of the NCCN Distress Thermometer. Moderated multiple regression analyses were conducted.

Results

We found high demoralization in 15% and moderate demoralization in 8% of the sample. Curative vs. palliative treatment phase moderated the impact of age and gender on demoralization (three-way interaction: b = 1.30, P = .02): the effect of age on demoralization was negative for women receiving palliative treatment (b = −.26, P = .02) and positive for men receiving palliative treatment (b = .25, P = .03). Effects of age and gender were not significant among patients receiving curative treatment. Female gender was associated with higher demoralization among younger patients receiving palliative treatment only. Analyses were controlled for significant effects of the number of physical problems (b = 6.10, P<.001) and social support (b = −3.17, P<.001).

Conclusions

Existential distress in terms of demoralization is a relevant problem within the spectrum of cancer-related distress. It is associated with a complex interaction of demographic and medical patient characteristics; existential challenges related to palliative treatment may exacerbate the impact of age- and gender-related vulnerability factors on demoralization. Psychosocial interventions should acknowledge this interaction in order to address the individual nature of existential distress in subgroups of cancer patients.     

Unique Gene Expression and MR T2 Relaxometry Patterns Define Chronic Murine Dextran Sodium Sulphate Colitis as a Model for Connective Tissue Changes in Human Crohn’s Disease

Introduction

Chronically relapsing inflammation, tissue remodeling and fibrosis are hallmarks of inflammatory bowel diseases. The aim of this study was to investigate changes in connective tissue in a chronic murine model resulting from repeated cycles of dextran sodium sulphate (DSS) ingestion, to mimic the relapsing nature of the human disease.

Materials and Methods

C57BL/6 mice were exposed to DSS in drinking water for 1 week, followed by a recovery phase of 2 weeks. This cycle of exposure was repeated for up to 3 times (9 weeks in total). Colonic inflammation, fibrosis, extracellular matrix proteins and colonic gene expression were studied. In vivo MRI T ₂ relaxometry was studied as a potential non-invasive imaging tool to evaluate bowel wall inflammation and fibrosis.

Results

Repeated cycles of DSS resulted in a relapsing and remitting disease course, which induced a chronic segmental, transmural colitis after 2 and 3 cycles of DSS with clear induction of fibrosis and remodeling of the muscular layer. Tenascin expression mirrored its expression in Crohn’s colitis. Microarray data identified a gene expression profile different in chronic colitis from that in acute colitis. Additional recovery was associated with upregulation of unique genes, in particular keratins, pointing to activation of molecular pathways for healing and repair. In vivo MRI T₂ relaxometry of the colon showed a clear shift towards higher T₂ values in the acute stage and a gradual regression of T₂ values with increasing cycles of DSS.

Conclusions

Repeated cycles of DSS exposure induce fibrosis and connective tissue changes with typical features, as occurring in Crohn’s disease. Colonic gene expression analysis revealed unique expression profiles in chronic colitis compared to acute colitis and after additional recovery, pointing to potential new targets to intervene with the induction of fibrosis. In vivo T₂ relaxometry is a promising non-invasive assessment of inflammation and fibrosis.     

Modular Control of Treadmill vs Overground Running

Motorized treadmills have been widely used in locomotion studies, although a debate remains concerning the extrapolation of results obtained from treadmill experiments to overground locomotion. Slight differences between treadmill (TRD) and overground running (OVG) kinematics and muscle activity have previously been reported. However, little is known about differences in the modular control of muscle activation in these two conditions. Therefore, we aimed at investigating differences between motor modules extracted from TRD and OVG by factorization of multi-muscle electromyographic (EMG) signals. Twelve healthy men ran on a treadmill and overground at their preferred speed while we recorded tibial acceleration and surface EMG from 11 ipsilateral lower limb muscles. We extracted motor modules representing relative weightings of synergistic muscle activations by non-negative matrix factorization from 20 consecutive gait cycles. Four motor modules were sufficient to accurately reconstruct the EMG signals in both TRD and OVG (average reconstruction quality = 92±3%). Furthermore, a good reconstruction quality (80±7%) was obtained also when muscle weightings of one condition (either OVG or TRD) were used to reconstruct the EMG data from the other condition. The peak amplitudes of activation signals showed a similar timing (pattern) across conditions. The magnitude of peak activation for the module related to initial contact was significantly greater for OVG, whereas peak activation for modules related to leg swing and preparation to landing were greater for TRD. We conclude that TRD and OVG share similar muscle weightings throughout motion. In addition, modular control for TRD and OVG is achieved with minimal temporal adjustments, which were dependent on the phase of the running cycle.