Ustekinumab in the treatment of acute disseminated pyoderma gangrenosum in a patient with Crohn's disease.

Pyoderma gangrenosum (PG) is an auto-inflammatory dermatosis characterized by lesions that often cause ulcers. We present a case of successful ustekinumab treatment for acute general PG in a 31-year-old woman with coexisting Crohn's disease (CD). For a month, the patient suffered from skin ulcers, two of them deep and necrotic; a histopathological examination revealed PG. Treatment included: methylprednisolone, azathioprine, betamethasone, gentamicin and zincic ointments, antiseptic compresses, and adalimumab therapy. Due to resistance to the implemented treatment, the patient was enrolled in a clinical trial that included the administration of an anti-cytokines drug, ustekinumab. Subsequently, a significant reduction was observed in the severity of symptoms of PG with no relapse. The use of ustekinumab in patients with PG who have an inadequate response to current treatment or cannot receive first-line treatment can be considered. This applies especially to patients with accompanying autoimmune diseases such as CD.

The significance of nutritional strategies in patients with inflammatory bowel disease in the context of malnutrition and the development of malnourished obesity.

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, despite the increasing incidence, still do not have a specific etiology. Diet seems to be an important factor, modifying the occurrence of the disease and its course. Diet can affect the symptoms of IBD both directly, e.g., by alleviating diarrhea, bloating and constipation, and indirectly by shaping the microbiota. Bacterial metabolites produced under the influence of supplied nutrients may contribute to the modulation of pro- and anti-inflammatory pathways, depending on the diet used. So far, IBD has been associated with weight loss and malnutrition. In recent years, a trend of sarcopenic obesity with concomitant malnutrition has been observed. The new phenomenon is called malnubesity. This work aims to review the most commonly used diets in IBD in order to evaluate them in terms of alleviating ailments, but also maintaining proper nutritional status and lack of obesity. Low-fiber, low FODMAPs, Mediterranean diet and Crohn's Disease Exclusion Diet diet were considered. We assume that diet is modifiable factor that is related to nutritional status and healthy body weight. In addition, the current knowledge on the relationship between nutrition strategies, obesity and IBD will be demonstrated.

The Importance of Nutritional Aspects in the Assessment of Inflammation and Intestinal Barrier in Patients with Inflammatory Bowel Disease.

Intestinal inflammation in inflammatory bowel disease (IBD) is closely linked to nutrition. This study aimed to evaluate associations between nutritional, inflammatory, and intestinal barrier parameters in patients with IBD. We assessed nutritional status, fecal short-chain fatty acid profile, serum cytokine levels, and mRNA expression of enzymes and tight junction proteins in intestinal biopsies obtained from 35 patients, including 11 patients with inactive IBD, 18 patients with active IBD, and six controls. Patients with active IBD were characterized by hypoalbuminemia, fluctuations in body weight, and restriction of fiber-containing foods. In addition, they had significantly reduced levels of isovaleric acid and tended to have lower levels of butyric, acetic, and propionic acids. Patients with active IBD had higher mRNA expression of peroxisome proliferator-activated receptor γ and inducible nitric oxide synthase, and lower mRNA expression of claudin-2 and zonula occludens-1, compared with patients with inactive IBD. Moreover, patients with a body mass index (BMI) of ≥25 kg/m2 had higher median tumor necrosis factor-α levels that those with a lower BMI. We comprehensively evaluated inflammatory parameters in relation to IBD activity and nutritional status. The discrepancies between proinflammatory and anti-inflammatory parameters depending on IBD activity may be related to nutritional factors, including diet and abnormal body weight.

Application of the Clustering Technique to Multiple Nutritional Factors Related to Inflammation and Disease Progression in Patients with Inflammatory Bowel Disease.

Diet and nutritional status affect intestinal inflammation in patients with inflammatory bowel disease (IBD). The aim of this study was to use a cluster analysis to assess structural similarity between different groups of parameters including short-chain fatty acid (SCFA) levels in stool as well as hematological and inflammatory parameters (such as serum C-reactive protein (CRP) and proinflammatory and anti-inflammatory cytokines). We also assessed similarity between IBD patients in terms of various biochemical features of disease activity and nutritional status. A total of 48 participants were enrolled, including 36 patients with IBD and 12 controls. We identified four main meaningful clusters of parameters. The first cluster included all SCFAs with strong mutual correlations. The second cluster contained red blood cell parameters and albumin levels. The third cluster included proinflammatory parameters such as tumor necrosis factor-α, CRP, platelets, and phosphoric, succinic, and lactic acids. The final cluster revealed an association between zonulin and interleukins IL-10, IL-17, and IL-22. Moreover, we observed an inverse correlation between IL-6 and body mass index. Our findings suggest a link between nutritional status, diet, and inflammatory parameters in patients with IBD, which contribute to a better adjustment of the nutritional treatment.

Association between fecal levels of Short-Chain Fatty Acids and serum Pro- and Anti-Inflammatory Cytokines in patients with Inflammatory Bowel Disease.

INTRODUCTION: Inflammatory bowel disease (IBD) represents a group of chronic inflammatory disorders characterized by dysbiosis and altered short-chain fatty acid (SCFA) level. The association between individual SCFA levels and cytokine levels is unknown. OBJECTIVES: We aimed to determine the fecal SCFA levels in patients with IBD in relation to disease severity and the serum levels of pro- and anti-inflammatory cytokines. PATIENTS AND METHODS: The study included 61 patients with IBD (inactive, 22; active, 39) and 16 controls. Fecal levels of organic acids (acetic, lactic, propionic, butyric, isovaleric, isobutyric, and valeric), serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), IL-17, and IL-22, complete blood count and C-reactive protein (CRP) were measured. RESULTS: Patients with active IBD had reduced butyric, acetic, valeric, and isovaleric acid levels and elevated lactic acid levels in stool. Hemoglobin levels were positively correlated with the levels of acetic and butyric acids (R = 0.266 and R = 0.346, respectively; P <0.05). In addition, CRP levels were inversely correlated with butyric acid levels (R = -0.573; P <0.05). Higher serum TNF-α levels were observed in patients with active IBD compared with controls (6.64 pg/ml vs 2.05 pg/ml, P <0.05). No relationship was noted between the SCFA profile and cytokine levels. CONCLUSIONS: The study showed that determination of SCFA levels can be used to evaluate the activity of IBD. The relationship between individual SCFA and cytokine levels seems to be complex and requires further studies.

Light-induced In Situ Transmission Electron Microscopy for Observation of the Liquid-Soft Matter Interaction.

The current protocol describes the modifications of the transmission electron microscope (TEM) setup for in situ light-induced observations. A glass optical fiber inserted into the electron column above the objective lens polepiece, and a laser, an adjustable light source, was used to fabricate the device. After the illuminator has been calibrated using an external measuring system, it allows one to adjust the intensity of the lighting to the needs of the observed process. This lighting system was utilized to image antimicrobial photodynamic therapy phenomena, which are currently the subject of intense research. The sample was prepared by spotting a suspension of bacteria on a carbon, graphene, or silicon nitride substrate, blotting the excess solution, spotting the photosensitizer solution, blotting the excess liquid again, and then assembling the liquid cell with a second substrate or graphene film. The process of the imaging experiment itself includes choosing the right place for observation with the use of low magnification and a minimum dose of electrons, and then cyclical activation of the light source to capture subsequent images at specified intervals with the minimum amount of electrons necessary. The electron dose of each exposure and the time and intensity of lighting used need to be carefully recorded due to the complexity of the observed phenomena as, at the same time, the process is both light- and electron-driven. After the actual experiment is performed, additional control observations must be made, in which the same doses of electrons are used but without additional light influence and smaller doses of electrons are used for higher doses of light. This makes it possible to distinguish light-induced microstructural effects from those caused by electrons in both the fields of life and materials science.

Association between Fecal Short-Chain Fatty Acid Levels, Diet, and Body Mass Index in Patients with Inflammatory Bowel Disease.

Disturbances in the production of bacterial metabolites in the intestine have been reported in diseases associated with dysbiosis, such as inflammatory bowel diseases (IBDs) that include two conditions: Crohn disease (CD) and ulcerative colitis (UC). Short-chain fatty acids (SCFAs) are the main dietary-fiber-derived bacterial metabolites associated with the course of intestinal inflammation. In this study, we assessed the relationship between body mass index (BMI), the type of diet used, and changes in fecal SCFA levels in patients with IBD. We performed nutritional assessments using a nutritional questionnaire and determined fecal SCFA levels in 43 patients with UC, 18 patients with CD, and 16 controls. Our results revealed that subjects with a BMI > 24.99 kg/m2 had higher levels of isobutyric acid, whereas those with a BMI < 18.5 kg/m2 had lower level of butyric, isovaleric, and propionic acids. Furthermore, we observed higher levels of valeric acid in controls than in IBD patients. We did not reveal a relationship between a specific SCFA and the type of diet, but eating habits appear to be related to the observed changes in the SCFA profile depending on BMI. In conclusion, we demonstrated that BMI is associated with SCFA levels in patients with IBD.

Photo-Responsivity Improvement of Photo-Mobile Polymers Actuators Based on a Novel LCs/Azobenzene Copolymer and ZnO Nanoparticles Network.

The efficiency of photomobile polymers (PMP) in the conversion of light into mechanical work plays a fundamental role in achieving cutting-edge innovation in the development of novel applications ranging from energy harvesting to sensor approaches. Because of their photochromic properties, azobenzene monomers have been shown to be an efficient material for the preparation of PMPs with appropriate photoresponsivity. Upon integration of the azobenzene molecules as moieties into a polymer, they act as an engine, allowing fast movements of up to 50 Hz. In this work we show a promising approach for integrating ZnO nanoparticles into a liquid crystalline polymer network. The addition of such nanoparticles allows the trapping of incoming light, which acts as diffusive points in the polymer matrix. We characterized the achieved nanocomposite material in terms of thermomechanical and optical properties and finally demonstrated that the doped PMP was better performing that the undoped PMP film.

Fecal Levels of Lactic, Succinic and Short-Chain Fatty Acids in Patients with Ulcerative Colitis and Crohn Disease: A Pilot Study.

Intestinal dysbiosis plays a crucial role in the development of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). The importance of bacterial metabolites, such as short-chain fatty acids (SCFAs), succinic and lactic acids, as well as environmental factors that affect their production in the course of IBD, remains unclear. The aim of this study was to evaluate a profile of organic acids in the stool of CD and UC patients with different disease activity. We assessed a correlation between used medications, patient's diet, and SCFA levels. A total of 35 adult patients were included in the study. We did not observe significant differences in the levels of organic acids between the CD and UC groups, irrespective of disease activity, and a control group. However, propionic acid levels were higher in IBD patients who received trimebutine vs. those who did not (p = 0.031). Higher isobutyric acid levels were observed in patients treated with biological drugs compared with those without such treatment (p = 0.014). No significant correlations were found between organic acid levels and the frequency of dietary fiber consumption. Our results reveal a new link between medication use and organic acid levels in patients with IBD.

Fiber-optic sample illuminator design for the observation of light induced phenomena with transmission electron microscopy in situ: Antimicrobial photodynamic therapy.

Antibacterial photodynamic therapy is a promising treatment for problematic infections caused by bacteria and fungi. Despite its undoubted effectiveness, the ultrastructural mechanism of microbial death remains not fully described and distinct organisms respond to the treatment with different efficacy. For this reason, it was decided to try imaging the process using the in situ transmission electron microscopy method. To conduct an observational experiment, the microscope was significantly modified. Liquid cell methods were used, electron doses and their influence on the sample were estimated, and a fiber-optic sample illuminator was designed and built. The modifications allowed for the light-induced characterization of photosensitizer-bacteria interaction. Microscope modification is a promising platform for further studies of light-induced phenomena in both life and material science.

Light-induced in situ transmission electron microscopy: Novel approach for antimicrobial photodynamic therapy imaging.

The novel approach for imaging of antimicrobial photodynamic therapy processes presented in this work is based on transmission electron microscopy methods. With the use of liquid cell, illumination system, and lowered electron dose the successful light-induced in-situ observations on Staphylococcus aureus encapsulated with methylene blue were performed. Results showed that with specified imaging parameters it is possible to conduct reliable research on bacteria in electron microscope despite the unfavorable damaging effect of the highly energetic electron beam used for imaging. This approach differs from the common methods, as it provides direct observations of the processes occurring upon light illumination. The effects obtained with the proposed method are very promising and may serve to answer why different microorganisms respond to the therapy differently.

Serum levels of selected micronutrients in patients with inflammatory bowel disease in clinical remission.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) can experience micronutrient deficiency regardless of disease activity and extent. OBJECTIVES: We aimed to evaluate serum concentrations of selected trace elements in adult patients with IBD in clinical remission with involvement limited to the colon who received immunosuppressive treatment. PATIENTS AND METHODS: We enrolled 32 patients with IBD (mean [SD] age, 41 [15.2] years) and 30 healthy controls (mean [SD] age, 39.1 [11.8] years). Serum selenium, iron, copper, and zinc levels as well as complete blood count were measured in both groups. RESULTS: Patients with IBD had lower zinc concentrations than controls (mean [SD], 0.76 [0.13] mg/l vs 0.83 [0.13] mg/l; P = 0.047). No differences were observed for selenium (mean [SD], 0.90 [0.24] µmol/l vs 0.93 [0.19] µmol/l) and copper levels (mean [SD], 1.03 [0.27] mg/l vs 0.97 [0.22] mg/l). Compared with controls, patients with IBD had lower red blood cell count (mean [SD], 4.4 [0.6] 106/µl vs 4.7 [0.4] 106/µl; P = 0.03), hemoglobin (mean [SD], 12.7 [2.2] g/dl vs 14.3 [0.8] g/dl; P = 0.001), and iron levels (mean [SD], 14.2 [9.4] µmol/l vs 23.4 [2.7] µmol/l; P = 0.0001). Patients with IBD showed a positive correlation between selenium and iron (R = 0.499; P = 0.004) as well as selenium and hemoglobin levels (R = 0.579; P = 0.001). CONCLUSIONS: Patients with IBD, despite maintaining clinical remission, should undergo systematic laboratory test for anemia or micronutrient deficiencies.

Effect of long-term proton pump inhibitor therapy on complete blood count parameters and selected trace elements: a pilot study.

INTRODUCTION: Proton pump inhibitors (PPIs) are widely prescribed for several gastrointestinal conditions, often as long­term therapy. The effects of term PPI use have not been fully elucidated. OBJECTIVES: We aimed to determine the association between long­term PPI use and complete blood count parameters, particularly red blood cell (RBC) count, white blood cell (WBC) count, and hemoglobin concentrations, as well as serum levels of selected micronutrients such as selenium (Se), iron (Fe), copper (Cu), and zinc (Zn). PATIENTS AND METHODS: We enrolled 37 patients on long­ term PPI therapy (mean [SD] age, 57.1 [15.4] years) and 30 healthy controls (mean [SD] age, 39.3 [11.8] years). In each group, complete blood count, and serum Fe levels were performed, and serum Cu, Zn, and Se levels were measured using atomic absorption spectrometry. RESULTS: Red blood cell and WBC counts were lower in the PPI group compared with controls (mean [SD], 4.24 [0.55] ×106/µl vs 4.7 [0.4] ×106/µl; P <0.001 and 6.13 [1.44] ×103/µl vs 7.3 [1.28] ×103/µl; P <0.001, respectively). Hemoglobin and serum Fe concentrations were also lower in the PPI group (mean [SD], 12.5 [1.8] g /dl vs 14.3 [0.8] g /dl; P <0.001 and 16.3 [5.4] µmol/l vs 23.4 [2.7] µmol/l; P <0.001, respectively). Serum Zn and Cu concentrations were higher in PPI users than in controls. CONCLUSIONS: Long­term PPI therapy may reduce RBC and WBC counts as well as hemoglobin levels, leading to iron deficiency. It may also aff ect concentrations of some micronutrients, although the underlying mechanism of this association is not fully clear.