[Mental disorders and diabetes mellitus (Update 2023)]. / Psychische und neurokognitive Erkrankungen und Diabetes mellitus (Update 2023).

Psychiatric disorders and psychological problems are common in patients with diabetes mellitus. There is a twofold increase in depression which is associated with suboptimal glycemic control and increased morbidity and mortality. Other psychiatric disorders with a higher incidence of diabetes are cognitive impairment, dementia, disturbed eating behavior, anxiety disorders, schizophrenia, bipolar disorders and borderline personality disorder. The coincidence of mental disorders and diabetes has unfavorable influences on metabolic control and micro- and macroangiopathic complications. Improvement of therapeutic outcome is a challenge in the modern health care system. The intentions behind this position paper are to rise awareness of this special set of problems, to intensify cooperation between involved health care providers and to reduce incidence of diabetes mellitus as well as morbidity and mortality from diabetes in this patient group.

The role of psychosomatic medicine in intensive care units.

Critically ill patients, their relatives, and intensive care staff are consistently exposed to stress. The principal elements of this exceptional burden are confrontation with a life-threatening disease, specific environmental conditions at the intensive care unit, and the social characteristics of intensive care medicine. The short- and long-term consequences of these stressors include a feeling of helplessness, distress, anxiety, depression, and even posttraumatic stress disorders. Not only the patients, but also their relatives and intensive care staff are at risk of developing such psychopathologies. The integration of psychosomatic medicine into the general concept of intensive care medicine is an essential step for the early identification of fear and anxiety and for understanding biopsychosocial coherence in critically ill patients. Preventive measures such as the improvement of individual coping strategies and enhancing the individual's resistance to stress are crucial aspects of improving wellbeing, as well as the overall outcome of disease. Additional stress-reducing measures reported in the published literature, such as hearing music, the use of earplugs and eye-masks, or basal stimulation, have been successful to a greater or lesser extent.

Increased trefoil factor 2 levels in patients with chronic kidney disease.

In chronically damaged tissue, trefoil factor family (TFF) peptides ensure epithelial protection and restitution. In chronic kidney disease (CKD), TFF1 and TFF2 are reported to be upregulated. Especially in the early phase, CKD is associated with silently ongoing renal damage and inflammation. Moreover, many patients are diagnosed late during disease progression. We therefore sought to investigate the potential of TFF2 as biomarker for CKD. We followed 118 patients suffering from predialysis CKD and 23 healthy volunteers. TFF2 concentrations were measured using ELISA. Our results showed, that median TFF2 serum levels were significantly higher in patients with later CKD stages as compared to healthy controls (p < 0.001) or early stages (p < 0.001). In patients with mid CKD stages TFF2 serum levels were significantly higher than in healthy controls (p = 0.002). Patients with early or mid CKD stages had significantly higher TFF2 urine concentrations than later CKD stages (p < 0.001 and p = 0.009, respectively). Fractional TFF2 excretion differed significantly between early CKD stages and healthy controls (p = 0.01). ROC curve showed that TFF2 levels can predict different CKD stages (AUC > 0.75). In conclusion, urine and serum TFF2 levels of CKD patients show a different profile dependent on CKD stages. Whereas TFF2 urine levels continuously decreased with disease progression, TFF2 serum concentrations progressively increased from the early to later CKD stages, indicating changes in renal function and offering the potential to examine the course of CKD.

Paracrine Factors from Irradiated Peripheral Blood Mononuclear Cells Improve Skin Regeneration and Angiogenesis in a Porcine Burn Model.

Burn wounds pose a serious threat to patients and often require surgical treatment. Skin grafting aims to achieve wound closure but requires a well-vascularized wound bed. The secretome of peripheral blood mononuclear cells (PBMCs) has been shown to improve wound healing and angiogenesis. We hypothesized that topical application of the PBMC secretome would improve the quality of regenerating skin, increase angiogenesis, and reduce scar formation after burn injury and skin grafting in a porcine model. Full-thickness burn injuries were created on the back of female pigs. Necrotic areas were excised and the wounds were covered with split-thickness mesh skin grafts. Wounds were treated repeatedly with either the secretome of cultured PBMCs (Sec(PBMC)), apoptotic PBMCs (Apo-Sec(PBMC)), or controls. The wounds treated with Apo-Sec(PBMC) had an increased epidermal thickness, higher number of rete ridges, and more advanced epidermal differentiation than controls. The samples treated with Apo-Sec(PBMC) had a two-fold increase in CD31+ cells, indicating more angiogenesis. These data suggest that the repeated application of Apo-Sec(PBMC) significantly improves epidermal thickness, angiogenesis, and skin quality in a porcine model of burn injury and skin grafting.

Impact of different sedation protocols and perioperative procedures on patients admitted to the intensive care unit after maxillofacial tumor surgery of the lower jaw: A retrospective study.

Maxillofacial tumor surgery often necessitates prolonged invasive ventilation to prevent blockage of the respiratory tract. To tolerate ventilation, continuously administered sedatives are recommended. Half-time of sedative or analgesic medication is an important characteristic by which narcotic drugs are chosen, due to the fact that weaning period increases with half-time. The aim of our study was to investigate whether a change in sedation regimen would affect the length of invasive ventilation or intensive care unit stay and medical costs. Additionally, the impact of various surgical procedures was analyzed. Data of 157 patients after mandibular surgery were retrospectively analyzed over 5 years in count regression models. Of those patients, 84 received a sedation regimen with sufentanil and midazolam and 73 with remifentanil and propofol. The impact of the surgical procedures (tracheostomy, tumor resection, neck dissection and length of operation) and the patient age and sex were analyzed with respect to length of ventilation and ICU days. Cost savings were calculated. Our data show that patients receiving remifentanil/propofol had fewer ventilation days (2.5 ± 2.5 versus 6.1 ± 4.6 days, P < 0.001) and were discharged earlier from the intensive care unit than patients receiving sufentanil/midazolam (5.1 ± 3.8 versus 9.2 ± 6.2 days, P < 0.001), leading to calculated cost savings of about 8000 Euro per patient. Length of operation negatively influenced length of ICU stay (P < 0.001). In conclusion, short-acting drugs such as remifentanil/propofol, as well as tracheostoma and shortened surgery duration may reduce the postoperative need for invasive ventilation and length of intensive care unit stay.

Plasma levels of chemokine ligand 20 and chemokine receptor 6 in patients with sepsis: A case control study.

BACKGROUND: Chemokine ligand 20 (CCL20) is a chemokine released by mainly liver and blood leucocytes. Particularly under pro-inflammatory circumstances it triggers chemotaxis of lymphocytes and dendritic cells via activating receptor chemokine receptor 6 (CCR6) that is specific to it. In experimental sepsis models, the chemokine-receptor pair has been identified as a potential pathophysiological axis affecting mortality. OBJECTIVE: Measurement of CCL20 and CCR6 plasma levels in septic patients compared with postsurgical, nonseptic patients. DESIGN: Case control study. SETTING: Surgical ICUs of the Department of Anaesthesiology, General Hospital of Vienna, Vienna, Austria. PATIENTS: Plasma levels were measured in 46 patients with sepsis, severe sepsis or septic shock according to current American College of Chest Physicians/Society of Critical Care Medicine criteria at the day of sepsis onset. Plasma levels in 36 postsurgical controls without sepsis admitted to the ICU were investigated. Plasma concentrations were determined by using commercially available ELISA kits. Data are given as median and interquartile range (IQR). MAIN OUTCOME MEASURES: CCL20 and CCR6 plasma levels. RESULTS: CCL20 plasma levels were significantly increased in the sepsis group: 220.9 pg ml (IQR, 72.8 to 540.1) compared with the ICU controls: 37.0 pg ml (IQR 6.5 to 83.6) (P < 0.0001). Significantly elevated CCR6 levels were found in the sepsis group: 2.47 ng ml (IQR 0.92 to 5.54) compared with the controls: 0.59 ng ml (IQR 0.17 to 1.48) (P < 0.0001). Both CCL20 and CCR6 correlated with the maximum sequential organ failure assessment score (CCL20: P < 0.0001, CCR6: P < 0.0001). Length of ICU admission depended significantly on the logarithm of CCR6 (P = 0.008) and sequential organ failure assessment maximum (P < 0.0001). CONCLUSION: There were early increased plasma concentrations of CCL20 and CCR6 in patients with sepsis. CCL20 and CCR6 correlate with severity of illness in ICU patients. Levels of CCR6 predicted the length of patients' admission.

Trefoil Factor 1 Excretion Is Increased in Early Stages of Chronic Kidney Disease.

Chronic kidney disease (CKD) is associated with high morbidity and mortality. In many patients CKD is diagnosed late during disease progression. Therefore, the implementation of potential biomarkers may facilitate the early identification of individuals at risk. Trefoil factor family (TFF) peptides promote restitution processes of mucous epithelia and are abundant in the urinary tract. We therefore sought to investigate the TFF peptide levels in patients suffering from CKD and their potential as biomarkers for CKD. We analysed TFF1 and TFF3 in serum and urine of 115 patients with CKD stages 1-5 without dialysis by ELISA. 20 healthy volunteers served as controls. Our results showed, that urinary TFF1 levels were significantly increased with the onset of CKD in stages 1-4 as compared to controls and declined during disease progression (p = 0.003, < 0.001, 0.005, and 0.007. median concentrations: 3.5 pg/mL in controls vs 165.2, 61.1, 17.2, and 15.8 pg/mL in CKD 1-4). TFF1 and TFF3 serum levels were significantly elevated in stages 3-5 as compared to controls (TFF1: p < 0.01; median concentrations: 12.1, 39.7, and 34.5 pg/mL in CKD 3-5. TFF3: p < 0.001; median concentrations: 7.1 ng/mL in controls vs 26.1, 52.8, and 78.8 ng/mL in CKD 3-5). TFF3 excretion was increased in stages 4 and 5 (p < 0.001; median urinary levels: 65.2 ng/mL in controls vs 231.5 and 382.6 ng/mL in CKD 4/5; fractional TFF3 excretion: 6.4 in controls vs 19.6 and 44.1 in CKD 4/5). ROC curve analyses showed, that monitoring TFF peptide levels can predict various CKD stages (AUC urinary/serum TFF > 0.8). In conclusion our results show increased levels of TFF1 and TFF3 in CKD patients with a pronounced elevation of urinary TFF1 in lower CKD stages. Furthermore, TFF1 and TFF3 seems to be differently regulated and show potential to predict various CKD stages, as shown by ROC curve analysis.

Liver transplantation reverses hypergammaglobulinemia in patients with chronic hepatic failure.

INTRODUCTION: Sparse data are available about the effect of therapy methods on antibody levels in patients with liver failure. The aim of this study was to determine serum immunoglobulin concentrations in patients with chronic hepatic failure (CHF), acute- (ALF), or acute-on-chronic liver failure (ACLF) and to evaluate the impact of MARS treatment or liver transplantation (LT) on antibody levels. MATERIALS AND METHODS: We followed ten patients with ALF, twelve with ACLF and 18 with CHF. Eight patients with ALF and seven with ACLF underwent MARS therapy, whereas the rest received LT. 13 healthy volunteers served as controls. Serum antibody concentrations were measured using ELISA-technique. RESULTS: Median serum levels of IgA, IgG and IgM were significantly increased in patients with CHF compared to ALF or controls (P<0.02, P<0.01, and P<0.01). IgM and IgG concentrations were also significantly elevated in patients with CHF compared to ACLF (IgM, 3.7 vs. 1 g/L, P<0.001; IgG, 8.7 vs. 3.1 g/L, P=0.004). Immediately after LT a significant decrease of IgA (6.9 vs. 3.1 g/L, P=0.004), IgG (8.7 vs. 5.1 g/L, P=0.02) and IgM (3.7 vs. 1.8 g/L, P=0.001) was detected in patients with CHF and antibody levels further decreased the days after LT reaching levels comparable to healthy individuals. MARS treatment had no apparent effect on the immunoglobulin profile in patients with ALF or ACLF. CONCLUSION: We provide evidence that LT reverses hypergammaglobulinemia in patients suffering from CHF within one day, which could be explained to a reconstituted hepatic antibody clearance, whereas MARS treatment has no immediate effect on immunoglobulin levels.

Alterations of Endothelial Glycocalyx During Orthotopic Liver Transplantation in Patients With End-Stage Liver Disease.

BACKGROUND: Endothelial glycocalyx participates in the maintenance of vascular integrity, and its perturbations cause capillary leakage, loss of vascular responsiveness, and enhanced adhesion of leukocytes and platelets. We hypothesized that marked shedding of the glycocalyx core protein, syndecan-1, occurs in end-stage liver disease (ESLD) and that it increases during orthotopic liver transplantation (OLT). We further evaluated the effects of general anesthesia on glycocalyx shedding and its association with acute kidney injury (AKI) after OLT. PATIENTS AND METHODS: Thirty consecutive liver transplant recipients were enrolled in this prospective study. Ten healthy volunteers served as a control. Acute kidney injury was defined by Acute Kidney Injury Network criteria. RESULTS: Plasma syndecan-1 was significantly higher in ESLD patients than in healthy volunteers (74.3 ± 59.9 vs 10.7 ± 9.4 ng/mL), and it further increased significantly after reperfusion (74.3 ± 59.9 vs 312.6 ± 114.8 ng/mL). The type of general anesthesia had no significant effect on syndecan-1. Syndecan-1 was significantly higher during the entire study in patients with posttransplant AKI stage 2 or 3 compared to patients with AKI stage 0 or 1. The area under the curve of the receiver operating characteristics curve of syndecane-1 to predict AKI stage 2 or 3 within 48 hours after reperfusion was 0.76 (95% confidence interval, 0.57-0.89, P = 0.005). CONCLUSIONS: Patients with ESLD suffer from glycocalyx alterations, and ischemia-reperfusion injury during OLT further exacerbates its damage. Despite a higher incidence of AKI in patients with elevated syndecan-1, it is not helpful to predict de novo AKI. Volatile anesthetics did not attenuate glycocalyx shedding in human OLT.

Increased plasma vaspin concentration in patients with sepsis: an exploratory examination.

INTRODUCTION: Vaspin (visceral adipose tissue-derived serpin) was first described as an insulin-sensitizing adipose tissue hormone. Recently its anti-inflammatory function has been demonstrated. Since no appropriate data is available yet, we sought to investigate the plasma concentrations of vaspin in sepsis. MATERIALS AND METHODS: 57 patients in intensive care, fulfilling the ACCP/SCCM criteria for sepsis, were prospectively included in our exploratory study. The control group consisted of 48 critically ill patients, receiving intensive care after trauma or major surgery. Patients were matched by age, sex, weight and existence of diabetes before statistical analysis. Blood samples were collected on the day of diagnosis. Vaspin plasma concentrations were measured using a commercially available enzyme-linked immunosorbent assay. RESULTS: Vaspin concentrations were significantly higher in septic patients compared to the control group (0.3 (0.1-0.4) ng/mL vs. 0.1 (0.0-0.3) ng/mL, respectively; P<0.001). Vaspin concentration showed weak positive correlation with concentration of C-reactive protein (CRP) (r=0.31, P=0.002) as well as with SAPS II (r=0.34, P=0.002) and maximum of SOFA (r=0.39, P<0.001) scoring systems, as tested for the overall study population. CONCLUSION: In the sepsis group, vaspin plasma concentration was about three-fold as high as in the median surgical control group. We demonstrated a weak positive correlation between vaspin and CRP concentration, as well as with two scoring systems commonly used in intensive care settings. Although there seems to be some connection between vaspin and inflammation, its role in human sepsis needs to be evaluated further.

Increased chemokine excretion in patients suffering from chronic kidney disease.

During chronic kidney disease (CKD) leukocytes attracted by chemokines can migrate into the kidney and further aggravate renal affliction by releasing proinflammatory and profibrotic factors. We therefore sought to investigate serum and urine chemokine levels of 114 patients with CKD and 21 healthy volunteers to examine their possible suitability as biomarkers for monitoring disease course and patient's risk assessment. Analyzed chemokines were CCL17, CCL20, CCL22, and CXCL11, which are especially involved in the development of chronic renal failure. Our results showed elevated fractional CCL22 excretion levels in patients with CKD stages 2-5 compared with healthy controls. Furthermore, fractional CCL22 excretion was increased in patients with CKD stages 4 and 5 compared with stages 1-3. Fractional CCL20 excretion showed a significant elevation in patients with CKD stage 5 compared with healthy individuals and patients with CKD stages 1-3. Fractional CXCL11 excretion was significantly elevated in patients with CKD stages 4 and 5 compared with healthy controls and patients with CKD stages 1-3. Moreover, receiver operating characteristic curve analysis showed the potential of chemokine excretion to predict various CKD stages (area under the curve [AUC] 0.835, P < 0.0001 for CCL22, stage 1 and higher; AUC 0.6887, P = 0.0007 for CCL20, stage 3 and higher; AUC 0.7549, P = 0.0003 for CXCL11, stage 3 and higher). Our results further uncovered trends in varying chemokine serum and excretion levels in different CKD etiologies. In conclusion, monitoring fractional chemokine excretion might be suitable for following CKD course and hence promoting individually adjusted treatment planning.

Increased plasma zonulin in patients with sepsis.

INTRODUCTION: Zonulin is a eukaryotic protein structurally similar to Vibrio cholerae's zonula occludens toxin. It plays an important role in the opening of small intestine tight junctions. The loss of gut wall integrity during sepsis might be pivotal and has been described in various experimental as well as human studies. Increased levels of zonulin could be demonstrated in diseases associated with increased intestinal inflammation, such as celiac disease and type 1 diabetes. We therefore investigated the role of plasma levels of zonulin in patients with sepsis as a non-invasive marker of gut wall integrity. MATERIALS AND METHODS: Plasma level of zonulin was measured in 25 patients with sepsis, severe sepsis or septic shock according to ACCP/SCCM criteria at the first day of diagnosed sepsis. 18 non-septic post-surgical ICU-patients and 20 healthy volunteers served as control. Plasma levels were determined by using commercially available ELISA kit. Data are given as median and interquartile range (IQR). RESULTS: Significantly higher plasma concentration of zonulin were found in the sepsis group: 6.61 ng/mL (IQR 3.51-9.46), as compared to the to the post-surgical control group: 3.40 ng/mL (IQR 2.14-5.70) (P = 0.025), as well as to the healthy group: 3.55 ng/mL (IQR 3.14-4.14) (P = 0.008). CONCLUSION: We were able demonstrate elevated levels of plasma zonulin, a potential marker of intestinal permeability in septic patients. Increased zonulin may serve as an additional mechanism for the observed increased intestinal permeability during sepsis and SIRS.

Keratin 18 and heat-shock protein in chronic kidney disease.

Chronic kidney disease (CKD) is an affliction associated with increased systemic stress and cell death. We will review the role of keratin 18 (K-18) and caspase-cleaved CK-18 (ccK-18) as markers for increased apoptosis and necrosis during renal failure progression. The importance of preventative expression of heat-shock proteins (HSPs) in response to cell stress will also be discussed. The frequent development of CKD leads to serious complications. The potential of use of K-18 and HSP as early biomarkers of renal failure will be reviewed. Also, the role of these proteins with respect to dialysis regimes and in acute ischemic kidney injury following renal transplantation will be discussed.

HSP27 and HSP70 serum and urine levels in patients suffering from chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a condition associated with inflammation and high levels of uremic toxins and reactive oxygen species. As a counterregulation to systemic stress heat shock proteins (HSP) are increased expressed to minimize cell death and preserve cell integrity by inhibiting apoptotic pathways. The aim of this study was to determine HSP27 and HSP70 concentrations in sera and urine of patients suffering from CKD. METHODS: Concentrations of HSP27 and HSP70 in urine and serum were determined in 119 patients with CKD stages 1 to 5 and 23 healthy volunteers by using ELISA technique. RESULTS: HSP27 serum levels were significantly elevated in patients suffering from CKD stages 3 to 5 as well as fractional HSP27 excretion in stages 2-5 versus healthy controls. Absolute HSP70 urinary values were significantly elevated in stages 4 and 5 and fractional HSP70 excretion was increased in stage 5 compared to controls. Moreover, ROC curve analysis showed the potential of urine and especially serum HSP levels to identify various stages of CKD. CONCLUSION: We provide evidence for elevated HSP27 concentrations in serum and urine and increased HSP70 excretion levels in patients suffering from CKD. Moreover, our results show that HSP levels might offer potential to examine the stages of CKD as well as the disease course which could further promote individually adjusted treatment planning.

Increased total cytokeratin-18 serum and urine levels in chronic kidney disease.

BACKGROUND: Increased cell death in chronic kidney disease (CKD) by either necrosis or apoptosis has been confirmed by a variety of studies. Possible sources are an inadequate persistent inflammation and ischemia as a consequence of CKD or caused by the underlying renal disease. Detection of total or caspase cleaved cytokeratin 18 (CK-18) is a novel and elegant method to determine necrosis or apoptosis of epithelial cells in the patients' sera and urine. METHODS: 120 patients with CKD stages 1 to 5 were included in the study. Twenty healthy volunteers served as controls. Total and caspase cleaved CK-18 urine and serum concentrations were determined by ELISA. RESULTS: The concentration of serum total CK-18 was significantly higher in CKD stages 3-5 as compared to the healthy controls. Urinary total CK-18 excretion was increased in patients with CKD 5 compared to controls. A significant correlation between urine total CK18 and urine protein and albumin levels was found. Moreover, ROC curve analysis showed the potential of serum and especially urine total CK-18 levels to predict various CKD stages. CONCLUSIONS: We provide evidence for increased total CK-18 serum and urine levels in CKD patients, possibly indicating that epithelial cell necrosis is prevalent in CKD.