Low T3 Syndrome in Head-Injured Patients is Associated with Prolonged Suppression of Markers of Cell-Mediated Immune Response

Purpose:: To clarify the association between disturbed thyroid hormone metabolism (low T3 syndrome) and release of cytokines and markers of cell-mediated immune response. Material and Methods:: Concentrations of cytokines as well as of thyroid hormones were determined in 32 patients suffering from severe traumatic brain injury: interleukin-( IL-)1, IL-6, IL-10, tumor necrosis factor, transforming growth factor-(TGF-)β, soluble interleukin-2 receptor (sIL-2R), neopterin, and β2-microglobulin (β2m) in serum and cerebrospinal fluid; triiodothyronine (T3), free T3, thyroxine (T4), free T4, thyrotropin, thyroxine-binding globulin, and albumin in serum. Additionally, clinical parameters were assessed: Glasgow Coma Score, CT scan, intracranial pressure, Glasgow Outcome Score, and occurrence of pneumonia. Results:: Among 31 patients with a low T3 syndrome, those with additional low serum T4 levels (n = 13) showed a prolonged suppression of serum β2m, neopterin, and sIL-2R, and a higher secondary increase of serum β2m, neopterin, and TGF-β, as well as lower T3 levels (all p < 0.05). These patients also had a longer stay in the intensive care unit (34 ± 6 days vs. 22 ± 12 days; p = 0.008). Increased levels of β2m correlated with a preceding decrease of thyrotropin (cerebrospinal fluid: r = -0.53; p = 0.004; serum: r = -0.41; p = 0.029). Associations of thyroid hormone metabolism with either other cytokines or with clinical parameters were not detected. Conclusion:: These results show that low T3 syndrome is a very common pathophysiological feature after severe traumatic brain injury. The association of a low T3 syndrome in combination with low serum T4 levels, with an altered time course of markers of cell-mediated immunity led the authors to hypothesize that a disturbed thyroid hormone metabolism may be interrelated with a prolonged cellular immune dysfunction after traumatic brain injur

Tumour assessment in advanced melanoma: value of FDG-PET/CT in patients with elevated serum S-100B

Purpose: To evaluate the usefulness of PET/CT in melanoma patients with an elevated serum S-100B tumour marker level. Methods: Out of 165 consecutive high-risk melanoma patients referred for PET/CT imaging, 47 had elevated (>0.2μg/l) S-100B serum levels and a contemporaneous 18F-FDG PET/CT scan. PET/CT scans were evaluated for the presence of metastases. To produce a composite reference standard, we used cytological, histological, MRI and PET/CT follow-up findings as well as clinical and S-100B follow-up. Results: Among the 47 patients with increased S-100B levels, PET/CT correctly identified metastases in 38 (30 distant metastases and eight lymph node metastases). In one patient with cervical lymph node metastases, PET/CT was negative. Eight patients had no metastases and PET/CT correctly excluded metastases in all of them. Overall sensitivity for metastases was 97% (38/39), specificity 100% (8/8) and accuracy 98% (46/47). S-100B was significantly higher in patients with distant metastases (mean 1.93μg/l, range 0.3-14.3μg/l) than in patients with lymph node metastases (mean 0.49μg/l, range 0.3-1.6μg/l, p = 0.003) or patients without metastases (mean 0.625μg/l, range 0.3-2.6μg/l, p = 0.007). However, 6 of 14 patients with a tumour marker level of 0.3μg/l had no metastases. Conclusion: In melanoma patients with elevated S-100B tumour marker levels, FDG-PET/CT accurately identifies lymph node or distant metastases and reliably excludes metastases. Because of the significant number of false positive S-100B tumour marker determinations (17%), we recommend repetition of tumour marker measurements if elevated S-100B levels occur before extensive imaging is use

Glucose-induced β cell production of IL-1β contributes to glucotoxicity in human pancreatic islets

Erratum / Corrigendu

Low T3 Syndrome in Head-Injured Patients is Associated with Prolonged Suppression of Markers of Cell-Mediated Immune Response

Purpose:: To clarify the association between disturbed thyroid hormone metabolism (low T3 syndrome) and release of cytokines and markers of cell-mediated immune response. Material and Methods:: Concentrations of cytokines as well as of thyroid hormones were determined in 32 patients suffering from severe traumatic brain injury: interleukin-( IL-)1, IL-6, IL-10, tumor necrosis factor, transforming growth factor-(TGF-)β, soluble interleukin-2 receptor (sIL-2R), neopterin, and β2-microglobulin (β2m) in serum and cerebrospinal fluid; triiodothyronine (T3), free T3, thyroxine (T4), free T4, thyrotropin, thyroxine-binding globulin, and albumin in serum. Additionally, clinical parameters were assessed: Glasgow Coma Score, CT scan, intracranial pressure, Glasgow Outcome Score, and occurrence of pneumonia. Results:: Among 31 patients with a low T3 syndrome, those with additional low serum T4 levels (n = 13) showed a prolonged suppression of serum β2m, neopterin, and sIL-2R, and a higher secondary increase of serum β2m, neopterin, and TGF-β, as well as lower T3 levels (all p < 0.05). These patients also had a longer stay in the intensive care unit (34 ± 6 days vs. 22 ± 12 days; p = 0.008). Increased levels of β2m correlated with a preceding decrease of thyrotropin (cerebrospinal fluid: r = -0.53; p = 0.004; serum: r = -0.41; p = 0.029). Associations of thyroid hormone metabolism with either other cytokines or with clinical parameters were not detected. Conclusion:: These results show that low T3 syndrome is a very common pathophysiological feature after severe traumatic brain injury. The association of a low T3 syndrome in combination with low serum T4 levels, with an altered time course of markers of cell-mediated immunity led the authors to hypothesize that a disturbed thyroid hormone metabolism may be interrelated with a prolonged cellular immune dysfunction after traumatic brain injur

Glucose-induced β cell production of IL-1β contributes to glucotoxicity in human pancreatic islets

In type 2 diabetes, chronic hyperglycemia is suggested to be detrimental to pancreatic β cells, causing impaired insulin secretion. IL-1β is a proinflammatory cytokine acting during the autoimmune process of type 1 diabetes. IL-1β inhibits β cell function and promotes Fas-triggered apoptosis in part by activating the transcription factor NF-κB. Recently, we have shown that increased glucose concentrations also induce Fas expression and β cell apoptosis in human islets. The aim of the present study was to test the hypothesis that IL-1β may mediate the deleterious effects of high glucose on human β cells. In vitro exposure of islets from nondiabetic organ donors to high glucose levels resulted in increased production and release of IL-1β, followed by NF-κB activation, Fas upregulation, DNA fragmentation, and impaired β cell function. The IL-1 receptor antagonist protected cultured human islets from these deleterious effects. β cells themselves were identified as the islet cellular source of glucose-induced IL-1β. In vivo, IL-1β–producing β cells were observed in pancreatic sections of type 2 diabetic patients but not in nondiabetic control subjects. Similarly, IL-1β was induced in β cells of the gerbil Psammomys obesus during development of diabetes. Treatment of the animals with phlorizin normalized plasma glucose and prevented β cell expression of IL-1β. These findings implicate an inflammatory process in the pathogenesis of glucotoxicity in type 2 diabetes and identify the IL-1β/NF-κB pathway as a target to preserve β cell mass and function in this condition

Glucose-induced β cell production of IL-1β contributes to glucotoxicity in human pancreatic islets

Erratum / Corrigendu

S-100B and FDG-PET/CT in therapy response assessment of melanoma patients

OBJECTIVE: To compare the value of the tumor marker S-100B protein and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients treated for melanoma metastases. METHODS: In 41 patients with proven melanoma metastases, S-100B measurements and FDG-PET/CT were performed before and after therapy. The change of S-100B levels (DeltaS-100B) was assessed. In all patients, therapy response was assessed with PET/CT using visual criteria and change of maximal standard uptake value (DeltaSUV(max.)) or total lesion glycolysis (DeltaTLG). RESULTS: In 15 of 41 patients (37%), S-100B values were not suitable because they were normal before and after therapy. In 26 patients, S-100B was suitable for therapy response assessment. PET/CT was suitable for response assessment in all patients. Correlations between DeltaS-100B and DeltaTLG (r = 0.850, p < 0.001) and between DeltaS-100B and DeltaSUV(max.) (r = 0.818, p < 0.001) were both excellent. A complete agreement between S-100B and PET/CT response assessment was achieved in 22 of 26 patients. In 4 patients, therapy response differed between the S-100B and PET/CT findings, but subsequent S-100B measurements realigned the S-100B results with the later PET/CT findings. CONCLUSION: In a third of our patients with metastases, the S-100B tumor marker was not suitable for therapy assessment. In these patients, imaging techniques remain necessary, and FDG-PET/CT can be used for response assessment