Genetic variation of TLR4 influences immunoendocrine stress response: an observational study in cardiac surgical patients

Introduction: Systemic inflammation (e.g. following surgery) involves Toll-like receptor (TLR) signaling and leads to an endocrine stress response. This study aims to investigate a possible influence of TLR2 and TLR4 single nucleotide polymorphisms (SNPs) on perioperative adrenocorticotropic hormone (ACTH) and cortisol regulation in serum of cardiac surgical patients. To investigate the link to systemic inflammation in this context, we additionally measured 10 different cytokines in the serum. Methods: 338 patients admitted for elective cardiac surgery were included in this prospective observational clinical cohort study. Genomic DNA of patients was screened for TLR2 and TLR4 SNPs. Serum concentrations of ACTH, cortisol, interferon (IFN)-, interleukin (IL)-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)- and granulocyte macro-phage-colony stimulating factor (GM-CSF) were determined before surgery, immediately post surgery and on the first postoperative day. Results: 13 patients were identified as TLR2 SNP carrier, 51 as TLR4 SNP carrier and 274 pa-tients as non-carrier. Basal levels of ACTH, cortisol and cytokines did not differ between groups. In all three groups a significant, transient perioperative rise of cortisol could be ob-served. However, only in the non-carrier group this was accompanied by a significant ACTH rise, TLR4 SNP carriers had significant lower ACTH levels compared to non-carriers ((mean[95% confidence intervals]) non-carriers: 201.9[187.7 to 216.1]pg/ml; TLR4 SNP car-riers: 149.9[118.4 to 181.5]pg/ml; TLR2 SNP carriers: 176.4[110.5 to 242.3]pg/ml). Compared to non-carriers, TLR4 SNP carriers showed significant lower serum IL-8, IL-10 and GM-CSF peaks ((mean[95% confidence intervals]): IL-8: non-carriers: 42.6[36.7 to 48.5]pg/ml, TLR4 SNP carriers: 23.7[10.7 to 36.8]pg/ml; IL-10: non-carriers: 83.8[70.3 to 97.4]pg/ml, TLR4 SNP carriers: 54.2[24.1 to 84.2]pg/ml; GM-CSF: non-carriers: 33.0[27.8 to 38.3]pg/ml, TLR4 SNP carriers: 20.2[8.6 to 31.8]pg/ml). No significant changes over time or between the groups were found for the other cytokines. Conclusions: Regulation of the immunoendocrine stress response during systemic inflamma-tion is influenced by the presence of a TLR4 SNP. Cardiac surgical patients carrying this ge-notype showed decreased serum concentrations of ACTH, IL-8, IL-10 and GM-CSF. This finding might have impact on interpreting previous and designing future trials on diagnosing and modulating immunoendocrine dysregulation (e.g. adrenal insufficiency) during systemic inflammation and sepsis

MRI-guided core needle biopsy of the prostate: acceptance and side effects

PURPOSEWe aimed to study side effects, complications, and patient acceptance of magnetic resonance imaging-guided real-time biopsy (MRI-GB) of the prostate.METHODSFifty-four men (49–78 years) with elevated prostate-specific antigen after at least one negative systematic transrectal ultrasound-guided biopsy (TRUS-GB) were included in a prospective clinical study. Suspicious areas on images were selectively sampled by obtaining a median of four specimens (range, 1–9 specimens) using MRI-GB. In TRUS-GB, a median of 10 specimens (range, 6–14 specimens) were obtained. Telephone interviews were conducted one week after outpatient MRI-GB, asking patients about pain and side effects (hematuria, hemospermia, rectal bleeding, fever, and chills) of the two biopsy procedures and which of the two procedures they preferred. Multinomial regression analysis and Fisher’s exact test was used to test for differences.RESULTSMRI-GB was preferred by 65% (35/54), and 82% (44/54) would undergo MRI-GB again. Pain intensity (P = 0.005) and bleeding duration (P = 0.004) were significantly lower for MRI-GB compared with TRUS-GB. Hematuria was less common after MRI-GB compared with TRUS-GB (P = 0.006). A high correlation was given between bleeding intensity and bleeding duration for TRUS-GB (r=0.77) and pain intensity and pain duration for MRI-GB (r=0.65). Although hemospermia, rectal hemorrhage, fever, and chills were less common in MRI, they showed no statistically significant difference.Z CONCLUSIONMRI-GB of the prostate seems to have fewer side effects and less pain intensity than TRUS-GB and was preferred by the majority of patients

insights on the right ventricle. A cardiovascular magnetic resonance study

OBJECTIVES Pectus excavatum (PE) is often regarded as a cosmetic disease, while its effect on cardiac function is under debate. Data regarding cardiac function before and after surgical correction of PE are limited. We aimed to assess the impact of surgical correction of PE on cardiac function by cardiovascular magnetic resonance (CMR). METHODS CMR at 1.5 T was performed in 38 patients (mean age 21 ± 8.3; 31 men) before and after surgical correction to evaluate thoracic morphology, indices and its relation to three-dimensional left and right ventricular cardiac function. RESULTS Surgery was successful in all patients as shown by the Haller Index ratio of maximum transverse diameter of the chest wall and minimum sternovertebral distance [pre: 9.64 (95% CI 8.18–11.11) vs post: 3.0 (2.84–3.16), P < 0.0001]. Right ventricular ejection fraction (RVEF) was reduced before surgery and improved significantly at the 1-year follow-up [pre: 45.7% (43.9–47.4%) vs 48.3% (46.9–49.5%), P = 0.0004]. Left ventricular ejection fraction was normal before surgery, but showed a further improvement after 1 year [pre: 61.0% (59.3–62.7%) vs 62.7% (61.3–64.2%), P = 0.0165]. Cardiac compression and the asymmetry index changed directly after surgery and were stable at the 1-year follow-up [3.93 (3.53–4.33) vs 2.08 (1.98–2.19) and 2.36 (2.12–2.59) vs 1.38 (1.33–1.44), respectively; P < 0.0001 for both]. None of the obtained thoracic indices were predictors of the improvement of cardiac function. A reduced preoperative RVEF was predictive of RVEF improvement. CONCLUSIONS PE is associated with reduced RVEF, which improves after surgical correction. CMR has the capability of offering additional information prior to surgical correction

99mTc-besilesomab (Scintimun®) in peripheral osteomyelitis: comparison with 99mTc-labelled white blood cells

The diagnosis of osteomyelitis is a challenge for diagnostic imaging. Nuclear medicine procedures including white blood cell imaging have been successfully used for the identification of bone infections. This multinational, phase III clinical study in 22 European centres was undertaken to compare anti-granulocyte imaging using the murine IgG antibody besilesomab (Scintimun) with (99m)Tc-labelled white blood cells in patients with peripheral osteomyelitis. A total of 119 patients with suspected osteomyelitis of the peripheral skeleton received (99m)Tc-besilesomab and (99m)Tc-hexamethylpropyleneamine oxime (HMPAO)-labelled white blood cells (WBCs) in random order 2-4 days apart. Planar images were acquired at 4 and 24 h after injection. All scintigraphic images were interpreted in an off-site blinded read by three experienced physicians specialized in nuclear medicine, followed by a fourth blinded reader for adjudication. In addition, clinical follow-up information was collected and a final diagnosis was provided by the investigators and an independent truth panel. Safety data including levels of human anti-mouse antibodies (HAMA) and vital signs were recorded. The agreement in diagnosis across all three readers between Scintimun and (99m)Tc-HMPAO-labelled WBCs was 0.83 (lower limit of the 95% confidence interval 0.8). Using the final diagnosis of the local investigator as a reference, Scintimun had higher sensitivity than (99m)Tc-HMPAO-labelled WBCs (74.8 vs 59.0%) at slightly lower specificity (71.8 vs 79.5%, respectively). All parameters related to patient safety (laboratory data, vital signs) did not provide evidence of an elevated risk associated with the use of Scintimun except for two cases of transient hypotension. HAMA were detected in 16 of 116 patients after scan (13.8%). Scintimun imaging is accurate, efficacious and safe in the diagnosis of peripheral bone infections and provides comparable information to (99m)Tc-HMPAO-labelled WBCs

Effects of heart valve prostheses on phase contrast flow measurements in Cardiovascular Magnetic Resonance - a phantom study

Background: Cardiovascular Magnetic Resonance is often used to evaluate patients after heart valve replacement. This study systematically analyses the influence of heart valve prostheses on phase contrast measurements in a phantom trial. Methods: Two biological and one mechanical aortic valve prostheses were integrated in a flow phantom. B-0 maps and phase contrast measurements were acquired at a 1.5 T MR scanner using conventional gradient-echo sequences in predefined distances to the prostheses. Results were compared to measurements with a synthetic metal-free aortic valve. Results: The flow results at the level of the prosthesis differed significantly from the reference flow acquired before the level of the prosthesis. The maximum flow miscalculation was 154 ml/s for one of the biological prostheses and 140 ml/s for the mechanical prosthesis. Measurements with the synthetic aortic valve did not show significant deviations. Flow values measured approximately 20 mm distal to the level of the prosthesis agreed with the reference flow for all tested all prostheses. Conclusions: The tested heart valve prostheses lead to a significant deviation of the measured flow rates compared to a reference. A distance of 20 mm was effective in our setting to avoid this influence