[What is the value of determining immunoreactive GHRH in acromegaly?]

Acromegaly is usually due to autonomous, excessive secretion of growth hormone from a pituitary adenoma. One would expect growth hormone-releasing factor (GHRH) in these patients to be suppressed. In the available literature referring to acromegaly, immunoreactive GHRH levels were determined in 259 acromegalic patients. When growth hormone was measured simultaneously, no correlation was found between serum growth hormone and plasma GHRH concentrations, irrespective of whether the acromegalic patients were treated or not. A possible explanation for this finding might be the lack of a feedback regulation between plasma growth hormone and GHRH. Also, since growth hormone is secreted in a pulsatile fashion the interpretation of single growth hormone values can be difficult. IGF I, which correlates well with mean growth hormone production, may therefore represent a more valuable criterion for the assessment of activity and GHRH plasma levels in acromegalics. However, no study has yet been performed to elucidate the relationship between GHRH and IGF I in acromegaly. To examine this relationship we measured the concentration of plasma GHRH and IGF I in 18 treated patients with acromegaly (age range 32-64 years median 50.5 years; median follow-up 6.5 years, range 3 months to 33 years). All immunoreactive GHRH levels were within the limits described as normal in the literature (mean +/- SD 22.89 +/- 2.72 pg/ml, range 19-28 pg/ml). The IGFI level was 396.78 +/- 224.26 ng/ml (mean +/- SD, range 71-876 ng/ml; reference ranges, age group 25-39 years: 114-492 ng/ml; 40-54 years: 90-360 ng/ml; > 55 years: 71-290 ng/ml). We found no correlation between IGF I and GHRH concentrations (r = 0.17). We therefore conclude that measuring plasma GHRH is not useful in the evaluation of the activity or therapy of acromegaly but may be helpful in its differential diagnosis since a massive elevation of GHRH is typically associated with the ectopic GHRH syndrome, a rare cause of acromegaly.

Predictive value of cerebrospinal fluid (CSF) lactate level versus CSF/blood glucose ratio for the diagnosis of bacterial meningitis following neurosurgery.

The value of cerebrospinal fluid (CSF) lactate level and CSF/blood glucose ratio for the identification of bacterial meningitis following neurosurgery was assessed in a retrospective study. During a 3-year period, 73 patients fulfilled the inclusion criteria and could be grouped by preset criteria in one of three categories: proven bacterial meningitis (n = 12), presumed bacterial meningitis (n = 14), and nonbacterial meningeal syndrome (n = 47). Of 73 patients analyzed, 45% were treated with antibiotics and 33% with steroids at the time of first lumbar puncture. CSF lactate values (cutoff, 4 mmol/L), in comparison with CSF/blood glucose ratios (cutoff, 0.4), were associated with higher sensitivity (0.88 vs. 0.77), specificity (0.98 vs. 0.87), and positive (0.96 vs. 0.77) and negative (0.94 vs. 0.87) predictive values. In conclusion, determination of the CSF lactate value is a quick, sensitive, and specific test to identify patients with bacterial meningitis after neurosurgery.

Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40-60 years.

The preferred type of post-remission therapy (PRT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1) is a subject of continued debate, especially in patients at higher risk of nonrelapse mortality (NRM), including patients >40 years of age. We report results of a time-dependent multivariable analysis of allogenic hematopoietic stem cell transplantation (alloHSCT) (n=337) versus chemotherapy (n=271) or autologous HSCT (autoHSCT) (n=152) in 760 patients aged 40-60 years with AML in CR1. Patients receiving alloHSCT showed improved overall survival (OS) as compared with chemotherapy (respectively, 57±3% vs 40±3% at 5 years, P<0.001). Comparable OS was observed following alloHSCT and autoHSCT in patients with intermediate-risk AML (60±4 vs 54±5%). However, alloHSCT was associated with less relapse (hazard ratio (HR) 0.51, P<0.001) and better relapse-free survival (RFS) (HR 0.74, P=0.029) as compared with autoHSCT in intermediate-risk AMLs. AlloHSCT was applied following myeloablative conditioning (n=157) or reduced intensity conditioning (n=180), resulting in less NRM, but comparable outcome with respect to OS, RFS and relapse. Collectively, these results show that alloHSCT is to be preferred over chemotherapy as PRT in patients with intermediate- and poor-risk AML aged 40-60 years, whereas autoHSCT remains a treatment option to be considered in patients with intermediate-risk AML.Leukemia advance online publication, 23 December 2014; doi:10.1038/leu.2014.332.

Prognostic value of histopathological regression in 850 neoadjuvantly treated oesophagogastric adenocarcinomas.

BACKGROUND Recently, histopathological tumour regression, prevalence of signet ring cells, and localisation were reported as prognostic factors in neoadjuvantly treated oesophagogastric (junctional and gastric) cancer. This exploratory retrospective study analyses independent prognostic factors within a large patient cohort after preoperative chemotherapy including clinical and histopathological factors. METHODS In all, 850 patients presenting with oesophagogastric cancer staged cT3/4 Nany cM0/x were treated with neoadjuvant chemotherapy followed by resection in two academic centres. Patient data were documented in a prospective database and retrospectively analysed. RESULTS Of all factors prognostic on univariate analysis, only clinical response, complications, ypTNM stage, and R category were independently prognostic (P<0.01) on multivariate analysis. Tumour localisation and signet ring cells were independently prognostic only when investigator-dependent clinical response evaluation was excluded from the multivariate model. Histopathological tumour regression correlates with tumour grading, Laurén classification, clinical response, ypT, ypN, and R categories but was not identified as an independent prognostic factor. Within R0-resected patients only surgical complications and ypTNM stage were independent prognostic factors. CONCLUSIONS Only established prognostic factors like ypTNM stage, R category, and complications were identified as independent prognostic factors in resected patients after neoadjuvant chemotherapy. In contrast, histopathological tumour regression was not found as an independent prognostic marker.

The value of serial serum lactate measurements in predicting the extent of ischemic bowel and outcome of patients suffering acute mesenteric ischemia

BACKGROUND Acute mesenteric ischemia (AMI) is an emergency with a mortality rate up to 50 %. Detecting AMI continues to be a major challenge. This study assed the correlation of repeated preoperative serum lactate with bowel necrosis and to identify risk factors for a lethal outcome in patients with AMI. METHODS A retrospective study of 91 patients with clinically and pathologically confirmed AMI from January 2006 to December 2012 was performed. RESULTS In-hospital mortality rate was 42.9 %. Two hundred nine preoperative lactate measurements were analyzed (2.3 ± 1.1 values per patient). Less than or equal to six hours prior to surgery, the mean serum lactate level was significantly higher (4.97 ± 4.21 vs. 3.24 ± 3.05 mmol/L, p = 0.006) and the mean pH significantly lower (7.28 ± 0.12 vs. 7.37 ± 0.08, p = 0.001) compared to >6 h before surgery. Thirty-four patients had at least two lactate measurements within 24 h prior to surgery. In this subgroup, 17 patients (50 %) exhibited an increase, 17 patients (50 %) a decrease in lactate levels. Forward logistic regression analysis showed that length of necrotic bowel and the highest lactate value 24 h prior to surgery were independent risk factors for mortality (r (2)  = 0.329). CONCLUSION The value of serial lactate and pH measurements to predict the length of necrotic bowel is very limited. Length of necrotic bowel and lactate values are independent risk factors for mortality.

Evaluation of three different families of bombesin receptor radioantagonists for targeted imaging and therapy of gastrin releasing peptide receptor (GRP-R) positive tumors.

Two new classes of radiolabeled GRP receptor antagonists are studied and compared with the well-established statine-based receptor antagonist DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (RM2, 1; DOTA:1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; Sta:(3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid). The bombesin-based pseudopeptide DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Leuψ(CHOH-CH2)-(CH2)2-CH3 (RM7, 2), and the methyl ester DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-OCH3 (ARBA05, 3) analogues are labeled with (111)In and evaluated in vitro in PC-3 cell line and in vivo in PC-3 tumor-bearing nude mice. Antagonist potency was assessed by immunofluorescence-based receptor internalization and Ca(2+) mobilization assays. The conjugates showed good binding affinity, the IC50 value of 2 (3.2 ± 1.8 nM) being 2 and 10 times lower than 1 and 3. Compared to (111)In-1, (111)In-2 showed higher uptake in target tissues such as pancreas (1.5 ± 0.5%IA/g and 39.8 ± 9.3%IA/g at 4 h, respectively), whereas the compounds had similar tumor uptake (11.5 ± 2.4%IA/g and 11.8 ± 3.9%IA/g at 4h, respectively). The displacement of the radioligand in vivo was different in different receptor positive organs and depended on the displacing peptide.

Nucleon and pion structure with lattice QCD simulations at physical value of the pion mass

We present results on the nucleon scalar, axial, and tensor charges as well as on the momentum fraction, and the helicity and transversity moments. The pion momentum fraction is also presented. The computation of these key observables is carried out using lattice QCD simulations at a physical value of the pion mass. The evaluation is based on gauge configurations generated with two degenerate sea quarks of twisted mass fermions with a clover term. We investigate excited states contributions with the nucleon quantum numbers by analyzing three sink-source time separations. We find that, for the scalar charge, excited states contribute significantly and to a less degree to the nucleon momentum fraction and helicity moment. Our result for the nucleon axial charge agrees with the experimental value. Furthermore, we predict a value of 1.027(62) in the MS¯¯¯¯¯ scheme at 2 GeV for the isovector nucleon tensor charge directly at the physical point. The pion momentum fraction is found to be ⟨x⟩π±u−d=0.214(15)(+12−9) in the MS¯¯¯¯¯ at 2 GeV.

Computational Comparison of Continuous and Discontinuous Galerkin Time-Stepping Methods for Nonlinear Initial Value Problems

This article centers on the computational performance of the continuous and discontinuous Galerkin time stepping schemes for general first-order initial value problems in R n , with continuous nonlinearities. We briefly review a recent existence result for discrete solutions from [6], and provide a numerical comparison of the two time discretization methods.