Histopathological growth patterns of resected non-colorectal,non-neuroendocrine liver metastases: a retrospective multicenter study

Background

Distinct Histopathological Growth Patterns can be identified in liver metastases from melanoma, breast and colorectal cancers. For each of these distinct liver metastasis types the HGP has proven a biomarker for survival after partial hepatectomy, with the desmoplastic type marking favourable prognosis. Whether HGPs can be considered a pan-cancer phenomenon remains unknown. This study therefore evaluates the presence of HGPs and their prognostic value across non-colorectal non-neuroendocrine liver metastases.

Methods

A retrospective multicentre cohort study was performed in patients who underwent curative intent resection of non-colorectal non-neuroendocrine liver metastasis. HGPs were assessed on Haematoxylin and Eosin slides according to consensus guidelines and classified as desmoplastic or non-desmoplastic. Overall- and recurrence-free survival were evaluated using Kaplan–Meier and multivariable Cox regression analysis.

Results

In total, 132 patients with liver metastasis from 25 different tumour types were eligible for analysis, of which 26 (20%) had a desmoplastic HGP. Five-year OS and RFS (95%CI) were 53% (36–78%) versus 40% (30–53%), and 33% (19–61%) versus 15% (9–27%) for patients with desmoplastic compared to non-desmoplastic metastases, respectively (p?=?0.031 & p?=?0.004). On multivariable analysis (adjusted HR [95%CI]) a desmoplastic HGP was prognostic for both OS (0.46 [0.25–0.86]) and RFS (0.38 [0.21–0.69]).

Conclusions

This study demonstrates that HGPs apply to liver metastases across a wide variety of primary tumour origins. They hold a prognostic value in these cases, suggesting that HGPs could represent a pan-cancer biomarker for survival after surgical resection of liver metastases.

     

Identification and characterization of an endogenous chemotactic ligand specific for FPRL2

Chemotaxis of dendritic cells (DCs) and monocytes is a key step in the initiation of an adequate immune response. Formyl peptide receptor (FPR) and FPR-like receptor (FPRL)1, two G protein-coupled receptors belonging to the FPR family, play an essential role in host defense mechanisms against bacterial infection and in the regulation of inflammatory reactions. FPRL2, the third member of this structural family of chemoattractant receptors, is characterized by its specific expression on monocytes and DCs. Here, we present the isolation from a spleen extract and the functional characterization of F2L, a novel chemoattractant peptide acting specifically through FPRL2. F2L is an acetylated amino-terminal peptide derived from the cleavage of the human heme-binding protein, an intracellular tetrapyrolle-binding protein. The peptide binds and activates FPRL2 in the low nanomolar range, which triggers intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases through the G(i) class of heterotrimeric G proteins. When tested on monocytes and monocyte-derived DCs, F2L promotes calcium mobilization and chemotaxis. Therefore, F2L appears as a new natural chemoattractant peptide for DCs and monocytes, and the first potent and specific agonist of FPRL2.     

Evaluation of indicators of cobalamin deficiency defined as cobalamin-induced reduction in increased serum methylmalonic acid

BACKGROUND: Early detection of cobalamin deficiency is clinically important, and there is evidence that such deficiency occurs more frequently than previously anticipated. However, serum cobalamin and other commonly used tests have limited ability to diagnose a deficiency state. METHODS: We investigated the ability of hematological variables, serum cobalamin, plasma total homocysteine (tHcy), serum and erythrocyte folate, gastroscopy, age, and gender to predict cobalamin deficiency. Patients (n = 196; age range, 17-87 years) who had been referred from general practice for determination of serum cobalamin were studied. Cobalamin deficiency was defined as serum methylmalonic acid (MMA) >0.26 micromol/L with at least 50% reduction after cobalamin supplementation. ROC and logistic regression analyses were used. RESULTS: Serum cobalamin and tHcy were the best predictors, with areas under the ROC curve (SE) of 0. 810 (0.034) and 0.768 (0.037), respectively, but age, intrinsic factor antibodies, and gastroscopy gave additional information. CONCLUSIONS: When cobalamin deficiency is suspected in general practice, serum cobalamin should be the first diagnostic test, and the result should be interpreted in relation to the age of the patient. When a definite diagnosis cannot be reached, MMA and tHcy determination will provide additional discriminative information, but MMA, being more specific, is preferable for assessment of cobalamin status.     

Sepsis erkennen im Rettungsdienst

Die Anaesthesiologie - Sepsis hat eine hohe Mortalität, die durch einen frühzeitigen Therapiebeginn reduziert werden kann. Da Patienten mit Sepsis häufig durch den Rettungsdienst in...     

Out-of-hospital airway management during manual compression or automated chest compression devices

Background

Airway management during resuscitation is pivotal for treating hypoxia and inducing reoxygenation. This German Resuscitation Registry (GRR) analysis investigated the influence of the type of airway used in patients treated with manual chest compression (mCC) and automated chest compression devices (ACCD) after out-of-hospital cardiac arrest (OHCA).

Methods

Out of 42,977 patients (1 January 2010–30 June 2016) information on outcome, airway management and method of chest compressions were available for 27,544 patients. Hospital admission under cardiopulmonary resuscitation (CPR), hospital admission with return of spontaneous circulation (ROSC), hospital discharge and discharge with cerebral performance categories 1 and 2 (CPC 1,2) were used to compare outcome in patients treated with mCC vs. ACCD, and classified by endotracheal intubation (ETI), initial supraglottic airway device (SAD) changed into ETI, and only SAD use.

Results

Outcomes for hospital admission under ongoing CPR, hospital admission with ROSC, hospital discharge and neurologically intact survival (CPC 1,2) for mCC (84.8%) vs. ACCD (15.2%) groups were: 8.4/38.6%, 39.2/27.2%, 10.6/6.8%, 7.9/4.7% (p < 0.001), respectively. Only mCC with SAD/ETI for ever ROSC (OR 1.466, 95% CI: 1.353–1.588, p < 0.001) and mCC group with SAD/ETI for hospital admission with ROSC showed better outcomes (odds ratio [OR] 1.277, 95% confidence interval [CI]: 1.179–1.384, p < 0.001) in comparison to mCC treated with ETI. Compared to mCC/ETI, all other groups were associated with a decrease in neurologically intact survival.

Conclusion

Better outcomes were found for mCC in comparison to ACCD and ETI showed better outcomes in comparison to SAD only. This observational registry study raised the hypothesis that SAD only should be avoided or SAD should be changed into ETI, independent of whether mCC or ACCD is used.

     

Plasma cortisol levels before and during "low-dose" hydrocortisone therapy and their relationship to hemodynamic improvement in patients with septic shock

OBJECTIVES: To compare cortisol levels during "low-dose" hydrocortisone therapy to basal and ACTH-stimulated endogenous levels and to assess whether clinical course and the need for catecholamines depend on cortisol levels and/or pretreatment adrenocortical responsiveness. DESIGN AND SETTING: Prospective observational study in a medical ICU of a university hospital. PATIENTS: Twenty consecutive patients with septic shock and a cardiac index of 3.5 l/min or higher, started on "low-dose" hydrocortisone therapy (100 mg bolus, 10 mg/h for 7 days and subsequent tapering) within 72 h of the onset of shock. MEASUREMENTS AND RESULTS: Basal total and free plasma cortisol levels ranged from 203 to 2169 and from 17 to 372 nmol/l. In 11 patients cortisol production was considered "inadequate" because there was neither a response to ACTH of at least 200 nmol/l nor a baseline level of at least 1000 nmol/l. Following the initiation of hydrocortisone therapy total and free cortisol levels increased 4.2- and 8.5-fold to median levels of 3,587 (interquartile range 2,679-5,220) and 1,210 (interquartile range 750-1,846) nmol/l on day 1, and thereafter declined to median levels of 1,310 nmol/l and 345 nmol/l on day 7. Patients with "inadequate" steroid production could be weaned from vasopressor therapy significantly faster, although their plasma free cortisol concentrations during the hydrocortisone treatment period did not differ. CONCLUSIONS: (a) During proposed regimens of "low-dose" hydrocortisone therapy, initially achieved plasma cortisol concentrations considerably exceed basal and ACTH stimulated levels. (b) Cortisol concentrations decline subsequently, despite continuous application of a constant dose. (c) "Inadequate" endogenous steroid production appears to sensitize patients to the hemodynamic effects of a "therapeutic rise" in plasma cortisol levels.     

Trimethoprim resistance of Escherichia coli in outpatients in Finland after ten years' use of plain trimethoprim

Development of trimethoprim resistance among Escherichia coli collected from urine samples in three areas in Finland was studied in 1978-1984. Three different trends of development of resistance were found: in the Turku area resistance has increased evenly during 1978-1982 from 5.4% to 10.1%, but thereafter a plateau seems to have been reached; in the Helsinki area resistance increased rapidly from 2.9% in 1980 to 11.1% in 1984, possibly due to the spread of a trimethoprim resistance transposon Tn7, which occurred significantly more often among E. coli strains in this area than in the Turku area; in the Rovaniemi area resistance has been at a plateau level, between 3.1 and 5.7%, during the whole study. No clear correlation between the consumption of trimethoprim and the level of resistance was found. The frequency of trimethoprim resistance in E. coli isolated from patients less than 65 years was 5.2% and in those isolated from patients greater than or equal to 65 years 14.7%.