The occurrence of occult malignancy in patients less than 50 years of age with venous thromboembolism: which diagnostic screening methods to use?

Trousseau was the first who describe an association of venous thromboembolism (VTE) with malignancy. The prevalence of occult cancer in patients with secondary VTE is comparable with the prevalence of cancer in general population (2-3%), while the prevalence of occult cancer in patients with idiopathic VTE is 4-10%. It has been demonstrated that the frequency of malignancy is higher in the first 6 to 12 months after diagnosis of VTE. 113 consecutive patients (50 males, 63 females) with first or recurrent VTE before the age 50, mean age (mean age 34.1 at time of VTE diagnosis) were followed retrospectively. Patients with known cancer were excluded for follow-up. The presence of known malignancy and concomitant cancer at the time of diagnosis of VTE and during follow-up (average 29 months) was investigated. The use of routine or extensive screening detection of occult cancer was also assessed. Extensive screening was performed in 61% of patients and compared with 39 % of routine screening. Overall of occult cancer was 1.8 %. The incidence of occult cancer was 1.2% during one year follow-up, and the prevalence at the time of diagnosis of VTE was 0.9%. The authors confirmed the low prevalence of occult cancer in cohort of consecutive young patients with VTE under the age of 50. It seems that only routine investigation with careful history taking, physical examination and simple laboratory tests are sufficient to detect of occult cancer in this age population. The authors recommend the follow-up of these patients, mainly those with idiopathic VTE. Inherited thrombophilia much more prevails in this young thrombophilia patients but risk of occult malignancy exists as well.     

Neopterin and a soluble interleukin-2 receptor in patients with systemic lupus erythematodes

Goal of this study was to monitor levels of serum neopterin and soluble interleukin-2 receptor (sIL-2r) and to evaluate their importance in monitoring activity of systemic lupus erythematodes (SLE). Levels of serum neopterin, anti-dsDNA antibodies, C3, C4 complement components, nucleosomes antibodies, IL-10, fas ligand, soluble thrombomodulin, sVCAM-1, and sICAM-1 were measured in a group of 52 patients with SLE. Positive correlations were proved between neopterin concentrations and disease activity (ECLAM), levels of sVCAM-1, sICAM-1, sIL-2r and thrombomodulin, further between sIL-2r level and disease activity (ECLAM), and concentrations sVCAM-1, sICAM-1 and neopterin. Higher values of neopterin and sIL-2r levels were identified in patients with lupus nephritis compared to patients without kidney impairment. Statistically significant differences were identified in levels of neopterin between a subgroup (A) with minimum disease activity and a subgroup (B) with increasing disease activity (p = 0.01) and a subgroup (C) with decreasing disease activity (p = 0.003 ) and a subgroup (LN) with lupus nephritis (0.007) during the first and the third series of measurements. sIL2r levels which had in all subgroups very varied values were the lowest in the subgroup A with minimum disease activity during the whole time of monitoring. The highest levels reached the free receptor IL-2 in the subgroup B with increasing disease activity and in the subgroup with lupus nephritis. Statistically significant differences in values were identified between the subgroup A (non-active) and the subgroup LN (lupus nephritis) with p = 0.01 during the first set of the measurements. Fluctuation of sIL-2r levels in individual subgroups during the time of monitoring did not reach statistically important levels. In conclusion it could be said that potential practical utilization of the measurement of concentrations of the two mentioned molecules should be seen especially in monitoring disease activity because they don't contribute to SLE with needed information. Their always low values have favourable prognostic impact in monitoring patients with SLE and vise versa.     

Different expression pattern of hepcidin genes in the liver and pancreas of C57BL/6N and DBA/2N mice

BACKGROUND/AIMS: Male C57BL/6 and DBA/2 mice differ in their liver iron content. The aim of this study was to examine possible differences in the expression of hepcidin genes (Hamp and Hamp2) between the two strains. METHODS: Hepatic mRNAs were quantified by real-time PCR. RESULTS: Ferroportin1, transferrin receptor 2 and HAMP mRNA levels displayed no significant strain differences. However, HAMP2 mRNA levels were higher in DBA/2N mice. In both strains, HAMP2 mRNA content was sex-dependent, with higher values in female animals. Both hepatic HAMP and HAMP2 mRNA levels were elevated by iron overload, but treatment with lipopolysaccharide increased only HAMP mRNA. Lipopolysaccharide also elevated the amount of HAMP mRNA in the pancreas, while pancreatic HAMP2 mRNA levels were decreased. Sequence analysis of hepcidin amplicons from DBA/2N mice predicted an Asn-->Lys substitution at position 73 of the HAMP peptide and a Ser-->Phe substitution at position 76 of the HAMP2 peptide. CONCLUSIONS: Hepatic Hamp2 expression displays considerable strain- and sex-dependent variation. Lipopolysaccharide increases expression of Hamp both in the liver and pancreas, but Hamp2 does not respond to lipopolysaccharide treatment. The significance of the amino acid substitutions in hepcidin peptides in DBA/2N mice is at present unknown.     

Raltitrexed plus oxaliplatin in the second-line treatment of metastatic colorectal cancer

The primary endpoint of this study was to evaluate the efficacy (objective response rate; ORR) of combined chemotherapy with raltitrexed plus oxaliplatin as second-line treatment in patients with metastatic colorectal cancer (CRC). Secondary endpoints were overall survival (OS), time to progression (TTP) and toxicity (NCI-CTC criteria). The target population were patients with metastatic colorectal adenocarcinoma who progressed after first-line chemotherapy. Treatment consisted of raltitrexed 3 mg/m2 as a 15-minute intravenous (IV) infusion followed 45 minutes later by oxaliplatin 130 mg/m(2) IV as a 2-h infusion on Day 1, repeated every 3 weeks until further disease progression (PD), unacceptable toxicity or the decision of the patient. A total of 51 patients, all with WHO performance status 0-2 received a median of 6 treatment cycles (range 1-11). After 3 cycles, 8 of the 47 evaluable patients (17%) had experienced an ORR, 28 patients (59.6%) had experienced stable disease (SD) and 11 patients (23.4%) had PD. After 6 cycles, 1 of the 29 evaluable patients (3.5%) had an ORR, 13 patients (44.8%) had SD and 15 patients (51.7%) had PD. After a median follow-up of 48.9 weeks, median TTP was 18 weeks and median overall survival was 54.4 weeks. Treatment was well tolerated; grade 3 toxicities occurred in only 5/51 patients (9.8%). The most common toxicities were paraesthesia (62.7%), diarrhoea (23.5%), nausea (41.2%), vomiting (33.3%), hepatotoxicity (25.5%), and hematological toxicity (41.2%). In conclusion, the combination of oxaliplatin plus raltitrexed appears to be effective and well tolerated as second-line therapy in patients with disseminated CRC.     

Stable Clinical Outcomes When a Stroke Thrombectomy Program Is Started in an Experienced Cardiology Cath Lab

ObjectivesThis study analyzed the learning curve effect when a new stroke thrombectomy program was initiated in a cardiac cath lab in close cooperation with neurologists and radiologists.BackgroundMechanical thrombectomy has proven to be the best treatment option for ischemic stroke patients, but this method is not widely available.MethodsAn endovascular treatment program for acute ischemic strokes was established in the cardiac cath lab of a tertiary university hospital in 2012. The decision to perform catheter-based thrombectomy was made by a neurologist and was based on acute stroke clinical symptoms and computed tomography angiographic findings. Patients with a large vessel occlusion of either anterior or posterior circulation were enrolled. The primary endpoint was the functional neurological outcome (Modified Rankin Scale [mRS] score) of the patient at 3 months. A total of 333 patients were enrolled between October 2012 and December 2019.ResultsThe clinical (mRS) outcomes did not vary significantly across years 2012 to 2019 (mRS 0 to 2 was achieved in 47.9% of patients). Symptomatic intracerebral hemorrhage occurred in 19 patients (5.7%). Embolization in a new vascular territory occurred in 6 patients (1.8%).ConclusionsWhen a catheter-based thrombectomy program was initiated in an experienced cardiac cath lab in close cooperation between cardiologists, neurologists, and radiologists, outcomes were comparable to those of neuroradiology centers. The desired clinical results were achieved from the onset of the program, without any signs of a learning curve effect. These findings support the potential role of interventional cardiac cath labs in the treatment of acute stroke in regions where this therapy is not readily available due to the lack of neurointerventionalists.     

Neointimal coverage and late apposition of everolimus-eluting bioresorbable scaffolds implanted in the acute phase of myocardial infarction: OCT data from the PRAGUE-19 study

Incomplete stent apposition and uncovered struts are associated with a higher risk of stent thrombosis. No data exist on the process of neointimal coverage and late apposition status of the bioresorbable vascular scaffold (BVS) when implanted in the highly thrombogenic setting of ST-segment elevation acute myocardial infarction (STEMI). The aim of this study was to assess the serial changes in strut apposition and early neointimal coverage of the BVS using optical coherence tomography (OCT) in selected patients enrolled in the PRAGUE-19 study. Intracoronary OCT was performed in 50 patients at the end of primary percutaneous coronary intervention for acute STEMI. Repeated OCT of the implanted BVS was performed in 10 patients. Scaffold area, scaffold mean diameter and incomplete strut apposition (ISA) were compared between baseline and control OCT. Furthermore, strut neointimal coverage was assessed during the control OCT. Mean scaffold area and diameter did not change between the baseline and control OCT (8.59 vs. 9.06 mm²; p = 0.129 and 3.31 vs. 3.37 mm; p = 0.202, respectively). Differences were observed in ISA between the baseline and control OCT (0.63 vs. 1.47 %; p < 0.05). We observed 83.1 % covered struts in eight patients in whom the control OCT was performed 4–6 weeks after BVS implantation, and 100 % covered struts in two patients 6 months after BVS implantation. Persistent strut apposition and early neointimal coverage were observed after biodegradable vascular scaffold implantation in patients with acute ST-segment elevation myocardial infarction.     

Sex differences in the pharmacokinetics of salicylates

The kinetics of disposition of total and free salicylic acid (SA) in blood plasma was evaluated after single and multiple oral administration of acetylsalicylic acid (ASA) to healthy female and male volunteers. In both single and multiple dose studies significant sex differences were found in the plasma levels of SA, which were due, at least in part, to individual, sex-determined differences in the rate of absorption and elimination of SA; a slower absorption rate in men reduced the magnitude of the peak plasma levels of SA. The corresponding area under concentration-time curves were always significantly lower. The elimination rate of SA in men was increased in comparison with women. The higher plasma clearance in men resulted from the kinetics of absorption and elimination. The sex differences appear to be clinical significance, since men achieved lower plasma levels of SA than women after the same weight-adjusted dose of ASA.     

The effect of alpha-glucosidase inhibition on intestinal disaccharidase activity in normal and diabetic mice

Acarbose is a potent alpha-glycosidase inhibitor which decreases postprandial hyperglycemia when administered with a carbohydrate-containing meal. The genetically diabetic mouse C57 BLKsJ db/db represents a model of type II, noninsulin dependent diabetes mellitus. Characteristic features of this animal include hyperglycemia, hyperinsulinemia, hyperphagia, and the development of obesity and widespread pathologic abnormalities. To evaluate the effects of Acarbose on intestinal disaccharidase activity, groups of normal and diabetic mice were given Acarbose as a drug-food mixture in doses of 20 (A-20) and $\text{40 (A-40) mg}\text{100 g}$ food. Sucrase activity was measured in intestinal homogenates and on the mucosal surface of proximal, middle, and distal segments of jejunoileum. In normal mice, sucrase activity was significantly increased in mid- and distal-intestinal segments following 2 wk of Acarbose in both A-20 and A-40 groups. No changes were noted following 5 and 10 days of drug treatment. Acarbose did not influence body weight, food:water intake or fasting blood glucose. When compared to normal mice, untreated diabetics had significantly more protein, DNA, and sucrase activity throughout the small intestine. Following 10 wk of Acarbose administration, both A-20 and A-40 groups showed increased sucrase activity in intestinal homogenates of distal segments. Surface mucosal sucrase activity however was slightly decreased in proximal intestinal segments as a result of drug therapy, with no changes in middle and distal segments. Acarbose did not influence body weight, food intake or fasting blood glucose, but water consumption and glucosuria were significantly decreased. Experimental diabetes mellitus is associated with significant alterations in enzyme activity and protein content of the brush border membrane of the small intestine. Acarbose administration influences both sucrase activity and distribution in normal and diabetic mice. The mechanisms responsible for these changes and their potential clinical importance remain to be determined.     

Causes of severe visual impairment and blindness in children attending schools for the visually handicapped in the Czech Republic

AIMS: To describe the causes of severe visual impairment and blindness in children in schools for the visually handicapped in the Czech Republic in 1998. METHODS: Pupils attending all 10 primary schools for the visually handicapped were examined. A modified WHO/PBL eye examination record for children with blindness and low vision was used. RESULTS: 229 children (146 males and 83 females) aged 6-15 years were included in the study: 47 children had severe visual impairment (20.5%) (visual acuity in their better eye less than 6/60), and 159 were blind (69.5%) (visual acuity in their better eye less than 3/60). Anatomically, the most affected parts of the eye were the retina (124, 54.2%), optic nerve (35, 15.3%), whole globe (25, 10.9%), lens (20, 8.7%), and uvea (12, 5.2%). Aetiologically (timing of insult leading to visual loss), the major cause of visual impairment was retinopathy of prematurity (ROP) (96, 41.9 %), followed by abnormalities of unknown timing of insult (97, 42.4%), and hereditary disease (21, 9.2%). In 90 children (40%), additional disabilities were present: mental disability (36, 16%), physical handicap (16, 7%), and/or a combination of both (19, 8%). It was estimated that 127 children (56%) suffer from visual impairment caused by potentially preventable and/or treatable conditions (for example, ROP, cataract, glaucoma). CONCLUSIONS: Establishing a study group for comprehensive evaluation of causes of visual handicap in children in the Czech Republic, as well as for detailed analysis of present practice of screening for ROP was recommended.     

Histamine liberation as a result of nonreceptor interaction

The highly lipophilic drug exaprolol liberates histamine from isolated mast cells and decreases the uptake of extracellular histamine in a dose-dependent manner. Intracellular histamine depletion was confirmed by electron microscopy and was accompanied by calcium displacement from intracellular storage sites. The significant decrease in membrane fluidity due to exaprolol was temperature-dependent and was most probably a result of its high membrane affinity and intracellular penetration. Membrane perturbation by exaprolol may account for this nonreceptor interaction. This could contribute to the understanding of adverse reactions to betaadrenoceptor blocking drugs.