Partial resection of native and prosthetic arteriovenous fistula as a treatment of late infections complications - series of case reports.

INTRODUCTION: Infection of arteriovenous fistula (AV) used for hemodialysis (HD) is associated with massive bleeding, sepsis development, formation of metastatic infectious foci, and a high risk of AV loss. Urgent management of an infected AV is crucial for successful treatment and AV salvage. CASE REPORTS: We present the use of partial resection as a successful method of dealing with late AV infection in two cases. In case 1, the resection was performed due to an infection of the native arteriovenous fistula (AVF) with two defects above the drainage vein aneurysms. In case 2, partial resection and replacement of the prosthetic arteriovenous fistula (AVG) were done due to an infection of HD puncture site. The AVs remained patent in both cases, with no further signs of infection postoperatively and, most importantly, without the need to use a temporary HD catheter. CONCLUSION: The establishment of a new AV is limited by the quality of the venous and arterial systems. All surgical, interventional and non-surgical means should be used to safely maintain the created AV patent. Provided that the requirements of an early indication are met, partial resection of the AV is the method of choice for AV infections and allows us to avoid using a permanent dialysis catheter in our patients.

Low-burden TP53 mutations in chronic phase of myeloproliferative neoplasms: association with age, hydroxyurea administration, disease type and JAK2 mutational status.

The multistep process of TP53 mutation expansion during myeloproliferative neoplasm (MPN) transformation into acute myeloid leukemia (AML) has been documented retrospectively. It is currently unknown how common TP53 mutations with low variant allele frequency (VAF) are, whether they are linked to hydroxyurea (HU) cytoreduction, and what disease progression risk they carry. Using ultra-deep next-generation sequencing, we examined 254 MPN patients treated with HU, interferon alpha-2a or anagrelide and 85 untreated patients. We found TP53 mutations in 50 cases (0.2-16.3% VAF), regardless of disease subtype, driver gene status and cytoreduction. Both therapy and TP53 mutations were strongly associated with older age. Over-time analysis showed that the mutations may be undetectable at diagnosis and slowly increase during disease course. Although three patients with TP53 mutations progressed to TP53-mutated or TP53-wild-type AML, we did not observe a significant age-independent impact on overall survival during the follow-up. Further, we showed that complete p53 inactivation alone led to neither blast transformation nor HU resistance. Altogether, we revealed patient's age as the strongest factor affecting low-burden TP53 mutation incidence in MPN and found no significant age-independent association between TP53 mutations and hydroxyurea. Mutations may persist at low levels for years without an immediate risk of progression.

Toxicity and survival outcomes of adjuvant chemoradiation for gastric and gastroesophageal junction cancer patients treated in period 2006-2009: an institutional experience.

Surgical resection is the mainstay of gastric or gastroesophageal junction cancer treatment and has curative potential for patients with early-stage disease. In order to improve the poor survival rates, there are two complementary treatment strategies used at most - perioperative chemotherapy based on UK Magic trial or adjuvant chemoradiation based on INT-0116 trial. Daily treatment decision making should be led also by institutional experiences with toxicity evaluation. We evaluated survival and toxicity outcomes of 47 consecutive patients who underwent adjuvant chemoradiation in our institution in the years 2006-2009. 45Gy in 5 weeks with concurrent two cycles of FUFA Mayo regimen chemotherapy were administrated as part of combined treatment. The acute toxicity was relatively mild (CTCAE scale): grade 2 nausea in 26%, vomiting in 13%, and diarrhoea grade 1 in 15% and general abdominal discomfort in 57% of patients. Grade 3 haematological and infectious complications in 6% and 2% respectively. Late adverse events were as follows: grade 1 esophageal toxicity in 17%, signs of mild chronic esophageal ulceration and esophageal stenosis in 9% of patients (50% of them had tracheoesophageal fistula). The Kaplan- Meier estimate of the median overall survival was 30.5 months with median 25.7 months disease free survival. The overall survival was statistically significantly affected by the amount of removed positive lymph nodes. For the proper evaluation of radiotherapy role in multimodal treatment approach, results of other clinical trials investigating role of concurrent radiotherapy in administration of perioperative chemotherapy will be necessary. Meanwhile, two equally approaches are possible, all having their pros and cons. Institutional toxicity evaluation is recommended in order to provide the best care possible.

Toxicity and survival outcomes of adjuvant chemoradiation for gastric and gastroesophageal junction cancer patients treated in period 2006-2009: an institutional experience.

Surgical resection is the mainstay of gastric or gastroesophageal junction cancer treatment and has curative potential for patients with early-stage disease. In order to improve the poor survival rates, there are two complementary treatment strategies used at most - perioperative chemotherapy based on UK Magic trial or adjuvant chemoradiation based on INT-0116 trial. Daily treatment decision making should be led also by institutional experiences with toxicity evaluation. We evaluated survival and toxicity outcomes of 47 consecutive patients who underwent adjuvant chemoradiation in our institution in the years 2006-2009. 45Gy in 5 weeks with concurrent two cycles of FUFA Mayo regimen chemotherapy were administrated as part of combined treatment. The acute toxicity was relatively mild (CTCAE scale): grade 2 nausea in 26%, vomiting in 13%, and diarrhoea grade 1 in 15% and general abdominal discomfort in 57% of patients. Grade 3 haematological and infectious complications in 6% and 2% respectively. Late adverse events were as follows: grade 1 esophageal toxicity in 17%, signs of mild chronic esophageal ulceration and esophageal stenosis in 9% of patients (50% of them had tracheoesophageal fistula). The Kaplan- Meier estimate of the median overall survival was 30.5 months with median 25.7 months disease free survival. The overall survival was statistically significantly affected by the amount of removed positive lymph nodes. For the proper evaluation of radiotherapy role in multimodal treatment approach, results of other clinical trials investigating role of concurrent radiotherapy in administration of perioperative chemotherapy will be necessary. Meanwhile, two equally approaches are possible, all having their pros and cons. Institutional toxicity evaluation is recommended in order to provide the best care possible. Keywords: adjuvant chemoradiation, gastric cancer, early toxicity, late toxicity, survival outcomes.

[Complex surgical management of hemodialysis vascular access infection caused by Clostridium perfringens]. / Kombinovaný chirurgický management infekce hemodialyzacního cévního prístupu bakteriologickým agens Clostridium perfringens.

Infection of prosthetic hemodialysis (HD) shunts is one of the most common complications of vascular access in hemodialysis patients. The incidence of anaerobic infection is very rare. In such a case, management of treatment represents a great challenge for the surgeon. We report a complicated case of autologous hemodialysis shunt infected by Clostridium perfringens on the right forearm in a polymorbid female patient with chronic renal failure and myelodysplastic syndrome. The patient has undergone repeated establishment of HD shunt with subsequent polybacterial local infectious complications. Destructive clostridial infection developed at the site of the infectious complications. This very rare complication involving infection by an atypical bacterial agent requires rapid diagnosis and comprehensive multimodal treatment including surgical, antibiotic and supportive therapy. Clinical implications and optimal therapy is not precisely defined in these cases.

Understanding the dialysis access steal syndrome. A review of the etiologies, diagnosis, prevention and treatment strategies.

Distal hypoperfusion ischemic syndrome (DHIS), commonly referred to as hand ischemia or 'steal' after dialysis access placement, occurs in 5-10% of cases when the brachial artery is used, or 10 times that of wrist arteriovenous fistulas (AVFs) using the radial artery. It is typically seen in elderly women with diabetes, and may carry severe morbidity including tissue or limb loss if not recognized and treated. Three distinct etiologies include (1) blood flow restriction to the hand from arterial occlusive disease either proximal or distal to the AV access anastomosis, (2) excess blood flow through the AV fistula conduit (true steal), and (3) lack of vascular (arterial) adaptation or collateral flow reserve (ie atherosclerosis) to the increased flow demand from the AV conduit. These three causes of steal may occur alone or in concert. The diagnosis of steal is based on an accurate history and physical examination and confirmed with tests including an arteriogram, duplex Doppler ultrasound (DDU) evaluation with finger pressures and waveform analysis. Treatment of steal includes observation of developing symptoms in mild cases. Balloon angioplasty is the appropriate intervention for an arterial stenosis. At least three distinct surgical corrective procedures exist to counteract the pathophysiology of steal. The ultimate treatment strategy depends on severity of symptoms, the extent of patient co-morbidity, and the local dialysis access technical team support and skills available.

Manipulation of host cytokine network by ticks: a potential gateway for pathogen transmission.

Ticks are obligatory blood-feeding arthropods that secrete various immunomodulatory molecules to antagonize host inflammatory and immune responses. Cytokines play an important role in regulating these responses. We investigated the extent to which ticks interact with the sophisticated cytokine network by comparing the effect of salivary gland extracts (SGE) of 3 ixodid tick species, Dermacentor reticulatus, Amblyomma variegatum and Ixodes ricinus, all of which are important vectors of tick-borne pathogens. Using specific ELISAs, anti-cytokine activity was demonstrated with 7 cytokines: IL-8, MCP-1, MIP-1alpha, RANTES, eotaxin, IL-2 and IL-4. The results varied between species, and between adult males and females of the same species. Relatively high activity levels were detected in saliva of female D. reticulatus, confirming that the observed anti-cytokine activities are an integral part of tick saliva secreted into the host. Results with fractionated SGE indicated that from 2 to 6 putative cytokine binding molecules are produced, depending on species and sex. Binding ability of SGE molecules was verified by cross-linking with radio-isotope labelled MIP-1alpha. By targeting different cytokines, ixodid ticks can manipulate the cytokine network, which will greatly facilitate blood-feeding and provide a gateway for tick-borne pathogens that helps explain why ticks are such efficient and effective disease vectors.

[Would ultrasonography contribute to the early detection of clinically silent dialysis access stenoses?]. / Prispela by ultrasonografie ke vcasnému záchytu klinicky nemých stenóz dialyzacních zkratu?

BACKGROUND: Stenoses are leading factors limiting dialysis vascular access patency. Both physical and haemodynamic examinations are used in stenoses screening. To estimate potential advantage of ultrasonography as a screening measure, we calculated both sensitivity and specificity of clinical (nephrological) diagnoses of access stenoses compared with ultrasound. METHODS AND RESULTS: 268 examinations of 193 subjects were included into this comparison. Linear-array 7.5 MHz ultrasound probe were used for whole-length access examination. Sensitivity of clinical examination was 35.8%, specificity 92.8%. Sensitivity did not differ significantly according to the stenosis localization. CONCLUSIONS: Ultrasound use in dialysis access screening would considerably increase the number of stenoses diagnosed in-time. On the contrary, clinical suspicion on access stenosis is highly specific, therefore it is not indispensable to confirm it by ultrasound.

[Ultrasonography of complications in vascular access for dialysis: initial experience]. / Ultrasonografie komplikací dialyzacních cévních zkratu: první zkusenosti.

BACKGROUND: Vascular access complications represent leading morbidity of hemodialyzed patients. Duplex Doppler ultrasonography is used rarely in the diagnosis of vascular access complications, despite its simplicity and widespread availability. Our first experience with this method is described, namely the most frequent indications, findings and the access blood flow correlation. METHODS AND RESULTS: 356 examinations of both natural and polytetrafluoroethylene (PTFE) accesses at 193 patients were performed. The 7.5 MHz linear array ultrasound transducer of Hewlett-Packard SONOS 2000 device was used. Both arterial and venous parts of fistulas were examined in all cases. Screening examinations represented the most frequent indication, the hemodynamically significant stenosis the most frequent finding. Only 12.5% of PTFE-shunts and 25.8% of natural fistulas were described as normal. Mean blood flow through antebrachial and brachial accesses was 575 and 1070 ml/min, respectively. CONCLUSIONS: Prevalence of vascular access complications (especially that of stenoses) is high. Wider use of this method could bring significantly improved care for the dialysed patients.

Vesicular stomatitis virus nucleocapsid protein production in cells treated with selected fast protein liquid chromatography fractions of tick salivary gland extracts.

A salivary gland extract (SGE) prepared from 5-days-fed Dermacentor reticulatus female ticks was fractionated by fast protein liquid chromatography (FPLC). The effect of three FPLC fractions selected on the basis of anti-interleukin 8 (anti-IL-8) activity on vesicular stomatitis virus (VSV) nucleocapsid (N) protein formation in mouse L-cells was determined. Infected 14C-labeled cells treated with the FPLC fractions were analyzed by two-dimensional (2D) electrophoresis. The yields of VSV N protein were evaluated by Imagemaster software analysis. Most noticeable was an increase in the N protein production after treatment with the fraction 39 corresponding to the major peak of the anti-IL-8 activity. The nature of the substance in SGE that was responsible for this effect remains unclear.

Heterogeneity in the effect of different ixodid tick species on human natural killer cell activity.

Tick saliva plays a vital role in blood-feeding, including manipulation of the host response to tick infestation. Furthermore, a diverse number of tick-borne pathogens are transmitted to vertebrate hosts via tick saliva, some of which exploit the immunomodulatory activities of their vector's saliva. We report that salivary gland extracts (SGE) derived from Dermacentor reticulatus adult ticks induce a decrease in the natural killer (NK) activity of effector cells obtained from healthy human blood donors. The decrease was observed with SGE from both female and male D. reticulatus fed for either 3 or 5 days on mice, but no significant effect was observed with SGE from unfed ticks or ticks that had fed for 1 day. These results indicate that the tick anti-NK factor(s) is only active after blood-feeding has commenced. Microscopic examination revealed that the first step of NK activity, namely effector/target cell conjugate formation, was affected by SGE. The observed reduction in conjugate formation occurred when effector (but not target) cells were treated with SGE for 30 min, and the effect persisted after 12 h of treatment. Similar but less potent anti-NK activity was detected for SGE from Amblyomma variegatum and Haemaphysalis inermis. By contrast, SGE derived from Ixodes ricinus and Rhipicephalus appendiculatus female ticks did not decrease NK activity. The apparent absence of such activity in these two important vectors of tick-borne viruses suggests that control of NK cells does not play an important role in promoting virus transmission, at least for these particular species.

Anti-interleukin-8 activity of tick salivary gland extracts.

Interleukin-8 (IL-8) is one of many mammalian chemokines (chemotactic cytokines) that direct mammalian inflammatory and immune cells to sites of injury and infection. Chemokines are produced locally and act on leucocytes through selective receptors. The principal role of IL-8 is to control the movement and activity of neutrophils. To date, several tick species have been shown to modulate the production or activity of certain cytokines but none of these are chemokines. Using an IL-8 specific ELISA, we showed that salivary gland extracts (SGE) from several ixodid tick species (Dermacentor reticulatus, Amblyomma variegatum, Rhipicephalus appendiculatus, Haemaphysalis inermis and Ixodes ricinus) reduced the level of detectable IL-8. Analyses of fractionated SGE revealed one similar peak of activity for D. reticulatus, A. variegatum and R. appendiculatus; a second peak, observed for D. reticulatus and A. variegatum, differed between the two species. Using radiolabelled IL-8, SGE and peak activity fractions of D. reticulatus were shown to bind the chemokine, and to inhibit binding of IL-8 to its receptors on human granuolocytes enriched for neutrophils. The biological significance of these observations was demonstrated by the ability of SGE to inhibit IL-8 induced chemotaxis of human blood granulocytes. Future isolation and characterization of the active molecules will enable determination of their functional roles in bloodfeeding and effect on tick-borne pathogen transmission.

[Hyperparathyroidism and parathyroidectomy in dialyzed patients]. / Hyperparatyreóza a paratyroidektomie u dialyzovaných nemocných.

The authors present older and more recent views regarding the pathogenesis of hypocalcaemia and secondary hyperparathyroidism in patients with chronic renal failure with emphasis on the impact of inorganic phosphate retention and lack of 1,25-dihydroxyvitamin D3 in body fluids. As regards therapeutic procedures the initial problem is to control hyperphosphataemia and to suppress the increased parathormone secretion in particular in dialyzed patients. When treating hyperphosphataemia it is necessary with regard to the severity of the finding to use concurrently several procedures and avoid aluminium phosphate binders. Aimed reduction of high parathormone levels in the blood stream can be achieved by medicamentous--pharmacological means, using 1,25 (OH)2 D3 or surgery of the hypertrophic parathyroid glands. The term parathyroidectomy can comprise also percutaneous infiltration of the parathyroid glands with ethanol. From this aspect under certain circumstances a combination of different therapeutic procedures may prove useful. In the conclusion the authors mention basic data on para-thyroidectomies performed in their department: the favourable long-term results of operations amounted to 80.4%.

The antibody response in breast-fed and non-breast-fed infants after artificial colonization of the intestine with Escherichia coli O83.

The local and systemic antibody response after oral administration of a nonenteropathogenic type 1 fimbriated Escherichia coli O83 strain was followed in nine breast-fed and eight formula-fed infants during their first 15 wk of life. Five breast-fed and six formula-fed infants were followed as controls. E. coli O83 was detected in the stools of colonized infants from d 2 after colonization and persisted in the intestine for up to 26 wk. The percentage of children successfully colonized with E. coli O83 was higher among breast-fed than among formula-fed colonized infants. Also, the O83 bacteria isolated from the breast-fed children had a higher capacity to attach to colonic epithelial cells of the HT-29 cell line than those isolated from bottle-fed infants. E. coli O83 IgA and IgM antibodies estimated by ELISA were significantly elevated in the saliva of colonized as compared with control infants 2-7 wk after colonization. IgA antibodies against O83 were also higher in the stool of colonized formula-fed infants than in formula-fed controls. The results suggest that the mucosal immune system of the newborn infant can be triggered early to produce specific antibodies against bacteria colonizing the intestine.

The influence of artificial colonization with E. coli strain O83 on the intestinal flora in infants.

Dominant bacterial strains present in stool (with particular emphasis on E. coli strains) were examined in 4 groups of healthy infants: breast-fed and bottle-fed, colonized with E. coli O83, and control (non-colonized) breast-fed and bottle-fed newborns. The presence of fimbriae was examined by hemagglutination, the P-fimbriae-bearing strains were tested by the PPA latex test. In addition, adherence to cell line HT-29 and serotyping was performed in selected strains. The E. coli strain O83 was found to possess type 1 fimbriae. Fewer bacterial strains possessing type 1 fimbriae were found in E. coli O83-colonized infants (except the O83 serotype) than in control infants. The E. coli O83 strain colonized significantly better the breast-fed than the bottle-fed infants; its higher adherence activity was demonstrated even in cell line HT-29. Finally, colonization with E. coli O83 influenced the character of microbial intestinal flora: the frequency of positive E. coli isolates was significantly higher in colonized (both breast- and bottle-fed) than noncolonized infants.