Textural features of hypoxia PET predict survival in head and neck cancer during chemoradiotherapy.

PURPOSE: The aim of this study was to investigate whether textural features of tumour hypoxia, assessed with serial [18F]fluoromisonidazole (FMISO)-PET, were able to predict clinical outcome in patients with head and neck squamous cell carcinoma (HNSCC, T1-4, N+, M0) during chemoradiotherapy (CRT). METHODS: In a preliminary evaluation of a prospective trial, tumour hypoxia was evaluated in 29 patients via serial FMISO-PET before and during CRT. All patients received an initial [18F]fluorodeoxyglucose (FDG)-PET before CRT, and tumour regions were defined on this FDG-PET. The first-order metrics tumour-to-background ratio (TBRmean, TBRmax, TBRpeak), coefficient of variation, total lesion uptake and integral non-uniformity were calculated for all scans. Further, 3 second-order (textural) features from two grey-level matrices were calculated, as well as differential non-uniformity (udiff). Prognostic value was examined by median split for group separation (GS) in Kaplan-Meier estimates and correlated with overall survival (OS), quantified via log-rank tests (p ≤ 0.05) and group-relative hazard ratios (HR). RESULTS: Within a median follow-up of 29.6 months (95% CI: 16.8-48.0 months), no first-order metrics predicted OS with a significant GS (all p > 0.05) on any FMISO-PET scan. Only udiff before and in week 2 during CRT (p = 0.03, HR = 10.8 and p = 0.05, HR = 5.2) and non-uniformity from grey-level run length matrix in week 2 separated prognostic groups (p = 0.05, HR = 5.3); lower values were correlated with better OS. Further, the decrease in udiff from before CRT to week 2 was correlated with better OS (p = 0.04, HR = 9.4). FDG-PET before CRT did not predict outcome in any measure. CONCLUSIONS: Textural features on FMISO-PET scans before CRT, in week 2 and, to a limited degree, the change of features during CRT, were able to identify head and neck squamous cell carcinoma patients with better OS, suggesting that a higher homogeneity of the degree of hypoxia in tumours could correlate with a better outcome after CRT.

Chemokines CXCL10 and CXCL11 in the cerebrospinal fluid of patients with tick-borne encephalitis.

OBJECTIVES: The aim of our study was to determine whether cerebrospinal fluid (CSF) of patients with tick-borne encephalitis (TBE) contains CXCL10, CXCL11, p40 subunit of interleukin-12 (IL-12)/IL-23, IL-18 and IL-15. We compared serum and CSF concentrations of CXCL10 and analysed the possible concentration gradient of this chemokine between the periphery and central nervous system. MATERIALS AND METHODS: The study enrolled 19 TBE patients and 10 patients with non-inflammatory neurological diseases. RESULTS: CSF of TBE patients contained CXCL10 (median 217 pg/ml), CXCL11 (8.3 pg/ml), p40 subunit of IL-12/IL-23 (38.9 pg/ml), IL-18 (30.1 pg/ml) and IL-15 (5.9 pg/ml). CXCL10 in the CSF of TBE patients was higher compared with serum (median 62 pg/ml, P < 0.001). CONCLUSION: CSF of TBE patients contains CXCL10, CXCL11, p40 subunit of IL-12/IL-23, IL-18 and IL-15. Increased CXCL10 concentration in CSF suggests a role for this chemokine in the recruitment of CXCR3-expressing T-cells into the CSF of TBE patients.

Comparison of azithromycin and doxycycline in the treatment of erythema migrans.

BACKGROUND: A randomized, multicenter, open clinical trial was undertaken in order to compare the efficacies of azithromycin and doxycycline in the treatment of patients with Lyme disease associated with erythema migrans. PATIENTS AND METHODS: A total of 48 patients was treated orally with azithromycin, 500 mg bid on the 1st day, followed by 500 mg once daily for the next 4 days or doxycycline (40 patients) 100 mg bid for 14 days. RESULTS: Intention-to-treat analysis of clinical efficacy showed no difference between the two treatment regimens. Clinical success was observed in 46 (95.8%) azithromycin- and 33 (82.5%) doxycycline-treated patients, (p = 0.0731). Minor symptoms persisted or appeared in the posttreatment period in two of 47 azithromycin- and three of 35 doxycycline-treated patients (p = 0.646). Major manifestations appeared only in two patients in the doxycycline group (p = 0.179). There was no difference in the tolerability of both drugs. CONCLUSION: Azithromycin (a total dose of 3 g) is equally effective as standard doxycycline treatment for erythema migrans in adult patients.

Detection and genotyping of Borrelia burgdorferi sensu lato by polymerase chain reaction.

AIM: To isolate and genotype Borrelia burgdorferi genospecies in serum samples of Croatian patients with erythema migrans. METHODS: DNA isolates from sera of patients with erythema migrans were analyzed by nested polymerase chain reaction (PCR), amplifying a segment of flagellin gene with primers encompassing the conserved region of the gene. To screen PCR products for heterogeneity, we performed single-stranded conformation polymorphism (SSCP) analysis. The samples showing differences in SSCP patterns were sequenced, and the sequence compared in the GeneBank for sequence homology with known Borrelia burgdorferi genospecies. We also constructed phylogenetic tree of all known borrelial sequences. RESULTS: The nested PCR method using specially designed flagellin gene primers, achieved the sensitivity of 10 genome copies (0.01 pg of purified Borrelia burgdorferi DNA from culture) by dilution analysis. The assay specificity was confirmed by amplification of a part of the flagellin gene from different bacterial species. The primer pairs successfully amplified only Borrelia burgdorferi flagellin gene. The genome of Borrelia burgdorferi sensu lato was detected in the sera of all 10 tested patients with erythema migrans. Sequence data and phylogenetic analysis confirmed that all amplified samples belonged to Borrelia afzelii genospecies. CONCLUSION: Phylogenetic tree analysis placed the borrelial isolates together with Borrelia afzelii sequences into a single group. This finding was additionally supported by sequence homology analysis, which produced a homology score of 99%. In patients with erythema migrans who come from the northwest Croatia, an endemic area for Lyme borreliosis, Borrelia afzelii was the cause of skin manifestations of Lyme borreliosis.

[Tularemia transmitted by arthropod bites]. / Tularemija prenesena ubodom clankonozaca.

The authors present four patients affected with tularaemia in Koprivnica-Krizevci region. The disease occurred in the period from April to September 1994, in 3 males and 1 female patient, aged 9-49 years. In all affected persons the infections were transmitted after bites of arthropods, ticks or other insects. The disease was clinically manifested as ulceroglandular form, without complications and relapses. The diagnosis was established by anamnestic and epidemiological data, clinical picture, the course of the disease, laboratory findings, tularin test and specific agglutination test (two samples). All patients were successfully treated with doxycyclin.