Incident Cancer Risk in Patients with Incident Type 2 Diabetes Mellitus in Hungary (Part 1).

(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal of this study was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. After exclusion of cases of age < 18 years, with gestational diabetes, with polycystic ovary syndrome, and with type 1 and prevalent type 2 diabetes mellitus, the incident T2DM (approx. 50,000 cases yearly) and for comparison, the diabetes-free Hungarian adult population (approx. 7,000,000 cases yearly) was included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14-4.53), p < 0.0001. The risk of having cancer was age dependent. The incidence of cancer was declining in the non-diabetic but was unchanged in the T2DM population. The average lag time of diagnosing cancer after the detection of T2DM was 3.86 months. (4) Conclusions: Incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months.

Opposite trends in incidence of breast cancer in young and old female cohorts in Hungary and the impact of the Covid-19 pandemic: a nationwide study between 2011-2020.

Background: This nationwide study examined breast cancer (BC) incidence and mortality rates in Hungary between 2011-2019, and the impact of the Covid-19 pandemic on the incidence and mortality rates in 2020 using the databases of the National Health Insurance Fund (NHIF) and Central Statistical Office (CSO) of Hungary. Methods: Our nationwide, retrospective study included patients who were newly diagnosed with breast cancer (International Codes of Diseases ICD)-10 C50) between Jan 1, 2011 and Dec 31, 2020. Age-standardized incidence and mortality rates (ASRs) were calculated using European Standard Populations (ESP). Results: 7,729 to 8,233 new breast cancer cases were recorded in the NHIF database annually, and 3,550 to 4,909 all-cause deaths occurred within BC population per year during 2011-2019 period, while 2,096 to 2,223 breast cancer cause-specific death was recorded (CSO). Age-standardized incidence rates varied between 116.73 and 106.16/100,000 PYs, showing a mean annual change of -0.7% (95% CI: -1.21%-0.16%) and a total change of -5.41% (95% CI: -9.24 to -1.32). Age-standardized mortality rates varied between 26.65-24.97/100,000 PYs (mean annual change: -0.58%; 95% CI: -1.31-0.27%; p=0.101; total change: -5.98%; 95% CI: -13.36-2.66). Age-specific incidence rates significantly decreased between 2011 and 2019 in women aged 50-59, 60-69, 80-89, and ≥90 years (-8.22%, -14.28%, -9.14%, and -36.22%, respectively), while it increased in young females by 30.02% (95%CI 17,01%- 51,97%) during the same period. From 2019 to 2020 (in first COVID-19 pandemic year), breast cancer incidence nominally decreased by 12% (incidence rate ratio [RR]: 0.88; 95% CI: 0.69-1.13; 2020 vs. 2019), all-cause mortality nominally increased by 6% (RR: 1.06; 95% CI: 0.79-1.43) among breast cancer patients, and cause-specific mortality did not change (RR: 1.00; 95%CI: 0.86-1.15). Conclusion: The incidence of breast cancer significantly decreased in older age groups (≥50 years), oppositely increased among young females between 2011 and 2019, while cause-specific mortality in breast cancer patients showed a non-significant decrease. In 2020, the Covid-19 pandemic resulted in a nominal, but not statistically significant, 12% decrease in breast cancer incidence, with no significant increase in cause-specific breast cancer mortality observed during 2020.

Morbidity and mortality of patients with diabetic neuropathy treated with pathogenetically oriented alpha-lipoic acid versus symptomatic pharmacotherapies - A nationwide database analysis from Hungary.

AIMS: Diabetic neuropathy is associated with increased risk of morbidity and all-cause mortality. It is unclear whether these outcomes differ in patients with diabetic neuropathy treated with pathogenetically oriented vs symptomatic pharmacotherapies. METHODS: We performed a retrospective (2009-2019) database analysis of patients treated with pathogenetically oriented alpha-lipoic acid (ALA) or symptomatic pharmacotherapies for diabetic neuropathy. We investigated clinical outcomes in propensity score matched patients in Hungary. Changes in hazard ratios and annualized event rates were assessed and sensitivity analyses performed. RESULTS: Hazard ratios favored treatment with ALA vs symptomatic pharmacotherapies regarding acute myocardial infarction (HR 0.73, 95% CI: 0.60-0.89, p = 0.0016), stroke (HR 0.71, 95% CI: 0.62-0.82, p < 0.0001), hospitalization for heart failure (HR 0.72, 95% CI: 0.66-0.78, p < 0.0001), cancer events (HR 0.83, 95% CI: 0.76-0.92, p = 0.0002) and all-cause mortality (HR 0.55, 95% CI: 0.49-0.61, p < 0.0001), but not for lower limb amputation (HR 1.05, 95% CI: 0.89-1.25, p = 0.5455). This association was supported by results of evaluating annual event rates and sensitivity analyses. CONCLUSIONS: This retrospective database analysis revealed a lower occurrence of cardio- and cerebrovascular morbidity, cancer events and all-cause mortality in patients with diabetic neuropathy treated with pathogenetically oriented ALA vs symptomatic pharmacotherapies. This hypothesis-generating result requires further investigations.

Mortality on DOACs Versus on Vitamin K Antagonists in Atrial Fibrillation: Analysis of the Hungarian Health Insurance Fund Database.

PURPOSE: Limited real-world data are available on the survival of patients treated with vitamin K antagonists (VKAs) versus with direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (AF). In this nationwide registry, we analyzed the mortality risk of patients with nonvalvular AF taking DOACs versus VKAs, with a special attention to the early treatment period. METHODS: The Hungarian National Health Insurance Fund (NHIF) database was searched to identify patients treated with VKA or DOAC as a thromboembolic prophylaxis for nonvalvular AF between 2011 and 2016. The overall and the early (0-3, 4-6, and 7-12 months) mortality risks with the 2 types of anticoagulation were compared. A total of 144,394 patients with AF treated with either a VKA (n = 129,925) or a DOAC (n = 14,469) were enrolled. FINDINGS: A 28% improvement in 3-year survival with DOAC treatment compared with VKA treatment was shown. Mortality reduction with DOACs was consistent across different subgroups. However, younger patients (30-59 years old) initiated on DOAC therapy had the greatest RRR (53%) in mortality. Furthermore, DOAC treatment also yielded a benefit of greater magnitude (HR = 0.55; 95% CI, 0.40-0.77, P = 0.001) in the lower (0-1) CHA2DS2-VASc score segment and in those with fewer (0-1) bleeding risk factors (HR = 0.50, CI 0.34-0.73, P = 0.001). The RRR in mortality with DOACs was 33% within the first 3 months, and 6% in the second year. IMPLICATIONS: Thromboembolic prophylaxis with DOACs in this study yielded significantly lower mortality compared with VKA treatment in patients with nonvalvular AF. The largest benefit was shown in the early period after treatment initiation, as well as in younger patients, those with a lower CHA2DS2-VASc score, and those with fewer bleeding risk factors.

Significant improvement in melanoma survival over the last decade: A Hungarian nationwide study between 2011 and 2019.

BACKGROUND: Recent real-world studies have reported significant improvements in the survival of malignant melanoma in the past few years, mainly as a result of modern therapies. However, long-term survival data from Central Eastern European countries such as Hungary are currently lacking. METHODS: This nationwide, retrospective study examined melanoma survival in Hungary between 2011-2019 using the databases of the National Health Insurance Fund (NHIF) and Central Statistical Office (CSO) of Hungary. Crude overall survival and age-standardized 5-year net survival as well as the association between age, sex and survival were calculated. RESULTS: Between 2011 and 2019, 22,948 newly diagnosed malignant melanoma cases were recorded in the NHIF database (47.89% male, mean age: 60.75 years (SD: ±16.39)). Five-year overall survival was 75.40% (women: 80.78%; men: 69.52%). Patients diagnosed between 2017-2019 had a 20% lower risk of mortality compared to patients diagnosed between 2011-2012 (HR 0.80, 95% CI 0.73-0.89; p < 0.0001). Age-standardized 5-year net survival rates in 2011-2014 and 2015-2019 were 90.6% and 95.8%, respectively (women: 93.1% and 98.4%, men: 87.8% and 92.7%, respectively). The highest age-standardized 5-year net survival rates were found in the 0-39 age cohort (94.6% in the 2015-2019 period). CONCLUSION: Hungary has similar melanoma survival rates to Western European countries. Based on net survival, the risk of dying of melanoma within 5 years was cut by more than half (55%) during the study period, which coincides with the successful implementation of awareness campaigns and the wide availability of modern therapies.

Sodium-Glucose Co-Transporter 2 Inhibitors May Change the Development of Urinary Tract and Hematological Malignancies as Compared With Dipeptidyl Peptidase-4 Inhibitors: Data of the Post-Hoc Analysis of a Nationwide Study.

BACKGROUND: In diabetes mellitus, during the last years, cancer became of equivalent importance as a cardiovascular disease in terms of mortality. In an earlier study, we have analyzed data of the National Health Insurance Fund (NHIF) of Hungary with regards all patients treated with sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2is) vs. those treated with dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP-4is) in a given timeframe. In propensity score-matched groups of SGLT2i- vs. DPP-4i-treated patients, we found a lower incidence of cancer in general. In this post-hoc analysis, we aimed to obtain data on the incidence of site-specific cancer. PATIENTS AND METHODS: All patients starting an SGLT2i or a DPP-4i between 2014 and 2017 in Hungary were included; the two groups (SGLT2i vs. DPP-4i) were matched for 54 clinical and demographical parameters. The follow-up period was 639 vs. 696 days, respectively. Patients with a letter "C" International Classification of Diseases, 10th Revision (ICD-10) code have been chosen, and those with a known malignancy within a year before the onset of the study have been excluded from the analysis. RESULTS: We found a lower risk of urinary tract [HR 0.50 (95% CI: 0.32-0.79) p = 0.0027] and hematological malignancies [HR 0.50 (95% CI: 0.28-0.88) p = 0.0174] in patients treated with SGLT2i vs. those on DPP-4i. Risk of other types of cancer (including lung and larynx, lower gastrointestinal (GI) tract, rectum, pancreas, non-melanoma skin cancers, breast, or prostate) did not differ significantly between the two groups. When plotting absolute risk difference against follow-up time, an early divergence of curves was found in case of prostate, urinary tract, and hematological malignancies, whereas late divergence can be seen in case of cancers of the lung and larynx, the lower GI tract, and the breast. CONCLUSIONS: Urinary tract and hematological malignancies were less frequent in patients treated with SGLT2i vs. DPP-4i. An early vs. late divergence could be observed for different cancer types, which deserves further studies.

Improving Quality Indicator of Melanoma Management - Change of Melanoma Mortality-to-Incidence Rate Ratio Based on a Hungarian Nationwide Retrospective Study.

INTRODUCTION: The incidence of melanoma has been increasing in the last decades. A retrospective Hungarian epidemiological study provided real-world data on incidence and mortality rates. There have been changing trends in incidence in Hungary in the last decade and mortality decreased, shifting mortality-to-incidence rate ratios (MIR). MIR is an indicator of cancer management quality. OBJECTIVES: Our aim is to show the changes of melanoma MIR in Hungary between 2011 and 2018 and to compare the real-world evidence-based results of our Hungarian nationwide retrospective study with other European countries. METHODS: MIR is calculated from the age-specific standardized incidence and mortality rates from our study. Annual MIR values are presented for the total population and for both sexes between 2011 and 2018, along with 95% confidence intervals. Comparison with European countries are shown for 2012 and 2018 based on the GLOBOCAN database and Eurostat health care expenditure per capita data. RESULTS: MIR decreased by 0.035 during the study years. The decrease was same in both sexes (0.031). Male had higher MIRs in all study years. In both 2012 and 2018, Hungarian MIR in both sexes was lower than the European Union average (males: 0.192 vs. 0.212 and 0.148 vs. 0.174 respectively, women: 0.107 vs. 0.129 and 0.083 vs. 0.107 respectively). DISCUSSION: Hungarian mortality-to-incidence ratio is the lowest in Central and Eastern Europe and is close to the level of Western and Northern European countries. The results are driven by the high number of new diagnosed melanoma cases.

Evaluation of corneal anaesthesia after the application of topical 0.5% bupivacaine, 2% lidocaine and 0.4% oxybuprocaine in normal horses.

OBJECTIVE: To compare the corneal anaesthetic effect of 0.5% bupivacaine, 2% lidocaine and 0.4% oxybuprocaine on normal equine eyes. STUDY DESIGN: Prospective, blinded crossover study. ANIMALS: A group of 10 clinically healthy horses. METHODS: Corneal sensitivity was determined in each eye by measuring corneal touch threshold (CTT). The study had three phases. Each subject was randomly given one of the three treatments followed by a 72 hour washout period. Every horse received all treatments. Baseline CTT was recorded prior to anaesthetic instillation (T0) then CTT was measured 5 and 10 minutes after (T1 and T2, respectively), then 20 to 90 minutes (T3 to T10) at 10 minute intervals. CTT data were compared among treatments at each time point using the Friedman test p < 0.05. RESULTS: Median (range) baseline CTT was 51.3 (25.0-60.0) mm for bupivacaine, 50.0 (40.0-55.0) mm for oxybuprocaine and 55.0 (30.0-60.0) mm for lidocaine. All treatments caused a significant decrease in CTT at T1. The lowest CTT was observed at T3 with bupivacaine and oxybuprocaine treatments. Median CTTs at this time point were 18.7 (5.0-25.0) mm and 28.7 (25.0-40.0) mm, respectively. The lowest CTT with lidocaine treatment was 28.7 (20.0-50.0) mm at T6 (50 minutes). At T3, CTT was significantly lower with the bupivacaine treatment compared with oxybuprocaine and lidocaine treatments (p < 0.0074). There was no significant difference in CTT values between T1 and T6 for bupivacaine, between T1 and T7 for lidocaine, and between T1 and T8 for oxybuprocaine. Duration of the maximum effect was 45 minutes for the bupivacaine, 55 minutes for the lidocaine and 65 minutes for the oxybuprocaine treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a 0.5% injectable solution of bupivacaine or a 2% lidocaine had similar anaesthetic effect to the commonly used oxybuprocaine. Therefore, they might be used as alternatives for corneal anaesthesia.

Risk of morbidity and mortality in patients with type 2 diabetes treated with sodium-glucose cotransporter-2 inhibitor and/or dipeptidyl peptidase-4 inhibitor: a nationwide study.

INTRODUCTION: Mortality and disability in diabetes mellitus are determined mostly by cardiovascular complications and cancer. The impact of dipeptidyl peptidase-4 inhibitor (DPP-4i) and sodium-glucose cotransporter-2 inhibitor (SGLT2i) monotherapy or combination on long-term complications of type 2 diabetes mellitus was studied. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes treated with DPP-4i or SGLT2i during a 3-year period were identified in the database of the National Institute of Health Insurance Fund in Hungary. All-cause mortality, acute myocardial infarction, stroke, hospitalization for heart failure (HHF), lower limb amputation (LLA) and cancer were assessed. Outcomes of add-on SGLT2i to DPP-4i treatment in comparison with switching DPP-4i therapy to SGLT2i were also evaluated. After propensity score matching, survival analysis was performed with a Cox proportional hazards model. RESULTS: After propensity score matching, both SGLT2i and DPP-4i groups included 18 583 patients. All-cause mortality (HR, 0.80; 95% CI 0.68 to 0.94; p=0.0057), HHF (HR, 0.81; 95% CI 0.71 to 0.92; p=0.0018), and risk of cancer (HR, 0.75; 95% CI 0.66 to 0.86; p<0.0001) were lower in the SGLT2i population compared with DPP-4i. Risk of LLA was higher in the SGLT2i group (HR, 1.35; 95% CI 1.03 to 1.77; p=0.0315). SGLT2i in combination with DPP-4i results in lower all-cause mortality (HR, 0.46; 95% CI 0.31 to 0.67; p=0.0001), with a lower trend in stroke, LLA, HHF and cancer, but without any statistical difference. CONCLUSIONS: SGLT2i treatment leads to a lower risk of overall mortality, HHF and cancer when compared with DPP-4i treatment. Adding SGLT2i to DPP-4i instead of switching from DPP-4i to SGLT2i further lowers the risk of all-cause mortality.

Changes in mortality rates and ratios in people with pharmacologically treated type 2 diabetes mellitus between 2001 and 2016 in Hungary.

AIMS: Type 2 diabetes mellitus (T2DM) is associated with a higher risk of all-cause mortality; however, detailed analyses of subgroups are rare. In this study we analyzed the changes of age- and gender-specific all-cause mortality rates and ratios in T2DM subjects (aged > 40 years) in Hungary between 2001 and 2016. METHODS: We used the central database of the National Institute of Health Insurance Fund. All-cause mortality rates in patients with T2DM and ratios (T2DM/non-T2DM) were determined in males/females and in different age-groups. Age-adjusted values were used for standardized mortality rates. RESULTS: Among pharmacologically treated T2DM subjects we found 117,700 and 329,845 males, 232,143 and 391,382 females in 2001 and 2016, respectively. Standardized all-cause mortality rate was higher in males than in females in 2001 (4540/100,000 vs. 3365/100,000) which decreased to 4125/100,000 in males (total change: -11.8%, p < 0.0001) and to 2977/100,000 in females (total change: -9.2%; p = 0.0558) in 2016. We found a significant increase (8.35%; p = 0.0272) in standardized all-cause mortality ratios between 2001 and 2016 which was higher in males (11.44%; p = 0.0096) than in females (2.78%; p = 0.3288). We observed the most pronounced increase in younger age-groups (age 41-60 years) in both genders (change varied from 54.2% to 101.8%; p < 0.05) which was due to distinct tendencies in changes of mortality curves. CONCLUSIONS: Pharmacologically treated T2DM subjects in lower age-groups (41-60 years) had the highest increase in all-cause mortality ratios between 2001 and 2016 in Hungary. These data indicate that relatively younger patients with T2DM need special attention for improving long-term outcomes.

Survival Benefits of Second-line Axitinib Versus Everolimus After First Line Sunitinib Treatment in Metastatic Renal Cell Carcinoma.

BACKGROUND: Targeted therapies significantly improve clinical outcomes among patients with metastatic renal cell carcinoma (mRCC). Several new agents have been approved for first- and second-line use. However, there is a lack of compelling evidence comparing sequencing strategies, and available comparative data regarding the real-world effectiveness of different therapeutic sequences are limited. MATERIALS AND METHODS: We identified mRCC patients who initiated targeted therapy between January 1, 2008 and May 31, 2017 from the National Health Insurance Fund (NHIF) database of Hungary. Overall survival (OS) and duration of first-line treatment (DFT) were obtained for patients receiving sunitinib-everolimus, sunitinib-axitinib, or pazopanib-everolimus treatment sequences. OS of sunitinib-everolimus and sunitinib-axitinib sequences was also determined for patients having better or worse response to sunitinib first-line therapy. RESULTS: Median OS was significantly longer among patients treated with sunitinib-axitinib compared to those receiving sunitinib-everolimus. Median DFT was also significantly longer in the sunitinib-axitinib vs. sunitinib-everolimus group. Sunitinib-axitinib was associated with significantly longer median OS compared to sunitinib-everolimus in patients with better response to first-line sunitinib in the pooled sunitinib population. In patients with worse response to sunitinib, sunitinib-axitinib was associated with a trend towards greater OS compared to sunitinib-everolimus, but the difference did not reach statistical significance. CONCLUSIONS: In this nationwide database analysis, mRCC patients treated with the sunitinib-axitinib sequence had significantly longer OS compared to those receiving sunitinib-everolimus therapy. The OS benefits of second-line axitinib were consistent among patients with better response to sunitinib defined by DFT values.

Changing Trends in Melanoma Incidence and Decreasing Melanoma Mortality in Hungary Between 2011 and 2019: A Nationwide Epidemiological Study.

BACKGROUND: The incidence of malignant melanoma has continually increased during the past few decades, however, certain reports suggest a recent change in trends. The aim of our study was to examine the epidemiology of melanoma in Hungary. METHODS: This nationwide, retrospective, longitudinal study included melanoma patients diagnosed between 1 January 2009 and 31 December 2019 using the databases of the National Health Insurance Fund (NHIF) and Central Statistical Office (CSO) of Hungary. Age-standardized incidence and cause-specific mortality rates were calculated. RESULTS: We identified 2,426 and 2,414 new melanoma cases in 2011 and in 2019. Age-standardized incidence rates were higher in males and varied between 28.28 and 34.57/100,000 person-years (PYs), and between 22.63 and 26.72/100,000 PYs in females. We found 16.14 and 18.82% increases in male and female incidence rates from 2011 to 2015 (p=0.067 and p<0.001, respectively), and 12.77 and 11.35% decreases from 2015 to 2019 (p=0.062 and p=0.004, respectively). The change of incidence trends (2011-2015 vs. 2015-2019) was significant in females (p=0.002) and in the total melanoma population (p=0.011), but not in the male population (p=0.063). A 16.55% (95% CI: -27.07 to -4.59; p=0.013) decrease in mortality rates was found in the overall melanoma population. CONCLUSIONS: We observed a significant trend change in melanoma incidence in the female and total melanoma population, and a significant decrease in mortality in the total melanoma population. These changes may be attributed to intensive melanoma awareness campaigns as well as to the increase in screening and access to modern therapies.

Biostatistics for Parasitologists - A Primer to Quantitative Parasitology.

The aggregated distributions of host-parasite systems require several different infection parameters to characterize them. We advise readers how to choose infection indices with clear and distinct biological interpretations, and recommend statistical tests to compare them across samples. A user-friendly and free software is available online to overcome technical difficulties.

Assessment of adrenocortical reserve capacity and inflammatory parameters in critically ill dogs.

Inflammatory markers and adrenocorticotropic hormone (ACTH) stimulation test results may help us recognise critically ill dogs with poor disease outcome. Systemic inflammatory response syndrome (SIRS) criteria, the fast version of the Acute Patient Physiologic and Laboratory Evaluation Score (APPLEfast), complete blood count, albumin and C-reactive protein (CRP) levels, baseline and stimulated cortisol levels and Δcortisol value were recorded in 50 client-owned dogs admitted to the Small Animal Hospital of the University of Veterinary Medicine Budapest with various inflammatory or neoplastic conditions. Increasing APPLEfast score was associated with a decreasing chance of survival (P = 0.0420). The Δcortisol value was significantly higher in SIRS dogs than in non-SIRS dogs (mean ± SD ΔcortisolSIRS: 342.5 ± 273.96; mean ± SD Δcortisolnon-SIRS: 175.3 ± 150.35; P = 0.0443). Elevated baseline or stimulated cortisol levels were associated with a higher chance of non-survival (P = 0.0135 and P = 0.0311, respectively). These data indicate that pathologically higher baseline and stimulated cortisol levels represent an exaggerated stress response in critically ill dogs, which is negatively associated with survival.

Evaluation of goose serum amyloid a acute phase response by enzyme-linked immunosorbent assay.

Serum amyloid A (SAA) is of interest as the circulating precursor of amyloid A protein, the fibrillar component of AA (secondary) amyloid deposits, and also as an extremely sensitive and rapid major acute phase protein. Serum concentrations of acute phase proteins (APPs) provide valuable information about the diagnosis and prognosis of various diseases, and thus the relevance of APPs for monitoring the health status of domestic animals is widely accepted. More importantly, the measurement of SAA concentration assists in assessing the prognosis in secondary amyloidosis, which is a common disease of geese, affecting an increasing number of animals. In the present study we introduce a highly sensitive goose-specific ELISA method for measuring SAA concentration in goose serum or plasma samples. Samples were taken from geese of the Landes Grey and Hungarian White breeds, which were stimulated for an acute phase reaction by administration of a commercially available fowl cholera vaccine containing inactivated Pasteurella multocida. Strong and characteristically rapid acute phase responses were measured in both breeds, peaking at approximately 24 h after inoculation. The maximum SAA concentration was 1200 microg/ml. At 72 h postinoculation, the concentrations returned to pre-inoculation values. There was significantly (p = 0.004) less intense response in the control groups; however, a very mild increase of SAA levels was detected due to the stress inevitably caused by the sampling procedure.