Viper envenomation in Central and Southeastern Europe: a multicentre study.

INTRODUCTION: Snakebite incidence varies across Europe. However, there is limited research from Central and Southeastern Europe. These regions are notable for the presence of the common European adder (Vipera berus) and the more venomous nose-horned viper (Vipera ammodytes). No standard European antivenom protocol exists. The aim was to assess the epidemiology and treatment of viper bites in this region, focusing on a comparison of bites from Vipera berus and Vipera ammodytes. METHODS: We conducted a prospective multicenter study in Central and Southeastern Europe from 2018 to 2020. This study included poison centres and toxicology-associated hospital wards in Poland, the Czech Republic, Slovakia, Hungary, Slovenia, Croatia, Serbia, and Bulgaria. The following data were collected: age, gender, Vipera species, snakebite site, clinical picture, laboratory results, Audebert's clinical severity grading score, and antivenom therapy. RESULTS: The annual incidence of viper bites in Central and Southeast Europe was estimated at 2.55 bites per million population. Within their respective geographical distribution areas, the incidence of Vipera ammodytes bites (1.61 bites per million population) was higher than Vipera berus bites (1.00 bites per million population). Patients bitten by Vipera ammodytes more frequently reported local pain and developed thrombocytopenia. Antivenom treatment was more commonly administered in Vipera ammodytes bites (72%) compared to Vipera berus bites (39%). The incidence of Vipera ammodytes bites treated with antivenom within its geographical distribution area was three times higher than Vipera berus bites treated with antivenom (1.16 bites per million population versus 0.39 bites per million population). No deaths were reported. CONCLUSIONS: The estimated incidence of viper bites in Central and Southeastern Europe is at least 2.55 per million population. Vipera ammodytes bites are more common and severe, characterized by higher frequencies of pain and thrombocytopenia. Antivenom is needed more often for Vipera ammodytes bites. It is vital that enough European Medicines Agency-approved Vipera ammodytes antivenom is produced and offered affordably.

A pilot sentinel surveillance system to monitor treatment and treatment outcomes of chronic hepatitis B and C infections in clinical centres in three European countries, 2019.

BackgroundThe World Health Organization European Action Plan 2020 targets for the elimination of viral hepatitis are that > 75% of eligible individuals with chronic hepatitis B (HBV) or hepatitis C (HCV) are treated, of whom > 90% achieve viral suppression.AimTo report the results from a pilot sentinel surveillance to monitor chronic HBV and HCV treatment uptake and outcomes in 2019.MethodsWe undertook retrospective enhanced data collection on patients with a confirmed chronic HBV or HCV infection presenting at one of seven clinics in three countries (Croatia, Romania and Spain) for the first time between 1 January 2019 and 30 June 2019. Clinical records were reviewed from date of first attendance to 31 December 2019 and data on sociodemographics, clinical history, laboratory results, treatment and treatment outcomes were collected. Treatment eligibility, uptake and case outcome were assessed.ResultsOf 229 individuals with chronic HBV infection, treatment status was reported for 203 (89%). Of the 80 individuals reported as eligible for treatment, 51% (41/80) were treated of whom 89% (33/37) had achieved viral suppression. Of 240 individuals with chronic HCV infection, treatment status was reported for 231 (96%). Of 231 eligible individuals, 77% (179/231) were treated, the majority of whom had received direct acting antivirals (99%, 174/176) and had achieved sustained virological response (98%, 165/169).ConclusionTreatment targets for global elimination were missed for HBV but not for HCV. A wider European implementation of sentinel surveillance with a representative sample of sites could help monitor progress towards achieving hepatitis control targets.

A RARE PRESENTATION OF GENITOURINARY TUBERCULOSIS MIMICKING ABDOMINAL TUMOR.

Genital tuberculosis is a rare and unexpected disease in European countries including Croatia. Diagnosis of female genital tract tuberculosis is challenging and is rarely pin-pointed by clinical symptoms because of their low specificity. The authors decided to present a case of genitourinary tuberculosis in a young, immunocompetent fertile woman with high clinical suspicion of abdominal tumor mass. Although considered a desease of the past, rare clinical presentation of genital tuberculosis should be expected and taken into account.

Intravenous Vipera berus Venom-Specific Fab Fragments and Intramuscular Vipera ammodytes Venom-Specific F(ab')2 Fragments in Vipera ammodytes-Envenomed Patients.

Vipera ammodytes (V. ammodytes) is the most venomous European viper. The aim of this study was to compare the clinical efficacy and pharmacokinetic values of intravenous Vipera berus venom-specific (paraspecific) Fab fragments (ViperaTAb) and intramuscular V. ammodytes venom-specific F(ab')2 fragments (European viper venom antiserum, also called "Zagreb" antivenom) in V.ammodytes-envenomed patients. This was a prospective study of V.ammodytes-envenomed patients that were treated intravenously with ViperaTAb or intramuscularly with European viper venom antiserum that was feasible only due to the unique situation of an antivenom shortage. The highest venom concentration, survival, length of hospital stay and adverse reactions did not differ between the groups. Patients treated with intravenous Fab fragments were sicker, with significantly more rhabdomyolysis and neurotoxicity. The kinetics of Fab fragments after one or more intravenous applications matched better with the venom concentration in the early phase of envenomation compared to F(ab')2 fragments that were given intramuscularly only on admission. F(ab')2 fragments given intramuscularly had 25-fold longer apparent total body clearance and 14-fold longer elimination half-time compared to Fab fragments given intravenously (2 weeks vs. 24 h, respectively). In V.ammodytes-envenomed patients, the intramuscular use of specific F(ab')2 fragments resulted in a slow rise of antivenom serum concentration that demanded their early administration but without the need for additional doses for complete resolution of all clinical signs of envenomation. Intravenous use of paraspecific Fab fragments resulted in the immediate rise of antivenom serum concentration that enabled their use according to the clinical progress, but multiple doses might be needed for efficient therapy of thrombocytopenia due to venom recurrence, while the progression of rhabdomyolysis and neurotoxic effects of the venom could not be prevented.

Anisakis Sensitization in the Croatian fish processing workers: Behavioral instead of occupational risk factors?

We undertook the first study systematically evaluating the risk of Anisakis-sensitization in Croatian fish-processing workers and potential genetic susceptibility to anisakiasis. Anti-Anisakis IgE seroprevalence and risk factors for 600 employees of Croatian fish processing facilities and 466 blood donor controls, were assessed by indirect ELISA targeted with: recombinant Ani s 1 and Ani s 7 allergens, an Anisakis crude extract, the commercial ImmunoCAP kit, and questionnaires. Genetic susceptibility to anisakiasis was evaluated by genotypisation of human leukocytes alleles (HLA). Anti-Anisakis seropositive and a fraction of negative subjects were also assessed by ELISA and Western Blot (WB) for IgG seroprevalence to Trichinella spp. Overall, the observed anti-Anisakis seroprevalence inferred by indirect ELISA was significantly higher in fish processing workers (1.8%, 95% CI 0.9-3.3%) compared to the controls (0%, 0-0.8%). Seven out of 11 Ani s 1 and Ani s 7-positives and none of selected 65 negative sera, tested positive on whole-Anisakis extract (ImmunoCAP), whereas Anisakis crude extract ELISA detected 3.9% (2.4-6.0%) seropositives in fish processing workers, three (14%) of which showed IgE reactivity to milk proteins. The highest risk associated with Anisakis-sensitization among workers was fishing in the free time, rather than any of attributes related to the occupational exposure. Although no association was observed between anti-Anisakis seropositivity and wearing gloves or protective goggles, the majority of workers (92%) wore protective gloves, minimizing the risk for Anisakis sensitization via skin contact. Six HLA alleles within DRB1 gene were significantly associated with seropositivity under dominant, allelic or recessive models. All sera confirmed negative for anti-Trichinella spp. IgG. The study exhaustively covered almost all marine fish processing workers in Croatia, reflecting real-time Anisakis sensitization status within the industry, already under the influence of wide array of allergens.

Vancomycin-resistant Enterococcus faecium COLONIZATION and Clostridium difficile infection in a HEMATOLOGIC patient.

Vancomycin-resistant enterococci (VRE), especially Enterococcus faecium, have emerged as significant nosocomial pathogens and patients with impaired host defenses are at a particular risk of VRE infection. The most common occurrence is asymptomatic colonization of the gastrointestinal tract that can persist for a long time and serve as a reservoir for transmission of VRE to other patients. We present a case of a patient who was diagnosed with acute myelogenous leukemia and suffered from bone marrow aplasia following induction therapy. The patient received prolonged broad-spectrum antimicrobial therapy. During hospital stay, the patient developed Clostridium difficile infection (CDI) and was found to be colonized with a strain of Enterococcus faecium resistant to vancomycin during therapy for CDI. This case also highlights the role of risk factors that could contribute to development of resistance, particularly CDI. Early detection of VRE colonization or infection is a crucial component in hospital program designed to prevent transmission of nosocomial infections. Surveillance cultures of such patients should be mandatory.

Usefulness of presepsin as diagnostic and prognostic marker of sepsis in daily clinical practice.

INTRODUCTION: Sepsis represents a major cause of morbidity and mortality in critically ill patients. Early diagnosis and appropriate treatment have a crucial influence on survival. The aim of this study was to evaluate the diagnostic and prognostic role of presepsin (sCD14) in patients with sepsis. METHODOLOGY: Fifty-four consecutive adult patients with sepsis and 26 patients with aseptic meningitis as a control group were included in this prospective observational study. In all patients included in the study, levels of C-reactive protein (CRP), presepsin, lactate, and a count of leukocytes and neutrophils were determined on admission. In those with suspected bacterial infection, two separate blood cultures were obtained and procalcitonin (PCT) concentration was detected. Plasma presepsin and PCT concentrations in septic group patients were followed on days 2, 3 and 7 after enrollment. RESULTS: The median presepsin serum concentration in patients with sepsis was 1614 pg/mL and in the control group it was 203 pg/mL (p < 0.001). Presepsin levels in patients with septic shock were higher than in sepsis patients (p < 0.014). The mean presepsin concentrations were higher in deceased than in surviving patients (p = 0.009). The trend of changes in presepsin concentrations in deceased patients was significantly different than in the surviving patients (p = 0.018). There were no statistically significant differences in the concentration of presepsin or other biomarkers in patients with Gram negative or Gram positive bacteria. CONCLUSIONS: Presepsin may be used as a diagnostic marker of systemic bacterial infection and can predict the severity and outcome of sepsis.

Thrombocytopenic purpura following envenomation by the nose-horned viper (Vipera ammodytes ammodytes): Two case reports.

RATIONALE: Two clinical cases are reported of envenomation by the nose-horned viper (Vipera ammodytes ammodytes) venom of a 9-year-old boy and of an 84-year-old woman. PATIENT CONCERNS: Both patients had been bitten on their extremities by such a snake in August near Split, a town in southern Croatia. DIAGNOSES: Clinical manifestation of envenomation was severe in the case of the boy, being characterized by a severe coagulopathy. This was only just apparent in the case of the elderly woman, who suffered extensive local edema and hematoma at the site of the bite, together with a neurotoxic effect-bilateral ptosis. This was the first occasion of thrombocytopenic purpura being observed in patients envenomed by nose-horned viper venom. This unexpected clinical finding was characterized by an unusually profound thrombocytopenia of 5 and 10 × 10/L platelets of the respective patients on their admission to the hospital, together with purpura, observed on the face and thorax of both individuals. In the most serious cases, such pathology can be life threatening if not promptly recognized and treated. INTERVENTIONS: The patients recovered quickly on receiving the specific antivenom along with all the usual supportive treatments. OUTCOMES: No serious sequels were noticed at the moment of discharge. LESSONS: Our finding constitutes an important message to clinicians to consider the possibility of such complications in the case of nose-horned viper envenomation.

Ammodytin L is the main cardiotoxic component of the Vipera ammodytes ammodytes venom.

Venom of the nose-horned viper (V. a. ammodytes) as also venoms of some related European viperids can induce also cardiotoxic effects in mammals. In this work we demonstrated that the protein in the V. a. ammodytes venom acting on heart is a myotoxic secreted phospholipase A2 analogue ammodytin L (AtnL). In the isolated perfused rat heart AtnL induced significant and irreversible cardiotoxicity characterized by atrioventricular (AV) blockade. This venom protein induced appearance of high levels of creatine kinase, lactate dehydrogenase, aspartate aminotransferase and troponin I in the sinus effluent of the isolated heart, indicative for myocardial damage, which is obviously the primary cause of its cardiotoxic action. Gel filtration chromatography subfractions C1 and C2 of the V. a. ammodytes venom harboured most of the venom cardiotoxicity. As we showed, just these two subfractions contained also AtnL. Subfraction C1 in the final CF concentration 11.3 µg/mL (containing 3.1 µg/mL AtnL) induced a complete cardiac arrest while subfraction C2 in the final CF concentration 6.0 µg/mL (containing 0.8 µg/mL AtnL) and the pure AtnL (1.0 µg/mL) did not. Contrary to AtnL, subfraction C1 at 11.3 µg/mL was not able to induce the AV blockade. This exposed the only other cardiotoxic subfractions-specific venom protein, a cysteine-rich secretory protein (CRISP), as an additional venom component potentially involved in modulation of the heart activity. Cardiotoxicity reported in some cases of the adder (V. berus) venom and the asp viper (V. aspis) venom poisonings may be assigned to AtnL in these venoms.

First case of imported chikungunya infection in Croatia, 2016.

In recent years, several European countries reported cases of imported chikungunya infection. We present the first imported clinically manifested chikungunya fever in Croatia. A 27-year-old woman returned to Croatia on 21 March 2016, after she stayed in Costa Rica for two months where she had noticed a mosquito bite on her left forearm. Five days after the mosquito bite she developed severe arthralgias, fever and erythematous papular rash. In next few days symptoms gradually subsided. After ten days she felt better, but arthralgias re-appeared accompanied with morning stiffness. Two weeks after the onset of the disease she visited the infectious diseases outpatient department. The physical examination revealed rash on the trunk, extremities, palms and soles. Laboratory findings showed slightly elevated liver transaminases. Serological tests performed on day 20 after disease onset showed a high titer of chikungunya virus (CHIKV) IgM and IgG antibodies which indicated CHIKV infection. CHIKV-RNA was not detected. Serology to dengue and Zika virus was negative. The patient was treated with nonsteroid anti-inflammatory drugs and paracetamol. Her symptoms ameliorated, however, three months later she still complaint of arthralgias. The presented case highlights the need for inclusion of CHIKV in the differential diagnosis of arthralgia in all travelers returning from countries with documented CHIKV transmission.

Perinatal risk factors in newborns with gastrointestinal perforation.

AIM: To investigate correlation of perinatal risk factors in newborns with gastrointestinal perforation (GIP). METHODS: Single-center retrospective cohort study was conducted between January 1990 and December 2012. Medical records on all newborns with GIP were reviewed (n = 35). Surgical records and histopathologic examination of all perforated intestine samples were also reviewed. RESULTS: The most common cause of GIP was necrotizing enterocolitis (51.4%). The most common site of perforation was large intestine. Mortality rate was 31%. Infants with GIP more frequently had very low birth weight (< 1500 g), especially birth weight below 10th percentile according to gestational age. Ponderal index was not differing between infants with GIP and control subjects. In infants with GIP anemia was more frequently found than in control group. CONCLUSION: GIP in newborns is mostly disease of infants with birth weight below 10th percentile according to gestational age. GIP occurs more often in infants with anemia.

Cardiotoxic effects of the Vipera ammodytes ammodytes venom fractions in the isolated perfused rat heart.

The nose-horned viper (Vipera ammodytes ammodytes) is the most venomous European snake. Its venom is known as haematotoxic, myotoxic and neurotoxic but it exerts also cardiotoxic effects. To further explore the cardiotoxicity of the venom we separated it into four fractions by gel filtration chromatography. Three fractions that contain polypeptides (A, B, and C) were tested for their effects on isolated rat heart. Heart rate (HR), incidence of arrhythmias (atrioventricular (AV) blocks, ventricular tachycardia, ventricular fibrillation, and asystolia), coronary flow (CF), systolic, developed and diastolic left ventricular pressure (LVP) were measured before, during, and after the application of venom fractions in three different concentrations. Fraction A, containing proteins of 60-100 kDa, displayed no effect on the rat heart. Fractions B and C disturbed heart functioning in similar way, but with different potency that was higher by the latter. This was manifested by significant decrease of HR and CF, the increase of diastolic, and the decrease of systolic and developed LVPs. All hearts treated with fraction C in the final CF concentrations 22.5 and 37.5 µg/mL suffered rapid and irreversible asystolia without AV blockade. They underwent also ventricular fibrillation and ventricular tachycardia. Fraction B affected hearts only at the highest dose inducing asystolia in all hearts, ventricular fibrillation in 80% and ventricular tachycardia in 70% of the hearts. Venom fraction C induced 71% of all recorded heart rhythm disturbances, significantly more than fraction B, which induced 29%. Most abundant proteins in fraction C were secreted phospholipases A2 among which the venom component acting on the heart is most probably to be looked for.

Venomous snakebites in children in southern Croatia.

This retrospective study represents observation of 160 children and adolescents aged up to 18 years that experienced venomous snakebites in southern Croatia and were treated in the Clinical Department of Infectious Diseases in the University Hospital Centre Split from 1979 to 2013. The main purpose of this research was to determine the epidemiological characteristics, clinical presentation, local and general complications, and received treatment. Most bites occurred during warm months, from early May to late August (80%), mostly in May and June. Upper limb bites were more frequent (59%) than lower limb bites (40%). Out of the total number of poisoned children, 24% developed local, and 25% general complications. The most common local complications were haemorrhagic blisters that occurred in 20% children, followed by compartment syndrome presented in 7.5% patients. The most dominated general complication was cranial nerve paresis or paralysis, which was identified in 11.2% patients, whereas shock symptoms were registrated in 7% children. According to severity of poisoning, 9.4% children had minor, 35% mild, 30.6% moderate, and 24.4% had severe clinical manifestation of envenomation. Only one (0.6%) child passed away because of snakebite directly on the neck. All patients received antivenom produced by the Institute of Immunology in Zagreb, tetanus prophylaxis as well, and almost all of them received antibiotics, and a great majority of them also received corticosteroids and antihistamines. Neighter anaphylactic reaction nor serum disease were noticed in our patients after administrating antivenom. A total of 26% children underwent surgical interventions, and incision of haemorrhagic blister was the most common applied surgical treatment, which was preformed in 15.6% patients, while fasciotomy was done in 7.5% subjects. All of our surgically treated patients recovered successfully.

Real-time two-dimensional shear wave ultrasound elastography of the liver is a reliable predictor of clinical outcomes and the presence of esophageal varices in patients with compensated liver cirrhosis.

AIM: Primary: to evaluate predictivity of liver stiffness (LS), spleen stiffness (SS), and their ratio assessed by real-time 2D shear wave elastography (RT-2D-SWE) for adverse outcomes (hepatic decompensation, hepatocellular carcinoma or death; "event") in compensated liver cirrhosis (LC) patients. Secondary: to evaluate ability of these measures to discriminate between cirrhotic patients with/without esophageal varices (EV). METHODS: Predictivity of LS, SS, and LS/SS was assessed in a retrospectively analyzed cohort of compensated LC patients (follow-up cohort) and through comparison with incident patients with decompensated cirrhosis (DC) (cross-sectional cohort). Both cohorts were used to evaluate diagnostic properties regarding EV. RESULTS: In the follow-up cohort (n=44) 18 patients (40.9%) experienced an "event" over a median period of 28 months. LS≥21.5 kPa at baseline was independently associated with 3.4-fold (95% confidence interval [CI] 1.16-10.4, P=0.026) higher risk of event. Association between SS and outcomes was weaker (P=0.056), while there was no association between LS/SS ratio and outcomes. Patients with DC (n=43) had higher LS (35.3 vs 18.3 kPa, adjusted difference 65%, 95% CI 43%-90%; P<0.001) than compensated patients at baseline. Adjusted odds of EV increased by 13% (95% CI 7.0%-20.0%; Plt;0.001) with 1 kPa increase in LS. At cut-offs of 19.7 and 30.3 kPa, LS and SS had 90% and 86.6% negative predictive value, respectively, to exclude EV in compensated patients. CONCLUSION: This is the first evaluation of RT-2D-SWE as a prognostic tool in LC. Although preliminary and gathered in a limited sample, our data emphasize the potential of LS to be a reliable predictor of clinical outcomes and the presence of EV in LC patients.

Liver and spleen stiffness and their ratio assessed by real-time two dimensional-shear wave elastography in patients with liver fibrosis and cirrhosis due to chronic viral hepatitis.

OBJECTIVES: To investigate the performance of real-time 2D shear wave elastography (RT 2D-SWE) for non-invasive staging of liver disease in patients with chronic viral hepatitis (CVH). MATERIALS AND METHODS: Naive CVH patients underwent liver (LS) and spleen stiffness (SS) measurements by an intercostal approach. Patients with ALT >3× upper limit of normal, cholestasis as revealed by dilated intrahepatic biliary tree, and liver congestion were excluded. Results were expressed in kPa and compared to histological stage (Ishak) of liver fibrosis (LF). Patients with decompensated liver cirrhosis (LC) were diagnosed using standard clinical, ultrasound, and endoscopic criteria. RESULTS: Of 123 patients, LS was successfully measured in 79.7% and SS in 53.7%. LS accurately differentiated between liver disease stages, with cut-off values of 8.1 (AUC 0.991) for F ≥ 3, 10.8 kPa (AUC 0.954) for F ≥ 5, and 27 kPa (AUC 0.961) for decompensated LC. SS was significantly different between non-cirrhotic stages (F0-4) and LC (cut-off 24 kPa; AUC 0.821). While both LS and SS increased with liver disease progression, the difference between them decreased, as reflected by the stiffness ratio index. CONCLUSIONS: RT 2D-SWE can accurately differentiate between the stages of LF, and can distinguish LF from LC and compensated from decompensated LC. KEY POINTS: • RT 2D-SWE is an accurate method for assessment of liver fibrosis. • RT 2D-SWE is applicable in 80% of patients with chronic viral hepatitis. • RT 2D-SWE accurately differentiates compensated from decompensated liver cirrhosis. • Both liver and spleen stiffness increase with progression of liver fibrosis. • In cirrhosis, the difference between liver and spleen stiffness decreases.

[Prognostic value of ophthalmic artery color Doppler sonography for progression to glaucoma in vitiligo patients]. / Prognosticka vrijednost ultrazvucnog nalaza arterije oftalmike u bolesnika s vitiligom za nastanak glaukoma.

The aim of this study was to assess the prognostic value, i.e. the role of hemodynamic changes in the ophthalmic artery determined by color Doppler imaging in patients with vitiligo in relation to the occurrence of primary open-angle glaucoma (POAG), and to call attention to the importance of examination of the vascular component in routine examinations of patients by clinical dermatologists and ophthalmologists, due to the possible correlation of vitiligo and ophthalmologic changes indicating POAG. Clinical observations and research have shown that patients treated for vitiligo are often diagnosed with POAG or have confirmed diagnosis in their medical history. These findings motivated the research of the vascular component as a possible correlation between vitiligo and POAG. The vascular component of POAG and its role in the dynamics of glaucoma progression has not been fully explained and is still somewhat controversial, and the resulting ischemic disorders are primarily related to optical nerve damage. During the course of a continuous two-year research started in March 2008 and completed in March 2010, a total of 42 patients with vitiligo were examined in the specialist dermatovenereology unit of the Department of Skin Diseases and Sexually Transmitted Diseases. Following clinical examination and Wood's lamp examination, patients with suspected glaucoma were referred to the glaucoma unit of the Department of Ophthalmology to detect or check the progression of POAG. At the Department of Internal Medicine, Split University Hospital Center, color Doppler imaging of ophthalmic artery was performed in all patients on both eyes to examine its hemodynamics. All study participants underwent complete ophthalmologic examination: visual acuity, fundus of the eye, eye pressure measurement, anterior eye segment biomicroscopy with gonioscopy and visual field. In conclusion, our study showed color Doppler imaging and investigation of vascular parameters in ophthalmic artery to provide an insight into the vascular function in differential analysis and can be determined as a correlation or potential risk factor related to vitiligo and POAG. For this reason, we suggest that patients treated for vitiligo, irrespective of their age, sex, affected area, localization and duration of the disease, should regularly undergo complete ophthalmologic examination with special emphasis on POAG diagnosis. Considering the relatively limited sample and trial period, we can already substantiate and confirm that the correlation is not random. Future research in a larger number of vitiligo and POAG patients should provide definitive answer concerning correlation between the two diseases and lead to final conclusion, along with investigation of other hematologic factors related to blood hypercoagulability in order to reach better understanding of the vascular component function.

Direct molecular detection of Mycobacterium tuberculosis suspected to be the specific infection in a case of recurrent tonsillitis.

We report a case of a 21-year-old man with recurrent tonsillitis caused by Mycobacterium tuberculosis. For a period of 5 months, the patient had tonsillitis seven times and was treated with several oral or parenteral antibiotics. On one of these occasions, tonsillitis was complicated with a peritonsillar abscess that was treated by incision. According to relevant bibliographic data, this is the first case of Mycobacterium tuberculosis confirmed by direct molecular microbiology methods from the tonsillar tissue of a young immunocompetent male reported in Europe. In a case of recurrent tonsillitis, Mycobacterium tuberculosis infection should be considered as a possible cause.

Endobronchial ALK+ anaplastic large-cell lymphoma resembling asthma in a 13-year-old girl.

Anaplastic large-cell lymphoma is a rare disease in children, and endobronchial localization is extremely rare in any age group. We report the case of a 13-year-old girl with endobronchial anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma presenting as asthma, and discuss the diagnostic, therapeutic, and clinical implications.

Acute appendicitis, a rare complication of varicella: a report of three cases.

Acute appendicitis is a very rare complication of varicella, and is rarely reported in studies of complications of varicella or appendicitis. This report describes three cases of acute appendicitis in the course of varicella, diagnosed in Clinical Department of Infectious Diseases at Split University Hospital, Croatia between 1998 and 2010. Varicella was diagnosed clinically, and in two cases confirmed by positive serological tests for varicella-zoster virus (VZV). In addition to routine histopathological examination, testing for viral antigens or DNA in the appendix, omentum and peripheral blood by genetic and immunohistochemistry methods may be important to confirm whether VZV and appendicitis are etiopathogenetically connected.

Iodine intake and epidemiological characteristics of thyroid cancer: comparison between inland and littoral Croatia.

The aim of the study was to determine epidemiological characteristics of thyroid cancer in Dalmatia and Slavonia, to analyze regional differences in its incidence, and to determine whether iodine intake had an impact on the incidence. This epidemiological study was based on data published by the Croatian National Cancer Registry (CNCR) in the Croatian Health Service Yearbook and CNCR Bulletin. Data on 651 thyroid cancer patients operated on in Dalmatian hospitals between 1997 and 2006 were analyzed. Control group consisted of thyroid cancer patients operated on in Slavonia (N = 498). Incidence rates recorded in Dalmatia were compared with those in Slavonia. Iodine intake was measured in elementary schoolchildren in the Split-Dalmatia and Osijek-Baranya Counties. Iodine excretion levels were measured in 131 children. In the 10-year period, the mean age-standardized incidence rate (ASR) of thyroid cancer was 9.32 per 100,000 inhabitants in Dalmatia and 6.02 in Slavonia. The difference was statistically significant (P < 0.001). Incidence rates (World ASR, European ASR, crude incidence rate and research rates) showed an increase and were significantly higher in Dalmatia than in Slavonia. Patient sex structure showed the disease to be 4 times more common in women than in men. In Dalmatia sample, women accounted for 81.4% of all patients and papillary cancer accounted for 80.03% of all thyroid cancers. Median age of new patients was 50 in Dalmatia and 48 in Slavonia. Papillary cancer accounted for 63.7% of all patients in Slavonia. Follicular thyroid cancer accounted for 20.9% of patients in Slavonia and 12.4% in Dalmatia. Epidemiological characteristics of thyroid cancer in Dalmatia were found to be consistent with the characteristics of this cancer in iodine-sufficient areas: papillary carcinoma was the most common type and the papillary to follicular ratio was 6.4:1. Follicular cancer accounted for 12.4% of the total number of patients. In Slavonia, the papillary form predominated, the papillary to follicular ratio was 3:1, and follicular cancer accounted for 20.88% of all patients. Median urinary iodine excretion in elementary schoolchildren was 23.6 microg/dL in the Split-Dalmatia County and 28.1 microg/dL in the Osijek-Baranya County. The difference was not statistically significant (P < 0.050). In conclusion, the average iodine intake levels in Dalmatia and Slavonia were not the cause of the high thyroid cancer incidence in the 1997-2006 period. Improved thyroid cancer diagnosis may be one of the causes of the increased thyroid cancer incidence in Dalmatia.