Is Antihelminthics Necessary in Postoperative Treatment of Intraventricular Neurocysticercosis? A Systematic Review.

OBJECTIVE: Patients with intraventricular neurocysticercosis (IVNCC) may require cerebrospinal fluid diversion surgery for late-onset hydrocephalus in the postsurgical period. Controversy exists regarding cysticidal treatment. Our main objective was to compare surgically treated cases of IVNCC that received postoperative anthelmintics with those that did not regard the incidence and treatment of late-onset hydrocephalus. METHODS: We searched the Medline database and extracted the following data: age, gender, stage of development of cysticercosis, type of operation, frequency of delayed hydrocephalus, cerebrospinal fluid diversion surgery, outcome, and follow-up. RESULTS: We analyzed 130 articles on intraventricular cysticercosis and identified 117 cases of isolated IVNCC and 314 patients in the case-control series who met inclusion criteria. There was no significant difference in postoperative delayed hydrocephalus between isolated IVNCC and case-control study groups. Children under the age of 16 received anthelmintic drugs more frequently during the postoperative period. Statistical relevance was observed in all patient groups regarding the application of steroids in favor of cysticidal therapy Endoscopy was a better option than craniotomy for cases of isolated IVNCC and case-control studies. Other variables were not relevant. CONCLUSIONS: Patients who received antihelminths did not show a statistically significant reduction in delayed hydrocephalus compared to individuals who did not receive after surgical resection of the parasite. Corticosteroid therapy prevailed in people who have been treated with anthelmintics. Children under the age of 16 were administered anthelmintic drugs more frequently during the postoperative period. Endoscopy was the preferred method for all groups, but some patients with cysts in the fourth ventricle required a craniotomy.

Antifungal Activity and Type of Interaction of Melissa officinalis Essential Oil with Antimycotics against Biofilms of Multidrug-Resistant Candida Isolates from Vulvovaginal Mucosa.

(1) Background: Vulvovaginal candidosis (VVC) is a major therapy issue due to its high resistance rate and virulence factors such as the ability to form biofilms. The possibility of combining commonly used antifungals with natural products might greatly improve therapeutic success. (2) Methods: A total of 49 vulvovaginal isolates, causative agents of recurrent VVC, were tested for their susceptibility to fluconazole, nystatin, and Melissa officinalis essential oil (MOEO). This examination included testing the antibiofilm potential of antifungals and MOEO and the determination of their types of interaction with mature biofilms. (3) Results: Antimicrobial testing showed that 94.4% of the Candida albicans isolates and all the Candida krusei isolates were resistant to fluconazole, while all strains showed resistance to nystatin. The same strains were susceptible to MOEO in 0.156-2.5 mg/mL concentrations. Additionally, the results revealed very limited action of fluconazole, while nystatin and MOEO reduced the amount of biofilm formed by as much as 17.7% and 4.6%, respectively. Testing of the combined effect showed strain-specific synergistic action. Furthermore, the lower concentrations exhibited antagonistic effects even in cases where synergism was detected. (4) Conclusions: This study showed that MOEO had a very good antibiofilm effect. However, combining MOEO with antimycotics demonstrated that the type of action depended on the choice of antifungal drugs as well as the applied concentration.

Intraventricular Neurocysticercosis: Comparative Analysis of Different Localizations. Clinical Course and Treatment. A Systematic Review.

Background Neurocysticercosis is significant due to its high prevalence and considerable morbidity and mortality. The intraventricular form of NCC is less common than parenchymal, may have a rapidly progressive course and it requires a corresponding therapeutic response. Despite the extensive literature dealing with NCC and intraventricular cystic lesions, no systematic reviews have addressed similar work related to the clinical course and treatment of the infestation. Our main objective was to analyze the clinical type of the disease and the management for each ventricle separately on the basis of case reports or series of patients with individual data on the course of the disease and its treatment. As a control group, we used data on signs&symptoms and treatment of patients from published series on intraventricular neurocysticercosis. Method We performed a search in the Medline database. Google Scholar was also randomly searched. We extracted the following data from the eligible case/series: age and gender, symptoms, clinical signs, diagnostic examinations and findings, localization, treatment, follow-up period, outcome, and publication year. All data are presented in the form of absolute and relative numbers. The frequency of signs and symptoms, treatment and outcomes of the observed groups were checked by the Chi-square test and Fisher's test. The hypothesis was tested with p <0.05 as statistical significance. Results We selected 160 cases of intraventricular neurocysticercosis (IVNCC) and divided them according to their localization into five categories. Hydrocephalus was recognized in 134 cases (83.4%). Patients with isolated IVNCCare are younger (P=.0264) and have a higher percentage of vesicular cysts (p <.00001). In mixed IVNCC, degenerative and multiple confluent cysts predominate (p = 0.00068). Individuals carrying fourth + third ventricular cysts (potentially obstructive form) are younger than individuals with lateral ventricles (potentially less obstructive forme) (p = .0083). The majority of patients had individual symptoms for a longer period before the acute onset of the disease (p <.00001). The predominant clinical manifestation is headache (88.7%); the proportion within the groups ranged from 100% to 75% without statistical significance (p.074214). The same was true for patients with symptoms of vomiting or nausea, who had a lower and roughly balanced percentage of 67.7% to 44.4% (p.34702). Altered level of consciousness (ranging from 21% to 60%) and focal neurological deficit (from 51.2% to 15%) are the only clinical category with statistical significance (p <0.001 and p.023948 ). Other signs and symptoms were less frequent and statistically irrelevant. Surgical resection of the parasite was the predominant type of treatment, varying from 55.5% to 87.5% (p- .02395); endoscopy (48.2%) and craniotomy (24.4%), each individually, showed statistical significance (.00001 and .000073, respectively). The difference was also relevant among patients who had CSF diversion performance with/without medical treatment (p-.002312. Postoperatively, 31.8% of patients received anthelmintics with/without anti-inflammatory or other drugs. Endoscopy, open surgery, and postoperative antiparasitic therapy showed statistical differences (p < 0.001). Favorable outcomes or regression of symptoms were recorded in 83.7%, mortality 7.5%. In the case series, the clinical signs&symptoms were as follows: headache-64%, nausea and vomiting 48.4%, focal neurological deficit 33.6% and altered level of consciousness 25%. Open surgery was the predominant form of intervention (craniotomy (57.6% or endoscopy 31.8%); with statistical significance between them (p< .00001). Conclusion. Ventricular neurocysticercosis is an alarming clinical condition. Hydrocephalus is the dominant diagnostic sign. Isolated IVNCC patients were recognized at a younger age than Mix.IVNCC individuals; poeple with cysts in the fourth and third ventricles (as a potentially more occlusive type of disease), presented their symptoms at a younger age than individuals with LVNCC. The majority of patients had long-term signs and symptoms before the acute onset of the disease. Headache, nausea& vomiting are the most common symptoms of infestation accompanied by altered sensorium and focal neurological deficits. Surgery is the best treatment option. A sudden increase in ICP due to cerebrospinal fluid obstruction with a successive cerebral hernia is the leading cause of fatal outcomes.

Knowledge about HPV Infection and the HPV Vaccine among Parents in Southeastern Serbia.

Background and Objectives: The vaccine against human papilloma virus (HPV) infection is recommended, according to the Serbian National Immunization Program, for children and adolescents aged 9−19 years. Three doses are given keeping in mind the recommendation that the second dose should be administered at least one month after the first dose, and the third at least three months after the second dose. No children who participated in this first study received the third dose because they did not meet these criteria. The study explored parents' knowledge about HPV infection and their awareness of the HPV vaccine. Materials and Methods: A cross-sectional questionnaire-based study was carried out in the city of Nis, in southeastern Serbia. According to the 2011 population census, the sample of children aged 9 to 19 was 850, and during the observed period, 631 children received the vaccine. A total of 615 fully completed questionnaires filled out by parents were included in the study. The study was carried out from 6 June 2022 to 7 October 2022. Multivariable logistic regression analysis was used. The odds ratio (OR) and 95% confidence intervals (CI) were calculated. The statistical significance was p < 0.05. Results: A total of 615 children were included in the study (499 were vaccinated with the first dose and 116 with the second). Out of 499 children vaccinated with the first dose, 398 (79.6%) were girls, which is significantly higher than the rate for boys (101). The independent variable sex was statistically significant at the level of p = 0.84, OR = 2.664 (95% CI from 0.879 to 7.954). Boys are 164% less likely to be vaccinated with the HPV vaccine than girls. We determined that the independent variable place of residence was significant at the level of p = 0.041, (OR = 3.809, 95% CI from 1.702 to 8.525). Based on these findings, we determined that parents who came from rural areas were 82% less likely to know about HPV infection and HPV vaccination. Children under 15 years of age were significantly more vaccinated than those ≥15 years (OR = 3.698, 95% CI from 1.354 to 12.598). The independent variable parental education was significant at the level of OR = 0.494, 95% CI from 0.301 to 0.791. Parents who had medical education showed significantly higher awareness about the infection caused by HPV and about the HPV vaccine (p = 0.004) than parents with no medical education. The possibility that a parent would decide to vaccinate a child significantly increased upon a pediatrician's recommendation, p = 0.000 with OR = 0.250 (95% CI from 0.127 to 0.707). Health insurance coverage of HPV vaccination for children aged 9−19 years significantly increased the probability of a positive parental decision to vaccinate a child, p = 0.001 with OR = 3.034 (95% CI from 1.063 to 8.662). Conclusion: We identified several significant factors that were important for HPV vaccination such as: children under 15 years, female sex, urban place of residence, medical education of parents, pediatrician's recommendation of the HPV vaccination, and HPV vaccination free of charge. Health education and the promotion of HPV vaccination as well as healthy sexual behavior are important factors in the preservation and improvement of the health of the whole population.

Cancer of unknown primary - incidence, mortality trend, and mortality-to-incidence ratio is associated with human development index in Central Serbia, 1999-2018: Evidence from the national cancer registry.

OBJECTIVES: The aim was to estimate the trend of incidence, mortality and mortality-to-incidence ratio (MIR) in Central Serbia in 1999-2018 and its possible association with the human development index (HDI). METHODS: In this study, cancer of unknown primary (CUP) was included as C77-C80 codes. Trend analysis was performed in the Joinpoint Regression Programme version 4.8.0.1. HDI combines life expectancy, educational attainment and gross national income. HDI values for Serbia are extracted from the global bank site. RESULTS: Joinpoint regression analysis of the age-standardised incidence rate of CUP showed a significantly increasing trend with annual percent change (APC) of 8.5% (95% confidence interval [CI] 3.0-14.3%) in males and 7.8% (95%CI 2.7-13.2) in females. The age-standardised mortality rate of CUP showed a significantly decreasing trend with APC of -1.7% (95%CI -2.8 to -0.5%) in males and -1.4% (95%CI -2.7 to -0.1%) in females. MIR showed a significantly decreasing trend with APC of -9.3% (95%CI -14.6 - -3.6%) in males and -7.1% (95%CI -10.5% to -4.2%) in females. The linear regression showed significant inverse association among HDI and the MIR of CUP in males (r2 = 0.464, p = 0.002) and in females (r2 = 0.612, p < 0.001). CONCLUSIONS: Decline of MIR was associated with HDI, suggesting that CUP prognosis follows socio-economic status.

New cases of human dirofilariosis on the Balkan Peninsula - "Masked intruders" uncovered by a surgeon.

Dirofilaria spp. nematodes are accidental parasites of humans causing mild to serious, superficial or visceral infections. Superficial dirofilariosis is rather common in Europe and is typically manifested as subcutaneous form. Herein we report 46 new cases of human dirofilariosis (19 patients with subcutaneous, 18 patients with ocular, 4 patients wih genital, 2 patients with submucosal, 2 patients with pulmonary and 1 patient with intramuscular form of infection) that were recorded from the beginning of 2015 to May 2021 on the Balkan Peninsula with a goal to update the prevalence of this parasitosis and point out potential problems in diagnosis and treatment. Besides, given the high possibility of misinterpretation as tumor, our second aim was to encourage the inclusion of this pathogen in the differential diagnosis of subcutaneous nodules. Although quite common forms, subcutaneous and ocular dirofilariosis can be very often misdiagnosed in clinical practice due to the absence of specific clinical manifestations. Therefore, raising awareness of clinicians about this zoonosis is needed as well as closer collaboration between physicians and veterinarians.

Knowledge about Cervical Cancer and Awareness of Human Papillomavirus (HPV) and HPV Vaccine among Female Students from Serbia.

Background and objectives: Persistent infection with carcinogenic human papillomavirus (HPV) is the leading cause of cervical cancer. The study explored students' knowledge about cervical cancer and awareness of human papillomavirus and the HPV vaccine. Materials and Methods: A questionnaire-based survey was carried out among 1616 first-year female college students at the University of Nis. It examined socio-demographic characteristics, measured the score of knowledge about cervical cancer, assessed awareness regarding HPV and the HPV vaccine and inquired about the source of information about cervical cancer and HPV. Results: The average cervical cancer knowledge score was 16.35 ± 7.92 (min 0, max 30), with medical professional education, parents' education level, place of residence and relationship status having significant effects on the score. The awareness about HPV and the HPV vaccine was low, with only 14.2% of students having heard about both HPV and its vaccine. The most commonly reported sources of information were the media, while the most competent one was organized health education. Conclusions: Health promotion campaigns and educational programs are necessary in order to reduce cervical cancer burden and should be directed particularly towards those who have demonstrated low cervical cancer knowledge and low awareness regarding HPV and its vaccine.

Diagnosis of Pneumocystis jirovecii Pneumonia in Pediatric Patients in Serbia, Greece, and Romania. Current Status and Challenges for Collaboration.

Pneumocystis jirovecii can cause fatal Pneumocystis pneumonia (PcP). Many children have been exposed to the fungus and are colonized in early age, while some individuals at high risk for fungal infections may develop PcP, a disease that is difficult to diagnose. Insufficient laboratory availability, lack of knowledge, and local epidemiology gaps make the problem more serious. Traditionally, the diagnosis is based on microscopic visualization of Pneumocystis in respiratory specimens. The molecular diagnosis is important but not widely used. The aim of this study was to collect initial indicative data from Serbia, Greece, and Romania concerning pediatric patients with suspected PcP in order to: find the key underlying diseases, determine current clinical and laboratory practices, and try to propose an integrative future molecular perspective based on regional collaboration. Data were collected by the search of literature and the use of an online questionnaire, filled by relevant scientists specialized in the field. All three countries presented similar clinical practices in terms of PcP prophylaxis and clinical suspicion. In Serbia and Greece the hematology/oncology diseases are the main risks, while in Romania HIV infection is an additional risk. Molecular diagnosis is available only in Greece. PcP seems to be under-diagnosed and regional collaboration in the field of laboratory diagnosis with an emphasis on molecular approaches may help to cover the gaps and improve the practices.

Population Pharmacokinetic Analysis of Bisoprolol in Patients With Acute Coronary Syndrome.

To date, many questions about the extent and cause of pharmacokinetic (PK) variability of even the most widely studied and prescribed ß1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was conducted using a nonlinear mixed-effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In each patient, the same formulation of bisoprolol was administered once or twice daily at a total daily dose of 0.625-7.5 mg. We separately assessed the effects of 31 covariates on the PKs of bisoprolol, and our results indicated that only 2 covariates could have possible influence on the variability of the clearance of bisoprolol: the mean daily dose of the drug and smoking habits of patients. These findings suggest that possible autoinduction of drug metabolism by higher total daily doses and induction of cytochrome P450 isoform 3A4 (CYP3A4) by cigarette smoke in liver could be the potential causes of increased total clearance of bisoprolol in patients with ACS.

Surveillance and characterization of Candida bloodstream infections in a Serbian tertiary care hospital.

INTRODUCTION: Candida spp. frequently cause hospital-acquired bloodstream infections (BSI) with a high mortality rate (up to 70%). We analyzed the frequency, infection characteristics, potential predisposing factors, susceptibility to antifungal drugs, biofilm production and other virulence characteristics of Candida spp. isolates obtained from a tertiary care hospital in Nis, Serbia, during a one year period. METHODS: Medical histories, characteristics of isolated strains and drug susceptibility, as well as the effect on the function of isolated macrophages and other virulence features were evaluated. The obtained results were subjected to student's t-test and multivariate statistical analyzes. RESULTS: Herein we report an annual incidence of 3.65 cases of C. albicans, C. lusitaniae and C. lipolytica infections per 105 population. Out of eight isolated strains, two (25%) were shown to be strong biofilm producers, one (12.5%) caused hemolysis on blood agar and in two (25%) cases macrophages were able to completely eliminate the yeast colonies. Chronic kidney disease, diabetes, malignant and other diseases were present in 37.5, 62.5, 50 and 75%, respectively, in the study group. All patients with Candida BSI received antifungal therapy (amphotericin B), however, hospital mortality was observed in 25% of patients. CONCLUSIONS: Evaluation of local Candida epidemiology, antifungal susceptibility and virulence factors, as well as personalized patient risk factors are important for the surveillance of Candida BSI, especially in intensive care unit patients and may contribute to the improved options and outcome for patients with Candida BSI.

Anorectal melanoma and seborrheic dermatitis ­ A case report.

Introduction: Anorectal melanoma (ARM) is a rare and aggressive neoplasm with predisposition for early infiltration, distant spread, and unfavorable prognosis. It has been speculated that Malassezia yeasts could possibly have an impact on skin carcinogenesis and development of melanoma, especially in patients with seborrheic dermatitis (SD), due to production of aryl hydrocarbon receptor (AhR) agonists. Case Outline: A 52-year-old man with intensive SD complained of a four-month-long rectal bleeding, tenesmus, pain, and difficulty during defecation. On examination, a rectal tumor was detected and histopathology of tumor tissue revealed ARM with positive protein S100, melanoma antigen HMB45 and melan-A expression. After the diagnosis was established, abdominoperineal resection of the anus and rectum was performed, since the tumor was large, obstructive, and the anal sphincter was invaded. Conclusion: Because of the possible impact of intensive SD to the cross-link between Malassezia yeasts AhR agonists and skin carcinogenesis, we discussed on this matter and reviewed the literature data regarding ARM. In addition to "pathogenic" and "non-pathogenic" Malassezia subtypes based on AhR agonist production, future studies on Malassezia metabolites, their carcinogenic effect in the skin and development of melanoma are needed. If the cross-link between Malassezia AhR agonists and skin carcinogenesis exists, timely prevention of ARM could be done with Malassezia eradication, especially in patients with severe SD.

Alternaria-Associated Fungus Ball of Orbit Nose and Paranasal Sinuses: Case Report of a Rare Clinical Entity.

Alternaria-associated fungus ball of maxillar, ethmoidal paranasal sinuses, nasal cavity and orbit with bone erosion is extremely rare. Till recently, only two cases of this infection in immune competitive patients have been reported. We are herein describing the case of immune-competent woman who suffered of nasal congestion for 10 years. Patient was treated for tumor-like lesion in right maxillar sinus, where propagation in right nose cavity, right ethmoidal cells and right orbita was present. The organism that was seen in surgical removal of fungal debris by histological study, in using mycological testing, was proven as Alternaria alternata. Combination of surgical intervention and treatment with itraconazole eradicated fungal infection, and the disease was not relapsed in follow-up period of 2 years.

In vitro protease inhibition and cytotoxicity of Aspergillus fumigatus biomolecules secreted under long-term aerated conditions.

The fatality rate of invasive aspergillosis (IA) is still very high, especially in prolonged and untreated pulmonary cases. Aspergillus fumigatus is the main causative agent of IA and investigation of its metabolites could provide valuable insight into virulence factor(s) associated with this organism. We evaluated the A. fumigatus culture filtrate (CF) products generated during short- and long-term aerated and non-aerated conditions and tested for (i) inhibition of cysteine or serine proteases and (ii) cytotoxicity. In addition, the mathematical model was determined using response surface methodology (RSM) to estimate the influence of different fermentation conditions on A. fumigatus CF characteristics, predict enzyme inhibition and make possible correlations with in vivo conditions. Biosynthesis of A. fumigatus low molecular weight proteinaceous products (from 6.4 to 15.4 kDa) was observed after 6 days of growth under aerated and alkaline conditions. Also, only these CFs showed significant reduction in cell lines survival (Caco-2 and WISH 35.6% and 54.6%, respectively). Obtained results provide solid starting point for further studies that would include: (i) detailed chemical characterization of A. fumigatus CF, (ii) activity relationships and in vivo correlation with pathogenicity of prolonged pulmonary IA and (iii) possible use of biomolecules as diagnostic or therapeutic markers.

Seroreactivity to Dirofilaria antigens in people from different areas of Serbia.

BACKGROUND: The Northern part of Serbia is hyperendemic-endemic for canine dirofilarioses. Considering this fact, many human dirofilarial infections could be expected, however only about 30 cases in Serbia have been described until today. Aims of this survey were to assess the people reactivity to the antigens of D. repens and D. immitis and to identify risk factors for the contact exposure. METHODS: Investigation included sera taken from 297 people (179 women and 118 men) living in different areas of Serbia (Pancevo, Novi Sad, Zajecar, Leskovac, Vranje, Nis, Pirot). Sera were analysed by means of two indirect enzyme-linked immunosorbent (ELISA) home-designed that use as antigens adult somatic/metabolic polyproteins of D. repens (DR) and D. immitis (DI), respectively. The results were elaborated using the statistical method of descriptive and quantitative analysis. RESULTS: Significant differences by area in the reactivity of human sera to dirofilarial antigens were not observed (p = 0.056). A high seroreactivity was demonstrated in people from the towns of northern Serbia (Pancevo = 27,1%; Novi Sad = 16,3%), as well as in people from Zajecar (eastern Serbia = 15,8%) and Vranje (southern Serbia = 15,1%). No differences were evidenced between people reactivity to polyproteins of the two dirofilarial species, nor differences related to the gender of examinees. Factor risks evidenced were: i) place of residence; ii) spending work time outdoors during the mosquito season; iii) spending time outdoors and nearby rivers, lakes, swamps or canals; unespectedly, iv) cat owning. CONCLUSION: The findings emerging from this investigation indicate that clinicians and public health authorities should pay greater attention to this zoonosis. Continuing education and training of physicians will greatly contribute to the knowledge of the actual impact of filarial worms on animal and public health, and allow for the planning of suitable measures to prevent the infections.

Canine Dirofilaria infections in two uninvestigated areas of Serbia: epidemiological and genetic aspects.

In 2009 canine filarial infections were investigated in two northern areas of Serbia (Pancevo and Veliko Gradiste), applying morphometry, biochemical staining, and immunological kit to detect Dirofilaria immitis antigens, and two home-made ELISAs to detect antibodies to D. repens and D. immitis somatic/metabolic polyproteins. Moreover, molecular tools were applied to analyze the phylogenetic relationships of the isolates. The microfilariae detected in 21/122 dogs (17.2%) were identified as D. repens (n=21) and D. immitis (n=2). D. immitis antigens were found in another 13 animals with occult infection. All of the 15 heartworm-positive dogs also had antibodies to this parasite, which were detected in another 13 subjects, indicating an overall D. immitis seroprevalence rate of 22.9%. Serology for D. repens revealed evidence of antibodies in 42.6% of the dogs, but was negative for 4 microfilaremic dogs. As for the two different areas, the prevalence of microfilariae and/or D. immitis antigens, mainly due to D. repens microfilaremic animals, was not significantly higher in Veliko Gradiste (33.3%) than in Pancevo (22%). However, serology showed a different epidemiological picture. Heartworm infection occurred more often in both areas, and antibodies to dirofilarial nematodes were detected in 72.9% of dogs living in Pancevo, a rate higher than in those living in Veliko Gradiste (57.1%). No risk factors for infection were found, confirming the uselessness of prophylactic drugs against D. repens, and suggesting the presence in these areas of sunrise- or sunset-biting mosquitoes as important vectors. The results indicate the need for both appropriate entomological studies and further research on the intra-species variability shown by D. repens.