Genomic profiling of thymoma using a targeted high-throughput approach.

Introduction: Thymomas and thymic carcinoma (TC) are the most common neoplasms localised in the thymus. These diseases are poorly understood, but progress made in next-generation sequencing (NGS) technology has provided novel data on their molecular pathology. Material and methods: Genomic DNA was isolated from formalin-fixed paraffin-embedded tumour tissue. We investigated somatic variants in 35 thymoma patients using amplicon-based TruSeq Amplicon Cancer Panel (TSACP) that covers 48 cancer related genes. We also analysed three samples from healthy individuals by TSACP platform and 32 healthy controls using exome sequencing. Results: The total number of detected variants was 4447, out of which 2906 were in the coding region (median per patient 83, range: 2-300) and 1541 were in the non-coding area (median per patient 44, range: 0-172). We identified four genes, APC, ATM, ERBB4, and SMAD4, having more than 100 protein-changing variants. Additionally, more than 70% of the analysed cases harboured protein-changing variants in SMAD4, APC, ATM, PTEN, KDR, and TP53. Moreover, this study revealed 168 recurrent variants, out of which 15 were shown to be pathogenic. Comparison to controls revealed that the variants we reported in this study were somatic thymoma-specific variants. Additionally, we found that the presence of variants in SMAD4 gene predicted shorter overall survival in thymoma patients. Conclusions: The most frequently mutated genes in thymoma samples analysed in this study belong to the EGFR, ATM, and TP53 signalling pathways, regulating cell cycle check points, gene expression, and apoptosis. The results of our study complement the knowledge of thymoma molecular pathogenesis.

Molecular profiling of rare thymoma using next-generation sequencing: meta-analysis.

BACKGROUND: Thymomas belong to rare tumors giving rise to thymic epithelial tissue. There is a classification of several forms of thymoma: A, AB, B1, B2, B3, thymic carcinoma (TC) and thymic neuroendocrine thymoma. In this meta-analysis study, we have focused on thymoma using articles based on the disease's next-generation sequencing (NGS) genomic profiling. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of the prevalence of studies that discovered the genes and variants occurring in the less aggressive forms of the thymic epithelial tumors. Studies published before 12th December 2022 were identified through PubMed, Web of Science (WoS), and SCOPUS databases. Two reviewers have searched for the bases and selected the articles for the final analysis, based on well-defined exclusion and inclusion criteria. RESULTS: Finally, 12 publications were included in the qualitative as well as quantitative analysis. The three genes, GTF2I, TP53, and HRAS, emerged as disease-significant in the observed studies. The Odds Ratio for all three extracted genes GTF2I (OR = 1.58, CI [1.51, 1.66] p < 0.00001), TP53 (OR = 1.36, CI [1.12, 1.65], p < 0.002), and HRAS (OR = 1.02, CI [1.00, 1.04], p < 0.001). CONCLUSIONS: According to obtained data, we noticed that the GTF2I gene exhibits a significant prevalence in the cohort of observed thymoma patients. Moreover, analyzing published articles NGS has suggested GTF2I, TP53, and HRAS genes as the most frequently mutated genes in thymoma that have pathogenic single nucleotide variants (SNV) and Insertion/Deletion (InDel), which contribute to disease development and progression. These variants could be valuable biomarkers and target points specific to thymoma.

Association between active pulmonary tuberculosis and miRNA-146a: A preliminary study from Serbia.

INTRODUCTION: Tuberculosis (TB) continues to be a significant public health problem. The role of small non-coding RNAs, such as microRNAs (miRNAs), was investigated extensively in Mycobacterium tuberculosis (MTB) infection as well as in a variety of other pathophysiological processes in recent years. It was found that miRNAs act as regulators of both early reaction to MTB infection and in process of adaptation of the host immune cells during latent course of the disease. Molecule miRNA-146a is expressed exclusively in immune cells and it has the most prominent role in modulation of innate immunity. METHODOLOGY: We investigated the level of expression of miRNA-146a using an RT-qPCR technique in peripheral blood mononuclear cells of 44 patients with active pulmonary TB and 17 healthy individuals. We also analyzed the significance of miRNA-146a rs2910164 SNV for expression profile of miRNA-146a, in order to investigate potential usage of miRNA-146a as a biomarker for TB. RESULTS: There was statistically significant decrease of expression of miRNA-146a in TB group compared to control group. When gender cohorts were analyzed, the expression levels in TB male and TB female subgroup were significantly lower than the expression levels in the same gender control subgroups. CONCLUSIONS: Our results indicate that miRNA-146a plays a significant role in the pathogenesis of TB, suggesting that miRNA-146a could be used as a biomarker for active pulmonary TB.

Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population.

Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity, currently is the focus of multiple genome-wide association studies (GWAS) in populations affected by the pandemic. This is the first study from Serbia that performed a GWAS of COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128 hospitalized COVID-19 patients from the Serbian population was enrolled in the study. We conducted a GWAS comparing (1) patients with pneumonia (n = 80) against patients without pneumonia (n = 48), and (2) severe (n = 34) against mild disease (n = 48) patients, using a genotyping array followed by imputation of missing genotypes. We have detected a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with a peak residing upstream of the gene KLHL1 (p = 1.91 × 10-8). Our study also replicated a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L and LZTFL1 genes suggestively associated with pneumonia (p = 7.54 × 10-6) and severe COVID-19 (p = 6.88 × 10-7), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6, MRPL36, p = 2.81 × 10-6), 5q11.2 (ESM1, p = 6.59 × 10-6), and 9p23 (TYRP1, LURAP1L, p = 8.69 × 10-6). The genes located in or near the risk loci are expressed in neural or lung tissues, and have been previously associated with respiratory diseases such as asthma and COVID-19 or reported as differentially expressed in COVID-19 gene expression profiling studies. Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which could contribute to a better understanding of the COVID-19 host genetics in different populations.

Understanding vaccination communication between health workers and parents: a Tailoring Immunization Programmes (TIP) qualitative study in Serbia.

Vaccine communication between health workers and parents affects parental acceptance, so understanding this is particularly important when vaccination rates drop. This paper presents the findings of a qualitative research study conducted in Serbia as part of a Tailoring Immunization Programmes (TIP) project. The aims were to explore the process of vaccination communication between health workers and parents (accepting, indecisive, delaying, refusing), and identify barriers and drivers to effective communication. In-depth interviews with 14 health workers were supplemented and qualified by observations of 40 consultations, using thematic analysis. Study sites were two community health centers in two Belgrade municipalities where a significant drop in childhood vaccination rates had occurred. Key findings were: (1) communication mainly took place between pediatricians and parents, while nurses focused on administering vaccines. (2) Health workers were confident in their skills to communicate and address concerns of accepting and indecisive parents, successfully applying specific strategies. (3) When interacting with delaying and refusing parents, they sometimes agreed to delay vaccination to maintain relationships, confident that most parents would vaccinate in due course. (4) Some refusing parents asked questions grounded in a socio-political agenda regarding vaccines or vaccination. Such questions exceeded the domain of health workers' expertise, which affected the communication between them. (5) Health workers' behavior in consultations was sometimes affected by parents' (dis) trust in their recommendations about vaccination. The study revealed that health workers in Serbia require additional skills and techniques to respond to parents who refuse and wish to delay vaccination, to secure timely vaccination.

Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity.

Background: COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The emerging amount of data indicates that vitamin D, zinc and selenium could be important for clinical presentation of COVID-19. Here, we investigated association of genetic variants related to the altered level and bioavailability of vitamin D, zinc and selenium with clinical severity of COVID-19. Methods: We analyzed variants in genes significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, CYP2R1 rs10741657, and VDR rs2228570), zinc (PPCDC rs2120019) and selenium (DMGDH rs17823744) in 120 Serbian adult and pediatric COVID-19 patients using allelic discrimination. Furthermore, we carried out comparative population genetic analysis among European and other worldwide populations to investigate variation in allelic frequencies of selected variants. Results: Study showed that DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017, respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the odds for developing severe disease, OR 0.21 (0.05-0.9) and OR 5.9 (1.4-25.2), respectively. There were no associations between selected genetic variants and disease severity in pediatric patients. Comparative population genetic analysis revealed that Serbian population had the lowest frequency of CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and 0.66 in Spanish and Italian population, respectively), suggesting that other populations should also investigate the relationship of CYP2R1 variant and the COVID-19 disease course. Conclusion: The results of the study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults. This could direct prevention strategies based on population specific nutrigenetic profiles.

Genetic variants in TNFA, LTA, TLR2 and TLR4 genes and risk of sepsis in patients with severe trauma: nested case-control study in a level-1 trauma centre in SERBIA.

INTRODUCTION: Single nucleotide variants (SNVs) represent important genetic risk factors for susceptibility to posttraumatic sepsis and a potential target for immunotherapy. We aimed to evaluate the association between 8 different SNVs within tumor necrosis factor alpha (TNFA), lymphotoxin alpha (LTA) and Toll-like receptor (TLR2 and TLR4) genes and the risk of posttraumatic sepsis. METHODS: Nested case-control study was conducted in the emergency department of the Clinical Centre of Serbia including 228 traumatized patients (44 with sepsis and 184 without sepsis). To compare the results of trauma subjects with the data from the general population, a control group of 101 healthy persons was included in the study. Genotyping of TNFA (rs1800629 and rs361525), LTA (rs909253), TLR2 (rs3804099, rs4696480 and rs3804100), and TLR4 (rs4986790 and rs4986791) was performed for all patients within all three groups using the real-time PCR method. MutationTaster database and in silico software SIFT were used to predict the variant pathogenic effect. RESULTS: Carriage of the G allele of the TNFA rs1800629 gene variant (OR 2.1, 95%CI 1.06-4.16) and T allele-carriage of the TLR4 rs4986791 genetic variant (OR 3.02, 95%CI 1.31-6.57) were associated with significantly higher risk of sepsis in trauma patients when compared to the general population prone to sepsis and traumatized patients without developing a sepsis, respectively. Of these two variants, only variant in TLR4 gene (rs4986791) has been labeled as disease causing by both the MutationTaster database and the in-silico software SIFT, which further supports the role of this variant in various pathologies including sepsis. For the remaining six variants no significant association with the susceptibility to sepsis was detected. CONCLUSIONS: Carriage of the G allele of the TNFA rs1800629 gene variant and T allele-carriage of the TLR4 rs4986791 genetic variant confer significant risk of posttraumatic sepsis. TLR4 gene variants (rs4986790 and rs4986791) has been labelled as disease causing.

Genes and metabolic pathway of sarcoidosis: identification of key players and risk modifiers.

INTRODUCTION: Sarcoidosis is a rare multisystem granulomatous disease with unknown etiology. The interplay of vitamin D deficiency and genetic polymorphisms in genes coding for the proteins relevant for metabolism of vitamin D is an important, but unexplored area. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in CYP2R1 (rs10741657), CYP27B1 (rs10877012), DBP (rs7041; rs4588), and VDR (rs2228570) genes and sarcoidosis, as well as the association between these SNPs and 25(OH)D levels in sarcoidosis patients. MATERIAL AND METHODS: For that purpose we genotyped 86 sarcoidosis patients and 50 healthy controls using the PCR-RFLP method. RESULTS: Subjects carrying the CC genotype of CYP27B1 rs10877012 have 10 times lower odds of suffering from sarcoidosis. Moreover, DBP rs4588 AA genotype was shown to be a susceptibility factor, where carriers of this genotype had eight times higher odds for developing sarcoidosis. In addition, the A allele of the DBP gene (rs4588) was associated with lower levels of 25(OH)D in sarcoidosis patients. CONCLUSIONS: These results suggest that patients with vitamin D deficiency should be regularly tested for genetic modifiers that are related to sarcoidosis in order to prevent development of serious forms of sarcoidosis.

Tumor characteristics, expressions of ERCC1, Bax, p53, IGF1R, Bcl2, Bcl2/Bax and prognostic factors for overall survival in patients with lung carcinoid.

PURPOSE: Neuroendocrine lung tumors (NET) include typical carcinoids (TC), atypical carcinoids (AC), large cell NE carcinoma (LCNEC) and small-cell carcinoma (SCLC), with different clinicopathological profiles and relative grades of malignancy. Although differences between carcinoids and high grade carcinomas are recognized, precise differences and behavior of TC and AC have not been clearly defined. The aim of this study was to better define the differences in the clinical behavior of TC and AC, and to establish new prognostic factors of overall survival (OS), by determining the levels of genetic expression of IGF1R, ERCC1, Bax, p53, Bcl2 and Bcl2/Bax ratio. METHODS: The histopathological diagnosis of 52 surgically resected pulmonary carcinoid tumors was made according to the WHO classification. Gene expressions were evaluated by quantitative real-time PCR. RESULTS: The confirmed prognostic factors for overall survival (OS) were pTNM T (p<0.01), pTNM N (p<0.05), clinical stage (p<0.05), type of surgery (p<0.01) and histopathological (HP) tumor type (p<0.05). Bcl2 mRNA level and Bcl2/Bax ratio were found to have a potential for discrimination of the HP type of tumor (AC vs TC, Receiver Operating Characteristics (ROC) cut-off values 0.1451 and 0.3015, respectively), but without statistically significant impact on OS. CONCLUSIONS: In patients with NETs, smaller primary tumor, absence of positive lymph nodes, and TC type of tumor predicted longer OS. Type of resection has influence on OS. Bcl2 expression and Bcl2/Bax ratio might be valuable as independent diagnostic parametars in lung carcinoids. Therapeutic approaches using attenuation of Bcl2 or upregulation of Bax might prove useful in lung NETs.

Relevance of TNF-α, IL-6 and IRAK1 gene expression for assessing disease severity and therapy effects in tuberculosis patients.

INTRODUCTION: Tuberculosis (TBC) is a contagious chronic respiratory disease which despite the known cause, Mycobacterium tuberculosis (Mtb), and many decades of successful therapy, remains one of the leading global health problems. Immune responses against Mtb infection involve both of types of immunity, but cellular immunity, in which certain cytokines and Th1 cells play a key role, is crucial. A better understanding of the functions of the cytokine network involved in the state and progression of TBC could identify specific molecular markers for monitoring of disease activity as well as therapy outcomes in TBC patients. METHODOLOGY: We investigated expression of TNF-α, IL-6 and IRAK1 genes using an RT-qPCR technique in peripheral blood mononuclear cells of 33 TBC patients and 10 healthy individuals. RESULTS: Comparison between TBC patients and healthy individuals revealed statistically significant differences for all analyzed genes. The levels of expression of TNF-α and IL-6 mRNA were higher, while the level of IRAK1 mRNA was lower in the TBC group compared to controls. Moreover, a strong positive correlation was observed between TNF-α and IL-6 gene expression. When clinical parameters were analyzed, increased levels of TNF-α mRNA were detected in patients with a longer duration of therapy (>2 months) compared to those with a shorter therapy duration (< 2 months), and in patients without anemia. CONCLUSIONS: Our results indicate that the inflammatory genes we examined play a crucial role in the pathogenesis of tuberculosis, and that the expression of the TNF-α gene could be a marker for monitoring the clinical effect of the ant-tuberculosis drugs during therapy.

Patient, Healthcare System and Total Delay in Tuberculosis Diagnosis and Treatment Among Serbian Population.

Currently, topical are studies that examine different reasons for delay of tuberculosis (TB) diagnosis and its impact on disease prognosis. The aim was to examine three time periods associated with treatment delay: patient related, health system related and total delay. This retrospective-prospective study included 100 consecutive patients hospitalized at Department of Pulmonology, Clinical Center of Serbia, in the period from March to December 2015. Study results showed median patient delay to be 92.5 days. Total delay was affected by patient related delay. Median healthcare delay was 18.5 days. Patients that reported excessive alcohol consumption were more likely to have prolonged time to seek medical help. Years of alcohol consumption yielded moderate positive correlation with patient related delay (r=0.362, p <0.001). Correlation between the number of cigarettes and patient delay was moderate, positive and statistically significant (r=0.314, p=0.001). Delay in seeking medical help was more likely in patients with negative family history of TB. There was no difference in the effect of the presence of symptoms on patient related delay (p>0.05). Clinical characteristics such as patient TB category and chest radiograph abnormalities were not associated with prolonged patient related delay (p>0.05). Study results point to the importance of health education and/or health intervention in the population group at a high risk of TB.

Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants.

Primary ciliary dyskinesia (PCD) is a rare inherited autosomal recessive or X-linked disorder that mainly affects lungs. Dysfunction of respiratory cilia causes symptoms such as chronic rhinosinusitis, coughing, rhinitis, conductive hearing loss and recurrent lung infections with bronchiectasis. It is now well known that pathogenic genetic changes lead to ciliary dysfunction. Here we report usage of clinical-exome based NGS approach in order to reveal underlying genetic causes in cohort of 21 patient with diagnosis of PCD. By detecting 18 (12 novel) potentially pathogenic genetic variants, we established the genetic cause of 11 (9 unrelated) patients. Genetic variants were detected in six PCD disease-causing genes, as well as in SPAG16 and SPAG17 genes, that were not detected in PCD patients so far, but were related to some symptoms of PCD. The most frequently mutated gene in our cohort was DNAH5 (27.77%). Identified variants were in homozygous, compound heterozygous and trans-heterozygous state. For detailed characterization of one novel homozygous genetic variant in DNAI1 gene (c. 947_948insG, p. Thr318TyrfsTer11), RT-qPCR and Western Blot analysis were performed. Molecular diagnostic approach applied in this study enables analysis of 29 PCD disease-causing and related genes. It resulted in mutation detection rate of 50% and enabled discovery of twelve novel mutations and pointed two possible novel PCD candidate genes.

Clinical features of infection caused by non-tuberculous mycobacteria: 7 years' experience.

INTRODUCTION: Non-tuberculous mycobacteria (NTM) are ubiquitous organisms associated with various infections. The aim of the study was to determine the most relevant clinical characteristics of NTM during the 7-year period. METHODOLOGY: A retrospective study of NTM infections was conducted between January 2009 and December 2016. The American Thoracic Society/Infectious Disease Society of America criteria were used to define cases of pulmonary or an extrapulmonary site. RESULTS: A total of 85 patients were included in the study. Pulmonary cases predominated 83/85 (98%), while extrapulmonary NTM were present in 2/95 (2%) patients. Overall, ten different NTM species were isolated. The most common organisms were slow-growing mycobacteria (SGM) presented in 70/85 (82.35%) patients. Isolated SGM strains were Mycobacterium avium complex (MAC) in 25/85 (29.41%) patients, M. xenopi in 20/85 (23.53%) patients, M. kansasii in 15/85 (17.65%) patients and M. peregrinum and M. gordonae in 5/85 (5.88%) patients each. Isolated rapid-growing mycobacteria (RGM) strains were M. abscessus in 8/85 (9.41%) patients, M. fortuitum in 4/85 (4.71%) patients and M. chelonae in 3/85 (3.53%) patients. Almost all patients (98%; 83/85) had comorbidities. Among 75 (88.24%) patients who completed follow-up, 59 (69.41%), 10 (11.76%) and 6 (7%), were cured, experienced relapse and died, respectively. CONCLUSION: In the present study, pulmonary NTM infections were more frequent compared to extrapulmonary disease forms. SGM were most common isolates with MAC pulmonary disease the most frequently found. Comorbidities have an important role in NTM occurrence. Further investigation should focus on an NTM drug susceptibility testing.

Membrane PD-L1 expression and soluble PD-L1 plasma levels in idiopathic pulmonary fibrosis-a pilot study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) has common risk factors with cancer and significant similarities in the pathobiology process, both diseases having poor outcomes. Immune checkpoint PD-L1 has become the target of checkpoint inhibitory therapy that unleashes antitumor T cells and has revolutionized cancer treatment. This is a pilot study exploring membrane immune checkpoint PD-L1 expression in human IPF lung tissue samples and its soluble form, soluble PD-L1 (sPD-L1) plasma concentrations in IPF patients, in order to investigate potential role of PD-L1 as an IPF biomarker. METHODS: Twelve human IPF lung tissue samples (formalin-fixed, paraffin-embedded) obtained by surgical biopsy, have been tested for PD-L1 expression by PD-L1 IHC 22C3 pharmDx assay, while plasma samples for examination of sPD-L1 forms, PD-L1 (B7-H1/CD274) blood concentration, originated from 23 patients with IPF who did not undergo surgical biopsy. RESULTS: Membrane PD-L1 expression in IPF lung tissue samples was positive to overexpression of PD-L1 in 9 samples out of 12. Only very few cells in the interstitium have shown a discrete PD-L1 expression, but not of a membrane type. As for sPD-L1 forms, we have found elevated concentrations of sPD-L1 in the serum of IPF patients 314.3 ng/L (117.7-483.1 ng/L), significantly higher compared with healthy control group 91.0 ng/L (52.4-119.7 ng/L), P<0.01. CONCLUSIONS: For IPF with PD-L1 expression on alveolar macrophages, further studies are necessary to elucidate this phenomenon. Serum sPD-1/PD-L1 is easily detected in clinical practice and should be further evaluated as a potential prognostic or/and predictive biomarker in IPF.

Identification and validation of differentially expressed transcripts by RNA-sequencing of formalin-fixed, paraffin-embedded (FFPE) lung tissue from patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease of unknown etiology. A major limitation in transcriptomic profiling of lung tissue in IPF has been a dependence on snap-frozen fresh tissues (FF). In this project we sought to determine whether genome scale transcript profiling using RNA Sequencing (RNA-Seq) could be applied to archived Formalin-Fixed Paraffin-Embedded (FFPE) IPF tissues. RESULTS: We isolated total RNA from 7 IPF and 5 control FFPE lung tissues and performed 50 base pair paired-end sequencing on Illumina 2000 HiSeq. TopHat2 was used to map sequencing reads to the human genome. On average ~62 million reads (53.4% of ~116 million reads) were mapped per sample. 4,131 genes were differentially expressed between IPF and controls (1,920 increased and 2,211 decreased (FDR < 0.05). We compared our results to differentially expressed genes calculated from a previously published dataset generated from FF tissues analyzed on Agilent microarrays (GSE47460). The overlap of differentially expressed genes was very high (760 increased and 1,413 decreased, FDR < 0.05). Only 92 differentially expressed genes changed in opposite directions. Pathway enrichment analysis performed using MetaCore confirmed numerous IPF relevant genes and pathways including extracellular remodeling, TGF-beta, and WNT. Gene network analysis of MMP7, a highly differentially expressed gene in both datasets, revealed the same canonical pathways and gene network candidates in RNA-Seq and microarray data. For validation by NanoString nCounter® we selected 35 genes that had a fold change of 2 in at least one dataset (10 discordant, 10 significantly differentially expressed in one dataset only and 15 concordant genes). High concordance of fold change and FDR was observed for each type of the samples (FF vs FFPE) with both microarrays (r = 0.92) and RNA-Seq (r = 0.90) and the number of discordant genes was reduced to four. CONCLUSIONS: Our results demonstrate that RNA sequencing of RNA obtained from archived FFPE lung tissues is feasible. The results obtained from FFPE tissue are highly comparable to FF tissues. The ability to perform RNA-Seq on archived FFPE IPF tissues should greatly enhance the availability of tissue biopsies for research in IPF.

Administering the Sarcoidosis Health Questionnaire to sarcoidosis patients in Serbia.

OBJECTIVE: The aim of this study was to use a Serbian-language version of the disease-specific, self-report Sarcoidosis Health Questionnaire (SHQ), which was designed and originally validated in the United States, to assess health status in sarcoidosis patients in Serbia, as well as validating the instrument for use in the country. METHODS: This was a cross-sectional study of 346 patients with biopsy-confirmed sarcoidosis. To evaluate the health status of the patients, we used the SHQ, which was translated into Serbian for the purposes of this study. We compared SHQ scores by patient gender and age, as well as by disease duration and treatment. Lower SHQ scores indicate poorer health status. RESULTS: The SHQ scores demonstrated differences in health status among subgroups of the sarcoidosis patients evaluated. Health status was found to be significantly poorer among female patients and older patients, as well as among those with chronic sarcoidosis or extrapulmonary manifestations of the disease. Monotherapy with methotrexate was found to be associated with better health status than was monotherapy with prednisone or combination therapy with prednisone and methotrexate. CONCLUSIONS: The SHQ is a reliable, disease-specific, self-report instrument. Although originally designed for use in the United States, the SHQ could be a useful tool for the assessment of health status in various non-English-speaking populations of sarcoidosis patients.

Food addiction-diagnosis and treatment.

In this article we summarized the recent research of the food addiction, diagnosis, treatment and prevention, which is carried out in this area. The concept of food addiction is new and complex, but proven to be very important for understanding and solving the problem of obesity. First part of this paper emphasizes the neurological studies, whose results indicate the similarity of brain processes that are being activated during drug abuse and during eating certain types of food. In this context, different authors speak of "hyper-palatable", industrial food, saturated with salt, fat and sugar, which favor an addiction. In the section on diagnostic and instruments constructed for assessing the degree of dependence, main diagnostic tool is standardized Yale Food Addiction Scale constructed by Ashley Gearhardt, and her associates. Since 2009, when it was first published, this scale is used in almost all researches in this area and has been translated into several languages. Finally, distinguish between prevention and treatment of food addiction was made. Given that there were similarities with other forms of addictive behavior, the researchers recommend the application of traditional addiction treatment.

Novel patched 1 mutations in patients with nevoid basal cell carcinoma syndrome--case report.

Nevoid basal cell carcinoma syndrome (Gorlin syndrome) is a rare autosomal dominant disorder characterized by numerous basal cell carcinomas, keratocystic odontogenic tumors of the jaws, and diverse developmental defects. This disorder is associated with mutations in tumor suppressor gene Patched 1 (PTCH1). We present two patients with Gorlin syndrome, one sporadic and one familial. Clinical examination, radiological and CT imaging, and mutation screening of PTCH1 gene were performed. Family members, as well as eleven healthy controls were included in the study. Both patients fulfilled the specific criteria for diagnosis of Gorlin syndrome. Molecular analysis of the first patient showed a novel frameshift mutation in exon 6 of PTCH1gene (c.903delT). Additionally, a somatic frameshift mutation in exon 21 (c.3524delT) along with germline mutation in exon 6 was detected in tumor-derived tissue sample of this patient. Analysis of the second patient, as well as two affected family members, revealed a novel nonsense germline mutation in exon 8 (c.1148 C>A).

Treatment of neurosarcoidosis--innovations and challenges.

INTRODUCTION: Sarcoidosis affects the central nervous system more frequently than it used to be believed. While the cranial nerves are most frequently affected, neurosarcoidosis can involve other nervous system tissues as well. TREATMENT OF NEUROSARCOIDOSIS: Although a lot of drugs have proved useful in treating neurosarcoidosis, corticosteroids are still the gold standard in treatment of these patients. Therapeutic protocols differ regarding the dose of these drugs. Symptomatic neurosarcoidosis should always be treated with pulse corticosteroid therapy. People with diabetes, high blood pressure, osteoporosis and tuberculosis should be carefully monitored, as they are prone to complications associated with treatment with corticosteroids. In cases when treatment with corticosteroids does not show the desired results or therapy is discontinued due to the development of side effects, there are other pharmacologic options, such as methotrexate, mycophenolate mofetil, cyclophosphamide, chloroquine, azathioprine, thalidomide, and infliximab. It should be noted that the treatment response to the above mentioned regimens, except for infliximab, is relatively slow compared to corticosteroids; therefore, corticosteroids should be taken into account in all states and particularly in the acute phase of the disease. CONCLUSION: It is the existence of different forms of the disease, lack of local diagnostic criteria and different and non standardized therapy that makes the treatment of this disease difficult. Despite advances in pharmacotherapy and radiological diagnosis, it is necessary to develop better diagnostic strategies in order to set the optimal therapeutic approach.

Diagnosis of neurosarcoidosis--necessity of biopsy.

INTRODUCTION: Sarcoidosis can affect any part of the central nervous system presenting with an extremely diverse clinical picture. Clinical presentations actually depend on the localization ofgranulomas in the central nervous system. Making diagnosis according to the localization and the clinical variations is often a clinical challenge. DIAGNOSIS OF NEUROSARCOIDOSIS: Diagnosis is based on the clinical picture, clinical and radiological findings (magnetic resonance imaging with contrast endocranium), laboratory findings (angio-tenzin-converting enzyme and chitotriosidase in cerebrospinal fluid); however, it is necessary first to exclude all other possible causes of granulomatous inflammation. Recent studies in patients with neurosarcoidosis show a high value of at least one marker of the disease. The safest way and the gold standard in diagnosing this disease would be histopathological confirmation, which is rarely performed due to its invasiveness. CONCLUSION: New diagnostic methods will contribute to better methods of bypassing invasive procedures, and they will significantly facilitate the diagnosis of neurosarcoidosis, which is a real challenge even for experienced clinicians who deal with this disease.