A fatal case of Ecthyma Gangrenosum in a critically ill and immunocompromised patient.

INTRODUCTION: This brief picture-oriented case report focuses on typical skin lesions in a patient who developed Ecthyma gangrenosum and pseudomonal sepsis after extensive immunosuppressive therapy for Pemphigus vulgaris. CASE PRESENTATION: The patient was immunosuppressed with high doses of glucocorticoids and azathioprine; the follow-up after the treatment was not carried out well due to the pandemic conditions and because the patient herself got a Covid infection, which resulted in the development of pseudomonal sepsis and Ecthyma gangrenosum. The outcome was fatal despite extensive broad-spectrum antibiotic therapy, plasmapheresis, and intravenous immunoglobulins. CONCLUSIONS: Infections with Pseudomonas aeruginosa have become a real concern in hospital-acquired infections, especially in critically ill and immunocompromised patients, because of multi-drug resistance in the first place.

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.

A Comparison of MGMT Testing by MSP and qMSP in Paired Snap-Frozen and Formalin-Fixed Paraffin-Embedded Gliomas.

Comparative analysis of the conventional methylation-specific PCR (MSP) vs. the quantitative MSP (qMSP) assessment of the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in 34 snap-frozen (SF) glioma samples was performed. The accuracy of the semi-quantitative MSP was compared with the corresponding qMSP semi-quantitative values using two semi-quantitative cut-off values (0-unmethylated and 1-weakly methylated) to discriminate methylated from unmethylated samples. In the case of the cut-off value 0, MSP test showed 80.0% sensitivity and 78.9% specificity compared to the reference qMSP analysis. However, when using the cut-off value 1, the diagnostic accuracy of the MSP test was significantly higher (85.7% sensitivity, 85.2% specificity). Fleiss' Kappa statistical analyses indicated moderate agreement (Fleiss' Kappa Coefficient = 0.509; 70.59% agreement) between MSP and qMSP semi-quantitative measurements of MGMT promoter methylation in glioma patients, justifying the conventional MSP use in diagnostics and confirming its high reliability. Further, we aimed to compare the validity of SF and formalin-fixed paraffin-embedded (FFPE) glioma samples for MGMT testing. Statistical analyses indicated moderate overall agreement of FFPE glioma samples and SF MSP semi-quantitative measurements (Fleiss' Kappa Coefficient = 0.516/0.509; 70.0% agreement) and emphasized their low reliability in the assessment of highly methylated MGMT promoter samples.

The Significance of MGMT Promoter Methylation Status in Diffuse Glioma.

A single-institution observational study with 43 newly diagnosed diffuse gliomas defined the isocitrate dehydrogenase 1 and 2 (IDH1/2) gene mutation status and evaluated the prognostic relevance of the methylation status of the epigenetic marker O6-methylguanine-DNA methyltransferase (MGMT). Younger patients (<50 years) with surgically resected glioma and temozolomide (TMZ) adjuvant chemotherapy were associated with better prognosis, consistent with other studies. The methylation status depends on the chosen method and the cut-off value determination. Methylation-specific PCR (MSP) established the methylation status for 36 glioma patients (19 (52.8%) positively methylated and 17 (47.2%) unmethylated) without relevancy for the overall survival (OS) (p = 0.33). On the other side, real-time methylation-specific PCR (qMSP) revealed 23 tumor samples (54%) that were positively methylated without association with OS (p = 0.15). A combined MSP analysis, which included the homogenous cohort of 24 patients (>50 years with surgical resection and IDH1/2-wildtype diffuse glioma), distinguished 10 (41.6%) methylated samples from 14 (58.4%) unmethylated samples. Finally, significant correlation between OS and methylation status was noticed (p ≈ 0.05). The OS of the hypermethylated group was 9.6 ± 1.77 months, whereas the OS of the unmethylated group was 5.43 ± 1.04 months. Our study recognized the MGMT promoter methylation status as a positive prognostic factor within the described homogenous cohort, although further verification in a larger population of diffuse gliomas is required.

Establishment of typical adult CT dose indicators for PET-CT scans in Slovenia.

The aim was to determine typical values of diagnostic reference level (DRL) quantities for the computed tomography (CT) part of the most common positron emission tomography-computed tomography (PET-CT) procedures in Slovenia. The most common PET-CT procedures were identified, and data collated for 565 patients imaged in all three PET-CT units in Slovenia during a time span of 11 months. As the number of facilities is too low to establish national DRLs, we followed ICRP recommendations and determined typical values of DRL quantities as the median values of the pooled set of data. Mean, median, and standard deviation of CT dose index (CTDIvol) and total dose length product (DLP) for the CT part of the most common PET-CT procedures were determined for pooled data as well as for each PET-CT unit. The data were compared between all three units to identify possible outliers that would likely benefit from optimization. Three most common CT protocols covering approximately 2/3 of all PET-CT imaging performed in Slovenia were considered: from the base of the cranium to the middle of the femur, from the top of the head to the middle of the femur, and for the whole-body PET-CT. The established typical values in terms of total DLP were 295, 359, and 676 mGyccm, respectively; and in terms of CTDIvol3.05, 3.22, and 3.60 mGy, respectively. Comparing the data between all three units showed significantly higher (p< 0.001) patient doses on one unit, indicating a need for optimization. The results present the first-time data on the national typical values of DRL quantities for the CT part of most common PET-CT procedures in Slovenia. While the determined typical values are within the DRL values established in some other countries, significant differences were found between the individual units included in the study.

Quality of life in children with atopic dermatitis: A one-year prospective cohort study.

BACKGROUND: Literature on the quality of life trends across time in children with atopic dermatitis are scarce. AIMS: To assess factors associated with quality of life of children with atopic dermatitis after a one-year follow-up and to examine the factors contributing to greater improvement in the atopic dermatitis-related quality of life over one year. METHODS: Our cohort consisted of 98 children who were treated for atopic dermatitis at the clinic of dermatovenereology. Data collection included atopic dermatitis scoring using the SCORing Atopic Dermatitis (SCORAD) index, Children's Dermatology Life Quality Index (CDLQI) for children aged > four years and Infants' Dermatitis Quality of Life Index (IDLQI) for children aged 0-4 years. Categorization of the impairment of quality of life score due to atopic dermatitis was as follows: mild (score from 0 to 6), moderate (score from 7 to 12) and severe (score from 13 to 30). The cohort was followed for one year after which a total of 80 children were reassessed. RESULTS: Improvements of both CDLQI and IDLQI were observed in children whose impairment of quality of life due to atopic dermatitis after one year was 'mild'. This was not observed in children whose atopic dermatitis caused either 'moderate' or 'severe impairment' of their quality of life. Adjusted analysis showed that lower initial SCORAD and greater improvement in SCORAD after the one-year follow-up were associated with a better quality of life at follow-up. LIMITATIONS: The size of our cohort was relatively small. Study participants were recruited from the largest urban and medical referral center in Serbia. Persons from suburban or rural regions may have had different perceptions of atopic dermatitis-related quality of life. CONCLUSION: Children with less severe atopic dermatitis were more likely to improve their atopic dermatitis-related quality of life. Lower SCORAD was associated with both better quality of life initially and greater improvement in quality of life after one year of follow-up.

Preeclamptic Women Have Disrupted Placental microRNA Expression at the Time of Preeclampsia Diagnosis: Meta-Analysis.

Introduction: Preeclampsia (PE) is a pregnancy-associated, multi-organ, life-threatening disease that appears after the 20th week of gestation. The aim of this study was to perform a systematic review and meta-analysis to determine whether women with PE have disrupted miRNA expression compared to women who do not have PE. Methods: We conducted a systematic review and meta-analysis of studies that reported miRNAs expression levels in placenta or peripheral blood of pregnant women with vs. without PE. Studies published before October 29, 2021 were identified through PubMed, EMBASE and Web of Science. Two reviewers used predefined forms and protocols to evaluate independently the eligibility of studies based on titles and abstracts and to perform full-text screening, data abstraction and quality assessment. Standardized mean difference (SMD) was used as a measure of effect size. Results: 229 publications were included in the systematic review and 53 in the meta-analysis. The expression levels in placenta were significantly higher in women with PE compared to women without PE for miRNA-16 (SMD = 1.51,95%CI = 0.55-2.46), miRNA-20b (SMD = 0.89, 95%CI = 0.33-1.45), miRNA-23a (SMD = 2.02, 95%CI = 1.25-2.78), miRNA-29b (SMD = 1.37, 95%CI = 0.36-2.37), miRNA-155 (SMD = 2.99, 95%CI = 0.83-5.14) and miRNA-210 (SMD = 1.63, 95%CI = 0.69-2.58), and significantly lower for miRNA-376c (SMD = -4.86, 95%CI = -9.51 to -0.20). An increased level of miRNK-155 expression was found in peripheral blood of women with PE (SMD = 2.06, 95%CI = 0.35-3.76), while the expression level of miRNA-16 was significantly lower in peripheral blood of PE women (SMD = -0.47, 95%CI = -0.91 to -0.03). The functional roles of the presented miRNAs include control of trophoblast proliferation, migration, invasion, apoptosis, differentiation, cellular metabolism and angiogenesis. Conclusion: miRNAs play an important role in the pathophysiology of PE. The identification of differentially expressed miRNAs in maternal blood creates an opportunity to define an easily accessible biomarker of PE.

Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children, whereas it is less common in adults. Identification of cytogenetic aberrations and a small number of molecular abnormalities are still the most important risk and therapy stratification methods in clinical practice today. Next generation sequencing (NGS) technology provides a large amount of data contributing to elucidation of mutational landscape of childhood (cALL) and adult ALL (aALL). METHODS: We analyzed DNA samples from 34 cALL and aALL patients, using NGS targeted sequencing TruSeq Amplicon - Cancer Panel (TSACP) which targets mutational hotspots in 48 cancer related genes. RESULTS: We identified a total of 330 variants in the coding regions, out of which only 95 were potentially protein-changing. Observed in individual patients, detected mutations predominantly disrupted Ras/RTK pathway (STK11, KIT, MET, NRAS, KRAS, PTEN). Additionally, we identified 5 patients with the same mutation in HNF1A gene, disrupting both Wnt and Notch signaling pathway. In two patients we detected variants in NOTCH1 gene. HNF1A and NOTCH1 variants were mutually exclusive, while genes involved in Ras/RTK pathway exhibit a tendency of mutation accumulation. CONCLUSIONS: Our results showed that ALL contains low number of mutations, without significant differences between cALL and aALL (median per patient 2 and 3, respectively). Detected mutations affect few key signaling pathways, primarily Ras/RTK cascade. This study contributes to knowledge of ALL mutational landscape, leading to better understanding of molecular basis of this disease.

Correlation of genomic alterations and PD-L1 expression in thymoma.

Thymic epithelial tumors (TETs) include several anterior mediastinal malignant tumours: thymomas, thymic carcinomas and thymic neuroendocrine cancers. There is significant variety in the biologic features and clinical course of TETs and many attempts have been made to identify target genes for successful therapy of TETs. Next generation sequencing (NGS) represents a huge advancement in diagnostics and these new molecular technologies revealed that thymic neoplasms have the lowest tumor mutation burden among all adult malignant tumours with a different pattern of molecular aberrations in thymomas and thymic carcinomas. As for the PD-L1 expression in tumor cells in thymoma and thymic carcinoma, it varies a lot in published studies, with findings of PD-L1 expression from 23% to 92% in thymoma and 36% to 100% in thymic carcinoma. When correlated PD-L1 expression with disease stage some controversial results were obtained, with no association with tumor stage in most studies. This is, at least in part, explained by the fact that several diverse PD-L1 immunohistochemical tests were used in each trial, with four different antibodies (SP142, SP263, 22C3, and 28-8), different definition of PD-L1 positivity and cutoff values throughout the studies as well. There is a huge interest in using genomic features to produce predictive genomic-based immunotherapy biomarkers, particularly since recent data suggest that certain tumor-specific genomic alterations, either individually or in combination, appear to influence immune checkpoint activity and better responses as the outcome, so as such in some cancer types they may complement existing biomarkers to improve the selection criteria for immunotherapy.

Determining the gas composition for the growth of BNNTs using a thermodynamic approach.

High-yield production of high-quality boron-nitride nanotubes (BNNTs) has been reported recently in several publications. A boron-rich material is evaporated using a laser or plasma in a nitrogen-rich atmosphere to supply precursor gaseous species for nucleation and growth of BNNTs. Either hydrogen was added or pressure was increased in the system to achieve high yield and high purity of the synthesized nanotubes. According to the widely-accepted "root grow" mechanism, upon gas cooling, boron droplets form first, then they adsorb nitrogen from the surrounding gas species, and BNNTs grow on their surfaces. However, what are the precursor species that provide nitrogen for the growth is still an open question. To answer this question, we performed thermodynamic calculations for determining the B-N mixture composition considering a broad set of gas species. For the first time, condensation of boron was taken into account and was shown to have a drastic effect on thegas chemical composition. B2N molecules were identified to be a major source of nitrogen for the growth of BNNTs. The presence of B2N molecules in a B-N gas mixture was verified by our spectroscopic measurements during laser ablation of boron-rich targets in nitrogen. It was shown that the increase of pressure has a quantitative effect on the mixture composition yielding an increase of the precursor density. Hydrogen addition might open an additional channel of nitrogen supply to support the growth of BNNTs. The nitrogen atoms react with abundant H2 molecules to form NH2 and then NH3 precursor species, instead of just recombining back to inert N2 molecules, as in the no-hydrogen case. In addition, thermodynamics was applied in conjunction with agglomeration theory to predict the size of the boron droplets upon growth of BNNTs. Analytical relations for the identification of crucial species densities were derived.

New Perspectives in the Treatment of Atopic Dermatitis in the Pediatric Population.

Treatment of children diagnosed with atopic dermatitis (AD) is an art. Age-dependent barrier function, skin physiology, body surface:weight ratio, the compliance of patient and caregivers, and legal considerations related to the license status of topical and systemic drugs must be considered. Mild to moderate AD can usually be treated sufficiently with a personalized regimen of emollients and topical anti-inflammatory therapy consisting of topical corticosteroids (TCSs) or topical calcineurin inhibitors. Emollients containing bacterial lysates, tailored wet wrap regimen, and proactive therapy with tacrolimus ointment or some TCSs are new developments in the field. Severe AD may need systemic therapy, but all currently available systemic agents for severe AD are either not licensed for children or not advisable on the long term, or both. Therapeutic patient education based on structured, interactive sessions with patients or caregivers and a multidisciplinary team is highly effective. This publication summarizes the current therapeutic options used in the pediatric AD population.

Evaluation of the quality of life in adolescents with acne.

BACKGROUND/AIM: Acne is well recognized condition that adversely affects quality of life (QoL) of the patients. The aim of this study was to determine the self-reported prevalence of acne and its main characteristics in high school pupils, and to assess their QoL. METHODS: The cross-sectional study conducted in May 2011 comprised 440 pupils from Serbia (281 from Belgrade and 159 from Uzice). Participation in the study was voluntary and anonymous. Two questionnaires were administered: a short demographic questionnaire, and Children's Dermatology Life Quality Index (CDLQI). Internal consistency was assessed using the Cronbach's alpha while item-total score correlations were assessed using Spearman's correlation analysis. RESULTS: The majority of the study population (84.3%) were girls, and 15.7% were boys. The total mean age of the pupils was 16.48 +/- 0.55 years. A total of 228 (51.8%) pupils self-reported their acne with significantly higher prevalence in Uzice (73.6%) than in Belgrade (39.5%). The mean CDLQI score was 3.55 with the similar quality of life impairment in adolescents from the two cities. The mean Cronbach's alpha was 0.83. There was a statistically significant positive correlation between the mean overall CDLQI score and CDLQI subscale scores that ranged from 0.401 to 0.841. CONCLUSION: Our study confirmed that acne is associated with impairment in QoL that is in accordance with previous studies performed on teenagers. The CDLQI is a reliable and valid measure, and can be used as a practical tool for measuring the impact of acne on patients' QoL.

Spectroscopic investigation of direct current (DC) plasma electrolytic oxidation of zirconium in citric acid.

Plasma electrolytic oxidation of zirconium in citric acid was investigated using optical spectroscopy. A rich emission spectrum consisting of about 360 zirconium and 170 oxygen atomic and ionic lines was identified in the spectral regions 313-320, 340-516, and 626-640 nm. It was shown that the remaining features observed in the spectrum could be ascribed to various molecular species, which involve zirconium, oxygen, hydrogen, and carbon. The temperature of the plasma core (T = 7500 ± 1000 K) was determined using measured Zr line intensities, and the temperature of peripheral plasma zone (T = 2800 ± 500 K) was estimated from the intensity distribution within a part of an OH spectrum. The composition of the plasma containing zirconium, oxygen, and hydrogen, under assumption of local thermal equilibrium, was calculated in the temperature range up to 12,000 K and for pressure of 10(5) and 10(7) Pa, in order to explain the appearance of the observed spectral features.

Prevalence and quality of life in high school pupils with acne in Serbia.

BACKGROUND/AIM: Acne is a common problem in adolescent children with considerable emotional and psychological effects. The aim of this study was to determine the self-reported prevalence of acne and to assess its impact on the quality of life in high school pupils in Serbia. METHODS: The cross-sectional study was conducted in May 2011 in two medical high schools in Serbia. Only pupils who gave a written informed consent to participate in the study (n = 440) were asked to fill in two questionnaires: short demographic questionnaire and Cardiff Acne Disability Index (CADI), a disease-specific questionnaire measuring disability induced by acne. Internal consistency (tested by Cronbach's alpha) and item-total score correlations (Spearman's correlation analysis) were used for reliability analyses. RESULTS: The study population consisted of 440 pupils, 281 from Belgrade and 159 from Uzice. Among them 371 (84.3%) were girls and 69 (15.7%) boys, with similar sex distribution in Belgrade and Uzice. The total mean age of pupils was 16.48 years (SD = 0.55). Out of 440 pupils 228 (51.8%) self-reported their acne. The acne prevalence was significantly higher in pupils from Uzice (73.6%) than in those from Belgrade (39.6%). The overall mean CADI score for the whole sample was 2.87 +/- 2.74, with the similar quality of life impairment in adolescents from Belgrade and from Uzice. The mean Cronbach's alpha was 0.82. CONCLUSION: This study shows that the quality of life impairment due to acne is mild for the majority of the affected pupils. The Serbian version of the CADI is a reliable, valid, and valuable tool for assessing the impact of acne on the quality of life.

Influence of temperature, chlorine residual and heavy metals on the presence of Legionella pneumophila in hot water distribution systems.

The microbiological colonisation of buildings and man-made structures often occurs on the walls of plumbing systems; therefore, monitoring of opportunistic pathogens such as Legionella pneumophila (L. pneumophila), both in water distribution mains and in consumers' plumbing systems, is an important issue according to the international and national guidelines that regulate the quality of drinking water. This paper investigates the presence of L. pneumophila in the Dalmatian County of Croatia and the relationship between L. pneumophila presence and heavy metals concentrations, free residual chlorine and water temperature in hot water distribution systems (WDS). Investigations were performed on a large number of hot water samples taken from taps in kitchens and bathrooms in hotels and homes for the elderly and disabled in the Split region. Of the 127 hot water samples examined, 12 (9.4%) were positive for Legionella spp. with median values concentration of 450 cfu × L(-1). Among positive isolates, 10 (83.3%) were L. pneumophila sg 1, and two of them (16.6%) belonged to the genera L. pneumophila sg 2-14. The positive correlation between the water temperature, iron and manganese concentrations, and L. pneumophila contamination was proved by statistical analysis of the experimental data. On the contrary, zinc and free residual chlorine had no observed influence on the presence of L. pneumophila. The presence of heavy metals in water samples confirms the corrosion of distribution system pipes and fittings, and suggests that metal plumbing components and associated corrosion products are important factors in the survival and growth of L. pneumophila in WDS.

Legionella species in year-round vs. seasonal accommodation water supply systems.

The purpose of this study was to compare the quality of hot water between eleven hotels in the Split-Dalmatia County, Croatia that are open year round and 10 summer season hotels and retirement homes with irregular use of water. We took 122 samples between May and December 2009. Water temperature and free residual chlorine were measured in situ. Physical and chemical analysis included pH, electrical conductivity, and concentrations of iron, manganese, copper, zinc, calcium, and magnesium that were measured using atomic absorption spectrophotometry, while the Legionella species were determined using a cultivation method on buffered charcoal yeast extract agar. Differences in metal concentrations between the seasonal and year-round accommodation facilities were negligible, save for zinc that was higher in year-round (0.341 mg L(-1)) than in seasonal facilities (0.130 mg L(-1)). Samples from all year-round and six summer season hotels were negative to the Legionella species, but four seasonal facilities turned up with positive samples to Legionella pneumophila. Our study has demonstrated that water quality differs between year-round and seasonal accommodation facilities. These findings suggest that metal plumbing components and associated corrosion products are important factors in the survival and growth of Legionella species in water distribution systems.