Determination of the Prevalence of Microsatellite Instability, BRAF and KRAS/NRAS Mutation Status in Patients with Colorectal Cancer in Slovakia.

Slovakia has one of the highest rates of colorectal cancer among the developed countries, ranking as the second highest in the incidence of this disease for men worldwide. Despite the significant burden on both quality of life and the healthcare system this disease imposes, data on molecular analysis of biomarkers in CRC-diagnosed patients is scarce. In our study, we analyzed confirmed CRC patients from the database of the National Cancer Institute (NCI) and evaluated the presence of 4 biomarkers in tumor tissues. Altogether, 83 FFPE tumor tissues from CRC patients listed in the NCI database were analyzed for microsatellite instability status, presence of BRAF and KRAS/NRAS mutations, and neoplastic cell percentage in tissue samples. We identified 4 MSI-high samples, 39 KRAS/NRAS mutations, and 5 BRAF p.V600E mutations, with one case of coexistence of all three markers in a single tumor sample. We also evaluated possible relationships between biomarkers, their coexistence, and the age and sex of the studied population.

SARS-CoV-2 testing in the Slovak Republic from March 2020 to September 2022 - summary of the pandemic trends.

The COVID-19 pandemic has been part of Slovakia since March 2020. Intensive laboratory testing ended in October 2022, when the number of tests dropped significantly, but the state of the pandemic continues to this day. For the management of COVID-19, it is important to find an indicator that can predict pandemic changes in the community. The average daily/weekly Ct value with a certain time delay can predict changes in the number of cases of SARS-CoV-2 infection, which can be a useful indicator for the healthcare system. The study analyzed the results of 1,420,572 RT-qPCR tests provided by one accredited laboratory during the ongoing pandemic in Slovakia from March 2020 to September 2022. The total positivity of the analyzed tests was 24.64%. The average Ct values found were the highest in the age group of 3-5 years, equal to the number 30.75; the lowest were in the age group >65 years, equal to the number 27. The average weekly Ct values ranged from 22.33 (pandemic wave week) to 30.12 (summer week). We have summarized the results of SARS-CoV-2 diagnostic testing in Slovakia with the scope defined by the rate and positivity of tests carried out at Medirex a.s. laboratories.

International Multicenter Study of Clinical Outcomes of Sinonasal Melanoma Shows Survival Benefit for Patients Treated with Immune Checkpoint Inhibitors and Potential Improvements to the Current TNM Staging System.

Objectives Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic ( p < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57-0.96, p = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25-1.00, p = 0.036). Conclusions We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.

Telomere Length Changes in Cancer: Insights on Carcinogenesis and Potential for Non-Invasive Diagnostic Strategies.

Telomere dynamics play a crucial role in the maintenance of chromosome integrity; changes in telomere length may thus contribute to the development of various diseases including cancer. Understanding the role of telomeric DNA in carcinogenesis and detecting the presence of cell-free telomeric DNA (cf-telDNA) in body fluids offer a potential biomarker for novel cancer screening and diagnostic strategies. Liquid biopsy is becoming increasingly popular due to its undeniable benefits over conventional invasive methods. However, the organization and function of cf-telDNA in the extracellular milieu are understudied. This paper provides a review based on 3,398,017 cancer patients, patients with other conditions, and control individuals with the aim to shed more light on the inconsistent nature of telomere lengthening/shortening in oncological contexts. To gain a better understanding of biological factors (e.g., telomerase activation, alternative lengthening of telomeres) affecting telomere homeostasis across different types of cancer, we summarize mechanisms responsible for telomere length maintenance. In conclusion, we compare tissue- and liquid biopsy-based approaches in cancer assessment and provide a brief outlook on the methodology used for telomere length evaluation, highlighting the advances of state-of-the-art approaches in the field.

Role of CRTC1/MAML2 Translocation in the Prognosis and Clinical Outcomes of Mucoepidermoid Carcinoma.

IMPORTANCE: The CRTC1/MAML2 fusion transcript, which arises from the CRTC1/MAML2 translocation, is a molecular marker unique to mucoepidermoid carcinoma (MEC), the most common malignant tumor of the salivary gland. The extent to which the transcript influences disease features and patient survival is unclear. OBJECTIVE: To determine whether the CRTC1/MAML2 fusion transcript is associated with disease stage, tumor grade, or survival outcomes in patients with MEC. DESIGN, SETTING, AND PARTICIPANTS: A retrospective medical record review was performed at a tertiary-care academic medical institution. The review included 90 patients with MEC who underwent treatment from January 1, 1995, to December 31, 2011, and for whom archived formalin-fixed, paraffin-embedded tumor specimens were available. Records were reviewed for clinical, demographic, and survival data. Tumor specimens underwent fluorescence in situ hybridization. Follow-up was completed on May 15, 2014, and data were analyzed from June 1 to July 1, 2014. MAIN OUTCOMES AND MEASURES: CRTC1/MAML2 fusion transcript status. Statistical analysis determined whether transcript status was associated with disease stage, tumor grade, and/or overall and disease-free survival. RESULTS: Among the 90 eligible patients (median [range] age, 55.1 [7.8-89.2] years), 42 were female and 48 were male. Fluorescence in situ hybridization revealed a CRTC1/MAML2 translocation in 50 patients (56%). The translocations were more prevalent in intermediate-grade tumors (31 of 49 [63%]) than in high-grade (11 of 49 [22%]) and low-grade (7 of 49 [14%]) tumors; 1 tumor sample had no available grading. Similar proportions of patients with translocation-positive disease had T1 (13 of 49 [26%]), T2 (15 of 49 [31%]), T4a (14 of 49 [28%]), or T0 or Tx (8 of 49 [16%]) stages of disease. Thirty-eight of 49 patients with translocation-positive MEC (78%) had N0 stage of disease. Rates of 5-year overall survival were similar for patients with translocation-positive and translocation-negative disease (76.8% vs 75.5%, respectively; P = .17), as were rates of disease-free survival (65.2% vs 57.4%, respectively; P = .28). CONCLUSIONS AND RELEVANCE: Detection of the CRTC1/MAML2 fusion transcript provides useful information for MEC diagnosis but is not associated with differences in survival outcomes.

Prognosis and biology in esthesioneuroblastoma: the emerging role of Hyams grading system.

Esthesioneuroblastoma is a sinonasal tumor with distinct clinicopathologic features, multiple facets, and a spectrum of behavior. Characterization of this disease is challenging, and clinically, several staging systems have been used with no consensus on a single scheme. Recently, the Hyams histological grading system has emerged as a promising prognostication tool that offers an added value to stage. This review addresses prognosis and biology in esthesioneuroblastoma. More specifically, we sought to present a critical appraisal on the value of each of these stratification systems, stage vs. grade, in identifying risk groups and guiding management.

Primary extradural meningioma presenting as a neck mass: Case report and review of the literature.

BACKGROUND: Primary extradural meningiomas (PEMs) are rare, particularly those involving the paraspinal cervical area, so little is known about them. We identified a new case and compared it with 10 previous cases, addressed the diagnostic challenges, and highlighted the clinical and pathologic characteristics. METHODS: We conducted a case report and literature review of PEM cases reported since 1976. RESULTS: A 59-year-old man presented with right neck stiffness and discomfort that was present over the last several months, which is consistent with other cases. CT scan and MRI revealed a paraspinal cervical mass. Fine-needle aspiration (FNA) and core biopsy revealed spindle cells with whorling consistent with meningioma. The patient underwent complete en bloc resection of the tumor. The PEM was histologically benign. CONCLUSION: Cervical PEMs should be considered in the differential diagnosis of a deep neck mass. These tumors are typically benign and are surgically resected.

FORMANT CHARACTERISTICS OF ENGLISH-SPEAKING LEBANESE MEN.

OBJECTIVE: To report the formant characteristics of English-speaking Lebanese men during steady prolongation of vowels /a/ and /i/. DESIGN: Cross-sectional study involving volunteer participants. PARTICIPANTS: Fifty healthy English-speaking males with a mean age of 32 ± 4.027 years and a range of 42 years (18-60). MATERIALS AND METHODS: A total of 50 healthy males between the age of 18 and 60 were recruited for the study. Each subject was asked to phonate a sustained /a/ and /i/ sound at a comfortable pitch and intensity level. Measures were made in real-time and formant frequencies across F1, F2, F3 and F4 were determined using the Real-time Spectrogram VP 3950 (Kay Elemetrics, New Jersey). MAIN OUTCOME MEASURES: The formant frequencies across F1, F2, F3 and F4 were recorded. RESULTS: For the vowel /a/, the mean values of F1, F2, F3 and F4 were 622.86 ± 61.293 Hz, 1264 ± 78.602 Hz, 2610.90 ± 206.359 Hz and 3483.56 ± 206.833 Hz, respectively. For the vowel /i/, the corresponding values were 378.88 ± 51.825 Hz, 2210.34 ± 124.077 Hz, 2847 ± 168.770 Hz and 3576.82 ± 242.760 Hz, respectively. CONCLUSION: Formant characteristics vary among cultures and ethnic groups.

Prognostic utility of Hyams histological grading and Kadish-Morita staging systems for esthesioneuroblastoma outcomes.

Esthesioneuroblastoma (ENB) is derived from the specialized olfactory neuroepithelium. Hyams grading and Kadish staging have been used to prognosticate and to guide treatment decisions. In this study, we sought to validate the prognostic utility of these systems in a large ENB cohort. We retrospectively analyzed the records of patients with ENB who had been evaluated and treated at our institution. The association of grade and stage with prognostic outcome was assessed; the Kaplan-Meier estimator was used to generate 5-year OS and DFS curves. Out of 124 cases we identified, 121 were assessed for grading and 109 for staging. Review of the tissue samples revealed that 62 % of tumors were low grade (I/II) and 21 % were high grade (III/IV); 17 % of tumors were metastasis. The OS rate was 75 % at 5 years. The DFS was 60 % at 5 years. The OS was significantly worse for metastatic ENB (low-grade ENB vs metastatic ENB p = 0.01598); the DFS was significantly worse for high grade versus low grade ENB. Of the 109 cases that had been staged, 16 % were stage A, 33 % stage B, 43 % stage C, and 8 % stage D. In the A, B, and C groups, there were no significant differences between recurrence, distant metastasis, or 5-year survival rates. Statistical significance was not reached with the T, N, M and overall staging system. Age cutoff of 65 years reliably predicted OS. High grade of ENB was significantly associated with poor outcome, while advanced stage was not associated with poor outcome in this large cohort. Grading should certainly be considered in prognostication and treatment decisions for ENB.

Mutational landscape of aggressive cutaneous squamous cell carcinoma.

PURPOSE: Aggressive cutaneous squamous cell carcinoma (cSCC) is often a disfiguring and lethal disease. Very little is currently known about the mutations that drive aggressive cSCC. EXPERIMENTAL DESIGN: Whole-exome sequencing was performed on 39 cases of aggressive cSCC to identify driver genes and novel therapeutic targets. Significantly, mutated genes were identified with MutSig or complementary methods developed to specifically identify candidate tumor suppressors based upon their inactivating mutation bias. RESULTS: Despite the very high-mutational background caused by UV exposure, 23 candidate drivers were identified, including the well-known cancer-associated genes TP53, CDKN2A, NOTCH1, AJUBA, HRAS, CASP8, FAT1, and KMT2C (MLL3). Three novel candidate tumor suppressors with putative links to cancer or differentiation, NOTCH2, PARD3, and RASA1, were also identified as possible drivers in cSCC. KMT2C mutations were associated with poor outcome and increased bone invasion. CONCLUSIONS: The mutational spectrum of cSCC is similar to that of head and neck squamous cell carcinoma and dominated by tumor-suppressor genes. These results improve the foundation for understanding this disease and should aid in identifying and treating aggressive cSCC.

The role of OM-85 BV (Broncho-Vaxom) in preventing recurrent acute tonsillitis in children.

OBJECTIVE: To evaluate the efficacy of an immunostimulant (bacterial lysate) Broncho-Vaxom in the management of children with recurrent acute tonsillitis. METHODS: A 5-year retrospective cohort study of 177 children presenting with a diagnosis of recurrent acute tonsillitis. Patients' demographics and laboratory studies at presentation were retrieved. For patients given Broncho-Vaxom, we defined response as a decrease in the frequency of acute tonsillitis episodes after 3 months of therapy (partial: by ≤50% and total: by >50%). Patients showing response to Broncho-Vaxom were further followed until study-end or need for tonsillectomy. RESULTS: The median age of patients was 4.5 years (range: 1-15 years) with 63.8% being males. 131 (74%) patients received Broncho-Vaxom as initial therapy, and 99 (75.6%) showed response (51.2% total and 24.4% partial response). A normal ESR level was the only predictor of total compared with no response (OR: 3.53, 95% CI: 1.03-12.07); while both normal ESR (OR: 7.15-times, 95% CI: 1.18-43.39) and normal CRP (OR: 12.66, 95% CI: 1.43-111.86) levels were independent predictors of total over partial response. None of the patients showing total response required tonsillectomy on long-term follow up while in those with partial response 34.4% required subsequent tonsillectomy (median follow-up: 9 months). CONCLUSIONS: A considerable proportion of children receiving Broncho-Vaxom for recurrent acute tonsillitis show a decrease in the frequency of episodes in the short term, and very few patients eventually require tonsillectomy on long-term follow up.

Relationship between acoustic parameters and body mass analysis in young males.

PURPOSE: To analyze the correlation between acoustic parameters and body height, weight, and mass composition in young males. MATERIAL: A total of 40 male subjects were included in this study. Each subject underwent acoustic analysis using the Kay Elemetric VISI Pitch (Model 3300, KayPentax, Lincoln Park, NJ) and complete body mass analysis. Pearson correlation was calculated to estimate the strength of the relationship between acoustic parameters and each of the weight analysis variables. RESULTS: The mean age of the male subjects was 24 years with a range between 18 and 40 years. The average weight and height were almost 80 and 180cm, with standard deviation (SD) of 7.42 and 10.46, respectively. The fat weight ranged between 3 and 25kg, with the main concentration being in the extremities, 61.84%±17.4 and less concentrated in the trunk, 16.20% ± 7.6. The mean fundamental frequency was 120.13Hz with an SD of 19.16Hz. The mean Habitual Pitch was 114.16Hz with an SD of 16.55Hz. There was no significant correlation between the acoustic parameters and any of the body composition variables, in particular fat weight and distribution. There was a weak correlation between Shimmer, trunk fat (r value=0.328, P=0.039), and muscle mass (r value=0.326, P=0.038). CONCLUSION: The body mass composition and distribution do not correlate significantly with the fundamental frequency and the Habitual pitch.