ABSTRACT
Oncolytic virus (OV) therapy has emerged as a promising frontier in cancer treatment, especially for solid tumours. While immunotherapies like immune checkpoint inhibitors and CAR-T cells have demonstrated impressive results, their limitations in inducing complete tumour regression have spurred researchers to explore new approaches targeting tumours resistant to current immunotherapies. OVs, both natural and genetically engineered, selectively replicate within cancer cells, inducing their lysis while sparing normal tissues. Recent advancements in clinical research and genetic engineering have enabled the development of targeted viruses that modify the tumour microenvironment, triggering anti-tumour immune responses and exhibiting synergistic effects with other cancer therapies. Several OVs have been studied for breast cancer treatment, including adenovirus, protoparvovirus, vaccinia virus, reovirus, and herpes simplex virus type I (HSV-1). These viruses have been modified or engineered to enhance their tumour-selective replication, reduce toxicity, and improve oncolytic properties.Newer generations of OVs, such as Oncoviron and Delta-24-RGD adenovirus, exhibit heightened replication selectivity and enhanced anticancer effects, particularly in breast cancer models. Clinical trials have explored the efficacy and safety of various OVs in treating different cancers, including melanoma, nasopharyngeal carcinoma, head and neck cancer, and gynecologic malignancies. Notably, Talimogene laherparepvec (T-VEC) and Oncorine have. been approved for advanced melanoma and nasopharyngeal carcinoma, respectively. However, adverse effects have been reported in some cases, including flu-like symptoms and rare instances of severe complications such as fistula formation. Although no OV has been approved specifically for breast cancer treatment, ongoing preclinical clinical trials focus on four groups of viruses. While mild adverse effects like low-grade fever and nausea have been observed, the effectiveness of OV monotherapy in breast cancer remains insufficient. Combination strategies integrating OVs with chemotherapy, radiotherapy, or immunotherapy, show promise in improving therapeutic outcomes. Oncolytic virus therapy holds substantial potential in breast cancer treatment, demonstrating safety in trials. Multi-approach strategies combining OVs with conventional therapies exhibit more promising therapeutic effects than monotherapy, signalling a hopeful future for OV-based breast cancer treatments.
Subject(s)
Breast Neoplasms , Melanoma , Nasopharyngeal Neoplasms , Oncolytic Virotherapy , Oncolytic Viruses , Female , Humans , Oncolytic Virotherapy/adverse effects , Oncolytic Virotherapy/methods , Melanoma/therapy , Oncolytic Viruses/genetics , Breast Neoplasms/therapy , Breast Neoplasms/etiology , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Neoplasms/therapy , Tumor MicroenvironmentABSTRACT
INTRODUCTION: Genome sequencing technologies reveal molecular mechanisms of differentiated thyroid cancer (DTC). Unlike somatic mutation analysis from thyroidectomy samples, germline mutations showing genetic susceptibility to DTC are less understood. OBJECTIVES: The study aimed to assess the prevalence of germline mutations predisposing to DTC in a cohort of Polish individuals based on their whole genome sequencing data. PATIENTS AND METHODS: We analyzed sequencing data from 1076 unrelated individuals totaling over 1018 billion read pairs and yielding an average 35.26 × read depth per genome, released openly for academic and clinical research as the Thousand Polish Genomes database (https://1000polishgenomes.com). The list of genes chosen for further analysis was based on the review of previous studies. RESULTS: The cohort contained 104 variants located within the coding and noncoding DNA sequences of 90 genes selected by ClinVar classification as pathogenic and potentially pathogenic. The frequency of variants in the Polish cohort was compared with the frequency estimated for the nonFinnish European population obtained from the gnomAD database (gnomad.broadinstitute.org). Significant differences in variant frequency were found for the APC, ARSB, ATM, BRCA1, CHEK2, DICER1, GPD1L, INSR, KCNJ10, MYH9, PALB2, PLCB1, PLEKHG5, PTEN, RET, SEC23B, SERPINA1, SLC26A4, SMAD3, STK11, TERT, TOE1, and WRN genes. CONCLUSIONS: Even though the Polish population is genetically similar to the other European populations, there are significant differences in variant frequencies contributing to the disease development and progression, such as those in the RET, CHEK2, BRCA1, SLC26A4, or TERT genes. Further studies are needed to identify genomic variants associated directly with DTC.
Subject(s)
Adenocarcinoma , Thyroid Neoplasms , Humans , Poland , Genetic Predisposition to Disease , Germ-Line Mutation , Ribonuclease III/genetics , DEAD-box RNA Helicases/genetics , Nuclear Proteins/geneticsABSTRACT
BACKGROUND: The recognition of the importance of effective communication in the healthcare system has been growing. Given that communication courses must be adjusted to the specificity of a particular culture, language, and other contextual issues, many countries and communities sharing a common language have proposed their recommendations for a communication curriculum for undergraduate medical education. To date, no recommendations have been developed for either any Central and Eastern Europe countries or for regions where Slavic languages are spoken. Their specificity of post-communist transformation should be acknowledged. This study aims to review communication curriculums and offer recommendations for medical communication training for undergraduate medical students in Poland. METHODS: The recommendations were developed through an iterative consultation process with lecturers, faculty members of medical schools, and education coordinators. PubMed and Google Scholar databases were searched to identify full text English and Polish language articles on communication curriculum for undergraduate medical education. Additionally, the new Regulation of the Polish Minister of Science and Higher Education, defining educational standards for undergraduate medical education was analysed in search of learning outcomes that could be applied in communication skills teaching. The authors extracted the most relevant communication skill competencies, as determined by the process participants, discussed current challenges, including those of the COVID-19 pandemic era, and indicated best practices. RESULTS: A review was conducted, and a set of recommendations was developed pertaining to the scope and methodology of teaching communication skills. The study included: (1) definition, (2) education content, (3) learning outcomes, (4) the recommended teaching methods. The recommendations are in concord with the graduate profile, as well as the current structure of medical studies. The authors listed and discussed the basic communication competencies expected of medical graduates, as well as medical communication course content viewed from different perspectives, including clinical, psychological, sociological, legal, and linguistic. CONCLUSIONS: Detailed recommendations aimed at integrating best practices into a comprehensive communication curriculum may promote successful teaching, learning, and assessment of medical communication.
Subject(s)
COVID-19 , Education, Medical, Undergraduate , Humans , Poland , Pandemics , Curriculum , CommunicationABSTRACT
Pre- and postsurgical differentiation between follicular thyroid adenoma (FTA) and follicular thyroid cancer (FTC) represents a significant diagnostic challenge. Furthermore, it remains unclear whether they share a common or distinct background and what the mechanisms underlying follicular thyroid lesions malignancy are. The study aimed to compare FTA and FTC by the comprehensive microarray and to identify recurrent regions of loss of heterozygosity (LOH). We analyzed formalin-fixed paraffin-embedded (FFPE) samples acquired from 32 Caucasian patients diagnosed with FTA (16) and FTC (16). We used the OncoScan™ microarray assay (Affymetrix, USA), using highly multiplexed molecular inversion probes for single nucleotide polymorphism (SNP). The total number of LOH was higher in FTC compared with FTA (18 vs. 15). The most common LOH present in 21 cases, in both FTA (10 cases) and FTC (11 cases), was 16p12.1, which encompasses many cancer-related genes, such as TP53, and was followed by 3p21.31. The only LOH present exclusively in FTA patients (56% vs. 0%) was 11p11.2-p11.12. The alteration which tended to be detected more often in FTC (6 vs. 1 in FTA) was 12q24.11-q24.13 overlapping FOXN4, MYL2, PTPN11 genes. FTA and FTC may share a common genetic background, even though differentiating rearrangements may also be detected.
ABSTRACT
BACKGROUND: Traditional repetitive Transcranial Magnetic Stimulation (rTMS) remains applicable in speech studies on healthy participants. Although the procedure of inducing speech arrest by rTMS has been used for over 25 years, there are still significant discrepancies in its methodology. OBJECTIVE: The study aimed to simplify and improve the old methodology of triggering speech arrest by (rTMS). Our goal was to establish the best step-by-step algorithm and verify the procedure on a representative group of participants. METHODS: 47 healthy, right-handed volunteers (23 men and 24 women) at a median age of 23 (range 19-34) were included in the study. Handedness was determined using the Edinburgh Handedness Inventory Test. After setting the individual's motor threshold (MT) and heuristic choice of the place of stimulation, which targeted Inferior Frontal Gyrus (IFG), participants were asked to count downwards from 20 to 10. While counting, a series of 2-second pulses was generated at a frequency of 2âHz at 120% or 150% of MT. The procedure was video-recorded and subsequently assessed by 3 independent reviewers and self-assessed by participants on visual analogue scales for the effect and comfort of stimulation. RESULTS: Speech arrest was induced in 45 people (95.7%). Language dominance was determined to be either left-sided (for 42.2%) or bilateral (55.3%). Total speech arrest was observed more often in participants for whom Broca's area was active exclusively in the left hemisphere. CONCLUSION: In our study, we present the step-by-step procedure for a simplified, as far as possible, methodology of inducing speech arrest using rTMS with its verification on a representative group of right-handed healthy individuals. Our results prove that the chosen stimulation parameters present a good efficacy ratio and seems to be justified. The traditional applications of rTMS in speech studies may be highly broadened if the methods used are further improved and simplified.
Subject(s)
Speech , Transcranial Magnetic Stimulation , Female , Functional Laterality/physiology , Humans , Language , Male , Speech/physiology , Transcranial Magnetic Stimulation/methodsABSTRACT
The purpose of the present paper is to review the progress in recognition and implementation of shared decision-making (SDM) practice in the Polish health care system. In Poland, equal access to health care is a constitutional right. The foundations for SDM practice within the Polish health care system are laid in legislation regulating the professions of doctors and dentists, as well as patients' rights, which assert the duty of physicians to provide clear and patient-adjusted information on diagnostic and treatment options, health status and prognosis before obtaining consent. Over recent years, patient organizations have gained voice in the institutional setting. At the same time participatory decision-making at the individual patient level remains uneven, with a considerable variety between health care settings or even physicians. The challenges related to the implementation of SDM practices include low health care funding and staff shortages, which limit both the scope of available choices and consultation time. Fragmentation of care and inadequate standardization constitute additional barriers to the elaboration and sharing of good SDM practices.
Subject(s)
Decision Making , Patient Participation , Germany , Health Policy , Humans , PolandABSTRACT
Thyroid hemiagenesis (THA) is an inborn absence of one thyroid lobe of largely unknown etiopathogenesis. The aim of the study was to reveal genetic factors responsible for thyroid maldevelopment in two siblings with THA. None of the family members presented with congenital heart defect. The samples were subjected to whole-exome sequencing (WES) (Illumina, TruSeq Exome Enrichment Kit, San Diego, CA 92121, USA). An ultra-rare variant c.839C>T (p.Pro280Leu) in NKX2-5 gene (NM_004387.4) was identified in both affected children and an unaffected father. In the mother, the variant was not present. This variant is reported in population databases with 0.0000655 MAF (GnomAD v3, dbSNP rs761596254). The affected amino acid position is moderately conserved (positive scores in PhyloP: 1.364 and phastCons: 0.398). Functional prediction algorithms showed deleterious impact (dbNSFP v4.1, FATHMM, SIFT) or benign (CADD, PolyPhen-2, Mutation Assessor). According to ACMG criteria, variant is classified as having uncertain clinical significance. For the first time, NKX2-5 gene variants were found in two siblings with THA, providing evidence for its potential contribution to the pathogenesis of this type of thyroid dysgenesis. The presence of the variant in an unaffected parent, carrier of p.Pro280Leu variant, suggests potential contribution of yet unidentified additional factors determining the final penetrance and expression.
Subject(s)
Siblings , Thyroid Dysgenesis , Child , Exome , Homeobox Protein Nkx-2.5/genetics , Humans , Mutation , Thyroid Dysgenesis/genetics , Thyroid Dysgenesis/pathologyABSTRACT
This study presents a modified Group Objective Structured Clinical Experience (GOSCE) focused on difficult conversations, in which, due to limited time and financial resources, only some students could actively participate in scenarios. We aimed to evaluate the intervention, including differences between them and observers. The intervention was organized for sixth-year medical students at a Polish medical university. The study protocol assumed a pre-post analysis of students' attitudes and self-efficacy of communication skills and their opinions about the intervention. Complete questionnaire pairs were returned by 126 students. The pre-post analysis revealed a significant improvement in their self-efficacy levels of almost all skills as well as their affective attitudes and belief in outcomes of communication learning. The improvement was significant among both the active participants and observers. It also showed a decrease in the motivation score, significant only in females. Regardless of their roles, students had positive opinions about the course and its particular aspects. The modified GOSCE may be an enjoyable and effective learning experience for students, especially in the light of limited resources. However, changes in their motivation score suggest the necessity to increase the importance of communication learning in the curriculum.
Subject(s)
Education, Medical, Undergraduate , Students, Medical , Clinical Competence , Communication , Curriculum , Female , Humans , MotivationABSTRACT
Certain ultrasound features are associated with an increased risk of thyroid malignancy. However, they were studied mainly in papillary thyroid cancers (PTCs); these results cannot be simply extrapolated for the differentiation of follicular thyroid adenomas and cancers (FTAs and FTCs). The aim of our study was to perform a meta-analysis to identify sonographic features suggesting malignancy in the case of follicular lesions, potentially differentiating FTA and FTC. We searched thirteen databases from January 2006 to December 2020 to find all relevant, full-text journal articles written in English. Analyses assessed the accuracy of malignancy detection in case of follicular lesions, potentially differentiating FTA and FTC included the odds ratio (OR), sensitivity, specificity, positive and negative predictive values. A random-effects model was used to summarize collected data. Twenty studies describing sonographic features of 10,215 nodules met the inclusion criteria. The highest overall ORs to increase the risk of malignancy were calculated for tumor protrusion (OR = 10.19; 95% confidence interval: 2.62-39.71), microcalcifications or mixed type of calcifications (coexisting micro and macrocalcifications): 6.09 (3.22-11.50), irregular margins: 5.11 (2.90-8.99), marked hypoechogenicity: 4.59 (3.23-6.54), and irregular shape: 3.6 (1.19-10.92). The most crucial feature associated with an increased risk of FTC is capsule protrusion, followed by the presence of calcifications, irrespectively of their type.
ABSTRACT
PURPOSE: Thyroid hemiagenesis (THA) is an inborn absence of one thyroid lobe of largely unknown etiopathogenesis, affecting 0.05-0.5% population. The aim of the study was an identification of genetic factors responsible for thyroid maldevelopment in two siblings with THA. METHODS: We evaluated a three-generation THA family with two sisters presenting the disorder. Proband (Patient II:3) was diagnosed at the age of 45 due to neck asymmetry. Left lobe agenesis and nontoxic multinodular goiter were depicted. Proband's sister (Patient II:6) was euthyroid, showed up at the age of 39 due to neck discomfort and left-sided THA was demonstrated. Affected individuals were subjected to whole-exome sequencing (WES) (Illumina, TruSeq Exome Kit) and all identified variants were evaluated for pathogenicity. Sanger sequencing was used to confirm WES data and check segregation among first-degree relatives. RESULTS: In both siblings, a compound heterozygous mutations NM_000168.6: c.[2179G>A];[4039C>A] (NP_000159.3: p.[Gly727Arg];[Gln1347Lys]) were identified in the GLI3 gene, affecting exon 14 and 15, respectively. According to the American College of Medical Genetics, variants are classified as of uncertain significance, and were found to be very rare (GnomAD MAF 0.007131 and 0.00003187). The segregation mapping and analysis of relatives indicated causativeness of compound heterozygosity. CONCLUSIONS: We demonstrated for the first time a unique association of THA phenotype and the presence of compound heterozygous mutations p.[Gly727Arg];[Gln1347Lys] of GLI3 gene in two siblings.
Subject(s)
Siblings , Thyroid Dysgenesis , Zinc Finger Protein Gli3 , Exome , Humans , Mutation , Nerve Tissue Proteins/genetics , Pedigree , Thyroid Dysgenesis/genetics , Zinc Finger Protein Gli3/geneticsABSTRACT
BACKGROUND: Conventional treatments for follicular thyroid cancer (FTC) can be ineffective, leading to poor prognosis. The aim of this study was to identify mutations associated with FTC that would serve as novel molecular markers of the disease and its outcome and could potentially identify new therapeutic targets. METHODS: FLT3 mutations were first detected in a 29-year-old White female diagnosed with metastasized, treatment-refractory FTC. Analyses of FLT3 mutational status through next-generation sequencing of formalin-fixed, paraffin-embedded FTC specimens were subsequently performed in 35 randomly selected patients diagnosed with FTC. RESULTS: FLT3 mutations were found in 69% of patients. FLT3 mutation-positive patients were significantly older than those that were FLT3 mutation-negative [median age at diagnosis 54 (36-82) versus 45 (27-58) (p = 0.023)]. Patients over 60 years were 23 times more likely to be FLT3 mutation-positive (p = 0.006). However, the number of FLT3 mutations did not correlate with age (r-Pearson: -0.244, p-value: 0.25). A total of 26 mutations were identified in the FLT3 gene with 2-16 FLT3 mutations in each FLT3 mutation-positive patient (mean: 5.6 mutations/patient). Tyrosine kinase domain (TKD) mutations in the FLT3 gene were detected in 58% of FLT3 mutation-positive patients. All FLT3 mutation-positive patients with a disease stage of pT2N1 or worse harbored at least one mutation in the TKD of FLT3. CONCLUSIONS: There is a wide spectrum and high frequency of FLT3 mutations in FTC. The precise role of FLT3 mutations in the genesis of FTC, as well as its potential role as a therapeutic target, requires further investigation.
ABSTRACT
BACKGROUND: Although differentiated thyroid cancer (DTC) has relatively favorable course, factors predicting the course of the disease are intensively searched. The aim of the study was to identify the clinical factors determining incomplete response to radioiodine therapy in patients with DTC. METHODS: We retrospectively analyzed 385 consecutive patients with DTC treated and followed-up at a single tertiary reference center. We investigated clinical factors detectable during first hospitalization 3-6 months following total thyroidectomy due to DTC, which may serve as prognostic factors determining response to DTC therapy in a long-term follow-up. RESULTS: Stimulated thyroglobulin (sTg) was the only parameter significantly correlated with the cumulative radioiodine activity (r=0.247, P<0.001). The need for repeated radioiodine administration (≥3 doses) was best predictable on the basis of sTg concentration assessed at the moment of qualification to radioiodine therapy (P=0.003). Predictive value of the sTg for incomplete response to radioiodine has been confirmed with the ROC curve analysis and the best proposed cut-off value was 8.17 ng/mL (sensitivity 55%, specificity 77%, positive predictive value 42.1%, negative predictive value 84.7%); sTg over 8.17 ng/mL increases the risk of incomplete response to therapy 2.5-folds (P=0.002). CONCLUSIONS: sTg, assessed at the moment of qualification to radioiodine therapy, as the most important factor determining incomplete response to radioiodine therapy in patients with DTC, should be particularly taken into consideration in predicting the future course of the disease as well as treatment and follow-up planning. Radical thyroidectomy may help to increase the effectiveness of treatment.
Subject(s)
Iodine Radioisotopes/therapeutic use , Thyroid Neoplasms/pathology , Thyroid Neoplasms/radiotherapy , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Neoplasm Staging , Retrospective Studies , Treatment Failure , Young AdultABSTRACT
The purpose of the study was to measure the hepcidin concentration and evaluate Fe homeostasis indices in a prospective study on patients with newly diagnosed hypothyroidism in the course of Hashimoto's thyroiditis (HT) and following successful therapy. The prospective observational study consisted of 34 patients. The clinical evaluation and laboratory tests were performed at diagnosis (T0) and after restoration of euthyreosis 12 weeks later (T1). The median level of hepcidin was significantly lower (p = 0.002) after recovery (7.7 [6.2-13.0] ng/mL) than that before treatment (17.4 [7.6-20.4] ng/mL), while creatinine (p = 0.011) and GFR (p < 0.001) significantly improved after euthyroidism was achieved. A positive correlation was observed between hepcidin and fT3 (p = 0.033, r = 0.465) at T0. In the females, the level of hepcidin positively correlated with ferritin concentration before (p < 0.001, r = 0.928) and after treatment (p < 0.001, r = 0.835). A statistically significant difference was observed in RDW-CV (red blood cell distribution width - coefficient of variation) between the hypothyroid and euthyroid states. In conclusion, a decrease in hepcidin concentration during the transition from the hypothyroid state to euthyroidism in patients with HT is associated with the observed dynamics in iron homeostasis, mainly reflected by improvement in RDW-CV and significant correlations between ferritin and hepcidin as well as between hepcidin and fT3.
Subject(s)
Hashimoto Disease/complications , Hashimoto Disease/therapy , Hepcidins/metabolism , Hypothyroidism/complications , Hypothyroidism/metabolism , Adult , Female , Humans , MaleABSTRACT
INTRODUCTION: Inconclusive cytologic results of thyroid fineneedle aspiration biopsy (FNAB) include atypia or follicular lesion of undetermined significance (FLUS) and follicular neoplasm or suspicious for follicular neoplasm (SFN). OBJECTIVES: We aimed to assess the genetic background of indeterminate thyroid nodules and to identify new genetic pathways potentially involved in the development of follicular thyroid cancer. PATIENTS AND METHODS: Genomic DNA was isolated from FNAB samples from 25 white patients (2 men; 23 women) diagnosed preoperatively with FLUS (n = 16) and SFN (n = 9). Nextgeneration sequencing (NGS) was performed. The results were compared with clinical data, including final postsurgical diagnoses. RESULTS: The malignancy rate was 28%. KDR, RET, and TP53 gene mutations were most frequent in FLUS and SFN samples finally diagnosed as cancers, whereas alterations in RET, TP53, FLT3, APC, and PDGFRA predominated in benign tumors. KDR tended to be more common in malignant samples (75% vs 20%, P = 0.1). A total number of mutated genes was higher in patients with benign tumors (17 vs 11, P = 0.02), but there was no difference between groups in the mean number of mutations per patient (4.9 [range, 1-9]). CONCLUSIONS: We showed that the heterogeneity in the genetic background of indeterminate thyroid nodules corresponds to their histopathologic diversity. The role of KDR as a possible malignancy marker needs to be confirmed. Glass slides with FNAB samples may constitute a reliable source of genetic material for NGS studies, providing a better insight into the molecular profile of thyroid nodules.
Subject(s)
Adenocarcinoma, Follicular/diagnosis , Adenocarcinoma, Follicular/genetics , Genetic Variation , High-Throughput Nucleotide Sequencing , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/genetics , Thyroid Nodule/genetics , Adenocarcinoma, Follicular/epidemiology , Humans , Molecular Diagnostic Techniques , Mutation , Pennsylvania/epidemiology , Retrospective Studies , Thyroid Neoplasms/epidemiologyABSTRACT
OBJECTIVE: Pre- and postoperative comparative evaluation of neurophysiological tests and clinical trials. Analysis of the diagnostic value of motor evoked potentials (MEP) induced by a magnetic field after supraspinal stimulation. Evaluation of the sensitivity and specificity of electromyography (EMG) and MEP is achieved. METHODS: EMG, ENG, M-wave, F-wave, and MEP tests were performed on 35 patients with confirmed cervical radiculopathy in pre- and postoperative evaluations. The clinical trial consisted of evaluation of muscle strength, a sensory perception test and evaluation of tendon reflexes and pain severity. RESULTS: The sensitivity of the resting EMG and MEP tests is 24%-67% and 6%-27%, while their specificity is 43%-80% and 86%-100%, respectively. The postoperative evaluation revealed a statistically significant reduction in pain severity (p=0001), an increase in muscle strength in DP (p=0.0431), BB (p=0,0431), and TB (p=0.0272), and improvement of touch sensation in terms of dermatomal innervation in C5 (p=0.0001) and C6 (p=0.0044). CONCLUSIONS: Tests comparing MRI sensitivity to neurophysiological tests show that neuroimaging is more sensitive in diagnostics of patients with cervical radiculopathy; however, clinical neurophysiology tests are more specific in reference to clinical trials.
Subject(s)
Electromyography , Evoked Potentials, Motor , Radiculopathy/physiopathology , Adult , Aged , Female , Humans , Male , Middle Aged , Postoperative Period , Preoperative Period , Radiculopathy/surgeryABSTRACT
We aimed to identify differences in mutational status between follicular thyroid adenoma (FTA) and follicular thyroid cancer (FTC). The study included 35 patients with FTA and 35 with FTC. DNA was extracted from formalin-fixed paraffin-embedded (FFPE) samples from thyroidectomy. Next-generation sequencing (NGS) was performed with the 50-gene Ion AmpliSeq Cancer Hotspot Panel v2. Potentially pathogenic mutations were found in 14 (40%) FTA and 24 (69%) FTC patients (OR (95%CI) = 3.27 (1.22-8.75)). The number of mutations was higher in patients with FTC than FTA (p-value = 0.03). SMAD4 and STK11 mutations were present only in patients with FTA, while defects in FBXW7, JAK3, KIT, NRAS, PIK3CA, SMARCB1, and TP53 were detected exclusively in FTC patients. TP53 mutations increased the risk of FTC; OR (95%CI) = 29.24 (1.64-522.00); p-value = 0.001. FLT3-positivity was higher in FTC than in the FTA group (51.4% vs. 28.6%; p-value = 0.051). The presence of FLT3 and TP53 with no RET mutations increased FTC detectability by 17.1%, whereas the absence of FLT3 and TP53 with a presence of RET mutations increased FTA detectability by 5.7%. TP53 and FLT3 are candidate markers for detecting malignancy in follicular lesions. The best model to predict FTA and FTC may consist of FLT3, TP53, and RET mutations considered together.
Subject(s)
Adenocarcinoma, Follicular/diagnosis , Adenocarcinoma, Follicular/genetics , Biomarkers, Tumor , Mutation , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Alleles , Diagnosis, Differential , Female , Gene Expression Profiling , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Odds RatioABSTRACT
The original version of the article unfortunately contained an error.
ABSTRACT
The objective of this meta-analysis was to evaluate the performance of the Gene Expression Classifier (GEC) and ThyroSeq v2 (ThyroSeq) in the preoperative diagnosis of thyroid nodules with indeterminate fine-needle aspiration biopsy results. We searched literature databases from January 2001 to April 2018. The bivariate model analysis was performed to estimate pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive predictive value (PPV), and negative predictive value (NPV). Pooled data from 1086 nodules with histopathologic confirmation from 16 GEC studies enabled calculation of diagnostic parameters (95% confidence interval): sensitivity 98% (96-99%), specificity 12% (8-20%), PPV 45% (37-53%), and NPV 91% (85-96%). Pooled data from five ThyroSeq studies assessing 459 nodules showed sensitivity of 84% (74-91%), specificity 78% (50-92%), PPV 58% (31-81%), and NPV 93% (89-97%). When both tools were compared, GEC had a significantly higher sensitivity (p = 0.003), while ThyroSeq had a significantly higher specificity (p < 0.001) and accuracy (p = 0.015). Pooled LR+ was higher for ThyroSeq: 3.79 (1.40-10.27) vs. 1.12 (1.05-1.20). Pooled LR- was higher for GEC, 0.20 (0.10-0.39) vs. 0.13 (0.05-0.31). The bivariate summary estimates of sensitivity and specificity for GEC and ThyroSeq and their pooled accuracy showed a superiority of the ThyroSeq test. The GEC with a high sensitivity and NPV may be helpful in ruling out malignancy in cases of indeterminate thyroid nodule cytology. ThyroSeq has a significantly higher specificity and accuracy with an acceptable sensitivity so that it has the potential for use as an all-round test of malignancy of thyroid nodules.
Subject(s)
High-Throughput Nucleotide Sequencing , Molecular Diagnostic Techniques , Thyroid Neoplasms/diagnosis , Thyroid Nodule/diagnosis , Biopsy, Fine-Needle , Gene Expression , Humans , Sensitivity and Specificity , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Thyroid Nodule/genetics , Thyroid Nodule/pathologyABSTRACT
INTRODUCTION Diabetes mellitus and the postmenopausal period are associated with increased risk of urinary tract infections (UTIs) in women. However, data on UTIs in postmenopausal diabetic women are scarce. OBJECTIVES The aim of this study was to determine the prevalence of UTIs in postmenopausal women with type 2 diabetes mellitus, identify the potential risk factors, describe the causative pathogens, and assess their susceptibility to quinolones. PATIENTS AND METHODS Patients were interviewed, examined, and had their hospital records analyzed. An uncontaminated midstream urine sample was collected and cultured in selective or enriched media. Colonyforming units were counted and susceptibility to quinolones was assessed. Univariate and multivariate logistic regression models were built. RESULTS Forty women were included in this prospective crosssectional study; their median age was 64 years (range, 52-84 years). UTIs occurred in 37.5% of the patients. The major implicated pathogens were Escherichia coli (66.7%) and enterococci (20%; most often Enterococcus faecalis). Most of the pathogens (93.8%) were susceptible to all tested quinolones. Patients with UTIs had a significantly lower glomerular filtration rate (P = 0.008) and higher comorbidity index (P = 0.01) compared with patients with sterile urine. Microangiopathic complications, including retinopathy and nephropathy, were identified as independent risk factor for UTIs (adjusted odds ratio, 3.5; 95% CI, 1.2-5.5; P = 0.006). The other clinical correlates of UTIs were urinary incontinence, hyperlipidemia, and microalbuminuria. CONCLUSIONS Postmenopausal diabetic patients with microangiopathy are at high risk of UTIs and therefore should be educated and vigilantly monitored. Attention should also be paid to urinary incontinence, hyperlipidemia, and microalbuminuria as other risk factors for UTIs. Quinolones are an attractive treatment option in this group of patients in Poland.