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Current literature lacks data regarding the influence of serous fluid volume (SFV) on next-generation sequencing (NGS) performed on malignant cases. In this study, we highlight the impact of SFV and other parameters influencing the outcome of NGS analysis. We evaluated 827 samples of serous fluids from 607 patients. Of these, 72 samples underwent NGS analysis. Effusion volume, tumor cellularity, DNA, and RNA quality metrics, as well as clinicopathologic and molecular data were evaluated. Pleural fluid accounted for 56.3% of the fluid samples collected. The most common primary tumor site was gastrointestinal/pancreatobiliary, adenocarcinoma was the most common histologic type. Overall mean volume was 293 mL. The mean Qubit DNA of the 72 effusion samples that underwent NGS analysis was 14.3 ng/µL and mean Qubit RNA was 28.2 ng/µL. The mean Qubit DNA concentration increases in SFV up to 100 mL only. No correlation exists between SFV and mean tumor cellularity. In addition, 74.6% (50 of 67) of sequenced samples showed oncogenic drivers; KRAS was the most common driver followed by EGFR. Three cases displayed ALK fusions, and 1 case displayed NTRK1 fusion. The DNA yield is higher in SFV of 100 mL as a cutoff. Beyond 100 mL, there is no impact of SFV on DNA yield. SFV does not impact RNA yield and mean tumor cellularity. Effusion samples should be submitted for molecular testing despite low tumor cellularity. Our results as a pilot study are important in optimization of SFV for both diagnosis as well as NGS analysis for improving management.
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IDH1 and IDH2 mutational status is a critical biomarker with diagnostic, prognostic, and treatment implications in glioma. Although IDH1 p.R132H-specific immunohistochemistry is available, it is unable to identify other mutations in IDH1/2. Next-generation sequencing can accurately determine IDH1/2 mutational status but suffers from long turnaround time when urgent treatment planning and initiation is medically necessary. The Idylla assay can detect IDH1/2 mutational status from unstained formalin-fixed paraffin-embedded (FFPE) slides in as little as a few hours. In a clinical validation, we demonstrate clinical accuracy of 97% compared to next-generation sequencing. Sensitivity studies demonstrated a limit of detection of 2.5-5% variant allele frequency, even at DNA inputs below the manufacturer's recommended threshold. Overall, the assay is an effective and accurate method for rapid determination of IDH1/2 mutational status.
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Neoplasias Encefálicas , Glioma , Isocitrato Desidrogenase , Mutação , Humanos , Isocitrato Desidrogenase/genética , Glioma/genética , Glioma/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/enzimologia , Análise Mutacional de DNA/métodos , Inclusão em Parafina , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Sequenciamento de Nucleotídeos em Larga Escala , Formaldeído , Fixação de Tecidos/métodos , Reprodutibilidade dos TestesRESUMO
Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.
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Ensaios Clínicos como Assunto , Consenso , Técnica Delphi , Rosácea , Rosácea/terapia , Rosácea/diagnóstico , Humanos , Ensaios Clínicos como Assunto/normas , Avaliação de Resultados em Cuidados de Saúde/normas , Resultado do TratamentoRESUMO
OBJECTIVES: Few cytologically indeterminate thyroid fine-needle aspirations (FNAs) harbor BRAF V600E. Here, we assess interobserver agreement for The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III (atypia of undetermined significance [AUS]) FNAs harboring BRAF V600E and contrast their features with those harboring non-BRAF V600E alterations, with attention to cytopathology experience. METHODS: Seven reviewers evaluated 5 AUS thyroid FNAs harboring BRAF V600E. To blind reviewers, cases were intermixed with 19 FNAs falling within other TBSRTC categories and in which genetic alterations other than BRAF V600E had been identified (24 FNAs total). Interobserver agreement against both "index" and most popular ("mode") diagnoses was calculated. Four additional BRAF V600E cases were independently reviewed. RESULTS: Reviewers included 3 trainees and 3 American Board of Pathology (board)-certified cytopathologists. Board-certified cytopathologists, whose experience ranged from 2 to more than 15 subspecialty practice years, had known AUS rates. BRAF V600E was identified in 5 of 260 (2%) AUS FNAs. Interobserver agreement was higher among cytopathologists with more experience. Mode diagnosis differed from index diagnosis in 6 of 11 cases harboring RAS-like alterations; mode diagnosis was AUS in 4 of 5 BRAF V600E FNAs. CONCLUSIONS: Atypia of undetermined significance of thyroid FNAs harboring BRAF V600E is uncommon yet relatively reproducible, particularly among pathologists with experience. It is advisable to sequence BRAF across V600 in such cases.
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BACKGROUND: Chromosomal rearrangements that result in oncogenic fusions can hold tremendous clinical significance in solid tumors, often with diagnostic or treatment implications. CONTENT: Traditionally, low-throughput methods such as fluorescence in situ hybridization were used to identify fusions in the clinical laboratory. With the rise of next-generation sequencing techniques and the broad adoption of comprehensive genomic profiling, the practice of screening for fusions as part of an oncologic workup has evolved. RNA sequencing methods are increasingly used, as these comprehensive high-throughput assays have many advantages over traditional techniques. Several RNA sequencing platforms are available, each with benefits and drawbacks. Regardless of the approach, systematic evaluation of the RNA sequencing results and the fusions identified by the assay should be performed. Assessment of fusion events relies upon evaluation of quality evidence, structural evidence, and functional evidence to ensure accurate fusion reporting and interpretation. SUMMARY: Given the clinical significance of gene fusions in oncology, understanding the variety of assays available for fusion detection, their benefits and drawbacks, and how they are used in the identification and interpretation of gene fusions is important for the modern precision oncology practice.
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Neoplasias , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Hibridização in Situ Fluorescente/métodos , Medicina de Precisão , Sequenciamento de Nucleotídeos em Larga Escala/métodosRESUMO
OBJECTIVES: Afirma has recently introduced its Xpression Atlas (XA) as an adjunct to its Genomic Sequencing Classifier (GSC) for risk stratification of cytologically indeterminate thyroid nodules. We evaluated the performance of Afirma XA and associated pathologic findings for Afirma GSC suspicious nodules. METHODS: Intradepartmental records of thyroid fine-needle aspirations (FNAs) from January 2021 to December 2022 were identified and reviewed for patient and nodule characteristics, FNA findings, molecular test results, and final surgical pathology, if available. RESULTS: Material for Afirma GSC testing was collected in 624 thyroid FNAs, and 148 (24%) were classified as cytologically indeterminate. Afirma GSC testing was successful in 132 (89%) of those cases, of which 35 (27%) were Afirma GSC suspicious. Afirma XA testing was positive in 11 cases (11/35 [31%]). Eight (73%) patients underwent surgery that revealed 7 patients with papillary thyroid carcinoma and 1 patient with noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) (risk of malignancy: 100% [8/8]). Among the 24 patients with negative Afirma XA results, 19 (79%) underwent surgery, revealing 5 patients with malignancy and 3 patients with NIFTP (risk of malignancy: 42% [8/19]). Overall, the risk of malignancy for Afirma GSC suspicious nodules was 59% (16/27). CONCLUSIONS: Afirma XA improved risk stratification of thyroid disease with a high risk of malignancy in Afirma GSC suspicious nodules. A negative Afirma XA result, however, should not be used as a rule-out test.
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Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Biópsia por Agulha Fina , Adulto , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Idoso , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/diagnóstico , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/cirurgia , Genômica , Estudos RetrospectivosRESUMO
BACKGROUND: There is a paucity of studies assessing awareness and prevention of skin cancer among Chinese populations. OBJECTIVE: The aim of the study is to compare attitudes and practices regarding skin cancer risks and prevention between Chinese Asian and North American Chinese populations and between Fitzpatrick scores. METHODS: A cross-sectional, internet-based, 74-question survey in Chinese was conducted focusing on Han Chinese participants internationally. The survey included Likert-type scales and multiple-choice questions. All participants were required to read Chinese and self-identify as being 18 years or older and Chinese by ethnicity, nationality, or descent. Participants were recruited on the internet over a 6-month period from July 2017 through January 2018 via advertisements in Chinese on popular social media platforms: WeChat, QQ, Weibo, Facebook, and Twitter. RESULTS: Of the 113 completed responses collected (participation rate of 65.7%), 95 (84.1%) were ethnically Han Chinese, of which 93 (96.9%) were born in China and 59 (62.1%) were female. The mean age of these 95 participants was 35.8 (SD 13.3) years; 72 (75.8%) participants were born after 1975. Few but more North American Chinese reported that Chinese Asian populations received annual skin checks (4/30, 4.2% vs 0/65, 0%; P=.009) and believed that their clinician provided adequate sun safety education (13/30, 43.3% vs 15/65, 23.1%; P=.04). Participants with higher Fitzpatrick scores less frequently received sun safety education from a clinician (4/34, 11.8% vs 22/61, 36.1%; P=.02). More participants with lower Fitzpatrick scores used sunscreen (41/61, 67.2% vs 16/34, 47.1%; P=.05), but alternative sun protection use rates are similar across groups. CONCLUSIONS: Cultural differences and Fitzpatrick scores can affect knowledge and practices with respect to sun protection and skin cancer among social media-using Chinese Asian and North American Chinese communities based on respondent demographics. Most participants in all groups understood that people of color have some risk of skin cancer, but >30% of all groups across regions and Fitzpatrick scores are unaware of current skin protection recommendations, receive insufficient sun safety education, and do not use sunscreen. Outreach efforts may begin broadly with concerted public and private efforts to train and fund dermatologists to perform annual total body skin exams and provide more patient education. They should spark community interest through mass media and empower Chinese people to perform self-examinations and recognize risks and risk mitigation methods.
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Herbarium collections shape our understanding of Earth's flora and are crucial for addressing global change issues. Their formation, however, is not free from sociopolitical issues of immediate relevance. Despite increasing efforts addressing issues of representation and colonialism in natural history collections, herbaria have received comparatively less attention. While it has been noted that the majority of plant specimens are housed in the Global North, the extent and magnitude of this disparity have not been quantified. Here we examine the colonial legacy of botanical collections, analysing 85,621,930 specimen records and assessing survey responses from 92 herbarium collections across 39 countries. We find an inverse relationship between where plant diversity exists in nature and where it is housed in herbaria. Such disparities persist across physical and digital realms despite overt colonialism ending over half a century ago. We emphasize the need for acknowledging the colonial history of herbarium collections and implementing a more equitable global paradigm for their collection, curation and use.
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Plantas , Humanos , Inquéritos e QuestionáriosRESUMO
Molecular alterations in PDGFRA are well-described as drivers of sporadic gastrointestinal stromal tumors (GISTs) and inflammatory fibroid polyps (IFPs). However, a small number of families with germline PDGFRA mutations in exons 12, 14, and 18 have been reported, forming the basis of an autosomal dominant inherited disorder with incomplete penetrance and variable expressivity, now referred to as PDGFRA-mutant syndrome or GIST-plus syndrome. Phenotypic manifestations of this rare syndrome include multiple gastrointestinal GISTS, IFPs, fibrous tumors, and other variable features. Herein, we report the case of a 58-year-old female who presented with a gastric GIST and numerous small intestinal IFPs, found to harbor a previously undescribed germline PDGFRA exon 15 p.G680R mutation. Somatic tumor testing was performed on the GIST, a duodenal IFP, and an ileal IFP utilizing a targeted next-generation sequencing panel, revealing additional and distinct secondary PDGFRA exon 12 somatic mutations in each of the 3 tumors. Our findings raise important considerations regarding mechanisms of tumor development in patients with underlying germline PDGFRA alterations and highlight the potential utility of expanding currently available germline and somatic testing panels to include exons outside the typical hotspot regions.
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Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Feminino , Humanos , Pessoa de Meia-Idade , Mutação em Linhagem Germinativa , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Mutação , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Receptores Proteína Tirosina Quinases , Éxons/genética , Proteínas Proto-Oncogênicas c-kitRESUMO
OBJECTIVE: Our aim was to summarize and evaluate the current quality of evidence regarding the efficacy of therapies for cutaneous psoriasis (PsO) in patients with psoriatic arthritis (PsA). METHODS: A literature search of MEDLINE, Embase, Cochrane Library databases, and conference abstracts was conducted to identify interventional randomized controlled trials in patients with PsA between February 2013 and December 2021. Studies were included if PsO outcomes included achieving at least 75% improvement in the Psoriasis Area and Severity Index and the blinded comparison period was ≥ 10 weeks. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was employed to assess quality of the evidence to inform and update the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations. RESULTS: A total of 116 studies and 36 abstracts identified in the initial search were screened. A total of 37 studies (40 treatment arms) met the criteria for final inclusion. Phosphodiesterase 4 inhibitors, Janus kinase inhibitors, and tyrosine kinase 2 inhibitors, interleukin 17 inhibitors (IL-17i), IL-12/23i, IL-23i, and tumor necrosis factor inhibitors (TNFi) had high-quality data broadly supporting the efficacy of each class for plaque PsO over placebo. Head-to-head studies with high-quality data supported both IL-17i and IL-23i over TNFi. CONCLUSION: Several pharmacologic therapeutic classes have high-quality evidence demonstrating efficacy for cutaneous PsO in the PsA population. The findings will be integrated into the 2021 GRAPPA treatment recommendations, intended to guide selection of a therapeutic class where efficacy in 1 or more cutaneous or musculoskeletal domains is required.
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Artrite Psoriásica , Psoríase , Humanos , Artrite Psoriásica/epidemiologia , Psoríase/tratamento farmacológico , Interleucina-12Assuntos
Procedimentos Cirúrgicos Dermatológicos , Complicações Pós-Operatórias , Humanos , Estudos de Casos e Controles , Fatores de Risco , Procedimentos Cirúrgicos Dermatológicos/efeitos adversos , Deiscência da Ferida Operatória/epidemiologia , Deiscência da Ferida Operatória/etiologia , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologiaRESUMO
Since the introduction of integrated histological and molecular diagnoses by the 2016 World Health Organization (WHO) Classification of Tumors of the Nervous System, an increasing number of molecular markers have been found to have prognostic significance in infiltrating gliomas, many of which have now become incorporated as diagnostic criteria in the 2021 WHO Classification. This has increased the applicability of targeted-next generation sequencing in the diagnostic work-up of neuropathology specimens and in addition, raises the question of whether targeted sequencing can, in practice, reliably replace older, more traditional diagnostic methods such as immunohistochemistry and fluorescence in-situ hybridization. Here, we demonstrate that the Oncomine Cancer Gene Mutation Panel v2 assay targeted-next generation sequencing panel for solid tumors is not only superior to IHC in detecting mutation in IDH1/2 and TP53 but can also predict 1p/19q co-deletion with high sensitivity and specificity relative to fluorescence in-situ hybridization by looking at average copy number of genes sequenced on 1p, 1q, 19p, and 19q. Along with detecting the same molecular data obtained from older methods, targeted-next generation sequencing with an RNA sequencing component provides additional information regarding the presence of RNA based alterations that have diagnostic significance and possible therapeutic implications. From this work, we advocate for expanded use of targeted-next generation sequencing over more traditional methods for the detection of important molecular alterations as a part of the standard diagnostic work up for CNS neoplasms.
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Glioma , Humanos , Glioma/diagnóstico , Glioma/genética , Glioma/patologia , Neuropatologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de RNA , DNARESUMO
PURPOSE: Clinical relevance thresholds and laboratory methods are poorly defined for MET amplification, a targetable biomarker across malignancies. EXPERIMENTAL DESIGN: The utility of next-generation sequencing (NGS) in assessing MET copy number alterations was determined in >50,000 solid tumors. Using fluorescence in situ hybridization as reference, we validated and optimized NGS analysis. RESULTS: Incorporating read-depth and focality analyses achieved 91% concordance, 97% sensitivity, and 89% specificity. Tumor heterogeneity, neoplastic cell proportions, and genomic focality affected MET amplification assessment. NGS methodology showed superiority in capturing overall amplification status in heterogeneous tumors and defining amplification focality among other genomic alterations. MET copy gains and amplifications were found in 408 samples across 23 malignancies. Total MET copy number inversely correlated with amplified segment size. High-level/focal amplification was enriched in certain genomic subgroups and associated with targeted therapy response. CONCLUSIONS: Leveraging our integrated bioinformatic approach, targeted therapy benefit was observed across diverse MET amplification contexts.
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Variações do Número de Cópias de DNA , Neoplasias , Humanos , Hibridização in Situ Fluorescente , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias/genética , GenômicaRESUMO
Genetic alterations in RET lead to activation of ERK and AKT signaling and are associated with hereditary and sporadic thyroid cancer and lung cancer. Highly selective RET inhibitors have recently entered clinical use after demonstrating efficacy in treating patients with diverse tumor types harboring RET gene rearrangements or activating mutations. In order to understand resistance mechanisms arising after treatment with RET inhibitors, we performed a comprehensive molecular and genomic analysis of a patient with RET-rearranged thyroid cancer. Using a combination of drug screening and proteomic and biochemical profiling, we identified an adaptive resistance to RET inhibitors that reactivates ERK signaling within hours of drug exposure. We found that activation of FGFR signaling is a mechanism of adaptive resistance to RET inhibitors that activates ERK signaling. Combined inhibition of FGFR and RET prevented the development of adaptive resistance to RET inhibitors, reduced cell viability, and decreased tumor growth in cellular and animal models of CCDC6-RET-rearranged thyroid cancer.
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Neoplasias Pulmonares , Neoplasias da Glândula Tireoide , Animais , Proteínas do Citoesqueleto/genética , Humanos , Neoplasias Pulmonares/patologia , Proteômica , Proteínas Proto-Oncogênicas c-ret/genética , Receptores de Fatores de Crescimento de Fibroblastos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genéticaRESUMO
BACKGROUND: Molecular testing (MT) of thyroid fine-needle aspiration (FNA)-derived genetic material is commonly used to assess malignancy risk for indeterminate cases. The Bethesda System for Reporting Thyroid Cytopathology (TBS) provides limited guidance for the appropriate use of category III (atypia of undetermined significance [AUS]). The authors combined MT with cytomorphology to monitor AUS diagnoses in a cytopathology laboratory. METHODS: Neoplasia-associated genetic alterations (NGAs) were determined by MT of preoperative FNA biopsies or resected malignancies and were categorized as BRAF V600E mutations, RAS-like mutations (HRAS, NRAS, or KRAS mutations or non-V600E BRAF mutations), or other mutations. RESULTS: Among 7382 thyroid FNA biopsies, the AUS rate was 9.3% overall and ranged from 4.3% to 24.2% among 6 cytopathologists (CPs) who evaluated >150 cases. The ratio of specimens falling into TBS category III to specimens falling into category VI (malignant) (the III:VI ratio) was 2.4 overall (range, 1.1-8.1), and the ratio of specimens falling into TBS categories III and IV (follicular neoplasm or suspicious for follicular neoplasm) combined (III+IV) to specimens falling into category VI (the [III+IV]:VI ratio) was 2.9 overall (range, 1.4-9.5). MT was performed on 588 cases from 560 patients (79% women) with a median age of 56 years (range, 8-89 years). BRAF V600E mutation was the most common (76% of cases) in TBS category VI and was rare (3%) in category III. RAS-like mutations were most common in TBS categories III (13%), IV (25%), and V (suspicious for malignancy) (17.5%). The NGA rate in AUS cases fell between 5% and 20% for 5 of 6 CPs and did not correlate with the III:VI ratio or the (III+IV):VI ratio. CONCLUSIONS: Lack of correlation between the NGA rate and easily calculable diagnostic ratios enables the calibration of diagnostic thresholds, even for CPs who have normal metrics. Specifically, calculation of the NGA rate and the III:VI ratio may allow individual CPs to determine whether they are overcalling or undercalling cases that other CPs might otherwise recategorize.
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Adenocarcinoma Folicular , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Mutação , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/patologia , Adulto JovemRESUMO
OBJECTIVES: Skin rejuvenation with radiofrequency has been a widely used treatment modality for the safe and efficient remodeling of the dermis and revision of textural irregularities, achieved with minimal downtime. The efficacy of fractional radiofrequency (FRF) specifically for acne scarring has not been widely established. The objective of this clinical trial was to establish the efficacy and safety of FRF for moderate to severe acne scarring in a wide range of Fitzpatrick skin types using two different applicator tips to deliver energy to the skin (80-pin of up to 124 mJ/pin and 160-pin of up to 62 mJ/pin). METHODS: Enrolled subjects received a series of three FRF treatments to the full face, each 4 weeks apart. A visual analog scale was utilized to assess pain of the treatment. Subject satisfaction questionnaires were completed at follow-up visits at 6 and 12 weeks post final treatment. Photographs were graded for change by three blinded evaluators using the Global Aesthetic Improvement Scale (GAIS). RESULTS: Image sets of 23 enrolled subjects were assessed by blinded evaluation, showing a statistically significant improvement (p = 0.009) from the baseline visit to the 12-week follow-up on the GAIS for acne scarring. Subject satisfaction was high with subjects giving an average satisfaction score of 3.27 ("satisfied") out of 4. Pain was "mild" as treatments were rated an average of 2.15 on a 10-point visual analog scale. The GAIS score of the 80-pin tip improved patients' acne scars treated with that applicator by 1.06 points and 0.85 for the 160-pin tip. Ninety-five percent (95.5%) of subjects reported either a mild, moderate, or significant improvement to their treatment area. Ninety-one percent of subjects reported that they would recommend the treatment to a friend. CONCLUSION: FRF produced a statistically significant improvement in acne scarring when assessed by independent blinded evaluators. No serious adverse events resulted from treatment by either applicator tip. Treatment pain was low and tolerable among subjects of all Fitzpatrick skin types. Subjects had high levels of satisfaction with the results.
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Acne Vulgar , Procedimentos de Cirurgia Plástica , Acne Vulgar/complicações , Cicatriz/etiologia , Cicatriz/patologia , Cicatriz/terapia , Humanos , Satisfação do Paciente , Estudos Prospectivos , Resultado do TratamentoRESUMO
Recently, the US Food and Drug Administration approved several targeted therapies directed against oncogenic fusions. One of the most effective such targeted therapies is Vitrakvi (larotrectinib), highly specific oral tropomyosin receptor kinase inhibitor indicated for the treatment of patients with any solid tumor harboring a fusion involving one of the neurotrophic receptor tyrosine kinase (NTRK) genes. Although several diagnostic approaches can be used to detect these NTRK fusions, RNA-based next-generation sequencing remains one of the most sensitive methods, as it can directly detect the transcribed end product of gene fusion at the mRNA level. In this study, performance characteristics of three RNA-based next-generation sequencing assays with distinct mechanisms and chemistries were investigated: anchored multiplex PCR, amplicon-based multiplex PCR, and hybrid capture-based enrichment method. Analytical sensitivity analysis shows that the amplicon-based multiplex PCR method has the lowest limit of detection. However, both hybrid-capture and anchored multiplex PCR methods can detect NTRK fusions with uncommon or novel fusion partners, which is challenging for the amplicon-based multiplex method. As for clinical sensitivity, all three methods were highly concordant in detecting NTRK fusions in patient samples. Additionally, they all presented equivalent high-level performance in specificity, suggesting that all three platforms can detect NTRK fusions in clinical samples with similar performance characteristics.
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Sequenciamento de Nucleotídeos em Larga Escala/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Fusão Oncogênica , Proteínas de Fusão Oncogênica/genética , RNA/genética , Receptores Proteína Tirosina Quinases/genética , Análise de Sequência de RNA/métodos , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Criança , Pré-Escolar , Feminino , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , RNA/isolamento & purificação , Neoplasias da Glândula Tireoide/patologia , Adulto JovemRESUMO
Field photographs of plant species are crucial for research and conservation, but the lack of a centralized database makes them difficult to locate. We surveyed 25 online databases of field photographs and found that they harboured only about 53% of the approximately 125,000 vascular plant species of the Americas. These results reflect the urgent need for a centralized database that can both integrate and complete the photographic record of the world's flora.
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Biodiversidade , Bases de Dados Factuais/estatística & dados numéricos , Geografia/estatística & dados numéricos , Fotografação/estatística & dados numéricos , Plantas , AméricaRESUMO
Gestational trophoblastic disease can lead to excess thyroid hormone release and rarely, thyroid storm. We present a case of complete molar pregnancy with hyperthyroidism that was not identified or treated before surgical evacuation of uterine contents. Untreated hyperthyroidism preoperatively led to unanticipated thyroid storm immediately after emergence from anesthesia. It is important for anesthesia providers to recognize the link between gestational trophoblastic disease and thyrotoxicosis, and appreciate the severe consequences than can occur if left untreated. Anesthesia providers should strongly consider preoperative consultation and treatment. Being prepared to treat intraoperative symptoms and thyroid storm is paramount.