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1.
Nature ; 601(7894): 573-578, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35082415

RESUMEN

Owing to rapid development in their efficiency1 and stability2, perovskite solar cells are at the forefront of emerging photovoltaic technologies. State-of-the-art cells exhibit voltage losses3-8 approaching the theoretical minimum and near-unity internal quantum efficiency9-13, but conversion efficiencies are limited by the fill factor (<83%, below the Shockley-Queisser limit of approximately 90%). This limitation results from non-ideal charge transport between the perovskite absorber and the cell's electrodes5,8,13-16. Reducing the electrical series resistance of charge transport layers is therefore crucial for improving efficiency. Here we introduce a reverse-doping process to fabricate nitrogen-doped titanium oxide electron transport layers with outstanding charge transport performance. By incorporating this charge transport material into perovskite solar cells, we demonstrate 1-cm2 cells with fill factors of >86%, and an average fill factor of 85.3%. We also report a certified steady-state efficiency of 22.6% for a 1-cm2 cell (23.33% ± 0.58% from a reverse current-voltage scan).

2.
Genes Chromosomes Cancer ; 63(1): e23207, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37787425

RESUMEN

Substantial progress has been made in understanding the molecular pathways associated with vascular tumors over the last two decades. In addition to mutations and copy number aberrations, fusions have emerged as significant contributors to the pathogenesis of a notable subset of vascular tumors. In this report, we present a case of an unusual intradermal vascular tumor with epithelioid cytomorphology. Immunohistochemistry revealed diffuse positivity for CD31, ERG and Factor VIII, supporting its endothelial lineage. RNA sequencing (ArcherFusion Plex) revealed the presence of an in-frame fusion between the genes TPM3 Exon 8 and ALK Exon 20. Immunohistochemistry confirmed ALK expression by the endothelial cells. To our knowledge, this is the first documented case of a vascular tumor harboring an ALK fusion. It may fall within the spectrum of epithelioid hemangiomas; nevertheless, we cannot definitively exclude the possibility of it being a distinct and potentially unique benign entity on its own.


Asunto(s)
Hemangioma , Neoplasias Cutáneas , Neoplasias Vasculares , Humanos , Quinasa de Linfoma Anaplásico/genética , Células Endoteliales/patología , Neoplasias Cutáneas/genética , Tropomiosina/genética
3.
Br J Haematol ; 205(1): 127-137, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38613141

RESUMEN

Histiocytic neoplasms are diverse clonal haematopoietic disorders, and clinical disease is mediated by tumorous infiltration as well as uncontrolled systemic inflammation. Individual subtypes include Langerhans cell histiocytosis (LCH), Rosai-Dorfman-Destombes disease (RDD) and Erdheim-Chester disease (ECD), and these have been characterized with respect to clinical phenotypes, driver mutations and treatment paradigms. Less is known about patients with mixed histiocytic neoplasms (MXH), that is two or more coexisting disorders. This international collaboration examined patients with biopsy-proven MXH with respect to component disease subtypes, oncogenic driver mutations and responses to conventional (chemotherapeutic or immunosuppressive) versus targeted (BRAF or MEK inhibitor) therapies. Twenty-seven patients were studied with ECD/LCH (19/27), ECD/RDD (6/27), RDD/LCH (1/27) and ECD/RDD/LCH (1/27). Mutations previously undescribed in MXH were identified, including KRAS, MAP2K2, MAPK3, non-V600-BRAF, RAF1 and a BICD2-BRAF fusion. A repeated-measure generalized estimating equation demonstrated that targeted treatment was statistically significantly (1) more likely to result in a complete response (CR), partial response (PR) or stable disease (SD) (odds ratio [OR]: 17.34, 95% CI: 2.19-137.00, p = 0.007), and (2) less likely to result in progression (OR: 0.08, 95% CI: 0.03-0.23, p < 0.0001). Histiocytic neoplasms represent an entity with underappreciated clinical and molecular diversity, poor responsiveness to conventional therapy and exquisite sensitivity to targeted therapy.


Asunto(s)
Enfermedad de Erdheim-Chester , Mutación , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Enfermedad de Erdheim-Chester/genética , Enfermedad de Erdheim-Chester/tratamiento farmacológico , Anciano , Adolescente , Terapia Molecular Dirigida , Adulto Joven , Histiocitosis de Células de Langerhans/genética , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Niño , Histiocitosis Sinusal/genética , Histiocitosis Sinusal/tratamiento farmacológico , Histiocitosis Sinusal/patología , Proteínas Proto-Oncogénicas B-raf/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Preescolar
4.
Genome Res ; 31(2): 225-238, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33361111

RESUMEN

Rootless plants in the genus Wolffia are some of the fastest growing known plants on Earth. Wolffia have a reduced body plan, primarily multiplying through a budding type of asexual reproduction. Here, we generated draft reference genomes for Wolffia australiana (Benth.) Hartog & Plas, which has the smallest genome size in the genus at 357 Mb and has a reduced set of predicted protein-coding genes at about 15,000. Comparison between multiple high-quality draft genome sequences from W. australiana clones confirmed loss of several hundred genes that are highly conserved among flowering plants, including genes involved in root developmental and light signaling pathways. Wolffia has also lost most of the conserved nucleotide-binding leucine-rich repeat (NLR) genes that are known to be involved in innate immunity, as well as those involved in terpene biosynthesis, while having a significant overrepresentation of genes in the sphingolipid pathways that may signify an alternative defense system. Diurnal expression analysis revealed that only 13% of Wolffia genes are expressed in a time-of-day (TOD) fashion, which is less than the typical ∼40% found in several model plants under the same condition. In contrast to the model plants Arabidopsis and rice, many of the pathways associated with multicellular and developmental processes are not under TOD control in W. australiana, where genes that cycle the conditions tested predominantly have carbon processing and chloroplast-related functions. The Wolffia genome and TOD expression data set thus provide insight into the interplay between a streamlined plant body plan and optimized growth.

5.
BMC Plant Biol ; 24(1): 577, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890560

RESUMEN

BACKGROUND: Seed retention is the basic prerequisite for seed harvest. However, only little breeding progress has been achieved for this trait in the major forage grasses. The aim of this study was to evaluate the potential of plant genetic resources of the important fodder grasses Festuca pratensis Huds. and Lolium perenne L. as source for seed retention in the breeding process. Furthermore, the morphology of the abscission zone, where shattering occurs, was studied on the cell tissue level in different developmental stages of contrasting accessions. RESULTS: 150 and 286 accessions of Festuca pratensis and Lolium perenne were screened for seed retention, respectively. Contrasting accessions were selected to be tested in a second year. We found a great variation in seed retention in Festuca pratensis and Lolium perenne, ranging from 13 to 71% (average: 35%) and 12 to 94% (average: 49%), respectively, in the first year. Seed retention was generally lower in the second year. Cultivars were within the accessions with highest seed retention in Festuca pratensis, but had lower seed retention than ecotypes in Lolium perenne. Field-shattered seeds had a lower thousand grain weight than retained seeds. Cell layers of the abscission zone appeared already in early seed stages and were nested within each other in accessions with high seed retention, while there were two to three superimposed layers in accessions with low seed retention. CONCLUSIONS: Plant genetic resources of Lolium perenne might be a valuable source for breeding varieties with high seed retention. However, simultaneous selection for high seed weight is necessary for developing successful commercial cultivars.


Asunto(s)
Festuca , Lolium , Fenotipo , Semillas , Lolium/crecimiento & desarrollo , Lolium/genética , Lolium/anatomía & histología , Festuca/genética , Festuca/crecimiento & desarrollo , Festuca/anatomía & histología , Semillas/crecimiento & desarrollo , Semillas/genética , Semillas/anatomía & histología
6.
Plant Cell ; 33(10): 3207-3234, 2021 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-34273173

RESUMEN

The aquatic Lemnaceae family, commonly called duckweed, comprises some of the smallest and fastest growing angiosperms known on Earth. Their tiny size, rapid growth by clonal propagation, and facile uptake of labeled compounds from the media were attractive features that made them a well-known model for plant biology from 1950 to 1990. Interest in duckweed has steadily regained momentum over the past decade, driven in part by the growing need to identify alternative plants from traditional agricultural crops that can help tackle urgent societal challenges, such as climate change and rapid population expansion. Propelled by rapid advances in genomic technologies, recent studies with duckweed again highlight the potential of these small plants to enable discoveries in diverse fields from ecology to chronobiology. Building on established community resources, duckweed is reemerging as a platform to study plant processes at the systems level and to translate knowledge gained for field deployment to address some of society's pressing needs. This review details the anatomy, development, physiology, and molecular characteristics of the Lemnaceae to introduce them to the broader plant research community. We highlight recent research enabled by Lemnaceae to demonstrate how these plants can be used for quantitative studies of complex processes and for revealing potentially novel strategies in plant defense and genome maintenance.


Asunto(s)
Araceae/genética , Genoma de Planta , Genómica
7.
J Am Acad Dermatol ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38704032

RESUMEN

Extramammary Paget disease (EMPD) is a rare skin cancer of apocrine-rich skin that mimics common inflammatory and infectious dermatoses, leading to delays in diagnosis and increased patient morbidity. Better clinical recognition of this entity, multidisciplinary patient assessment, and deeper understanding of the underlying pathophysiology are essential to improve patient care and disease outcomes. It is important to distinguish primary intraepithelial/micro-invasive EMPD from invasive EMPD or cases with adenocarcinoma arising within EMPD. This 2-part continuing medical education series provides a complete picture of EMPD. Part 1 of this continuing medical education series reviews the epidemiology, oncogenesis, clinical and histopathologic presentation, workup, and prognosis of this rare cancer.

8.
J Am Acad Dermatol ; 90(1): 52-57, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37634737

RESUMEN

BACKGROUND: Lentigo maligna (LM) can mimic benign, flat, pigmented lesions and can be challenging to diagnose. OBJECTIVE: To describe a new dermatoscopic feature termed "perifollicular linear projections (PLP)" as a diagnostic criterion for LM on the face. METHODS: Retrospective study on reflectance confocal microscopy and dermatoscopy images of flat facial pigmented lesions originating from 2 databases. PLP were defined as short, linear, pigmented projections emanating from hair follicles. Dermatoscopy readers were blinded to the final histopathologic diagnosis. RESULTS: From 83 consecutive LMs, 21/83 (25.3%) displayed "bulging of hair follicles" on reflectance confocal microscopy and 18 of these 21 (85.7%), displayed PLP on dermatoscopy. From a database of 2873 consecutively imaged and biopsied lesions, 252 flat-pigmented facial lesions were included. PLP was seen in 47/76 melanomas (61.8%), compared with 7/176 lesions (3.9%) with other diagnosis (P < .001). The sensitivity was 61.8% (95% CI, 49.9%-72.7%), specificity 96.0% (95% CI, 92.9%-98.4%). PLP was independently associated with LM diagnosis on multivariate analysis (OR 26.1 [95% CI, 9.6%-71.0]). LIMITATIONS: Retrospective study. CONCLUSION: PLP is a newly described dermatoscopic criterion that may add specificity and sensitivity to the early diagnosis of LM located on the face. We postulate that PLP constitutes an intermediary step in the LM progression model.


Asunto(s)
Peca Melanótica de Hutchinson , Melanoma , Neoplasias Cutáneas , Humanos , Peca Melanótica de Hutchinson/diagnóstico por imagen , Peca Melanótica de Hutchinson/patología , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Estudios Retrospectivos , Diagnóstico Diferencial , Melanoma/patología , Microscopía Confocal/métodos , Dermoscopía/métodos
9.
J Cutan Pathol ; 51(3): 226-229, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38088454

RESUMEN

Porocarcinomas are rare sweat gland cancers representing the malignant counterpart to benign poromas. Their diagnosis can be challenging, especially in the absence of an associated poroma or when the tumor is poorly differentiated. Since recurrent YAP1::MAML2 and YAP1::NUTM1 fusions have been identified in poroid tumors, molecular studies provide an opportunity to support the diagnosis in challenging cases. We describe a case of a female patient in her early 90s, with a polypoid mass of the hip. Histopathologically, there was a poorly differentiated malignant spindle cell tumor adjacent to a poroma. Because of the close association with a poroma and immunoreactivity for p40, a diagnosis of spindle cell porocarcinoma was rendered, which was further supported by YAP1 immunohistochemical studies. Antibodies targeting both the N-terminus and C-terminus confirmed YAP1 rearrangement in both the poroma and the spindle cell neoplasm. Subsequent targeted RNA sequencing revealed a YAP1::MAML3 gene fusion. MAML3 has previously not yet been reported as a YAP1 fusion partner in porocarcinoma. With the illustration of a rare spindle cell variant of porocarcinoma and the identification of a novel gene fusion, this case report expands the spectrum of morphologic and genomic aberrations associated with porocarcinoma.


Asunto(s)
Porocarcinoma Ecrino , Poroma , Neoplasias de las Glándulas Sudoríparas , Femenino , Humanos , Porocarcinoma Ecrino/genética , Porocarcinoma Ecrino/patología , Poroma/patología , Neoplasias de las Glándulas Sudoríparas/genética , Neoplasias de las Glándulas Sudoríparas/patología , Transactivadores , Factores de Transcripción/genética , Anciano de 80 o más Años
10.
Am J Dermatopathol ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-39008470

RESUMEN

ABSTRACT: Melanocyte differentiation antigens refer to molecules expressed in cells of melanocytic lineage such as gp100/PMEL, tyrosinase, and Melan-A. Corresponding antibodies such as HMB45, T311, and A103 have become key immunohistochemical tools in surgical pathology for the diagnosis of pigmented and related lesions. Little is known about tyrosinase-related protein 1 (TRP1), another melanocyte differentiation antigen, which is an enzymatic component of melanogenesis and known as the brown locus in mice. In this study, we tested several commercial reagents to TRP1 and identified one clone, EPR13063, which we further characterized by testing its specificity and usefulness for surgical pathology. Subsequently, we analyzed the expression of TRP1 in panels of normal tissues and tumors. TRP1 is regularly expressed in normal skin and in cutaneous nevi predominantly present in junctional and to a lesser extent in dermal nevocytes. In melanoma, TRP1 is present in 100% and 44% of primary and metastatic melanomas, respectively. TRP1 was absent in 5 desmoplastic melanomas but heterogeneously present in 9 of 11 PEComas/angiomyolipomas. No TRP1 was found in neoplasms of nonmelanocytic lineage. We demonstrate that EPR13063 is a valuable reagent for the analysis of TRP1 expression in archival surgical pathology material. The TRP1 expression pattern in melanocytic and related lesions appears to parallel other melanocyte differentiation antigens with a higher incidence in primary and a lower incidence in metastatic melanomas.

11.
Eur Spine J ; 33(4): 1607-1616, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38367026

RESUMEN

PURPOSE: To evaluate feasibility, internal consistency, inter-rater reliability, and prospective validity of AO Spine CROST (Clinician Reported Outcome Spine Trauma) in the clinical setting. METHODS: Patients were included from four trauma centers. Two surgeons with substantial amount of experience in spine trauma care were included from each center. Two separate questionnaires were administered at baseline, 6-months and 1-year: one to surgeons (mainly CROST) and another to patients (AO Spine PROST-Patient Reported Outcome Spine Trauma). Descriptive statistics were used to analyze patient characteristics and feasibility, Cronbach's α for internal consistency. Inter-rater reliability through exact agreement, Kappa statistics and Intraclass Correlation Coefficient (ICC). Prospective analysis, and relationships between CROST and PROST were explored through descriptive statistics and Spearman correlations. RESULTS: In total, 92 patients were included. CROST showed excellent feasibility results. Internal consistency (α = 0.58-0.70) and reliability (ICC = 0.52 and 0.55) were moderate. Mean total scores between surgeons only differed 0.2-0.9 with exact agreement 48.9-57.6%. Exact agreement per CROST item showed good results (73.9-98.9%). Kappa statistics revealed moderate agreement for most CROST items. In the prospective analysis a trend was only seen when no concerns at all were expressed by the surgeon (CROST = 0), and moderate to strong positive Spearman correlations were found between CROST at baseline and the scores at follow-up (rs = 0.41-0.64). Comparing the CROST with PROST showed no specific association, nor any Spearman correlations (rs = -0.33-0.07). CONCLUSIONS: The AO Spine CROST showed moderate validity in a true clinical setting including patients from the daily clinical practice.


Asunto(s)
Traumatismos Vertebrales , Humanos , Reproducibilidad de los Resultados , Traumatismos Vertebrales/cirugía , Columna Vertebral , Encuestas y Cuestionarios , Medición de Resultados Informados por el Paciente
12.
BMC Bioinformatics ; 24(1): 355, 2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37735349

RESUMEN

BACKGROUND: Genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with kidney function. By combining these findings with post-GWAS information (e.g., statistical fine-mapping to identify independent association signals and to narrow down signals to causal variants; or different sources of annotation data), new hypotheses regarding physiology and disease aetiology can be obtained. These hypotheses need to be tested in laboratory experiments, for example, to identify new therapeutic targets. For this purpose, the evidence obtained from GWAS and post-GWAS analyses must be processed and presented in a way that they are easily accessible to kidney researchers without specific GWAS expertise. MAIN: Here we present KidneyGPS, a user-friendly web-application that combines genetic variant association for estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics consortium with annotation of (i) genetic variants with functional or regulatory effects ("SNP-to-gene" mapping), (ii) genes with kidney phenotypes in mice or human ("gene-to-phenotype"), and (iii) drugability of genes (to support re-purposing). KidneyGPS adopts a comprehensive approach summarizing evidence for all 5906 genes in the 424 GWAS loci for eGFR identified previously and the 35,885 variants in the 99% credible sets of 594 independent signals. KidneyGPS enables user-friendly access to the abundance of information by search functions for genes, variants, and regions. KidneyGPS also provides a function ("GPS tab") to generate lists of genes with specific characteristics thus enabling customizable Gene Prioritisation (GPS). These specific characteristics can be as broad as any gene in the 424 loci with a known kidney phenotype in mice or human; or they can be highly focussed on genes mapping to genetic variants or signals with particularly with high statistical support. KidneyGPS is implemented with RShiny in a modularized fashion to facilitate update of input data ( https://kidneygps.ur.de/gps/ ). CONCLUSION: With the focus on kidney function related evidence, KidneyGPS fills a gap between large general platforms for accessing GWAS and post-GWAS results and the specific needs of the kidney research community. This makes KidneyGPS an important platform for kidney researchers to help translate in silico research results into in vitro or in vivo research.


Asunto(s)
Estudio de Asociación del Genoma Completo , Insuficiencia Renal Crónica , Humanos , Animales , Ratones , Fenotipo , Riñón , Mapeo Cromosómico
13.
BMC Plant Biol ; 23(1): 68, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36721096

RESUMEN

BACKGROUND: Phosphorus (P) is an essential macronutrient required for plant metabolism and growth. Its acquisition by plants depends on the availability of dissolved P in the rhizosphere and on the characteristics of P uptake mechanisms such as root-system architecture (RSA). Compared to other crops, potato (Solanum tuberosum L.) has a relatively poor P acquisition efficiency. This is mainly due to its shallow and sparsely branched root system, resulting in a rather limited exploitable soil volume. Information about potato genotypes with RSA traits suitable to improve adaptation to nutrient scarcity is quite rare. Aim of this study is to assess phenotypic variation of RSA in a potato diversity set and its reactions to P deficiency. RESULTS: Only one out of 22 RSA-traits showed a significant increase under low-P conditions. This indicates an overall negative effect of P scarcity on potato root growth. Differences among genotypes, however, were statistically significant for 21 traits, revealing a high variability in potato RSA. Using a principal component analysis (PCA), we were able to classify genotypes into three groups with regard to their root-system size. Genotypes with both small and large root systems reacted to low-P conditions by in- or decreasing their relative root-system size to medium, whereas genotypes with an intermediate root system size showed little to no changes. CONCLUSIONS: We observed a huge variation in both the potato root system itself and its adaptation to P deficiency. This may enable the selection of potato genotypes with an improved root-zone exploitation. Eventually, these could be utilized to develop new cultivars adapted to low-P environments with better resource-use efficiencies.


Asunto(s)
Solanum tuberosum , Solanum tuberosum/genética , Genotipo , Fenotipo , Aclimatación , Variación Biológica Poblacional
14.
Mod Pathol ; 36(8): 100165, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36990277

RESUMEN

The distinction between undifferentiated melanoma (UM) or dedifferentiated melanoma (DM) from undifferentiated or unclassifiable sarcoma can be difficult and requires the careful correlation of clinical, pathologic, and genomic findings. In this study, we examined the utility of mutational signatures to identify patients with UM/DM with particular attention as to whether this distinction matters for treatment because the survival of patients with metastatic melanoma has dramatically improved with immunologic therapy, whereas durable responses are less frequent in sarcomas. We identified 19 cases of UM/DM that were initially reported as unclassified or undifferentiated malignant neoplasm or sarcoma and submitted for targeted next-generation sequencing analysis. These cases were confirmed as UM/DM by harboring melanoma driver mutations, UV signature, and high tumor mutation burden. One case of DM showed melanoma in situ. Meanwhile, 18 cases represented metastatic UM/DM. Eleven patients had a prior history of melanoma. Thirteen of 19 (68%) of the tumors were immunohistochemically completely negative for 4 melanocytic markers (S100, SOX10, HMB45, and MELAN-A). All cases harbored a dominant UV signature. Frequent driver mutations involved BRAF (26%), NRAS (32%), and NF1 (42%). In contrast, the control cohort of undifferentiated pleomorphic sarcomas (UPS) of deep soft tissue exhibited a dominant aging signature in 46.6% (7/15) without evidence of UV signature. The median tumor mutation burden for DM/UM vs UPS was 31.5 vs 7.0 mutations/Mb (P < .001). A favorable response to immune checkpoint inhibitor therapy was observed in 66.6% (12/18) of patients with UM/DM. Eight patients exhibited a complete response and were alive with no evidence of disease at the last follow-up (median 45.5 months). Our findings support the usefulness of the UV signature in discriminating DM/UM vs UPS. Furthermore, we present evidence suggesting that patients with DM/UM and UV signatures can benefit from immune checkpoint inhibitor therapy.


Asunto(s)
Histiocitoma Fibroso Maligno , Melanoma , Neoplasias Primarias Secundarias , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Melanoma/genética , Melanoma/terapia , Melanoma/patología , Sarcoma/genética , Sarcoma/terapia , Sarcoma/patología , Biomarcadores de Tumor/genética , Inmunoterapia , Mutación , Melanoma Cutáneo Maligno
15.
J Am Acad Dermatol ; 88(2): 371-379, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-31812621

RESUMEN

BACKGROUND: Lentigo maligna/lentigo maligna melanoma (LM/LMM) can present with subclinical extension that may be difficult to define preoperatively and lead to incomplete excision and potential recurrence. Preliminarily studies have used reflectance confocal microscopy (RCM) to assess LM/LMM margins. OBJECTIVE: To evaluate the correlation of LM/LMM subclinical extension defined by RCM compared with the gold standard histopathology. METHODS: Prospective study of LM/LMM patients referred for dermatologic surgery. RCM was performed at the clinically defined initial surgical margin followed by margin-controlled staged excision with paraffin-embedded tissue, and histopathology was correlated with RCM results. RESULTS: Seventy-two patients were included. Mean age was 66.8 years (standard deviation, 11.1; range, 38-89); 69.4% were men. Seventy of 72 lesions (97.2%) were located on the head and neck with mean largest clinical diameter of 1.3 cm (range, 0.3-5). Diagnostic accuracy for detection of residual melanoma in the tumor debulk (after biopsy) had a sensitivity of 96.7% and a specificity of 66.7% when compared with histopathology. RCM margin assessment revealed an overall agreement with final histopathology of 85.9% (κ = 0.71; P < .001). LIMITATIONS: No RCM imaging beyond initial planned margins was performed. CONCLUSION: RCM showed moderate to excellent overall agreement between RCM imaging of LM/LMM and histopathology of staged excision margins.


Asunto(s)
Peca Melanótica de Hutchinson , Melanoma , Neoplasias Cutáneas , Masculino , Humanos , Anciano , Femenino , Peca Melanótica de Hutchinson/diagnóstico por imagen , Peca Melanótica de Hutchinson/cirugía , Peca Melanótica de Hutchinson/patología , Estudios Prospectivos , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología , Melanoma/diagnóstico por imagen , Melanoma/cirugía , Melanoma/patología , Márgenes de Escisión , Microscopía Confocal/métodos
16.
Dermatol Surg ; 49(8): 747-754, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37235869

RESUMEN

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) of the ear is associated with poor outcomes. No studies have evaluated current staging system performance in this specific location. OBJECTIVE: Describe clinicopathologic characteristics and outcomes of ear cSCC and evaluate the performance of current staging systems. METHODS: Retrospective study including cases diagnosed and treated at a cancer center from January 2000 to December 2014. Demographic, clinical, and pathologic data were collected from clinical records. Biopsy slides were rereviewed and patients were staged according to the American Joint Committee on Cancer (AJCC) seventh, eighth, and Brigham Women's Hospital (BWH) staging. RESULTS: Of 125 patients, the mean age at diagnosis was 71.9 years (SD 12.5), with most men (89.6%, n = 112). Median follow-up was 22.3 months. Local recurrence and survival risk factors were similar to cSCC outside the ear. The Akaike's Information Criterion (AIC) estimates showed that the BWH system better predicted outcomes than the AJCC seventh, and the AJCC eighth, with AIC values of 189.9, 270.5, and 274.1, respectively. Limitations of the study include retrospective design, single center study, and no control group. CONCLUSION: Current staging systems perform well at stratifying risk in ear cSCC.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias del Oído , Neoplasias Cutáneas , Masculino , Humanos , Femenino , Anciano , Carcinoma de Células Escamosas/patología , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Estadificación de Neoplasias , Factores de Riesgo , Neoplasias del Oído/patología , Pronóstico
17.
Am J Dermatopathol ; 45(11): 733-747, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37856737

RESUMEN

ABSTRACT: Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen first identified in a melanoma patient and found to be expressed in most melanomas as well as in variable levels in other malignant neoplasms of epithelial, mesenchymal, or hematolymphoid lineage. Detection of PRAME expression in formalin-fixed paraffin-embedded tissue is possible by immunohistochemistry (IHC) with commercially available monoclonal antibodies. In situ and invasive melanoma frequently show a diffuse pattern of nuclear PRAME immunoreactivity which contrasts with the infrequent and typically nondiffuse staining seen in nevi. In many challenging melanocytic tumors, results of PRAME IHC and other ancillary tests correlate well, but not always: The tests are not interchangeable. Most metastatic melanomas are positive for PRAME, whereas nodal nevi are not. Numerous studies on PRAME IHC have become available in the past few years with results supporting the value of PRAME IHC as an ancillary tool in the evaluation of melanocytic lesions and providing insights into limitations in sensitivity and specificity as well as possible pitfalls that need to be kept in mind by practicing pathologists.


Asunto(s)
Melanoma , Nevo , Neoplasias Cutáneas , Humanos , Antígenos de Neoplasias , Biomarcadores de Tumor/metabolismo , Inmunohistoquímica , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Nevo/diagnóstico , Nevo/genética , Nevo/metabolismo , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Factores de Transcripción , Melanoma Cutáneo Maligno
18.
Am J Dermatopathol ; 45(7): 437-447, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37338065

RESUMEN

ABSTRACT: Proliferative nodules (PNs) are benign melanocytic proliferations that typically develop within congenital melanocytic nevi. These tumors have overlapping histological features with melanoma. Ancillary immunohistochemistry and genomic sequencing are often used in diagnostically challenging cases. To assess the utility of preferentially expressed antigen in melanoma (PRAME) immunoreactivity and telomerase reverse transcriptase (TERT) promoter mutation analysis in distinguishing PNs from melanoma arising in congenital nevi cases. Twenty-one PNs and 2 melanomas arising in congenital nevi were immunohistochemically stained with PRAME. Cases with adequate tissue were also assessed for TERT promoter mutations through sequencing studies. The positivity rates in the PN cases were compared with those of the melanomas. Two of 21 PN cases were diffusely positive for PRAME (≥75% of the tumor cells positive). Two of 2 melanomas arising in congenital nevus cases were also diffusely PRAME positive. The difference was statistically significant using a Fisher exact test. None of the tumors harbored TERT promoter mutations. PRAME immunohistochemical marker may have diagnostic value in distinguishing diagnostically challenging PNs from melanoma, but diffuse expression is not specific for melanoma.


Asunto(s)
Melanoma , Nevo de Células Epitelioides y Fusiformes , Nevo Pigmentado , Neoplasias Cutáneas , Telomerasa , Humanos , Nevo Pigmentado/diagnóstico , Nevo Pigmentado/genética , Nevo Pigmentado/congénito , Biomarcadores de Tumor/análisis , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Diagnóstico Diferencial , Telomerasa/genética , Antígenos de Neoplasias/análisis
19.
Eur Spine J ; 32(6): 2120-2130, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37031293

RESUMEN

PURPOSE: The AO Spine PROST (Patient Reported Outcome Spine Trauma) was developed for people with spine trauma and minor or no neurological impairment. The purpose is to investigate health professionals' perspective on the applicability of the AO Spine PROST for people with motor-complete traumatic or non-traumatic spinal cord injury (SCI), using a discussion meeting and international survey study. METHODS: A discussion meeting with SCI rehabilitation physicians in the Netherlands was performed, followed by a worldwide online survey among the AO Spine International community, involved in the care of people with SCI. Participants rated the comprehensibility, relevance, acceptability, feasibility and completeness of the AO Spine PROST on a 1-5 point scale (5 most positive). Comments could be provided per question. RESULTS: The discussion meeting was attended by 13 SCI rehabilitation physicians. The survey was completed by 196 participants. Comprehensibility (mean ± SD: 4.1 ± 0.8), acceptability (4.0 ± 0.8), relevance (3.9 ± 0.8), completeness (3.9 ± 0.8), and feasibility (4.1 ± 0.7) of the AO Spine PROST were rated positively for use in people with motor-complete traumatic or non-traumatic SCI. Only a few participants questioned the relevance of items on the lower extremities (e.g., walking) or missed items on pulmonary functioning and complications. Some recommendations were made for improvement in instructions, terminology and examples of the tool. CONCLUSION: Health professionals found the AO Spine PROST generally applicable for people with motor-complete traumatic or non-traumatic SCI. This study provides further evidence for the use of the AO Spine PROST in spine trauma care, rehabilitation and research, as well as suggestions for its further development.


Asunto(s)
Traumatismos de la Médula Espinal , Traumatismos Vertebrales , Humanos , Transferencia Intrafalopiana del Cigoto , Columna Vertebral , Traumatismos de la Médula Espinal/cirugía , Medición de Resultados Informados por el Paciente
20.
Eur Spine J ; 32(5): 1525-1535, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36595136

RESUMEN

AIM: Osteoporotic thoracolumbar fractures are of increasing importance. To identify the optimal treatment strategy this multicentre prospective cohort study was performed. PURPOSE: Patients suffering from osteoporotic thoracolumbar fractures were included. Excluded were tumour diseases, infections and limb fractures. Age, sex, trauma mechanism, OF classification, OF-score, treatment strategy, pain condition and mobilization were analysed. METHODS: A total of 518 patients' aged 75 ± 10 (41-97) years were included in 17 centre. A total of 174 patients were treated conservatively, and 344 were treated surgically, of whom 310 (90%) received minimally invasive treatment. An increase in the OF classification was associated with an increase in both the likelihood of surgery and the surgical invasiveness. RESULTS: Five (3%) complications occurred during conservative treatment, and 46 (13%) occurred in the surgically treated patients. 4 surgical site infections and 2 mechanical failures requested revision surgery. At discharge pain improved significantly from a visual analogue scale score of 7.7 (surgical) and 6.0 (conservative) to a score of 4 in both groups (p < 0.001). Over the course of treatment, mobility improved significantly (p = 0.001), with a significantly stronger (p = 0.007) improvement in the surgically treated patients. CONCLUSION: Fracture severity according to the OF classification is significantly correlated with higher surgery rates and higher invasiveness of surgery. The most commonly used surgical strategy was minimally invasive short-segmental hybrid stabilization followed by kyphoplasty/vertebroplasty. Despite the worse clinical conditions of the surgically treated patients both conservative and surgical treatment led to an improved pain situation and mobility during the inpatient stay to nearly the same level for both treatments.


Asunto(s)
Fracturas por Compresión , Cifoplastia , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Vertebroplastia , Humanos , Estudios Prospectivos , Pacientes Internos , Fracturas de la Columna Vertebral/cirugía , Fracturas de la Columna Vertebral/etiología , Fracturas por Compresión/cirugía , Fracturas Osteoporóticas/cirugía , Vertebroplastia/métodos , Cifoplastia/métodos , Dolor/etiología , Resultado del Tratamiento , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/cirugía , Vértebras Torácicas/lesiones
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