RESUMEN
Peripheral ulcerative keratitis (PUK) is an inflammatory disease of the peripheral cornea, which may frequently be associated with several rare, but potentially life-threatening systemic diseases. The inflammatory pathogenesis of PUK results from humoral and cell-mediated inflammation. The diagnosis is usually based on the typical clinical findings and always requires detailed diagnostic testing to identify a potential systemic underlying disease. Treatment includes topical and systemic immunosuppressive and immunomodulatory therapeutic strategies and, in the event of impending or existing perforation, also various surgical interventions. PUK is a potentially blinding disease that initially affects the periphery, but, if left untreated, can lead to destruction of the entire cornea. Interdisciplinary diagnostic testing and therapy are crucial to preserve vision in the affected patients and reduce morbidity and mortality. The following article provides an overview of the pathophysiology, clinical findings, possible underlying systemic diseases, relevant differential diagnoses and therapeutic strategies.
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Úlcera de la Córnea , Inmunosupresores , Humanos , Diagnóstico Diferencial , Úlcera de la Córnea/diagnóstico , Úlcera de la Córnea/terapia , Úlcera de la Córnea/etiología , Inmunosupresores/uso terapéuticoRESUMEN
Giant cell arteritis (GCA) is the most common primary vasculitis and is associated with potential bilateral blindness. Neither clinical nor laboratory evidence is simple and unequivocal for this disease, which usually requires rapid and reliable diagnosis and therapy. The ophthalmologist should consider GCA with the following ocular symptoms: visual loss or visual field defects, transient visual disturbances (amaurosis fugax), diplopia, eye pain, or new onset head or jaw claudication. An immediate ophthalmological examination with slit lamp, ophthalmoscopy, and visual field, as well as color duplex ultrasound of the temporal artery should be performed. If there is sufficient clinical suspicion of GCA, corticosteroid therapy should be initiated immediately, with prompt referral to a rheumatologist/internist and, if necessary, temporal artery biopsy should be arranged. Numerous developments in modern imaging with colour duplex ultrasonography, MRI, and PET-CT have the potential to compete with the classical, well-established biopsy of a temporal artery. Early determination of ESR and CRP may support RZA diagnosis. Therapeutically, steroid-sparing immunosuppression with IL-6 blockade or methotrexate can be considered. These developments have led to a revision of both the classification criteria and the diagnostic and therapeutic recommendations of the American College of Rheumatologists and the European League against Rheumatism, which are summarised here for ophthalmology.
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Arteritis de Células Gigantes , Arteritis de Células Gigantes/diagnóstico , Arteritis de Células Gigantes/tratamiento farmacológico , Arteritis de Células Gigantes/terapia , Humanos , Diagnóstico Diferencial , Corticoesteroides/uso terapéutico , Inmunosupresores/uso terapéutico , Arterias Temporales/patología , Arterias Temporales/diagnóstico por imagen , Medicina Basada en la Evidencia , Resultado del Tratamiento , BiopsiaRESUMEN
Endogenous endophthalmitis represents an ophthalmological emergency requiring immediate diagnostics and treatment. Pathogens should be detected using appropriate methods, such as the Freiburg endophthalmitis set. In bacterial endophthalmitis both Gram-positive and Gram-negative bacteria can be detected. Frequent underlying sources include endocarditis, gastrointestinal or urogenital surgery, indwelling venous catheters, liver abscesses, skin or soft tissue infections, meningitis or less commonly, intravenous drug abuse. The treatment consists of systemic and intraocular administration of antibiotics and vitrectomy. Systemic or intraocular corticosteroids can additionally be considered.
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Endoftalmitis , Infecciones Bacterianas del Ojo , Humanos , Antibacterianos/uso terapéutico , Bacterias Gramnegativas , Bacterias Grampositivas , Infecciones Bacterianas del Ojo/diagnóstico , Endoftalmitis/diagnóstico , BacteriasRESUMEN
BACKGROUND: Endogenous endophthalmitis results from hematogenous spread of bacterial or fungal infection in severely diseased patients. Specific systemic and intraocular therapy is required. The basis for this treatment is causal pathogen detection in blood culture or vitreous sample. However, functional results are limited. OBJECTIVE: The current article provides practical hints for surgical therapy and pathogen detection in patients with endogenous endophthalmitis. METHODS: A retrospective analysis of anonymous data of 68 male and female patients from 2018-2023 from five ophthalmology clinics in Germany was performed. RESULTS: Mean age of affected patients was 71.4 years (31-96 years). Surgical therapy included pars plana vitrectomy (ppV) and intravitreal injection (IVOM). In 44 of 68 patients (65%), 1-3 surgeries were performed, 4-6 surgeries were required in 14/68 (21%) of patients, and 10 or more surgeries were required in 4/68 patients (6%). Pathogen detection was possible in 34% of vitreous specimens and in 11% of anterior chamber samples. Mean initial visual acuity was logMAR 1.5. After treatment and a mean follow-up of 2.5 months, mean visual acuity was logMAR 1.3. Preanalytical methods for specimen collection like the Freiburg endophthalmitis set to optimize pathogen detection are presented. CONCLUSION: Severe inflammatory intraocular reactions in endogenous endophthalmitis necessitate a combination of ppV and repeated IVOM. In addition to providing a vitreous sample, ppV also serves to remove inflammatory fibrin membranes. Early pars plana vitrectomy with specific antibiotic or antifungal therapy should be sought in addition to the focus search and systemic therapy.
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Endoftalmitis , Infecciones Fúngicas del Ojo , Humanos , Masculino , Femenino , Anciano , Estudios Retrospectivos , Infecciones Fúngicas del Ojo/diagnóstico , Endoftalmitis/diagnóstico , Vitrectomía/efectos adversos , HospitalesRESUMEN
PURPOSE: To evaluate the efficacy of XEN®-45 gel stent ab interno implantation for medically uncontrolled uveitic glaucoma. METHODS: Retrospective analysis of 25 eyes receiving XEN® gel stent for medically uncontrolled uveitic glaucoma from February 2019 to February 2023 with recording of intraocular pressure (IOP) values, ocular hypotensive medication, requirement for revision or secondary surgery and complications. Prerequisites for XEN® implantation were a clear cornea, an open iridocorneal angle and an unscarred, mobile conjunctiva at the implantation site. Minimum follow-up required for inclusion was 3 months. The primary outcome measure was IOP compared to baseline. Complete and qualified success were defined as final IOP of ≤ 18 mmHg without or with topical antiglaucomatous treatment, respectively. Failure was defined as IOP > 18 mmHg on two consecutive visits, IOP reduction < 20%, persisting complications from hypotony and open conjunctival bleb revision. Further glaucoma surgical intervention was defined as complete failure. RESULTS: Mean preoperative IOP was 35.3 ± 10.9 mmHg on 2.9 ± 0.9 topical antiglaucomatous agents. 19 of 25 patients (76%) received additional oral acetazolamide. 19 eyes were pseudophakic, 5 eyes phakic and 1 aphakic. Early postoperatively, mean IOP reduced to 7.7 ± 3.0 mmHg (75.8% reduction). At final follow-up (mean 17.7 months) mean IOP was 12.0 ± 3.8 mmHg (62.5% reduction) on 0.2 ± 0.6 medications. Six eyes (24%) required bleb revision at mean 28 weeks and therefore were categorized as failure. One eye failed despite bleb revision and restart of topical ocular hypotensive medication. Three other eyes (12%) had IOP spikes with uveitis flare-ups. Transient hypotony complications occurred in 32%. At final follow-up, 18 eyes (72%) achieved complete success and one eye (4%) qualified success. CONCLUSION: The XEN® gel stent effectively reduced IOP in uncontrolled uveitic glaucoma, with 72% complete success. Bleb revision was required in 24%. IOP spikes occurred in 12% despite functioning blebs. Further follow-up is needed to determine long-term outcomes.
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Glaucoma , Humanos , Estudios Retrospectivos , Glaucoma/etiología , Glaucoma/cirugía , Presión Intraocular , Tonometría Ocular , Conjuntiva , Antihipertensivos/uso terapéuticoRESUMEN
The extraembryonic yolk sac (YS) ensures delivery of nutritional support and oxygen to the developing embryo but remains ill-defined in humans. We therefore assembled a comprehensive multiomic reference of the human YS from 3 to 8 postconception weeks by integrating single-cell protein and gene expression data. Beyond its recognized role as a site of hematopoiesis, we highlight roles in metabolism, coagulation, vascular development, and hematopoietic regulation. We reconstructed the emergence and decline of YS hematopoietic stem and progenitor cells from hemogenic endothelium and revealed a YS-specific accelerated route to macrophage production that seeds developing organs. The multiorgan functions of the YS are superseded as intraembryonic organs develop, effecting a multifaceted relay of vital functions as pregnancy proceeds.
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Desarrollo Embrionario , Saco Vitelino , Femenino , Humanos , Embarazo , Coagulación Sanguínea/genética , Macrófagos , Saco Vitelino/citología , Saco Vitelino/metabolismo , Desarrollo Embrionario/genética , Atlas como Asunto , Expresión Génica , Perfilación de la Expresión Génica , Hematopoyesis/genética , Hígado/embriologíaRESUMEN
PURPOSE: Single center study to evaluate the incidence and long-term outcome of laser pointer maculopathy (LPM). METHODS: Medical records of 909,150 patients visiting our institution between 2007 and 2020 were screened in our electronic patient record system using the keywords "laserpointer," "laser pointer," and "solar." RESULTS: Eight patients (6/2 male/female, 11 eyes) with a history of LPM were identified by fundoscopy and optical coherence tomography (OCT), all of whom were children (6/2 male/female). Mean age at injury was 12.1 years (range 6-16). Five children (62.5%) were injured between 2019 and 2020, three (37.5%) between 2007 and 2018. Median best-corrected visual acuity (BCVA) of affected eyes at first presentation was 20/25 (range 20/50-20/16). Follow-up examination was performed in seven children (10 eyes) with a median follow-up period of 18 months (range 0.5-96). BCVA improved in 4 children (5 eyes; BCVA at follow-up 20/22.5, range 20/40-20/16). Three of these four children were treated with oral steroids. OCT revealed acute signs such as intraretinal fluid to resolve quickly, while outer retinal disruption persisted until the last follow-up in eight of eleven eyes. These lesions resembled lesions of patients with solar retinopathy of which seven cases (11 eyes) were identified between 2007 and 2020. CONCLUSION: Readily available consumer laser pointers can damage the retina and the underlying retinal pigment epithelium, possibly leading to long-lasting visual impairments. The number of laser pointer injuries has increased over the last years. Therefore, access to laser pointers for children should be strictly controlled.
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Degeneración Macular , Enfermedades de la Retina , Humanos , Femenino , Masculino , Niño , Adolescente , Incidencia , Agudeza Visual , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/epidemiología , Enfermedades de la Retina/etiología , Rayos Láser , Degeneración Macular/complicaciones , Tomografía de Coherencia Óptica/métodosAsunto(s)
Neoplasias Pancreáticas , Trastornos de la Visión , Humanos , Femenino , Neoplasias PancreáticasRESUMEN
BACKGROUND: The application of artificial intelligence (AI) to whole slide images has the potential to improve research reliability and ultimately diagnostic efficiency and service capacity. Image annotation plays a key role in AI and digital pathology. However, the work-streams required for tissue-specific (skin) and immunostain-specific annotation has not been extensively studied compared with the development of AI algorithms. OBJECTIVES: The objective of this study is to develop a common workflow for annotating whole slide images of biopsies from inflammatory skin disease immunostained with a variety of epidermal and dermal markers prior to the development of the AI-assisted analysis pipeline. METHODS: A total of 45 slides containing 3-5 sections each were scanned using Aperio AT2 slide scanner (Leica Biosystems). These slides were annotated by hand using a commonly used image analysis tool which resulted in more than 4000 images blocks. We used deep learning (DL) methodology to first sequentially segment (epidermis and upper dermis), with the exclusion of common artefacts and second to quantify the immunostained signal in those two compartments of skin biopsies and the ratio of positive cells. RESULTS: We validated two DL models using 10-fold validation runs and by comparing to ground truth manually annotated data. The models achieved an average (global) accuracy of 95.0% for the segmentation of epidermis and dermis and 86.1% for the segmentation of positive/negative cells. CONCLUSIONS: The application of two DL models in sequence facilitates accurate segmentation of epidermal and dermal structures, exclusion of common artefacts and enables the quantitative analysis of the immunostained signal. However, inaccurate annotation of the slides for training the DL model can decrease the accuracy of the output. Our open source code will facilitate further external validation across different immunostaining platforms and slide scanners.
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Inteligencia Artificial , Enfermedades de la Piel , Humanos , Inmunohistoquímica , Reproducibilidad de los Resultados , Programas InformáticosRESUMEN
Toxoplasma gondii, Treponema pallidum and Mycobacterium tuberculosis are the most important infectious causes of posterior uveitis. The epidemiology, clinical picture, diagnostic and treatment strategies of these diseases are presented.
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Infecciones del Ojo , Toxoplasma , Toxoplasmosis Ocular , Toxoplasmosis , Tuberculosis , Uveítis Posterior , Uveítis , Infecciones del Ojo/complicaciones , Humanos , Toxoplasmosis Ocular/diagnóstico , Toxoplasmosis Ocular/terapia , Treponema , Uveítis/diagnóstico , Uveítis/etiología , Uveítis/terapia , Uveítis Posterior/diagnóstico , Uveítis Posterior/terapiaRESUMEN
INTRODUCTION: Uveitic glaucoma remains challenging despite medical and surgical advancements and can potentially lead to blindness if left uncontrolled. Conservative alternatives as well as microinvasive surgeries can postpone the necessity of a highly invasive intervention. However, such procedures are still necessary to treat some refractive glaucoma cases. Since previous studies have reported excellent results following the primary implantation of glaucoma drainage devices, it was our study's aim to evaluate long-term results following a Baerveldt 250 implantation in highly complex and surgically burdened uveitic glaucoma eyes (UG) and compare these to a similar population suffering from other forms of glaucoma (OFG). MATERIAL AND METHODS: We performed a retrospective analysis of all eyes (UG vs. OFG) following a Baerveldt 250 implant between 2013 and 2019. Efficacy parameters as well as post-operative complication data were extracted from our electronic data system for statistical analysis. RESULTS: A total of 62 eyes were included in our study (24 UG and 38 OFG). UG baseline mean IOP was 35.04 mmHg (± 11.85 mmHg) with 3.08 (± 1.13) topical agents, and OFG was 32.63 mmHg (± 7.74 mmHg) with 2.68 (± 1.28) topical agents. A majority of eyes also required systemic acetazolamide (UG: 79% OFG: 87%) and had undergone at least one glaucoma-related operation prior to the Baerveldt 250 implant ((UG: 1.21 (± 0.66)), OFG: 1.74 (± 1.33)). At the median follow-up period (UG 592, OFG 764 days), 52.5%/32.5% of UG/OFG cases showed qualified success (IOP below 21 mmHg with either topical or/and systemic medication), 15%/30% no longer required topical medication, and 47.5% /47.5% were free of acetazolamide systemically. Moreover, 75%/72.5% of eyes experienced no further pressure-related surgical event. Although sight-threatening complications such as corneal and macular edema were reported in both groups, most either maintained or improved their visual acuity at the last follow-up (58.33%/57.89%). CONCLUSION: The Baerveldt 250 implant is shown to be both effective and safe for advanced glaucoma cases in uveitis and other forms. No further glaucoma-related surgery is required in the majority of eyes in either group within a follow-up period of almost 2 years. Despite sight-threatening complications such as macular and corneal edema, visual acuity can be either maintained or improved in most eyes.
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Implantes de Drenaje de Glaucoma , Glaucoma , Uveítis , Acetazolamida , Estudios de Seguimiento , Humanos , Presión Intraocular , Complicaciones Posoperatorias , Implantación de Prótesis , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Especially in rural areas, access of visually impaired people to ophthalmic care and counselling can be limited. The Eye Van is a project supported by the Ministry for Rural Affairs and Consumer Protection Baden-Württemberg which offers visually impaired people an on-the-spot ophthalmological examination and counselling on low-vision aids and social support services. The aim of this project was to evaluate the quality of care provided to visually impaired people in the rural areas of South Baden. MATERIALS AND METHODS: Between 2016 and 2019, 45 villages in South Baden participated in this project. The visits were advertised in the local press. Appointments were assigned and participant eligibility was assessed over the telephone by the local Federation of the Blind and Partially Sighted in South Baden. During the on-site visits, a medical history was obtained from participants, who then received a comprehensive ophthalmological examination and counselling on low-vision aids and social support services. Interviews were conducted in order to determine the expectations of the participants and to assess their quality of life. A second interview, focused on the measures that had been implemented and changes in the participants' quality of life, was carried out three months later. RESULTS: In total, 264 participants were examined. Of these, 101 participants fulfilled the criteria of moderate/severe visual impairment or blindness defined by the WHO (World Health Organization). The mean age of the visually impaired participants was 85 years. The median decimal visual acuity was 0.08. The median length of time since the participants' last ophthalmological examination was one year. Among the visually impaired participants, 13% did not have any low-vision aids. Their use was recommended to 62% of the visually impaired participants. The main expectation of participants was counselling on low-vision aids and support services. Among all the participants, 42 did one interview and 28 did two interviews. In the second interview, 72% of the participants claimed to have implemented the recommendations. There was no statistically significant change in their quality of life. CONCLUSION: The access of visually impaired people to ophthalmic care does not seem to be limited in the rural areas of South Baden. Nevertheless, there was a high demand for counselling on low-vision aids and social support services.
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The basal-like molecular subtype of pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis and upregulation in TP63ΔN (p40) network. Adenosquamous histology can be observed. This study assessed immunohistochemical p40 expression in fine needle biopsy (FNB) samples with PDAC and association with cytomorphological features of squamous differentiation and clinical data. 106 EUS FNBs with PDAC were assessed for eight cytomorphological features of squamous differentiation. P40 H-score (intensity 0-3 × percentage positive nuclei) was analysed for association with morphological features, patient age, gender, operability, chemotherapy and survival. P40 H-score in 14 paired FNBs and resections was compared. P40 h-score was 1-3 in 31%, 4-30 in 16% and > 30 in 13% of FNBs. It was significantly associated with intercellular bridges, elongated cell shape, sharp cell borders, angular nuclei with homogenous chromatin (p < 0.001) and dense cytoplasm (p = 0.002). Keratinisation was not seen. Inoperable patients (n = 81) had a shorter median survival for h-score > 30 (n = 9, 1.8 months) than for h-score ≤ 30 (n = 66, 6.7 months) not quite reaching statistical significance (p = 0.08). P40 was significantly associated with squamous morphology in FNBs with PDAC. P40 H-score > 30 showed a trend towards shorter survival in inoperable patients. Squamous differentiation may be a treatment target in PDAC.
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Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/metabolismo , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Inmunohistoquímica , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Carcinoma Ductal Pancreático/mortalidad , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Femenino , Humanos , Inmunohistoquímica/métodos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Pronóstico , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genéticaRESUMEN
Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11-12 weeks after conception1,2, yet almost nothing is known about how fetal BM (FBM) evolves to meet the highly specialized needs of the fetus and newborn. Here we detail the development of FBM, including stroma, using multi-omic assessment of mRNA and multiplexed protein epitope expression. We find that the full blood and immune cell repertoire is established in FBM in a short time window of 6-7 weeks early in the second trimester. FBM promotes rapid and extensive diversification of myeloid cells, with granulocytes, eosinophils and dendritic cell subsets emerging for the first time. The substantial expansion of B lymphocytes in FBM contrasts with fetal liver at the same gestational age. Haematopoietic progenitors from fetal liver, FBM and cord blood exhibit transcriptional and functional differences that contribute to tissue-specific identity and cellular diversification. Endothelial cell types form distinct vascular structures that we show are regionally compartmentalized within FBM. Finally, we reveal selective disruption of B lymphocyte, erythroid and myeloid development owing to a cell-intrinsic differentiation bias as well as extrinsic regulation through an altered microenvironment in Down syndrome (trisomy 21).
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Células de la Médula Ósea/citología , Médula Ósea , Síndrome de Down/sangre , Síndrome de Down/inmunología , Feto/citología , Hematopoyesis , Sistema Inmunológico/citología , Linfocitos B/citología , Células Dendríticas/citología , Síndrome de Down/metabolismo , Síndrome de Down/patología , Células Endoteliales/patología , Eosinófilos/citología , Células Eritroides/citología , Granulocitos/citología , Humanos , Inmunidad , Células Mieloides/citología , Células del Estroma/citologíaRESUMEN
PURPOSE: To provide recommendations for diagnosis of vitreoretinal lymphoma (VRL). METHODS: Literature was reviewed for reports supporting the diagnosis of VRL. A questionnaire (Delphi 1 round) was distributed to 28 participants. In the second round (Delphi 2), items of the questionnaire not reaching consensus (75% agreement) were discussed to finalize the recommendations. RESULTS: Presenting symptoms include floaters and painless loss of vision, vitreous cells organized into sheets or clumps. Retinal lesions are usually multifocal creamy/white in the outer retina. Other findings include retinal lesions with "leopard-skin" appearance and retinal pigment epithelium atrophy. Severe vitreous infiltration without macular edema is the most likely presentation. Diagnostic vitrectomy should be performed. Systemic corticosteroid should be discontinued at least 2 weeks before surgery. An interleukin (IL)-10:IL-6 ratio > 1, positive mutation for the myeloid differentiation primary response 88 gene and monoclonality are indicators of VRL. Multi-modal imaging (optical coherence tomography, fundus autofluorescence) are recommended. CONCLUSIONS: A consensus meeting allowed the establishment of recommendations important for the diagnosis of VRL.
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Linfoma Intraocular/diagnóstico , Linfoma de Células B Grandes Difuso/diagnóstico , Neoplasias de la Retina/diagnóstico , Cuerpo Vítreo/patología , Biomarcadores de Tumor/metabolismo , Análisis Mutacional de ADN , Técnica Delphi , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Linfoma Intraocular/genética , Linfoma Intraocular/metabolismo , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Mutación Missense , Factor 88 de Diferenciación Mieloide/genética , Neoplasias de la Retina/genética , Neoplasias de la Retina/metabolismo , Estudios Retrospectivos , Encuestas y Cuestionarios , Cuerpo Vítreo/metabolismoRESUMEN
We describe a case of a 65-year old patient presenting with unusual mucocutaneous melanocytic proliferations of a Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) imitating a multifocal melanoma in situ, which improved dramatically after plasmapheresis. The patient first presented at the dermatology department due to rapidly evolving brown and black macules on the glans penis. Further skin involvement of the perineal and perianal region, mamillae and oral mucosa was stated. Histology from a penile biopsy was compatible with a melanoma in situ. Due to the distribution pattern and elevated serum tumor marker S100B, metastatic melanoma was considered. Staging examinations using PET-CT scan however, revealed a lung tumor, later confirmed as a Non-small-cell lung cancer (NSCLC). Primary radio chemotherapy was initiated to treat NSCLC. Shortly after initiation of radio chemotherapy the patient developed massive vision impairment and a NSCLC-associated BDUMP was diagnosed which led to the correct classification of melanocytic skin lesions as mucocutaneous BDUMP manifestation. Plasmapheresis was started resulting in a rapid improvement of vision starting ten days after the first plasmapheresis. In contrast skin manifestations started to disappear with a marked delay 4 months after the last plasmapheresis cycle. This case highlights the importance of memorizing multiple rapidly progressing melanocytic skin and/or mucous membrane spots together with visual impairment as a possible paraneoplastic BDUMP that needs a fundamentally different therapeutic approach compared to multifocal melanoma in situ. What is already known about this topic? Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) is a paraneoplastic syndrome with melanocytic uveal proliferation leading to vision impairment. Extraocular manifestation is rare, mainly affect the subepidermal compartment and is hard to treat. Plasmapheresis has been shown to be an effective treatment mainly for vision improvement in some but not all cases. What does this study add? Our BDUMP case with widespread skin and mucosal involvement initially mimicked a multifocal melanoma in situ and showed an excellent treatment response to plasmapheresis. Improvement of mucocutaneous lesions has not been documented well in the literature so far. We show a more than one year lasting follow up still underlining the beneficial effect of plasmapheresis in this case. In-vitro data supports the hypothesis that plasma exchange eliminates a "Cultured melanocyte elongation and proliferation (CMEP)" factor out of patient blood leading to decreased melanocyte proliferation shown numerically in-vitro and clinically in-vivo. Our case clearly indicates that before establishing a definite diagnosis and therapy in patients with rapidly evolving melanocytic skin and/or mucosal lesions BDUMP mimicking multifocal melanoma in situ should be considered making a thorough diagnostic workup mandatory.
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The skin confers biophysical and immunological protection through a complex cellular network established early in embryonic development. We profiled the transcriptomes of more than 500,000 single cells from developing human fetal skin, healthy adult skin, and adult skin with atopic dermatitis and psoriasis. We leveraged these datasets to compare cell states across development, homeostasis, and disease. Our analysis revealed an enrichment of innate immune cells in skin during the first trimester and clonal expansion of disease-associated lymphocytes in atopic dermatitis and psoriasis. We uncovered and validated in situ a reemergence of prenatal vascular endothelial cell and macrophage cellular programs in atopic dermatitis and psoriasis lesional skin. These data illustrate the dynamism of cutaneous immunity and provide opportunities for targeting pathological developmental programs in inflammatory skin diseases.
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Dermatitis Atópica/embriología , Dermatitis Atópica/patología , Psoriasis/embriología , Psoriasis/patología , Piel/embriología , Animales , Atlas como Asunto , Movimiento Celular , Conjuntos de Datos como Asunto , Células Dendríticas/inmunología , Dermatitis Atópica/inmunología , Fármacos Dermatológicos/farmacología , Humanos , Inmunidad Innata/genética , Metotrexato/farmacología , Ratones , Fagocitos/inmunología , Psoriasis/inmunología , Análisis de la Célula Individual , Piel/citología , Piel/inmunología , Linfocitos T/inmunología , TranscriptomaRESUMEN
Clinically available prosthetic heart valves are life-saving, but imperfect: mechanical valves requiring anticoagulation therapy, whilst bioprosthetic valves have limited durability. Polymer valves offer the prospect of good durability without the need for anticoagulation. We report the design and development of a polymeric heart valve, its bench-testing at ISO standards, and preliminary extra-vivo and in vivo short-term feasibility. Prototypes were manufactured by injection moulding of styrenic block copolymers to achieve anisotropic mechanical properties. Design was by finite element stress-strain modelling, which has been reported previously, combined with feedback from bench and surgery-based testing using various combinations of materials, valve geometry and processing conditions. Bench testing was according to ISO 5840:2015 standards using an in vitro cardiovascular hydrodynamic testing system and an accelerated fatigue tester. Bench comparisons were made with a best-in-class bio-prosthesis. Preliminary clinical feasibility evaluations included extra-vivo and short-term (1-24 hours) in vivo testing in a sheep model. The optimised final prototype met the requirements of ISO standards with hydrodynamic performance equivalent to the best-in-class bioprosthesis. Bench durability of greater than 1.2 billion cycles (30 years equivalent) was achieved (still ongoing). Extra-vivo sequential testing (n = 8) allowed refinement of external diameter, 3D shape, a low profile, flexibility, suturability, and testing of compatibility to magnetic resonance imaging and clinical sterilisation. In vivo short-term (1-24 hours) feasibility (n = 3) confirmed good suturability, no mechanical failure, no trans-valvular regurgitation, competitive trans-valvular gradients, and good biocompatibility at histopathology. We have developed and tested at ISO standards a novel prosthetic heart valve featuring competitive bench-based hydrodynamics and durability, well beyond the ISO requirements and comparable to a best-in-class bioprosthesis. In vivo short-term feasibility testing confirmed preliminary safety, functionality and biocompatibility, supporting progression to a long-term efficacy trial.
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Bioprótesis , Prótesis Valvulares Cardíacas , Animales , Estudios de Factibilidad , Ensayo de Materiales , Polímeros , Diseño de Prótesis , OvinosRESUMEN
Correction for 'Design, development, testing at ISO standards and in vivo feasibility study of a novel polymeric heart valve prosthesis' by Joanna R. Stasiak et al., Biomater. Sci., 2020, DOI: .