RESUMEN
BACKGROUND: In a princeps study we conducted in patients with advanced cutaneous squamous cell carcinoma treated with concomitant anti-Programmed cell death protein 1 (PD-1) and radiotherapy, we demonstrated a clinico radiological response to cemiplimab that appeared to persist over time, 1 year after treatment discontinuation. METHOD: We conducted a single-center descriptive study at Caen Hospital from September 1, 2021 to September 2023, in 14 patients with advanced carcinoma treated with cemiplimab until September 1, 2021. The aim of this update is to examine clinical and radiological follow-up 2 years after discontinuation of cemiplimab. RESULTS: Of the 12 patients with a partial or complete response, we report 8 (66.7%) persistent responses 2 years after stopping cemiplimab, with only 2 patients progressing to distant disease, one lost to follow-up, and one death a priori unrelated to the disease. CONCLUSION: Our study confirms a long-term and persistent effect despite discontinuation of cemiplimab at least up to 2 years later.
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Anticuerpos Monoclonales Humanizados , Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/radioterapia , Masculino , Femenino , Anciano , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Persona de Mediana Edad , Anciano de 80 o más Años , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Estudios de Seguimiento , Quimioradioterapia/métodosRESUMEN
BACKGROUND: Adverse pregnancy outcomes (APO) occur in 35% of patients with pemphigoid gestationis (PG). No biological predictor of APO has been established yet. OBJECTIVES: To assess a potential relationship between the occurrence of APO and the serum value of anti-BP180 antibodies at the time of PG diagnosis. METHODS: Multicentre retrospective study conducted from January 2009 to December 2019 in 35 secondary and tertiary care centres. INCLUSION CRITERIA: (i) diagnosis of PG according to clinical, histological and immunological criteria, (ii) ELISA measurement of anti-BP180 IgG antibodies determined at the time of PG diagnosis with the same commercial kit and (iii) obstetrical data available. RESULTS: Of the 95 patients with PG included, 42 had one or more APO, which mainly corresponded to preterm birth (n = 26), intrauterine growth restriction (IUGR) (n = 18) and small weight for gestational age at birth (n = 16). From a ROC curve, we identified a threshold of 150 IU ELISA value as the most discriminating to differentiate between patients with or without IUGR, with 78% sensitivity, 55% specificity, 30% positive and 91% negative predictive value. The threshold >150 IU was confirmed using a cross-validation based on bootstrap resampling, which showed that the median threshold was 159 IU. Upon adjusting for oral corticosteroid intake and main clinical predictors of APO, an ELISA value of >150 IU was associated with the occurrence of IUGR (OR = 5.11; 95% CI: 1.48-22.30; p = 0.016) but not with any other APO. The combination of blisters and ELISA values higher than 150 IU led to a 2.4-fold higher risk of all-cause APO (OR: 10.90; 95% CI: 2.33-82.3) relative to patients with blisters but lower values of anti-BP180 antibodies (OR of 4.54; 95% CI 0.92-34.2). CONCLUSION: These findings suggest that anti-BP180 antibody ELISA value in combination with clinical markers is helpful in managing the risk of APO, in particular IUGR, in patients with PG.
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Penfigoide Gestacional , Penfigoide Ampolloso , Nacimiento Prematuro , Embarazo , Femenino , Humanos , Recién Nacido , Penfigoide Gestacional/diagnóstico , Estudios Retrospectivos , Penfigoide Ampolloso/diagnóstico , Vesícula , Resultado del Embarazo , Colágenos no Fibrilares , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina G , Autoantígenos , AutoanticuerposRESUMEN
BACKGROUND AND PURPOSE: Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by clinical manifestations involving the brain, eye and skin. SWS is commonly caused by somatic mutations in G protein subunit Alpha Q (GNAQ). Five cases of subunit Alpha 11 (GNA11) mutations have been reported. We studied phenotypic features of GNA11-SWS and compared them with those of classic SWS. METHODS: Within two European multidisciplinary centers we looked for patients with clinical characteristics of SWS and a GNA11 mutation. Clinical and radiological data were collected retrospectively and prospectively. RESULTS: We identified three patients with SWS associated with a somatic GNA11 mutation. All had disseminated capillary malformation (CM) and hyper- or hypotrophy of an extremity. At birth, the CMs of the face, trunk and limbs were pink and patchy, and slowly darkened with age, evolving to a purple color. Two of the patients had glaucoma. All had neurological symptoms and moderate brain atrophy with a lower degree of severity than that classically associated with SWS. Susceptibility-weighted imaging (SWI) and contrast-enhanced fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging demonstrated the best sensitivity to reveal the pial angiomas. CONCLUSIONS: We have differentiated two distinct clinical/radiological phenotypes of SWS; GNAQ- and GNA11-SWS. The classic GNAQ-SWS is characterized by a homogeneous dark-red CM, commonly associated with underlying soft tissue hypertrophy. The CM in GNA11-SWS is more reticulate and darkens with time, and the neurological picture is milder. SWI and post-contrast FLAIR sequences appear to be necessary to demonstrate leptomeningeal angiomatosis. Anti-epileptic medication or future targeted therapies may be useful, as in classic SWS.
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Subunidades alfa de la Proteína de Unión al GTP , Síndrome de Sturge-Weber , Anticonvulsivantes , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Subunidades alfa de la Proteína de Unión al GTP/genética , Humanos , Imagen por Resonancia Magnética , Estudios Retrospectivos , Síndrome de Sturge-Weber/complicaciones , Síndrome de Sturge-Weber/genética , Síndrome de Sturge-Weber/patologíaRESUMEN
AIMS: The risk and incidence of cardiovascular (CV) immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) in cancer patients remain unknown. METHODS AND RESULTS: We systematically reviewed all randomized clinical trials (RCTs) including at least one ICI-containing arm and available CV adverse event (CVAE) data in cancer patients in the ClinicalTrials.gov registry, Medline, and the Cochrane CENTRAL Register of Controlled Trials, up to 31 August 2020 (CRD42020165672). The primary outcome was the summary risk of 16 different CVAEs associated with ICI exposure vs. controls (placebo and non-placebo) in RCTs. CVAEs with an increased risk associated with ICI exposure were considered as CV irAEs. Summary incidences of CV irAEs identified in our primary outcome analyses were computed using all RCTs including at least one ICI-containing arm. We used a random-effects meta-analysis to obtain Peto odds ratios (ORs) with 95% confidence intervals (CIs) and logit transformation and inverse variance weighting to compute summary incidences. Sixty-three unique RCTs with at least one ICI-containing arm (32 518 patients) were retrieved, among which 48 (29 592 patients) had a control arm. Among the 16 CVAEs studied, ICI use was associated with an increased risk of 6 CV irAEs including myocarditis, pericardial diseases, heart failure, dyslipidemia, myocardial infarction, and cerebral arterial ischaemia with higher risks for myocarditis (Peto OR: 4.42, 95% CI: 1.56-12.50, P < 0.01; I2 = 0%, P = 0.93) and dyslipidemia (Peto OR: 3.68, 95% CI: 1.89-7.19, P < 0.01; I2 = 0%, P = 0.66). The incidence of these CVAEs ranged from 3.2 (95% CI 2.0-5.1) to 19.3 (6.7-54.1) per 1000 patients, in studies with a median follow-up ranging from 3.2 to 32.8 months. CONCLUSION: In RCTs, ICI use was associated with six CV irAEs, not confined to myocarditis and pericarditis.
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Sistema Cardiovascular , Neoplasias , Humanos , Inhibidores de Puntos de Control Inmunológico , Incidencia , Neoplasias/tratamiento farmacológicoRESUMEN
BACKGROUND: Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials. OBJECTIVE: We sought to assess the effectiveness and safety of dupilumab in adults with AD in a real-life French multicenter retrospective cohort. METHODS: We included patients treated during March 2017-April 2018. Efficacy outcomes, including Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) scores, were collected at baseline and 3 months when available. Adverse events (AEs) were recorded at follow-up. RESULTS: We included 241 patients. The median ± interquartile range (IQR) follow-up time was 3.8 ± 3.7 months. A ≥75% improvement in SCORAD was achieved in 27 of 163 (16.6%) patients, and a ≥75% improvement in EASI was achieved in 40 of 82 (48.8%) patients. The median SCORAD and EASI scores at 3 months were significantly lower than those at baseline (SCORAD ± IQR, 25 ± 21 vs 56 ± 27.4, P < 10-9 and EASI ± IQR, 4.1 ± 6.8 vs 17.9 ± 15.4, P < 10-9, respectively). Conjunctivitis was reported in 84 of 241 (38.2%) patients. The proportion with eosinophilia (>500 cells/mm3) during follow-up (57%) was higher than that at baseline (33.7%) (n = 172, P < 10-6). Dupilumab was stopped in 42 cases; 27 patients stopped because of AEs. LIMITATIONS: No control group, missing data. CONCLUSION: This real-life study demonstrated a similar dupilumab effectiveness as that seen in clinical trials, but it also revealed a higher frequency of conjunctivitis and eosinophilia.
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Anticuerpos Monoclonales/uso terapéutico , Conjuntivitis/inducido químicamente , Dermatitis Atópica/tratamiento farmacológico , Eosinofilia/inducido químicamente , Seguridad del Paciente/estadística & datos numéricos , Adulto , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Estudios de Cohortes , Conjuntivitis/epidemiología , Dermatitis Atópica/diagnóstico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Eosinofilia/epidemiología , Femenino , Francia , Humanos , Inyecciones Subcutáneas , Estimación de Kaplan-Meier , Masculino , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Most arteriovenous malformations (AVMs) are localized and occur sporadically. However, they also can be multifocal in autosomal-dominant disorders, such as hereditary hemorrhagic telangiectasia and capillary malformation (CM)-AVM. Previously, we identified RASA1 mutations in 50% of patients with CM-AVM. Herein we studied non-RASA1 patients to further elucidate the pathogenicity of CMs and AVMs. METHODS: We conducted a genome-wide linkage study on a CM-AVM family. Whole-exome sequencing was also performed on 9 unrelated CM-AVM families. We identified a candidate gene and screened it in a large series of patients. The influence of several missense variants on protein function was also studied in vitro. RESULTS: We found evidence for linkage in 2 loci. Whole-exome sequencing data unraveled 4 distinct damaging variants in EPHB4 in 5 families that cosegregated with CM-AVM. Overall, screening of EPHB4 detected 47 distinct mutations in 54 index patients: 27 led to a premature stop codon or splice-site alteration, suggesting loss of function. The other 20 are nonsynonymous variants that result in amino acid substitutions. In vitro expression of several mutations confirmed loss of function of EPHB4. The clinical features included multifocal CMs, telangiectasias, and AVMs. CONCLUSIONS: We found EPHB4 mutations in patients with multifocal CMs associated with AVMs. The phenotype, CM-AVM2, mimics RASA1-related CM-AVM1 and also hereditary hemorrhagic telangiectasia. RASA1-encoded p120RASGAP is a direct effector of EPHB4. Our data highlight the pathogenetic importance of this interaction and indicts EPHB4-RAS-ERK signaling pathway as a major cause for AVMs.
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Malformaciones Arteriovenosas/diagnóstico , Malformaciones Arteriovenosas/genética , Capilares/anomalías , Mutación de Línea Germinal/genética , Sistema de Señalización de MAP Quinasas/fisiología , Mancha Vino de Oporto/diagnóstico , Mancha Vino de Oporto/genética , Receptor EphB4/genética , Proteína Activadora de GTPasa p120/genética , Bases de Datos Genéticas , Femenino , Estudio de Asociación del Genoma Completo/métodos , Humanos , Masculino , LinajeRESUMEN
BACKGROUND: Self-healing juvenile cutaneous mucinosis (SHJCM) is a rare disorder, and its pathogenesis and long-term prognosis are unknown. OBJECTIVE: To elucidate the clinical and histopathologic characteristics, pathogenesis, and outcome in patients with SHJCM. METHODS: Retrospective study of 9 patients with SHCJM. To complement initial findings, data collection forms were sent to the referring physicians. RESULTS: All patients had an acute onset of firm nodules. Of the 9 patients, 6 presented initially with waxy papules on the dorsum of the hands; 5 suffered from periorbital edema, and 6 had a febrile prodrome. Histopathologic assessment of the papules revealed dermal mucin deposition, whereas the nodules showed proliferative fasciitis-like features or nonspecific chronic lobular panniculitis. Laboratory studies elicited evidence of active viral infection in 2 patients (human herpes virus 6 and rotavirus). Seven cases had spontaneous resolution within 6 months, and 2 patients with incomplete resolution showed subsequent transition to fibroblastic rheumatism and an autoinflammatory rheumatologic disease, respectively. LIMITATIONS: This was a retrospective study with incomplete data from referring physicians. CONCLUSIONS: Although spontaneous complete regression is expected, patients with SHJCM need long-term follow-up because of the possible development of dematorheumatolgic conditions. The pathogenetic role of microbial agents deserves further investigation.
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Mucinosis/patología , Mucinosis/fisiopatología , Remisión Espontánea , Enfermedades Cutáneas Papuloescamosas/patología , Enfermedades Cutáneas Papuloescamosas/fisiopatología , Factores de Edad , Biopsia con Aguja , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Incidencia , Lactante , Masculino , Monitoreo Fisiológico/métodos , Mucinosis/epidemiología , Estudios Retrospectivos , Medición de Riesgo , Muestreo , Índice de Severidad de la Enfermedad , Factores Sexuales , Enfermedades Cutáneas Papuloescamosas/epidemiología , Factores de TiempoRESUMEN
BACKGROUND: Chronic wounds are frequent, affect quality of life, and increase care costs. Telemedicine provides potential for effective wound care management, especially for the monitoring of complex wounds at home. OBJECTIVES: The objective of the present study was to determine the clinical effects and costs of telemedicine for the follow-up of complex chronic wounds from the perspective of the public health insurance. The study ran over a period of 9 months. METHODS: We conducted a prospective, pragmatic, open-label, observational study and carried out a cost-effectiveness analysis. A total of 116 patients with chronic wounds were assigned to their choice of two groups: telemedicine (N = 77) and traditional follow-up (control; N = 39). The primary outcome was the time to healing. Secondary outcomes included percentage of wounds reaching target objective, percentage of wounds healed completely, outpatient care costs, travel costs, and hospitalizations. RESULTS: Time to healing was shorter in the telemedicine group than in the control group (137 versus 174 days; p .05). Outpatient care and hospitalization costs were not significantly different. The main results in terms of economic savings were medical transport costs reimbursed by the French public health insurance, which were significantly lower in the telemedicine group. Telemedicine costs were found to be 4,583 less per patient compared with standard practice over 9 months. CONCLUSIONS: This trial suggests that telemedicine saves travel costs and results in a shorter healing time than traditional follow-up.
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Análisis Costo-Beneficio , Telemedicina/economía , Cicatrización de Heridas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenAsunto(s)
COVID-19 , Dermatología , Motivación , Enfermedades de la Piel , Telemedicina/tendencias , Francia , Humanos , PandemiasRESUMEN
BACKGROUND: Transplant recipients in whom cutaneous squamous-cell carcinomas develop are at high risk for multiple subsequent skin cancers. Whether sirolimus is useful in the prevention of secondary skin cancer has not been assessed. METHODS: In this multicenter trial, we randomly assigned transplant recipients who were taking calcineurin inhibitors and had at least one cutaneous squamous-cell carcinoma either to receive sirolimus as a substitute for calcineurin inhibitors (in 64 patients) or to maintain their initial treatment (in 56). The primary end point was survival free of squamous-cell carcinoma at 2 years. Secondary end points included the time until the onset of new squamous-cell carcinomas, occurrence of other skin tumors, graft function, and problems with sirolimus. RESULTS: Survival free of cutaneous squamous-cell carcinoma was significantly longer in the sirolimus group than in the calcineurin-inhibitor group. Overall, new squamous-cell carcinomas developed in 14 patients (22%) in the sirolimus group (6 after withdrawal of sirolimus) and in 22 (39%) in the calcineurin-inhibitor group (median time until onset, 15 vs. 7 months; P=0.02), with a relative risk in the sirolimus group of 0.56 (95% confidence interval, 0.32 to 0.98). There were 60 serious adverse events in the sirolimus group, as compared with 14 such events in the calcineurin-inhibitor group (average, 0.938 vs. 0.250). There were twice as many serious adverse events in patients who had been converted to sirolimus with rapid protocols as in those with progressive protocols. In the sirolimus group, 23% of patients discontinued the drug because of adverse events. Graft function remained stable in the two study groups. CONCLUSIONS: Switching from calcineurin inhibitors to sirolimus had an antitumoral effect among kidney-transplant recipients with previous squamous-cell carcinoma. These observations may have implications concerning immunosuppressive treatment of patients with cutaneous squamous-cell carcinomas. (Funded by Hospices Civils de Lyon and others; TUMORAPA ClinicalTrials.gov number, NCT00133887.).
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Inhibidores de la Calcineurina , Carcinoma de Células Escamosas/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Sirolimus/uso terapéutico , Neoplasias Cutáneas/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Ciclosporina/efectos adversos , Ciclosporina/uso terapéutico , Inhibidores Enzimáticos/efectos adversos , Inhibidores Enzimáticos/uso terapéutico , Femenino , Humanos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Sirolimus/efectos adversos , Tacrolimus/efectos adversos , Tacrolimus/uso terapéuticoRESUMEN
The prognostic value of the sentinel lymph node in Merkel cell carcinoma (MCC) has been examined previously in heterogeneous retrospective studies. The current retrospective study included a homogeneous population of patients with a localized MCC, all staged with sentinel lymph node biopsy. Factors associated with 3-year progression-free survival were analysed using logistic regression. The sentinel lymph node was positive in 32% of patients. The recurrence rate was 26.9%. In first analyses (n = 108), gender (p = 0.0115) and the presence of immunosuppression (p = 0.0494) were the only significant independent factors. In further analyses (n = 80), excluding patients treated with regional radiotherapy, sentinel lymph node status was the only significant prognostic factor (p = 0.0281). Immunosuppression and positive sentinel lymph node are associated with a worse prognosis in patients with MCC. Nodal irradiation impacts on the prognostic value of the sentinel lymph node status.
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Carcinoma de Células de Merkel/terapia , Huésped Inmunocomprometido , Ganglios Linfáticos/patología , Recurrencia Local de Neoplasia , Neoplasias Cutáneas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células de Merkel/inmunología , Carcinoma de Células de Merkel/mortalidad , Carcinoma de Células de Merkel/patología , Distribución de Chi-Cuadrado , Supervivencia sin Enfermedad , Estudios de Factibilidad , Femenino , Francia , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Biopsia del Ganglio Linfático Centinela , Factores Sexuales , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
The treatment of advanced stage primary cutaneous T-cell lymphomas remains challenging. In particular, large-cell transformation of mycosis fungoides is associated with a median overall survival of two years for all stages taken together. Little is known regarding allogeneic hematopoietic stem cell transplantation in this context. We performed a multicenter retrospective analysis of 37 cases of advanced stage primary cutaneous T-cell lymphomas treated with allogeneic stem cell transplantation, including 20 (54%) transformed mycosis fungoides. Twenty-four patients (65%) had stage IV disease (for mycosis fungoides and Sézary syndrome) or disseminated nodal or visceral involvement (for non-epidermotropic primary cutaneous T-cell lymphomas). After a median follow up of 29 months, 19 patients experienced a relapse, leading to a 2-year cumulative incidence of relapse of 56% (95%CI: 0.38-0.74). Estimated 2-year overall survival was 57% (95%CI: 0.41-0.77) and progression-free survival 31% (95%CI: 0.19-0.53). Six of 19 patients with a post-transplant relapse achieved a subsequent complete remission after salvage therapy, with a median duration of 41 months. A weak residual tumor burden before transplantation was associated with increased progression-free survival (HR=0.3, 95%CI: 0.1-0.8; P=0.01). The use of antithymocyte globulin significantly reduced progression-free survival (HR=2.9, 95%CI: 1.3-6.2; P=0.01) but also transplant-related mortality (HR=10(-7), 95%CI: 4.10(-8)-2.10(-7); P<0.001) in univariate analysis. In multivariate analysis, the use of antithymocyte globulin was the only factor significantly associated with decreased progression-free survival (P=0.04). Allogeneic stem cell transplantation should be considered in advanced stage primary cutaneous T-cell lymphomas, including transformed mycosis fungoides.
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Trasplante de Células Madre Hematopoyéticas , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/terapia , Adolescente , Adulto , Trasplante de Médula Ósea/efectos adversos , Niño , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Francia , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Linfoma Cutáneo de Células T/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Recurrencia , Donantes de Tejidos , Acondicionamiento Pretrasplante , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Negative-pressure wound therapy (NPWT) was developed in the early 1990s and reported in 1997 by Argenta and Morykwas. Ignored at first, this technique progressively came to be considered as an outstanding advancement in reconstructive surgery. Several randomized controlled studies produced evidence for the effect of NPWT on promotion of granulation tissue formation and prevention of tissue damage and amputation. However, no important longitudinal study has yet produced clinical and economic data on the consequences of integrating NPWT into practice in multiple institutions. This prospective, comparative longitudinal study of NPWT as a clinical-practice innovation was conducted in 1,126 patients between March 2006 and June 2009 in 30 university and nonuniversity public and private hospitals in France. NPWT was proposed in a nonrandomized fashion for various clinical indications, and the patients were divided into two groups, one using NPWT, the second using standard care. Efficacy criteria were spontaneous closure, closure after surgical coverage using skin grafts or flaps, or achievement of 40% wound area regression. The results, observed in a pragmatic but not randomized study, are suggestive of a favorable impact of NPWT in multiple clinical situations. The significance of differences between surgical patients who underwent NPWT and those who did not was unclear, as NPWT had already been adopted by most of the surgical wards.
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Terapia de Presión Negativa para Heridas , Infección de la Herida Quirúrgica/prevención & control , Cicatrización de Heridas , Heridas y Lesiones/terapia , Adolescente , Adulto , Comorbilidad , Femenino , Francia/epidemiología , Tejido de Granulación/patología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Trasplante de Piel , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/patología , Resultado del Tratamiento , Heridas y Lesiones/epidemiología , Heridas y Lesiones/patologíaRESUMEN
BACKGROUND: Infantile myofibromatosis (IM) is a rare disorder of fibroblastic/myofibroblastic proliferation in children. OBJECTIVES: We sought to document common and unusual characteristics of patients with IM. METHODS: This was a retrospective study of 28 children diagnosed with histopathologically confirmed IM between 1992 and 2012. Epidemiologic, clinical, and treatment data were reviewed. RESULTS: IM was more frequent in boys (60.8%). Skin lesions were congenital in 64.3% of cases. The solitary form accounted for 50% of cases. Most nodules were painless, arising in cutaneous or subcutaneous tissue. The multicentric form accounted for 39% of cases; the skin, subcutaneous tissue, or muscle was involved in 97.8% of cases, and the bones in 50% of cases. The generalized form had a mortality rate of 33% (one-third of cases). Multicentric and generalized forms regressed spontaneously; severe local complications were observed, and late recurrent nodules developed in a few cases. LIMITATIONS: The retrospective review and the ascertainment of patients (from the departments of obstetrics and pediatrics) may have introduced bias in the analysis of severity of the different forms of IM. CONCLUSION: The diagnosis of IM must be confirmed histopathologically because the clinical presentation can be misleading. The prognosis is usually good, although local morbidity can occur. The generalized and multicentric forms merit long-term follow-up.
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Miofibromatosis/congénito , Neoplasias Cutáneas/patología , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Miofibromatosis/patología , Remisión Espontánea , Estudios Retrospectivos , Factores Sexuales , Neoplasias Cutáneas/congénitoRESUMEN
BACKGROUND: A variety of treatment modalities have been proposed to treat keloid scars, but outcomes are often disappointing. Intralesional cryosurgery may significantly reduce these scars. OBJECTIVE: To evaluate the clinical safety and efficacy of intralesional cryosurgery to treat keloid scars. Feedback from patients on pain, pruritus and aesthetic discomfort was recorded before and after treatment. METHODS: A total of 10 patients with 14 keloid scars resistant to conventional treatments were enrolled in a retrospective study between October 2007 and October 2013. The efficacy of this treatment was evaluated by measuring the reduction in scar surface. RESULTS: Scar surface was reduced by an average of 58.5% after intralesional cryosurgery treatment for all scars (average pre-operative keloid scar surface: 874.6 ± 954.1 mm2; average post-operative keloid scar surface: 505.8 ± 1,024.7 mm2; p = 0.002). Pain and aesthetic discomfort were significantly decreased after treatment in all patients (p = 0.008 and p = 0.012, respectively). CONCLUSION: Our data suggest that intralesional cryosurgery is an effective treatment for keloids.
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Cicatriz/complicaciones , Criocirugía/métodos , Queloide/patología , Queloide/cirugía , Adolescente , Adulto , Anciano , Cicatriz/fisiopatología , Estética , Femenino , Estudios de Seguimiento , Humanos , Queloide/etiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
Common capillary malformations are red vascular skin lesions, most commonly associated with somatic activating GNAQ or GNA11 mutations. We focused on capillary malformations lacking such a mutation to identify previously unreported genetic causes. We used targeted next-generation sequencing on 82 lesions. Bioinformatic analysis allowed the identification of 9 somatic pathogenic variants in PIK3R1 and PIK3CA, encoding for the regulatory and catalytic subunits of phosphoinositide 3-kinase, respectively. Recharacterization of these lesions unraveled a common phenotype: a pale capillary malformation associated with visible dilated veins. Primary endothelial cells from 2 PIK3R1-mutated lesions were isolated, and PI3k-Akt-mTOR and RAS-RAF-MAPK signaling were assessed by western blot. This unveiled an abnormal increase in Akt phosphorylation, effectively reduced by PI3K pathway inhibitors, such as mTOR, Akt, and PIK3CA inhibitors. The effects of mutant PIK3R1 were further studied using zebrafish embryos. Endothelium-specific expression of PIK3R1 mutants resulted in abnormal development of the posterior capillary-venous plexus. In summary, capillary malformation associated with visible dilated veins emerges as a clinical entity associated with somatic pathogenic variants in PIK3R1 or PIK3CA (nonhotspot). Our findings suggest that the activated Akt signaling can be effectively reversed by PI3K pathway inhibitors. In addition, the proposed zebrafish model holds promise as a valuable tool for future drug screening aimed at developing patient-tailored treatments.
RESUMEN
Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal-dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for fast-flow lesions. A limited number of patients have been reported, raising the question of the phenotypic borders. We identified new patients with a clinical diagnosis of CM-AVM, and patients with overlapping phenotypes. RASA1 was screened in 261 index patients with: CM-AVM (n = 100), common CM(s) (port-wine stain; n = 100), Sturge-Weber syndrome (n = 37), or isolated AVM(s) (n = 24). Fifty-eight distinct RASA1 mutations (43 novel) were identified in 68 index patients with CM-AVM and none in patients with other phenotypes. A novel clinical feature was identified: cutaneous zones of numerous small white pale halos with a central red spot. An additional question addressed in this study was the "second-hit" hypothesis as a pathophysiological mechanism for CM-AVM. One tissue from a patient with a germline RASA1 mutation was available. The analysis of the tissue showed loss of the wild-type RASA1 allele. In conclusion, mutations in RASA1 underscore the specific CM-AVM phenotype and the clinical diagnosis is based on identifying the characteristic CMs. The high incidence of fast-flow lesions warrants careful clinical and radiologic examination, and regular follow-up.
Asunto(s)
Malformaciones Arteriovenosas/diagnóstico , Malformaciones Arteriovenosas/genética , Capilares/anomalías , Mutación , Fenotipo , Mancha Vino de Oporto/diagnóstico , Mancha Vino de Oporto/genética , Proteína Activadora de GTPasa p120/genética , Sustitución de Aminoácidos , Análisis Mutacional de ADN , Femenino , Orden Génico , Estudios de Asociación Genética , Humanos , Masculino , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Telemedicine is a medical practice which uses new technologies to connect together health professionals and a patient. This enables, for example, chronic wounds to be followed up at home. This article presents examples of how telemedicine can be applied to wounds.
Asunto(s)
Úlcera por Presión/terapia , Telemedicina , Francia , Humanos , Evaluación de Programas y Proyectos de Salud , Calidad de VidaRESUMEN
BACKGROUND: Skin tumors are common. Recommended treatment in most cases is surgery, with margins adapted. Except in the case of simple resection and suture, it is necessary to know the status of the margins before reconstructing the defect. A one-stage technique is possible with frozen section analysis, which gives the surgeon an intraoperative assessment of resection quality. The aim of our work is to study the reliability of the frozen section procedure. METHOD: A retrospective study included 689 patients who underwent surgery for skin tumor (excluding melanoma) between January 2011 and December 2019 at the University Hospital of Caen, France. RESULTS: In 639 patients (92.75%), the frozen section analysis found healthy margins. There were 21 cases of discrepancy between the frozen section analysis and final histology. Infiltrating and scleroderma-like basal cell carcinomas showed a significantly higher frequency of affected margins on frozen section analysis (p < 0.001). The tumor size and location played a significant role in the margin status. CONCLUSION: In our department, the frozen section procedure is the reference examination indicating immediate flap reconstruction. The present study demonstrated its interest and overall reliability. However, it is to be used according to histologic type, size, and location.