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1.
Artigo em Inglês | MEDLINE | ID: mdl-31876783

RESUMO

In recent years, monogenic causes of immune dysregulation syndromes, with variable phenotypes, have been documented. Mutations in the lipopolysaccharide-responsive beige-like anchor (LRBA) protein are associated with common variable immunodeficiency, autoimmunity, chronic enteropathy, and immune dysregulation disorders. The LRBA protein prevents degradation of cytotoxic T-lymphocyte antigen 4 (CTLA4) protein, thus inhibiting immune responses. Both LRBA and CTLA4 deficiencies usually present with immune dysregulation, mostly characterized by autoimmunity and lymphoproliferation. In this report, we describe a patient with an atypical clinical onset of LRBA deficiency and the patient's response to abatacept, a fusion protein-drug that mimics the action of CTLA4.

2.
Br J Haematol ; 187(4): 502-508, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31309545

RESUMO

Autoimmune lymphoproliferative syndrome (ALPS) is a congenital disorder that results in an apoptosis impairment of lymphocytes, leading to chronic lymphoproliferation and autoimmunity, mainly autoimmune cytopenias. FAS gene defects are often responsible for the disease, the phenotype of which can vary from asymptomatic/mild forms to severe disease. More rarely, defects are associated to  other genes involved in apoptosis pathway, such as CASP10. Few data are available on CASP10-mutated patients. To date, two CASP10 mutations have been recognized as pathogenic (I406L and L258F) and others have been reported with controversial result on their pathogenicity (V410l, Y446C) or are known to be polymorphic variants (L522l). In this study, we evaluated apoptosis function in patients with an ALPS/ALPS-like phenotype carrying CASP10 variants. Molecular findings were obtained by next generation sequencing analysis of genes involved in immune dysregulation syndromes. Functional studies were performed after inducing apoptosis by FAS-ligand/TRIAL stimulation and analysing cell death and the function of CASP10, CASP8 and PARP proteins. We identified 6 patients with an ALPS (n = 2) or ALPS-like (n = 4) phenotype, carrying I406L (n = 1),V410l (n = 2),Y446C (n = 1) heterozygous CASP10 variants or the L522l polymorphisms (n = 2) associated with another polymorphic homozygote variant on CASP8 or a compound heterozygous mutation on TNFRSF13C. Apoptosis was impaired in all patients showing that such variants may play a role in the development of clinical phenotype.

5.
Biol Blood Marrow Transplant ; 24(5): 1088-1093, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29292059

RESUMO

It is recognized that chimerism following hematopoietic stem cell transplantation (HSCT) is a dynamic process. The aims of this study were to describe the evolution of chimerism in children with nonmalignant diseases who underwent allogeneic HSCT, and to analyze the risk factors influencing chimerism status. A total of 101 HSCTs were performed in 85 patients with nonmalignant diseases. The donor was unrelated in 62.4% of HSCTs. Reduced-intensity conditioning (RIC) regimen was administered in 48.5% of patients. Acute graft-versus-host disease (aGVHD) occurred in 51.7% and chronic GVHD (cGVHD) in 39.7% of patients. Analysis of chimerism was performed through amplification of 9 specific short tandem repeats by polymerase chain reaction at engraftment and 1, 6, and 12 months after HSCT. Upon first evaluation, complete chimerism (CC) was detected in 34.7% and mixed chimerism (MC) in 55.4%, whereas graft failure occurred in 9.9% of patients. Severe aGVHD was associated with CC (P = .031). The last chimerism evaluation showed CC in 72.1%, stable MC in 12.8%, and progressive MC in 3.5%. CC was associated with a higher incidence of aGVHD (P = .016) and cGVHD (P = .022), whereas the RIC regimen was associated with graft failure (P = .026). One- and 3-year overall survival (OS) was 87.4% and 80.5%, respectively, with a lower OS at 3 years in patients with CC compared with those with MC (P = .008). aGVHD and cGVHD represent factors favoring CC, thus close, careful follow-up of chimerism is recommended in patients affected by nonmalignant disease.


Assuntos
Quimerismo/estatística & dados numéricos , Transplante de Células-Tronco Hematopoéticas/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Reação em Cadeia da Polimerase , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Doadores de Tecidos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo
7.
Exp Clin Transplant ; 2017 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-28969530

RESUMO

Dyskeratosis congenita is a rare congenital telomeropathy characterized by cutaneous and nail dystrophy, oral leukoplakia, and bone marrow failure. Pulmonary fibrosis and cancers are late manifestations. Allogeneic hematopoietic stem cell transplant represents the only cure for those with bone marrow failure with this disease, but outcomes reported are overall poor, with organ toxicities, graft failure, and graft-versus-host disease as main issues. Although reduced intensity conditioning regimens seem to be related to better outcomes, a standard regimen for dyskeratosis congenita has never been defined. Here, we report a successful long-term outcome of an 8-year-old girl with dyskeratosis congenita who received 2 consecutive allogeneic hematopoietic stem cell transplants from different unrelated donors, because of rejection after the first one, both conditioned with fludarabine-based reduced intensity conditioning regimen. The second transplant was complicated by severe hemorrhagic cystitis and acute grade IV graft-versus-host disease in the early phase and mild chronic graft-versus-host disease and ureteral stenosis in the late phase. This experience confirms that dyskeratosis congenita is at high risk for transplant-related morbidity but that a fludarabine-based reduced intensity conditioning regimen is a safe and feasible option as a preparative regimen, as shown here in a second transplant after first graft rejection. To reduce the risk of graft-versus-host disease, more effective prophylaxis schedules should be chosen in cases of unrelated donor, and haploidentical hematopoietic stem cell transplant with in vitro α/ ß + and CD19+ depletion should be considered.

8.
Am J Rhinol Allergy ; 29(6): 449-56, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26637586

RESUMO

BACKGROUND: The management of frontal sinus disease still remains a challenging issue for rhinologists. Although endoscopic frontal sinus surgery has significantly advanced over the past years, there are some conditions in which the external approaches are still necessary. Recently, the increasing experience in endoscopic sinus surgery together with important technologic advancements have allowed expansion of the indications for selected lesions localized more and more lateral into the frontal sinus. OBJECTIVE: The aim of this study was to describe the endoscopic endonasal approach to the far lateral portion of the frontal sinus and to evaluate the outcomes of this technique. METHODS: A retrospective evaluation was carried out with patients at a single institution, who, from 2004 to 2012, underwent an exclusive endoscopic transnasal approach to the far lateral portion of the frontal sinus at a single institution. The surgical technique included the Draf IIb procedure, a modified Lothrop procedure (Draf III), and endoscopic lateralization of the orbit, differently associated according to the needs of each case. RESULTS: Twenty-four patients were eligible for the present study. The lesions included were mucoceles in 9 cases, fibro-osseous lesions in 10 cases, and inverted papillomas in 5 cases. The overall follow-up ranged from 12 to 120 months (mean, 40.6 months). At the time of the last follow-up, no recurrence of disease was observed in the patients treated; in one case of osteoma, a small and stable in size (1 mm) persistent lesion was observed in an asymptomatic patient. One scheduled and one accidental cerebrospinal fluid leak with immediate skull base reconstruction occurred. No intraoperative or postoperative early or late orbital complication was observed in any case. CONCLUSION: The endoscopic endonasal orbital transposition seems to facilitate the endoscopic management of selected far-lateral frontal sinus lesions. However, it is a demanding procedure that requires experience and skill to avoid intraoperative skull base and orbital complications.


Assuntos
Seio Frontal/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Órbita , Osteotomia/métodos , Doenças dos Seios Paranasais/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Doenças dos Seios Paranasais/diagnóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
9.
Br J Haematol ; 171(2): 247-253, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26058843

RESUMO

The management of refractory autoimmune cytopenias in childhood is challenging due to the lack of established evidence on escalating treatments. The long-term efficacy of immunosuppressive drugs was evaluated in children with refractory autoimmune cytopenias referred to the Haematology Unit of the Gaslini Children's Hospital between 2001 and 2014. Patients were grouped into three categories: autoimmune lymphoproliferative syndrome (ALPS), ALPS-related syndrome (at least one absolute/primary additional criterion for ALPS) and primary autoimmune cytopenia (PAC, cytopenia with no other immunological symptoms/signs). Fifty-eight children (aged 1-16 years) entered the study: 12 were categorized with ALPS, 24 were ALPS-related and 22 had PAC. Five didn't receive treatment. Fifty-three were initially treated with steroids/intravenous immunoglobulin. Fourteen responded, whereas 39 did not. Of these 39 patients, 34 (87%) received mycophenolate mofetil (MMF) as second/further-line treatment and 22 (65%) responded. Within these 34 subjects, ALPS patients responded better (11/11, 100%) than the two other groups pooled together (11/23, 48%; P = 0·002). Sirolimus was given as second/further-line treatment to 16 children, and 12 (75%) responded, including 8 who previously failed MMF therapy. Median follow-up was 3·46 years. MMF and Sirolimus were well-tolerated and enabled partial/complete and sustained remission in most children. These drugs may be successfully and safely used in children with refractory autoimmune cytopenias with or without ALPS/ALPS-related disorders and may represent a valid second/further line option.

10.
Int Forum Allergy Rhinol ; 5(8): 747-53, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25821119

RESUMO

BACKGROUND: Nowadays the endoscopic approach represents a useful alternative to traditional surgical approaches in the treatment of cholesterol granulomas (CGs) of the petrous apex (PA). Recently the nasoseptal flap (NSF) has been employed to permit long-term patency of drainage site. The purpose of this study is to report our experience with the NSF in the endoscopic management of CG and to analyze the advantages, limitations, and outcomes of the technique. METHODS: A retrospective analysis was carried out on 10 patients affected by CG of the PA who had been treated endoscopically, using the NSF. RESULTS: An endoscopic transpterygoid approach was used for 6 patients and the remaining 4 were treated using the transclival approach. A NSF was used in all 10 cases. In 6 cases the flap was ipsilateral to the lesion whereas in 4 it was contralateral. In 90% of our patients no evidence of disease was observed after a mean follow-up period of 35.7 months, with resolution of their symptoms. One patient presented a recurrence because of a technical error (inadequate placement of the flap in the cavity), and has been retreated endoscopically. CONCLUSION: The pedicled NSF seems to be helpful in avoiding the concentric growth of the granulomatous cyst epithelium while assuring ventilation and drainage of the cyst. However, bigger studies with longer-term follow-up are needed to confirm these findings. Correct and meticulous placement of the flap inside the cystic cavity is the most critical issue for the success of the procedure.


Assuntos
Colesterol , Endoscopia/métodos , Granuloma/cirurgia , Osso Petroso/cirurgia , Retalhos Cirúrgicos , Adolescente , Adulto , Idoso , Feminino , Humanos , Complicações Intraoperatórias , Masculino , Complicações Pós-Operatórias , Estudos Retrospectivos
11.
Cytokine ; 73(1): 203-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25769809

RESUMO

Fanconi anemia (FA) is a genetic disorder characterized by bone marrow failure and cancer predisposition. Several studies show alterations of the immunological status of FA patients including defects in peripheral blood lymphocyte subsets, serum immunoglobulin levels, and inflammatory cytokines. However scanty information is available on the response of FA cells to specific infectious antigens. In this work we examined the response of FA cells to different immunological stimuli and found a defective response of IL-1ß, TNF-α and IL-17 to Candida albicans stimulation thus pointing to a potentially impaired response to fungal infections of FA patients.


Assuntos
Candida albicans/imunologia , Anemia de Fanconi/imunologia , Anemia de Fanconi/microbiologia , Imunidade , Adolescente , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células , Células Cultivadas , Criança , Pré-Escolar , Citocinas/biossíntese , Anemia de Fanconi/patologia , Humanos , Lactente , Adulto Jovem
12.
Laryngoscope ; 125(7): 1568-72, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25647632

RESUMO

OBJECTIVE: To evaluate the necessity of reconstructing the eroded bony boundaries after mucocele marsupialization when the mucoperiosteum has been spared. STUDY DESIGN: Retrospective review of 308 patients treated for a sinonasal mucocele. Of these, 116 showed areas of bone reabsorption in their preoperative computed tomography (CT) scan. METHODS: Of 116 patients showing one or more areas of bone reabsorption who underwent marsupialization of the mucocele, whether using a purely endonasal endoscopic approach or a combined approach, the common factor was that the mucoperiosteum of the paranasal sinus had always been spared and the eroded bone had never been reconstructed. After rigorous selection, 12 adult patients were enrolled to undergo a postoperative CT scan in order to verify what had happened to the eroded bone at least 3 years following the surgical marsupialization of the mucocele. RESULTS: In 66,6% of patients, the postoperative CT scan showed complete self-reconstruction of bone that had previously been eroded by the mucocele. No enophthalmus, meningocele, or other facial deformities were noted in our selection group, despite not having undergone surgical reconstruction of the bone. CONCLUSIONS: Even taking into account the small number of patients enrolled in the present study, indications are that there is no need to reconstruct the eroded bone, as would appear from our results that sparing the mucoperiosteum is enough to enable the bone to regenerate. Nevertheless, larger scale studies of the subject are merited.


Assuntos
Regeneração Óssea , Mucocele/cirurgia , Doenças dos Seios Paranasais/cirurgia , Seios Paranasais/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças dos Seios Paranasais/diagnóstico por imagem , Seios Paranasais/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
13.
Eur Arch Otorhinolaryngol ; 271(11): 2951-5, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24609647

RESUMO

Despite advances in endoscopic approaches, instrumentations and imaging guidance systems, the management of frontal sinus is still challenging. Failure of the endoscopic procedure and restenosis of the newly formed ostium have been demonstrated even with large frontal sinusotomy. We describe a newly designed double nasoseptal flap to cover the bare bone after endoscopic modified Lothrop procedure (EMLP). Five fresh, double-injected cadavers were dissected through an endoscopic endonasal approach. Posteriorly based nasoseptal flap on one side and laterally based nasoseptal flap on the other side were harvested before performing wide EMLP. Feasibility of the procedure, versatility of the flap, coverage area and measurements were calculated. Harvesting the mucoperichondrial/mucoperiosteal flap over the septectomy site was straightforward step. Two different designed flaps (one on each side) are more practical to avoid torsion of the flap. The flap measures 2 × 3 cm on average that was able to cover the bare bone of the anterior and posterior wall of frontal sinus. Osteoneogenesis and progressive osteoplastic activity after EMLP plays a major role in restenosis of frontal sinus. Vascularized nasoseptal flap helps in preventing closure of the newly formed ostium. Applying these flaps over the bare bone enhances the healing process and minimizes the crust formation.


Assuntos
Endoscopia/métodos , Seio Frontal/patologia , Seio Frontal/cirurgia , Retalhos Cirúrgicos , Cadáver , Doença Crônica , Constrição Patológica/prevenção & controle , Humanos , Doenças dos Seios Paranasais/patologia , Doenças dos Seios Paranasais/prevenção & controle , Doenças dos Seios Paranasais/cirurgia , Recidiva , Estudos Retrospectivos
14.
Head Neck ; 36(5): 624-30, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23595801

RESUMO

BACKGROUND: The purpose of this study was to evaluate the clinical behavior of oncocytic Schneiderian papillomas in relation to the rate of malignant transformation and recurrences and to report the long-term results of the endoscopic endonasal treatment. METHODS: A retrospective analysis was carried out on patients with oncocytic papilloma, endoscopically managed over the past 20 years, at 2 university centers following a uniform policy. RESULTS: Thirty-three patients were treated between November 1991 and December 2010. The mean follow-up period was 62 months. We observed 2 cases of persistence (6%) at the maxillary sinus level. Both of these patients underwent endoscopic surgical revision. Squamous cell carcinoma (SCC) was observed in 1 patient (3%). CONCLUSION: The endonasal endoscopic technique proved to be a safe and effective approach for the treatment of oncocytic papillomas. An oncocytic papilloma is not to be considered a negative prognostic factor in terms of malignant transformation or recurrence.


Assuntos
Endoscopia/métodos , Recidiva Local de Neoplasia/patologia , Neoplasias Nasais/patologia , Neoplasias Nasais/cirurgia , Papiloma Invertido/patologia , Papiloma Invertido/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Transformação Celular Neoplásica , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Itália , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/cirurgia , Mucosa Nasal/patologia , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasias Nasais/mortalidade , Células Oxífilas/patologia , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/cirurgia , Estudos Retrospectivos , Medição de Risco , Amostragem , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento
16.
Am J Hematol ; 88(6): 472-6, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23483621

RESUMO

In this study, the immunological status of 61 patients with Fanconi anemia (FA) with advanced marrow failure before hematopoietic stem cell transplantation was analyzed by assessing the phenotype of peripheral blood lymphocytes, serum immunoglobulin (Ig) levels, and inflammatory cytokines. In patients with FA, total absolute lymphocytes (P < 0.0001), B cells (P < 0.0001), and NK cells (P = 0.003) were reduced when compared with normal controls. T cells (CD3), that is, cytotoxic T cells, naïve T cells, and regulatory T cells, showed a relative increase when compared with controls. Serum levels of IgG (P < 0.0001) and IgM (P = 0.004) were significantly lower, whereas IgA level was higher (P < 0.0001) than in normal controls. TGF-ß (P = 0.007) and interleukin (IL)-6 (P = 0.0007) levels were increased in the serum of patients when compared with controls, whereas sCD40L level decreases (P < 0.0001). No differences were noted in the serum levels of IL-1ß, IL-2, IL-4, IL-10, IL-13, IL-17, and IL-23 between FA subjects and controls. This comprehensive immunological study shows that patients with FA with advanced marrow failure have an altered immune status. This is in accordance with some characteristics of FA such as the proinflammatory and proapoptotic status. In addition, B lymphocyte failure may make tight and early immunological monitoring advisable.


Assuntos
Anemia de Fanconi/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Citocinas/sangue , Citocinas/imunologia , Anemia de Fanconi/sangue , Feminino , Humanos , Imunoglobulinas/sangue , Imunoglobulinas/imunologia , Imunofenotipagem , Subpopulações de Linfócitos/imunologia , Masculino , Estudos Retrospectivos , Adulto Jovem
17.
Arch Otolaryngol Head Neck Surg ; 138(5): 498-504, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22652949

RESUMO

OBJECTIVE: To review our experience with the surgical treatment of frontoethmoidal osteomas, focusing on the osteomas that were either localized laterally in the frontal sinus or showing intraorbital involvement. DESIGN: Retrospective evaluation. SETTING: Tertiary care center. PATIENTS: Patients with symptomatic frontoethmoidal or intraorbital osteomas who had been treated surgically from 1996 through 2011. INTERVENTION: Sixty frontoethmoidal osteomas were treated surgically. The lesion involved the far lateral portion of the frontal sinus in 23 cases and the orbital region in 6 cases. In 31 cases, a purely endoscopic approach was performed while a combined procedure was used in 25 patients. In 4 patients, an exclusively external approach was required. MAIN OUTCOME MEASURE: No recurrence of osteoma. RESULTS: Radical resection was obtained, except in the case of 2 lesions. No osteoma recurrence was observed during a mean follow-up of 72.6 months. CONCLUSIONS: The size of the osteoma, far lateral extension of the tumor in the frontal sinus beyond the lamina papyracea, and intraorbital involvement are no longer absolute contraindications for purely transnasal endoscopic resection. What is important is that the surgeon should not be dogmatic but rather be ready to change his or her mind during surgery, shifting to an external approach when required.


Assuntos
Endoscopia/métodos , Seio Etmoidal/cirurgia , Seio Frontal/cirurgia , Neoplasias Orbitárias/cirurgia , Osteoma/cirurgia , Neoplasias dos Seios Paranasais/cirurgia , Adolescente , Adulto , Idoso , Criança , Seio Etmoidal/diagnóstico por imagem , Seio Etmoidal/patologia , Feminino , Seio Frontal/diagnóstico por imagem , Seio Frontal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias Orbitárias/patologia , Osteoma/diagnóstico por imagem , Osteoma/patologia , Neoplasias dos Seios Paranasais/diagnóstico por imagem , Neoplasias dos Seios Paranasais/patologia , Estudos Retrospectivos , Retalhos Cirúrgicos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
Rhinology ; 45(4): 315-20, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18085027

RESUMO

OBJECTIVE: Management of symptomatic osteomas involving the frontal sinus is challenging. Traditional external approaches have been used in the surgical management of these lesions. Recently, endonasal endoscopic surgery has become a valid alternative to the traditional external approach in selected cases. METHOD OF STUDY: Retrospective evaluation of the patients with symptomatic fronto-ethmoidal osteomas surgically managed in the last 10 years at a tertiary care facility. RESULTS: Twenty-six osteomas involving the frontal sinus were treated surgically. In 11 cases a purely endoscopic approach was performed while in 13 patients a combined procedure was used. In two patients, an exclusively external procedure was performed. No osteoma recurrence has been observed yet (mean follow up: 40 +/- 31.75 SD months). CONCLUSIONS: Endonasal endoscopic resection of a frontal sinus osteoma is feasible when the lesion is medial to a virtual plane through the lamina papyracea and is attached in the lower portion of the posterior wall of the frontal sinus.


Assuntos
Seio Frontal , Osteoma/cirurgia , Neoplasias dos Seios Paranasais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoma/diagnóstico por imagem , Osteoma/patologia , Neoplasias dos Seios Paranasais/diagnóstico por imagem , Neoplasias dos Seios Paranasais/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
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