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1.
Clin Immunol ; 259: 109901, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38218209

RESUMEN

Chronic human norovirus (HuNoV) infections in immunocompromised patients result in severe disease, yet approved antivirals are lacking. RNA-dependent RNA polymerase (RdRp) inhibitors inducing viral mutagenesis display broad-spectrum in vitro antiviral activity, but clinical efficacy in HuNoV infections is anecdotal and the potential emergence of drug-resistant variants is concerning. Upon favipiravir (and nitazoxanide) treatment of four immunocompromised patients with life-threatening HuNoV infections, viral whole-genome sequencing showed accumulation of favipiravir-induced mutations which coincided with clinical improvement although treatment failed to clear HuNoV. Infection of zebrafish larvae demonstrated drug-associated loss of viral infectivity and favipiravir treatment showed efficacy despite occurrence of RdRp variants potentially causing favipiravir resistance. This indicates that within-host resistance evolution did not reverse loss of viral fitness caused by genome-wide accumulation of sequence changes. This off-label approach supports the use of mutagenic antivirals for treating prolonged RNA viral infections and further informs the debate surrounding their impact on virus evolution.


Asunto(s)
Amidas , Norovirus , Pirazinas , Virus , Animales , Humanos , Norovirus/genética , Antivirales/farmacología , Antivirales/uso terapéutico , Pez Cebra , Mutagénesis , ARN Polimerasa Dependiente del ARN/genética , Huésped Inmunocomprometido
2.
J Clin Immunol ; 43(6): 1360-1366, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37145392

RESUMEN

BACKGROUND AND AIMS: Subcutaneous immunoglobulin (SCIG) home infusion is widely used as an alternative to intravenous immunoglobulin (IVIG). This study aimed to determine the quality of life (QoL) of patients with primary immunodeficiency (PID) after switching to home-based SCIG. METHODS: In this prospective open-label single-center study, QoL was determined using the validated Arabic version of the Child Health Questionnaire at baseline and 3 and 6 months after switching from IVIG to SCIG. RESULTS: Twenty-four patients were recruited from July 2018 to August 2021, including 14 females and 10 males. The median age of the patients was 5 years (range, 0-14 years). The patients' diagnoses included severe combined immunodeficiency, combined immunodeficiency, agammaglobulinemia, Omenn syndrome, immunodysregulation, hyper-IgE syndrome, common variable immunodeficiency, and bare lymphocyte syndrome. The median duration on IVIG before inclusion was 40 months (range, 5-125 months). The QoL score showed a significant improvement in the patients' global health at 3 and 6 months compared with those at baseline and a significant improvement in the patients' general health at 3 and 6 months compared with that at baseline. The mean baseline serum IgG trough level was 8.8 ± 2.1 g/L. The mean serum IgG level was significantly higher on SCIG at both 3 and 6 months (11.7 ± 2.3 and 11.7 ± 2.5 g/L, respectively). CONCLUSIONS: This is the first study involving an Arab population to show improvement in the QoL of patients with PID after switching from hospital-based IVIG to home-based 20% SCIG.


Asunto(s)
Síndromes de Inmunodeficiencia , Enfermedades de Inmunodeficiencia Primaria , Masculino , Femenino , Humanos , Niño , Recién Nacido , Lactante , Preescolar , Adolescente , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunoglobulina G/uso terapéutico , Calidad de Vida , Arabia Saudita , Estudios Prospectivos , Síndromes de Inmunodeficiencia/terapia , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Enfermedades de Inmunodeficiencia Primaria/tratamiento farmacológico , Infusiones Subcutáneas
3.
Blood ; 135(12): 954-973, 2020 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-31932845

RESUMEN

MHC class II deficiency is a rare, but life-threatening, primary combined immunodeficiency. Hematopoietic cell transplantation (HCT) remains the only curative treatment for this condition, but transplant survival in the previously published result was poor. We analyzed the outcome of 25 patients with MHC class II deficiency undergoing first HCT at Great North Children's Hospital between 1995 and 2018. Median age at diagnosis was 6.5 months (birth to 7.5 years). Median age at transplant was 21.4 months (0.1-7.8 years). Donors were matched family donors (MFDs; n = 6), unrelated donors (UDs; n = 12), and haploidentical donors (HIDs; n = 7). Peripheral blood stem cells were the stem cell source in 68% of patients. Conditioning was treosulfanbased in 84% of patients; 84% received alemtuzumab (n = 14) or anti-thymocyte globulin (n = 8) as serotherapy. With a 2.9-year median follow-up, OS improved from 33% (46-68%) for HCT before 2008 (n = 6) to 94% (66-99%) for HCT after 2008 (n = 19; P = .003). For HCT after 2008, OS according to donor was 100% for MFDs and UDs and 85% for HIDs (P = .40). None had grade III-IV acute or chronic graft-versus-host disease. Latest median donor myeloid and lymphocyte chimerism were 100% (range, 0-100) and 100% (range, 64-100), respectively. Latest CD4+ T-lymphocyte number was significantly lower in transplant survivors (n = 14) compared with posttransplant disease controls (P = .01). All survivors were off immunoglobulin replacement and had protective vaccine responses to tetanus and Haemophilus influenzae. None had any significant infection or autoimmunity. Changing transplant strategy in Great North Children's Hospital has significantly improved outcomes for MHC class II deficiency.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/mortalidad , Antígenos de Histocompatibilidad Clase II/genética , Edad de Inicio , Alelos , Biomarcadores , Niño , Preescolar , Femenino , Genotipo , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Lactante , Recién Nacido , Masculino , Cuidados Paliativos , Evaluación del Resultado de la Atención al Paciente , Pronóstico , Acondicionamiento Pretrasplante , Donante no Emparentado
4.
Lupus ; 31(5): 628-636, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35306918

RESUMEN

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with significant disease-related comorbidity and considerably high mortality. AIM OF THE WORK: Explore the survival rates and the spectrum of disease related comorbidities in an Egyptian cohort afflicted by SLE. METHODS: This is a single center observational cohort study performed in one of the leading medical Schools governmental hospitals for teaching and training in the North African region and Middle East sectors Kasr Alainy School of Medicine-Cairo University. Inclusion criteria: the investigators of the research question went for planned review of the medical records of adult SLE patients ≥16 years classified according to American College of Rheumatology (ACR) 1997 SLE classification criteria set forth by Hochberg, 1997 who received longitudinal clinical care during the time period from 1999 to 2019. Exclusion criteria: patients seen only once, other collagen vascular diseases, endocrinal, cardiovascular, or other multisystem disease diagnosed prior to the onset of SLE. DATA ANALYSIS: Survival was determined from the time of SLE diagnosis to the last contact or date of death. The cumulative probability of survival was estimated using Kaplan-Meier method. Differences in survival between patient groups were determined using the long-rank test. RESULTS: The study included records of two hundred and two SLE patients, 184 (91.1%) were females and 18 (8.9%) patients were males. The mean age at the time of diagnosis was 26.71 ± 7.93 years with a mean follow-up between mean: 6.6 ± 4.58 years, 34.15% had damage in at least one of the organ systems by Systemic Lupus International Collaborating Clinics American college of rheumatology damage index SLICC/ACR-DI in the first 6 months. Considering an outcome label of dead or alive at the end of follow-up period, results showed a total of 52 mortalities, 88.5% were females and 11.5% were males, mean age at death onset was 30.9 ± 8.8 years. Results of the Kaplan-Meier survival curve showed an overall cumulative probability of survival at 5, 10, 15, and 20 years after SLE diagnosis was 82.9, 68.8, 51.4, and 20.4%, respectively. CONCLUSION: The cumulative probability of survival at 5, 10, 15, and 20 years after SLE diagnosis was 82.9, 68.8, 51.4, and 20.4%, respectively.


Asunto(s)
Lupus Eritematoso Sistémico , Adulto , Preescolar , Estudios de Cohortes , Comorbilidad , Egipto , Femenino , Humanos , Lactante , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Masculino , Índice de Severidad de la Enfermedad
5.
Lupus ; 30(13): 2135-2143, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34528835

RESUMEN

OBJECTIVES: This study aims to present the manifestations of juvenile systemic lupus erythematosus (JSLE) across Egypt, to focus on age at onset and gender-driven influence on disease characteristics, and to compare findings to other countries. METHODS: The study included 404 Egyptian children with systemic lupus erythematosus (SLE) presenting to one of the specialized rheumatology centers corresponding to 13 major governorates. Juvenile cases age was ≤ 16°years at the time of recruitment. The SLE Disease Activity Index (SLEDAI) and damage index (DI) were assessed. RESULTS: The mean age was 13.2 ± 2.4°years; 355 females and 49 males (7.2:1), and the disease duration was 2.3 ± 1.6 years, while age at disease onset was 11.1 ± 2.5°years. Their SLEDAI was 13.5 ± 12.3, and DI, 0.36 ± 0.78. The overall estimated prevalence of childhood-SLE patients in the recruited cohort in Egypt was 1/100,000 population (0.24/100000 males and 1.8/100000 females). 7.4% developed pre-pubertal SLE (≤ 7 years); 73.3%, peri-pubertal; and 19.3% during early adolescence. The differences according to age group were equal for gender and clinical manifestations except skin lesions present in 59.3% of pre-pubertal onset, 74.6% of peri-pubertal, and 84.2% of adolescents (p = 0.029), and renal involvement in 73.8% of peripubertal, 62.1% of pre-pubertal and 58.9% of adolescents (p = 0.03). Laboratory investigations, SLEDAI, and DI were similar among age categories. Lupus nephritis was more common in Egypt compared to JSLE from other countries. CONCLUSION: Our large multicenter study identified that female gender influenced disease characteristics with more frequent skin involvement. Skin lesions were significantly higher in adolescents, while renal involvement in peri-pubertal children.


Asunto(s)
Lupus Eritematoso Sistémico , Nefritis Lúpica , Adolescente , Niño , Estudios de Cohortes , Egipto/epidemiología , Femenino , Humanos , Lupus Eritematoso Sistémico/epidemiología , Masculino , Índice de Severidad de la Enfermedad
6.
Rheumatol Int ; 41(9): 1607-1616, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34244818

RESUMEN

OBJECTIVES: The aim of the present work was to explore the perspectives of Egyptian Rheumatology staff members as regards the coronavirus disease-19 (COVID-19) vaccine. METHODS: The survey is composed of 25 questions. Some questions were adapted from the global rheumatology alliance COVID-19 survey for patients. RESULTS: 187 rheumatology staff members across Egypt from 18 universities and authorizations actively participated with a valid response. The mean time needed to complete the survey was 17.7 ± 13 min. Participants were 159 (85%) females (F:M 5.7:1). One-third agreed that they will be vaccinated once available, 24.6% have already received at least one dose, 29.4% are unsure while 16% will not take it. Furthermore, 70.1% agreed that they will recommend it to the rheumatic diseases (RD) patients once available, 24.1% are not sure while 5.9% will not recommend it. RD priority to be vaccinated against COVID-19 in descending order include SLE (82.9%), RA (55.1%), vasculitis (51.3%), systemic sclerosis (39.6%), MCTD (31.6%), Behcet's disease (28.3%). The most common drugs to be avoided before vaccination included biologics (71.7%), DMARDs (44.4%), biosimilars (26.7%), IVIg (17.1%) and NSAIDs (9.1%). CONCLUSIONS: The results of the study and specifically the low rate of acceptability are alarming to Egyptian health authorities and should stir further interventions to reduce the levels of vaccine hesitancy. As rheumatic disease patients in Egypt were not systematically provided with the vaccine till present, making the vaccine available could as well enhance vaccine acceptance. Further studies to investigate any possible side effects, on a large scale of RD patients are warranted.


Asunto(s)
Actitud del Personal de Salud , Vacunas contra la COVID-19/administración & dosificación , Reumatología/métodos , Vacunación/psicología , COVID-19 , Vacunas contra la COVID-19/efectos adversos , Egipto , Femenino , Humanos , Masculino , Pandemias , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/psicología , SARS-CoV-2 , Encuestas y Cuestionarios , Universidades , Vacunación/estadística & datos numéricos , Negativa a la Vacunación/psicología
7.
J Allergy Clin Immunol ; 146(1): 192-202, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31862378

RESUMEN

BACKGROUND: The gene AK2 encodes the phosphotransferase adenylate kinase 2 (AK2). Human variants in AK2 cause reticular dysgenesis, a severe combined immunodeficiency with agranulocytosis, lymphopenia, and sensorineural deafness that requires hematopoietic stem cell transplantation for survival. OBJECTIVE: We investigated the mechanisms underlying recurrent sinopulmonary infections and hypogammaglobulinemia in 15 patients, ranging from 3 to 34 years of age, from 9 kindreds. Only 2 patients, both of whom had mildly impaired T-cell proliferation, each had a single clinically significant opportunistic infection. METHODS: Patient cells were studied with next-generation DNA sequencing, tandem mass spectrometry, and assays of lymphocyte and mitochondrial function. RESULTS: We identified 2 different homozygous variants in AK2. AK2G100S and AK2A182D permit residual protein expression, enzymatic activity, and normal numbers of neutrophils and lymphocytes. All but 1 patient had intact hearing. The patients' B cells had severely impaired proliferation and in vitro immunoglobulin secretion. With activation, the patients' B cells exhibited defective mitochondrial respiration and impaired regulation of mitochondrial membrane potential and quality. Although activated T cells from the patients with opportunistic infections demonstrated impaired mitochondrial function, the mitochondrial quality in T cells was preserved. Consistent with the capacity of activated T cells to utilize nonmitochondrial metabolism, these findings revealed a less strict cellular dependence of T-cell function on AK2 activity. Chemical inhibition of ATP synthesis in control T and B cells similarly demonstrated the greater dependency of B cells on mitochondrial function. CONCLUSIONS: Our patients demonstrate the in vivo sequelae of the cell-specific requirements for the functions of AK2 and mitochondria, particularly in B-cell activation and antibody production.


Asunto(s)
Adenilato Quinasa/genética , Linfocitos B/inmunología , Homocigoto , Activación de Linfocitos/genética , Mutación Missense , Inmunodeficiencia Combinada Grave/genética , Adenilato Quinasa/inmunología , Adulto , Sustitución de Aminoácidos , Niño , Preescolar , Femenino , Humanos , Masculino , Inmunodeficiencia Combinada Grave/inmunología , Linfocitos T/inmunología
8.
Clin Immunol ; 213: 108365, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32092470

RESUMEN

Leukocyte adhesion deficiency type III (LAD-III) is caused by mutations in FERMT3 that encodes Kindlin-3 which regulates integrins activation. LAD-III predisposes to infections and bleeding. Osteopetrosis was reported in some cases. We report three patients who presented as malignant infantile osteopetrosis. One had recurrent infections and none had bleeding. Exome sequencing revealed a novel homozygous mutation in FERMT3 c.1555C > T (p.Gln519Ter). Two patients underwent successful hematopoietic stem cell transplant (HSCT) from matched siblings with resolution of osteopetrosis. The third patient died secondary to sepsis prior to HSCT. Our results support early HSCT in LAD-III prior to the occurrence of life-threatening complications.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Síndrome de Deficiencia de Adhesión del Leucocito/complicaciones , Síndrome de Deficiencia de Adhesión del Leucocito/terapia , Osteopetrosis/genética , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Proteínas de la Membrana/genética , Mutación , Proteínas de Neoplasias/genética
9.
J Clin Immunol ; 40(8): 1103-1110, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32851577

RESUMEN

PURPOSE: Combined immunodeficiency (CID), due to mutations in TFRC gene that encodes the transferrin receptors (TfR1), is a rare monogenic disorder. In this study, we further characterize the clinical and immunological phenotypes in a cohort of eight patients. METHODS: A retrospective review of clinical and immunological features of patients diagnosed with a TFRC gene mutation between 2015 and 2019 in three tertiary centers. RESULTS: Eight patients from six unrelated families were enrolled. The patients had a median age of 7 years (4-32 years). All patients presented with recurrent sinopulmonary infections, chronic diarrhea, and failure to thrive in early life. Less common features were skin abscesses, conjunctivitis, global developmental delay, optic nerve atrophy, vitiligo, multinodular goiter, and hemophagocytic lymphohistiocytosis-like symptoms. All patients had intermittent neutropenia and 87% of the patients had recurrent thrombocytopenia. Anemia was found in 62%. All patients had hypogammaglobinemia and one had a persistent high IgM level. All patients had impaired function of T cells. The same homozygous missense mutation c.58T>C:p.Y20H, in the TFRC gene, was detected in all patients. Stem cell transplantation from matched donors was successful in two patients. Five patients did not receive stem cell transplantation, and they are on prophylactic treatment. One patient died due to severe sepsis and neurological complications. CONCLUSION: This report provides a large cohort with a long follow up of patients with this disease. Our cohort showed variable disease severity.


Asunto(s)
Antígenos CD/genética , Mutación , Fenotipo , Enfermedades de Inmunodeficiencia Primaria/diagnóstico , Enfermedades de Inmunodeficiencia Primaria/genética , Receptores de Transferrina/genética , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/genética , Adolescente , Adulto , Biomarcadores , Niño , Preescolar , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Imagen por Resonancia Magnética , Masculino , Neuroimagen , Estudios Retrospectivos , Adulto Joven
11.
Pediatr Blood Cancer ; 65(4)2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29271561

RESUMEN

Adenosine deaminase-2 (ADA2) deficiency (DADA2) is associated with early onset polyarteritis nodosa and vasculopathy. Classic presentation includes livedo reticularis, vasculitis, and stroke. However, the phenotype and disease severity are variable. We present a 5-year-old female who presented with features that mimicked autoimmune lymphoproliferative syndrome (ALPS) in the absence of classic features of DADA2. Exome sequencing identified a novel homozygous splicing variant in ADA2 c.882-2A > G. Patient responded to anti- tumor necrosis factor medication and is in complete remission. Hematologists should be aware of various hematological presentations of DADA2, including ALPS-like disorder, that might lack vasculitis and livedo reticularis to prevent delay in initiating optimal therapy.


Asunto(s)
Adenosina Desaminasa/deficiencia , Síndrome Linfoproliferativo Autoinmune , Exoma , Péptidos y Proteínas de Señalización Intercelular/deficiencia , Livedo Reticularis , Mutación Puntual , Vasculitis , Síndrome Linfoproliferativo Autoinmune/diagnóstico , Síndrome Linfoproliferativo Autoinmune/enzimología , Síndrome Linfoproliferativo Autoinmune/genética , Preescolar , Femenino , Humanos
12.
J Clin Immunol ; 37(8): 811-819, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29058101

RESUMEN

PURPOSE: The dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive-combined immunodeficiency whose clinical spectra include recurrent infections, autoimmunity, malignancies, elevated serum IgE, eczema, and food allergies. Here, we report on patients with loss of function DOCK8 mutations with profound immune dysregulation suggestive of an immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)-like disorder. METHODS: Immunophenotyping of lymphocyte subpopulations and analysis of DOCK8 protein expression were evaluated by flow cytometry. T regulatory (Treg) cells were isolated by cell sorting, and their suppressive activity was analyzed by flow cytometry. Gene mutational analysis was performed by whole-exome and Sanger sequencing. RESULTS: Patient 1 (P1) presented at 10 months of age with chronic severe diarrhea and active colitis in the absence of an infectious trigger, severe eczema with elevated serum IgE, and autoimmune hemolytic anemia, suggestive of an IPEX-related disorder. Whole-exome sequencing revealed a homozygous nonsense mutation in DOCK8 at the DOCK-homology region (DHR)-1 (c.1498C>T; p. R500X). Patient P2, a cousin of P1 who carries the same DOCK8 nonsense mutation, presented with eczema and recurrent ear infections in early infancy, and she developed persistent diarrhea by 3 years of age. Patient P3 presented with lymphoproliferation, severe eczema with allergic dysregulation, and chronic diarrhea with colitis. She harbored a homozygous loss of function DOCK8 mutation (c.2402 -1G→A). Treg cell function was severely compromised by both DOCK8 mutations. CONCLUSION: DOCK8 deficiency may present severe immune dysregulation with features that may overlap with those of IPEX and other IPEX-like disorders.


Asunto(s)
Trastornos de los Cromosomas/diagnóstico , Diabetes Mellitus Tipo 1/congénito , Diarrea/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Factores de Intercambio de Guanina Nucleótido/genética , Hipersensibilidad/diagnóstico , Enfermedades del Sistema Inmune/congénito , Infecciones/diagnóstico , Mutación/genética , Linfocitos T Reguladores/inmunología , Anemia Hemolítica , Preescolar , Diabetes Mellitus Tipo 1/diagnóstico , Femenino , Genes Recesivos/genética , Humanos , Enfermedades del Sistema Inmune/diagnóstico , Inmunoglobulina E/metabolismo , Inmunofenotipificación , Lactante
14.
J Int Med Res ; 51(5): 3000605231169895, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37203384

RESUMEN

OBJECTIVE: To study the effectiveness of infliximab for the treatment of refractory central neuro-Behçet's disease. METHODS: In this systematic review and meta-analysis, the research question was designed using the 'Population, Intervention, Comparator, and Outcomes' (PICO) model and the search methodology was developed according to the PRISMA statement. The study was registered on PROSPERO. Web of Science, PubMed, and Cochrane Library databases were searched for articles published in English between January 2000 and January 2020. Data were analysed using Meta-Essentials software, version 10.12. Treatment effect size was determined by a random effects model. Interstudy heterogeneity was explored using I2 statistics. Cumulative meta-analysis was conducted to assess the temporal trend for accumulating evidence. RESULTS: Twenty-one studies, comprising 64 patients (mean age, 38 .21 years and mean disease duration, 84.76 months) were included. Effect-size analysis showed that 93.7% of the treated patients in the analysis were responders to infliximab therapy (95% confidence interval 0.88, 0.993). There was no significant inter-study heterogeneity (I2 = 0%). Cumulative analysis showed accumulating evidence favoring increasing effectiveness over the last 20 years. CONCLUSION: Infliximab showed considerable therapeutic effectiveness in the treatment of refractory neuro-Behçet's disease.


Asunto(s)
Síndrome de Behçet , Humanos , Adulto , Infliximab/uso terapéutico , Síndrome de Behçet/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Factor de Necrosis Tumoral alfa , Necrosis
15.
J Int Med Res ; 51(9): 3000605231200270, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37773730

RESUMEN

Biologic drugs are therapeutic modalities designed to inhibit specific cytokine signaling pathways. The introduction of these drugs in the management of autoimmune diseases has dramatically changed the treatment paradigm of chronic systemic immune-mediated inflammatory disorders. However, despite their overall acceptable safety profiles, paradoxical reactions have been reported in some real-life cases including case studies and clinical trials. In this study, we report a patient with Crohn's disease who developed infliximab-induced psoriasis vulgaris after starting infliximab treatment. In this case, infliximab was discontinued, and low-dose steroids and subcutaneous methotrexate were introduced to control both his psoriasis and bowel condition with satisfying responses.


Asunto(s)
Enfermedades Autoinmunes , Enfermedad de Crohn , Psoriasis , Humanos , Infliximab/efectos adversos , Enfermedad de Crohn/tratamiento farmacológico , Metotrexato/uso terapéutico , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológico
16.
Antibiotics (Basel) ; 12(9)2023 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-37760698

RESUMEN

Cephalexin is a first-generation ß-lactam antibiotic used in adults and pediatrics to treat various streptococcal and staphylococcal infections. This review aims to summarize and evaluate all the pharmacokinetic (PK) data on cephalexin by screening out all pertinent studies in human beings following the per oral (PO) route. By employing different online search engines such as Google Scholar, PubMed, Cochrane Central, and Science Direct, 23 studies were retrieved, among which nine were in healthy subjects, five in diseased ones, and the remaining were drug-drug, drug-food, and bioequivalence-related. These studies were included only based on the presence of plasma concentration-time profiles or PK parameters, i.e., maximum plasma concentration (Cmax), half-life (t1/2) area under the curve from time 0-infinity (AUC0-∞), and clearance (CL/F). A dose-proportional increase in AUC0-∞ and Cmax can be portrayed in different studies conducted in the healthy population. In comparison to cefaclor, Cmax was recorded to be 0.5 folds higher for cephalexin in the case of renal impairment. An increase in AUC0-∞ was seen in cephalexin on administration with probenecid, i.e., 117 µg.h/mL vs. 68.1 µg.h/mL. Moreover, drug-drug interactions with omeprazole, ranitidine, zinc sulfate, and drug-food interactions for cephalexin and other cephalosporins have also been depicted in different studies with significant changes in all PK parameters. This current review has reported all accessible studies containing PK variables in healthy and diseased populations (renal, dental, and osteoarticular infections, continuous ambulatory peritoneal dialysis) that may be favorable for health practitioners in optimizing doses among the latter.

18.
Diabetes Metab Syndr ; 17(12): 102897, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37979221

RESUMEN

BACKGROUND: Gout comprises a heterogeneous group of disorders; however, comorbidities have been the focus of most efforts to classify disease subgroups. OBJECTIVES: We applied cluster analysis using musculoskeletal ultrasound (MSUS) combined with clinical and laboratory findings in patients with gout to identify disease phenotypes, and differences across clusters were investigated. PATIENTS AND METHODS: Patients with gout who complied with the ACR/EULAR classification criteria were enrolled in the Egyptian College of Rheumatology (ECR)-MSUS Study Group, a multicenter study. Selected variables included demographic, clinical, and laboratory findings. MSUS scans assessed the bilateral knee and first metatarsophalangeal joints. We performed a K-mean cluster analysis and compared the features of each cluster. RESULTS: 425 patients, 267 (62.8 %) males, mean age 54.2 ± 10.3 years were included. Three distinct clusters were identified. Cluster 1 (n = 138, 32.5 %) has the lowest burden of the disease and a lower frequency of MSUS characteristics than the other clusters. Cluster 2 (n = 140, 32.9 %) was mostly women, with a low rate of urate-lowering treatment (ULT). Cluster 3 (n = 147, 34.6 %) has the highest disease burden and the greatest proportion of comorbidities. Significant MSUS variations were found between clusters 2 and 3: joint effusion (p < 0.0001; highest: cluster 3), power Doppler signal (p < 0.0001; highest: clusters 2), and aggregates of crystal deposition (p < 0.0001; highest: cluster 3). CONCLUSION: Cluster analysis using MSUS findings identified three gout subgroups. People with more MSUS features were more likely to receive ULT. Treatment should be tailored according to the cluster and MSUS features.


Asunto(s)
Gota , Reumatología , Masculino , Humanos , Femenino , Adulto , Persona de Mediana Edad , Reumatología/métodos , Egipto , Ultrasonografía , Gota/diagnóstico por imagen , Gota/epidemiología
19.
J Clin Invest ; 133(12)2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-36976641

RESUMEN

STAT2 is a transcription factor activated by type I and III IFNs. We report 23 patients with loss-of-function variants causing autosomal recessive (AR) complete STAT2 deficiency. Both cells transfected with mutant STAT2 alleles and the patients' cells displayed impaired expression of IFN-stimulated genes and impaired control of in vitro viral infections. Clinical manifestations from early childhood onward included severe adverse reaction to live attenuated viral vaccines (LAV) and severe viral infections, particularly critical influenza pneumonia, critical COVID-19 pneumonia, and herpes simplex virus type 1 (HSV-1) encephalitis. The patients displayed various types of hyperinflammation, often triggered by viral infection or after LAV administration, which probably attested to unresolved viral infection in the absence of STAT2-dependent types I and III IFN immunity. Transcriptomic analysis revealed that circulating monocytes, neutrophils, and CD8+ memory T cells contributed to this inflammation. Several patients died from viral infection or heart failure during a febrile illness with no identified etiology. Notably, the highest mortality occurred during early childhood. These findings show that AR complete STAT2 deficiency underlay severe viral diseases and substantially impacts survival.


Asunto(s)
COVID-19 , Encefalitis por Herpes Simple , Gripe Humana , Neumonía , Virosis , Humanos , Preescolar , Virosis/genética , Alelos , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT2/genética
20.
Sci Rep ; 12(1): 18153, 2022 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-36307472

RESUMEN

In this work, hybrid nanocomposites of CuS QDs @ ZnO photocatalysts are fabricated through a facile microwave-assisted (MW) hydrothermal method as a green preparation process. The prepared photocatalysts (PCs) are employed under simulated sunlight (SL) for the degradation of ciprofloxacin, ceftriaxone, ibuprofen pharmaceuticals, methylene blue dye, and 2,4,5-trichlorophenoxyacetic acid (2,4-D) pesticide. The prepared photocatalysts are characterized in detail using several compositional, optical, and morphological techniques. The influence of the CuS (QDs) wt. % on morphological, structural, as well as photocatalytic degradation efficiency have been investigated. The small displacement between the (107) plane of CuS and the (102) plane of ZnO can confirmed the existence of lattice interaction, implying the formation of p-n heterojunctions. TEM and XRD results demonstrated that the CuS QDs are established and uniformly decorated on the surface of ZnO NRs, confirming the forming of an efficient CuS QDs @ ZnO heterojunction nanostructures. The CuS QDs @ ZnO hybrid nanocomposites showed enhancement in crystallinity, light absorption, surface area, separation of e-h pair and inhibition in their recombination at an interfacial heterojunction. In addition it is found that, 3 wt% CuS QDs @ ZnO has the foremost influence. The results showed improvement of photocatalytic activity of the 3% CuS QDs @ ZnO hybrid nanocomposite as compared to the bare ZnO nanorods. The impressive photocatalytic performance of CuS @ ZnO heterostructure nanorods may be attributed to efficient charge transfer. The prepared CuS QDs @ ZnO hybrid nanocomposites exhibited 100% removal for MB dye, after 45 min, and after 60 min for ibuprofen, ciprofloxacin pharmaceuticals, and 2.4.5 trichloro phenoxy acetic acid pesticide with the catalyst amount of 0.2 g/L. Although 100% removal of ceftriaxone pharmaceutical acheived after 90 min. In addition CuS QDs @ ZnO hybrid nanocomposites exhibited complete removal of COD for ibuprofen, ceftriaxone pharmaceuticals and 2.4.5 trichloro phenoxy acetic acid pesticide after 2 h with no selectivity. Briefly, 3% CuS QDs@ZnO hybrid nanocomposites can be considered as promising photoactive materials under simulated sunlight for wastewater decontamination.


Asunto(s)
Nanocompuestos , Plaguicidas , Óxido de Zinc , Óxido de Zinc/química , Cobre/química , Aguas Residuales , Ceftriaxona , Ibuprofeno , Descontaminación , Nanocompuestos/química , Sulfuros , Ciprofloxacina , Preparaciones Farmacéuticas , Acetatos
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