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1.
Pharm. pract. (Granada, Internet) ; 21(3): 1-12, jul.-sep. 2023.
Artículo en Inglés | IBECS | ID: ibc-226173

RESUMEN

The principal goal of pharmacogenomics (PGx) is to achieve the highest drug efficacy while maintaining a low toxicity profile. Historically, health care systems used to target treatment for all individuals with the same diagnosis using a standardized medication or dose that fits all. However, a recent pattern in medicine has emerged focusing on personalized and precision medicine. For effective implementation of PGx, there is a need for more collaborations between all the stakeholders in the healthcare system to integrate the pharmacogenetics concept into practice. When it comes to the knowledge and attitudes towards pharmacogenomics, the majority of medical professionals, including pharmacists and physicians, appear to lack appropriate knowledge and training. Across the Middle East and Arab Region, only few studies have addressed this topic. The current review objective is to shed light on pharmacists’ and physicians’ knowledge and attitudes towards PGx practice in the UAE, Arab and the Middle East region as compared to the rest of the world. Moreover, highlighting the role of the pharmacists in the application of PGx services and the educational challenges that are faced. Proposed solutions to improve the knowledge gaps will also be discussed. We also aim to provide the international readers as well as the local researchers with a summary of the trends and distribution of the results across these countries. (AU)


Asunto(s)
Humanos , Farmacogenética , Conocimientos, Actitudes y Práctica en Salud , Medio Oriente , Emiratos Árabes Unidos , Farmacéuticos , Médicos
2.
Noncoding RNA Res ; 8(3): 413-425, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37305178

RESUMEN

Background: Wilms tumour (WT) is caused by aberrant embryonic kidney development and associated with dysregulated expression of short, non-protein-coding RNAs termed microRNAs (miRNAs). At present, there is no reliable circulating biomarker of WT, and this remains an urgent unmet clinical need. Such biomarkers may assist diagnosis, subtyping/prognostication, and disease-monitoring. Here, we established the list of dysregulated circulating miRNAs in WT from the existing published literature. Methods: Regardless of publication date, PubMed, Scopus, Web-of-Science, and Wiley online library databases were searched for English/French studies on WT circulating miRNAs. The PRISMA-compliant search was registered in PROSPERO. The QUADAS tool measured retained article quality. The meta-analysis assessed the sensitivity and specificity of miRNAs for WT diagnosis. Results: Qualitative analysis included 280 samples (172 WT patients; 108 healthy controls) from five of 450 published articles. The study uncovered 301 dysregulated miRNAs (144 up-regulated, 143 down-regulated, 14 conflicting). The pooled sensitivity, specificity, and AUC of the 49 significantly dysregulated microRNAs from two studies was 0.67 [0.62; 0.73], 0.95 [0.92; 0.96] and 0.77 [0.73; 0.81] respectively, indicating a stronger diagnostic potential for WT. Conclusions: Circulating miRNAs show promise for WT diagnosis and prognosis. More research is needed to confirm these findings and determine associations with tumour stage/subtype. Prospero registration number: CRD42022301597.

3.
Ann Hematol ; 102(8): 2039-2049, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37227493

RESUMEN

Iron chelation therapy (ICT) is the mainstay of treatment in patients with thalassemia requiring blood transfusions. This phase 2 JUPITER study evaluated patient preference between film-coated tablet (FCT) and dispersible tablet (DT) in transfusion-dependent thalassemia (TDT) or non-TDT (NTDT) patients treated with both formulations in a sequential manner. The primary endpoint was patient-reported preference for FCT over DT, while secondary outcomes included patient reported outcomes (PROs) evaluated by overall preference, and by age, thalassemia transfusion status, and previous ICT status. Out of 183 patients screened, 140 and 136 patients completed the treatment periods 1 and 2 of the core study, respectively. At week 48, the majority of patients preferred FCT over DT (90.3 vs. 7.5%; difference of percentage: 0.83 [95% confidence interval (CI), 0.75-0.89; P < 0.0001]). FCT scored better on secondary PROs and showed less severe gastrointestinal symptoms than DT, except in the change of modified Satisfaction with Iron Chelation Therapy (mSICT) preference scores, which were similar for both the formulations. Patients with TDT had stable ferritin levels, while it showed a downward trend up to week 48 in patients with NTDT on deferasirox treatment. Overall, 89.9% of patients reported ≥ 1 adverse event (AE), of which 20.3% experienced ≥ 1 serious AE. The most common treatment-emergent AEs were proteinuria, pyrexia, urine protein/creatinine ratio increase, diarrhea, upper respiratory tract infections, transaminase increase, and pharyngitis. Overall, this study reinforced the observations from the previous study by showing a distinct patient preference for FCT over DT formulation and further supported the potential benefits of life-long compliance with ICT.


Asunto(s)
Sobrecarga de Hierro , Talasemia , Humanos , Deferasirox , Sobrecarga de Hierro/complicaciones , Prioridad del Paciente , Talasemia/tratamiento farmacológico , Comprimidos , Hierro , Quelantes del Hierro/efectos adversos , Benzoatos/efectos adversos
4.
Front Microbiol ; 14: 1098703, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36778864

RESUMEN

Background: The global COVID-19 pandemic led to substantial clinical and economic outcomes with catastrophic consequences. While the majority of cases has mild to moderate disease, minority of patients progress into severe disease secondary to the stimulation of the immune response. The hyperinflammatory state contributes towards progression into multi-organ failure which necessitates suppressive therapy with variable outcomes. This study aims to explore the safety and efficacy of anakinra in COVID-19 patients with severe disease leading to cytokine release syndromes. Methods: In this open-label, multi-center, randomized clinical trial, patients with confirmed COVID-19 infection with evidence of respiratory distress and signs of cytokine release syndrome were randomized in 1:1 ratio to receive either standard of care (SOC) or anakinra (100 mg subcutaneously every 12 h for 3 days then 100 mg subcutaneously once daily for 4 days) in addition to SOC. The primary outcome was treatment success at day 14 as defined by the WHO clinical progression score of ≤3. Primary analysis was based upon intention-to-treat population, with value of p of <0.05. Results: Out 327 patients screened for eligibility, 80 patients were recruited for the study. The mean age was 49.9 years (SD = 11.7), with male predominance at 82.5% (n = 66). The primary outcome was not statistically different (87.5% (n = 35) in anakinra group vs. 92.5% (n = 37) in SOC group, p = 0.712; OR = 1.762 (95%CI: 0.39-7.93). The majority of reported adverse events were mild in severity and not related to the study treatment. Elevated aspartate aminotransferase was the only significant adverse event which was not associated with discontinuation of therapy. Conclusion: In patients with severe COVID-19 infection, the addition of anakinra to SOC treatment was safe but was not associated with significant improvement according to the WHO clinical progression scale. Further studies are warranted to explore patients' subgroups characteristics that might benefit from administered therapy. Clinical Trial Registration: Trial registration at ClinicalTrials.gov, identifier: NCT04643678.

5.
Mol Biol Rep ; 49(9): 8291-8300, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35705773

RESUMEN

BACKGROUND: TP53 gene plays a pivotal role in maintaining genetic stability and prevention of malignancies. Alterations of this gene are implicated in more than half of human cancers. To the best of our knowledge, this study is the first to explore TP53 polymorphisms in Moroccan childhood acute lymphoblastic leukemia (ALL). METHODS AND RESULTS: DNA samples of 45 ALL children were obtained from peripheral blood. A total of 333 healthy Moroccans were used as controls. Polymerase chain reaction and Sanger sequencing were performed to analyze TP53 hotspot exons in cases. We identified a significant protective effect of the TP53-Arg variant at rs1042522 [OR 0.4593 (0.249-0.8472), p = 0.0127] and the Pro/Arg genotype [OR 0.0350 (0.0047-0.2583), p = 0.0010]. Additionally, we found a novel association between the C-allele of Arg213Arg 1800372 [OR 2.7736 (1.3821-5.5664), p = 0.0041] and the risk of childhood ALL. Importantly, TC/CC genotypes of this polymorphism were revealed to enhance the risk of ALL among females [OR 9.0 (3.1555-25.6693), p < 0.0001]. Arg213Arg was also noticed to be associated with the hemoglobin count of patients at diagnosis by linear regression (p = 0.0318). The analysis of penetrance showed a significant association of the CG/GG genotypes at rs1042522 and TC/CC genotypes at rs1800372 to childhood ALL via dominant model [OR 0.2090 (0.09074-0.4814), p = 0.0002 and OR 3.4205 (1.6084-7.2742), p = 0.0014 for rs1042522 and rs1800372 respectively]. No association was found between TP53 polymorphisms and patients survival. CONCLUSION: Altogether, our findings indicated that TP53 polymorphisms are significantly involved in the genetic susceptibility to childhood ALL in Morocco.


Asunto(s)
Genes p53 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Estudios de Casos y Controles , Niño , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Polimorfismo de Nucleótido Simple/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteína p53 Supresora de Tumor/genética
6.
PLoS One ; 17(5): e0267884, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35507606

RESUMEN

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is an evolving pandemic that urged the need to investigate various antiviral therapies. This study was conducted to compare efficacy and safety outcomes of darunavir-cobicistat versus lopinavir-ritonavir in treating patients with COVID-19 pneumonia. METHODS AND FINDINGS: This retrospective, multicenter, observational study was conducted on adult patients hospitalized in one of the COVID-19 facilities in Qatar. Patients were included if they received darunavir-cobicistat or lopinavir-ritonavir for at least three days as part of their COVID-19 treatments. Data were collected from patients' electronic medical records. The primary outcome was a composite endpoint of time to clinical improvement and/or virological clearance. Descriptive and inferential statistics were used at alpha level of 0.05. A total of 400 patients was analyzed, of whom 100 received darunavir-cobicistat and 300 received lopinavir-ritonavir. Majority of patients were male (92.5%), with a mean (SD) time from symptoms onset to start of therapy of 7.57 days (4.89). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement and/or virological clearance than patients received darunavir-cobicistat (4 days [IQR 3-7] vs. 6.5 days [IQR 4-12]; HR 1.345 [95%CI: 1.070-1.691], P = 0.011). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement (5 days [IQR 3-8] vs. 8 days [IQR 4-13]; HR 1.520 (95%CI: 1.2-1.925), P = 0.000), and slower time to virological clearance than darunavir-cobicistat (25 days [IQR 15-33] vs. 21 days [IQR 12.8-30]; HR 0.772 (95%CI: 0.607-0.982), P = 0.035). No significant difference in the incidence or severity of adverse events between groups. The study was limited to its retrospective nature and the possibility of covariates, which was accounted for by multivariate analyses. CONCLUSION: In patients with COVID-19 pneumonia, early treatment with lopinavir-ritonavir was associated with faster time to clinical improvement and/or virological clearance than darunavir-cobicistat. Future trials are warranted to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04425382.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Infecciones por VIH , Adulto , Cobicistat , Darunavir/uso terapéutico , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Lopinavir/uso terapéutico , Masculino , Estudios Retrospectivos , Ritonavir , Resultado del Tratamiento
7.
Clin Ophthalmol ; 16: 1207-1213, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35480620

RESUMEN

Purpose: To correlate functional and morphological parameters with foveal avascular zone's (FAZ) size in diabetic patients with mild to moderate stage nonproliferative diabetic retinopathy. Methods: Monocentric and prospective study of a consecutive case series of diabetic patients. Medical history, best corrected visual acuity (BCVA), best corrected high/low contrast visual acuity (BChcVA/BClcVA), mean sensitivity (MS) and mean defect (MD) in central visual field testing, and FAZ size in fluorescein-angiography (FAG) were recorded. Macular thickness (central point thickness CPT, central subfield thickness CST) and volume measurements (central subfield volume CSV, total macular volume) were taken from SD-OCT (6x6mm ETDRS-grid). Groups were categorised as presenting FAZ sizes smaller (G1) or larger (G2) than 0.35mm2. Smallest (Q1) and largest quartiles (Q3) were also compared. Results: Thirty-six of 40 patients were included. MS differed significantly between G1 (n = 6) and G2 (n = 30), and BChcVA/BClcVA as well as TMV correlated significantly with FAZ size in correlation analysis. Mean HbA1c tended to be lower in G1 than G2. Patients in G1 were slightly older than in G2. Treatment period with insulin was shorter in G1/Q1 than in G2/Q3. CPT and TMV were lower in G1/Q1 than in G2/Q3. Our analysis of the FAZ in terms of patient age, HbA1c, disease duration and insulin therapy duration revealed no significance. That lack of significance also applies to BCVA, MS, MD, CPT, CST and CSV. Conclusion: As significantly associated, contrast sensitivity, central visual field parameters and potentially retinal thickness or volume seem to be suitable to detect early macular ischaemia. However, we failed to establish any correlation between FAZ and BCVA.

8.
Rev Diabet Stud ; 18(1): 27-33, 2022 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-35300754

RESUMEN

OBJECTIVE: In this study, we aimed to evaluate the prevalence of high sensitivity C-reactive protein (hsCRP) as an inflammatory mediator and its association with renal function and other biochemical markers in patients with type 2 diabetes mellitus. METHODS: We carried out a cross-sectional study at private healthcare center. We included 453 patients (48.6% males and 51.4% females) with type 2 diabetes mellitus. We obtained socio- demographic, clinical, and laboratory data from patient medical records. We carried out statistical analysis to ascertain associations between parameters. RESULTS: The overall risk of cardiovascular disease (hsCRP > 1 mg/L) among the study participants was 27.2%. Age, gender, body mass index, fasting blood glucose and serum creatinine were significantly associated with risk of cardiovascular disease (hsCRP > 1 mg/L) whereas estimated glomerular filtration rate, vitamin B12, calcium, sodium and metformin users were negatively associated with the hsCRP. CONCLUSIONS: We found a significant positive association of elevated level of C-reactive protein with type 2 diabetes mellitus. Moreover, additional to increased cardiovascular disease risk, hsCRP also seems to be a major inflammatory risk marker indicating renal function loss.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Enfermedades Renales , Biomarcadores , Proteína C-Reactiva/metabolismo , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Estudios Transversales , Femenino , Humanos , Enfermedades Renales/complicaciones , Masculino
9.
Biomed Res Int ; 2022: 1141280, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35281597

RESUMEN

Leukocyte adhesion deficiency type 1 (LAD1) is a rare autosomal recessive hereditary disorder characterized by recurrent infections, impaired pus formation, delayed wound healing, omphalitis, and delayed separation of the umbilical cord as hallmark features of the disease. It results from mutations in the integrin ß2 subunit gene ITGB2, which encodes the integrin beta chain-2 protein CD18. In this study, we aimed to investigate the case of a five-month-old boy who presented with a clinical phenotype and flow cytometry results suggesting LAD1 disease. Sanger sequencing of all exons and intron boundaries of ITGB2 identified a novel in-frame deletion in exon 7 (ITGB2 c.844_846delAAC, p.Asn282del) in the patient. The p.Asn282del mutation was heterozygous in the child's parents, whereas it was absent in the 96 control individuals from North Africa. This variant was evaluated by two in silico mutation analysis tools, PROVEAN and MutationTaster, which predicted that the mutation was likely to be pathogenic. In addition, molecular modeling with the YASARA View software suggested that this novel mutation may affect the structure of integrin beta-2 and, subsequently, its interaction with integrin alpha-X. In summary, we report a novel pathogenic mutation p.Asn282del associated with LAD1 that expands the mutation diversity of ITGB2 and suggest the combination of flow cytometry and ITGB2 sequencing as a first-line diagnostic approach for LAD disease.


Asunto(s)
Antígenos CD18 , Síndrome de Deficiencia de Adhesión del Leucocito , Antígenos CD18/genética , Antígenos CD18/metabolismo , Humanos , Lactante , Síndrome de Deficiencia de Adhesión del Leucocito/diagnóstico , Síndrome de Deficiencia de Adhesión del Leucocito/genética , Síndrome de Deficiencia de Adhesión del Leucocito/patología , Masculino , Mutación/genética , Fenotipo
10.
Leuk Res Rep ; 17: 100289, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35079568

RESUMEN

Acute leukemias are often of myeloid or lymphoid origin. However, some acute leukemias revealed an undefined differentiation into a single lineage. Mixed phenotype acute leukemia (MPAL) is an uncommon diagnosis were blasts can share B/T/myeloid phenotype. Here, we report a rare case of a 17-year-old Moroccan female diagnosed with B/T mixed phenotype acute leukemia and a high hyperdiploid karyotype who relapsed after one year of complete remission with a lineage switch to B-cell acute lymphoblastic leukemia. This case report corroborates the disclosed findings about the high occurence of abnormal karyotypes and poor prognosis of MPAL.

11.
Pediatr Blood Cancer ; 69(4): e29568, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35084087

RESUMEN

BACKGROUND: Tumor boards are part of standard care of patients with complex cancers, but appropriate multidisciplinary expertise and infrastructure are often not available in low- and middle-income countries (LMIC) for pediatric cancers, such as neuroblastoma. Our goal was to review results of a Global Neuroblastoma Network (GNN) tumor board accessible to LMIC. METHODS: De-identified clinical cases presented via internet conference during a weekly GNN virtual tumor board from 2010 through 2020 were evaluated in a standardized format, including diagnostic imaging, pathology, therapy information, resource limitations, and questions for discussion. Information summarized included the presentations, a survey of the impact on care, and a resource questionnaire. RESULTS: Registered GNN participants included 575 individuals from 77 countries, with a median of 39 participants per session. Total 412 cases were presented from 32 countries, including 351 unique neuroblastoma patients, 52 follow-up cases, and nine non-neuroblastoma diagnoses. Twenty-eight educational sessions were presented. Limited critical resources for diagnostics and staging of cases included MYCN analysis (54.7%), metaiodobenzylguanidine (MIBG) scans (38.7%), and International Neuroblastoma Pathology Classification (49%). Therapies were also limited, with markedly decreased use of radiation and autologous stem cell transplant for high-risk cases, and no availability of anti-GD2 antibody in LMIC. Limited sampling with a post-presentation survey showed that 100% found the GNN helpful, and 70% altered the care plan based on the discussion. CONCLUSION: This report shows the utility of an international tumor board for LMIC focused on a challenging solid tumor where local expertise may be limited, with international multidisciplinary expert participation and educational sessions.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Neuroblastoma , 3-Yodobencilguanidina , Niño , Humanos , Neuroblastoma/patología , Cintigrafía , Trasplante Autólogo
12.
Obes Surg ; 32(4): 1141-1148, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35050483

RESUMEN

PURPOSE: Secondary hyperparathyroidism (SHPT) is linked to obesity. Bariatric surgery may be associated with calcium and vitamin D deficiencies leading to SHPT. This study aimed to detect the prevalence of SHPT before and after bariatric surgery. METHODS: This prospective study assessed the prevalence of SHPT after sleeve gastrectomy (SG, n = 38) compared to one-anastomosis gastric bypass (OAGB, n = 86). All patients were followed up for 2 years. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. RESULTS: Of the 124 patients, 71 (57.3%) were females, and 53 (42.7%) were males, with a mean age of 37.5 ± 8.8 years. Before surgery, 23 patients (18.5%) suffered from SHPT, and 40 (32.3%) had vitamin D deficiency. The prevalence of SHPT increased to 29.8% after 1 year and 36.3% after 2 years. SHPT was associated with lower levels of vitamin D and calcium and higher reduction of BMD in the hip but not in the spine. After 2 years, SHPT was associated with a significantly lower T-score in the hip. SHPT and vitamin D deficiency were significantly more common in patients subjected to OAGB compared to SG (p = 0.003, and p < 0.001, respectively). There is a strong negative correlation between vitamin D levels and parathormone levels before and after surgery. CONCLUSION: Prevalence of SHPT is high in obese patients seeking bariatric surgery, especially with lower vitamin D levels. Bariatric surgery increases the prevalence of SHPT up to 2 years. Gastric bypass is associated with a higher risk of developing SHPT compared to SG.


Asunto(s)
Cirugía Bariátrica , Derivación Gástrica , Hiperparatiroidismo Secundario , Obesidad Mórbida , Deficiencia de Vitamina D , Adulto , Cirugía Bariátrica/efectos adversos , Calcio , Femenino , Estudios de Seguimiento , Derivación Gástrica/efectos adversos , Humanos , Hiperparatiroidismo Secundario/complicaciones , Hiperparatiroidismo Secundario/etiología , Masculino , Persona de Mediana Edad , Obesidad Mórbida/cirugía , Estudios Prospectivos , Vitamina D , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología
13.
Pediatr Blood Cancer ; 69(3): e29464, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34913572

RESUMEN

BACKGROUND AND AIM: The establishment of an international hospital-based register (HBR) for the French African Pediatric Oncology Group (GFAOP) was a necessary step in the group's clinical research program. With help from the Sanofi Espoir Foundation's "My Child Matters" program, the GFAOP resolved to develop an international HBR network to collect quality data on children attending the Pediatric Oncology Units (POUs). METHODS: All children entering POUs from January 2016 to December 2018 were registered using an online questionnaire. Data collection included information on diagnosis, disease stage, demographics, socioeconomic status, and outcome. An intensive training program was developed to improve both data quality and quantity. RESULTS: Among the 3348 children registered, 3230 had a suspected cancer, 681 were not confirmed. A diagnosis was confirmed on radiological, clinical, or histological examination for 2549 children including Burkitt lymphoma (516: 20%)-the most frequent diagnosis, Wilms' tumor (459: 18%), retinoblastoma (357: 14%), and acute lymphoblastic leukemia (345: 13%). Of these, 2187 children were treated. Early deaths, abandonment, economic difficulties, and lack of equipment were some of the reasons offered to explain the numbers of undiagnosed and untreated children. Vital status is known for 1994 children: 1187 died and 807 were alive, 551 of these with a follow-up > 12 months. CONCLUSION: This work has provided reliable data on children attending the POUs, especially clarifying reasons and occasions for care rupture. The data will help to identify material, human resources, and staff training needs, to evaluate progress, and to encourage consideration of pediatric cancer in national cancer plans.


Asunto(s)
Neoplasias Renales , Neoplasias , Tumor de Wilms , Instituciones Oncológicas , Niño , Femenino , Hospitales , Humanos , Masculino , Oncología Médica , Neoplasias/epidemiología , Neoplasias/terapia , Tumor de Wilms/patología
14.
Clin Case Rep ; 9(12): e05207, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34963805

RESUMEN

In this work, we present the first case of a Ph-positive ALL Moroccan girl with t(9;22)(q34;q11) and monosomy-7. She was diagnosed with Ph-positive ALL based on bone marrow examination, immunophenotyping, and cytogenetic analysis. She relapsed after treatment with the persistence of the Ph chromosome and the appearance of a monosomy-7.

15.
Sci Rep ; 11(1): 14090, 2021 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-34238985

RESUMEN

MAIT cells have been shown to be activated upon several viral infections in a TCR-independent manner by responding to inflammatory cytokines secreted by antigen-presenting cells. Recently, a few studies have shown a similar activation of MAIT cells in response to severe acute respiratory coronavirus 2 (SARS-CoV-2) infection. In this study, we investigate the effect of SARS-CoV-2 infection on the frequency and phenotype of MAIT cells by flow cytometry, and we test in vitro stimulation conditions on the capacity to enhance or rescue the antiviral function of MAIT cells from patients with coronavirus disease 2019 (COVID-19). Our study, in agreement with recently published studies, confirmed the decline in MAIT cell frequency of hospitalized donors in comparison to healthy donors. MAIT cells of COVID-19 patients also had lower expression levels of TNF-alpha, perforin and granzyme B upon stimulation with IL-12 + IL-18. 24 h' incubation with IL-7 successfully restored perforin expression levels in COVID-19 patients. Combined, our findings support the growing evidence that SARS-CoV-2 is dysregulating MAIT cells and that IL-7 treatment might improve their function, rendering them more effective in protecting the body against the virus.


Asunto(s)
COVID-19/prevención & control , COVID-19/virología , Interleucina-7/farmacología , Células T Invariantes Asociadas a Mucosa/fisiología , Células T Invariantes Asociadas a Mucosa/virología , SARS-CoV-2/patogenicidad , Células Cultivadas , Femenino , Granzimas/metabolismo , Humanos , Masculino , Células T Invariantes Asociadas a Mucosa/metabolismo , Perforina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
16.
Obes Surg ; 31(9): 4064-4069, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34169483

RESUMEN

BACKGROUND: Obesity is a worldwide prevalent problem which negatively affects most of the human body systems. Male sexual dysfunction is a frequent problem in obese individuals. Nowadays, bariatric surgery is the most successful way for the management of morbid obesity. Recent research has concluded that it has a significant improving effect on sexual function. AIM OF THE STUDY: This study aimed to assess the long-term effect of bariatric surgery on male sexual function. PATIENTS AND METHODS: Sixty-six male patients indicated for bariatric surgery were enrolled in this prospective study. Only forty-eight of them completed the study. Patients were invited to fill the International Index of Erectile Function (IIEF) questionnaire twice, preoperatively (T1) and 12 months postoperatively (T2). Simultaneously, patients' serum testosterone levels were assayed. RESULTS: At T2, the patients showed highly significant increase in the IIEF scores and the serum testosterone levels (p<0.001). Only weight and BMI were significant predictors of the IIEF scores. The same factors as well as the patients' age were predictors of the serum testosterone levels. CONCLUSION: Bariatric surgery improves male sexual health. It is associated with significant increase in IIEF score and serum testosterone levels.


Asunto(s)
Cirugía Bariátrica , Disfunción Eréctil , Obesidad Mórbida , Salud Sexual , Humanos , Masculino , Obesidad Mórbida/cirugía , Estudios Prospectivos , Encuestas y Cuestionarios , Testosterona
17.
Ophthalmol Sci ; 1(2): 100031, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36249305

RESUMEN

Purpose: To examine the interrater and intrarater reliability of qualitatively and quantitatively assessed disorganization of retinal inner layers (DRIL) and disorganization of retinal outer layers (DROL) by multiple raters. Subjectively assessing these surrogate biomarkers can be challenging in daily routine, despite the high resolution of spectral-domain (SD) OCT scans. Design: Retrospective trial. Participants: Three hundred six pooled SD OCT scans of 34 patients treated for macular edema caused by retinal vein occlusion (RVO) between January 2016 and December 2017. Methods: SD OCT scans were assessed by 6 raters regarding presence of cystoid macular edema, subretinal fluid (SRF), vitreoretinal traction, and epiretinal membrane and extent of DRIL and DROL. Main Outcome Measures: Interrater and intrarater reliability were calculated applying κ statistics for qualitative assessment regarding each pathologic feature's presence in all evaluated OCT scans, and for quantified horizontal DRIL and DROL extent within each OCT cross-section. Results: Cystoid macular edema and SRF assessments revealed excellent inter- and intrarater reliability with almost perfect strength of agreement, whereas subjective DRIL and DROL evaluations yielded low κ statistics with slight to moderate strength of agreement. Furthermore, the presence of SRF remarkably compromised the reliability of DROL detection. Conclusions: Our data highlight the limited subjective assessibility of DRIL and DROL, underscoring the need for automated image analysis to improve the reliability of OCT biomarkers for clinical studies and daily practice.

18.
Ophthalmologe ; 118(4): 399-403, 2021 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-32613256

RESUMEN

A 9­year-old patient presented with a reduction of visual acuity in the left eye, which was incidentally noticed 2 weeks previously. Funduscopy revealed a mild vitritis, a pale optic disk, narrowed blood vessels and an increased reflex of the retinal surface. The values in the blood examination were normal apart from eosinophilia and an elevated immunoglobulin E (IgE) antibody titer.


Asunto(s)
Atrofia Óptica , Disco Óptico , Niño , Humanos , Atrofia Óptica/diagnóstico , Retina , Agudeza Visual
19.
Curr Diabetes Rev ; 17(2): 233-242, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32674733

RESUMEN

OBJECTIVES: To determine the overall prevalence of metabolic syndrome using the World Health Organization (WHO); National Cholesterol Education Program (NCEP), and the International Diabetes Federation (IDF) guidelines and to study its association with vitamin D and other biochemical parameters in patients with type 2 Diabetes mellitus, as well as to identify the set of biochemical parameters that jointly influence the metabolic syndrome using different diagnostic criteria. METHODS: A cross-sectional study was carried out at a private health care center in -a total of 291 diabetic patients. Socio-demographic, clinical, and laboratory data were obtained from the medical records of patients. Statistical analysis was carried out using the Statistical Package for the Social Sciences (SPSS, version 23). RESULTS: A total number of 291 patients with T2DM were included in this study. The overall prevalence of metabolic syndrome among the study subjects was 48.1%, 87.3%, 64.9% using the WHO, IDF, and NCEP-ATPIII criteria, respectively. The highest prevalence was reported following IDF diagnostic criteria. Sex, triglyceride, and fasting blood sugar were associated factors of metabolic syndrome by all the three diagnostic criteria of metabolic syndrome. CONCLUSION: The study revealed a high prevalence rate of metabolic syndrome among type 2 diabetic patients, which was highest at 87.3% according to IDF and lowest was observed according to the WHO criteria i.e, 48.1%. A significant variance in the prevalence of metabolic syndrome was reported between WHO, IDF, and NCEP criteria.


Asunto(s)
Diabetes Mellitus Tipo 2 , Síndrome Metabólico , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Prevalencia , Factores de Riesgo , Vitamina D
20.
Ir J Med Sci ; 190(1): 387-393, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32474811

RESUMEN

OBJECTIVES: This study aimed to determine the role of ONSD measurement by US for diagnosis of high ICP in TBI patients. METHODS: ONSD measurement by US was performed in adult TBI patients within 1 h of planned CT brain, while CT signs of high ICP were determined. Invasive ICP measurement was performed simultaneously in patients who had intraventricular device in situ. High ICP was determined as ICP > 22 mmHg. RESULTS: A total of 48 patients were enrolled. Twenty-eight patients had positive CT criteria for high ICP, while 20 patients were negative. The mean value of ONSD was 0.63 ± 0.06 cm in positive group compared with 0.55 ± 0.07 cm in negative one with significant difference (p < 0.001). A total of 22 patients had intraventricular device. Thirteen patients had high ICP, while 9 patients had normal ICP. The mean value of ONSD was 0.66 ± 0.05 cm in high ICP group compared with 0.58 ± 0.08 cm in normal one with significant difference (p = 0.004). ONSD with cut-off value > 0.61 cm predicted high ICP with sensitivity of 84.62% and specificity of 66.67% with significant AUC of 0.85 (p = 0.006). CONCLUSION: ONSD measurement by ultrasound is a good screening tool for high ICP in traumatic brain injury patients.


Asunto(s)
Lesiones Traumáticas del Encéfalo/complicaciones , Presión Intracraneal/fisiología , Nervio Óptico/diagnóstico por imagen , Nervio Óptico/fisiopatología , Ultrasonografía/métodos , Adulto , Femenino , Humanos , Masculino
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