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1.
Pediatr Nephrol ; 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38904753

RESUMEN

BACKGROUND: Steroid-resistant nephrotic syndrome is the second leading cause of chronic kidney disease among patients < 25 years of age. Through exome sequencing, identification of > 65 monogenic causes has revealed insights into disease mechanisms of nephrotic syndrome (NS). METHODS: To elucidate novel monogenic causes of NS, we combined homozygosity mapping with exome sequencing in a worldwide cohort of 1649 pediatric patients with NS. RESULTS: We identified homozygous missense variants in MYO1C in two unrelated children with NS (c.292C > T, p.R98W; c.2273 A > T, p.K758M). We evaluated publicly available kidney single-cell RNA sequencing datasets and found MYO1C to be predominantly expressed in podocytes. We then performed structural modeling for the identified variants in PyMol using aligned shared regions from two available partial structures of MYO1C (4byf and 4r8g). In both structures, calmodulin, a common regulator of myosin activity, is shown to bind to the IQ motif. At both residue sites (K758; R98), there are ion-ion interactions stabilizing intradomain and ligand interactions: R98 binds to nearby D220 within the myosin motor domain and K758 binds to E14 on a calmodulin molecule. Variants of these charged residues to non-charged amino acids could ablate these ionic interactions, weakening protein structure and function establishing the impact of these variants. CONCLUSION: We here identified recessive variants in MYO1C as a potential novel cause of NS in children.

2.
Pediatr Nephrol ; 39(2): 455-461, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37670083

RESUMEN

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of kidney failure in children and adults under the age of 20 years. Previously, we were able to detect by exome sequencing (ES) a known monogenic cause of SRNS in 25-30% of affected families. However, ES falls short of detecting copy number variants (CNV). Therefore, we hypothesized that causal CNVs could be detected in a large SRNS cohort. METHODS: We performed genome-wide single nucleotide polymorphism (SNP)-based CNV analysis on a cohort of 138 SRNS families, in whom we previously did not identify a genetic cause through ES. We evaluated ES and CNV data for variants in 60 known SRNS genes and in 13 genes in which variants are known to cause a phenocopy of SRNS. We applied previously published, predefined criteria for CNV evaluation. RESULTS: We detected a novel CNV in two genes in 2 out of 138 families (1.5%). The 9,673 bp homozygous deletion in PLCE1 and the 6,790 bp homozygous deletion in NPHS2 were confirmed across the breakpoints by PCR and Sanger sequencing. CONCLUSIONS: We confirmed that CNV analysis can identify the genetic cause in SRNS families that remained unsolved after ES. Though the rate of detected CNVs is minor, CNV analysis can be used when there are no other genetic causes identified. Causative CNVs are less common in SRNS than in other monogenic kidney diseases, such as congenital anomalies of the kidneys and urinary tract, where the detection rate was 5.3%. A higher resolution version of the Graphical abstract is available as Supplementary information.


Asunto(s)
Síndrome Nefrótico , Adulto , Niño , Humanos , Adulto Joven , Variaciones en el Número de Copia de ADN , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Homocigoto , Mutación , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/genética , Síndrome Nefrótico/congénito , Eliminación de Secuencia
3.
Pediatr Nephrol ; 39(5): 1559-1566, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38091245

RESUMEN

BACKGROUND: This study aimed to determine the prevalence and etiology of kidney failure (KF) among children below 15 years of age receiving chronic dialysis in Saudi Arabia and describe their dialysis modalities. METHODS: This cross-sectional descriptive study was conducted on 8 August 2022, encompassing all 23 pediatric dialysis centers in Saudi Arabia. Data gathered comprised patient demographics, causes of KF, and the dialysis methods employed. Collected data underwent analysis to determine prevalence of children undergoing chronic dialysis, discern underlying causes of KF, and evaluate distribution of patients across different dialysis modalities. RESULTS: The prevalence of children on chronic dialysis is 77.6 per million children living in Saudi Arabia, equating to 419 children. The predominant underlying cause of KF was congenital anomalies of the kidneys and urinary tract (CAKUT), representing a substantial 41% of cases. Following this, others or unknown etiologies accounted for a noteworthy 25% of cases, with focal segmental glomerulosclerosis (FSGS) comprising 13%, glomerulonephritis at 11%, and congenital nephrotic syndrome contributing 10% to etiological distribution. Regarding dialysis modalities employed, 67% of patients were on peritoneal dialysis (PD), while the remaining 33% were on hemodialysis (HD). CONCLUSIONS: This first nationwide study of pediatric chronic dialysis in Saudi Arabia sheds light on the prevalence of children undergoing chronic dialysis and underlying causes of their KF, thereby contributing to our understanding of clinical management considerations. This research serves as a stepping stone for the development of national registries.


Asunto(s)
Glomerulonefritis , Fallo Renal Crónico , Diálisis Peritoneal , Insuficiencia Renal , Humanos , Niño , Diálisis Renal/efectos adversos , Diálisis Renal/métodos , Prevalencia , Estudios Transversales , Diálisis Peritoneal/métodos , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia
4.
Am J Med Genet A ; 191(8): 2083-2091, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37213061

RESUMEN

Neurogenic bladder is caused by disruption of neuronal pathways regulating bladder relaxation and contraction. In severe cases, neurogenic bladder can lead to vesicoureteral reflux, hydroureter, and chronic kidney disease. These complications overlap with manifestations of congenital anomalies of the kidney and urinary tract (CAKUT). To identify novel monogenic causes of neurogenic bladder, we applied exome sequencing (ES) to our cohort of families with CAKUT. By ES, we have identified a homozygous missense variant (p.Gln184Arg) in CHRM5 (cholinergic receptor, muscarinic, 5) in a patient with neurogenic bladder and secondary complications of CAKUT. CHRM5 codes for a seven transmembrane-spanning G-protein-coupled muscarinic acetylcholine receptor. CHRM5 is shown to be expressed in murine and human bladder walls and is reported to cause bladder overactivity in Chrm5 knockout mice. We investigated CHRM5 as a potential novel candidate gene for neurogenic bladder with secondary complications of CAKUT. CHRM5 is similar to the cholinergic bladder neuron receptor CHRNA3, which Mann et al. published as the first monogenic cause of neurogenic bladder. However, functional in vitro studies did not reveal evidence to strengthen the status as a candidate gene. Discovering additional families with CHRM5 variants could help to further assess the genes' candidate status.


Asunto(s)
Vejiga Urinaria Neurogénica , Sistema Urinario , Anomalías Urogenitales , Reflujo Vesicoureteral , Humanos , Ratones , Animales , Vejiga Urinaria Neurogénica/genética , Anomalías Urogenitales/genética , Reflujo Vesicoureteral/genética , Riñón/anomalías , Ratones Noqueados
5.
Pediatr Nephrol ; 38(6): 1801-1810, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36409364

RESUMEN

BACKGROUND: Primary hyperoxalurias (PHs) constitute rare disorders resulting in abnormal glyoxalate metabolism. PH-associated phenotypes range from progressive nephrocalcinosis and/or recurrent urolithiasis to early kidney failure. METHODS: A retrospective study was conducted for patients with confirmed PH diagnoses from three tertiary centers in Saudi Arabia. Detailed clinical molecular diagnosis was performed for 25 affected individuals. Whole exome sequencing (WES)-based molecular diagnosis was performed for all affected individuals. RESULTS: The male:female ratio was 52% male (n = 13) and 48% female (n = 12), and consanguinity was present in 88%. Nephrolithiasis and/or nephrocalcinosis were present in all patients. Kidney stones were present in 72%, nephrocalcinosis in 60%, hematuria in 32%, proteinuria in 16%, abdominal pain in 36%, developmental delay in 8%, and chronic kidney disease stage 5 (CKD stage 5) was observed in 28% of the patients. The most common PH disorder was type I caused by variants in the AGXT gene, accounting for 56%. The GRHPR gene variants were identified in 4 patients, 16% of the total cases. Seven patients did not reveal any associated variants. Missense variants were the most commonly observed variants (48%), followed by frame-shift duplication variants (28%). CONCLUSIONS: Characterization of the genetic and clinical aspects of PH in this unique population provides direction for improved patient management and further research. A higher resolution version of the Graphical abstract is available as Supplementary information.


Asunto(s)
Hiperoxaluria Primaria , Nefrocalcinosis , Nefrolitiasis , Masculino , Humanos , Femenino , Nefrocalcinosis/epidemiología , Nefrocalcinosis/genética , Nefrocalcinosis/diagnóstico , Hiperoxaluria Primaria/complicaciones , Hiperoxaluria Primaria/diagnóstico , Hiperoxaluria Primaria/epidemiología , Estudios Retrospectivos , Arabia Saudita/epidemiología , Nefrolitiasis/genética
6.
BMC Pregnancy Childbirth ; 22(1): 201, 2022 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-35287618

RESUMEN

BACKGROUND: Objective to assess the value of preoperative tranexamic acid (TXA) in reduction of intraoperative and postoperative blood loss in high-risk cesarean delivery (CD). METHODS: A double blind randomized controlled trial included 160 high risk women who underwent elective lower segment CD. They were equally randomized to receive either 1 g of TXA or placebo 15 min before surgery. The primary outcome was Intraoperative blood loss. RESULTS: The estimated blood loss was significantly higher in the placebo group when compared to TXA group (896.81 ± 519.6 vs. 583.23 ± 379.62 ml, P < 0.001). Both postoperative hemoglobin and hematocrit were lower (9.2 ± 1.6 and 27.4 ± 4.1 vs. 10.1 ± 1.2 and 30.1 ± 3.4, P values < 0.001and 0.012 respectively) and their change percentages (15.41 vs. 7.11%, P < 0.001) were higher in the placebo group when compared to TXA one. The need for further ecbolics was higher in placebo group when compared to TXA group (46.25 vs. 13.75%, P < 0.001). CONCLUSION: Preoperative TXA is safe and effective in reducing blood loss during and after high-risk CD. TRIAL REGISTRATION: ClincalTrial.gov ID: NCT03820206 .


Asunto(s)
Antifibrinolíticos/uso terapéutico , Pérdida de Sangre Quirúrgica/prevención & control , Cesárea , Hemorragia Posoperatoria/prevención & control , Ácido Tranexámico/uso terapéutico , Adulto , Método Doble Ciego , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Periodo Posoperatorio , Embarazo , Embarazo de Alto Riesgo
7.
Anal Chem ; 93(4): 2627-2634, 2021 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-33471510

RESUMEN

In March 2020, the SARS-CoV-2 virus outbreak was declared as a world pandemic by the World Health Organization (WHO). The only measures for controlling the outbreak are testing and isolation of infected cases. Molecular real-time polymerase chain reaction (PCR) assays are very sensitive but require highly equipped laboratories and well-trained personnel. In this study, a rapid point-of-need detection method was developed to detect the RNA-dependent RNA polymerase (RdRP), envelope protein (E), and nucleocapsid protein (N) genes of SARS-CoV-2 based on the reverse transcription recombinase polymerase amplification (RT-RPA) assay. RdRP, E, and N RT-RPA assays required approximately 15 min to amplify 2, 15, and 15 RNA molecules of molecular standard/reaction, respectively. RdRP and E RT-RPA assays detected SARS-CoV-1 and 2 genomic RNA, whereas the N RT-RPA assay identified only SARS-CoV-2 RNA. All established assays did not cross-react with nucleic acids of other respiratory pathogens. The RT-RPA assay's clinical sensitivity and specificity in comparison to real-time RT-PCR (n = 36) were 94 and 100% for RdRP; 65 and 77% for E; and 83 and 94% for the N RT-RPA assay. The assays were deployed to the field, where the RdRP RT-RPA assays confirmed to produce the most accurate results in three different laboratories in Africa (n = 89). The RPA assays were run in a mobile suitcase laboratory to facilitate the deployment at point of need. The assays can contribute to speed up the control measures as well as assist in the detection of COVID-19 cases in low-resource settings.


Asunto(s)
COVID-19/diagnóstico , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Recombinasas/metabolismo , SARS-CoV-2/aislamiento & purificación , COVID-19/virología , Humanos , Sensibilidad y Especificidad
8.
BMC Nephrol ; 22(1): 202, 2021 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-34059010

RESUMEN

BACKGROUND: Acute kidney injury (AKI) is a complication of coronavirus disease 2019 (COVID-19). The reported incidence of AKI, however, varies among studies. We aimed to evaluate the incidence of AKI and its association with mortality and morbidity in children infected with severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) who required hospital admission. METHODS: This was a multicenter retrospective cohort study from three tertiary centers, which included children with confirmed COVID-19. All children were evaluated for AKI using the Kidney Disease Improving Global Outcomes (KDIGO) definition and staging. RESULTS: Of 89 children included, 19 (21 %) developed AKI (52.6 % stage I). A high renal angina index score was correlated with severity of AKI. Also, multisystem inflammatory syndrome in children (MIS-C) was increased in children with AKI compared to those with normal kidney function (15 % vs. 1.5 %). Patients with AKI had significantly more pediatric intensive care admissions (PICU) (32 % vs. 2.8 %, p < 0.001) and mortality (42 % vs. 0 %, p < 0.001). However, AKI was not associated with prolonged hospitalization (58 % vs. 40 %, p = 0.163) or development of MIS-C (10.5 % vs. 1.4 %, p = 0.051). No patient in the AKI group required renal replacement therapy. Residual renal impairment at discharge occurred in 9 % of patients. This was significantly influenced by the presence of comorbidities, hypotension, hypoxia, heart failure, acute respiratory distress, hypernatremia, abnormal liver profile, high C-reactive protein, and positive blood culture. CONCLUSIONS: AKI occurred in one-fifth of children with SARS-CoV-2 infection requiring hospital admission, with one-third of those requiring PICU. AKI was associated with increased morbidity and mortality, and residual renal impairment at time of discharge.


Asunto(s)
Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/virología , COVID-19/complicaciones , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/mortalidad , Niño , Preescolar , Creatinina/sangre , Cuidados Críticos , Femenino , Tasa de Filtración Glomerular , Humanos , Incidencia , Tiempo de Internación , Masculino , Prevalencia , Factores de Riesgo , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones
9.
Mol Cell Probes ; 50: 101511, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31953221

RESUMEN

Highly pathogenic avian influenza H5N1 virus causes heavy losses in poultry farms worldwide. Molecular diagnostic techniques like RT-PCR and real-time RT-PCR are considered the gold standard for identification of H5 influenza viruses in clinical samples. These techniques are hampered by the need of well-equipped laboratories, large space requirement, and relatively long time-to-result. Recombinase polymerase amplification (RPA) assay represents an excellent alternative to PCR since it is more simple, rapid, economic, and portable. Reverse transcription RPA (RT-RPA) assay was recently developed for sensitive and specific detection of H5N1 virus in 6-10 min. To ensure the accuracy of the developed assay, two approaches for using a positive control were evaluated in this study. These approaches included: 1) all-in-one (internal positive control; IPC), 2) two-tubes-per-one-sample (external positive control; EPC). Sigma virus (SIGV) RNA and turkey mitochondrial DNA were tested as positive controls in both approaches. For all-in-one approach, both targets (H5 and IPC) were strongly inhibited. In contrast, very good amplification signals were obtained for the two types of EPC with no effect on the analytical sensitivity and specificity of H5 RT-RPA assay in two-tubes-per-one-sample approach. The performance of EPC-based H5 RT-RPA was further validated using 13 tracheal swabs. The results were compared to real-time RT-PCR and proved superior specificity in detecting H5N1 but not H5N8 viruses. Inclusion of EPC did not affect the aptitude of both assays in terms of sensitivity, specificity and reproducibility. In conclusion, the two-tubes-per-one-sample approach was more reliable to control the false negative results in H5 RT-RPA assay.


Asunto(s)
Subtipo H5N1 del Virus de la Influenza A/genética , Recombinasas/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/normas , Animales , Pollos/virología , Gripe Aviar/virología , Estándares de Referencia
10.
Pediatr Nephrol ; 35(8): 1445-1453, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32337638

RESUMEN

BACKGROUND: Approximately 50% of children with steroid-sensitive nephrotic syndrome (SSNS) will suffer from frequent relapses or steroid dependency, prompting the use of so-called steroid-sparing drugs. In this pilot study, we compare the efficacy and safety of rituximab to oral cyclophosphamide as first-line steroid-sparing medications. METHODS: A prospective open-label non-randomized study of children with frequent relapsing or steroid-dependant SSNS. Exclusion criteria were steroid-resistant disease, prescription of immunosuppressive agents other than prednisolone or levamisole, evidence of impaired kidney function, leucopenia, or active infection. The recruited children were allocated either to the oral cyclophosphamide (3 mg/kg/day for 8 weeks) or intravenous rituximab treatment (two doses of 375 mg/m2/dose, 2 weeks apart) and were monitored for relapses and side effects for 12 months. RESULTS: Forty-six subjects were included from two centers; 27 received cyclophosphamide and 19 received rituximab. One-year relapse-free survival was reached in 17 (58.6%) patients treated with cyclophosphamide compared to 16 (84.2%) with rituximab (adjusted HR 0.36; 95% CI 0.09-1.45; p = 0.151). The mean interval to relapse was 6.9 months in the cyclophosphamide group (N = 10) and 6.3 months in the rituximab group (N = 3). Both treatments were associated with a significant (p < 0.001) reduction in prescribed dose of oral alternate-day steroid from 1.02 to 0.36 mg/kg (cyclophosphamide) and 0.86 to 0.08 mg/kg (rituximab). Importantly, a significantly (p = 0.003) higher percentage of patients achieved complete withdrawal of steroid within 3 months of commencing study treatment in the rituximab (73.7%) versus cyclophosphamide (29.6%) group. Transient leucopenia was the most frequent adverse effect observed in the cyclophosphamide group (18.5%) and one patient (3.4%) had acute hepatotoxicity besides severe leucopenia and neutropenia in the 7th week of treatment with complete recovery with the withdrawal of cyclophosphamide and maintenance of remission. A minor infusion-related reaction in the form of a generalized macular skin rash was observed in one patient (5%) in the rituximab group. CONCLUSIONS: Rituximab is non-inferior to cyclophosphamide and safe as a first-line steroid-sparing agent in children with SSNS. A larger multicenter study is required to assess superiority over cyclophosphamide. Graphical abstract.


Asunto(s)
Ciclofosfamida/administración & dosificación , Inmunosupresores/administración & dosificación , Síndrome Nefrótico/tratamiento farmacológico , Rituximab/administración & dosificación , Niño , Preescolar , Femenino , Humanos , Masculino , Proyectos Piloto , Estudios Prospectivos , Inducción de Remisión/métodos
12.
BMC Nephrol ; 20(1): 89, 2019 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-30866849

RESUMEN

BACKGROUND: Acute kidney injury (AKI) in critically ill children is associated with increased mortality and morbidity. In this study we evaluated the effect of AKI severity on the incidence of short-term mortality and morbidity. METHODS: Multicenter prospective cohort study was conducted over two years period. We used the Kidney Disease Improving Global Outcomes (KDIGO) to diagnose and stage AKI. RESULTS: A total of 511 out of 1367 included children (37.4%; 95% CI: 34.8-40.0) were diagnosed with AKI. They were categorized into three KDIGO stages: stage I (mild) in 47.5% (95% CI: 43.2-52.0), stage II (moderate) in 32.8% (95% CI: 28.8-37.1) and stage III (severe) in 19.7% (95% CI: 16.4-23.5). Stage II and III AKI had higher risk of mortality and longer length of stay (LOS) in hospital. Children with stage III AKI were more likely to require mechanical ventilation, referral to pediatric nephrology and discharge with abnormal creatinine level (above 100 uml\L). Hypervolemia, hypocalcemia, anemia, and acidosis were found to be independent risk factors of mortality. CONCLUSION: The extent of severity of AKI is directly associated with increased mortality, LOS and short-term morbidity.


Asunto(s)
Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Enfermedad Crítica , Unidades de Cuidado Intensivo Pediátrico , Índice de Severidad de la Enfermedad , Equilibrio Hidroelectrolítico/fisiología , Lesión Renal Aguda/epidemiología , Preescolar , Estudios de Cohortes , Enfermedad Crítica/epidemiología , Femenino , Humanos , Unidades de Cuidado Intensivo Pediátrico/tendencias , Masculino , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento
13.
Pediatr Nephrol ; 33(9): 1617-1624, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29869723

RESUMEN

BACKGROUND: Acute kidney injury (AKI) is common in neonates admitted to the neonatal intensive care unit (NICU). AKI is associated with increased morbidity and mortality and a greater long-term risk of chronic kidney disease. OBJECTIVES: To study the incidence and outcome of neonatal AKI in a single Saudi Arabian center, level 2\3 NICU. METHODS: This single-center prospective cohort study included all infants who received level II or III NICU care during 2015 (January to December). We excluded infants who survived less than 48 h after admission, had evidence of congenital renal anomalies, or had insufficient data. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Both AKI and non-AKI neonates were prospectively followed up until NICU discharge. Outcomes studied included mortality and length of NICU stay. The results of adjusted risk analyses were expressed as relative risk (RR) with 95% confidence interval (95% CI). RESULTS: The incidence of AKI (modified neonatal KDIGO stages) was 56% (120/214 patients). Compared with neonates without AKI, those with AKI had a lower birth weight (2202 ± 816 vs. 1570 ± 776 g; p < 0.001) and a lower gestational age (35 ± 3 vs. 32 ± 4 weeks; p < 0.001). After adjustment for potential confounders, only gestational age (RR, 4.8; 95% CI, 3-9) and perinatal depression (RR, 10; 95% CI, 2-46) were significantly associated with an increased risk of AKI. For infants with gestational age < 32 weeks, only the Clinical Risk Index for Babies (CRIB II) score was associated with an increased risk of AKI (RR, 1.9; 95% CI, 1-3). After adjustment for gestational age, AKI was significantly associated with mortality (RR, 5.4; 95% CI, 2-14), but not with the length of hospital stay (LOS) (p = 0.133). However, the AKI group had a significantly longer LOS (mean difference: 14 days; 95% CI, 5.5-23 days), and 33 patients (27.5%) with AKI were discharged with abnormally high serum creatinine levels (> 65 µmol/L). CONCLUSION: AKI occurred in more than half of all NICU admissions, was associated with an increased risk of mortality, and had a higher incidence among smaller and sicker infants. Therefore, close monitoring of renal function during hospitalization and after discharge is warranted in such infants.


Asunto(s)
Lesión Renal Aguda/epidemiología , Enfermedades del Recién Nacido/epidemiología , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Evaluación del Resultado de la Atención al Paciente , Lesión Renal Aguda/terapia , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Recien Nacido con Peso al Nacer Extremadamente Bajo , Recién Nacido , Enfermedades del Recién Nacido/terapia , Recien Nacido Prematuro , Tiempo de Internación/estadística & datos numéricos , Masculino , Estudios Prospectivos , Factores de Riesgo , Arabia Saudita/epidemiología , Tasa de Supervivencia
14.
Pediatr Nephrol ; 33(2): 335-340, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28917005

RESUMEN

BACKGROUND: Acute kidney injury (AKI) is a common problem encountered in critically ill children with an increasing incidence and evolving epidemiology. AKI carries a serious morbidity and mortality in patients requiring admission to a pediatric intensive care unit (PICU). METHODS: We undertook a prospective cohort study of PICU admissions at three tertiary care hospitals in the Kingdom of Saudi Arabia over 2 years. The Kidney Disease Improving Global Outcomes (KDIGO) definition was used to diagnose AKI. RESULTS: A total of 1367 pediatrics PICU admissions were included in the study. AKI affected 511 children (37.4%), with 243 children (17.8%) classified as stage I (mild), 168 patients (12.3%) stage II (moderate), and 100 children (7.3%) were classified as stage III (severe). After adjustment for age, sex, and underlying diagnosis, in-hospital mortality was six times more likely among patients with AKI as compared to patients with normal renal function (adjusted OR: 6.5, 95% CI: 4.2-10). AKI was also a risk factor for hypertension (adjusted OR: 4.1, 95% CI: 2.8-5.9) and prolonged stay in the PICU and hospital, as it increased the average number of admission days by 10 (95% CI: 8.6-11) days in the PICU and 12 (95% CI: 10-14) days in the hospital. CONCLUSIONS: One-third of PICU admissions were complicated with AKI. AKI was associated with increased hospital mortality and the length of stay in both PICU and hospital.


Asunto(s)
Lesión Renal Aguda/epidemiología , Niño , Preescolar , Estudios de Cohortes , Femenino , Mortalidad Hospitalaria , Humanos , Lactante , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Masculino , Estudios Prospectivos , Factores de Riesgo
16.
BMC Vet Res ; 12(1): 244, 2016 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-27806722

RESUMEN

BACKGROUND: Lumpy skin disease virus (LSDV) is a Capripoxvirus infecting cattle and Buffalos. Lumpy skin disease (LSD) leads to significant economic losses due to hide damage, reduction of milk production, mastitis, infertility and mortalities (10 %). Early detection of the virus is crucial to start appropriate outbreak control measures. Veterinarians rely on the presence of the characteristic clinical signs of LSD. Laboratory diagnostics including virus isolation, sequencing and real-time polymerase chain reaction (PCR) are performed at well-equipped laboratories. In this study, a portable, simple, and rapid recombinase polymerase amplification (RPA) assay for the detection of LSDV-genome for the use on farms was developed. RESULTS: The LSDV RPA assay was performed at 42 °C and detected down to 179 DNA copies/reaction in a maximum of 15 min. Unspecific amplification was observed with neither LSDV-negative samples (n = 12) nor nucleic acid preparations from orf virus, bovine papular stomatitis virus, cowpoxvirus, Peste des petits ruminants and Blue tongue virus (serotypes 1, 6 and 8). The clinical sensitivity of the LSDV RPA assay matched 100 % (n = 22) to real-time PCR results. In addition, the LSDV RPA assay detected sheep and goat poxviruses. CONCLUSION: The LSDV RPA assay is a rapid and sensitive test that could be implemented in field or at quarantine stations for the identification of LSDV infected case.


Asunto(s)
Bovinos/virología , Virus de la Dermatosis Nodular Contagiosa/aislamiento & purificación , Reacción en Cadena de la Polimerasa/veterinaria , Animales , ADN Viral , Reacción en Cadena de la Polimerasa/métodos , Sensibilidad y Especificidad
18.
Comp Immunol Microbiol Infect Dis ; 110: 102190, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38815398

RESUMEN

Canine parvovirus type 2 (CPV-2) is a major cause of fatal gastroenteritis and myocarditis in puppies of domestic and wild carnivores. CPV-2 has accumulated changes over time lead to the emergence of three antigenic variants CPV-2a, CPV-2b, and CPV-2c. VP2 is the major capsid protein that determines virus antigenicity, and host range. Although the three CPV-2 variants were previously identified in Egypt, most reports covered a restricted geographic region and/or time period, and only analyzed partial fragments of VP2 gene. Therefore, this study was designed to test 100 rectal swabs collected from 7 Egyptian governorates between 2019 and 2021 for CPV-2 using PCR. A total of 65 positive samples were identified, mostly in pure dog breeds of young age. The three variants co-circulated in 2019, while CPV-2b was not detected in 2020 and 2021. The frequency of CPV-2b and CPV-2c was higher in 2019 and 2021, respectively. Analysis of CPV-2 full-length VP2 gene sequence from 19/65 positive samples has identified four common amino acid substitutions F267Y, S297A, A300G, Y324I, which are characteristic for the new CPV-2 variants currently circulating worldwide. Unique substitutions including A5G, G36R, V38E, Q370R, and G392V were recognized in certain samples, and appears to have distinct effect on receptor binding, nuclear translocation, and inter-species transmission. Phylogenetic analysis showed separation of CPV-2 strains into two clades. All strains of this study were classified in clade I with Asian strains. In conclusion, this study provides updated comprehensive molecular analysis of CPV-2 variants in Egypt.


Asunto(s)
Proteínas de la Cápside , Enfermedades de los Perros , Infecciones por Parvoviridae , Parvovirus Canino , Filogenia , Animales , Egipto/epidemiología , Perros , Parvovirus Canino/genética , Parvovirus Canino/clasificación , Parvovirus Canino/aislamiento & purificación , Proteínas de la Cápside/genética , Infecciones por Parvoviridae/veterinaria , Infecciones por Parvoviridae/virología , Infecciones por Parvoviridae/epidemiología , Enfermedades de los Perros/virología , Enfermedades de los Perros/epidemiología , Sustitución de Aminoácidos
19.
Trop Med Infect Dis ; 8(5)2023 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-37235308

RESUMEN

Background: COVID-19 is a respiratory disease that eventually became a pandemic, with 300 million people infected around the world. Alongside the improvement in COVID-19 management and vaccine development, identifying biomarkers for COVID-19 has recently been reported to help in early prediction and managing severe cases, which might improve outcomes. Our study aimed to find out if there is any correlation between clinical severity and elevated hematological and biochemical markers in COVID-19 patients and its effect on the outcome. Methods: We have collected retrospective data on socio-demographics, medical history, biomarkers, and disease outcomes from five hospitals and health institutions in the Kingdom of Saudi Arabia. Results: Pneumonia was the most common presentation of COVID-19 in our cohort. The presence of abnormal inflammatory biomarkers (D-dimer, CRP, troponin, LDH, ferritin, and t white blood cells) was significantly associated with unstable COVID-19 disease. In addition, patients with evidence of severe respiratory disease, particularly those who required mechanical ventilation, had higher biomarkers when compared to those with stable respiratory conditions (p < 0.001). Conclusion: Identifying biomarkers predicts outcomes for COVID-19 patients and may significantly help in their management.

20.
Healthcare (Basel) ; 11(24)2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38132016

RESUMEN

BACKGROUND: Organ transplantation is inherently dependent on the availability of organ donors. There is a noticeable paucity of literature addressing the rates of organ donation registration and the awareness of Islamic regulations (Fatwa) regarding organ donation within Saudi Arabia. Our study aimed to evaluate the level of organ donation registration, awareness of Islamic regulations, and knowledge of the Saudi Center for Organ Transplantation (SCOT) within the Saudi society. METHODS: We conducted a cross-sectional survey from 30 March to 9 April 2023. This survey aimed to assess the awareness of Islamic (Fatwa) guidance on organ donation, the role of SCOT, and the rate of organ donation registration facilitated through the Tawakkalna app, the official health passport application in Saudi Arabia. RESULTS: Out of 2329 respondents, 21% had registered as potential deceased organ donors, despite 87% acknowledging the importance of organ donation. Awareness of the Islamic Fatwa regarding organ donation was reported by 54.7% of respondents, and 37% recognized the Fatwa's acceptance of brain death criteria. The likelihood of registration as organ donors was higher among Saudi citizens under 45 years of age, females, healthcare workers (HCWs), individuals with higher education, relatives of patients awaiting organ donations, those informed about the Islamic Fatwas, and those willing to donate organs to friends. Conversely, being over the age of 25, Saudi nationality, employment as an HCW, awareness of SCOT, and prior organ donation registration were predictive of a heightened awareness of Islamic Fatwas. However, perceiving the importance of organ donation correlated with a lower awareness of the Fatwas. Significant positive correlations were found between awareness of SCOT, awareness of Fatwas, and registration for organ donation. CONCLUSIONS: While the Saudi population exhibits a high regard for the importance of organ donation, this recognition is not adequately translated into registration rates. The discrepancy may be attributable to limited awareness of SCOT and the relevant Islamic Fatwas. It is imperative to initiate organ donation awareness campaigns that focus on religious authorization to boost organ donation rates and rectify prevalent misconceptions.

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