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1.
Sensors (Basel) ; 23(12)2023 Jun 16.
Article in English | MEDLINE | ID: mdl-37420818

ABSTRACT

With the evolution in technology, communication based on the voice has gained importance in applications such as online conferencing, online meetings, voice-over internet protocol (VoIP), etc. Limiting factors such as environmental noise, encoding and decoding of the speech signal, and limitations of technology may degrade the quality of the speech signal. Therefore, there is a requirement for continuous quality assessment of the speech signal. Speech quality assessment (SQA) enables the system to automatically tune network parameters to improve speech quality. Furthermore, there are many speech transmitters and receivers that are used for voice processing including mobile devices and high-performance computers that can benefit from SQA. SQA plays a significant role in the evaluation of speech-processing systems. Non-intrusive speech quality assessment (NI-SQA) is a challenging task due to the unavailability of pristine speech signals in real-world scenarios. The success of NI-SQA techniques highly relies on the features used to assess speech quality. Various NI-SQA methods are available that extract features from speech signals in different domains, but they do not take into account the natural structure of the speech signals for assessment of speech quality. This work proposes a method for NI-SQA based on the natural structure of the speech signals that are approximated using the natural spectrogram statistical (NSS) properties derived from the speech signal spectrogram. The pristine version of the speech signal follows a structured natural pattern that is disrupted when distortion is introduced in the speech signal. The deviation of NSS properties between the pristine and distorted speech signals is utilized to predict speech quality. The proposed methodology shows better performance in comparison to state-of-the-art NI-SQA methods on the Centre for Speech Technology Voice Cloning Toolkit corpus (VCTK-Corpus) with a Spearman's rank-ordered correlation constant (SRC) of 0.902, Pearson correlation constant (PCC) of 0.960, and root mean squared error (RMSE) of 0.206. Conversely, on the NOIZEUS-960 database, the proposed methodology shows an SRC of 0.958, PCC of 0.960, and RMSE of 0.114.


Subject(s)
Noise , Speech , Communication , Computers, Handheld
2.
J Proteome Res ; 20(1): 549-564, 2021 01 01.
Article in English | MEDLINE | ID: mdl-33089695

ABSTRACT

Cystic fibrosis is a genetic pathology characterized by abnormal accumulation of mucus in the respiratory, gastrointestinal, and reproductive tracts, caused by mutations in the CFTR gene. Although the classical presentation of the condition is well known, there is still a need for a better characterization of metabolic alterations related to cystic fibrosis and different genotypic mutations. We employed untargeted, comprehensive lipidomics of blood serum samples to investigate alterations in the lipid metabolism related to the pathology, mutation classes, and lung function decline. Six unique biomarker candidates were able to independently differentiate diseased individuals from healthy controls with excellent performance. Cystic fibrosis patients showed dyslipidemia for most lipid subclasses, with significantly elevated odd-chain and polyunsaturated fatty acyl lipids. Phosphatidic acids and diacylglycerols were particularly affected by different genotypic mutation classes. We selected a biomarker panel composed of four lipids, including two ceramides, one sphingomyelin, and one fatty acid, which correctly classified all validation samples from classes III and IV. A biomarker panel of five oxidized lipids was further selected to differentiate patients with reduced lung function, measured as predicted FEV1%. Our results indicate that cystic fibrosis is deeply related to lipid metabolism and provide new clues for the investigation of the disease mechanisms and therapeutic targets.


Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator , Cystic Fibrosis , Lipidomics , Cystic Fibrosis/diagnosis , Cystic Fibrosis/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Humans , Lung/physiopathology , Mutation
3.
Metabolomics ; 17(1): 4, 2021 01 04.
Article in English | MEDLINE | ID: mdl-33394183

ABSTRACT

INTRODUCTION: Cystic fibrosis (CF) is a lethal multisystemic disease of a monogenic origin with numerous mutations. Functional defects in the cystic fibrosis transmembrane conductance receptor (CFTR) protein based on these mutations are categorised into distinct classes having different clinical presentations and disease severity. OBJECTIVES: The present study aimed to create a comprehensive metabolomic profile of altered metabolites in patients with CF, among different classes and in relation to lung function. METHODS: A chemical isotope labeling liquid chromatography-mass spectrometry metabolomics was used to study the serum metabolic profiles of young and adult CF (n = 39) patients and healthy controls (n = 30). Comparisons were made at three levels, CF vs. controls, among mutational classes of CF, between CF class III and IV, and correlated the lung function findings. RESULTS: A distinctive metabolic profile was observed in the three analyses. 78, 20, and 13 significantly differentially dysregulated metabolites were identified in the patients with CF, among the different classes and between class III and IV, respectively. The significantly identified metabolites included amino acids, di-, and tri-peptides, glutathione, glutamine, glutamate, and arginine metabolism. The top significant metabolites include 1-Aminopropan-2-ol, ophthalmate, serotonin, cystathionine, and gamma-glutamylglutamic acid. Lung function represented by an above-average FEV1% level was associated with decreased glutamic acid and increased guanosine levels. CONCLUSION: Metabolomic profiling identified alterations in different amino acids and dipeptides, involved in regulating glutathione metabolism. Two metabolites, 3,4-dihydroxymandelate-3-O-sulfate and 5-Aminopentanoic acid, were identified in common between the three anlayses and may represent as highly sensitive biomarkers for CF.


Subject(s)
Biomarkers , Cystic Fibrosis/genetics , Cystic Fibrosis/metabolism , Metabolome , Metabolomics , Mutation , Case-Control Studies , Chromatography, Liquid , Cystic Fibrosis/diagnosis , Humans , Mass Spectrometry , Metabolomics/methods , Respiratory Function Tests , Severity of Illness Index
4.
J Proteome Res ; 19(6): 2346-2357, 2020 06 05.
Article in English | MEDLINE | ID: mdl-32312052

ABSTRACT

Mucoviscidosis of the respiratory, gastrointestinal, and genitourinary tracts is the major pathology in patients with cystic fibrosis (CF), a lethal monogenic panethnic and multisystemic disease most commonly identified in Caucasians. Currently, the measurement of immuno reactive trypsinogen in dry blood spots (DBSs) is the gold-standard method for initial newborn screening for CF, followed by targeted CF transmembrane regulator (CFTR) mutation analysis, and ultimate confirmation with abnormally elevated sweat chloride. Previous metabolomics studies in patients with CF reported on different biomarkers such as breath 2-aminoacetophenone produced during acute and chronic infection in human tissues, including the lungs of CF patients. Herein, we used liquid and gas chromatography-mass spectrometry-based targeted metabolomics profiling to identify potentially reliable, sensitive, and specific biomarkers in DBSs collected from 69 young and adult people including CF patients (n = 39) and healthy control (n = 30). A distinctive metabolic profile including 26 significantly differentially expressed metabolites involving amino acids, glycolysis, mitochondrial and peroxisomal metabolism, and sorbitol pathways was identified. Specifically, the osmolyte (sorbitol) was remarkably downregulated in CF patients compared to healthy controls indicating perturbation in the sorbitol pathway, which may be responsible for the mucoviscidosis seen in patients with CF. The significance of our findings is supported by the clinical utility of inhaled mannitol and hypertonic saline in patients with CF. The systemic administration of sorbitol in such patients may confer additional benefits beyond the respiratory system, especially in those with misfolded CFTR proteins.


Subject(s)
Cystic Fibrosis , Adult , Cystic Fibrosis/diagnosis , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Humans , Infant, Newborn , Metabolome , Metabolomics , Mutation , Neonatal Screening
5.
Int J Mol Sci ; 21(19)2020 Oct 08.
Article in English | MEDLINE | ID: mdl-33050003

ABSTRACT

Cystic fibrosis (CF), the most common lethal autosomal recessive disorder among Caucasians, is caused by mutations in the CF transmembrane conductance regulator (CFTR) chloride channel gene. Despite significant advances in the management of CF patients, novel disease-related biomarkers and therapies must be identified. We performed serum proteomics profiling in CF patients (n = 28) and healthy subjects (n = 10) using the 2D-DIGE MALDI-TOF proteomic approach. Out of a total of 198 proteins identified, 134 showed a statistically significant difference in abundance and a 1.5-fold change (ANOVA, p < 0.05), including 80 proteins with increased abundance and 54 proteins with decreased abundance in CF patients. A multiple reaction monitoring-mass spectrometry analysis of six differentially expressed proteins identified by a proteomic approach (DIGE-MALD-MS) showed a significant increase in C3 and CP proteins and a decrease in APOA1, Complement C1, Hp, and RBP4proteins compared with healthy controls. Fifteen proteins were identified as potential biomarkers for CF diagnosis. An ingenuity pathway analysis of the differentially regulated proteins indicates that the central nodes dysregulated in CF subjects involve pro-inflammatory cytokines, ERK1/2, and P38 MAPK, which are primarily involved in catalytic activities and metabolic processes. The involved canonical pathways include those related to FXR/RXR, LXR/RXR, acute phase response, IL12, nitric oxide, and reactive oxygen species in macrophages. Our data support the current efforts toward augmenting protease inhibitors in patients with CF. Perturbations in lipid and vitamin metabolism frequently observed in CF patients may be partly due to abnormalities in their transport mechanism.


Subject(s)
Cystic Fibrosis/blood , Cystic Fibrosis/genetics , Proteome , Signal Transduction/genetics , Transcriptome , Adolescent , Adult , Biomarkers/metabolism , Child , Cohort Studies , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Female , Gene Expression Profiling , Humans , Male , Mutation , Protein Interaction Maps , Proteomics/methods , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Two-Dimensional Difference Gel Electrophoresis/methods , Young Adult
6.
Comput Biol Med ; 152: 106426, 2023 01.
Article in English | MEDLINE | ID: mdl-36565485

ABSTRACT

Brain tumors are one of the most fatal cancers. Magnetic Resonance Imaging (MRI) is a non-invasive method that provides multi-modal images containing important information regarding the tumor. Many contemporary techniques employ four modalities: T1-weighted (T1), T1-weighted with contrast (T1c), T2-weighted (T2), and fluid-attenuation-inversion-recovery (FLAIR), each of which provides unique and important characteristics for the location of each tumor. Although several modern procedures provide decent segmentation results on the multimodal brain tumor image segmentation benchmark (BraTS) dataset, they lack performance when evaluated simultaneously on all the regions of MRI images. Furthermore, there is still room for improvement due to parameter limitations and computational complexity. Therefore, in this work, a novel encoder-decoder-based architecture is proposed for the effective segmentation of brain tumor regions. Data pre-processing is performed by applying N4 bias field correction, z-score, and 0 to 1 resampling to facilitate model training. To minimize the loss of location information in different modules, a residual spatial pyramid pooling (RASPP) module is proposed. RASPP is a set of parallel layers using dilated convolution. In addition, an attention gate (AG) module is used to efficiently emphasize and restore the segmented output from extracted feature maps. The proposed modules attempt to acquire rich feature representations by combining knowledge from diverse feature maps and retaining their local information. The performance of the proposed deep network based on RASPP, AG, and recursive residual (R2) block termed RAAGR2-Net is evaluated on the BraTS benchmarks. The experimental results show that the suggested network outperforms existing networks that exhibit the usefulness of the proposed modules for "fine" segmentation. The code for this work is made available online at: https://github.com/Rehman1995/RAAGR2-Net.


Subject(s)
Brain Neoplasms , Humans , Brain Neoplasms/diagnostic imaging , Benchmarking , Image Processing, Computer-Assisted , Magnetic Resonance Imaging
7.
Comput Biol Med ; 163: 107132, 2023 09.
Article in English | MEDLINE | ID: mdl-37343468

ABSTRACT

Retinal vessel segmentation is an important task in medical image analysis and has a variety of applications in the diagnosis and treatment of retinal diseases. In this paper, we propose SegR-Net, a deep learning framework for robust retinal vessel segmentation. SegR-Net utilizes a combination of feature extraction and embedding, deep feature magnification, feature precision and interference, and dense multiscale feature fusion to generate accurate segmentation masks. The model consists of an encoder module that extracts high-level features from the input images and a decoder module that reconstructs the segmentation masks by combining features from the encoder module. The encoder module consists of a feature extraction and embedding block that enhances by dense multiscale feature fusion, followed by a deep feature magnification block that magnifies the retinal vessels. To further improve the quality of the extracted features, we use a group of two convolutional layers after each DFM block. In the decoder module, we utilize a feature precision and interference block and a dense multiscale feature fusion block (DMFF) to combine features from the encoder module and reconstruct the segmentation mask. We also incorporate data augmentation and pre-processing techniques to improve the generalization of the trained model. Experimental results on three fundus image publicly available datasets (CHASE_DB1, STARE, and DRIVE) demonstrate that SegR-Net outperforms state-of-the-art models in terms of accuracy, sensitivity, specificity, and F1 score. The proposed framework can provide more accurate and more efficient segmentation of retinal blood vessels in comparison to the state-of-the-art techniques, which is essential for clinical decision-making and diagnosis of various eye diseases.


Subject(s)
Deep Learning , Algorithms , Image Processing, Computer-Assisted/methods , Retinal Vessels/diagnostic imaging , Fundus Oculi
8.
J Pharm Biomed Anal ; 216: 114801, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35504217

ABSTRACT

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel found on the apical surface of epithelial cells in the airway and gastrointestinal tract. A mutation in the CFTR protein is responsible for developing cystic fibrosis (CF) disease. Therefore, circulating CFTR protein could be a promising biomarker of CF disease. Multiple methodological challenges are associated with CF's available diagnostic and screening methods, such as low specificity and potential false discovery rate, mainly for ethnic groups whose CFTR mutations are not covered in the mutation panels. Herein, we have developed an absolute quantification (AQUA) method based on two CFTR signature peptides (SPs). A liquid chromatography-tandem spectrometry (LC-MS/MS) method in multiple reaction monitoring (MRM) mode (MRM transitions 1168.90 > 85.929 and 707.19 > 85.93 of SP1 and SP2, respectively) enabled the accurate quantification of CFTR protein in a dried blood spot (DBS). The method was validated successfully based on international guidelines in terms of signal linearity, precision (within-run CV 3.37-8.54%; between-run CV 5.15-11.06% for the selected SPs), and accuracy (within-run 93.4-105.59%; between-run 97.45-103.28% for the selected SPs). The level of soluble CFTR protein was evaluated as a potential biomarker for CF using patients (n = 39) and healthy controls (n = 30), were found to be in CF patients lower than controls. For instant, the level of signature peptide 1 (SP1) was 2.09 ± 0.55 nM, 68.77 ± 1.40 nM in CF patients compared to Ctrl, respectively; p < 0.0001. This study is the first to report CFTR levels in DBS using signature peptides by LC-MS/MS as a diagnostic marker for CF. The receiver operating characteristic (ROC) for CFTR SP1 and SP2 showed a significant area under the curves (AUC) 0.7714 (99% CI, p < 0.0001), and 0.8234 (99% CI, p < 0.0001), respectively. The presented MRM method provides a highly specific and sensitive approach to CFTR quantification in a DBS and could be applied in CF screening.


Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator , Cystic Fibrosis , Biomarkers , Chromatography, Liquid , Cystic Fibrosis/diagnosis , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Humans , Tandem Mass Spectrometry
9.
Exp Clin Transplant ; 19(4): 359-366, 2021 04.
Article in English | MEDLINE | ID: mdl-33535940

ABSTRACT

OBJECTIVES: Tuberculosis is an important opportunist infection that can complicate the posttransplant course of solid-organ transplant recipients. Lung transplant recipients are at higher risk of tuberculosis after transplant than are other solid-organ transplant recipients. Significant drug-drug interactions between antituberculous medications, especially rifampin, and immunosuppressant medications render treatment in this patient population especially challenging. Data on the management of tuberculosis in lung transplant recipients with rifamycin-sparing regimens are so far limited. Therefore, we evaluated the incidence, clinical features, treatment, and outcomes of active tuberculosis in lung transplant patients from a single center in Riyadh, Saudi Arabia. MATERIALS AND METHODS: Cases of active tuberculosis in lung transplant recipients diagnosed between January 2005 and December 2017 at our center were included. Data on patient demographics, clinical presentations, diagnosis, treatment regimens, and outcomes were collected. RESULTS: Seven of 133 lung transplant recipients (5.3%) were diagnosed with active tuberculosis during the study period, corresponding to an incidence rate of 2147/100 000 person-years. Patients were diagnosed at median time of 94 days posttransplant. Fever and weight loss were the most common presenting symptoms. All patients were initially treated with a regimen consisting of isoniazid, ethambutol, pyrazinamide, and moxifloxacin. Isoniazid was later substituted with rifabutin in 2 patients with isoniazid-resistant tuberculosis. All patients were treated for a total of 9 to 12 months, without any adverse event-related interruptions. All patients were alive at 12 months after the diagnosis of tuberculosis. There was no evidence of relapse in any of the patients after a median of 32 (range, 9-51) months of follow-up after treatment. CONCLUSIONS: Rifamycin-sparing regimens appear to be safe and highly efficacious in the treatment of active tuberculosis in lung transplant recipients.


Subject(s)
Lung Transplantation , Transplant Recipients , Tuberculosis , Ethambutol/therapeutic use , Humans , Isoniazid/therapeutic use , Lung , Moxifloxacin/therapeutic use , Pyrazinamide/therapeutic use , Rifamycins , Treatment Outcome , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis/epidemiology
10.
Int J Pediatr Adolesc Med ; 8(1): 25-28, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33718573

ABSTRACT

INTRODUCTION: Cystic fibrosis (CF) has been reported before in Saudi Arabia and the Gulf area. It has been found that screening for 10 most common cystic fibrosis transmembrane conductance regulator (CFTR) mutations can detect 80% of positive CFTR cases. OBJECTIVES: To determine the geographic distribution of the most common CFTR variants in 5 regions of Saudi Arabia. METHODOLOGY: A retrospective chart review of all CFTR variants conducted from January 1, 1992 to December 1, 2017. RESULTS: The ten most common CFTR mutations in the Saudi population were as follows: p.Gly473GlufsX54 (17%), p.Phe508del (12%), p.Ile1234Val (12%), 3120+1G > A (11%), 711+1G > T (9%), p.His139Leu (6%), p.Gln637Hisfs (5%), p.Ser549Arg (3%), p.N1303K (3%), and delExon19-21 (2%) along with other variants 79 (20%). In terms of the highest frequency, the c.2988+1G > A (3120+1G > A) variant was found in the eastern province (7.3%) of Saudi Arabia, the c.1418delG (p.Gly473GlufsX54) variant in the northern province (6.8%), the c.579+1G > T (711+1G > T) variant in the southern province (4.8%), the c.3700A > G (p.Ile1234Val) variant in the central province (4.8%), and c.1521_1523delCTT (p.Phe508del) variant in the western province (4.3%). CONCLUSION: The eastern and the northern provinces have the highest prevalence of CF, with the c.2988+1G > A (3120+1G > A) and c.1418delG (p.Gly473GlufsX54) variants showing the highest distribution in the Saudi CF population, which may reflect the effect of consanguinity within the same tribe. Proper family screening and counseling should be emphasized.

11.
Exp Clin Transplant ; 19(1): 58-63, 2021 01.
Article in English | MEDLINE | ID: mdl-33441058

ABSTRACT

OBJECTIVES: Lung transplant guidelines recommend nebulized amphotericin B with or without systemic antifungal agents for fungal prophylaxis. However, amphotericin formulation, dosing, and frequency vary between studies. We assessed the safety and effectiveness of nebulized amphotericin B to prevent Aspergillus infection in 2 regimens, ie, twice daily compared with 3 times daily. MATERIALS AND METHODS: This was a single-center retrospective cohort study. We included patients at least 14 years old who underwent lung transplant and received nebulized amphotericin B alone or in combination with another antifungal agent either twice daily or 3 times daily. The primary endpoint was the incidence of lung Aspergillus infection, and the secondary endpoints were nebulized amphotericin B side effects and breakthrough Aspergillus infection. RESULTS: A total of 84 patients were included. The group given nebulized amphotericin twice daily had a higher rate of Aspergillus infection at 17% compared with 4% in the group treated 3 times daily (P = .24). No serious side effects were reported, but coughing and diarrhea were more common in patients who received amphotericin B 3 times daily. CONCLUSIONS: A systemic antifungal agent combined with nebulized amphotericin either twice or 3 times daily has been effective to prevent Aspergillus infection. Nebulized amphotericin twice daily may be a more viable option to increase a patient's adherence and decrease medication cost and side effects. However, a larger randomized controlled trial is needed to determine the best dosing regimen for nebulized amphotericin B as a fungal prophylaxis after lung transplant.


Subject(s)
Amphotericin B/administration & dosage , Antifungal Agents/administration & dosage , Aspergillosis , Lung Transplantation , Aspergillosis/diagnosis , Aspergillosis/prevention & control , Aspergillus , Humans , Lung Transplantation/adverse effects , Retrospective Studies
12.
Cureus ; 12(6): e8733, 2020 Jun 21.
Article in English | MEDLINE | ID: mdl-32596091

ABSTRACT

Brucella is one of the most common zoonotic diseases worldwide. It is endemic in the Mediterranean basin. Brucella pneumonia is a rare complication of brucellosis that can present with a variety of clinical and radiological manifestations. It was described only once previously in the setting of solid organ transplant. A 32-year-old female from Saudi Arabia with cystic fibrosis and bronchiectasis presented five weeks after a bilateral lung transplant with fever and cough. Investigation showed high inflammatory markers in addition to a pulmonary infiltrate in the chest imaging. All microbiological workups were negative including bronchoalveolar lavage cultures. Brucella serology was positive and she was started on anti-Brucella therapy which resulted in complete resolution of her symptoms and radiological changes. This case demonstrates an unusual presentation of Brucellosis. It highlights the importance of epidemiology in evaluating post-transplant infections. We reviewed and summarized the literature on brucellosis post solid organ transplant and the various treatment regimens for Brucella pneumonia. This is the first case report of Brucella pneumonia in a lung transplant patient. Brucella is a rare complication post solid organ transplant but it has a good prognosis.

13.
Int J Pediatr Adolesc Med ; 7(2): 83-87, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32292813

ABSTRACT

INTRODUCTION: Studies have shown that pulmonary exacerbations in cystic fibrosis (CF) patients are associated with respiratory viruses. The most common agent causing viral infections in patients with CF before the age of 3 years is respiratory syncytial virus. OBJECTIVES: To obtain the prevalence of the different types of viral infection in CF patients and to identify its relation with the type of bacterial infection, (CFTR) mutations and pulmonary function test (PFT). METHODOLOGY: A retrospective charts review of 387 patients with CF of all age groups who were screened for the detection of viruses during respiratory exacerbation from the period of January 1, 1984 to June 1, 2016. RESULTS: A total of 159 CF patients had pulmonary exacerbation and had viral PCR obtained. Fifty-eight patients (36%) had positive viral PCR. Males were more commonly infected in 30/58 patients (52%) compared to females in 28 patients (48%). Forty-five of 58 patients (78%) were alive and 13 patients (22%) died. Rhinovirus was the most frequently reported viral PCR in 33/74 sample (45%). Out of 74 viral PCR, 41 (55.4%) were during the colder seasons (October-February) and 33 (44.5%) during the warmer seasons (March-September). During viral infection and viral recurrence, there was an increase in bacterial colonization specifically of H. influenza and staphylococcus aureus. The most common CFTR mutation for the CF viral infection is: 3120+1G>A in Intron 16 in 11/57 patients (19%). The Eastern Province had the highest viral infection of 24 out of 57 patients (42%). Follow-up PFT post viral infection showed no significant difference in the type and the severity of PFT compared to the initial PFT during the viral illness. CONCLUSION: Viral infections contributed to the increase in morbidity and mortality of CF patients in our population, and rhinovirus was the most common causative agent. Viral infections and viral recurrence increased the prevalence of bacterial infection of specific pathogens such as H. influenza and S. aureus. Physicians should be aware to prevent progressive lung damage in CF patients by treating the concomitant viral and bacterial infections. Viral infection may be associated with some common CFTR mutations.

14.
Ann Saudi Med ; 40(1): 15-24, 2020.
Article in English | MEDLINE | ID: mdl-32026723

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) occurs in populations in Saudi Arabia and the Gulf area. Approximately 2000 known variants have been identified for the CF transmembrane conductance regulator (CTFR) gene. Screening for ten of the most common variants can detect 80% of alleles. OBJECTIVE: Determine the pattern of CFTR variants in the CF population of Saudi Arabia. DESIGN: A retrospective, descriptive. SETTING: Tertiary care center. PATIENTS AND METHODS: We examined the medical records of 396 confirmed CF patients of all age groups that were positive for a CFTR variant from the period of 1 January 1998 to 1 December 2017. MAIN OUTCOME MEASURES: Zygosity, morbidity and mortality patterns of different types of CFTR variants. SAMPLE SIZE: 312 families that included 396 patients. RESULTS: Of 48 variants identified, 6 were novel, having not been described in the medical literature. A homozygous state was found in 283 families (90.7%) and compound heterozygosity in 23 (7.4%). Six families were heterozygous (1.9%). Median age (interquartile range) was 10.2 months (4.4 months to 5.7 years) at diagnosis and 9.7 (5.4-16.5) years at follow up. Of 396 patients, 378 patients (95.5%) survived and 18 (4.5%) died. The ten most common variants identified in descending frequency were: p.Gly473GlufsX54 in 98 alleles (16%), p.Ile1234Val in 66 alleles (11%), F508del in 64 alleles (11%), 711+1G>T in 62 alleles (10%), 3120+1G>A in 62 alleles (11%), p.His139Leuin 38 alleles (6.4%), p.Gln637Hisfs in 30 alleles (5.2%), p.Ser549Arg in 27 alleles (4.5%), p.Asn1303Lys in 14 alleles (2.3%), delExon19-21in 10 alleles (1.6%). This analysis identified 79.2% of our CFTR variants. CONCLUSION: CFTR mutational patterns in our CF population are characterized by a high allelic heterogeneity. The high prevalence of homozygous variants reflects the high level of consanguinity between parents. LIMITATIONS: Our CFTR screening reflected only about 80% of CF patients in Saudi Arabia. CONFLICT OF INTEREST: None.


Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis/genetics , Genotype , Adolescent , Alleles , Child , Child, Preschool , Consanguinity , Female , Gene Frequency , Heterozygote , Homozygote , Humans , Infant , Male , Mutation , Retrospective Studies , Saudi Arabia
15.
Ann Saudi Med ; 39(4): 221-228, 2019.
Article in English | MEDLINE | ID: mdl-31381371

ABSTRACT

BACKGROUND: Lung transplantation has become a standard of care for a select group of patients with advanced lung diseases. Lung transplantation has undergone rapid growth in the last few years in Saudi Arabia. OBJECTIVE: Describe five years of experience with lung transplantation. DESIGN: Retrospective, descriptive. SETTINGS: Major tertiary care hospital. PATIENTS: All patients who underwent lung transplant surgery between 2010 to 2015. MAIN OUTCOME MEASURES: Indications for lung transplant demographics, body mass index, blood group, type of transplant surgery, morbidity rate using the Clavien-Dindo classification, rate of early- and late-onset bronchiolitis obliterans syndrome (BOS), bronchiolitis obliterans-free survival, 30- and 90-day mortality rate, and survival (30 days, 90 days, 1-year, 3-years and 5-years) for lung transplant recipients. The duration of mechanical ventilation, colonization by bacteria and need for lung volume reduction surgery for lung donors. SAMPLE SIZE: 80, 45% women and 55% men. RESULTS: The most common indication for lung transplant in Saudi Arabia is pulmonary fibrosis (45%), followed by non-cystic fibrosis bronchiectasis (25%) and cystic fibrosis-related bronchiectasis (20%). Only 45% of our lung transplant recipients had a normal BMI (18-28 kg/m2). The most frequent blood group was A (40%), followed by blood group O (32.5%). Most (85%) lung transplants were bilateral while 15% were single lung transplants. Postoperative complications developed in 64 patients, 34 (42.5%) had minor grade 1 complications, while 13 (16.5%) had severe complications leading to death (grade V). Early onset BOS developed in 6 (7.5%) patients while 16 (20%) had late onset BOS. The BOS-free survival rate was 72.5%. The mean duration of mechanical ventilation in lung donors was 9 days and most were infected by bacteria. The majority of recipients required lung volume reduction. The 30-day mortality rate was 12.5% and the 90-day mortality rate was 17.5%. Survival rates at our center were 87.5% at 30 days, 82.5% at 90 days, 81.2% at 1 year, 67.9% at 2 years and 62.1% at 5 years. CONCLUSIONS: Lung transplantation has become an invaluable approach for the treatment of end-stage respiratory disease. Our 5-year experience has shown exciting promises for lung transplantation in Saudi Arabia. LIMITATIONS: Retrospective design, single center experience. CONFLICT OF INTEREST: None.


Subject(s)
Bronchiolitis Obliterans/epidemiology , Lung Diseases/surgery , Lung Transplantation/statistics & numerical data , Postoperative Complications/epidemiology , Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Retrospective Studies , Saudi Arabia , Survival Rate , Time Factors , Transplant Recipients/statistics & numerical data , Young Adult
16.
Bone Marrow Transplant ; 54(2): 190-203, 2019 02.
Article in English | MEDLINE | ID: mdl-30082851

ABSTRACT

Solid organ transplantation (SOT) following haematopoietic cell transplantation (HCT) is a rare event. Uncertainty exists whether such recipients are at higher risk of relapse of underlying haematological disease or at increased risk of developing infectious or immunological complications and malignancies following SOT. The experience at our referral organ transplantation center and the present literature of SOT (n = 198) in recipients following previous HCT was systematically reviewed. Outcome analysis of 206 SOT recipients following HCT challenges the validity of the frequently stated comparable outcome with recipients without prior HCT. SOT recipients after HCT are younger and have a higher mortality and morbidity in comparison with "standard" recipients. Rejection rates for SOT recipients following HCT appear to be lower for all organs, except for liver transplantation. In the setting of liver transplantation following HCT, mortality for recipients of deceased donor grafts appears to be exceptionally high, although experience with grafts of living donors are favourable. Morbidity was mostly associated with infectious and malignant complications. Of note some SOT recipients who received solid organ donation from the same HCT donor were able to achieve successful withdrawal of immune suppression. Despite limited follow-up, recipients with prior HCT show a different course after SOT, necessitating attention and closer follow-up.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Organ Transplantation/mortality , Referral and Consultation , Reoperation/mortality , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Kidney Transplantation , Liver Transplantation , Male , Middle Aged , Tissue Donors , Transplantation, Homologous , Treatment Outcome , Young Adult
17.
Biosens Bioelectron ; 117: 84-90, 2018 Oct 15.
Article in English | MEDLINE | ID: mdl-29890394

ABSTRACT

Simultaneous and point-of-care detection of multiple protein biomarkers has significant impact on patient care. Spinal Muscular Atrophy (SMA), Cystic Fibrosis (CF) and Duchenne Muscular Dystrophy (DMD) are well known progressive hereditary disorders associated with increased morbidity as well as mortality. Therefore, rapid detection of biomarkers specific for these three disorders in newborns offers new opportunities for early diagnosis, delaying symptoms and effective treatment. Here, we report the development of a disposable carbon nanofiber (CNF)-based electrochemical immunosensor for simultaneous detection of survival motor neuron 1 (SMN1), cystic fibrosis transmembrane conductance regulator (CFTR) and DMD proteins. The CNF-modified array electrodes were first functionalized by electroreduction of carboxyphenyl diazonium salt. Then, the immunosensor was fabricated by the covalent immobilization of the three antibodies on the working electrodes of the array sensor via carbodiimide (EDC/NHS) chemistry. Simultaneous detection of CFTR, DMD and SMN1 was achieved with high sensitivity and detection limits of 0.9 pg/ml, 0.7 pg/ml and 0.74 pg/ml, respectively. The multiplexed immunosensor has also shown strong selectivity against non-specific proteins. Moreover, high recovery percentage was obtained when the immunosensor was applied in spiked whole blood samples. This voltammetric immunosensor offers cost effective, easy to use, rapid and high throughput potential screening method for these three hereditary disorders using only few drops of blood.


Subject(s)
Blood Chemical Analysis/instrumentation , Blood Chemical Analysis/methods , Genetic Diseases, Inborn/diagnosis , Nanofibers/chemistry , Neonatal Screening/methods , Carbon/chemistry , Cystic Fibrosis/blood , Cystic Fibrosis/diagnosis , Cystic Fibrosis Transmembrane Conductance Regulator/analysis , Cystic Fibrosis Transmembrane Conductance Regulator/blood , Genetic Diseases, Inborn/blood , Humans , Infant, Newborn , Limit of Detection , Muscle Proteins/analysis , Muscle Proteins/blood , Muscular Atrophy, Spinal/diagnosis , Muscular Dystrophy, Duchenne/blood , Muscular Dystrophy, Duchenne/diagnosis , Survival of Motor Neuron 1 Protein/analysis , Survival of Motor Neuron 1 Protein/blood
19.
Turk J Gastroenterol ; 15(4): 207-12, 2004 Dec.
Article in English | MEDLINE | ID: mdl-16249972

ABSTRACT

Surgical intervention among cirrhotic individuals carries a high risk for peri-and postoperative complications. We review the literature regarding the frequency and consequences of pulmonary complications in cases of cirrhosis. The experience with hepato-pulmonary syndrome and porto-pulmonary hypertension in liver transplant recipients is also presented.


Subject(s)
Intraoperative Complications , Liver Cirrhosis/complications , Liver Cirrhosis/surgery , Lung Diseases/etiology , Postoperative Complications , Humans
20.
Ann Saudi Med ; 34(5): 447-9, 2014.
Article in English | MEDLINE | ID: mdl-25827705

ABSTRACT

We describe a case of pulmonary epitheloid hemangioendothelioma (PEH) in a 13 years old girl, the aggressive nature of the tumor in this particular case and the PET CT findings. PEH are rare tumors of vascular origin, first described by Dial and Liebow in 1975. This is an uncommon pulmonary neoplasm, 4 times more common in young women. This tumor can affect multiple organs (lung, liver, bones and soft tissue, skin, heart, central nervous system). However lung and liver represent 2 main locations. Clinical manifestations are variable; typically patients are asymptomatic, and PEH is detected on routine chest radiographs as bilateral small (1 cm or less) nodules in the lungs Diagnosis usually requires a surgical lung biopsy. The prognosis is very unpredictable, with life expectancy ranging from 1 to 15 years. The tumor is usually considered as low to intermediate grade sarcoma. There is no single effective treatment however spontaneous remissions and aggressive behavior has been described.


Subject(s)
Hemangioendothelioma, Epithelioid/diagnosis , Lung Neoplasms/diagnosis , Neoplasms, Multiple Primary/diagnosis , Pleural Neoplasms/diagnosis , Positron-Emission Tomography , Tomography, X-Ray Computed , Adolescent , Fatal Outcome , Female , Hemangioendothelioma, Epithelioid/pathology , Humans , Lung Neoplasms/pathology , Multimodal Imaging , Neoplasms, Multiple Primary/pathology , Pleural Neoplasms/pathology
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