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1.
Virol J ; 21(1): 102, 2024 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698421

RESUMO

Human parechovirus, a member of the Picornaviridae family (PeVs), can lead to severe infections, including severe meningitis, meningoencephalitis, and sepsis-like syndrome. We report a case of human parechovirus-related encephalitis in a 52-year-old woman diagnosed with glioblastoma multiforme. She underwent surgical resection in June 2022. Unfortunately, her disease recurred, and she underwent a second resection in August 2022, followed by radiation therapy and Temozolomide therapy. She presented to the hospital with acute confusion followed by seizures, necessitating intubation for airway support. A cerebrospinal fluid (CSF) sample was obtained and processed using the Biofire FilmArray, which reported the detection of HSV-1. Despite being on Acyclovir, the patient did not show signs of improvement. Consequently, a second CSF sample was obtained and sent for next-generation sequencing (NGS), which returned a positive result for Parechovirus. In this presented case, the patient exhibited symptoms of an unknown infectious cause. The utilization of NGS and metagenomic analysis helped identify Parechovirus as the primary pathogen present, in addition to previously identified HSV. This comprehensive approach facilitated a thorough assessment of the underlying infection and guided targeted treatment. In conclusion, the application of NGS techniques and metagenomic analysis proved instrumental in identifying the root cause of the infection.


Assuntos
Hospedeiro Imunocomprometido , Parechovirus , Infecções por Picornaviridae , Humanos , Feminino , Pessoa de Meia-Idade , Infecções por Picornaviridae/virologia , Infecções por Picornaviridae/diagnóstico , Parechovirus/genética , Parechovirus/isolamento & purificação , Parechovirus/classificação , Arábia Saudita , Sequenciamento de Nucleotídeos em Larga Escala , Glioblastoma/virologia , Metagenômica , Encefalite Viral/virologia , Encefalite Viral/diagnóstico , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/isolamento & purificação , Hospitalização
2.
Clin Case Rep ; 12(4): e8736, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38634089

RESUMO

This report described a patient not known to have a hepatic disease, found to have a drug-induced autoimmune hepatitis from denosumab. This is an unreported side effect, and here, we presented the possible predisposing factors and suggested monitoring parameters.

3.
J Biomol Struct Dyn ; : 1-18, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441606

RESUMO

Dengue fever, a major global health challenge, affects nearly half the world's population and lacks effective treatments or vaccines. Addressing this, our study focused on natural compounds that potentially inhibit the dengue virus's RNA-dependent RNA polymerase (RdRp), a crucial target in the viral replication cycle. Utilizing the MTiOpenScreen webserver, we screened 1226 natural compounds from the NP-lib database. This screening identified four promising compounds ZINC000059779788, ZINC0000044404209, ZINC0000253504517 and ZINC0000253499146), each demonstrating high negative binding energies between -10.4 and -9.9 kcal/mol, indicative of strong potential as RdRp inhibitors. These compounds underwent rigorous validation through re-docking and a detailed 100 ns molecular dynamics (MD) simulation. This analysis affirmed the dynamic stability of the protein-ligand complexes, a critical factor in the effectiveness of potential drug candidates. Additionally, we conducted essential dynamics and free energy landscape calculations to understand the structural transitions in the RdRp protein upon ligand binding, providing valuable insights into the mechanism of inhibition. Our findings present these natural molecules as promising therapeutic agents against the dengue virus. By targeting the allosteric site of RdRp, these compounds offer a novel approach to hinder the viral replication process. This research significantly contributes to the search for effective anti-dengue treatments, positioning natural compounds as potential key players in dengue virus control strategies.Communicated by Ramaswamy H. Sarma.

4.
Saudi Pharm J ; 32(1): 101889, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38090737

RESUMO

The present study utilized molecular docking and density functional theory (DFT) approaches, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties to investigate the binding interactions, reactivity, stability, and drug-likeness of curcumin (1), tetrahydrocurcumin (2), and tetrahydrocurcumin derivatives (3-6) as potential anti-cancer agents. MGL (Molecular Graphic Laboratory) and Discovery Studio Visualizer (DSV) software employed for docking studies. Pharmacokinetic and pharmacodynamic (ADME-Tox) analyses were conducted using SwissADME and pKCSM web servers. Total Electron Density (TED) measurements identified molecular adsorption sites, considering various factors, including quantum chemical characteristics, to assess compound effectiveness using DFT method implanted in the Gaussian software. The binding energy (Eb) from docking simulations was used to evaluate inhibitory potential. ADMET analysis suggested favorable oral bioavailability and pharmacokinetics for all studied substances, excluding compound 4. DFT and docking investigations highlighted compounds 1, 2, and 6 as optimal scaffolds for drug design based on in silico screening tests.

5.
Medicina (Kaunas) ; 59(11)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-38003976

RESUMO

Streptococcus pneumoniae (S. pneumoniae) is a bacterial species often associated with the occurrence of community-acquired pneumonia (CAP). CAP refers to a specific kind of pneumonia that occurs in individuals who acquire the infection outside of a healthcare setting. It represents the leading cause of both death and morbidity on a global scale. Moreover, the declaration of S. pneumoniae as one of the 12 leading pathogens was made by the World Health Organization (WHO) in 2017. Antibiotics like ß-lactams, macrolides, and fluoroquinolones are the primary classes of antimicrobial medicines used for the treatment of S. pneumoniae infections. Nevertheless, the efficacy of these antibiotics is diminishing as a result of the establishment of resistance in S. pneumoniae against these antimicrobial agents. In 2019, the WHO declared that antibiotic resistance was among the top 10 hazards to worldwide health. It is believed that penicillin-binding protein genetic alteration causes ß-lactam antibiotic resistance. Ribosomal target site alterations and active efflux pumps cause macrolide resistance. Numerous factors, including the accumulation of mutations, enhanced efflux mechanisms, and plasmid gene acquisition, cause fluoroquinolone resistance. Furthermore, despite the advancements in pneumococcal vaccinations and artificial intelligence (AI), it is not feasible for individuals to rely on them indefinitely. The ongoing development of AI for combating antimicrobial resistance necessitates more research and development efforts. A few strategies can be performed to curb this resistance issue, including providing educational initiatives and guidelines, conducting surveillance, and establishing new antibiotics targeting another part of the bacteria. Hence, understanding the resistance mechanism of S. pneumoniae may aid researchers in developing a more efficacious antibiotic in future endeavors.


Assuntos
Anti-Infecciosos , Infecções Comunitárias Adquiridas , Pneumonia , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Streptococcus pneumoniae , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , beta-Lactamas/farmacologia , beta-Lactamas/uso terapêutico , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Inteligência Artificial , Farmacorresistência Bacteriana , Pneumonia/tratamento farmacológico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia
6.
Mol Divers ; 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37925643

RESUMO

Marburg virus disease (MVD) is caused by the Marburg virus, a one-of-a-kind zoonotic RNA virus from the genus Filovirus. Thus, this current study employed AI-based QSAR and molecular docking-based virtual screening for identifying potential binders against the target protein (nucleoprotein (NP)) of the Marburg virus. A total of 2727 phytochemicals were used for screening, out of which the top three compounds (74977521, 90470472, and 11953909) were identified based on their predicted bioactivity (pIC50) and binding score (< - 7.4 kcal/mol). Later, MD simulation in triplicates and trajectory analysis were performed which showed that 11953909 and 74977521 had the most stable and consistent complex formations and had the most significant interactions with the highest number of hydrogen bonds. PCA (principal component analysis) and FEL (free energy landscape) analysis indicated that these compounds had favourable energy states for most of the conformations. The total binding free energy of the compounds using the MM/GBSA technique showed that 11953909 (ΔGTOTAL = - 30.78 kcal/mol) and 74977521 (ΔGTOTAL = - 30 kcal/mol) had the highest binding affinity with the protein. Overall, this in silico pipeline proposed that the phytochemicals 11953909 and 74977521 could be the possible binders of NP. This study aimed to find phytochemicals inhibiting the protein's function and potentially treating MVD.

7.
J Infect Public Health ; 16(11): 1837-1847, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37769584

RESUMO

Infectious diseases present a global challenge, requiring accurate diagnosis, effective treatments, and preventive measures. Artificial intelligence (AI) has emerged as a promising tool for analysing complex molecular data and improving the diagnosis, treatment, and prevention of infectious diseases. Computer-aided detection (CAD) using convolutional neural networks (CNN) has gained prominence for diagnosing tuberculosis (TB) and other infectious diseases such as COVID-19, HIV, and viral pneumonia. The review discusses the challenges and limitations associated with AI in this field and explores various machine-learning models and AI-based approaches. Artificial neural networks (ANN), recurrent neural networks (RNN), support vector machines (SVM), multilayer neural networks (MLNN), CNN, long short-term memory (LSTM), and random forests (RF) are among the models discussed. The review emphasizes the potential of AI to enhance the accuracy and efficiency of diagnosis, treatment, and prevention of infectious diseases, highlighting the need for further research and development in this area.

8.
J Infect Public Health ; 16(9): 1500-1509, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37353430

RESUMO

INTRODUCTION: Understanding the pathophysiology of HIV infection has been crucial to the design of effective anti-viral strategies. HIV infection is declining worldwide due to early diagnosis and the effective long-term use of anti-retroviral therapy. New infections decreased from 3.3 million in 2002-2.3 million in 2012. However, in the Middle East and North Africa (MENA), an estimated 83,000 individuals still acquired the virus, with 37,000 morbidities reported. The first incidence of acquired immunodeficiency syndrome (AIDS) from the Kingdom of Saudi Arabia (KSA) was reported in 1984. By the end of 2013, around 1509 patients had been diagnosed with HIV infection. HIV surveillance has improved in KSA with advances in medical care, counseling, family planning, diagnostic evaluation, and anti-retroviral therapy, but challenges remain. Patients receiving anti-retroviral therapy still show significant morbidity and mortality. Further targeted treatment regimens and preventive strategies are required to control HIV infection in KSA. Progress towards meeting the 90-90-90 goals for HIV in the MENA has also not been systematically monitored. METHOD: In this review, we examine current screening programs, therapeutic modalities, the emergence of drug resistance, and future perspectives for HIV-associated health care in KSA. CONCLUSION: The aim is to offer insight for healthcare policymakers to comply with the UNAIDS 2020 vision program and help establish the prevailing paradigms in the HIV community for an AIDS-free generation and the 90-90-90 goals for diagnosis.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/diagnóstico , HIV , Arábia Saudita/epidemiologia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Oriente Médio/epidemiologia
9.
Saudi Med J ; 44(5): 492-497, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37182927

RESUMO

OBJECTIVES: Idiopathic inflammatory myositis (IIM) in Saudi patients has been poorly studied owing to the lack of available data. This study aimed to identify the clinical and laboratory features of patients at a single tertiary care center. METHODS: This retrospective study reviewed the medical records of Prince Sultan Military Medical City, Riyadh, Saudi Arabia to collect clinical and laboratory data between December 2022 and February 2017 as follows: age at disease onset, gender, follow-up duration and disease duration; clinical symptoms; laboratory result; presence and type of myositis-specific autoantibody or myositis-associated autoantibody; and type of immunosuppression, presence of malignancy, disease course, and outcome. RESULTS: There were 26 patients with a mean age of 36.16±13.48, and 84.6% were women. The most prevalent form of IIM was dermatomyositis (n=16, 61.5%), and the most affected organ was the skin. weakness was observed in 25 patients (96.2%), and dysphagia was the most common alarm sign (n=10, 38.5%). During follow-up, the creatine kinase level was elevated at the beginning of the disease and then decreased following treatment, with a mean of 277.73 IU/L. Of the total patients, 17 (68%) were positive for anti-nuclear antibody and 5 (19.2%) were positive for anti-Jo-1. CONCLUSION: In our patients, dermatomyositis was the most common form of myositis, and skin manifestations were the most prevalent clinical characteristics. None of the patients developed a malignancy or died.


Assuntos
Dermatomiosite , Miosite , Neoplasias , Humanos , Feminino , Masculino , Estudos Retrospectivos , Dermatomiosite/diagnóstico , Dermatomiosite/epidemiologia , Arábia Saudita/epidemiologia , Miosite/diagnóstico , Miosite/epidemiologia , Autoanticorpos
10.
Front Pharmacol ; 14: 1149909, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37214444

RESUMO

Mpox (earlier known as monkeypox) virus infection is a recognized public health emergency. There has been little research on the treatment options. This article reviews the specific drugs used to treat mpox virus infection and the vaccines used here. Instead of focusing on the mechanistic basis, this review narrates the practical, real-life experiences of individual patients of mpox virus disease being administered these medicines. We conducted a bibliometric analysis on the treatment of the mpox virus using data from several databases like PubMed, Scopus, and Embase. The research on this topic has grown tremendously recently but it is highly concentrated in a few countries. Cidofovir is the most studied drug. This is because it is indicated and also used off-label for several conditions. The drugs used for mpox virus infection include tecovirimat, cidofovir, brincidofovir, vaccinia immune globulin, and trifluridine. Tecovirimat is used most frequently. It is a promising option in progressive mpox disease in terms of both efficacy and safety. Brincidofovir has been associated with treatment discontinuation due to elevated hepatic enzymes. Cidofovir is also not the preferred drug, often used because of the unavailability of tecovirimat. Trifluridine is used topically as an add-on agent along with tecovirimat for ocular manifestations of mpox virus disease. No study reports individual patient data for vaccinia immune globulin. Though no vaccine is currently approved for mpox virus infection, ACAM 2000 and JYNNEOS are the vaccines being mainly considered. ACAM 2000 is capable of replicating and may cause severe adverse reactions. It is used when JYNNEOS is contraindicated. Several drugs and vaccines are under development and have been discussed alongside pragmatic aspects of mpox virus treatment and prevention. Further studies can provide more insight into the safety and efficacy of Tecovirimat in actively progressing mpox virus disease.

11.
Molecules ; 28(7)2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37049881

RESUMO

Development in the fields of natural-product-derived and synthetic small molecules is in stark contrast to the ongoing demand for novel antimicrobials to treat life-threatening infections caused by extended-spectrum ß-lactamase producing Escherichia coli (ESBL E. coli). Therefore, there is an interest in the antibacterial activities of synthesized N-(4-methylpyridin-2-yl) thiophene-2-carboxamides (4a-h) against ESBL-producing E. coli ST131 strains. A blood sample was obtained from a suspected septicemia patient and processed in the Bactec Alert system. The isolate's identification and antibacterial profile were determined using the VITEK 2® compact system. Multi-locus sequence typing of E. coli was conducted by identifying housekeeping genes, while ESBL phenotype detection was performed according to CLSI guidelines. Additionally, PCR was carried out to detect the blaCTX-M gene molecularly. Moreover, molecular docking studies of synthesized compounds (4a-h) demonstrated the binding pocket residues involved in the active site of the ß-lactamase receptor of E. coli. The result confirmed the detection of E. coli ST131 from septicemia patients. The isolates were identified as ESBL producers carrying the blaCTX-M gene, which provided resistance against cephalosporins and beta-lactam inhibitors but sensitivity to carbapenems. Among the compounds tested, 4a and 4c exhibited high activity and demonstrated the best fit and interactions with the binding pocket of the ß-lactamase enzyme. Interestingly, the maximum of the docking confirmations binds at a similar pocket region, further strengthening the importance of binding residues. Hence, the in vitro and molecular docking studies reflect the promising antibacterial effects of 4a and 4c compounds.


Assuntos
Infecções por Escherichia coli , Escherichia coli , Humanos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Tipagem de Sequências Multilocus , Simulação de Acoplamento Molecular , Antibacterianos/farmacologia , beta-Lactamases/genética , beta-Lactamases/metabolismo , Testes de Sensibilidade Microbiana
12.
Microorganisms ; 11(2)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36838306

RESUMO

The scale at which the SARS-CoV-2/COVID-19 pandemic has spread remains enormous. Provided the genetic makeup of the virus and humans is readily available, the quest for knowing the mechanism and epidemiology continues to prevail across the entire scientific community. Several aspects, including immunology, molecular biology, and host-pathogen interaction, are continuously being dug into for preparing the human race for future pandemics. The exact reasons for vast differences in symptoms, pathophysiological implications of COVID-infections, and mortality differences remain elusive. Hence, researchers are also looking beyond traditional genomics, proteomics, and transcriptomics approach, especially entrusting the environmental regulation of the genetic landscape of COVID-human interactions. In line with these questions lies a critical process called epigenetics. The epigenetic perturbations in both host and parasites are a matter of great interest to unravel the disparities in COVID-19 mortalities and pathology. This review provides a deeper insight into current research on the epigenetic landscape of SARS-CoV-2 infection in humans and potential targets for augmenting the ongoing investigation. It also explores the potential targets, pathways, and networks associated with the epigenetic regulation of processes involved in SARS-CoV-2 pathology.

13.
Molecules ; 27(20)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36296578

RESUMO

Mycobacterium tuberculosis (Mtb), an acid-fast bacillus that causes Tuberculosis (TB), is a pathogen that caused 1.5 million deaths in 2020. As per WHO estimates, another 4.1 million people are suffering from latent TB, either asymptomatic or not diagnosed, and the frequency of drug resistance is increasing due to intrinsically linked factors from both host and bacterium. For instance, poor access to TB diagnosis and reduced treatment in the era of the COVID-19 pandemic has resulted in more TB deaths and an 18% reduction in newly diagnosed cases of TB. Additionally, the detection of Mtb isolates exhibiting resistance to multiple drugs (MDR, XDR, and TDR) has complicated the scenario in the pathogen's favour. Moreover, the conventional methods to detect drug resistance may miss mutations, making it challenging to decide on the treatment regimen. However, owing to collaborative initiatives, the last two decades have witnessed several advancements in both the detection methods and drug discovery against drug-resistant isolates. The majority of them belong to nucleic acid detection techniques. In this review, we highlight and summarize the molecular mechanism underlying drug resistance in Mtb, the recent advancements in resistance detection methods, and the newer drugs used against drug-resistant TB.


Assuntos
COVID-19 , Mycobacterium tuberculosis , Ácidos Nucleicos , Tuberculose , Humanos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Pandemias , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Tuberculose/microbiologia , Resistência a Medicamentos , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana
14.
J Infect Public Health ; 15(1): 142-151, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34764042

RESUMO

BACKGROUND: The rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU). METHODS: The SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations. RESULTS: The SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations. CONCLUSION: The SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available.


Assuntos
COVID-19 , Cuidados Críticos , Humanos , Unidades de Terapia Intensiva , SARS-CoV-2 , Arábia Saudita
15.
J Family Med Prim Care ; 10(10): 3657-3663, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34934662

RESUMO

CONTEXT: World Health Organization recommending initiation of breastfeeding within hour of birth, exclusive breastfeeding for the first 6 months. In Saudi Arabia, there is a paucity of studies on the factors associated with early cessation of exclusive breastfeeding. AIMS: We aimed to assess the exclusive breastfeeding rates and to identify the risk factors for early breastfeeding cessation at maternal and institutional levels. SETTINGS AND DESIGN: A prospective observational study carried out at King Abdullah bin Abdulaziz University Hospital, Riyadh, Saudi Arabia. METHODS AND MATERIALS: It included all postpartum women who had given birth to full term, singleton, healthy newborns, and were breastfeeding before discharge. Data were collected before discharge, 2 weeks, and 8 weeks postpartum using an adapted instrument. STATISTICAL ANALYSIS: Using JMP14 software with appropriate statistical tests. RESULTS: The study included 136 mothers, of whom 37.5% were exclusively breastfeeding in the first 2 weeks; this rate dropped to 19% with a statistically significant difference (P < 0.0001). Early breastfeeding cessation was significantly associated with maternal age, health status, mother's knowledge, and attitude, in addition to other modifiable factors that was encountered during hospital stay such as latching difficulties and introduction of formula feeding. CONCLUSIONS: This study reported low exclusive breastfeeding rates in the first 2 months postpartum among Saudi mothers. Multiple factors were associated with breastfeeding, and some are modifiable. Breastfeeding promotion and support for is a critical role required from healthcare workers in all settings, including primary health care. Healthcare professionals play a major role in promoting, protecting, and supporting exclusive breastfeeding.

16.
Cureus ; 13(11): e19955, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34868792

RESUMO

Aim This study aimed to assess the relationship between loneliness and hypothyroidism in patients with hypothyroidism and to determine predictors of loneliness. Materials and methods A cross-sectional study was conducted on hypothyroid patients attending the endocrine clinics at Alhada Military Hospital and Prince Mansour Military Hospital, Taif, Saudi Arabia between the period of December 2020 and May 2021. Patients with more than 18 years of hypothyroidism were included and those with other thyroid diseases were excluded as well as those with other comorbidities and psychiatric disorders and those who were living alone. Data were collected using an online pre-structured questionnaire. Results The study included 231 hypothyroid patients with a mean age of 43.34 ± 12.9 years, and 90.9% were females. The majority (96.5%) were taking levothyroxine, and 27.3% were practicing physical activity. Only 2.2% of the participants had a high degree of loneliness, whereas 47.2%, 34.6%, and 16% had low, moderate, and moderately high degrees of loneliness, respectively. Discussion In this study, 2.2% of sampled hypothyroid patients had high (2.2%) or moderately high degrees of loneliness feelings (16%). Duration of hypothyroidism was a significant predictor for high loneliness score.

17.
J Inflamm Res ; 14: 4313-4328, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511970

RESUMO

PURPOSE: This study aimed to understand the pathophysiology of host responses to infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/(COVID-19) and Middle East respiratory syndrome coronavirus (MERS-CoV) and to identify proteins for patient stratification with different grades of illness severity. PATIENTS AND METHODS: Peripheral blood samples from 43 patients with different grades of COVID-19, 7 MERS-CoV patients admitted to the ICU, and 10 healthy subjects were analyzed using label-free quantitative liquid chromatography-mass spectrometry (LC-MS). RESULTS: We identified 193 and 91 proteins that differed significantly between COVID-19 and MERS-CoV sample groups, respectively, and 49 overlapped between datasets. Only 10 proteins are diagnostic of asymptomatic cases, 12 are prognostic of recovery from severe illness, and 28 are prognostic of a fatal outcome of COVID-19. These proteins are implicated in virus-specific/related signaling networks. Notable among the top canonical pathways are humoral immunity, inflammation, acute-phase response signaling, liver X receptor/retinoid X receptor (LXR/RXR) activation, coagulation, and the complement system. Furthermore, we confirmed positive viral shedding in 11.76% of 51 additional peripheral blood samples, indicating that caution should be taken to avoid the possible risk of transfusion of infected blood products. CONCLUSION: We identified COVID-19 and MERS-CoV protein panels that have potential as biomarkers and might assist in the prognosis of SARS-CoV-2 infection. The identified markers further our understanding of COVID-19 disease pathophysiology and may have prognostic or therapeutic potential in predicting or managing host cell responses to human COVID-19 and MERS-CoV infections.

18.
Front Oncol ; 11: 715794, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490115

RESUMO

The correlation between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load and risk of disease severity in cancer patients is poorly understood. Given the fact that cancer patients are at increased risk of severe coronavirus disease 2019 (COVID-19), analysis of viral load and disease outcome in COVID-19-infected cancer patients is needed. Here, we measured the SARS-CoV-2 viral load using qPCR cycle threshold (Ct) values collected from 120 noncancer and 64 cancer patients' nasopharyngeal swab samples who are admitted to hospitals. Our results showed that the in-hospital mortality for high viral load cancer patients was 41.38%, 23.81% for medium viral load and 14.29% for low viral load patients (p < -0.01). On the other hand, the mortality rate for noncancer patients was lower: 22.22% among patients with high viral load, 5.13% among patients with medium viral load, and 1.85% among patients with low viral load (p < 0.05). In addition, patients with lung and hematologic cancer showed higher possibilities of severe events in proportion to high viral load. Higher attributable mortality and severity were directly proportional to high viral load particularly in patients who are receiving anticancer treatment. Importantly, we found that the incubation period and serial interval time is shorter in cancer patients compared with noncancer cases. Our report suggests that high SARS-CoV-2 viral loads may play a significant role in the overall mortality and severity of COVID-19-positive cancer patients, and this warrants further study to explore the disease pathogenesis and their use as prognostic tools.

19.
Saudi J Med Med Sci ; 9(1): 16-23, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33519339

RESUMO

OBJECTIVE: To present the interim findings from a national study investigating the safety and efficacy of convalescent plasma (CP) containing detectable IgG antibodies as a treatment strategy for severe coronavirus disease 2019 (COVID-19). TRIAL DESIGN AND PARTICIPANTS: An open label, two-arm, phase-II clinical trial conducted across 22 hospitals from Saudi Arabia. The intervention group included 40 adults (aged ≥18 years) with confirmed severe COVID-19 and the control group included 124 patients matched using propensity score for age, gender, intubation status, and history of diabetes and/or hypertension. Intervention group included those (a) with severe symptoms (dyspnea; respiratory rate, ≥30/min; SpO2, ≤93%, PaO2/FiO2 ratio, <300; and/or lung infiltrates >50% within 24-48 h), (b) requiring intensive care unit (ICU) care or (c) experiencing life-threatening conditions. The control group included confirmed severe COVID-19 patients of similar characteristics who did not consent for CP infusion or were not able to receive CP due to its nonavailability. INTERVENTIONS: The intervention group participants were infused 300 ml (200-400 ml/treatment dose) CP at least once, and if required, daily for up to 5 sessions, along with receiving the best standard of care. The control group only received the best standard of care. OUTCOMES: The primary endpoints were safety and ICU length of stay (LOS). The secondary endpoints included 30-day mortality, days on mechanical ventilation and days to clinical recovery. RESULTS: CP transfusion did not result in any adverse effects. There was no difference in the ICU LOS (median 8 days in both groups). The mortality risk was lower in the CP group: 13% absolute risk reduction (P = 0.147), hazard ratio (95% confidence interval): 0.554 (0.299-1.027; P = 0.061) by log-rank test. There was no significant difference in the days on mechanical ventilation and days to clinical recovery. CONCLUSION: CP containing detectable antibodies is a safe strategy and may result in a decrease in mortality in patients with severe COVID-19. The results of the completed trial with a larger study sample would provide more clarity if this difference in mortality is significant. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04347681; Saudi Clinical Trials Registry No.: 20041102.

20.
Neurosciences (Riyadh) ; 25(1): 38-42, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31982893

RESUMO

OBJECTIVE: To study the prevalence and nature of stroke mimics (SM) among Saudi patients who came to the emergency department with a sudden neurological deficit and suspected stroke. METHODS: The electronic health records from February 2016 to July 2018 of patients who were admitted to the Stroke Unit at King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia (KAMC-RD) with a suspected stroke were all reviewed. A comparison between SM and stroke was established. Our study identified the predictors of SM by using logistic regression analysis. This study was approved by the local institutional review board. RESULTS: Out of 1,063 patients, 131 (12.3%) had SM. The most common causes were a peripheral vestibular disorder (27.4%) followed by psychogenic causes (24.4%). Stroke mimics were more common among younger individuals and women. Arterial hypertension, diabetes, and smoking were less likely to be found in SMs. At discharge, individuals with SM were more likely to be independent, had milder deficits, and shorter hospital stays. Predictors of SM were young age, female gender, mild deficit at presentation, and good functional status before the stroke. CONCLUSION: The incidence of stroke mimics is common among suspected stroke patients. Practicing physicians should consider potential diagnostic errors, particularly in the hyperacute phase of the stroke.


Assuntos
Admissão do Paciente/tendências , Transtornos Psicofisiológicos/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Neuronite Vestibular/diagnóstico por imagem , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Diagnóstico Diferencial , Registros Eletrônicos de Saúde/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicofisiológicos/epidemiologia , Fatores Sexuais , Acidente Vascular Cerebral/epidemiologia , Resultado do Tratamento , Neuronite Vestibular/epidemiologia
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