RESUMO
BACKGROUND: The purpose of the study was to assess visual outcomes, complications, intraocular lens (IOL) stability, and corneal status after sutured scleral-fixated intraocular lens implantation combined with penetrating keratoplasty (PKP). METHODS: This retrospective single-arm cohort study included patients who underwent PKP and sutured scleral-fixated intraocular lens implantation between 2013 and 2018 at the Dhahran Eye Specialty Hospital. The eyes were examined postoperatively at 1, 3, 6, 12, and 24 months. Corneal status, complications, and IOL status were also evaluated periodically, and the number of eyes with a BCVA of > 20/200 was recorded. RESULTS: Twenty-two eyes from 22 patients were included. The median duration of follow-up was 3 (IQR 1.8; 4.4) years. Reasons for surgery were traumatic globe rupture (six eyes, 27.3%), bullous keratopathy (nine eyes, 40.1%), failed previous graft (five eyes, 22.7%), and corneal scarring (two eyes, 9.1%). Twelve (54.5%) eyes showed a BCVA of > 20/200 (non-blind) at 12 months after surgery and only five (22.7%) before surgery. Twelve months after surgery, 13 patients showed an improvement in BCVA in two lines (59.1%), seven remained the same (31.8%), and 2 deteriorated (9.1%). The indication for surgery (p = 0.2) and the stability of the sutured-scleral fixated IOL (p = 0.8) were not associated with an improvement in BCVA at the final follow-up. The corneal graft remained clear in nine eyes (40.9%) at a median duration of 3 years. The overall average survival period for all corneal grafts was 42.9 months. CONCLUSIONS: The combination of sutured scleral-fixated intraocular lens implants and PKP is an effective intervention for preserving visual acuity in patients with complex cases. However, the risk of graft failure and then need for repeat transplantation should be taken into consideration.
Assuntos
Ceratoplastia Penetrante , Implante de Lente Intraocular , Esclera , Técnicas de Sutura , Acuidade Visual , Humanos , Ceratoplastia Penetrante/métodos , Feminino , Estudos Retrospectivos , Masculino , Implante de Lente Intraocular/métodos , Pessoa de Meia-Idade , Esclera/cirurgia , Idoso , Adulto , Seguimentos , Doenças da Córnea/cirurgia , Resultado do Tratamento , Lentes Intraoculares , Complicações Pós-OperatóriasRESUMO
BACKGROUND: Subclinical hypothyroidism is defined as an increase in serum levels of Thyroid Stimulating Hormone (TSH) above the normal range, without alteration of total T4 concentrations that is reported to have association with various metabolic conditions. The study aimed to investigate any association between subclinical hypothyroidism and metabolic disorders in Al Kharj city. METHODS: This is a cross-sectional study that included review of patients' charts from prince Sattam bin Abdul-Aziz University, Al Kharj, Saudi Arabia, from August 1 to November 30, 2016. Data were analyzed with SPSS version 21. Descriptive statistics were obtained as frequencies. Pearson chi-square analysis was used to assess any differences between disease status and study variables. P-value < 0.05 was considered significant. RESULTS: The mean age was 30.65 ± 13.3 with a female predominance. The average BMI was 29.5 ± 7.71; 46 (11.5%) had hypertension, 52 (46.8%) had diabetes, 173 (44%) had anemia, and 192 (56%) had vitamin D deficiency. Due to increased TSH levels, male gender had higher prevalence of subclinical hypothyroidism with P-value < 0.001 and 0.011, respectively. CONCLUSION: Subclinical hypothyroidism is a significant topic worldwide whose prevalence is rising. In this study, we could not find any significant association between subclinical hypothyroidism and metabolic disorder. Further longitudinal studies with large sample size are needed to study this association.
Assuntos
Hospitais Universitários , Hipotireoidismo/complicações , Doenças Metabólicas/complicações , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To evaluate sun exposure behaviours, sun protection practices, general knowledge, attitudes and awareness of University students about the benefits of sun exposure and harmful effects of too much or avoidance of sun exposure. METHODS: This cross-sectional survey study was conducted in December 2014 and January2015 at Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia. A questionnaire consisting of multiple-choice closed questions was used. Sample was collected using cluster sampling method. SPSS 16 was used for data analysis. RESULTS: Of the 399 participants, 200(50.1%) were men and 199(49.9%) were women. The overall mean age was 21±1.82years (range: 18-30 years). Moreover, 217(54.4%) participants intentionally exposed themselves to sun. Spending summer holidays in coastal areas was reported by 150(37.6%). Sunglasses were used by 161(40.4%) participants. Besides, 274(68.7%) participants agreed that sun exposure of 5 to 10 minutes for two or three times per week was very important; 189(47.4%) were aware of the importance of sun exposure for child health. 165(66%), knew that too much sun exposure was harmful and might cause skin cancer. CONCLUSIONS: Most of the participants were aware of both beneficial effects of the appropriate sun exposure and harmful effects of too much exposure or its avoidance. However, proper sun exposure practices and sun protection practices need further guidance and encouragements from health-promoting programmes.
Assuntos
Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias Cutâneas , Luz Solar , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Arábia Saudita , Estudantes , Inquéritos e Questionários , Universidades , Adulto JovemRESUMO
Spontaneous splenic rupture (SSR), a rare but potentially life-threatening condition, typically occurs in the absence of trauma or underlying splenic disease. This report aims to contribute to the limited body of knowledge regarding its occurrence, diagnosis, and management in this demographic. We describe the case of a 20-year-old patient with no significant medical history who presented with acute abdominal pain and hypovolemic shock. Imaging revealed an unexpected splenic rupture without any preceding trauma or identifiable risk factors. The patient's clinical progression, diagnostic challenges, and therapeutic approach are discussed in detail. This case underscores the importance of considering SSR in the differential diagnosis of acute abdomen in young patients, even in the absence of predisposing factors. We review the literature to highlight the epidemiology, possible etiologies, diagnostic modalities, and treatment options for SSR. The peculiarities of managing such cases in young patients are also discussed, emphasizing a tailored approach to balance the risks of conservative management against surgical intervention. In conclusion, SSR, though rare in young patients, should be a diagnostic consideration in cases of unexplained acute abdomen. Early recognition and appropriate management are crucial for favorable outcomes. This case adds to the existing literature by providing insight into the presentation and management of this condition in a young, healthy individual, thereby aiding in enhancing clinical vigilance and patient care.
RESUMO
BACKGROUND: Clubfoot, or congenital talipes equinovarus, is a widely recognized cause of disability and congenital deformity worldwide, which significantly impacts the quality of life. Effective management of clubfoot requires long-term, multidisciplinary intervention. It is important to understand how common this condition is in order to assess its impact on the population. Unfortunately, few studies have investigated the prevalence of clubfoot in Saudi Arabia. AIM: To determine the prevalence of clubfoot in Saudi Arabia via the patient population at King Fahad University Hospital (KFUH). METHODS: This was a retrospective study conducted at one of the largest hospitals in the country and located in one of the most densely populated of the administrative regions. RESULTS: Of the 7792 births between 2015 to 2023 that were included in the analysis, 42 patients were diagnosed with clubfoot, resulting in a prevalence of 5.3 per 1000 live births at KFUH. CONCLUSION: The observed prevalence of clubfoot was significantly higher than both global and local estimates, indicating a substantial burden in the study population.
RESUMO
Background and aim: Nutrition plays a vital role in maintaining and improving vision health. However, little is known about dietary intake habits and their correlation with vision health among adults in the Kingdom of Saudi Arabia (KSA). The present survey was aimed to assess dietary patterns and vision health among Saudi adults and to determine the association between dietary patterns and vision health. Methods: The present analytical study was carried out among 1,234 Saudi adults in the Makkah, Riyadh, and Qassim regions of KSA. We used the Arabic version of the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) and the diet quality screener (DQS). We applied Mann-Whitney U and Kruskal-Wallis tests to determine the association between vision function score and demographic characteristics. Furthermore, the Spearman correlation test was used to determine the relationship between the DQS and the NEI VFQ-25. Results: Of the studied population, the highest score obtained through the NEI VFQ-25 was in the social function domain (mean ± SD = 76.64 ± 18.63), followed by the general vision domain (mean ± SD = 75.21 ± 15.16) and was negatively correlated with age. Regarding dietary patterns, the intake of lean protein sources per week was the highest, with a mean intake of 4.17 days per week, followed by that of whole grains and milk or dairy products, with a mean intake of around four days per week. There was a significant correlation between various dietary intakes and visual function scores. Conclusion: The present survey underscores the significance of understanding regional dietary patterns and their implications for vision health. Furthermore, our study's findings indicate a need for targeted nutritional intervention measures to improve the vision health of this population.
RESUMO
EBV latent membrane protein 1 (LMP-1) is an important oncogene involved in the induction and maintenance of EBV infection and the activation of several cell survival and proliferative pathways. The genetic diversity of LMP-1 has an important role in immunogenicity and tumorigenicity allowing escape from host cell immunity and more metastatic potential of LMP-1 variants. This study explored the evolutionary of LMP-1 in EBV-infected patients at an advanced stage of nasopharyngeal carcinoma (NPC). Detection of genetic variability in LMP-1 genes was carried out using Sanger sequencing. Bioinformatic analysis was conducted for translation and nucleotide alignment. Phylogenetic analysis was used to construct a Bayesian tree for a deeper understanding of the genetic relationships, evolutionary connections, and variations between sequences. Genetic characterization of LMP-1 in NPC patients revealed the detection of polymorphism in LMP-1 Sequences. Motifs were identified within three critical LMP-1 domains, such as PQQAT within CTAR1 and YYD within CTAR2. The presence of the JACK3 region at specific sites within CTAR3, as well as repeat regions at positions (122-132) and (133-143) within CTAR3, was also annotated. Additionally, several mutations were detected including 30 and 69 bp deletions, 33 bp repeats, and 15 bp insertion. Although LMP-1 strains appear to be genetically diverse, they are closely related to 3 reference strains: prototype B95.8, Med- 30 bp deletion, and Med + 30 bp deletion. In our study, one of the strains harboring the 30 bp deletion had both bone and bone marrow metastasis which could be attributed to the fact that LMP-1 is involved in tumor metastasis, evasion and migration of NPC cells. This study provided valuable insights into genetic variability in LMP-1 sequences of EBV in NPC patients. Further functional studies would provide a more comprehensive understanding of the molecular characteristics, epidemiology, and clinical implications of LMP-1 polymorphisms in EBV-related malignancies.
Assuntos
Biologia Computacional , Infecções por Vírus Epstein-Barr , Variação Genética , Herpesvirus Humano 4 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Filogenia , Proteínas da Matriz Viral , Proteínas da Matriz Viral/genética , Humanos , Carcinoma Nasofaríngeo/virologia , Carcinoma Nasofaríngeo/genética , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/virologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Biologia Computacional/métodos , Evolução Molecular , Teorema de Bayes , MasculinoRESUMO
In the literature, midgut volvulus is a well-known surgical complication following gastric bypass surgery that is serious and necessitates an immediate intervention. Here, we report a case of internal herniation that was misdiagnosed twice but eventually managed appropriately. A 27-year-old male with a surgical history of Roux-en-Y gastric bypass came to the emergency department complaining of severe epigastric abdominal pain. Two months earlier, he had a similar pain which was treated with Helicobacter pylori eradication therapy. Despite completing the eradication therapy, the pain reoccurred. Computed tomography angiography showed a filling defect in the superior mesenteric artery that was followed by a diagnostic laparoscopy ending with internal hernia reduction. Physicians should consider internal herniation as a differential diagnosis for every patient with a history of gastric bypass surgery presenting with abdominal pain.
RESUMO
Positive vitreous pressure (PVP) is common during open anterior segment surgery and penetrating keratoplasty (PKP) has a reported incidence rate of 40-50%. Despite adequate perioperative preventive precautions, positive pressure occurs during surgery and optimum management of PVP is required to avoid serious complications. Many pharmacological and mechanical approaches can be employed either preoperatively or intraoperatively to decrease vitreous pressure. Surgical techniques such as graft-over-host technique, the modified graft-over-host technique, techniques employed mattress sutures and needle, or Vitreous aspiration or vitrectomy can be effectively used to manage intraoperative PVP during PPK. This article reviews the incidence, risk factors, prevention, and different approaches to the management of positive vitreous pressure during PKP to analyze the available evidence in order to improve the safety profile of PKP and prevent sight-threatening complications.
RESUMO
Introduction Surgical procedures present substantial healthcare costs, patient discomfort, and potential adverse outcomes. In response, enhanced recovery after surgery (ERAS) protocols have emerged as comprehensive, evidence-based preoperative care pathways designed to optimize preoperative, intra-operative, and postoperative management. These protocols incorporate various interventions, such as preoperative education, nutritional optimization, minimally invasive techniques, multimodal pain management, early mobilization, and patient engagement. Despite their global success and growing popularity, the adoption and influence of ERAS protocols in Saudi Arabia have not been extensively explored. This study aims to assess the ERAS effects on surgical outcomes and evaluate its relationship with patient satisfaction, considering factors such as cost-effectiveness and compliance in the Saudi context. Methods This cross-sectional study encompassed data collection from 1,452 patients who underwent surgical procedures such as bariatric surgery and cholecystectomy, employing systematic random sampling across multiple healthcare facilities in Saudi Arabia. Data were gathered through structured questionnaires, medical records, and cost-effectiveness analysis within the period spanning from January to August 2023. The relationship between ERAS protocol implementation, surgical outcomes, patient satisfaction, and cost-effectiveness was analyzed using statistical tests, including correlation, regression analysis, and chi-square tests. A statistical significance threshold was set at p < 0.05, and Statistical Product and Service Solutions (SPSS, version 28.0) (IBM SPSS Statistics for Windows, Armonk, NY) was used for data analysis. Results Among the 1,452 respondents, 1,152 (79.3%) reported the implementation of ERAS protocols during their surgical procedures. Those receiving ERAS protocols exhibited significantly lower rates of surgical complications, readmissions, and reduced dependency on pain medication (p < 0.001). Additionally, participants subjected to ERAS protocols reported significantly higher satisfaction levels based on the mean satisfaction scale score, with a p-value of less than 0.001. Conclusion The results highlight substantial improvements associated with the implementation of ERAS protocols, particularly in terms of reduced surgical site infections, shortened hospitalization periods, and decreased pain management-related complications. Moreover, ERAS protocol implementation demonstrated enhanced surgical outcomes, increased postoperative satisfaction, and overall improved recovery experiences. These findings underscore the potential benefits of integrating ERAS protocols into the surgical practices of Saudi Arabia. This research contributes to a better understanding of the advantages offered by ERAS protocols and their potential for enhancing healthcare delivery in the region.
RESUMO
BACKGROUND: Strabismus is the misalignment of the visual axis of both eyes caused by abnormalities in binocular vision or anomalies of neuromuscular control of ocular motility. This study aimed to assess the community knowledge, attitude, and practices related to strabismus and strabismus treatment and surgery in the Al-Jouf region of Saudi Arabia. METHODS: This study utilized a quantitative cross-sectional design. The consented volunteering adult participants were randomly selected through sequential enrollment to the completion of the target sample size from five population groups constituting the Al-Jouf region of Saudi Arabia. The data were collected through an online validated self-administered questionnaire. The collected data were analyzed using descriptive and inferential statistics. RESULTS: The study included 340 participants; 67.6% of them were females and 32.4% were males. Only 66.8% of participants correctly defined strabismus. Symptoms of strabismus were identified as double vision (58.5%), blurred vision (48.2%), headache (31.8%), eye fatigue (41.5%), and difficulty reading (47.1%). Regarding risk factors of strabismus, 48.5% reported family history, 39.4% reported uncorrected refractive errors, and 23.2% reported long screen time. Complications of untreated strabismus were reported as low self-confidence (39.1%), vision loss (27.6%), poor interpersonal relationships (25.9%), amblyopia (42.6%), and cosmetic stigma (14.1%). Only 45.6% of the participants agreed to marry someone with strabismus or allow their relatives to do so. The majority of participants (72.6%) would advise a strabismus patient to visit an ophthalmologist. Despite a higher knowledge regarding strabismus among females, younger agers, higher education, single persons, workers/students, and those inhabiting the capital city of the region, such association did not reach significance. CONCLUSION: The study shows a moderate level of knowledge, attitude, and practices among the general population of Al-Jouf Saudis toward strabismus. There was no significant relationship between knowledge of strabismus and any of the demographic characteristics of the participants. This might prove detrimental to the early detection and treatment of strabismus to prevent its complications and improve its outcomes and the quality of patients' lives. Institution of correlation plans are mandated by the Ministry of Health and interested stakeholders.
RESUMO
Epstein Barr Virus (EBV) is implicated in the carcinogenesis of nasopharyngeal carcinoma (NPC) and currently associated with at least 1% of global cancers. The differential prognosis analysis of NPC in EBV genotypes remains to be elucidated. Medical, radiological, pathological, and laboratory reports of 146 NPC patients were collected retrospectively over a 6-year period between 2015 and 2020. From the pathology archives, DNA was extracted from tumor blocks and used for EBV nuclear antigen 3C (EBNA-3C) genotyping by nested polymerase chain reaction (PCR). We found a high prevalence of 96% of EBV infection in NPC patients with a predominance of genotype I detected in 73% of NPC samples. Histopathological examination showed that most of the NPC patients were in the advanced stages of cancer: stage III (38.4%) or stage IV-B (37.7%). Only keratinized squamous cell carcinoma was significantly higher in EBV negative NPC patients compared with those who were EBV positive (OR = 0.01, 95%CI = (0.004-0.32; p = 0.009)), whereas the majority of patients (91.8%) had undifferentiated, non-keratinizing squamous cell carcinoma, followed by differentiated, non-keratinizing squamous cell carcinoma (7.5%). Although NPC had metastasized to 16% of other body sites, it was not associated with EBV infection, except for lung metastasis. A statistically significant reverse association was observed between EBV infection and lung metastasis (OR = 0.07, 95%CI = (0.01-0.51; p = 0.008)). Although 13% of NPC patients died, the overall survival (OS) mean time was 5.59 years. Given the high prevalence of EBV-associated NPC in our population, Saudi could be considered as an area with a high incidence of EBV-associated NPC with a predominance of EBV genotype I. A future multi-center study with a larger sample size is needed to assess the true burden of EBV-associated NPC in Saudi Arabia.
RESUMO
Nuclear factor I-C (NFIC) belongs to a family of NFI transcription factors that binds to DNA through CAATT-boxes and are involved in cellular differentiation and stem cell maintenance. Here we show NFIC protein is significantly overexpressed in 69% of acute myeloid leukemia patients. Examination of the functional consequences of NFIC overexpression in HSPCs showed that this protein promoted monocytic differentiation. Single-cell RNA sequencing analysis further demonstrated that NFIC overexpressing monocytes had increased expression of growth and survival genes. In contrast, depletion of NFIC through shRNA decreased cell growth, increased cell cycle arrest and apoptosis in AML cell lines and AML patient blasts. Further, in AML cell lines (THP-1), bulk RNA sequencing of NFIC knockdown led to downregulation of genes involved in cell survival and oncogenic signaling pathways including mixed lineage leukemia-1 (MLL-1). Lastly, we show that NFIC knockdown in an ex vivo mouse MLL::AF9 pre-leukemic stem cell model, decreased their growth and colony formation and increased expression of myeloid differentiation markers Gr1 and Mac1. Collectively, our results suggest that NFIC is an important transcription factor in myeloid differentiation as well as AML cell survival and is a potential therapeutic target in AML.
Assuntos
Leucemia Mieloide Aguda , Fatores de Transcrição NFI , Animais , Camundongos , Diferenciação Celular/fisiologia , Sobrevivência Celular/genética , Hematopoese , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Proteína de Leucina Linfoide-Mieloide/genética , Fatores de Transcrição NFI/metabolismoRESUMO
Households' economic burden associated with chronic non-communicable diseases (NCDs) is a deterrent to healthcare access, adversely impacting patients' health. Therefore, we investigated the extent of out-of-pocket (OOP) spending among individuals diagnosed with chronic NCDs among household members in Riyadh, Saudi Arabia. Face-to-face interviews were conducted among households in Riyadh Province from the beginning of January 2021 to the end of June 2021. The respondents were asked to record OOP spending throughout the past three months in their health. A generalized linear regression model was used to determine the effects of several factors on the level of OOP spending. A total of 39.6% of the households studied had at least one member with a chronic NCD. Diabetes patients spent an average of SAR 932 (USD 248), hypertension patients SAR 606 (USD 162), and hypothyroid patients SAR 402 (USD 107). It was shown that households with older and more educated members had greater OOP spending. Households with an employed head of household, more family members, higher SES status, health insurance coverage, and urban residency had significantly higher OOP expenditure. The burden of OOP spending for chronic NCD households remains high, with some disparities. The research offers important information for decision making to lower OOP cost among NCD households.
Assuntos
Doenças não Transmissíveis , Características da Família , Estresse Financeiro , Gastos em Saúde , Humanos , Doenças não Transmissíveis/epidemiologia , Infecção Persistente , Arábia Saudita/epidemiologiaRESUMO
Chronic lymphocytic leukemia (CLL) is an incurable malignancy of B-cells. In this study, bioinformatics analyses were conducted to identify possible pathogenic roles of CK2α, which is a protein encoded by CSNK2A1, in the progression and aggressiveness of CLL. Furthermore, various computational tools were used to search for a competent inhibitor of CK2α from fungal metabolites that could be proposed for CLL therapy. In CLL patients, high-expression of CSNK2A1 was associated with early need for therapy (n = 130, p < 0.0001) and short overall survival (OS; n = 107, p = 0.005). Consistently, bioinformatics analyses showed CSNK2A1 to associate with/play roles in CLL proliferation and survival-dependent pathways. Furthermore, PPI network analysis identified interaction partners of CK2α (PPI enrichment p value = 1 × 10-16) that associated with early need for therapy (n = 130, p < 0.003) and have been known to heavily impact on the progression of CLL. These findings constructed a rational for targeting CK2α for CLL therapy. Consequently, computational analyses reported 35 fungal metabolites out of 5820 (filtered from 19,967 metabolites) to have lower binding energy (ΔG: - 10.9 to - 11.7 kcal/mol) and better binding affinity (Kd: 9.77 × 107 M-1 to 3.77 × 108 M-1) compared with the native ligand (ΔG: - 10.8, Kd: 8.3 × 107 M--1). Furthermore, molecular dynamics simulation study established that Butyl Xanalterate-CK2α complex continuously remained stable throughout the simulation time (100 ns). Moreover, Butyl Xanalterate interacted with most of the catalytic residues, where complex was stabilized by more than 65% hydrogen bond interactions, and a significant hydrophobic interaction with residue Phe113. Here, high-expression of CSNK2A1 was implicated in the progression and poor prognosis of CLL, making it a potential therapeutic target in the disease. Butyl Xanalterate showed stable and strong interactions with CK2α, thus we propose it as a competitive inhibitor of CK2α for CLL therapy.
Assuntos
Leucemia Linfocítica Crônica de Células B , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/metabolismo , Ligantes , Linfócitos B/metabolismo , Biologia Computacional , PrognósticoRESUMO
Background: The cardiovascular complications of Coronavirus Disease 2019 (COVID-19) may be attributed to the hyperinflammatory state leading to increased mortality in patients with COVID-19. HMG-CoA Reductase Inhibitors (statins) are known to have pleiotropic and anti-inflammatory effects and may have antiviral activity along with their cholesterol-lowering activity. Thus, statin therapy is potentially a potent adjuvant therapy in COVID-19 infection. This study investigated the impact of statin use on the clinical outcome of critically ill patients with COVID-19. Methods: A multicenter, retrospective cohort study of all adult critically ill patients with confirmed COVID-19 who were admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on the statin use during ICU stay and were matched with a propensity score based on patient's age and admission APACHE II and SOFA scores. The primary endpoint was in-hospital mortality, while 30 day mortality, ventilator-free days (VFDs) at 30 days, and ICU complications were secondary endpoints. Results: A total of 1,049 patients were eligible; 502 patients were included after propensity score matching (1:1 ratio). The in-hospital mortality [hazard ratio 0.69 (95% CI 0.54, 0.89), P = 0.004] and 30-day mortality [hazard ratio 0.75 (95% CI 0.58, 0.98), P = 0.03] were significantly lower in patients who received statin therapy on multivariable cox proportional hazards regression analysis. Moreover, patients who received statin therapy had lower odds of hospital-acquired pneumonia [OR 0.48 (95% CI 0.32, 0.69), P < 0.001], lower levels of inflammatory markers on follow-up, and no increased risk of liver injury. Conclusion: The use of statin therapy during ICU stay in critically ill patients with COVID-19 may have a beneficial role and survival benefit with a good safety profile.
Assuntos
COVID-19 , Inibidores de Hidroximetilglutaril-CoA Redutases , Adulto , Estudos de Coortes , Estado Terminal , Humanos , Estudos RetrospectivosRESUMO
Inappropriate localization of proteins can interfere with normal cellular function and drive tumor development. To understand how this contributes to the development of acute myeloid leukemia (AML), we compared the nuclear proteome and transcriptome of AML blasts with normal human CD34+ cells. Analysis of the proteome identified networks and processes that significantly affected transcription regulation including misexpression of 11 transcription factors with seven proteins not previously implicated in AML. Transcriptome analysis identified changes in 40 transcription factors but none of these were predictive of changes at the protein level. The highest differentially expressed protein in AML nuclei compared with normal CD34+ nuclei (not previously implicated in AML) was S100A4. In an extended cohort, we found that over-expression of nuclear S100A4 was highly prevalent in AML (83%; 20/24 AML patients). Knock down of S100A4 in AML cell lines strongly impacted their survival whilst normal hemopoietic stem progenitor cells were unaffected. These data are the first analysis of the nuclear proteome in AML and have identified changes in transcription factor expression or regulation of transcription that would not have been seen at the mRNA level. These data also suggest that S100A4 is essential for AML survival and could be a therapeutic target in AML.
Assuntos
Núcleo Celular/genética , Leucemia Mieloide Aguda/genética , Proteoma/genética , Proteína A4 de Ligação a Cálcio da Família S100/genética , Transcriptoma/genética , Adolescente , Adulto , Idoso , Antígenos CD34/genética , Proliferação de Células/genética , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/patologia , Proteômica/métodosRESUMO
Citrate synthase (CS) is a key mitochondrial enzyme. The aim of this study was to test the hypothesis that low CS activity impairs the metabolic health of mice fed a high fat diet (HFD) and promotes palmitate-induced lipotoxicity in muscle cells. C57BL/6J (B6) mice and congenic B6.A-(rs3676616-D10Utsw1)/KjnB6 (B6.A), a strain which carries the A/J allele of CS on the B6 strain background, were fed HFD (45% kcal from fat) for 12 weeks. C2C12 mouse muscle cells were used to investigate effects of CS knockdown on cell viability and signalling after incubation in 0.8 mM palmitate. CS activity, but not that of ß-hydroxyacyl-coenzyme-A dehydrogenase was lower in the gastrocnemius muscle and heart of B6.A mice compared to B6 mice (P < 0.001). During HFD feeding, glucose tolerance of mice decreased progressively and to a greater extent in B6.A females compared to B6 females, with males showing a similar trend. Body weight and fat gain did not differ between B6.A and B6 mice. After an 18 h incubation in 0.8 mM palmitate C2C12 muscle cells with â¼50% shRNA mediated reduction in CS activity showed lower (P < 0.001) viability and increased (P < 0.001) levels of cleaved caspase-3 compared to the scramble shRNA treated C2C12 cells. A/J strain variant of CS is associated with low enzyme activity and impaired metabolic health. This could be due to impaired lipid metabolism in muscle cells.