Common Cause Research Articles

Finerenone: A Novel Drug Discovery for the Treatment of Chronic Kidney Disease.

The most common cause of chronic kidney disease (CKD) is diabetic nephropathy (DN). Primarilymineralocorticoid receptor antagonists (MRAs) (spironolactone and eplerenone), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were used for the treatment of CKD, but due to the high risk of hyperkalaemia, the combination was infrequently used. Currently after approval by FDA in 2021, finerenone was found to be effective in the treatment of CKD. Finerenone slowdowns the progression of diabetic nephropathy and lessens the cardiovascular morbidity in DN patients. The main objective of this review article is to provide a comprehensive and insightful overview of the role of finerenone by mainly focusing on its pharmacological properties, toxicity, uses, bioanalytical technique used for determination, and treatment options. Finerenone works by inhibiting the action of the mineralocorticoid receptor. Finerenone is quickly absorbed from the digestive tract after oral treatment and achieves peak plasma concentrations in 1-2 hours. Finerenone is actively metabolized through oxidation, epoxidation substitution, and direct hydroxylation. Elimination of finerenone is done through urine and feces. Determination of finerenone can be done through HPLC-MS and LSC. The present review covers the complete picture of ADME properties, bioanalytical techniques, clinical trials, toxicity, and possible avenues in this arena. Finerenone is effective compared to other mineralocorticoid receptor-like spironolactone and eplerenone, for the treatment of chronic kidney disease.

Data-driven covariate selection for confounding adjustment by focusing on the stability of the effect estimator.

Valid inference of cause-and-effect relations in observational studies necessitates adjusting for common causes of the focal predictor (i.e., treatment) and the outcome. When such common causes, henceforth termed confounders, remain unadjusted for, they generate spurious correlations that lead to biased causal effect estimates. But routine adjustment for all available covariates, when only a subset are truly confounders, is known to yield potentially inefficient and unstable estimators. In this article, we introduce a data-driven confounder selection strategy that focuses on stable estimation of the treatment effect. The approach exploits the causal knowledge that after adjusting for confounders to eliminate all confounding biases, adding any remaining non-confounding covariates associated with only treatment or outcome, but not both, should not systematically change the effect estimator. The strategy proceeds in two steps. First, we prioritize covariates for adjustment by probing how strongly each covariate is associated with treatment and outcome. Next, we gauge the stability of the effect estimator by evaluating its trajectory adjusting for different covariate subsets. The smallest subset that yields a stable effect estimate is then selected. Thus, the strategy offers direct insight into the (in)sensitivity of the effect estimator to the chosen covariates for adjustment. The ability to correctly select confounders and yield valid causal inferences following data-driven covariate selection is evaluated empirically using extensive simulation studies. Furthermore, we compare the introduced method empirically with routine variable selection methods. Finally, we demonstrate the procedure using two publicly available real-world datasets. A step-by-step practical guide with user-friendly R functions is included. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A Rationalized Approach to Design and Discover Novel Non-steroidal Derivatives through Computational Aid for the Treatment of Prostate Cancer.

Prostate cancer is one of the most prevalent cancers in men, leading to the second most common cause of death in men. Despite the availability of multiple treatments, the prevalence of prostate cancer remains high. Steroidal antagonists are associated with poor bioavailability and side effects, while non-steroidal antagonists show serious side effects, such as gynecomastia. Therefore, there is a need for a potential candidate for the treatment of prostate cancer with better bioavailability, good therapeutic effects, and minimal side effects. This current research work focused on identifying a novel non-steroidal androgen receptor antagonist through computational tools, such as docking and in silico ADMET analysis. Molecules were designed based on a literature survey, followed by molecular docking of all designed compounds and ADMET analysis of the hit compounds. A library of 600 non-steroidal derivatives (cis and trans) was designed, and molecular docking was performed in the active site of the androgen receptor (PDBID: 1Z95) using Auto- Dock Vina 1.5.6. Docking studies resulted in 15 potent hits, which were then subjected to ADME analysis using SwissADME. ADME analysis predicted three compounds (SK-79, SK-109, and SK-169) with the best ADME profile and better bioavailability. Toxicity studies using Protox-II were performed on the three best compounds (SK-79, SK-109, and SK-169), which predicted ideal toxicity for these lead compounds. This research work will provide ample opportunities to explore medicinal and computational research areas. It will facilitate the development of novel androgen receptor antagonists in future experimental studies.

Genetic Aspects of Glaucoma: An Updated Review.

Glaucoma is a group of diverse diseases characterized by cupping of the optic nerve head due to the loss of retinal ganglion cells. It is the most common cause of irreversible blindness throughout the word; therefore, its timely diagnosis and early detection through an ophthalmological examination are very important. We, herein, present the information on the epidemiology, pathophysiology, clinical diagnosis, and treatment of glaucoma. We also emphasize the investigations of the last decades that have allowed identifying numerous genes and susceptible genetic factors. We have also described in detail the genes whose mutations cause or contribute to the development of the disease.

Clinical Features of Tachycardia-induced Cardiomyopathy in Patients with Atrial Fibrillation.

Objective Atrial fibrillation (AF) is the most common cause of tachycardia-induced cardiomyopathy (TIC). However, which patients with AF are prone to developing TIC remains unclear. In this study, we investigated the clinical features of AF patients with TIC. Methods This single-center study included 722 patients with AF (average age, 63.1±10.2 years old; 191 women) who underwent radiofrequency catheter ablation. We defined TIC as an initial left ventricular ejection fraction (LVEF) of <40% and a >20% recovery of the LVEF after successful AF ablation and compared the clinical characteristics between the TIC and control groups. Results The proportions of type 2 diabetes (30.5% vs. 14.7%), renal dysfunction (34.2% vs. 23.8%), hypertension (67.1% vs. 54.8%), and persistent AF (62.2% vs. 32.2%) were significantly higher in the TIC group (n=82) than in the control group (n=640). The atrioventricular nodal effective refractory period (AVNERP) (303±72 ms vs. 332±86 ms; p=0.017) was significantly shorter in the TIC group than in the control group. A multivariable analysis found that persistent AF [odds ratio (OR), 3.19; 95% confidence interval (CI), 1.94-5.24], renal dysfunction (OR, 1.87; 95% CI, 1.06-3.32), and type 2 diabetes (OR, 2.30; 95% CI, 1.31-4.05) were significantly associated with TIC. Conclusion Comorbid renal dysfunction and type 2 diabetes were clinical features of AF patients with TIC. Persistent AF, and short AVNERP may be involved in the development of TIC.

Cracking the Code of Lumpy Skin Disease: Identifying Causes, Symptoms and Treatment Options for Livestock Farmers.

The novel bovine viral infection known as lumpy skin disease is common in most African and Middle Eastern countries, with a significant likelihood of disease transfer to Asia and Europe. Recent rapid disease spread in formerly disease-free zones highlights the need of understanding disease limits and distribution mechanisms. Capripox virus, the causal agent, may also cause sheeppox and Goatpox. Even though the virus is expelled through several bodily fluids and excretions, the most common causes of infection include sperm and skin sores. Thus, vulnerable hosts are mostly infected mechanically by hematophagous arthropods such as biting flies, mosquitoes, and ticks. As a result, milk production lowers, abortions, permanent or temporary sterility, hide damage, and mortality occur, contributing to a massive financial loss for countries that raise cattle. These illnesses are economically significant because they affect international trade. The spread of Capripox viruses appears to be spreading because to a lack of effectual vaccinations and poverty in rural areas. Lumpy skin disease has reached historic levels; as a consequence, vaccination remains the only viable option to keep the illness from spreading in endemic as well as newly impacted areas. This study is intended to offer a full update on existing knowledge of the disease's pathological characteristics, mechanisms of spread, transmission, control measures, and available vaccinations.

The VanS sensor histidine kinase from type-B VRE recognizes vancomycin directly.

When v ancomycin- r esistant e nterococci (VRE) sense the presence of vancomycin, they remodel their cell walls to block antibiotic binding. This resistance phenotype is controlled by the VanS protein, a histidine kinase that senses the antibiotic or its effects and signals for transcription of resistance genes. However, the mechanism by which VanS detects the antibiotic has remained unclear, with no consensus emerging as to whether the protein interacts directly with vancomycin, or instead detects some downstream consequence of vancomycin's action. Here, we show that for one of the most clinically relevant types of VRE, type B, VanS is activated by direct binding of the antibiotic. Such mechanistic insights will likely prove useful in circumventing vancomycin resistance.

Neuroprotection or Sex Bias: A Protective Response to Traumatic Brain Injury in the Females

Traumatic brain injury (TBI) is a major healthcare problem and a common cause of mortality and morbidity. Clinical and preclinical research suggests sex-related differences in short- and long-term outcomes following TBI; however, males have been the main focus of TBI research. Females show a protective response against TBI. Female animals in preclinical studies and women in clinical trials have shown comparatively better outcomes against mild, moderate, or severe TBI. This reflects a favorable protective nature of the females compared to the males, primarily attributed to various protective mechanisms that provide better prognosis and recovery in the females after TBI. Understanding the sex difference in the TBI pathophysiology and the underlying mechanisms remains an elusive goal. In this review, we provide insights into various mechanisms related to the anatomical, physiological, hormonal, enzymatic, inflammatory, oxidative, genetic, or mitochondrial basis that support the protective nature of females compared to males. Furthermore, we sought to outline the evidence of multiple biomarkers that are highly potential in the investigation of TBI's prognosis, pathophysiology, and treatment and which can serve as objective measures and novel targets for individualized therapeutic interventions in TBI treatment. Implementations from this review are important for the understanding of the effect of sex on TBI outcomes and possible mechanisms behind the favorable response in females. It also emphasizes the critical need to include females as a biological variable and in sufficient numbers in future TBI studies.

Procedure-Specific Thromboprophylaxis in Urological Surgeries: A Narrative Review.

Postoperative pulmonary embolism is a leading cause of mortality in patients undergoing major urologic surgeries, presenting a complex challenge in balancing the risks of venous thromboembolism (VTE) and perioperative bleeding. This study examines the current evidence on thromboprophylaxis in urological procedures, focusing on procedure-specific considerations. Literature on thromboprophylaxis in urological procedures was reviewed during the past decade. Various mechanical thromboprophylaxis methods, such as compression stockings, pneumatic compression devices, foot pumps, mobilization, and exercises, are available preventive measures. Additionally, unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are commonly used pharmacological agents for VTE prevention, with the choice between mechanical, pharmacological, or combined approaches tailored to individual patient characteristics and surgical requirements. Patient risk stratification into low, medium, and highrisk categories based on age, BMI, and VTE history guides the selection of thromboprophylaxis strategies. Surgical procedures are categorized as oncological or non-oncological, with uro-oncological surgeries posing a higher VTE risk than non-oncological procedures. Consequently, a combination of pharmacological and mechanical prophylaxis is typically recommended for uro-oncological patients, while pharmacological prophylaxis is reserved for high-risk individuals undergoing non-oncological surgeries. Mechanical prophylaxis is advised for high-risk patients undergoing procedures with elevated VTE risk. This study summarized an optimal thromboprophylaxis protocol taking into account patient risk factors and the specific urological procedure.

A Comprehensive Review of Preclinical Models for Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is a reproductive, metabolic, and endocrine disorder with unclear aetiology. PCOS, the most common cause of female reproductive and metabolic disorders, is known to affect more than one in ten women globally. PCOS and associated clinical manifestations are probably underdiagnosed despite their high occurrence. Objective: Alternative animal models have been employed to investigate the causes of PCOS or assess potential treatments. In light of this piece of information, it is challenging to create an animal model that accurately captures all components of this condition; nonetheless, the resemblance of an animal model's biology and/or biochemical characteristics to the phenotypes of PCOS in humans may boost its applicability. Result: The key characteristics of these models are closer to human situations when compared to women with PCOS, as shown by this comparison. The creation and testing of drugs for the treatment of PCOS are necessary. Conclusion:: The overview of PCOS, current preclinical models, and appropriate models chosen in different studies to mimic various phenotypes in PCOS studies are all covered in this review paper. Additionally, we have outlined the benefits and drawbacks of PCOS animal models.

Synthesis and In Silico Studies of Quinazolinones as PARP-1 Inhibitors.

Cancer is a leading threat to humankind, accounting for nearly one million deaths in 2018, and the expected number of cancer-related deaths in 2040 is more than 16 million. The most common causes of cancer deaths are lung, colorectal, stomach, liver and breast cancer, while the highest number of new cancer cases belong to lung, breast, colorectal, prostate, stomach and liver cancer. PARP-1 is an enzyme that plays an important role in DNA repair, cell propagation/survival and death due to its influence on numerous biological processes. Quinazolinones represent an important scaffold in medicinal chemistry and have a broad spectrum of biological activities. In this study, we have synthesized quinazolinones by reaction of 2-aminobenzamide and substituted aldehydes. Molecular docking studies of synthesized compounds were performed for their PARP-1 binding affinities using Schrodinger 2016 software. In silico ADME studies were also performed for the synthesized compounds using the QikProp tool of Schrodinger software. Results of molecular docking studies indicated that synthesized quinazolinones had a good affinity towards active site of PARP-1 and compound 4 had the best docking score (-10.343). Results of ADME studies indicated the drug-like properties of synthesized compounds, which make them suitable drug candidates. All the synthesized compounds have a better docking score than niraparib (-9.05). Further, the synthesized compounds have a favorable ADME profile. Therefore, they may serve as important leads in discovering PARP-1 inhibitors.

Physiological and radiological parameters predicting outcome from penetrating traumatic brain injury treated in the deployed military setting

IntroductionPenetrating traumatic brain injury (TBI) is the most common cause of death in current military conflicts, and results in significant morbidity in survivors. Identifying those physiological and radiological parameters associated...

A comparison of the phonation quotient between patients with voice disorders caused by benign vocal fold lesions and normal adults 20-80 years of age

Background: A voice evaluation is an important first step in analyzing voice symptoms and determining appropriate treatment plans. The phonation quotient is a valid aerodynamic parameter in voice evaluations which is an indirect source of information for evaluating the valve function of the vocal folds of patients with voice disorders, especially patients with voice disorders caused by tumors of the vocal folds which is the most common cause in the patients with voice disorders. Objective: The present study aims to determine and compare the phonation quotient between patients with voice disorders caused by benign vocal fold lesions and normal adults between 20-80 years of age. Materials and methods: The participants comprised 40 adults with voice disorders caused by benign vocal fold lesions and 40 with normal voices. All participants’ voices were evaluated in the Speech Clinic at Ramathibodi Hospital, Bangkok. The phonation quotient (PQ) was calculated by the ratio of vital capacity (VC) to the maximum phonation time (MPT). VC and MPT were measured using a phonatory aerodynamic system (PAS). Results: The results of the present study indicated that the mean value of the PQ of adults with normal voices was 122.60 cc/sec (SD=16.36). The mean value of the PQ of adults with voice disorders caused by benign vocal fold lesions was 292.08 cc/ sec (SD=97.14). The mean value of the PQ in the group with voice disorders caused by benign vocal fold lesions was significantly more significant than the mean value of the PQ in the group with normal voice. Conclusion: The significant difference between the phonation quotient of adults with voice disorders caused by benign vocal fold lesions and adults with normal voice was that the PQ might be an indicator for indirect evaluation of the airflow leakage related to the efficiency of vocal fold movement during phonation. The PQ can be the optional voice measurement for monitoring and analyzing the outcomes of voice therapy.

Arenobufagin inhibits lung metastasis of colorectal cancer by targeting c-MYC/Nrf2 axis

Colorectal cancer (CRC) is one of the commonest cancers worldwide. Metastasis is the most common cause of death in patients with CRC. Arenobufagin is an active component of bufadienolides, extracted from toad skin and parotid venom. Arenobufagin reportedly inhibits epithelial-to-mesenchymal transition (EMT) and metastasis in various cancers. However, the mechanism through which arenobufagin inhibits CRC metastasis remains unclear. This study aimed to elucidate the molecular mechanisms by which arenobufagin inhibits CRC metastasis. Wound-healing and transwell assays were used to assess the migration and invasion of CRC cells. The expression of nuclear factor erythroid-2-related factor 2 (Nrf2) in the CRC tissues was assessed using immunohistochemistry. The protein expression levels of c-MYC and Nrf2 were detected by immunoblotting. A mouse model of lung metastasis was used to study the effects of arenobufagin on CRC lung metastasis in vivo. Arenobufagin observably inhibited the migration and invasion of CRC cells by downregulating c-MYC and inactivating the Nrf2 signaling pathway. Pretreatment with the Nrf2 inhibitor brusatol markedly enhanced arenobufagin-mediated inhibition of migration and invasion, whereas pretreatment with the Nrf2 agonist tert‑butylhydroquinone significantly attenuated arenobufagin-mediated inhibition of migration and invasion of CRC cells. Furthermore, Nrf2 knockdown with short hairpin RNA enhanced the arenobufagin-induced inhibition of the migration and invasion of CRC cells. Importantly, c-MYC acts as an upstream modulator of Nrf2 in CRC cells. c-MYC knockdown markedly enhanced arenobufagin-mediated inhibition of the Nrf2 signaling pathway, cell migration, and invasion. Arenobufagin inhibited CRC lung metastasis in vivo. Together, these findings provide evidence that interruption of the c-MYC/Nrf2 signaling pathway is crucial for arenobufagin-inhibited cell metastasis in CRC. Collectively, our findings show that arenobufagin could be used as a potential anticancer agent against CRC metastasis. The arenobufagin-targeted c-MYC/Nrf2 signaling pathway may be a novel chemotherapeutic strategy for treating CRC.

Deep Learning Models and Fusion Classification Technique for Accurate Diagnosis of Retinopathy of Prematurity in Preterm Newborn

اعتلال الشبكية الخداجي (ROP) هو السبب الأكثر شيوعًا لعمى الأطفال الذي لا رجعة فيه، ويعتمد تشخيصه وعلاجه على الدرجات الذاتية بناءً على سمات الأوعية الدموية في شبكية العين. ومع ذلك، فإن هذه الطريقة شاقة وعرضة للخطأ، لذا فإن الأساليب الآلية مرغوبة لمزيد من الدقة والإنتاجية. تهدف هذه الدراسة إلى تطوير نهج قائم على التعلم العميق للتشخيص الدقيق لمرض اعتلال الشبكية الخداجي الزائد عند الأطفال الخدج باستخدام نماذج التعلم التحويلية وتقنية تصنيف الاندماج. زودنا مركز الأمل للعيون في العيادة الخاصة في بغداد، العراق، بـ 2776 صورة لقاعدة فحص مرضى اعتلال الشبكية الخداجي بين عامي 2015 و2020، واستخدمنا هذه الصور لتدريب ثلاثة نماذج للشبكات العصبية التلافيفية العميقة (ResNet50 وDensenet161 وEfficientNetB5). تم استخدام نهج مصنف الاندماج لدمج النماذج الثلاثة من أجل تشخيص شامل ودقيق. تتميز النماذج الثلاثة بمعدلات دقة نسبية تبلغ 69.78٪ و80.57٪ و81.29٪ في تصنيفاتها الخاصة. ومع ذلك، زادت الدقة الإجمالية إلى 90.28 في المائة عند استخدام مصنف الاندماج. هذا يدل على أن الطريقة المقترحة مفيدة لتحديد اعتلال الشبكية الخداجي عند الخدج. تشير نتائج الدراسة إلى أن الطريقة المقترحة لديها القدرة على تعزيز الدقة والسرعة التي يتم بها تشخيص اعتلال الشبكية الخداجي بشكل كبير، مما قد يؤدي بدوره إلى الكشف المبكر عن المرض وعلاجه وتقليل احتمالية الإصابة بعمى الأطفال.

New Insights into the Relationship between Nutrition and Neuroinflammation in Alzheimer's Disease: Preventive and Therapeutic Perspectives.

Neurodegenerative diseases are progressive brain disorders characterized by inexorable synaptic dysfunction and neuronal loss. Since the most consistent risk factor for developing neurodegenerative diseases is aging, the prevalence of these disorders is intended to increase with increasing life expectancy. Alzheimer's disease is the most common cause of neurodegenerative dementia, representing a significant medical, social, and economic burden worldwide. Despite growing research to reach an early diagnosis and optimal patient management, no disease-modifying therapies are currently available. Chronic neuroinflammation has been recognized as a crucial player in sustaining neurodegenerative processes, along with pathological deposition of misfolded proteins, including amyloid-β and tau protein. Modulating neuroinflammatory responses may be a promising therapeutic strategy in future clinical trials. Among factors that are able to regulate neuroinflammatory mechanisms, diet, and nutrients represent easily accessible and modifiable lifestyle components. Mediterranean diet and several nutrients, including polyphenols, vitamins, and omega-3 polyunsaturated fatty acids, can exert antioxidant and anti-inflammatory properties, impacting clinical manifestations, cognitive decline, and dementia. This review aims to provide an updated overview of the relationship between neuroinflammation, nutrition, gut microbiota, and neurodegeneration. We summarize the major studies exploring the effects of diet regimes on cognitive decline, primarily focusing on Alzheimer's disease dementia and the impact of these results on the design of ongoing clinical trials.

Acroparesthesias: An Overview.

Acroparesthesia is a symptom characterized by a subjective sensation, such as numbness, tingling, prickling, and reduced sensation, affecting the extremities (fingers and toes). Despite its frequency, data regarding its diagnostic approach and management are scarce. The etiological diagnosis of acroparesthesia is sometimes challenging since it can be due to abnormality anywhere along the sensory pathway from the peripheral nervous system to the cerebral cortex. Acroparesthesia can reveal several diseases. It can be associated with rheumatic complaints such as arthritis or myalgia. Further cautions are required when paresthesia is acute (within days) in onset, rapidly progressive, severe, asymmetric, proximal, multifocal, or associated with predominant motor signs (limb weakness) or severe dysautonomia. Acroparesthesia may reveal Guillain-Barré syndrome or vasculitis, requiring rapid management. Acroparesthesia is a predominant symptom of polyneuropathy, typically distal and symmetric, often due to diabetes. However, it can occur in other diseases such as vitamin B12 deficiency, monoclonal gammopathy of undetermined significance, or Fabry's disease. Mononeuropathy, mainly carpal tunnel syndrome, remains the most common cause of acroparesthesia. Ultrasonography contributes to the diagnosis of nerve entrapment neuropathy by showing nerve enlargement, hypoechogenic nerve, and intraneural vascularity. Besides, it can reveal its cause, such as space-occupying lesions, anatomical nerve variations, or anomalous muscle. Ultrasonography is also helpful for entrapment neuropathy treatment, such as ultrasound-guided steroid injection or carpal tunnel release. The management of acroparesthesia depends on its causes. This article aimed to review and summarize current knowledge on acroparesthesia and its causes. We also propose an algorithm for the management of acroparesthesia.

Revisiting the Role of B-RAF Kinase as a Therapeutic Target in Melanoma.

Malignant melanoma is the rarest but most aggressive and deadly skin cancer. Melanoma is the result of a malignant transformation of melanocytes, which leads to their uncontrolled proliferation. Mutations in the mitogen-activated protein kinase (MAPK) pathway, which are crucial for the control of cellular processes, such as apoptosis, division, growth, differentiation, and migration, are one of its most common causes. BRAF kinase, as one of the known targets of this pathway, has been known for many years as a prominent molecular target in melanoma therapy, and the following mini-review outlines the state-of-the-art knowledge regarding its structure, mutations and mechanisms.

Regulatory Effects of the Silymarin on Expression of OCT4, NANOG, and P53 in MCF7 Cell Lines

Background:: Breast cancer was known as the second most common cause of death in the world, natural sources compound derived from milk thistle called silymarin had already shown anticancer properties. Objective: In the present study, silymarin was used to treat MCF7 cells and inhibition of stem cell pluripotency genes, as well as cell proliferation. Methods: MCF7 cells were cultured in the presence of RPMI-1640 medium consisting of various silymarin extract concentrations (10, 100, 500, 1000, 2000, 3000, 4000, and 5000 µg/mL) for 24, 48, and 72 hours. The inhibitory effects of the compound on cellular proliferation were assessed via employing MTT assay techniques. Following confirming apoptosis, the fold changes of OCT4, NANOG and P53 expression were determined by quantitative Real-Time PCR. Results: There was a significant difference (p value&lt;0.05) in cell viability when various concentrations of silymarin extract were used for 24, 48, and 72 h in comparison to the control. Real-Time- PCR analysis indicated that the expression of OCT4 and NANOG was downregulated while P53 upregulated in compare to untreated control cells (p value &lt;0.05). Conclusion: According to these findings, the silymarin effects on MCF7 cell line and act via modulating OCT4, NANOG, and P53 pathway mediators. Silymarin may introduce this compound as a promising therapeutic compound against MCF7.

Mild Thrombocytopenia, a Predictor of Outcomes After Laparoscopic Cholecystectomy: Assessment of Surgical Risk in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease.

A common cause of mild thrombocytopenia is chronic liver disease, the most common etiology being metabolic dysfunction-associated steatotic liver disease (MASLD). Mild thrombocytopenia is a well-defined, independent marker of hepatic fibrosis in patients with chronic liver disease. Currently, there is a paucity of information available to characterize perioperative risk in patients with MASLD; therefore, the characterization of perioperative morbidity is paramount. We used a platelet threshold of 150×10 9 as a surrogate for fibrosis in patients undergoing laparoscopic cholecystectomy to study its effect on perioperative complications and mortality. We queried the American College of Surgeons National Surgical Quality Improvement Program database for laparoscopic cholecystectomies occurring from 2005 through 2018. Demographic differences between patients with and without thrombocytopenia were evaluated using the t test or the χ 2 test, whereas adjusted and unadjusted differences in outcome risk were evaluated using log-binomial regression models. We identified 437,630 laparoscopic cholecystectomies of which 6.9% included patients with thrombocytopenia. Patients with thrombocytopenia were more often males, older, and with chronic disease. Patients with thrombocytopenia and higher Aspartate Aminotransferase to Platelet Ratio Index scores had 30-day mortality rates risk ratio of 5.3 (95% CI: 4.8-5.9), with higher complication rates risk ratio of 2.4 (95% CI: 2.3-2.5). The most frequent complications included the need for transfusion, renal, respiratory, and cardiac. Perioperatively, patients with mild thrombocytopenia undergoing laparoscopic cholecystectomy had higher mortality rates and complications compared with patients with normal platelet counts. Thrombocytopenia may be a promising, cost-effective tool to identify patients with MASLD and estimate perioperative risk, especially if used in high-risk populations.