Karimi MA, Paryan M, Behrouzian Fard G
… +3 more, Sadeghian H, Zarrinfar H, Hosseini Bafghi M
Med Princ Pract
· 2026 · PMID 40675140
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<p>Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and the CRISPR-associated protein 9 (Cas9) constitute a revolutionary gene-editing technology, allowing precise DNA modifications with vast potential...<p>Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and the CRISPR-associated protein 9 (Cas9) constitute a revolutionary gene-editing technology, allowing precise DNA modifications with vast potential for disease treatment and the creation of genetically modified organisms. This system consists of various components designed to target specific genes, requiring efficient nuclear access within target cells through diverse delivery methods, including physical techniques and carrier-based approaches. Despite its transformative promise, CRISPR faces several challenges, including efficient cellular delivery, off-target effects, immune responses, optimizing editing efficiency, and ethical concerns. Overcoming these hurdles is crucial for fully harnessing its applications. However, CRISPR-Cas9 offers remarkable opportunities for pioneering gene therapies across various disorders, including cancer, and could revolutionize agriculture by engineering disease-resistant crops. A key strength of CRIScPR lies in its adaptability to a broad spectrum of genes, significantly enhancing its versatility. The technology's potential further expands through emerging interdisciplinary integrations, such as artificial intelligence, machine learning, and biological imaging. These advancements can refine CRISPR's precision, improve efficiency, and mitigate existing limitations, positioning it as an indispensable tool in future genetic research. Overall, CRISPR-Cas9 promises transformative progress in healthcare and agriculture, solidifying its role as a cornerstone in the evolution of genetic engineering. </p>.
Med Princ Pract
· 2025 · PMID 40659017
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UNLABELLED: <p>Objective: This review examines pharmacist-led interventions for their impact on health outcomes and their effectiveness. METHODS: A systematic search was conducted across PubMed, Cochrane Library, and Web...UNLABELLED: <p>Objective: This review examines pharmacist-led interventions for their impact on health outcomes and their effectiveness. METHODS: A systematic search was conducted across PubMed, Cochrane Library, and Web of Science, targeting RCTs up to November 2023 focused on pharmacist-led interventions for chronic obstructive pulmonary disease (COPD) patients. Studies were reviewed for bias risk and evidence quality, followed by a narrative summary of the outcomes. RESULTS: Nine RCTs with 2,094 participants were included, focusing on educational interventions to promote awareness, medication adherence, quality of life, and effective use of inhaler techniques. Significant health improvements were noted in the intervention groups in eight out of nine studies compared to control groups, though concerns about high bias risk and lack of blinding were noted. The GRADE evaluation showed evidence quality ranged from "low" to "very low." CONCLUSION: Pharmacist-led interventions show promise in improving COPD health outcomes, reinforcing the pharmacist's role in disease management. However, the current evidence base is limited by methodological weaknesses, highlighting the need for high-quality research to validate and expand these findings. </p>.
Tsuchie H, Emori M, Murata S
… +6 more, Murahashi Y, Mizushima E, Shimizu J, Nagasawa H, Teramoto A, Miyakoshi N
Med Princ Pract
· 2025 · PMID 40652919
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UNLABELLED: <p>Objectives: Unplanned excision (UE) of soft tissue sarcoma (STS) impacts recurrence and prognosis, influenced by various factors. However, few studies have thoroughly analyzed these patients. This study ai...UNLABELLED: <p>Objectives: Unplanned excision (UE) of soft tissue sarcoma (STS) impacts recurrence and prognosis, influenced by various factors. However, few studies have thoroughly analyzed these patients. This study aimed to comprehensively evaluate prognostic factors in patients with STS who underwent UE. SUBJECT AND METHODS: We retrospectively identified 62 patients with STS who underwent UE. Data on clinical information and detailed assessment were collected. Clinical data were evaluated as risk factors for overall survival, local recurrence, and distant metastases. Furthermore, associations of influencing factors and survival outcomes were analyzed. RESULTS: Multivariate analysis identified consultation after local recurrence following previous surgery and histological high grade as significant predictors of poor prognosis (p = 0.0390 and p = 0.0282, respectively). Histological high grade was the only risk factor for distant metastasis (p = 0.0173). Kaplan-Meier curves demonstrated significant differences in overall survival based on the presence or absence of local recurrence at referral after UE (p = 0.0476, p = 0.0022). The use of local anesthetics in previous surgeries was the only risk factor for consultation after local recurrence. CONCLUSION: Referral after local recurrence after UE and histological high grade were poor prognostic factors. Physicians must be aware that patients with UE should be referred to specialists promptly. </p>.
Takasaki I, Takeuchi F, Miyamae R
… +7 more, Mochizuki Y, Kinoshita H, Hagiyama M, Yoneshige A, Inoue T, Narumi T, Ito A
Med Princ Pract
· 2025 · PMID 40633531
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UNLABELLED: <p>Objective: Cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is abundantly expressed on nerve fibers. Recently, the anti-CADM1 ectodomain antibody 3E1 has been shown to be potentially...UNLABELLED: <p>Objective: Cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is abundantly expressed on nerve fibers. Recently, the anti-CADM1 ectodomain antibody 3E1 has been shown to be potentially useful as a local anesthetic due to its high affinity for subcutaneous nerve fibers. When injected intrathecally into mice, where 3E1 accumulates, and whether it serves as an analgesic was examined. METHODS: The 3E1 injection was detected using indocyanine green-based imaging and immunohistochemistry. As a neuropathic pain model, mechanical allodynia-affected mice were created by spinal nerve ligation (SNL). These mice were administered intrathecally with 3E1, control antibody, or pregabalin, and then the pain threshold of the hind paw was measured using von Frey monofilaments. After SNL, followed by intrathecal injection of 3E1, real-time PCR was conducted to examine the expression of pain-related genes, interleukin (IL)-1β, IL-2, IL-6, IL-10, tumor necrosis factor-α, chemokine (C-C motif) ligand (CCL) 2, CCL7, and CCL11. RESULTS: Intrathecally, injected 3E1 was localized mainly on the dorsal root ganglion cell bodies and spinal dorsal horn nerve fibers, with no motor side effects. In the von Frey test, 3E1-injected mice exhibited higher pain thresholds for up to 2 weeks compared to control mice. Pregabalin also raised the threshold, but the effect dissipated within 1 day. While SNL increased mRNA expression of all pain-related genes examined in spinal dorsal horn neurons, 3E1 injection suppressed the increased expression of IL-6. CONCLUSION: 3E1 was suggested to be a potential ganglion-blocking analgesic and spinal anesthetic that acts ten or more times longer than pregabalin. </p>.
Med Princ Pract
· 2025 · PMID 40628241
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<p>Gastrointestinal (GI) cancers are among the leading causes of cancer-related morbidity and mortality worldwide, presenting a significant public health challenge. Even with medical research advancements, their incidenc...<p>Gastrointestinal (GI) cancers are among the leading causes of cancer-related morbidity and mortality worldwide, presenting a significant public health challenge. Even with medical research advancements, their incidence remains rising due to modifiable and non-modifiable risk factors across lifestyle, environmental, genetic, and socioeconomic factors. This narrative review identifies and synthesizes key risk factors contributing to GI cancers, including unhealthy diets (high consumption of processed foods, red meat, and added sugars), physical inactivity, obesity, smoking, alcohol use, infections (e.g., Helicobacter pylori), environmental pollution, chronic stress, and socioeconomic disparities. The review emphasizes the interaction among these factors and how this interplay is responsible for the development and progression of GI cancer. It emphasizes the importance of early detection, lifestyle modifications, and public health interventions tailored to specific populations. Understanding these interconnected risk factors provides critical insights for guiding prevention strategies, policymaking, and health education. Addressing modifiable risk factors through a comprehensive, multi-sectoral approach may significantly reduce the global burden of GI cancers and improve long-term health outcomes. </p>.
Haq AU, Suhail A, Ahsan W
… +14 more, Maqbool H, Nawal A, Hassan H, Bungish MK, Shahid MA, Wazir HU, Yousaf H, Rehman MEU, Ahmad Cheema H, Alsubari AAAMA, Khan MA, Nadeem B, Ahmed R, Ahmad A
Med Princ Pract
· 2025 · PMID 40582348
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UNLABELLED: <p>Objectives: This meta-analysis compared the efficacy and safety of drug-coated balloon (DCB) angioplasty with drug-eluting stent (DES) for the treatment of de novo coronary artery disease. METHODS: Followi...UNLABELLED: <p>Objectives: This meta-analysis compared the efficacy and safety of drug-coated balloon (DCB) angioplasty with drug-eluting stent (DES) for the treatment of de novo coronary artery disease. METHODS: Following PRISMA guidelines, we conducted a systematic search of major databases, including Cochrane, Medline, Embase and ClinicalTrials.gov, to identify eligible randomized controlled trials (RCTs) comparing DCB and DES. Mantel-Haenszel model was used for dichotomous outcomes. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model using RevMan software. RESULTS: Thirteen RCTs with a total of 4,686 patients were included. The analysis found no significant differences between DCB and DES for all-cause mortality (RR: 1.11, 95% CI: 0.81-1.53, p = 0.51) or myocardial infarction (RR: 0.80, 95% CI: 0.56-1.15, p = 0.23). Similarly, no significant differences were observed for cardiac death (RR: 1.33, 95% CI: 0.86-2.05, p = 0.19), target lesion revascularization (RR: 1.19, 95% CI: 0.64-2.21, p = 0.59), or target vessel revascularization (RR: 1.34, 95% CI: 0.79-2.28, p = 0.28). CONCLUSION: This meta-analysis demonstrates comparable efficacy and safety outcomes for DCBs and DES in the treatment of de novo coronary artery disease. While DCBs offer a viable alternative, particularly for high-risk patients or those unsuitable for prolonged dual antiplatelet therapy, further large-scale studies are warranted to strengthen these findings and refine clinical recommendations. </p>.
Med Princ Pract
· 2025 · PMID 40562021
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<p>The physiological roles played by red blood cells (RBCs), i.e., oxygen transport to all cells and tissues, CO delivery to the lungs, control of pH in blood, and ions transport into and out of the cell membrane, have b...<p>The physiological roles played by red blood cells (RBCs), i.e., oxygen transport to all cells and tissues, CO delivery to the lungs, control of pH in blood, and ions transport into and out of the cell membrane, have been investigated extensively over the past decades. The roles mature and immature RBCs play, while in the blood vessels, when they come in contact with other blood and endothelial cells, are only partially known. Here we will focus on the ability of RBC to modulate innate and adaptive immune responses when they interact with cells or molecules encountered during their flow in the vessels. We will outline the possible clinical impact on treatment of some diseases, such as autoimmune diseases, inflammatory pathologies, or tumors, where immunotherapy can be applied. </p>.
Li Y, Hu M, Chen Y
… +4 more, Yang XY, Wang Q, Ding J, Hu Y
Med Princ Pract
· 2025 · PMID 40545809
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<p>Vedolizumab (VDZ) is a key therapeutic option for inflammatory bowel disease (IBD) patients, not responding to conventional treatments. An α4β7 integrin antagonist, VDZ, primarily prevents T-cell migration to the gut...<p>Vedolizumab (VDZ) is a key therapeutic option for inflammatory bowel disease (IBD) patients, not responding to conventional treatments. An α4β7 integrin antagonist, VDZ, primarily prevents T-cell migration to the gut by inhibiting the binding of integrins to mucosal vascular address in cellular adhesion molecule. Its gut-selective mechanism of action and safety profile makes it a valuable intervention for treating non-IBD-related diseases, which are difficult to treat and lack standardized guidelines. There is plenty of evidence to suggest that VDZ has therapeutic potential beyond its primary indication in IBD, with clinical applications now extending to immune checkpoint inhibitor-associated colitis, chronic pouchitis, gastrointestinal graft-versus-host disease, and acquired immunodeficiency syndrome. This review aimed to analyze the therapeutic value of VDZ for non-IBD-related diseases and provide a reference for treating these patients. It has been observed that long-term follow-up data are lacking, and additional well-designed large-scale studies are still needed to further validate the efficacy and safety of VDZ. </p>.
Magdits M, AlShammari A, Majdalani R
… +2 more, Devarajan S, Raiszadeh F
Med Princ Pract
· 2025 · PMID 40451182
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UNLABELLED: <p>Objectives: This study aimed to investigate the obesity paradox in patients with congestive heart failure (CHF) at Harlem Hospital Center (HHC), examine the role of diabetes in CHF readmissions, and explor...UNLABELLED: <p>Objectives: This study aimed to investigate the obesity paradox in patients with congestive heart failure (CHF) at Harlem Hospital Center (HHC), examine the role of diabetes in CHF readmissions, and explore the combined impact of obesity and diabetes on readmission rates. METHODS: A retrospective chart review was conducted on 390 patients from HHCs CHF registry (January 2019-December 2021). CHF admissions and 30-day readmissions were analyzed, focusing on obesity, diabetes, and their interplay. RESULTS: Preliminary analyses revealed a correlation between obesity and reduced 30-day readmission rates. Diabetes alone did not significantly influence readmissions; however, patients with both obesity and diabetes had higher readmission rates than those with obesity alone. However, after adjusting for confounders, none of the observed associations remained statistically significant, highlighting the complexity of interpreting the obesity paradox in this population. CONCLUSIONS: These findings suggest that the obesity paradox may exist but is attenuated by the presence of diabetes. Further research is needed to elucidate these relationships and their implications for managing CHF in obese diabetic patients. </p>.
Med Princ Pract
· 2025 · PMID 40418923
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UNLABELLED: <p>Objectives: This study aimed to predict and classify magnetic resonance imaging (MRI) Prostate Imaging Reporting and Data System (PI-RADS) scores using different machine learning algorithms and to detect t...UNLABELLED: <p>Objectives: This study aimed to predict and classify magnetic resonance imaging (MRI) Prostate Imaging Reporting and Data System (PI-RADS) scores using different machine learning algorithms and to detect the concordance of PI-RADS scoring with the outcome target of prostate biopsy. METHODS: Machine learning (ML) algorithms were used to develop best-fitting models for the prediction and classification of MRI PI-RAD. The Random Forest and Extra Trees models achieved the best performance compared to the other methods. RESULTS: The accuracy of both models was 91.95%. The AUC was 0.9329 for the Random Forest model and 0.9404 for the Extra Trees model. PSA level, PSA density, and diameter of the largest lesion were the most important features for the importance of outcome classification. ML prediction enhanced the PI-RAD classification, where clinically significant prostate cancer (csPCa) cases increased from 0% to 1.9% in the low-risk PI-RAD class, this showed that the model identified some previously missed cases. CONCLUSIONS: Predictive machine learning models showed an excellent ability to predict MRI Pi-RAD scores and discriminate between low- and high-risk scores. However, caution should be exercised, as a high percentage of negative biopsy cases were assigned Pi-RAD 4 and Pi-RAD 5 scores. ML integration may enhance PI-RAD's utility by reducing unnecessary biopsies in low-risk patients (via better csPCa detection) and refining the high-risk categorization. Combining such PI-RAD scores with significant parameters, such as PSA density, lesion diameter, number of lesions, and age, in decision curve analysis and utility paradigms would assist physicians' clinical decisions. </p>.
Med Princ Pract
· 2025 · PMID 40418914
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UNLABELLED: <p>Objective: Postoperative pain during endodontic treatment can impair patient comfort and complicate clinical management, particularly in symptomatic irreversible pulpitis. Vital pulpotomy treatment (VPT) i...UNLABELLED: <p>Objective: Postoperative pain during endodontic treatment can impair patient comfort and complicate clinical management, particularly in symptomatic irreversible pulpitis. Vital pulpotomy treatment (VPT) is less invasive than total pulpectomy for symptomatic irreversible pulpitis. SUBJECT: This study aimed to evaluate postoperative pain in patients after VPT of permanent molars with symptomatic pulpitis and explore the relationship between postoperative pain and patient-related factors. METHODS: A total of 114 patients, aged 7-39, were included. Permanent molars (n = 114) with symptomatic irreversible pulpitis (periapical index ≤2) were selected. Preoperative pain levels, analgesic intake, and demographic data were recorded. All participants underwent a standardized pulpotomy procedure. Hemostasis was achieved within 5 min using a saline-embedded cotton pellet. A mineral trioxide aggregate was used as a pulpotomy agent, and the teeth were restored using a base of resin-modified glass ionomer, followed by composite restoration. Using a 4-point pain scale, the patients recorded their pain preoperatively before the administration of local anesthesia and postoperatively at 24 h, 72 h, and 1 week. Fisher's exact test was used to assess the relationships between categorical variables. Statistical significance was set at p < 0.05. RESULTS: Among the 114 patients, 110 (96.49%) had complete relief from preoperative pain after treatment, and no postoperative pain was recorded at 1 week, irrespective of patient-related factors, such as age, sex, and painkiller intake (95% CI: 0.529-0.554). CONCLUSIONS: Vital pulpotomy is an effective treatment for relieving preoperative pain and preventing postoperative pain in teeth with symptomatic irreversible pulpitis independent of patient-related factors. </p>.
Mayer O, Bílková S, Nezbedová T
… +5 more, Karnosová P, Windrichová J, Hirmerová J, Pazdiora P, Filipovský J
Med Princ Pract
· 2025 · PMID 40398396
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UNLABELLED: <p>Objectives: The overexpression of plasminogen activator inhibitor-1 (PAI-1) was frequently observed during coronavirus disease 2019 (COVID-19), and it was found to be closely associated with disease severi...UNLABELLED: <p>Objectives: The overexpression of plasminogen activator inhibitor-1 (PAI-1) was frequently observed during coronavirus disease 2019 (COVID-19), and it was found to be closely associated with disease severity. We have analyzed the PAI-1 status in fully recovered post-COVID patients. SUBJECTS AND METHODS: In a case-control and cross-sectional study, we compared 377 patients, 30-210 days after PCR-verified COVID-19 and 884 COVID-naive controls. RESULTS: Post-COVID patients ("cases") showed significantly higher plasma PAI-1 concentrations than COVID-naive controls. This difference remained significant even after complex adjustment by multiple regression. On the other hand, since the strongest covariate of increased PAI-1 was antihypertensive treatment, the difference between cases and controls in those who were on antihypertensives completely disappeared. In the subgroup of post-COVID patients only, we also found that highly symptomatic patients or those who required hospitalization in the acute phase showed significantly higher PAI-1 than patients with only mild symptoms of the disease. Similarly, the presence of β mutation increased the relative risk (≈11 times) of high post-COVID concentrations of PAI-1. Similarly, the presence of β mutation increased the relative risk (≈11 times) of high post-COVID concentrations of PAI-1. CONCLUSIONS: Increased values of PAI-1 can persist for several months after complete recovery from COVID-19 (namely, by β variant of the virus), and their expression also corresponded to clinical course of the disease. </p>.
Tomaino L, Roncarati I, Rodríguez-Mireles S
… +9 more, Rivas-Wagner E, López-Valcárcel BG, La Vecchia C, Negri E, Di Maio V, Contucci S, Falsetti L, Moroncini G, Serra-Majem L
Med Princ Pract
· 2025 · PMID 40319869
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UNLABELLED: <p>Objective: The aim of the study was to analyze the changes in the emergency department (ED) activity of two hospitals during the 2020 lockdown and corresponding timeframes in 2019 and 2021 to assess whethe...UNLABELLED: <p>Objective: The aim of the study was to analyze the changes in the emergency department (ED) activity of two hospitals during the 2020 lockdown and corresponding timeframes in 2019 and 2021 to assess whether a more structured primary healthcare service could have influenced the COVID-19 pressure on the ED. SUBJECT AND METHODS: This is a multicenter, retrospective study on adult subjects registered to the selected ED during the timeframes considered. Patients <16 years old and women with obstetric or gynecological complaints were excluded. Study period was from 9 March to 3 May for the Italian ED (55 days) and March 14 to May 10 for the Spanish ED (57 days) in 2019, 2020, and 2021. Primary outcome includes difference in the number of ED admissions. Secondary outcomes consist of differences in hospital admission rates, priority code at triage, and disease group. RESULTS: Overall, a greater number of patients flowed through the Spanish ED (14,034 vs. 8,569 in 2019, 7,208 vs. 3,101 in 2020, and 13,214 vs. 5,555 in 2021), with smaller proportional declines and lower admission rates (13% vs. 16.9% in 2019, 19.6% vs. 34.3% in 2020, and 14.3% vs. 26.3% in 2021) observed. Most referrals were for nonemergency conditions, followed by trauma and intoxications. CONCLUSIONS: In comparison with the Italian setting, the Spanish ED showed increased activity alongside lower hospitalization rates. Further investigation is required to evaluate the potential role of more structured primary healthcare assistance in enhancing the discharge rate to homecare or primary healthcare facilities during the specified timeframes. </p>.
Kokturk U, Köktürk U, Püşüroğlu H
… +5 more, Çetin İ, Somuncu MU, Altunova M, Avcı A, Ertürk M
Med Princ Pract
· 2025 · PMID 40288365
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UNLABELLED: <p>Objective: We investigated the relationship between D-dimer levels and long-term major adverse cardiovascular events (MACEs) in masked hypertension patients admitted to the cardiology outpatient clinic. ME...UNLABELLED: <p>Objective: We investigated the relationship between D-dimer levels and long-term major adverse cardiovascular events (MACEs) in masked hypertension patients admitted to the cardiology outpatient clinic. METHODS: A total of 512 masked hypertension patients with a median 6 years of follow-up data who underwent serum D-dimer measurement in the hypertension outpatient clinic between April 2014 and June 2016 were retrospectively enrolled. The patients were stratified according to their D-dimer levels and were then divided into tertiles. Clinical outcomes were assessed for MACEs, which were defined as all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke. RESULTS: The long-term incidence of MACE in masked hypertension patients was higher in the highest tertile of D-dimer. In multivariable analysis, D-dimer was an independent predictor of long-term MACE in masked hypertensive patients (OR: 1.006 [1.004-1.007]; p < 0.001). Compared to the lowest tertile, MACE was approximately 3 times higher in tertile 2 and approximately 10.5 times higher in the highest tertile. In addition, MACE was approximately 3.5 times more common in tertile 3 than in tertile 2. D-dimer was able to predict MACE in patients with masked hypertension (AUC for MACE 0.778; 95% CI: 0.724-0.832; p < 0.001) based on receiver operating characteristic curve analysis. In the Kaplan-Meier curve showing follow-up without MACE (MACE free) according to the D-dimer cutoff value, the long-term incidence of MACE was significantly higher in the high D-dimer group (p < 0.001). CONCLUSIONS: D-dimer levels in patients with masked hypertension showed a significant association with increased long-term risk of MACE in this study. </p>.
Med Princ Pract
· 2025 · PMID 40288362
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UNLABELLED: <p>Background: Medications exhibiting serotonergic properties, such as selective serotonin reuptake inhibitors (SSRIs) antidepressants, opioids, and other antidepressants can induce serotonin syndrome, a rare...UNLABELLED: <p>Background: Medications exhibiting serotonergic properties, such as selective serotonin reuptake inhibitors (SSRIs) antidepressants, opioids, and other antidepressants can induce serotonin syndrome, a rare but potentially life-threatening adverse event. AIM: This study aims to investigate the risks of serotonin syndrome among different SSRIs and assess the influence of drug-drug interactions with other medications. METHODS: We analyzed the suspected adverse events in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. RESULTS: We identified 13,312 reports of serotonin syndrome, 52% of which involved SSRIs (n = 6,921), with reporting odds ratios (RORs) of 24.19. Among the safety reports involving SSRIs, 4,851 cases reported at least one severe outcome. All active substances of the SSRI group were associated with serotonin syndrome, sertraline, and fluoxetine had the most reports, while fluvoxamine had the highest ROR and risk compared to all other SSRIs (ROR: 2.66, 95% confidence interval: 2.33-3.05). The combinations of SSRIs with other drugs with the most reported cases were SSRIs-antidepressants (n = 2,395) and SSRIs-opioids (n = 2,252). The combinations of SSRIs with serotonin-norepinephrine reuptake inhibitors (ROR 25.42) and "other antidepressants" (ROR 22.74) were associated with a signal for serotonin syndrome. The combination SSRIs-opioids was associated with a safety signal, particularly those with higher risk for serotonin syndrome, like tramadol and fentanyl (ROR 41.95). CONCLUSION: Close monitoring for symptoms of serotonin syndrome should be considered in patients with depression with a combination of antidepressants, and in those on SSRIs who also require linezolid, monoamine oxidase inhibitors or high-risk opioids, like tramadol, or fentanyl. </p>.