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Background and Objectives: This study aimed to investigate the role of the pre- and postoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting intensive care unit (ICU) admission and postoperative length of stay (LOS) in bariatric surgery. Materials and Methods: We retrospectively analysed 96 patients who underwent bariatric surgery at our institution. The NLR and PLR were calculated in the pre- and postoperative stages. Changes in pre- and postoperative hematological ratios were compared using the Wilcoxon signed-rank test. The optimal cutoff values and area under the curve (AUC) for each ratio were calculated using receiver operating characteristic (ROC) analysis. Multivariate linear regression analysis was used to assess the relationship between each ratio and the postoperative LOS after adjusting for age, sex, and American Society of Anesthesiologists (ASA) score. Results: The median age of our patients was 35.50 years, and 54.2% were male. The preoperative NLR showed a significant increase from 1.44 to 6.38 postoperatively (p < 0.001). The PLR increased from 107.08 preoperatively to 183.58 postoperatively, p < 0.001). ROC analysis showed that the postoperative NLR was a moderate to high predictor of ICU admission (AUC = 0.700, optimal cutoff point = 5.987). The postoperative PLR had less predictive power for ICU admission (AUC = 0.641, optimal cutoff point = 170.950). Ratios that had a statistically significant relationship with the postoperative LOS were the preoperative NLR (standardized β [95% CI]: 0.296 [0.115–0.598]), postoperative NLR (0.311 [0.034–0.161]), and postoperative PLR (0.236 [0.000–0.005]). Conclusions: The NLR and PLR demonstrated an independent relationship with the postoperative LOS after bariatric surgery and the predictive ability of ICU admission. Both ratios might be useful as simple markers to predict patient outcome after surgery. [ABSTRACT FROM AUTHOR]

Background: Genomic instability is increased alterations in the genome during cell division and is common among most cancer cells. Genome instability enhances the risk of initial carcinogenic transformation, generating new clones of tumor cells, and increases tumor heterogeneity. Although genome instability contributes to malignancy, it is also an "Achilles' heel" that constitutes a therapeutically-exploitable weakness--when sufficiently advanced, it can intrinsically reduce tumor cell survival by creating DNA damage and mutation events that overwhelm the capacity of cancer cells to repair those lesions. Furthermore, it can contribute to extrinsic survival-reducing events by generating mutations that encode new immunogenic antigens capable of being recognized by the immune system, particularly when anti-tumor immunity is boosted by immunotherapy drugs. Here, we describe how genome-destabilization can induce immune activation in cancer patients and systematically review the induction of genome instability exploited clinically, in combination with immune checkpoint blockade. Methods: We performed a systematic review of clinical trials that exploited the combination approach to successfully treat cancers patients. We systematically searched PubMed, Cochrane Central Register of Controlled Trials, Clinicaltrials. gov, and publication from the reference list of related articles. The most relevant inclusion criteria were peer-reviewed clinical trials published in English. Results: We identified 1,490 studies, among those 164 were clinical trials. A total of 37 clinical trials satisfied the inclusion criteria and were included in the study. The main outcome measurements were overall survival and progression-free survival. The majority of the clinical trials (30 out of 37) showed a significant improvement in patient outcome. Conclusion: The majority of the included clinical trials reported the efficacy of the concept of targeting DNA repair pathway, in combination with immune checkpoint inhibitors, to create a "ring of synergy" to treat cancer with rational combinations. [ABSTRACT FROM AUTHOR]

Zeb1, a zinc finger E-box binding homeobox epithelial-mesenchymal transition (EMT) transcription factor, confers properties of 'sternness,' such as self-renewal, in cancer. Yet little is known about the function of Zeb1 in adult stem cells. Here, we used the hematopoietic system as a well-established paradigm of stem cell biology to evaluate Zeb1-mediated regulation of adult stem cells. We employed a conditional genetic approach using the Mx1- Cre system to specifically knock out (KO) Zeb1 in adult hematopoietic stem cells (HSCs) and their downstream progeny. Acute genetic deletion of Zeb1 led to rapid-onset thymic atrophy and apoptosis-driven loss of thymocytes and T cells. A profound cell-autonomous self-renewal defect and multilineage differentiation block were observed in Zeb1-KO HSCs. Loss of Zeb1 in HSCs activated transcriptional programs of deregulated HSC maintenance and multilineage differentiation genes and of cell polarity consisting of cytoskeleton-, lipid metabolism/lipid membrane-, and cell adhesion-related genes. Notably, epithelial cell adhesion molecule (EpCAM) expression was prodigiously upregulated in Zeb1-KO HSCs, which correlated with enhanced cell survival, diminished mitochondrial metabolism, ribosome biogenesis, and differentiation capacity and an activated transcriptomic signature associated with acute myeloid leukemia (AML) signaling. ZEB1 expression was downregulated in AML patients, and Zeb1 KO in the malignant counterparts of HSCs--leukemic stem cells (LSCs)--accelerated MLL-AF9- and Meis1a/Hoxa9-driven AML progression, implicating Zeb1 as a tumor suppressor in AML LSCs. Thus, Zeb1 acts as a transcriptional regulator in hematopoiesis, critically coordinating HSC self-renewal, apoptotic, and multilineage differentiation fates required to suppress leukemic potential in AML., Introduction Epithelial-mesenchymal transition (EMT) is a complex process that organizes specific changes in cellular fate and phenotype and is usually accompanied by loss of cell polarity and adhesion and increased [...]

Background and Objectives: An understanding of the anatomical complexity of teeth is a significant factor for a successful endodontic treatment outcome. The aim of this study was to explore the frequency and pattern of distribution of radix entomolaris (RE) in mandibular first molars (MFMs) of a Saudi Arabian subpopulation using CBCT scans. Materials and Methods: This study was conducted at dental clinics of Qassim University from February to May 2023 by evaluating CBCT scans that were previously obtained for diagnostic purposes. Scans of Saudi national patients with bilaterally present MFMs and fully formed root apices were included. Conversely, scans with one/or two missing MFMs, MFMs with incomplete root apices, full- or partial-coverage prosthesis, endodontic treatment, and associated radicular resorption were excluded from study. A total of 303 CBCT scans with 606 bilateral MFMs were analyzed by two calibrated evaluators for the presence of, and type according to Song's typolgy of RE. The data were analyzed using SPPS-24. The descriptive variables were documented as frequencies and percentages. The chi-square test was used to determine the association between the prevalence of RE with the gender, jaw side and age group. Both inter-rater and intra-rater agreements were estimated for detecting and classifying RE using Cohen's kappa test. Results: The sample had 63.7% males and 36.3% females. The prevalence of RE was 6.6%, with Song's type III (57.5%) as the most common variant. Absolute agreement was noted between the raters about the presence of RE and very strong agreement was noted for the classification of the RE. Conclusions: RE is an uncommon finding among the mandibular first molars of the Saudi population without any gender and quadrant predilection. The clinicians' knowledge of the presence and Song's type of RE may contribute towards the enhancement of endodontic treatment outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Many risk factors, such as the duration of surgery and higher ASA scores, are associated with longer hospitalization in patients undergoing orthopedic surgery. However, no studies have evaluated the relationship between the preoperative systemic immune-inflammation index (SII) and length of hospital stay in orthopedic surgical patients. Therefore, this study aimed to investigate whether the SII is associated with the length of hospital stay in orthopedic surgery in adults.Patients and Methods: This was a retrospective cohort study, and data were extracted from electronic health records. Patients were included if they were older than 18 years and had undergone orthopedic surgery between [2016– 2021]. The patients were divided into two groups according to the median duration of hospitalization and according to SII cut-off value (high-SII group: ≥ 799.86, low-SII group: < 799.86). Univariate and multivariate linear regression analyses were used to identify the association between SII and length of hospitalization.Results: A total of 196 patients who underwent orthopedic surgery were included, and 62 were hospitalized for > 21 days. There were significant differences in terms of ASA score (P =  0.041). Patients who required a longer hospitalization of > 21 days had significantly lower hemoglobin level (P <  0.001), higher duration of surgery (P = 0.015), and increased requirement of ICU admission (P <  0.001). The optimal cut-off value for preoperative SII of 799.86 stratified the patients into high-SII and low-SII groups. Patients in high-SII group had higher median LOHS (22 days) compared to low-SII group (17 days; P = 0.006). In the multivariable linear regression analysis, the SII was significantly related to the length of hospital stay (β = 0.246, 95% confidence interval [CI] 0.000– 0.005, P = 0.031).Conclusion: A high-SII value is associated with an increased risk of longer hospitalization after orthopedic surgery. [ABSTRACT FROM AUTHOR]

The global COVID-19 pandemic has strained healthcare systems around the globe, necessitating extensive research into the variables that affect patient outcomes. This study examines the relationships between key haematology parameters, duration of hospital stay (LOS), and mortality rates in COVID-19 cases in paediatric patients. Researchers analyse relationships between independent variables (COVID-19 status, age, sex) and dependent variables (mortality, LOS, coagulation parameters, WBC count, RBC parameters) using multivariate regression models. Although the R-square values (0.6–3.7%) indicate limited explanatory power, coefficients with statistical significance establish the impact of independent variables on outcomes. Age emerges as a crucial predictor of mortality; the mortality rate decreases by 1.768% per age group. Both COVID-19 status and age have an inverse relationship with length of stay, emphasising the milder hospitalisation of children. Platelet counts decline with age and male gender, potentially revealing the influence of COVID-19 on haematological markers. There are significant correlations between COVID-19 status, age, gender and coagulation measures. Lower prothrombin time and D-dimer concentrations in elder COVID-19 patients are indicative of distinct coagulation profiles. WBC and RBC parameters exhibit correlations with variables: COVID-19-positive patients have lower WBC counts, whereas male COVID-19-positive patients have higher RBC counts. In addition, correlations exist between independent variables and the red cell distribution width, mean corpuscular volume, and mean corpuscular haemoglobin. However, there is no correlation between mean corpuscular haemoglobin concentration and outcomes, indicating complex interactions between haematological markers and outcomes. In essence, this study underlines the importance of age in COVID-19 mortality, provides novel insights into platelet counts, and emphasises the complexity of the relationships between haematological parameters and disease outcomes. [ABSTRACT FROM AUTHOR]

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Introduction: Rotary nickel-titanium files for root canal therapy have become standard treatment modalities in general practice and specialized dental centers. Undergraduate dental students should receive proper training in using rotary files before graduation. Therefore, this study aimed to provide detailed insight into the implementation of rotary root canal instruments in the clinical training of undergraduate students in Saudi Arabia. Materials and Methods: Two randomly selected private schools and 13 government-owned schools were selected to represent all administrative regions in Saudi Arabia. The SurveyMonkey® questionnaire was sent to each dental school through direct communication. It covered most aspects of the rotary root canal instruments used in the clinical training of undergraduate students before graduation. Results: Approximately 92.9% of the included dental schools reported using rotary files in undergraduate teaching; however, only 57.1% had specific clinical requirements for rotary root canal instrumentation in their curricula. Laboratory simulation sessions were the most commonly used preclinical training methods for rotary instrumentation (85.7%). Most dental schools implemented rotary file training in the 4th and 5th years (53.8% and 38.5%, respectively). The ProTaper® (Universal, Next, Gold) was the most commonly used rotary system. Most dental schools had an instructor-to-student ratio of 1:5. Conclusion: Most Saudi dental schools have adopted rotary files during their undergraduate training. However, the curricula of some dental schools do not include a predetermined number of clinical cases treated with rotary instrumentation to ensure better training for students before graduation. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) vaccines have been developed to help prevent the spread of the virus infections. The COVID-19 vaccines, including Pfizer, Moderna, and AstraZeneca, have undergone rigorous testing and have demonstrated both safety and effectiveness. Extensive evidence supports their effectiveness in preventing severe illness, hospitalization, and mortality associated with COVID-19 infection. The administration of COVID-19 vaccines can directly affect hematological and biochemical parameters, with reported cases showing an association with thrombosis and thrombocytopenia. Therefore, it was hypothesized that COVID-19 vaccines may also influence hematological and biochemical markers in sickle cell patients. This study aimed to investigate the side effects of COVID-19 vaccines on sickle cell patients, providing a comprehensive evaluation of hematological and biochemical parameters. To our knowledge, this is the first study of its kind conducted in Saudi Arabia. The study included the evaluation of Pfizer and Oxford-AstraZeneca vaccines in sickle cell patients, measuring key parameters. Our findings revealed varying impacts of both vaccines on the ALT, AST, and CRP levels. Notably, CRP and ALT exhibited potential as indicators for renal disease, diabetes, and arthritis. However, further investigations are necessary to uncover the underlying mechanisms that drive these observed differences and comprehend their clinical implications for this vulnerable patient population. The unique nature of our study fills a crucial research gap and underscores the need for additional research in this area. [ABSTRACT FROM AUTHOR]

Objective: Photon-induced photoacoustic streaming (PIPS) with pineapple peel extract (PPE) and ethylenediaminetetraacetic acid (EDTA) as a final endodontic irrigant on the push-out bond strength (PBS) of root filling material to conventional irrigation NaOCl with EDTA. Methods: An in vitro study at Dar Al Uloom University was conducted over three months. Root canal preparation was performed. Based on final irrigation, all the specimens were divided randomly into four groups (n=10) Group 1: 2.25% NaOCl+ 17% EDTA (control), Group-2: 2.25% NaOCl+PIPS + 6.25% PPE, Group-3: 2.25% NaOCl+PIPS + 17% EDTA, Group-4: 2.25% NaOCl + 6.25% PPE. Canals were obturated and sealed with AH Plus sealer. Root sectioning was performed at 1mm thickness and PBS testing was performed using the universal testing machine. The debonded samples were analyzed for failure mode. ANOVA compared the means and standard deviations (SD) of all investigated group. Assessment of multiple comparisons was performed using Tukey's post hoc test. Results: The maximum PBS was demonstrated by the coronal section of Group-2 (2.25%NaOCl +PIPS+6.25%PPE) specimens (8.21±0.81MPa). The apical section of Group-1 (2.25% NaOCl+17% EDTA) specimens demonstrated minimum bond strength (2.80±0.18 MPa). The intergroup comparison revealed that Group-3 (2.25% NaOCl +PIPS +17% EDTA) and Group-2 demonstrated comparable outcomes (p>0.05). Group-4 (2.25% NaOCl +6.25% PPE) specimens established significantly lower values than Group-3 and Group-4 (p<0.05). Conclusion: Photon-induced photoacoustic streaming with pineapple peel extract and EDTA demonstrated better bond strength of root canal sealer and have the potential to be used as the final irrigant. [ABSTRACT FROM AUTHOR]

Glucose-6-phosphate dehydrogenase (G6PD) insufficiency is a common enzymatic defect worldwide; it affects over 400 million people and is associated with various disorders. Recent research suggests that G6PD-deficient cells are susceptible to infection by human coronaviruses, as the G6PD enzyme is involved in the metabolism of oxidative stress, which may enhance COVID-19 mortality. This retrospective study aimed to examine the effect of COVID-19 on patients with G6PD deficiency by comparing the laboratory parameters of patients with G6PD enzyme deficiency alone, COVID-19 alone, and those with both COVID-19 and G6PD enzyme deficiency treated at a major Saudi tertiary center. The results indicated significant differences in hematological and biochemical parameters between the three patient groups, indicating that COVID-19 may influence these parameters, and that they could be used to measure the severity of COVID-19 disease. Moreover, this study suggests that patients with G6PD enzyme deficiency may be at higher risk for severe COVID-19 outcomes. Although the study is limited by the lack of a random selection method for group membership, the Kruskal–Wallis H-test was used to statistical assess the data. The study's findings can enhance the understanding of the relation between COVID-19 infected and G6PD-deficiency patients and inform clinical decision making for an improved patient outcome. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) patients may experience an acute ischemic stroke; however, risk factors, in-hospital deaths, and outcomes have not been thoroughly investigated. This study investigates the risk factors, comorbidities, and outcomes in patients with SARS-VoV-2 infection and acute ischemic stroke compared to patients without these conditions. The present retrospective study was conducted in the King Abdullah International Medical Research Centre (KAIMRC), Ministry of National Guard, Health Affairs, Riyadh, Saudi Arabia, during the period from April 2020 to February 2022. This study investigates the risk variables among the individuals who were diagnosed with either SARS-CoV-2 with stroke or patients with stroke alone. A total of 42,688 COVID-19 patients were registered, 187 cases of strokes were listed in COVID-19 patients, however, 5395 cases with stroke without SARS-CoV-2 infection. The results revealed that factors including age, hypertension, deep vein thrombosis, and ischemic heart disease are associated with an increased risk of ischemic stroke. The results also displayed an elevated frequency of in-hospital deaths in COVID-19 patients with acute ischemic stroke. The results also showed that SARS-CoV-2 together predicts the probability of stroke and death in the study sample. The study findings conclude that ischemic strokes were infrequent in patients with SARS-CoV-2 and usually occur in the presence of other risk factors. The risk factors of ischemic strokes in patients with SARS-CoV-2 are old age, male gender, hypertension, hyperlipidaemia, DVT, ischemic heart disease, and diabetes mellitus. Furthermore, the results showed a higher frequency of in-hospital deaths in COVID-19 patients with stroke compared to COVID-19 patients without stroke. [ABSTRACT FROM AUTHOR]

The Kingdom of Saudi Arabia was one of the countries earliest affected by the coronavirus 2019 (COVID-19) pandemic and had taken precautions including compulsory COVID-19 vaccination. Both the ChAdOx1 nCoV-19 vaccine (Oxford AstraZeneca) and the BNT162b2 vaccine (Pfizer) were approved by the Saudi Ministry of Health, followed by mRNA-1273 (Moderna), all of which were used for population-wide vaccination. This study aimed to assess the short-term side effects following the COVID-19 vaccinations among participants who had received all three doses in the western region of Saudi Arabia. An online survey was distributed to the participants who received either BNT162b2, ChAdOx1 nCoV-19, or mRNA-1273 vaccines, and the type of side effects and their severity were evaluated. Fatigue and headache, pain at the site of the injection and muscle pain were the most common side effects in all three doses. However, the severity depending on the type of vaccination was significant only for the first and second dose, but not the third dose. In contrast, there was a higher percentage of participants who encountered severe side effects from the third dose compared to the first and second. Nevertheless, the majority of participants described all three doses' side effects to be moderately severe. A future evaluation could be made to access the individual types of vaccination and compare between the side effects of the BNT162b2, ChAdOx1 nCoV-19, and mRNA-1273 vaccines specifically for the booster dose. [ABSTRACT FROM AUTHOR]

Background: The current study is a retrospective study designed to evaluate changes in complete blood count and coagulation parameters in adult coronavirus disease 2019 (COVID-19) patients at a prominent Saudi tertiary center to predict disease severity and mortality., Methods: The cohort consisted of 74 800 adult patients divided into four groups based on a COVID-19 test and the patient's sex: 35 985 in the female negative COVID-19 group, 23 278 in the male negative COVID-19 group, 8846 in the female positive COVID-19 group and 6691 in the male positive COVID-19 group., Results: Patients with COVID-19 demonstrated decreased white blood cell counts and increased red blood cell counts. Also, COVID-19-positive participants exhibited more prolonged partial thromboplastin time and lower D-dimer levels than those of COVID-19-negative subjects (p<0.05). The study also revealed gender-dependent impacts on platelet counts, implying a possible relationship with the greater infection mortality rate in men than in women (p<0.001). In addition, the study found a link between changes in coagulation test results and death in COVID-19 patients (p<0.001). The evidence regarding the effects of COVID-19 on blood cell counts and coagulation, on the other hand, is conflicting, most likely due to variances in study populations and the timing of testing postinfection., Conclusions: According to the findings, COVID-19-related alterations in blood cell count and clotting ability may be risk factors for death., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

(1) Background: Aspirin and clopidogrel have been found helpful in improving clinical outcomes among patients with chronic obstructive lung disease (COPD). However, the evidence on the efficacy of aspirin and/or clopidogrel on clinical outcomes has not been synthesized and summarized in the prior reviews. Hence, we undertook a meta-analysis of the research studies examining the effect of aspirin and/or clopidogrel on varying clinical outcomes among COPD patients; (2) Methods: Using key search terms, we searched databases, including MEDLINE, CINAHL, Google Scholar, and EMBASE to find observational studies and RCTs. Our search was limited to research written in English. We used a random effect model to calculate the 95% confidence intervals and pooled hazard ratio; (3) Results: We included 12 eligible research studies (33,8008 patients) in the current meta-analysis. Among COPD patients, the hazard of all-cause mortality among users of aspirin or clopidogrel was 17% lower (HR: 0.83; 95% CIs (0.70, 0.97; I 2 = 73%, X2: 33.34) compared to non-users of anticoagulants (aspirin or clopidogrel). The hazard of dyspnea among users of aspirin or clopidogrel was 3% lower (HR: 0.97; 95% CIs (0.27, 3.49; I 2 = 93%, X2: 42.15) compared to non-users of anticoagulants (aspirin or clopidogrel). There was no statistically significant effect of aspirin on other clinical outcomes such as myocardial infarction (HR: 2.04; 95% CIs (0.02, 257.33) and major bleeding (HR: 1.93; 95% CIs (0.07, 1002.33). The funnel plot and Egger's regression test did not show any evidence of publication bias; (4) Conclusions: Overall, we found a positive and beneficial effect of aspirin and/or clopidogrel in reducing all-cause mortality among COPD patients. However, there is uncertainty of evidence for other clinical outcomes such as exacerbation of dyspnea, myocardial infarction, and major bleeding. A limited number of studies examining other clinical outcomes warrant conducting more robust epidemiological studies to assess the efficacy and safety of aspirin and clopidogrel on other clinical outcomes among COPD patients.

Objectives: The objectives of this study were to: (1) assess the frequency of missed canals in the mesiobuccal root (MB) of endodontically treated maxillary molars and its association with apical periodontitis (AP); (2) examine the correlation between the presence of a confluent or separate missed MB2 canal and the prevalence of AP; and (3) examine the correlation between the technical quality of endodontic treatment in the MB1 canal and the prevalence of AP., Methods: We obtained and examined 800 cone-beam computed tomography (CBCT) scans from 800 patient records over 6 months. The parameters noted for each tooth included the tooth number; presence of missed canals in the MB root; configuration of missed MB2 canals (confluent or separate); technical acceptability of root canal treatment (RCT) of treated MB1 canals; and the CBCT periapical index score. Data were analyzed in SPSS version 24., Results: A total of 203 maxillary molars from 148 CBCT scans were included. The MB2 canal prevalence was 88.2% in maxillary first molars and 62.7% in maxillary second molars. MB2 was found in 164 endodontically treated maxillary molars. During treatment, MB2 was missed in 150 (91.5%) and treated in 14 (8.5%) teeth. A total of 103 teeth (50.73%) had AP, which was observed in 67.3% of teeth with a missed MB2 canal but only 14.3% of teeth with a treated MB2 canal. The prevalence of AP was 43.7% in teeth with confluent MB2 canals and 80.9% in teeth with separate MB2 canals., Conclusion: The MB2 canal frequency was significantly higher in the examined maxillary first molars than the maxillary second molars. The MB2 canal was missed in most teeth that underwent endodontic treatment. The AP prevalence was relatively higher in endodontically treated maxillary molars with missed MB2 canals., (© 2023 The Authors.)

Background: Postoperative pain is a common concern in root canal treatment, and the choice of instrumentation technique can significantly impact patient comfort. This study aimed to evaluate the impact of different instrumentation techniques on the incidence of postoperative pain in patients undergoing root canal treatment., Methods: A randomized controlled trial was conducted on 208 patients randomly assigned to four groups: step-back preparation, crown-down preparation, hybrid technique, and conventional instrumentation. Pain intensity was assessed using a verbal rating scale (VRS) at six, 12, 24, 48, and 72 hours postoperatively. Data were analyzed using appropriate statistical methods., Results: The mean pain scores and standard deviations (SDs) were calculated for each instrumentation technique at different time intervals. At six hours, the step-back preparation group reported a mean pain score of 2.3 (SD = 0.8), the crown-down preparation group had a score of 2.8 (SD = 0.9), the hybrid technique group had a score of 2.5 (SD = 0.7), and the conventional instrumentation group had a score of 3.1 (SD = 0.1). The differences in pain scores between the groups were statistically significant at all time intervals (p < 0.05)., Conclusion: The choice of instrumentation technique significantly influenced the incidence of postoperative pain in root canal treatment. The step-back preparation technique was associated with lower pain intensity than the crown-down preparation, hybrid technique, and conventional instrumentation. These findings highlight the importance of considering the instrumentation technique to optimize patient comfort during and after root canal treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Agrawal et al.)