A systematic review and meta-analysis on utilizing anti-CD19 chimeric antigen receptor T-cell therapy as a second-line treatment for relapsed and refractory diffuse large B-cell lymphoma.

Introduction: Inconsistent results observed in recent phase III trials assessing chimeric antigenic receptor T (CAR-T) cell therapy as a second-line treatment compared to standard of care (SOC) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) prompted a meta-analysis to assess the effectiveness of CAR-T cell therapy in this setting. Methods: Random-effects meta-analysis was conducted to pool effect estimates for comparison between CAR-T cell therapy and SOC. Mixed treatment comparisons were made using a frequentist network meta-analysis approach. Results: Meta-analysis of three trials with 865 patients showed significant improvement in event-free survival (EFS: HR: 0.51; 95% CI: 0.27-0.97; I2: 92%), progression-free survival (PFS: HR: 0.47; 95% CI: 0.37-0.60; I2: 0%) with CAR-T cell therapy compared to SOC. Although there was a signal of potential overall survival (OS) improvement with CAR-T cell therapy, the difference was not statistically significant between the two groups (HR 0.76; 95% CI: 0.56 to 1.03; I2: 29%). Mixed treatment comparisons showed significant EFS benefit with liso-cel (HR: 0.37; 95% CI: 0.22-0.61) and axi-cel (HR: 0.42; 95% CI: 0.29-0.61) compared to tisa-cel. Discussion: CAR-T cell therapy, as a second-line treatment, appears to be effective in achieving higher response rates and delaying the disease progression compared to SOC in R/R DLBCL.

"One blade, two cuts?" A multidisciplinary survey investigating practice variability of scalpel blade change for simultaneous excision of multiple skin lesions in the same patient.

BACKGROUND: Skin cancer incidence increases globally, requiring effective preventive measures and evidence-based treatment strategies. Current guidelines advocate for surgical excision as a first-line treatment for most early skin cancers. The study investigated practices regarding changing scalpel blades when excising multiple skin lesions in the same patient during the same visit (CSB) and explored how beliefs about iatrogenic seeding influence individual norms of practice. METHODS: A multidisciplinary survey was conducted among 173 medical specialists involved in skin cancer care. Participants provided demographic information, years of experience, and practices regarding CSB in four clinical scenarios (first excised tumor: basal cell carcinoma, squamous cell carcinoma, melanoma suspect, and evident melanoma). Practice variations based on specialty, experience, and beliefs about seeding risk were statistically assessed. RESULTS: Surgeons exhibited a significantly higher tendency to change blades compared to non-surgeons across all diagnoses. Iatrogenic seeding (56.52%) and clinical training (18.84%) were the main reasons provided for CSB. Beliefs about seeding risk did not differ significantly between specialties. CONCLUSIONS: Although the practice of CSB lacks strong scientific rationale, the approach to this practice significantly varies among different medical specialties. Healthcare professionals should critically evaluate and standardize evidence-based practices to ensure optimal patient care and mitigate potential harm.

Conscience, Disobedience, and Standard of Care.

In the article "Principled Conscientious Provision: Referral Symmetry and Its Implications for Protecting Secular Conscience," Abram L. Brummett, Tanner Hafen, and Mark C. Navin reject what they call the "referral asymmetry" in U.S. conscientious objection law in medicine, which recognizes rights of conscientiously objecting physicians to withhold referrals for medical interventions but does not (yet) recognize rights of physicians to make referrals for medical interventions to which they are morally committed but to which their health care institutions are morally opposed. This commentary concentrates on a second asymmetry, namely, the relationship of a health care provider's referral or nonreferral to the medical standard of care. The commentary argues that this second asymmetry seems to require action more appropriately recognized as civil disobedience than conscientious provision of referral.

Impact of fecal microbiota transplantation in severe alcoholic hepatitis: A systematic review and meta-analysis.

Background and Aim: Severe alcoholic hepatitis (SAH) is a serious condition with few treatments. By modifying the gut-liver axis, fecal microbiota transplantation (FMT) was proposed as a treatment for SAH. The purpose of this meta-analysis was to evaluate the efficacy of FMT versus the standard of care (SOC) in improving SAH patient survival rates. Methods: A thorough search of electronic databases was conducted till September 2023. The survival rates of SAH patients undergoing FMT versus SOC were compared. Using Review Manager 5.4, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: The meta-analysis consisted of six studies with a total of 371 patients with SAH. Patients who received FMT had significantly higher survival rates at 1 and 3 months compared to those who received SOC, with pooled OR of 2.91 (95% CI: 1.56-5.42, P = 0.0008) and 3.07 (95% CI: 1.81-5.20, P < 0.0001), respectively. However, the survival advantage disappeared after 6 months (OR: 2.96, 95% CI: 0.99-8.85, P = 0.05) and 1 year of follow-up (OR: 1.81, 95% CI: 0.44-7.46, P = 0.41). Conclusion: This meta-analysis highlights the potential of FMT to significantly improve short-term survival rates in SAH patients. However, the survival benefit did not last 6-12 months. These findings call for additional research into the effectiveness of FMT over the long term, along with strategies for extending the survival benefit.

Micro-costing of genetic diagnostics in acute leukemia in Sweden: from standard-of-care to whole-genome sequencing.

AIMS AND BACKGROUND: Whole-genome sequencing (WGS) is increasingly applied in clinical practice and expected to replace standard-of-care (SoC) genetic diagnostics in hematological malignancies. This study aims to assess and compare the fully burdened cost ('micro-costing') per patient for Swedish laboratories using WGS and SoC, respectively, in pediatric and adult patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). METHODS: The resource use and cost details associated with SoC, e.g. chromosome banding analysis, fluorescent in situ hybridization, and targeted sequencing analysis, were collected via activity-based costing methods from four diagnostic laboratories. For WGS, corresponding data was collected from two of the centers. A simulation-based scenario model was developed for analyzing the WGS cost based on different annual sample throughput to evaluate economy of scale. RESULTS: The average SoC total cost per patient was €2,465 for pediatric AML and €2,201 for pediatric ALL, while in adults, the corresponding cost was €2,458 for AML and €1,207 for ALL. The average WGS cost (90x tumor/30x normal; sequenced on the Illumina NovaSeq 6000 platform) was estimated to €3,472 based on an annual throughput of 2,500 analyses, however, with an annual volume of 7,500 analyses the average cost would decrease by 23% to €2,671. CONCLUSION: In summary, WGS is currently more costly than SoC, however the cost can be reduced by utilizing laboratories with higher throughput and by the expected decline in cost of reagents. Our data provides guidance to decision-makers for the resource allocation needed when implementing WGS in diagnostics of hematological malignancies.

Glioblastoma Standard of Care: Effects on Tumor Evolution and Reverse Translation in Preclinical Models.

Glioblastoma (GBM) presents a significant public health challenge as the deadliest and most common malignant brain tumor in adults. Despite standard-of-care treatment, which includes surgery, radiation, and chemotherapy, mortality rates are high, underscoring the critical need for advancing GBM therapy. Over the past two decades, numerous clinical trials have been performed, yet only a small fraction demonstrated a benefit, raising concerns about the predictability of current preclinical models. Traditionally, preclinical studies utilize treatment-naïve tumors, failing to model the clinical scenario where patients undergo standard-of-care treatment prior to recurrence. Recurrent GBM generally exhibits distinct molecular alterations influenced by treatment selection pressures. In this review, we discuss the impact of treatment-surgery, radiation, and chemotherapy-on GBM. We also provide a summary of treatments used in preclinical models, advocating for their integration to enhance the translation of novel strategies to improve therapeutic outcomes in GBM.

Individualized clinical decisions within standard-of-care pragmatic clinical trials: Implications for consent.

Pragmatic clinical trials of standard-of-care interventions compare the relative merits of medical treatments already in use. Traditional research informed consent processes pose significant obstacles to these trials, raising the question of whether they may be conducted with alteration or waiver of informed consent. However, to even be eligible, such a trial in the United States must have no more than minimal research risk. We argue that standard-of-care pragmatic clinical trials can be designed to ensure that they are minimal research risk if the random assignment of an intervention in a pragmatic clinical trial can accommodate individualized, clinically motivated decision-making for each participant. Such a design will ensure that the patient-participants are not exposed to any risks beyond the clinical risks of the interventions, and thus, the trial will have minimal research risk. We explain the logic of this view by comparing three scenarios of standard-of-care pragmatic clinical trials: one with informed consent, one without informed consent, and one recently proposed design called Decision Architecture Randomization Trial. We then conclude by briefly showing that our proposal suggests a natural way to determine when to use an alteration versus a waiver of informed consent.

Unmet needs in relapsed/refractory mantle cell lymphoma (r/r MCL) post-covalent Bruton tyrosine kinase inhibitor (BTKi): a systematic literature review and meta-analysis.

To quantify the clinical unmet need of r/r MCL patients who progress on a covalent Bruton tyrosine kinase inhibitor (BTKi), we conducted a systematic review to identify studies that reported overall survival (OS), progression-free survival (PFS), or response outcomes of patients who received a chemo(immunotherapy) ± targeted agent standard therapy (STx) or brexucabtagene autoleucel (brexu-cel) in the post-BTKi setting. Twenty-six studies (23 observational; three trials) reporting outcomes from 2005 to 2022 were included. Using two-stage frequentist meta-analyses, the estimated median PFS/OS for patients treated with an STx was 7.6 months (95% CI: 3.9-14.6) and 9.1 months (95% CI: 7.3-11.3), respectively. The estimated objective response rate (ORR) was 45% (95% CI: 34-57%). For patients treated with brexu-cel, the estimated median PFS/OS was 14.9 months (95% CI: 10.5-21.0) and 32.1 months (95% CI: 25.2-41.2), with a pooled ORR of 89% (95% CI: 86-91%). Our findings highlight a significant unmet need for patients whose disease progresses on a covalent BTKi.

Evaluation of the information provided in the instruction manuals of dental light-curing units.

OBJECTIVE: This study evaluated the completeness and accuracy of information in LCU instruction manuals from 40 manufacturers. MATERIALS AND METHODS: Instruction manuals from 40 LCUs (20 from leading manufacturers and 20 budget units) were reviewed. Twenty-eight parameters across five categories were assessed using a binary scale (0=incorrect/missing, 1=correct). The categories and their respective evaluation scores were: LCU characteristics (43%), instructions for use (7%), safety precautions (14%), maintenance recommendations (29%), and regulatory certification (7%). These scores were combined to produce a final score. RESULTS: Scores from leading manufacturers ranged between 46-86%, while the budget category ranged from 18-68%. All manuals provided information about the wavelength/spectrum of the LCU. Only Valo X and Valo Cordless reported power values and used the term "irradiance" instead of "intensity." Details such as LED type and active tip emission area were often missing. Instructions on how to use the LCU to photo-cure resins were frequently limited. Although most manuals addressed safety precautions, several lacked details on heat issues and general health precautions. All manuals included maintenance instructions, though information on replacement parts was often missing. Among the LCUs, 85% stated they were CE certified, 32% held both FDA and CE certification, and 63% claimed compliance with ISO and/or IEC standards. CONCLUSIONS: There were notable differences in the completeness and accuracy of the instruction manuals. Manuals from major manufacturers generally provided more comprehensive information than their budget counterparts. CLINICAL SIGNIFICANCE: Instruction manuals should contain accurate information to help clinicians deliver the highest standard of care. The lack of important information about the LCUs in the manuals is concerning.

[Interdisciplinary centers for autoimmune diseases in Germany]. / Interdisziplinäre Zentren für Autoimmunerkrankungen in Deutschland.

BACKGROUND: Interdisciplinary medical treatment is required to care for patients with complex autoimmune diseases. Although there are an increasing number of interdisciplinary centers for autoimmune diseases in Germany, they are not yet available throughout the country and the focuses and interdisciplinary structures are not organized according to a generally agreed standard. Furthermore, they are not regularly reflected in the general care structure. THE AIM OF THE WORK: To analyze the care structure using as an example an established center and a clinical case to demonstrate the usefulness of in-house standardized procedures. MATERIAL AND METHODS: In order to determine the status quo regarding interdisciplinary centers for autoimmune diseases in Germany, a university hospital is exemplarily presented for a structural analysis and a case presentation from another center to demonstrate the importance of an interdisciplinary patient care. RESULTS: At the selected center for autoimmune diseases of the university hospital, patients with autoimmune diseases receive interdisciplinary care from experts from various disciplines. The structures are anchored in an organizational chart. The case report demonstrates a standardized diagnostic and therapeutic pathway (standardized operating procedures, SOP) in a patient with systemic sclerosis and lung involvement. DISCUSSION: The article discusses which measures are necessary across disciplines for comprehensive diagnostics and treatment of certain autoimmune diseases, which challenges arise during implementation and which advantages can arise compared to guidelines because, among other things, they can be immediately adapted. The establishment of a national consensus for the structure, necessary settings and implementation into patient care within an interdisciplinary center for autoimmune diseases is desirable.

Interhospital Transfer for Endovascular Stroke Treatment in Canada: Results From the OPTIMISE Registry.

BACKGROUND: Interhospital transfer for patients with stroke due to large vessel occlusion for endovascular thrombectomy (EVT) has been associated with treatment delays. METHODS: We analyzed data from Optimizing Patient Treatment in Major Ischemic Stroke With EVT, a quality improvement registry to support EVT implementation in Canada. We assessed for unadjusted differences in baseline characteristics, time metrics, and procedural outcomes between patients with large vessel occlusion transferred for EVT and those directly admitted to an EVT-capable center. RESULTS: Between January 1, 2018, and December 31, 2021, a total of 6803 patients received EVT at 20 participating centers (median age, 73 years; 50% women; and 50% treated with intravenous thrombolysis). Patients transferred for EVT (n=3376) had lower rates of M2 occlusion (22% versus 27%) and higher rates of basilar occlusion (9% versus 5%) compared with those patients presenting directly at an EVT-capable center (n=3373). Door-to-needle times were shorter in patients receiving intravenous thrombolysis before transfer compared with those presenting directly to an EVT center (32 versus 36 minutes). Patients transferred for EVT had shorter door-to-arterial access times (37 versus 87 minutes) but longer last seen normal-to-arterial access times (322 versus 181 minutes) compared with those presenting directly to an EVT-capable center. No differences in arterial access-to-reperfusion times, successful reperfusion rates (85% versus 86%), or adverse periprocedural events were found between the 2 groups. Patients transferred to EVT centers had a similar likelihood for good functional outcome (modified Rankin Scale score, 0-2; 41% versus 43%; risk ratio, 0.95 [95% CI, 0.88-1.01]; adjusted risk ratio, 0.98 [95% CI, 0.91-1.05]) and a higher risk for all-cause mortality at 90 days (29% versus 25%; risk ratio, 1.15 [95% CI, 1.05-1.27]; adjusted risk ratio, 1.14 [95% CI, 1.03-1.28]) compared with patients presenting directly to an EVT center. CONCLUSIONS: Patients transferred for EVT experience significant delays from the time they were last seen normal to the initiation of EVT.

Enhancing Treatment Outcomes in Atrial Fibrillation: A Contemporary Literature Review of the Impact of Optimizing Patient Well-Being in Treatment Management.

Atrial fibrillation (AF) is the most common heart rhythm disorder, defined by an irregular and rapid heartbeat. It is the most prevalent cardiac arrhythmia in the United States, characterized by irregular heartbeats due to asynchrony between atrial and ventricular contractions. AF can be categorized as paroxysmal or persistent and, as such, poses significant health risks, including heart failure and stroke. Factors like age, sex, lifestyle, and existing health conditions elevate AF risk. There have been a lot of debates around AF risk management and its impact on prognosis. This literature review aims to explore the influence of addressing modifiable risk factors in AF patients on its morbidity and mortality, exploring various treatment options and their effectiveness. Current guidelines suggest rate control and anticoagulation for persistent AF with medications like beta blockers and non-vitamin K oral anticoagulants. Catheter ablation for rhythm control is contentious. Studies on supplemental treatments, lifestyle changes, and managing comorbidities show mixed results, necessitating further research for comprehensive treatment effectiveness in AF patients, which this literature review will discuss.

Antiemetic prophylaxis regimens in haematologic malignancies patients undergoing a hematopoietic stem cell transplantation. Which is the best standard of care? A systematic review.

INTRODUCTION: This systematic review, adhering to PRISMA guidelines, aimed to evaluate the efficacy and safety of antiemetic prophylaxis in haematological patients undergoing high-dose chemotherapy as part of their hematopoietic stem cell transplantation (HSCT) conditioning regimens. METHODS: We performed a comprehensive search in PubMed, EMBASE, ClinicalTrials.gov and the Cochrane database to identify randomised controlled trials (RCTs) and systematic reviews of antiemetic prophylaxis. Studies in English, French, Italian or Spanish were included. This review is registered with PROSPERO, ID CRD42023406380. RESULTS: Eight RCTs were analysed. The antiemetic regimens evaluated ranged from monotherapy with 5-Hydroxytryptamine Receptor 3 antagonists (5-HT3RAs) to complex combinations including olanzapine, neurokinin-1 receptor antagonists, 5-HT3RAs and corticosteroids. Complete response rates for triplet or quadruple regimens varied between 23.5% and 81.9%. Although no significant adverse effects were observed, minor symptoms such as diarrhoea, constipation, sedation and headaches were reported. CONCLUSION: Existing evidence on HSCT antiemetic therapy highlights its benefits but fails to provide clear clinical directions. The choice between triplet and quadruplet therapies for different patient scenarios is still uncertain. Until more detailed research is available, healthcare providers must rely on the latest guidelines and their judgement to customise antiemetic care for each patient's specific needs and risks.

FDG-PET/MRI in colorectal cancer care: an updated systematic review.

PURPOSE: Since its introduction in 2011, FDG-PET/MRI has been advocated as a useful adjunct in colorectal cancer care. However, gaps and limitations in current research remain. This systematic review aims to review the current literature to quantify the utility of FDG-PET/MRI in colorectal cancer care. METHODS: An up-to-date review was performed on the available literature between 2000 and 2023 on PubMed, EMBASE, Medline, databases. All studies reporting on the use of FDG-PET/MRI in colorectal cancer care were analyzed. The main outcome measures were accuracy in initial staging, restaging, and detection of metastatic disease in both rectal as well as colon cancers. The secondary outcome was comparing the performance of FDG-PET/MRI versus Standard of Care Imaging (SCI). Finally, the clinical significance of FDG-PET/MRI was measured in the change in management resulting from imaging findings. RESULTS: A total of 22 observational studies were included, accounting for 988 patients. When individually compared to current Standard of Care Imaging (SCI)-MRI pelvis for rectal cancer and thoraco-abdominal contrast CT, PET/MRI proved superior in terms of distant metastatic disease detection. This led to as much as 21.0% change in management. However, the technological limitations of PET/MRI were once again highlighted, suggesting SCI should retain its place as first-line imaging. CONCLUSION: FDG-PET/MRI appears to be a promising adjunct in staging and restaging of colorectal cancer in carefully selected patients.

Effect of essential phospholipids on hepatic steatosis in metabolic dysfunction-associated steatotic liver disease associated with type 2 diabetes mellitus and/or hyperlipidemia and/or obesity: study protocol of a randomized, double-blind, phase IV clinical trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a predominant chronic liver condition globally and is strongly associated with obesity, diabetes mellitus, and dyslipidemia. Essential phospholipids (EPL) are recommended as supportive treatment for managing liver conditions, including MASLD or metabolic dysfunction-associated steatohepatitis, cirrhosis, and viral hepatitis. While efficacy of EPL as an adjunctive therapy in MASLD treatment has been established earlier, certain aspects of its usage such as the impact of standard-of-care parameters, effect of EPL on quality of life (QoL) and change in symptoms evaluation in patients with MASLD remain unexplored. The proposed trial aims to assess the efficacy and safety of EPL and the subsequent QoL of patients with MASLD associated with type 2 diabetes mellitus (T2DM) and/or hyperlipidemia and/or obesity. METHODS: This is a multicenter, multinational, double-blind, randomized, two-arm, placebo-controlled, parallel-group, phase IV clinical trial. The trial is being conducted in approximately 190 patients who are randomized on a 1:1 basis either to the EPL arm (Essentiale® 1800 mg/day orally + standard of care) or placebo arm (placebo + standard of care). The primary outcome is to assess the efficacy of EPL on hepatic steatosis, as measured by transient elastography, from baseline to 6 months. The secondary outcomes include change in QoL parameters, as measured by the Chronic Liver Disease Questionnaire-metabolic dysfunction-associated steatotic liver disease/ metabolic dysfunction-associated steatohepatitis and change in symptom evaluation (using the Global Overall Symptom scale) from baseline to 6 months for symptoms, including asthenia, feeling depressed, abdominal pain/discomfort, or fatigue. DISCUSSION: The current protocol design will allow to comprehensively explore the efficacy of EPL added to the standard of care on hepatic steatosis and QoL and its safety in patients with MASLD associated with T2DM and/or hyperlipidemia and/or obesity by assessing various outcome measures. TRIAL REGISTRATION: European Union Clinical Trials Register, EudraCT, 2021-006069-39. Registered on March 13, 2022.

Cytarabine dose intensification improves survival in older patients with secondary/high-risk acute myeloid leukemia in matched real-world versus clinical trial data.

Since 1980's, the established/standard treatment of acute myeloid leukemia (AML) is cytarabine infusion with anthracycline (7 + 3 regimen). We compared the 7 + 3 regimen in older secondary/high-risk AML patients from a clinical trial with a matched population from the Swedish AML Registry treated with an increased cytarabine dose in induction and consolidation as recommended in the Swedish National Guidelines since 2005. After successful propensity score matching, 104 patients per group were included. The primary outcome was overall survival (OS), and standard dosed patients had a median OS of 6.4 versus 10.7 months with increased dose intensity (hazard ratio: 0.69, p = 0.012), with 5-year OS of 8.7% and 18.1%, and remission rates of 36% and 60%, respectively (p < 0.001). Median OS after allogeneic hematopoietic cell transplantation (in 27.9% per group) was 10.4 and 20.7 months, respectively. We conclude that the more intensive cytarabine schedule seems to provide improved outcomes inthe investigated AML patient group.

The Evolving Standard of Care for Autoimmune Neuropsychiatric Illness.

In recent decades, there has been increasing biomedical and public understanding of the role of autoimmunity in neuropsychiatric illness. Popular media have highlighted patients with psychiatric illnesses who were eventually diagnosed with autoimmune neuropsychiatric illnesses such as anti- N-methyl-D-aspartate receptor encephalitis. Coverage of these cases has often drawn attention to the effects of misdiagnosis or delayed diagnosis of such diseases in psychiatric patients. Autoimmune encephalitis can have varied presentations and often involves evaluation and management from multiple medical specialties. As a result, there remains considerable uncertainty regarding how courts might gauge the legal standard of care with regard to psychiatric workup of new-onset psychiatric symptoms, and the degree to which autoimmune encephalitis must be considered. In this article we provide a brief overview of autoimmune encephalitis and autoimmune psychosis, including current diagnostic approaches to these conditions. We review case law regarding the standard of care for psychiatric disorders caused by general medical conditions. Finally, we provide a medicolegal perspective on the responsibilities of psychiatrists and other mental health professionals in the evaluation of possible autoimmune encephalitis.

Histopathological predictors of lymph node metastasis in oral cavity squamous cell carcinoma: a systematic review and meta-analysis.

Objectives: Lymph node metastasis (LNM) is the most significant parameter affecting overall survival in patients with oral cavity squamous cell carcinomas (OCSCC). Elective neck dissection (END) is the standard of care in the early management of OCSCC with a depth of invasion (DOI) greater than 2-4 mm. However, most patients show no LNM in the final pathologic report, indicating overtreatment. Thus, more detailed indicators are needed to predict LNM in patients with OCSCC. In this study, we critically evaluate the existing literature about the risk of different histological parameters in estimating LNM. Methods: A systematic review was conducted using PRISMA guidelines. PubMed, Web of Science, Cochrane, and Scopus were searched from inception to December 2023 to collect all relevant studies. Eligibility screening of records was performed, and data extraction from the selected studies was carried out independently. Inclusion in our systematic review necessitated the following prerequisites: Involvement of patients diagnosed with OCSCC, and examination of histological parameters related to lymph node metastasis in these studies. Exclusion criteria included animal studies, non-English articles, non-availability of full text, and unpublished data. Results: We included 217 studies in our systematic review, of which 142 were eligible for the meta-analysis. DOI exceeding 4 mm exhibited higher risk for LNM [Risk ratio (RR) 2.18 (1.91-2.48), p<0.00001], as did perineural invasion (PNI) [RR 2.04 (1.77-2.34), p<0.00001], poorly differentiated tumors [RR 1.97 (1.61-2.42), p<0.00001], lymphovascular invasion (LVI) [RR 2.43 (2.12-2.78), p<0.00001], groups and single pattern of invasion [RR 2.47 (2.11-2.89), p<0.00001], high tumor budding [RR 2.65 (1.99-3.52), p<0.00001], tumor size over 4 cm [RR 1.76 (1.43-2.18), p<0.00001], tumor thickness beyond 4 mm [RR 2.72 (1.91-3.87), p<0.00001], involved or close margin [RR 1.73 (1.29-2.33), p = 0.0003], and T3 and T4 disease [RR 1.98 (1.62-2.41), p <0.00001]. Conclusion: Our results confirm the potential usefulness of many histopathological features in predicting LNM and highlight the promising results of others. Many of these parameters are not routinely incorporated into pathologic reports. Future studies must focus on applying these parameters to examine their validity in predicting the need for elective neck treatment.