Endothelial function in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors is not related to cardiovascular risk assessed by SCORE2 algorithm.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia (CML) but are endowed with negative effects on endothelial function. OBJECTIVES: To characterize endothelial function in patients with CML treated with various TKIs. PATIENTS AND METHODS: Forty-eight patients diagnosed with chronic phase CML treated with TKIs, such as imatinib, bosutinib, nilotinib, ponatinib, and asciminib were included. Endothelial function was assessed in the brachial artery and microcirculation based on flow-mediated dilation (FMD), reactive hyperemia peripheral arterial tonometry (RH-PAT) and Flow Mediated Skin Fluorescence (FMSF). RESULTS: Reactive Hyperemia Index (RHI), FMD [%], Reactive Hyperemia Response (RHR [%]), Normoxia Oscillatory index (NOI [%]) and Hyperemic Response index (HR index [%]) did not differentiate between the group of patients with low / moderate risk in the Systemic Coronary Risk Estimation 2 (SCORE2), SCORE2-Older Persons (SCORE2-OP) and those with high / very high-risk scores. Among patients with low/intermediate risk based on the SCORE2 algorithms, some had lower (

The Complete Anatomy of the Anterior Ethmoidal Artery: A Meta-Analysis with Implications for Sinus and Skull Base Surgery.

Background: The anatomical characteristics of the anterior ethmoidal artery (AEA) exhibit a high degree of variability, especially regarding its topography. Methods: PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Google Scholar were searched to identify all studies that included information regarding the morphometric and topographical characteristics of the AEA. Results: Ultimately, a compilation of 38 studies meeting the predetermined criteria, and possessing comprehensive and pertinent data, were incorporated into the current meta-analysis. In the overall analysis, reports of the AEA being embedded within the skull base or at the level of the skull base producing a bony protrusion were found in 56.91% of cases (95% CI: 43.55-69.80%). The mean diameters of the AEA in the intraorbital and intracranial areas were 0.94 mm and 0.76 mm, respectively. Moreover, the artery coursed most commonly between the second and third lamellae, with a prevalence of 65.82% (95% CI: 55.39-75.56%). Conclusions: The AEA may be at a high risk of iatrogenic injury during various sinus and skull base surgeries, especially if the surgeon performing these procedures is unfamiliar with the vast number of variations this vessel may exhibit. The spatial relationship between this vessel and the skull base is especially variable, and understanding this variability goes hand in hand with intraoperative safety.

Management and outcome of patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era - analysis of the European LeukemiaNet Blast Phase Registry.

Blast phase (BP) of chronic myeloid leukemia (CML) still represents an unmet clinical need with a dismal prognosis. Due to the rarity of the condition and the heterogeneity of the biology and clinical presentation, prospective trials and concise treatment recommendations are lacking. Here we present the analysis of the European LeukemiaNet Blast Phase Registry, an international collection of the clinical presentation, treatment and outcome of blast phases which had been diagnosed in CML patients after 2015. Data reveal the expected heterogeneity of the entity, lacking a clear treatment standard. Outcomes remain dismal, with a median overall survival of 23.8 months (median follow up 27.8 months). Allogeneic stem cell transplantation (alloSCT) increases the rate of deep molecular responses. De novo BP and BP evolving from a previous CML do show slightly different features, suggesting a different biology between the two entities. Data show that outside clinical trials and in a real-world setting treatment of blast phase is individualized according to disease- and patient-related characteristics, with the aim of blast clearance prior to allogeneic stem cell transplantation. AlloSCT should be offered to all patients eligible for this procedure.

Investigating the Contraction Pattern of the Zygomaticus Major Muscle and its Clinical Relevance: A Functional MRI Study.

BACKGROUND: Our understanding of facial anatomy has significantly evolved, yet the detailed contraction patterns of facial muscles and their presentation during clinical imaging remain largely unexplored. Understanding the contraction patterns and visual presentation of these muscles, particularly the zygomaticus major could enhance pre-surgical facial assessments and the development of new treatment strategies. METHODS: A total of 34 healthy young individuals (17 female, 17 male) with a mean age of 23.6 (2.4) years [range: 20-30] were investigated regarding the length, thickness, width, and angle of the zygomaticus major muscle in five different facial expressions (i.e., repose, anger, joy, surprise, and sadness) utilizing MR imaging. RESULTS: Joyful expressions caused a reduction in muscle length to 85.6% of its original length and an increase in width (103.4%), thickness (108.4%), and facial angle (2.72°) when compared to that in repose, suggesting isotonic contraction. Conversely, expressions of anger, surprise, and sadness generally led to muscle stretching, seen through changes in length (98.9%, 104.3%, and 102.7%, respectively), width (98.8%, 96.5%, and 99.4%, respectively), and thickness (91.2%, 91.0%, and 102.7%, respectively), with variable alterations in facial angle (0.55°, 1.85°, and 1.00°, respectively) depending on the specific expression. CONCLUSION: This MRI-based study indicates that the zygomaticus major muscle experiences isotonic contraction, characterized by decreased length and increased width and thickness. The findings underline the importance of muscle thickness as a reliable parameter in assessing facial muscle function and offer valuable guidance for practitioners in accurately evaluating muscle performance during different facial expressions. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The SNP rs460089 in the gene promoter of the drug transporter OCTN1 has prognostic value for treatment-free remission in chronic myeloid leukemia patients treated with imatinib.

Membrane transporters are important determinants of drug bioavailability. Their expression and activity affect the intracellular drug concentration in leukemic cells impacting response to therapy. Pharmacogenomics represents genetic markers that reflect allele arrangement of genes encoding drug transporters associated with treatment response. In previous work, we identified SNP rs460089 located in the promotor of SLC22A4 gene encoding imatinib transporter OCTN1 as influential on response of patients with chronic myeloid leukemia treated with imatinib. Patients with rs460089-GC pharmacogenotype had significantly superior response to first-line imatinib treatment compared to patients with rs460089-GG. This study investigated whether pharmacogenotypes of rs460089 are associated with sustainability of treatment-free remission (TFR) in patients from the EUROpean Stop Kinase Inhibitor (EURO-SKI) trial. In the learning sample, 176 patients showed a significantly higher 6-month probability of molecular relapse free survival (MRFS) in patients with GC genotype (73%, 95% CI: 60-82%) compared to patients with GG (51%, 95% CI: 41-61%). Also over time, patients with GC genotype had significantly higher MRFS probabilities compared with patients with GG (HR: 0.474, 95% CI: 0.280-0.802, p = 0.0054). Both results were validated with data on 93 patients from the Polish STOP imatinib study. In multiple regression models, in addition to the investigated genotype, duration of TKI therapy (EURO-SKI trial) and duration of deep molecular response (Polish study) were identified as independent prognostic factors. The SNP rs460089 was found as an independent predictor of TFR.

The prevalence and anatomy of the pyramidal lobe of the thyroid gland: A meta-analysis with implications for thyroid surgery.

The pyramidal lobe (PL), also known as the third lobe of the thyroid gland or lobe of Lalouette is an embryological remnant of the caudal end of the thyroglossal tract. The following meta-analysis aims to provide a detailed analysis of the anatomical variations of the PL using the available data in the literature. Major online medical databases such as PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Google Scholar were searched in order to find all studies considering the prevalence and anatomy of the PL of the thyroid gland. Finally, a total of 24 studies that met the required criteria and contained complete and relevant data were included in the present meta-analysis. The pooled prevalence of the PL was found to be 42.82% (95% CI: 35.90%-49.89%). An analysis showed that the mean length was 23.09 mm (SE: 0.56). The mean width was found to be 10.59 mm (SE: 0.77). The pooled prevalence of the PL originating from the left lobe (LL) was established at 40.10% (95% CI: 28.83%-51.92%). In conclusion, we believe that this is the most accurate and up-to-date study regarding the complete surgical anatomy of the PL. The PL was prevalent in 42.82% of the cases, being slightly more prevalent in males (40.35%) than females (37.43%). The mean length and width of the PL were 23.09 mm and 10.59 mm, respectively. Our results should be taken into consideration when performing procedures on the thyroid gland, such as thyroidectomies. The presence of the PL can affect the completeness of this procedure and lead to postoperative complications.

The complete anatomy of the lingual nerve: A meta-analysis with implications for oral and maxillofacial surgery.

Lingual nerve (LN) injury during surgical procedures in the third molar region warrants a detailed study of its common pathway and important variations. Therefore, the objective of this study was to analyze and compile the multiple anatomical variations of the LN for use in oral and maxillofacial surgery. It is anticipated that the results of the present meta-analysis may help to minimize the possible complications when performing procedures associated with this anatomical entity. Major online databases such as PubMed, Web of Science, Scopus, Embase were used to gather all relevant studies regarding the LN anatomy. The results were established based on a total of 1665 LNs. The pooled prevalence of the LN being located below the lingual/ alveolar crest was found to be 77.87% (95% CI: 0.00%-100.00%). The LN was located above the lingual/ alveolar crest in 8.21% (95% CI: 4.63%-12.89%) of examined nerves. The most common shape of the LN was established to be round with a prevalence of 40.96% (95% CI: 23.96%-59.06%), followed by oval at 37.98% (95% CI: 23.98%-53.02%) and flat at 25.16% (95% CI: 12.85%-39.77%). In conclusion, we believe that this is the most accurate and up-to-date study regarding the anatomy of the LN. The LN was found to be located below the lingual/alveolar crest in 77.87% of the cases. Furthermore, the LN was found to enter the tongue under the submandibular duct in 68.39% of the cases. Knowledge about the anatomy of the LN is crucial for numerous oral and maxillofacial procedures such as during the extraction of the third molar.

A 3D map of the lingual artery-The perfect tool for transoral robotic surgeries on the base of tongue.

BACKGROUND: Knowledge about the anatomy of the lingual artery (LA) is of immense importance when performing procedures on the base of tongue (BOT). METHODS: A retrospective analysis was performed to establish morphometric data of the LA. The measurements were performed on 55 consecutive patients who underwent head and neck computed tomography angiographies (CTA). RESULTS: A total of 96 LAs were analyzed. Additionally, a three-dimensional heat map (showing the oropharyngeal region from the lateral, anterior, and superior point of view) of the occurrence of the LA and its branches was created. CONCLUSION: The length of the main trunk of the LA was measured to be 31.94 ± 11.44 mm. This reported distance is thought to be a surgical safe zone when performing transoral robotic surgery (TORS) on the BOT because it represents the area where the LA does not give off any major branches.

Treatment options for oropharyngeal carcinoma - An umbrella review.

INTRODUCTION: Our umbrella review aimed to summarize and revisit the evidence from all of the meta-analyses and systematic reviews regarding the treatments of oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: Major medical databases such as PubMed, Scopus, Embase, Web of Science, Google Scholar, Cochrane Library, BIOSIS, and EBSCO were searched. The overall search process was conducted in 3 stages. RESULTS: Finally, a total of 28 studies met the inclusion criteria and were included in this study. Out of those 28 meta-analyses, a total of 315 primary studies were screened in order to extract the data and perform the statistical analysis. In total, data from 22,619 patients was analyzed. CONCLUSION: The main objective of the present umbrella review was to summarize and analyze all of the evidence-based data provided by numerous meta-analyses and systematic reviews regarding the treatment of OPSCC. Our study delivers the most up-to-date and evidence-based results regarding the different therapeutic modalities of this malignancy in one concise review, making it the ultimate tool for physicians treating OPSCC.

Solitary Extramedullary Plasmacytoma of the Larynx and Secondary Laryngeal Involvement in Plasma Cell Myeloma: Single-Centre Retrospective Analysis and Systematic Literature Review.

The involvement of the larynx in plasma cell myeloma (PCM) may manifest as solitary extramedullary plasmacytoma of the larynx (sEMP-L) or as infiltration of the larynx during newly diagnosed or relapsed systemic disease with bone marrow involvement (plasma cell myeloma with laryngeal involvement, PCM-L). To increase knowledge about these rare conditions, we performed a retrospective analysis along with a comprehensive literature review of cases of sEMP-L or PCM-L. Six patients (two sEMP-L and four PCM-L) were identified in our tertiary laryngological centre from 2009 to 2021, constituting 0.88% of all malignant laryngeal tumours. The literature search yielded 187 cases, including 152 sEMP-L and 35 sPCM-L. A comparison of baseline characteristics between sEMP-L and PCM-L performed in the combined cohort of cases from literature review and retrospective analysis revealed that patients with sEMP-L were younger (56 vs. 64 years, p ≤ 0.001) and presented less commonly with thyroid or cricoid cartilage involvement (2.2% vs. 30.8%, p ≤ 0.001). The prognosis of sEMP-L was better than PCM-L (overall survival 86% vs. 55% at 5 years, p = 0.002). Analysis of potential factors that could influence progression-free survival (PFS) in the group of sEMP-L revealed that male sex and cartilage involvement negatively affected PFS in univariate analyses, while only cartilage involvement retained statistical significance in multivariate analysis (HR = 19.94, p = 0.024). In conclusion, PCM with laryngeal involvement is sporadic. Secondary involvement of the larynx during PCM might be more common than sEMP-L and is associated with worse survival. The involvement of cartilage adversely influences the outcome of sEMP-L.

Long-term outcomes of patients with Chronic Myeloid Leukemia who commenced treatment with imatinib: a 20-year single-centre experience.

We report on long-term outcomes of 267 patients (pts) with chronic myeloid leukemia (CML) treated with imatinib administered as initial therapy. The median follow-up time was 11.4 years. 38 (14.2%) pts attempted to discontinue imatinib therapy after achieving sustained deep molecular response (≥MR4), 15 of them achieved treatment-free remission (TFR). 144 pts (53.9%) have been switched to other TKI during the follow-up period. The estimated OS for 267 pts for 10, 15 and 18 years was 98.8%, 75.6% and 52.1%. According to prognostic scores (Sokal, Euro, ELTS), OS and PFS were significantly better in low-risk pts than in high-risk pts. According to ELTS, low-risk pts have a better chance of achieving MR4 than both intermediate (p = 0.03) and high-risk (p = 0.04) groups. It suggests that a specific ELTS-adapted treatment could help to optimize treatment results. In the study population, imatinib has demonstrated sustained efficacy and an acceptable rate of late toxic effects.

The Outcomes of Ponatinib Therapy in Patients With Chronic Myeloid Leukemia Resistant or Intolerant to Previous Tyrosine Kinase Inhibitors, Treated in Poland Within the Donation Program.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have greatly improved the treatment outcome for most patients with chronic myeloid leukemia (CML). Ponatinib is a new pan-inhibitor of TK active in resistant CML. This study aimed to evaluate the efficacy and safety of ponatinib in patients suffering from CML. PATIENTS AND METHODS: This multicenter, non-randomized, observational, retrospective study evaluated the efficacy and safety of ponatinib administered in adult CML patients in any disease phase, including those with a detected ABL T315I mutation, which were resistant or intolerant to previous-generation TKIs. The study comprised 43 patients benefiting from the ponatinib donation program who were treated in 16 Polish centers. RESULTS: For patients who started treatment with ponatinib in chronic phase (CP) (n = 23) and in accelerated phase (AP) (n = 3) the median time on ponatinib was 19.5 months (range: 1.0-35.4), and 31.7 months (range: 31.0-34.1), respectively. All these patients were in CP after 1 month of treatment and at the end of observation - none of them progressed to AP or blastic phase (BP) during the study, meaning that progression-free survival was 100% at the end of observation (35.4 months). The estimated 2-year survival in this group of patients was 84%. For all 43 patients, median survival was not reached (lower quartile 6.3 months), and estimated 2-year survival was 60%. CONCLUSION: Our analysis confirmed ponatinib efficacy in a significant proportion of patients heavily pre-treated with TKIs achieving durable responses in both CP and AP/BP CML groups.