4th Edition Research Articles

Genetic and immunological features of immune deficiency and dysregulation-associated lymphoproliferations and lymphomas as a basis for classification.

Immune deficiency and dysregulation-associated lymphoproliferative disorders and lymphomas (IDD-LPDs) encompass a heterogeneous clinical and pathological spectrum of disorders that range from indolent lymphoproliferations to aggressive lymphomas. They arise in a variety of clinical settings and are associated with oncogenic viruses such as the Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus/human herpes virus (KSHV/HHV8) in some, but not all, cases. The recognition of IDD-LPDs as distinct from LPDs in immune competent patients is essential to tailor clinical management options for affected patients. The 5th edition of the World Health Organisation classification has introduced an integrated classification of IDD-LPDs with the goal of standardising diagnoses among different settings to enhance clinical decision support. In parallel, new knowledge in the field, particularly surrounding the role of oncogenic viruses and the tumour microenvironment, has led to clearer understanding of the complex pathogenesis of IDD-LPDs and how these features can be precisely harnessed for therapeutic purposes. In this perspective, we highlight the need for multidisciplinary decision-making to augment patient care as well as key areas where evolving concepts offer challenges and opportunities for clinical management, research and future iterations of the classification.

Research on the origin and evolution of technical management regulations for railway

PurposeTo facilitate technical managers and field workers to master and understand the provisions of Technical Management Regulations for Railway more accurately, so as to better serve the comprehensive revision of the Regulations, this paper carries out the research on the traceability and evolution of the provisions of the Regulations.Design/methodology/approachThis paper studies and analyzes the evolution of the 11th edition of the Regulations by analyzing the relevance of clauses and summarizes the historical background of the development of calendar editions of the Regulations. The basic research on the traceability and evolution of the Regulations is carried out from four aspects: the continuity of the development of the Regulations, the authority of contents, the relevance of clauses and the richness of historical materials.FindingsFrom the first edition of the Regulations issued by the former Ministry of Railways in 1950 to the 11th edition, there have been ten comprehensive revisions. There is a strong correlation and continuity between the calendar editions of the Regulations in terms of chapter structure and clauses. Studying the context of the terms of the Regulations is an important way to understand and master the current clauses of the Regulations.Originality/valueThrough the research on the traceability and evolution of the clauses of the Regulations, one is to explore the context of the development of railway technical equipment in China, the other is to clarify the historical background when the provisions were formulated and the third is to trace the development and evolution of the provisions. The revision of the Regulations is based on an accurate grasp of the context of the provisions, which can effectively judge the possible security risks caused by the revision of the provisions and avoid the possible risks in field implementation from the source.

Chronic myelomonocytic leukemia: A case report

Chronic myelomonocytic leukemia is a clonal stem cell disorder characterized by persistent monocytosis along with myelodysplasia and/or myeloproliferation. According to the World Health Organization 2016 4th edition, Chronic myelomonocytic leukemia is categorized as a myeloproliferative/myelodysplastic disorder and its diagnosis requires the presence of persistent monocytosis and dysplasia involving one or more myeloid cell lineages. Chronic myelomonocytic leukemia is a rare disease with a heterogeneous clinical presentation. Recent progress in the molecular and cellular pathogenesis of Chronic myelomonocytic leukemia has stirred a renewed interest in this clinically heterogeneous disorder. Herein, we report of case of Chronic myelomonocytic leukemia in a 70-years male patient.

The School Years Screening Test for Evaluation of Mental Status-Revised (SYSTEMS-R) as a cognitive function screening tool in children with epilepsy

Background Children with epilepsy are at high risk of cognitive impairment that can affect quality of life. Intelligence quotient (IQ) measurement using the Wechsler Intelligence Scale for Children (WISC) is the gold standard test of cognitive function, but it is time-consuming and costly. The School Years Screening Test for Evaluation of Mental Status-Revised (SYSTEMS-R) is a potential cognitive function screening tool that can be used in children with epilepsy. Objective To assess the performance of SYSTEMS-R as a cognitive function screening tool in children aged 6-15 years with epilepsy. Methods This cross-sectional diagnostic test study was conducted in children aged 6-15 years with epilepsy. All subjects were assessed using both SYSTEMS-R and WISC 4th edition. The sensitivity, specificity, positive and negative predictive value, likelihood ratios of the positive and negative tests, and accuracy of SYSTEMS-R was calculated, with WISC as the gold standard test. Results Based on the SYSTEMS-R, the prevalence of cognitive impairment in children aged 6-15 years with epilepsy in our population was 86.4%. With WISC as the gold SYSTEMS-R had 84% sensitivity, 91% specificity, 98% positive predictive value, and 47% negative predictive value. The likelihood ratio of a positive SYSTEMS-R test was 10.11 and the likelihood ratio of a negative test was 0.17. The overall accuracy of SYSTEMS-R to detect cognitive impairment was 85%. Conclusion SYSTEMS-R has good sensitivity and specificity to assess cognitive function in children 6-15 years with epilepsy. It can be considered for widespread use in the early detection of cognitive impairment in pediatric epilepsy patients aged 6-15 years.

Utility Assessment of Follow-up Evaluation for Commotio Retinae

Purpose: To perform an outcome-and-cost analysis of follow-up visits and associated imaging in patients presenting to the Massachusetts Eye and Ear (MEE) emergency department with commotio retinae. Methods: This retrospective consecutive case series comprised consecutive patients presenting to the emergency department from January 1, 2020, to January 1, 2022, who were diagnosed with contusion or other injuries of the eye or orbit (International Classification of Diseases, 10th edition, codes S05.1 and S05.8). Cost analysis was performed using Medicare fee data and previously described methods. Costs considered included follow-up examinations, optical coherence tomography (OCT), and fundus photography. Results: Of the 490 patients presenting to the emergency department, 201 had findings of commotio retinae on examination and were included in this study. Of the 201 patients with initial commotio retinae, 142 (70.6%) returned for follow-up. OCT was performed in 34% of patients and fundus photography in 33%. A total of 254 follow-up visits were conducted. Four patients (2.8%) had retinal tears on follow-up, with only 1 (0.7%) developing a retinal detachment. Complications requiring intervention were always heralded by worsening symptoms. The total cost of follow-up was $60,436 for the cohort and $425.60 per patient. Conclusions: Patients with commotio retinae infrequently develop retinal complications and have a high rate of loss to follow-up. Significant resources are dedicated to following up and imaging patients with commotio retinae. Our results underscore the low utility in multiple follow-up visits among asymptomatic patients.

S100 and CD34 positive spindle cell tumors of the uterine cervix with EGFR mutation: a hitherto unrecognized neoplasm phenotypically and epigenetically overlapping with "NTRK-rearranged spindle cell neoplasms" of the uterus.

NTRK-rearranged spindle cell neoplasm represents an emerging entity included in the latest 5th edition of WHO classification of both soft tissue and female genital tumors. By immunohistochemistry, they are commonly positive for CD34, S100 protein, and CD30 and typically harbor fusions of kinase genes such as NTRK1/2/3, RET, and BRAF. In the gynecological tract, they typically affect the uterine cervix or uterine body. Most of the reported cases had fibrosarcoma-like morphology, occasionally showing perivascular and stromal hyalinization with only a few cases showing a less cellular spindle cell proliferation. Except for one case with RET fusion, all other gynecological cases harbored exclusively NTRK1/2/3 fusions. Besides kinase gene fusions, the analogous tumors in soft tissues may also harbor activating EGFR or BRAF point mutations, but no such case has been described in the uterus. Herein we are reporting two cases from the uterine cervix showing morphology and molecular features previously unreported at this anatomic site. The patients were 46 and 34years old and clinically presented with unremarkable cervical polyps each measuring 8mm in diameter. Histologically, both cases had a rounded polypoid outline and were composed of hypocellular proliferation of bland spindle cells lacking mitotic activity and growing in a fibrotic stroma which was punctuated by prominent small vessels with thick hyalinized walls. Immunohistochemically, both showed a diffuse expression of CD34, CD30, and S100 protein, whereas SOX10 was negative. Both cases harbored exon 20 EGFR mutation and did not reveal any fusions or significant copy number changes. The patient in case 1 was treated by hysterectomy with salpingectomy with no other residual tumor detected, and she was alive and well 27months after the diagnosis. The patient in case 2 had no other known tumors at the time of diagnosis, but no follow-up is available. We believe the reported cases represent a hitherto unrecognized variant of "NTRK-rearranged spindle cell neoplasms" of the uterine cervix with novel EGFR mutations.

Breast Cancer Management in the Radiotherapy Department of Mali Hôpital

The aim of our study was to evaluate the clinical, diagnostic and therapeutic aspects of breast cancers followed up in the radiotherapy department of Hôpital du Mali Methods: All breast cancer patients managed in the radiotherapy department of Hôpital du Mali were selected from January 1, 2016 to December 31, 2018 during a retrospective study. The variables studied were socio-demographic aspects, family and personal history, clinical and paraclinical features (anatomopathological examination, histopathological grade, immunohistochemistry, TNM classification of breast cancer, 6th edition 2002), therapeutic modalities. Surgery was performed in 65 patients (100%). Radical surgery was performed in 62 patients (94.3%), but conservative surgery in 5.6%. Of these, 69.4% had received adjuvant chemotherapy and 30.7% neoadjuvant chemotherapy. Radiotherapy was adjuvant in 65 patients (100%). Hormone therapy was initiated in 23.07% of our patients. After an average follow-up of 36 months, 30 patients were in complete remission. The overall survival rate at three years was 50.7%. Discussion and Conclusion: The three-year survival rate was 50.7% in our series. This rate can be improved by early diagnosis and prompt, appropriate management.

7478 Effects of RAI on Papillary Thyroid Carcinoma with Positive Lymph Nodes

Abstract Disclosure: K.N. Rachmasari: None. A. Osman: None. D. Toro Tobon: None. S.B. Lund: None. D.J. Merlino: None. A.R. Hsu: None. M.M. Ryder: None. Background: In low-risk papillary thyroid cancer (PTC), radioactive iodine (RAI) remnant ablation has shown no impact on disease recurrence rates, which are overall low. The role of adjuvant RAI in intermediate risk disease (i.e. T3, N1) remains unproven with no randomized clinical trials to objectively assess efficacy. Thus, in our institution, its use is highly heterogenous. We retrospectively investigated the effects of adjuvant RAI on recurrence and recurrence free survival (RFS) in patients with PTC and positive cervical lymph nodes (CLN). Methods: We performed a retrospective review of patients who underwent surgery at Mayo Clinic Rochester, MN for PTC between January 2007 and December 2016. Adult patients with Tx-T3 disease according to the 8th edition of American Joint Committee on Cancer (AJCC) were identified. Patients with positive CLN (N1) and a minimum follow up of 36 months were included. Demographics, clinicopathologic characteristics, use of RAI therapy and recurrence were analyzed. Results: A total of 367 patients with PTC, Tx-3, N1, M0 were identified, of which 187 received adjuvant RAI and 180 did not. Most patients were female (63.8%), with a median age of 44 years (IQR 34-54), and a median follow up of 77 months (IQR 58.5-101.5). There were no differences in age, type of surgery, histology, multifocality, and follow up period between the RAI and no RAI subgroups. Adjuvant Thyrogen-stimulated or thyroid hormone withdrawal-based RAI was recommended at the discretion of the treating provider and/or per patient preference. Diagnostic I-123 whole body scans were performed in all patients and mostly demonstrated remnant uptake. The median dose of I-131 was 75 mCi (range 50-100). Recurrence was defined by new occurrence of disease after at least a year of absence of clinical, biochemical, and imaging evidence of disease since initial surgery. Within the entire cohort, 35 (9.5%) developed recurrence with a median time of 41 months (28-59.5). Overall, recurrence rate and RFS were not significantly different between both subgroups (p = 0.2). A subanalysis was performed in patients with clinically detectable nodal disease (n = 161), defined by abnormal cervical lymph node on preoperative neck ultrasound with or without positive fine needle aspiration biopsy. Overall recurrence rates were 17 (10.6%) in this group. There were no differences in recurrence rates and RFS in those that received RAI versus those that did not (p = 0.8). Conclusions: In patients with intermediate risk PTC defined by nodal disease and/or T3 disease, recurrences were not different between patients that did or did not receive adjuvant I-131 therapy postoperatively. A randomized, noninferiority study of adjuvant I-131 compared to no I-131 postoperatively for N1 disease is needed to determine the benefit of near total thyroidectomy and adjuvant I-131 for this cohort. Presentation: 6/3/2024

7838 Improvement of Cognition and Memory Scores in Transgender Individuals Within One Year of Initiating Gender-Affirming Hormone Therapy

Abstract Disclosure: C.M. Godar: None. S.C. De La Torre: None. O. Bonsu: None. M.K. Shakir: None. T.D. Hoang: None. Introduction: The use of gender-affirming hormone therapy (GAHT) in transgender individuals is known to provide many beneficial health effects to reduce gender dysphoria, reduce depressive symptoms, and increase overall quality of life. Cognitive function and memory ability are known to be influenced by sex hormone levels in studies of hormone replacement therapy in post-menopausal women, but studies of GAHT’s effects on cognition and memory in transgender patients have been scarcely reported. We discuss a study of cognitive testing in transgender individuals before and after 12 months of gender-affirming feminizing or masculinizing hormone therapy using a validated cognitive assessment tool. Methods: A prospective study of 32 transgender patients aged 18-45 years was approved by IRB at an academic medical center. The Wechsler Memory Scale 4th edition (WMS®-IV, Pearson) was administered to 19 transgender females and 13 transgender males prior to initiation of GAHT and again after one year of GAHT use. Mean scores were analyzed and reported for five categories of cognitive and memory function: auditory memory (AMI), visual memory (VMI), visual working memory (VWMI), immediate memory (IMI), and delayed memory (DMI). Mean scores for baseline and 12-month data were analyzed for total population and male and female subgroups. Results: Baseline mean WMS-IV values for the total study population were: AMI 105 points, VMI 78 points, VWMI 107 points, IMI 88 points, DMI 91 points. Mean values after 12 months of GAHT were: AMI 120 points, VMI 81 points, VWMI 110 points, IMI 99 points, DMI 102 points. Mean percent change from baseline to 12 months was as follows: AMI 13.4%, VMI 8.9%, VWMI 2.6%, IMI 12.8%, DMI 13%. Similar patterns were noted for both gender subgroups. Discussion: It is well-known that transgender individuals are subject to higher rates of depression, anxiety, and suicidality compared to the general population. Decreased cognitive function and memory are known effects of untreated depression. Our study demonstrated that treatment of gender dysphoria with GAHT provided a tangible cognitive and memory benefit. The long-term impact of GAHT on cognition and memory is not known and deserves additional study. Limitations of this study included the absence of a cis-gender control group and inability to stratify data based on age, which may provide additional significance. Presentation: 6/2/2024

7838 Improvement of Cognition and Memory Scores in Transgender Individuals Within One Year of Initiating Gender-Affirming Hormone Therapy

Abstract Disclosure: C.M. Godar: None. S.C. De La Torre: None. O. Bonsu: None. M.K. Shakir: None. T.D. Hoang: None. Introduction: The use of gender-affirming hormone therapy (GAHT) in transgender individuals is known to provide many beneficial health effects to reduce gender dysphoria, reduce depressive symptoms, and increase overall quality of life. Cognitive function and memory ability are known to be influenced by sex hormone levels in studies of hormone replacement therapy in post-menopausal women, but studies of GAHT’s effects on cognition and memory in transgender patients have been scarcely reported. We discuss a study of cognitive testing in transgender individuals before and after 12 months of gender-affirming feminizing or masculinizing hormone therapy using a validated cognitive assessment tool. Methods: A prospective study of 32 transgender patients aged 18-45 years was approved by IRB at an academic medical center. The Wechsler Memory Scale 4th edition (WMS®-IV, Pearson) was administered to 19 transgender females and 13 transgender males prior to initiation of GAHT and again after one year of GAHT use. Mean scores were analyzed and reported for five categories of cognitive and memory function: auditory memory (AMI), visual memory (VMI), visual working memory (VWMI), immediate memory (IMI), and delayed memory (DMI). Mean scores for baseline and 12-month data were analyzed for total population and male and female subgroups. Results: Baseline mean WMS-IV values for the total study population were: AMI 105 points, VMI 78 points, VWMI 107 points, IMI 88 points, DMI 91 points. Mean values after 12 months of GAHT were: AMI 120 points, VMI 81 points, VWMI 110 points, IMI 99 points, DMI 102 points. Mean percent change from baseline to 12 months was as follows: AMI 13.4%, VMI 8.9%, VWMI 2.6%, IMI 12.8%, DMI 13%. Similar patterns were noted for both gender subgroups. Discussion: It is well-known that transgender individuals are subject to higher rates of depression, anxiety, and suicidality compared to the general population. Decreased cognitive function and memory are known effects of untreated depression. Our study demonstrated that treatment of gender dysphoria with GAHT provided a tangible cognitive and memory benefit. The long-term impact of GAHT on cognition and memory is not known and deserves additional study. Limitations of this study included the absence of a cis-gender control group and inability to stratify data based on age, which may provide additional significance. Presentation: 6/2/2024

Hypofractionated Radiotherapy for Breast Cancer: Experience of the Radiotherapy Department of the Mali Hospital

Aim: To evaluate the outcomes of hypofractionated radiotherapy in breast cancer. Patients and Methods: It was a retrospective study over a 3-year period, from January 2016 to December 2018, of breast cancer patients treated with hypofractionated radiotherapy at Mali Hospital. All patients with histologically confirmed breast cancer without distant metastases were included. We excluded all patients treated for breast cancer with palliative or normofractionated radiotherapy, patients with metastatic disease on admission and incomplete records. Patients were classified according to the 7th edition TNM classification. Radiotherapy was administered using an Elekta Compact 6MV linear accelerator with the 3D conformal technique, at a total dose of 42 Gy at a rate of 2.8Gy/fraction in 15 sessions, and 5 sessions/week. Data were collected from medical records and treatment sheets, entered into Excel and analysed using SPSS version 23 software. Results: Sixty-four patients out of 129 met our selection criteria (49.61%). The mean age was 44.65+/-11.11 with extremes of 25 and 88 years. Previous hormonal contraception was found in 23.43% of cases, familial breast cancer in 6.25% and nulliparity in 4.68% of cases. Ultramammography was performed in all patients. Assessment of distant extension consisted of a thoraco-abdominal CT scan in 92.18% of cases, and abdominal ultrasound combined with a chest X-ray in 7.82% of cases. Histology of the biopsy specimen showed non-specific carcinoma in 96.87% of cases, Scarf-Bloom and Richardson (SBR) grade II in 64.81% and grade III in 27.78%. Immunohistochemistry was performed in 26 patients, hormone receptor positive in 57.69% (n=15) and triple negative in 42.31% (n=11). Patients were classified as stage T3 or T4 in 82.68% of cases. 95.4% of patients underwent mastectomy and 4.6% lumpectomy; all patients underwent axillary curage. The patients were treated with hypofractionated radiotherapy on the wall and the supra- and sub-clavicular lymph

Emotional interference and attentional bias in compulsive sexual behaviors disorder - An fMRI study on heterosexual males.

Despite the inclusion of the Compulsive Sexual Behavior Disorder (CSBD) in the 11th edition of the International Classification of Diseases, emotional and cognitive impairments related to CSBD remains unclear. This study aimed to investigate the behavioral and neuronal effects of emotional interference on cognition among CSBD patients. Thirty heterosexual males with CSBD and matched healthy controls (HC) were studied with the Emotional Stroop Task using 5 categories of emotionally arousing words (sex-related, positive, fear-related, negative, neutral) during functional magnetic imaging. At the behavioral level, we found the main effect of the condition: sex-related words evoked a stronger Stroop effect than other conditions. At the neural level, we found a significant group effect. Among CSBD patients processing of sex-related words was related to increased activity in the right putamen, right thalamus, hippocampi, and left pulvinar, when compared to HC. We also found a negative correlation between neuronal activation and time spent on sexual activity during the week preceding study and numerous group differences in brain regions connected to the emotional and motivational processing of sexually explicit material, correlating with CSBD symptoms. Behavioral results indicate a specific attentional bias toward sex-related stimuli in both groups, while neural data uncovered stronger reactivity to sex-related words in CSBD compared to HC. This reactivity is related to CSBD symptoms and provides evidence for the interference of sex-related stimuli with cognition. Such results are firmly in line with the Incentive Salience Theory and conceptualizing CSBD as a behavioral addiction.

The Necessary Rapprochement of Negative Affectivity, Personality Disorder, and Depression.

The relationship between depression and personality has long been a topic of interest in the fields of psychiatry and psychology, but consensus remains elusive. This lack of consensus poses a significant challenge in both diagnosis and treatment, especially in situations when otherwise effective therapies for depression fail. Our article aims to address this issue by reviewing the historical and recent conceptualizations of the relationship between depression and personality pathology. Specifically, we focus on the trait domain of negative affectivity found in the International Classification of Diseases, 11th Edition (ICD-11) and the Alternative Model for Personality Disorders (AMPD) as a connecting link between the two phenomena. We review recent empirical studies evaluating the association of negative affectivity, personality, and depression, along with investigations of the relationship between depressive disorders and personality disorders. Additionally, we describe the Hierarchical Taxonomy of Psychopathology (HiTOP) and the AMPD as organizing frameworks for understanding depression within a broader personality framework. Based on the available evidence, we propose that depressive disorders must be assessed within the context of the patient's personality in order to maximize treatment outcomes. Ultimately, this integrated approach can guide clinicians in developing unified treatment protocols and facilitate early detection and intervention for factors contributing to depression in order to minimize treatment resistance.

Verification of five-factor models and reference scores for personality dysfunction and trait domains of the Personality Assessment Questionnaire for ICD-11 (PAQ-11), revised version.

A brief self-reported measure of the Personality Assessment Questionnaire for the 11th edition of the World Health Organization's International Classification of Disease (ICD-11) (PAQ-11) was developed to evaluate ICD-11 personality traits. The aim of this study was to investigate the validity of the revised PAQ-11 version (PAQ-11R) with an additional item in the Dissociality domain and thresholds for the severity of personality dysfunction and domains. Study 1 examined the construct validity of the PAQ-11R in 192 university students in Korea. Study 2 estimated tentative reference scores of personality dysfunction and domains of the PAQ-11R in 91 patients in Korea. In study 1, the PAQ-11R had a five-factor structure and the revised Dissociality scale had better convergent and discriminant validities than the previous version. In study 2, the receiver operating characteristic (ROC) curve of the PAQ-11R identified a threshold score of 35. Reference scores for domains were estimated as 15 for Negative Affectivity, 10 for Detachment, 8 for Anankastia, and 5 each for Disinhibition and Dissociality. These scores contribute to severity of personality disturbance but remain qualifiers only; they are not diagnostic. The results suggest that the PAQ-11R is useful as a quick assessment tool for identifying the domains of personality dysfunction in clinical practice in harmony with the ICD-11 guidelines.

A case of neoadjuvant targeted therapy with pralsetinib for locally advanced lung adenocarcinoma with RET fusion mutation

This case report details the successful treatment of a 68-year-old male patient with locally advanced RET-rearranged lung adenocarcinoma using neoadjuvant pralsetinib. The patient initially presented with a suspicious right upper lobe nodule, which was later diagnosed as lung adenocarcinoma following genetic testing that revealed a RET exon 12 fusion. After 2 months of neoadjuvant treatment with pralsetinib, a significant radiological response was observed, with a reduction in tumor size and metabolic activity. Subsequently, the patient underwent video-assisted thoracoscopic right upper lobectomy and mediastinal lymph node dissection. Postoperative pathological analysis revealed a major pathological response, with only 5% residual tumor cells in the primary lesion and no viable tumor cells in the lymph nodes. Postoperative pathological staging of TNM was ypT1aN0M0, stage IA1(AJCC, 8th edition). The patient recovered well after surgery, demonstrating the potential efficacy of neoadjuvant pralsetinib in locally advanced RET-rearranged lung adenocarcinoma. However, further clinical validation is required to establish the role of neoadjuvant targeted therapy and postoperative adjuvant therapy in this patient population.

The efficacy of loco-regional ropivacaine analgesia via intercostal catheters after lung resection: a randomized, double-blind, placebo-controlled, superiority study.

Postoperative pain remains a burden for patients after minimally invasive anatomic lung resection. Current guidelines recommend the intraoperative placement of intercostal catheters to promote faster recovery. This trial aimed to determine the analgesic efficacy of continuous loco-regional ropivacaine application via intercostal catheter and establish this method as a possible standard of care. Between December 2021 and October 2023, patients were randomly assigned to receive ropivacaine 0.2% or a placebo through an intercostal catheter with a flow rate of 6-8 ml/h for 72 h after surgery. Patients were undergoing anatomic VATS lung resection under general anaesthesia for confirmed or suspected stage I lung cancer (UICC, 8th edition). The sample size was calculated to assess a difference in numerical rating scale associated with pain reduction of 1.5 points. Fourteen patients were included in the ropivacaine group, whereas the placebo group comprised 18 participants. Patient characteristics and preoperative pain scores were similar in both groups. There was no statistically significant difference in postoperative pain scores and morphine consumption between the 2 groups. The mean numerical rating scale when coughing during the first 24 h postoperatively was 4.9 (SD: 2.2) in the ropivacaine group and 4.3 (SD: 2.4); P = 0.47 in the placebo group. We were unable to determine any effect of administered ropivacaine on the postoperative pulmonary function (FEV1, PEF). Our preliminary results suggest that continuous loco-regional ropivacaine administration via surgically placed intercostal catheter has no positive effect on postoperative pain scores or morphine requirements. NCT04939545.

Solar elastosis correlates with high tumor mutation burden and better 5-year disease-specific survival in patients with stage II/III melanoma

ObjectiveTo evaluate the relation between solar elastosis and tumor mutation burden (TMB) in a large clinically annotated cohort of stage II and III melanoma patients. MethodsPrimary cutaneous melanomas from 469 AJCC (8th edition) stage II and III patients with clinical annotation including outcome at 5 years of diagnosis were histopathologically evaluated for solar elastosis. Next-generation sequencing assay MSK-IMPACTTM was employed to determine TMB. Analysis by Fisher’s exact test, chi-square, and Kruskal-Wallis were performed, as well as uni- and multivariate logistic regression. ResultsTumors stratified by low and high TMB showed marked and statistically significant differences in presence and extent of associated solar elastosis. Lower risk patient stage (II versus III by AJCC 8th edition) as well as better 5-year melanomaspecific survival (as binary variable of controls-survivors versus cases-dead of disease at 5 years of diagnosis) were associated with severe solar elastosis. On univariate and multivariate logistic regression models, severe solar elastosis predicted significantly decreased odds of dying of melanoma within 5 years of diagnosis (OR 0.60, 95% CI 0.39-0.89; and OR 0.42, 95% CI 0.20-0.83, respectively; both p<0.05) ConclusionThe association of solar elastosis to TMB and 5-year melanoma specific survival points to its potential as a biomarker of clinical relevance that can be assessed by routine histopathology.

Vitamin D Levels and Temporomandibular Disorders: A Bidirectional Two-Sample Mendelian Randomization Analysis.

Growing researches explore vitamin D's role in temporomandibular disorders (TMDs), but the link between vitamin D and TMDs remains debated. To clarify the causal relationship, we conducted a Mendelian randomization (MR) analysis using data from genome-wide association studies (GWAS). The GWAS dataset of vitamin D (GWAS ID: ukb-d-30890_irnt; sample size: 329247) was obtained from the IEU Open GWAS project. And that of TMDs (GWAS ID: finn-b-TEMPORO; sample size: 134280), initiated on August 25th, 2017 and publicly released on December 18th, 2023, was extracted from the FinnGen dataset, whose cases were diagnosed based on the revised International Classification of Diseases, 10th Edition (ICD-10) code K07.6. Both datasets were obtained from the European population. According to three assumptions of MR analysis, a bi-directional MR analysis was performed to measure the causal relationship, with Inverse variance weighted (IVW) as the primary method and MR Egger and Weighted median as supplement. Moreover, diverse sensitivity analyses, including Cochran's Q test, MR Egger intercept, Mendelian randomized polymorphism RESidual Sum and Outlier (MR-PRESSO), and leave-one-out analysis, were used to verify the stability of the findings. The MR analysis supported causal effects of vitamin D levels on TMDs risks within the European population using IVW method [odds ratio = 1.316; 95% confidence interval = 1.086 to 1.595; P = 0.005], supported by MR Egger and Weighted median. While there was no indication that TMDs have a direct impact on vitamin D levels [β: -0.00738, standard error = 0.00665; P = 0.568]. The study revealed that within the European population higher levels of vitamin D led to higher risks of developing temporomandibular disorders, but found no obvious evidence that TMDs are causally associated with vitamin D. The conclusion should be cautiously interpreted, given the selection bias of TMDs patients sample.

Validation of clinical tumor depth of invasion measure in patients with oral cavity cancer

ObjectivesThe 8th edition of the American Joint Committee on Cancer (AJCC) for head and neck malignancies incorporated depth of invasion (DOI) for oral cavity squamous cell carcinoma (OCSCC). Currently, there is no standardized method to determine clinical DOI (cDOI). We aim to validate radiologic DOI (rDOI) utilizing contrast-enhanced computed tomography (CECT) imaging. Materials and MethodsRadiographic DOI was defined as the coronal measurement of the deepest margin parallel to the expected normal mucosal plane. To establish a valid, accurate and repeatable rDOI, a retrospective cohort at a single institution tertiary hospital underwent preoperative CECT. Radiographic DOI was independently assessed by 2 neuroradiologists. Correlation was determined between rDOI and pDOI. A prospective pilot study of 49 patients with newly diagnosed OCSCC underwent rDOI assessment compared to final pDOI to assess our rDOI method clinical applicability. ResultsNeuroradiologists demonstrated a high degree of predictability between rDOI and pDOI with as great as 90.91% accuracy for readable CECTs. Inter-observer correlations were strong in the retrospective (Session 1: ICC= 0.956; Session 2: ICC= 0.932) and prospective cohorts (Session 1: ICC= 0.859; Session 2: ICC=0.913) illustrating reliability. Intraobserver correlations were also strong (Retrospective Reader 1 ICC=0.968, Reader 2 ICC=0.941; prospective Reader 1 ICC=0.965, Reader 2 ICC=0.800, p<0.001). T1 lesions were immeasurable 25-62.5% of the time. ConclusionsUsing CECT, the coronal measurement of the deepest margin parallel to the expected normal mucosal plane can enhance determination of a reliable cDOI in OCSCC corresponding to pDOI without change in staging for T2 and greater lesions.

Role of Surgery in Potentially Resectable Small-Cell Lung Cancer Based on the Eighth Edition of the TNM Classification: A Population Study of the US SEER Database.

This study aimed to identify a specific SCLC population that would benefit from surgery. This study utilized patient data retrieved from the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2017. To mitigate clinical biases, the propensity score matching (PSM) technique was employed. Separate cohorts were aligned using PSM according to the AJCC 8th edition TNM classification. The Kaplan-Meier method and a competing risk model were applied to evaluate overall survival (OS) and lung cancer-specific survival (LCSS), respectively. Among the 3394 patients with potentially resectable SCLC included in the study, 3062 underwent chemoradiotherapy and 332 underwent surgical treatment with adjuvant chemotherapy. Surgery was associated with better OS (median OS: 49 months; 95% CI: 35-63 months vs. 27 months; 95% CI: 21-33 months, p < 0.001) and LCSS (SHR, 0.578; 95% CI: 0.411-0.815, p < 0.001) in stage I patients after PSM. However, there was no significant difference in OS and LCSS between the surgery and nonsurgery groups in stage II and III patients after PSM. In the entire cohort, lobectomy was associated with improved OS (median OS: 48.6 vs. 28.7 months, p < 0.0001), but not LCSS (SHR, 0.696; 95% CI: 0.466-1.040, p = 0.078) compared with sublobar resection after PSM. Surgery with adjuvant chemotherapy significantly improved the survival prognosis of patients with early-stage SCLC. However, surgical treatment should be carefully considered in patients with stage II/III disease. Lobectomy is oncologically equal to sublobar resection.