Selection Of Treatment Strategies Research Articles

Putative mechanisms of primary resistance to EGFR-targeted therapies: A retrospective study

BackgroundsAdvanced lung adenocarcinoma (LUAD) patient with EGFR mutations often experience resistance to first-line epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) therapy. Nonetheless, the mechanism and biomarkers of primary resistance remain unclear. Further exploration of independent prognostic factors will help clinicians identify patients who may not respond to EGFR-TKIs and select appropriate treatment strategies. MethodsA retrospective study involving 124 patients with stage IV LUAD harboring a common sensitizing EGFR mutation (exon 19 deletion or L858R mutation) who received EGFR-TKIs as first-line therapy was performed. All participants were tested by DNA-targeted sequencing in baseline samples, and there were 19 patients with progression-free survival (PFS) ≤ 3 months (cohort 1, C1, primary resistance), 22 patients with 3 < PFS < 8 months (cohort 2, C2, poor response) without known mutations associated with resistance, and 83 patients with PFS ≥ 8 months (cohort 3, C3, normal). ResultsThe most commonly mutated genes at baseline in patients prior to treatment within the entire study population. were TP53 (65 %), MYC (19 %), CDKN2A (12 %), MUC16 (12 %) and RBM10 (12 %). The baseline characteristics, except for the proportions of patients with EGFR L858R mutation and exon 19 deletion in C1 plus C2 compared to C3 (p = 0.036), were not significantly different among the cohorts. The frequencies of PIK3C2G, STK11, EPAS1, RARA and BTG2 variation were significantly higher in C1, the primary resistance group. Multivariate Cox analysis revealed that PIK3C2G (HR 15.70 95 % CI 3.24–76.05, p < 0.001), STK11 (HR 17.04, 95 % CI 3.68–78.92, p < 0.001), EPAS1 (HR 11.99, 95 % CI 2.57–56.03, p = 0.002), and BTG2 amplification (HR 9.53, 95 % CI 1.67–54.28, p = 0.011) were significantly associated with shorter PFS. ConclusionsThe genomic landscape varies significantly among patients with LUAD, which should be considered when making personalized treatment decisions. This information could provide insights into molecular changes and their effects on clinical treatment in diverse patients with LUAD harboring sensitizing EGFR mutations.

Multimodal machine learning-based technical success prediction in patients undergoing transcatheter aortic valve implantation

Abstract Background Procedural success is fundamental to achieving optimal clinical outcome, and prediction of procedural success and failure is of key importance in the selection of the appropriate treatment strategy in patients with severe aortic stenosis requiring aortic valve replacement. Purpose We aimed to develop a prediction model for procedural success in patients undergoing transcatheter aortic valve implantation (TAVI) using multimodal information and employing machine learning algorithms. Method In a prospective TAVI registry, patient baseline demographics, clinical history, medication, laboratory, procedural characteristics, electrocardiogram, angiography, transthoracic and transesophagel echocardiography, and computed tomography information were collected prospectively and extracted as numeric data. Data preprocessing included the imputation of missing values and the elimination of features with high collinearity. We incorporated several feature selection (FS) and classification algorithms for model development. Datasets for each target were randomly split into train/validation sets (70/10%) and hold-out test sets (20%). All machine learning processes, including preprocessing, feature selection, parameter, and hyperparameter optimization, were carried out on training and validation sets in 10-fold cross-validation. Different metrics, including area under the curve (AUC) in receiver operating characteristic curve analyses, sensitivity, and specificity, were calculated for model evaluation on the holdout test set. Procedural success was defined as technical success in the Valve Academic Research Consortium-3 (VARC-3). Technical failure differentiated between vascular and cardiac complications. Results In a total of 2,576 patients undergoing TAVI with a contemporary device between March 2012 and June 2023, 242 (9.4%) had technical failure: 70 (2.7%) had cardiac and 178 (6.9%) had vascular technical failure. The sensitivity and specificity for overall technical failure were 0.71 and 0.77, respectively, with AUC of 0.76 (95% CI: 0.69-0.84) achieved by the recursive feature elimination and AdaBoost algorithm. For cardiac technical failure, the ANOVA FS and Random Forest (RF) model yielded sensitivity and specificity of 0.71 and 0.77, with an AUC of 0.76 (95% CI: 0.65 to 0.87). Vascular technical failure showed AUC of 0.76 (95% CI: 0.69 to 0.84), with sensitivity and specificity of 0.72 and 0.73, respectively, with achieved using the ANOVA FS and RF model. Conclusion The initial results of the novel prediction model for technical success are promising. Further improvements and external validation are warranted to support the use of the proposed model in clinical practice.Central Illustration

Diagnostic considerations and orthodontic treatment approaches of adolescents with the dentoalveolar form of class II malocclusion

Relevance. Class II malocclusion (distal occlusion) is a common pathology of the maxillofacial region in the sagittal plane and is one of the most prevalent malocclusions. Studies confirm that Class II malocclusion in adolescents exhibits significant variability, prompting the development of various treatment approaches using both removable and fixed orthodontic appliances. The challenges of adolescence include concurrent physiological and psychological changes, which can complicate the treatment process.Purpose. To enhance the effectiveness of orthodontic treatment for patients with the dentoalveolar form of Class II malocclusion by utilizing the Rotation-Torque Index (RTI).Material and methods. A study was conducted on 49 residents of St. Petersburg with physiological occlusion types, who were included in the control group. The main group comprised 95 adolescents (aged 12-18) with the dentoalveolar form of Class II malocclusion classified into three levels of severity, based on the proposed working prognostic classification.Results. A new method was developed to calculate a coefficient that describes the relationship between the position of the upper and lower jaws and the torque of the central incisors. This coefficient helps predict treatment outcomes and guides the selection of the optimal treatment strategy. The Rotation-Torque Index (RTI) was introduced to quantify the relationship between the position of the jaws in the skull (SNA, SNB) and the inclination of the central incisors of the upper jaw relative to the nasal line (NL) and those of the lower jaw relative to the mandibular line (ML).Conclusions. Based on the Rotation-Torque Index (RTI), a working prognostic classification and treatment strategies for patients with the dentoalveolar form of Class II malocclusion were proposed.

Anatomical analysis of the abdominal aorta in a South African sample: influence of age and sex.

The anatomy of the abdominal aorta (AA) varies with age and sex; however, limited studies exist from South Africa. Given the increased incidence of endovascular treatment of the AA, reference values are relevant for interventionalists for improving the safety of endovascular procedures. Therefore, the study aimed to determine the lengths, diameters and tortuosity of the AA and their association with age and sex in a South African sample. After ethical approval, 97 computed tomography angiography (CTA) scans from an adult sample (54 male and 43 female), mean age 48.5 ± 17.2 years were analysed. The aortic length was measured from the origin of the coeliac trunk to the bifurcation point of the AA. The lumen diameters of the aorta were measured at three landmarks. Tortuosity of the AA was quantified with the tortuosity index and its prevalence was determined. The AA was longer in males and showed a significant weak positive correlation with age. The mean diameters of the AA were larger in males and had a significant strong positive correlation with age in both sexes (p < .001). There was a strong positive correlation between age and tortuosity in both sexes (p < .001). The prevalence of a tortuous c-shaped-curve phenotype was 8.2%, with a 7:1 male-to-female ratio. The dimensions and tortuosity differed between sexes and varied significantly with age. These findings may contribute towards reference values in the South African setting, inform patient selection and complement decision-making of endovascular treatment strategies.

ULTRASOUND IMAGING OF COMLICATIONS IN COMBAT CHEST TRAUMA

Abstract. Objective. The aim is to evaluate the effectiveness of ultrasound diagnostics in combat chest trauma at the stage of specialized surgical care. Materials and Methods: 53 cases of complications from combat chest trauma were analyzed during patient evacuation at the stage of specialized surgical care to assess the specificity, accuracy, and sensitivity of the ultrasound method for early detection of complications and to guide further treatment tactics. Results. The ultrasound diagnostic method has advantages in detecting complications of gunshot wounds to the chest, not only during the qualified medical care stages but also where continuous monitoring of these complications is required during further medical evacuation and treatment strategy selection. Conclusions.Therefore, the monitoring of chest trauma complications should be informative at all stages of medical care, accessible, and effective in determining the subsequent treatment strategy.

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor A (VEGF-A) expressions in Ethiopian female breast cancer and their association with histopathologic features.

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGF) play important role in breast tumor growth, invasion, metastasis, patient survival and drug resistance. The aim of this study was to evaluate the protein expression status of EGFR and VEGF-A, as well as their association with hormone receptor status and histopathological characteristics in the invasive type of female breast cancer among Ethiopians. The primary breast tumor tissues were obtained from 85 Ethiopian invasive breast cancer cases that underwent modified radical mastectomy (MRM) from June 2014 to June 2015. Their FFPE blocks were analyzed for EGFR and VEGF protein expressions using immunohistochemical techniques. The expressions were also correlated with histopathologic features. Epidermal growth factor receptor over-expression was observed in 22% of the tumor samples. VEGF-A expression was negative in 13.41%, low in 63.41%, moderate in 20.73%, and high in 2.44%. EGFR expression, but not VEGF-A, showed a significant inverse correlation with both estrogen receptor (ER) (P = 0.01) and progesterone receptor (PR) statuses (P = 0.04). EGFR and VEGF expressions did not show significant association with tumor size, grade, lymph node status or age at diagnosis. Epidermal growth factor receptor expression was most likely associated with ER and PR negative tumors. Assessments of multiple molecular markers aid to understand the biological behavior of the disease in Ethiopian population. It might also help to predict which group of patients might get more benefit from the selected treatment strategies and which are not.

The continuous improvement of digital assistance in the radiation oncologist's work: from web-based nomograms to the adoption of large-language models (LLMs). A systematic review by the young group of the Italian association of radiotherapy and clinical oncology (AIRO).

Recently, the availability of online medical resources for radiation oncologists and trainees has significantly expanded, alongside the development of numerous artificial intelligence (AI)-based tools. This review evaluates the impact of web-based clinical decision-making tools in the clinical practice of radiation oncology. We searched databases, including PubMed, EMBASE, and Scopus, using keywords related to web-based clinical decision-making tools and radiation oncology, adhering to PRISMA guidelines. Out of 2161 identified manuscripts, 70 were ultimately included in our study. These papers all supported the evidence that web-based tools can be transversally integrated into multiple radiation oncology fields, with online applications available for dose and clinical calculations, staging and other multipurpose intents. Specifically, the possible benefit of web-based nomograms for educational purposes was investigated in 35 of the evaluated manuscripts. As regards to the applications of digital and AI-based tools to treatment planning, diagnosis, treatment strategy selection and follow-up adoption, a total of 35 articles were selected. More specifically, 19 articles investigated the role of these tools in heterogeneous cancer types, while nine and seven articles were related to breast and head & neck cancers, respectively. Our analysis suggests that employing web-based and AI tools offers promising potential to enhance the personalization of cancer treatment.

Prediction and validation of pathologic complete response for locally advanced rectal cancer under neoadjuvant chemoradiotherapy based on a novel predictor using interpretable machine learning

BackgroundPrecise evaluation of pathological complete response (pCR) is essential for determining the prognosis of patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (NCRT) and can offer clues for the selection of subsequent treatment strategies. Most current predictive models for pCR focus primarily on pre-treatment factors, neglecting the dynamic systemic changes that occur during neoadjuvant chemoradiotherapy, and are constrained by low accuracy and lack of integrity. PurposeThis study devised a novel predictor of pCR using dynamic alterations in systemic inflammation-nutritional marker indexes (SINI) during neoadjuvant therapy and developed a machine-learning model to predict pCR. MethodsTwo cohorts of patients with LARC from center one from 2012 to 2017 and from center two from 2020 to 2023 were integrated for analysis. This study compared dynamic changes in blood indexes before and after neoadjuvant therapy and surgical operation. A least absolute shrinkage and selection operator (LASSO) regression analysis was conducted to mitigate collinearity and identify key indexes, constructing the SINI. Univariate and multiple logistic regression analyses were used to identify the independent risk factors associated with pCR. Additionally, 10 machine learning algorithms were employed to develop predictive models to assess risk. The hyperparameters of the machine learning models were optimized using a random search and 10-fold cross-validation. The models were assessed by examining various metrics, including the area under the receiver operating characteristic curves (AUC), the area under the precision-recall curve (AUPRC), decision curve analysis, calibration curves, and the precision and accuracy of the internal and external validation cohorts. Additionally, Shapley's additive explanations (SHAP) were employed to interpret the machine learning models. ResultsThe study cohort comprised 677 patients from the center one and 224 patients from the center two. Six key indexes were identified, and a predictive index, SINI, was constructed. Univariate and multiple logistic regression analyses revealed that SINI, clinical T-stage, clinical N-stage, tumor size, and the distance from the anal verge were independent risk factors for pCR in patients with LARC following NCRT. The mean AUC value of the extreme gradient boosting (XGB) model in the 10-fold cross-validation of the training set was 0.877. The XGB model demonstrated superior performance in the internal and external validation sets. Specifically, in the internal test set, the XGB model achieved an AUC of 0.86, AUPRC of 0.707, accuracy of 0.82, and precision of 0.80. In the external validation set, the XGB model exhibited an AUC of 0.83, AUPRC of 0.702, accuracy of 0.81, and precision of 0.81. Additionally, the predictions generated by the XGB model were analyzed using SHAP. ConclusionThis study involved developing and validating an XGB model using SINI to predict pCR in patients with LARC. Besides, a SINI-based machine learning model shows promise in accurately predicting pCR following NCRT in patients with resectable LARC, offering valuable insights for personalized treatment approaches.

Dosimetric comparison of gamma knife and linear accelerator (VMAT and IMRT) plans of SBRT of Lung tumours

This study evaluates dosimetric differences in Stereotactic Body Radiation Therapy (SBRT) for lung tumors using plans of Gamma Knife, and Volumetric Modulated Arc Therapy (VMAT), Intensity-Modulated Radiation Therapy (IMRT) plans based on Linear Accelerator, aiming to inform the reader of appropriate treatment strategy selection. Ten patients with 23 lung tumor lesions treated with SBRT at Zhongshan Hospital of Dalian University were analyzed. Plans of Gamma Knife, and VMAT, IMRT plans based on Linear Accelerator were created for each lesion, totaling 18 plans per type. Lesions were treated with 30–50 Gy in 5–10 fractions. Dosimetric parameters, including gradient index (GI), heterogeneity index (HI), conformity index (CI), and doses to the plan target volumes (PTVs), the gross tumor volumes (GTVs) and organs at risk (OARs) were compared. Plans of Gamma Knife showed superior HI and GI, higher PTV and GTV doses, and reduced doses to the ipsilateral and contralateral lungs, esophagus, spinal cord, and heart compared to VMAT and IMRT plans (p < 0.05). However, Plans of Gamma Knife required longer delivery times. When comparing VMAT and IMRT plans, VMAT plans had shorter delivery times than IMRT plans, but required more monitor units (MUs). Additionally, IMRT plans delivered a lower mean dose to the ipsilateral lung compared to VMAT plans. Gamma Knife SBRT plans achieves steeper dose falloff and minimizes radiation to normal lung tissue compared to VMAT and IMRT plans, but with longer delivery times. VMAT and IMRT plans displayed similar dose distributions for lung SBRT.

Trends in Antimicrobial Resistance of Uropathogens Isolated from Urinary Tract Infections in a Tertiary Care Hospital in Dhaka, Bangladesh.

Background/Objectives: Urinary tract infection (UTI) is a prevalent microbial infection in medical practise, leading to significant patient morbidity and increased treatment costs, particularly in developing countries. This retrospective study, conducted at a tertiary care hospital in Dhaka, Bangladesh, aims to examine the antimicrobial resistance (AMR) patterns of uropathogens and evaluate whether these patterns are influenced by demographic factors such as gender, age, or patient status. Methods: Standard microbiological techniques were used to identify uropathogens, and AMR patterns were determined using the Kirby-Bauer disc diffusion method. Results: Out of 6549 urine samples, 1001 cultures were positive. The infection was more prevalent in females compared to males. The incidence of UTIs in children aged 0-10 years accounted for 12.59% of the total cases, with this age group also exhibiting the highest rate of polymicrobial infections. Among the bacterial uropathogens, 71.19% of isolates were multidrug resistant (MDR) and 84.27% were resistant to at least one antibiotic. Escherichia coli (n = 544, 73.90% MDR) and Klebsiella species (n = 143, 48.95% MDR) were the most common Gram-negative uropathogens, while Enterococcus species (n = 78, 94.87% MDR) was the predominant Gram-positive isolate in this study. Our results indicate that most uropathogens showed resistance against ceftazidime, followed by cefuroxime, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate, and netilmicin. Moderate levels of resistance were observed against ciprofloxacin, levofloxacin, aztreonam, and cefpodoxime. Conclusions: Amikacin was observed to be effective against Gram-negative uropathogens, whereas cefixime was more active against Gram-positive microorganisms, such as Enterococcus species. Moreover, a principal coordinate analysis (PCoA) depicted no significant influence of gender, patient status, or age on AMR patterns. For the continued usefulness of most antibiotics, periodic analysis of the AMR patterns of uropathogens can help assess the rise of MDR bacteria, and therefore guide the selection of appropriate antibiotic treatment strategies.

A Novel Compound from the Phenylsulfonylpiperazine Class: Evaluation of In Vitro Activity on Luminal Breast Cancer Cells.

Breast cancer (BC) is the most common cancer in women, and is characterized by its histological and molecular heterogeneity. Luminal BC is an estrogen receptor-positive subtype, with varied clinical courses. Although BC patients are eligible for hormone therapy, both early and late relapses still occur, and thus there is a demand for new cytotoxic and selective treatment strategies for these patients. In the present study, inspired by the structure of phenylsulfonylpiperazine, a series of 20 derivatives were tested in bioassays against MCF7, MDA-MB-231 and MDA-MB-453 BC cells to discover new hit compounds. After 48 h of treatment, 12 derivatives impaired cell viability and presented significant IC50 values against at least one of the tumor lineages. Overall, the luminal BC cell line MCF7 was more sensitive to treatments. Compound 3, (4-(1H-tetrazol-1-yl)phenyl)(4-((4-chlorophenyl)sulfonyl)piperazin-1-yl)methanone, was the most promising, with IC50 = 4.48 μM and selective index (SI) = 35.6 in MCF7 cells. Compound 3 also presented significant antimigratory and antiproliferative activities against luminal BC cells, possibly by affecting the expression of genes involved in the epithelial-mesenchymal transition mechanism, upregulating E-Cadherin transcripts (CDH1). Our findings suggest that phenylsulfonylpiperazine derivatives are potential candidates for the development of new therapies, especially those targeting luminal BC.

Risk assessment for femoral head collapse in osteonecrosis utilizing MRI-derived large lesion ratio: a retrospective cohort study

PurposeThis study aimed to developed a novel and practical method to quantify the involvement of lesion in osteonecrosis of the femoral head (ONFH). We hypothesized that the new metric large lesion ratio (LLR) had promising prognostic value.MethodsA total of 131 hips with non-traumatic ONFH were included in this retrospective study. Patient aged 18–60 with MRI-confirmed diagnosis, and a minimum of 2-year follow-up or radiographic collapse progression during follow-up were included. Patients with prior hip surgery, incomplete data or advanced ONFH at baseline (femoral head collapse > 2 mm or osteoarthritis) were excluded. Involvement of necrotic lesion was evaluated by calculating LLR. The differences of LLR between collapse progression and non-progression groups were investigated, and the differences among different scanning parameters groups were also examined. Prognostic value of LLR was examined by multivariate regression analysis. Receiver operating characteristic curves (ROC) were constructed and areas under the curve (AUC) were compared.ResultsThe median of LLR was 66.67% in the collapse progression group, which was significantly higher compared with 25.00% in the non-progression group (P < 0.001). Subgroups analysis showed that LLR were significantly higher in the collapse progression group of Japanese Investigation Committee type C1 (P < 0.001)and C2 (P = 0.002). Multivariate regression showed that LLR were independently correlated with collapse progression (OR, 1.46 [95% CI, 1.24–1.78]; P < 0.001). ROC analysis showed that the AUC for LLR was 0.84, outperforming the 0.74 AUC OF the JIC classification.ConclusionLLR could served as a efficient tool to assess the risk of collapse progression and guide the selection of treatment strategy.

Comparison of prognosis between oncocytic thyroid carcinoma and follicular thyroid carcinoma: a population-based propensity score matching analysis.

Oncocytic thyroid carcinoma (OTC) is a rare subtype of thyroid cancer known for its distinctive morphology and high likelihood of recurrence, setting it apart from follicular thyroid carcinoma (FTC). Despite this, there is limited research comparing the clinicopathological characteristics and outcomes of OTC and FTC. We retrospectively searched through the Surveillance, Epidemiology, and End-Results (SEER) database (2004-2015) for histologically diagnosed OTC and FTC patients. Kaplan-Meier analysis, propensity score matching (PSM), univariate Cox proportional risk regression model, and subgroup analysis were employed to investigate the prognostic effect of clinicopathological features and treatment regimens on survival outcomes of OTC and FTC patients. 2329 OTC patients and 5679 FTC patients were included in the study. OTC patients were prone to older age, white race, lymph node metastasis, distal metastasis, extension and multiple primary tumors compared with FTC patients. After using a 1:1 PSM matching ratio, there were no significant differences in demographic and clinicopathological characteristics between the matched groups. Further Cox regression analysis showed that OTC patients had lower overall survival (OS) and cancer-specific survival (CSS) in contrast with FTC patients. Subgroup survival analysis suggested that the OTC patients were related to lower OS in subgroups including those over 55years old, male sex, white ethnicity, extrathyroidal extension, single primary tumor, surgery and without chemotherapy compared with the FTC patients in these subgroups. In addition, the OTC patients were connected with lower CSS in subgroups including male sex, white ethnicity, married status, tumor size is less than 20mm or more than 40mm, N0 stage, localized stage, single primary tumor, surgery, radiotherapy, and without chemotherapy compared with the FTC patients in these subgroups. Meanwhile, the OTC patients had lower CSS compared to FTC patients regardless of age and extrathyroidal extension. The results suggested that OTC patients have unique clinical features and poorer prognoses compared to FTC patients. Surgical resection and radioactive iodine therapy are recommended for OTC patients and FTC patients. It is worth noting that the prognosis of OTC relies largely on the selection of treatment strategies. Therefore, our results highlighted the clinical significance of the early distinguishment and the correct choice of treatment in OTC patients.

Synthetic lumbar MRI can aid in diagnosis and treatment strategies based on self-pix networks

CT and MR tools are commonly used to diagnose lumbar fractures (LF). However, numerous limitations have been found in practice. The aims of this study were to innovate and develop a spinal disease-specific neural network and to evaluate whether synthetic MRI of the LF affected clinical diagnosis and treatment strategies. A total of 675 LF patients who met the inclusion and exclusion criteria were included in the study. For each participant, two mid-sagittal CT and T2-weighted MR images were selected; 1350 pairs of LF images were also included. A new Self-pix based on Pix2pix and Self-Attention was constructed. A total of 1350 pairs of CT and MR images, which were randomly divided into a training group (1147 pairs) and a test group (203 pairs), were fed into Pix2pix and Self-pix. The quantitative evaluation included PSNR and SSIM (PSNR1 and SSIM1: real MR images and Pix2pix-generated MR images; PSNR2 and SSIM2: real MR images and Self-pix-generated MR images). The qualitative evaluation, including accurate diagnosis of acute fractures and accurate selection of treatment strategies based on Self-pix-generated MRI, was performed by three spine surgeons. In the LF group, PSNR1 and PSNR2 were 10.884 and 11.021 (p < 0.001), and SSIM1 and SSIM2 were 0.766 and 0.771 (p < 0.001), respectively. In the ROI group, PSNR1 and PSNR2 were 12.350 and 12.670 (p = 0.004), and SSIM1 and SSIM2 were 0.816 and 0.832 (p = 0.005), respectively. According to the qualitative evaluation, Self-pix-generated MRI showed no significant difference from real MRI in identifying acute fractures (p = 0.689), with a good sensitivity of 84.36% and specificity of 96.65%. No difference in treatment strategy was found between the Self-pix-generated MRI group and the real MRI group (p = 0.135). In this study, a disease-specific GAN named Self-pix was developed, which demonstrated better image generation performance compared to traditional GAN. The spine surgeon could accurately diagnose LF and select treatment strategies based on Self-pix-generated T2 MR images.

309. COMPARATIVE OUTCOMES OF OPEN VS. MINIMALLY INVASIVE ESOPHAGECTOMY FOR ESOPHAGEAL AND GASTRO-ESOPHAGEAL JUNCTION TUMORS: INSIGHTS FROM A THORACO-ABDOMINAL STRATIFICATION MODEL

Abstract Background Minimally invasive esophagectomy (MIE) has demonstrated improved outcomes for fit patients with esophageal/gastro-esophageal junction tumors. However, challenges arise in patients less tolerant of prolonged anesthesia or harboring extensive advanced-stage tumors, which limit the utilization of MIE, increasing the risk of referral to nonsurgical strategies. To date, the criteria for considering left thoraco-abdominal esophagectomy (TAE) and the corresponding outcomes in this specific patient population remain unclear. Therefore, our institutional study aimed to identify clinical characteristics for the consideration of TAE, offering insights into treatment selection strategies for esophageal cancer patients. Additionally, we compared the short-term outcomes between TAE and MIE. Methods We included all consecutive patients who underwent esophagectomy with gastric conduit reconstruction for stage I-IVa esophageal and gastro-esophageal junction tumors at a tertiary referral center from 2015 to 2023. Predictors for considering TAE were identified through a multivariable regression model utilizing multivariate imputation by chain equation for missing data of pulmonary and cardiac function, using the predicted mean matching method. Significant variables were used to develop a stratification model, evaluated through the receiver-operating curve. Differences in outcome were assessed using the Kruskal-Wallis rank sum for continuous and Pearson’s chi-squared or Fischer’s exact test for categorical variables. Results This study included 744 patients; 317 (43%) underwent TAE and 427 (57%) had MIE. Patient characteristics were significantly different. Following multivariable analysis, age (1.04 [1.02-1.06]; p&amp;lt;0.001), ECOG-status (1.43 [1.09-1.87]; p=0.009), comorbidity index (1.26 [1.10-1.46]; p&amp;lt;0.001), DLCO (0.98 [0.97-0.99]; p&amp;lt;0.001), ejection fraction (0.97 [0.94-1.00]; p=0.021), tumor location (GEJ: 1.58 [1.10-2.27], Middle: 0.38 [0.18-0.79]; p&amp;lt;0.001), cStage (II: 2.03 [1.02-4.19], III: 3.29 [1.78-6.33], IVa: 3.42 [1.74-6.97]; p&amp;lt;0.001) and adenocarcinoma (2.44 [1.39-4.55]; p=0.002) were identified as predictors for TAE. The stratification model demonstrated an area-under-the-curve of 0.76 [0.73-0.80]. Leave-one-out-cross-validation demonstrated a 70% accuracy. The short-term outcomes were comparable between TAE and MIE (Table 1). Conclusion Our study demonstrated that age, ECOG status, comorbidity index, diffusion capacity, ejection fraction, tumor location, stage and histology were independent predictors for the consideration of thoraco-abdominal esophagectomy. In this context, our stratification model demonstrated a robust predictive value. Moreover, our model suggests considering MIE below a probability threshold of 30% and TAE above 60%, demonstrating an 85% sensitivity and 90% specificity at these thresholds, respectively. Decisions within the 30% to 60% range should be individualized and based on specific patient and tumor characteristics. Short-term outcomes were comparable between TAE and MIE, emphasizing the significance of adequate stratification before surgery.

Factors associated with the long-term use of benzodiazepine receptor agonists as hypnotics among patients with major depressive disorder and comorbid insomnia

BackgroundPatients with major depressive disorder (MDD) and comorbid insomnia are often co-prescribed benzodiazepines (BZDs) or Z-drugs as hypnotics with antidepressants to manage persistent insomnia. However, factors associated with their long-term use remain unclear among MDD patients. MethodsWe retrospectively analyzed data from 351 MDD patients who started antidepressants with co-prescribed hypnotics (BZDs/Z-drugs) and investigated the prevalence of and factors associated with their long-term use at 12 months. We conducted logistic regression analyses of their long-term use, and compared insomnia severities between the continued and discontinued groups of hypnotics in 32 patients whose insomnia severities had been longitudinally assessed. Results66.1% of patients had continued hypnotics for 12 months. Multiple logistic regression analysis revealed that the diazepam-equivalent dose of hypnotics at the start of the combined treatment (>5 mg), the presence of chronic insomnia prior to MDD, and hospitalization correlated with their long-term use (all p < 0.01). We also found the relationship between the insufficient amelioration of insomnia severities and their long-term use. However, confidence in these results is tempered by various factors, including the dependence on hypnotics, the patient's attitude about hypnotic treatment, and the exclusion of subjects treated with other drugs such as sedative antidepressants or antipsychotics. ConclusionsThese clinical indicators may facilitate the selection of treatment strategies for MDD with comorbid insomnia. To avoid the long-term use of hypnotics, their dose at the start of the combined treatment needs to be adequate (≤5 mg) and alternative treatments to BZDs/Z-drugs are required for refractory insomnia.

Myocardial ischemia caused by the synergistic effect of myocardial bridge and moderate stenosis: case report

BackgroundClinical events such as angina pectoris, acute coronary syndrome, and sudden death caused by myocardial bridge (MB) have attracted increasing attention. It is still a challenge to diagnose whether MB can cause the symptoms of patients with MB. For most MB patients, medication remains the primary treatment.Case presentationThis article reports a case of chest pain in a patient with MB in the middle segment of the left anterior descending artery (LADm) with moderate stenosis in the proximal segment (LADp). Through functional assessment, we found that neither MB nor fixed stenosis had sufficient effect on coronary blood flow to cause myocardial ischemia, but their synergistic effect resulted in myocardial ischemia. Finally, a stent was implanted in LADp and good clinical results were achieved.ConclusionsFor symptomatic patients with MB combined with fixed stenosis, functional evaluation may be necessary, which has significant guiding significance for treatment strategy selection. For asymptomatic patients, early detection of myocardial ischemia may also improve the prognosis of patients.

Autoimmune Neuromuscular Disorders Associated With Neural Antibodies.

This article reviews autoimmune neuromuscular disorders and includes an overview of the diagnostic approach, especially the role of antibody testing in a variety of neuropathies and some other neuromuscular disorders. In the past few decades, multiple antibody biomarkers associated with immune-mediated neuromuscular disorders have been reported. These biomarkers are not only useful for better understanding of disease pathogenesis and allowing more timely diagnosis but may also aid in the selection of an optimal treatment strategy. Recognition of autoimmune neuromuscular conditions encountered in inpatient or outpatient neurologic practice is very important because many of these disorders are reversible with prompt diagnosis and early treatment. Antibodies are often helpful in making this diagnosis. However, the clinical phenotype and electrodiagnostic testing should be taken into account when ordering antibody tests or panels and interpreting the subsequent results. Similar to other laboratory investigations, understanding the potential utility and limitations of antibody testing in each clinical setting is critical for practicing neurologists.

Efficacy of endoscopic surgical management for recurrent nasopharyngeal carcinoma

Compared with re-radiotherapy or open surgery, endoscopic surgery for recurrent nasopharyngeal carcinoma has a better effect, which not only improves the overall survival rate, but also reduces serious complications, improves the quality of life and saves medical costs. With the advancement of modern surgical equipment and instruments, the deepening of anatomical research in the field of skull base, the improvement of surgical techniques and the development of multidisciplinary teamwork, the safety of endoscopic surgery and the rate of complete tumor resection will also increase. The indications for surgery are further expanded, and more patients with recurrent nasopharyngeal carcinoma benefit from endoscopic minimally invasive surgery. This article reviews the efficacy of endoscopic surgery for recurrent nasopharyngeal carcinoma, and then provides insights for the selection of clinical treatment strategies for recurrent nasopharyngeal carcinoma.

Molecular signatures of Haemonchus contortus infection in sheep: A comparative serum proteomic study on susceptible and resistant sheep breeds

Due to the negative impact of Haemonchus contortus in the tropics and subtropics, the detection of serum protein profiles that occur in infected sheep is of high relevance for targeted selective treatment strategies (TST). Herein, we integrated proteomics with phenotypic traits to elucidate physiological mechanisms associated to H. contortus infection in susceptible (Dorper – D) and resistant (Santa Inês – S) sheep breeds. Naïve female lambs were infected with H. contortus third-stage larvae on day zero (D0), and samples were collected weekly, for 28 days. Feces were used for individual fecal egg counts (FEC) blood for packed cell volume (PCV) and serum for specific antibody quantification through ELISA. Sera was collected on D0 (-) and D21 (+), and analyzed using a LC-MS/MS based proteomics approach. FEC, PCV, and anti-H. contortus antibody levels confirmed the absence of infection on D0. On D28 there was a significant difference between the two breeds for logFEC means (D = 3774 and S = 3141, p=0.033) and PCV means (D = 16.3 % and S = 24.3 %, p=0.038). From a total of 754 proteins identified, 68 differentially abundant proteins (DAPs) were noted. Phosphopyruvate hydratase (ENO3) was a DAP in all comparisons, while S+ vs D+ and S- vs D- shared the highest number of DAPs (8). Each of the four experimental groups clustered separately in a principal component analysis (PCA) of protein profile. Among the DAPs, proteins associated with the innate and adaptive immune system were detected when comparing S- vs D- and S+ vs D+. In D-, some proteins were linked to stress response to handling, sampling and heat. Focusing on the consequences of infection in each breed, in the D+ vs D- comparison, upregulated proteins were associated with inflammation control and immune response, where downregulated proteins pointed to a negative impact of infection on tissue anabolism, compromising muscle growth and fat deposition. In the S+ vs S- comparison, upregulated proteins were related to immune response, while the downregulated proteins were possibly linked to muscular development and growth, impaired by infection. Collectively, it can be concluded that ENO3 regulation emerges as a potential factor underlying the differential immune response observed between Santa Inês and Dorper sheep infected with H. contortus. In turn, detected acute phase proteins (APPs) reinforce their relation with infection, inflammation and stress conditions, whereas THEMIS-like may contribute to the immune system in Dorper. GSDMD, Guanylate-binding protein and ACAN warrant further investigation as possible biomarkers for TST strategy development.