Invasion Index Research Articles

Mitigating Medical Adverse Events Following Spinal Surgery: The Effectiveness of a Postoperative Quality Improvement (QI) Care Bundle.

Spine surgery is associated with a high incidence of postoperative medical adverse events (AEs). Many of these events are considered "minor" though their cost and effect on outcome may be underestimated. We sought to examine the clinical and cost-effectiveness of a postoperative quality improvement (QI) care bundle in mitigating postoperative medical AEs in adult surgical spine patients. We collected 14-year prospective observational interrupted time series (ITS) with two historical cohorts: 2006 to 2008, pre-implementation of the postoperative QI care bundle; and 2009 to 2019, post-implementation of the postoperative QI care bundle. Adverse Events were identified and graded (Minor I and II) using the previously validated Spine AdVerse Events Severity (SAVES) system. Pearson Correlation tested for changes across patient and surgical variables. Adjusted segmented regression estimated the effect of the postoperative QI care bundle on the annual and absolute incidences of medical AEs between the two periods. A cost model estimated the annual cumulative cost savings through preventing these "minor" medical AEs. We included 13,493 patients over the study period with a mean of 964 per year (SD±73). Mean age, mean Charlson Comorbidity Index (CCI), and mean spine surgical invasiveness index (SSII) increased from 48.4 to 58.1years; 1.7 to 2.6; and 15.4 to 20.5, respectively (p<0.001). Unadjusted analysis confirmed a significant decrease in the annual number of all medical AEs (p<0.01). When adjusting for age, CCI and SSII, segmented regression demonstrated a significant absolute reduction in the annual incidence of cardiac, pulmonary, nausea and medication-related AEs by 9.58%, 7.82%, 11.25% and 15.01%, respectively (p<0.01). The postoperative QI care bundle was not associated with reducing the annual incidence of delirium, electrolyte levels or GI AEs. Annual projected cost savings for preventing Grade I and II medical AEs were $1,808,300 CAD and $11,961,500 CAD. Postoperative QI care bundles are effective for improving patient care and preventing medical care-related AEs, with significant cost savings. Postoperative QI care bundles should be tailored to the specific vulnerability of the surgical population for experiencing AEs.

Phylogeographic Analysis for Understanding Origin, Speciation, and Biogeographic Expansion of Invasive Asian Hornet, Vespa velutina Lepeletier, 1836 (Hymenoptera, Vespidae)

The Asian hornet, Vespa velutina, is an invasive species that has not only expanded its range in Asia but has also invaded European countries, and it incurs significant costs on local apiculture. This phylogeographic study aims to trace the evolutionary trajectory of V. velutina and its close relatives; it aims to identify features that characterize an invasive species. The last successful invasion of Vespa velutina into France occurred in late May, 2002, and into South Korea in early October, 2002, which were estimated by fitting a logistic equation to the number of observations over time. The instantaneous rate of increase is 1.3667 for V. velutina in France and 0.2812 in South Korea, which are consistent with the interpretation of little competition in France and strong competition from local hornet species in South Korea. The invasive potential of two sister lineages can be compared by their distribution area when proper statistical adjustments are made to account for differences in sample size. V. velutina has a greater invasive potential than its sister lineage. The ancestor of V. velutina split into two lineages, one found in Indonesia/Malaysia and the other colonizing the Asian continent. The second lineage split into a sedentary clade inhabiting Pakistan and India and an invasive lineage colonizing much of Southeast Asia. This latter lineage gave rise to the subspecies V. v. nigrithorax, which invaded France, South Korea, and Japan. My software PGT version 1.5, which generates geophylogenies and computes geographic areas for individual taxa, is useful for understanding biogeography in general and invasive species in particular. I discussed the conceptual formulation of an index of invasiveness for a comparison between sister lineages.

How Morphology Shapes Survival in Invasive Squamous Cell Carcinoma of the Lung.

Squamous cell carcinoma (SQCC) represents a significant proportion of human malignancies affecting various anatomical sites, including the lung. Understanding the prognostic factors is crucial for establishing effective risk stratification in these patients, as multiple critical aspects significantly impact overall survival. A retrospective study was conducted on 99 patients with operable lung SQCC treated at a tertiary center. The exclusion criteria included patients under 18, those with in situ or metastatic SQCC, and those who received neoadjuvant therapy. The surgical specimens were re-analyzed, and data were collected on multiple variables, including pTNM staging, tumor characteristics, and overall survival (OS). The Kaplan-Meier survival analysis and Cox regression models were used to identify significant prognostic factors. The Kaplan-Meier analysis showed a median survival of 36 months with a 65.65% mortality rate. Significant factors influencing survival included keratinization, histological grading, tumor size and stage, pleural invasion, tumor cell arrangement, tumor budding, spread through air space (STAS), and mitotic index. A multiple Cox regression highlighted the nonkeratinizing tumors, advanced pT stages, single-cell invasion, and high mitotic index as key predictors of poorer outcomes. The nonkeratinizing tumors showed higher mortality and shorter median survival rates compared to keratinizing tumors. The tumor staging, cell arrangement, and tumor budding significantly impacted the survival curves. The study underscores the importance of detailed histopathological evaluations in lung SQCC. The nonkeratinizing tumors, advanced pT stage, single-cell invasion, and high mitotic index were associated with higher hazard rates, emphasizing the need for a comprehensive grading system incorporating these factors to improve prognostic accuracy and guide treatment strategies.

7248 Spliceosome component TCERG1 regulates the aggressiveness of somatotroph adenoma

Abstract Disclosure: K. Kim: None. The role of the spliceosome in the development of pituitary tumors is not well understood, despite preliminary studies indicating abnormal expression of oncogenic splicing variants in these neuroendocrine tumors. We aimed to identify differentially expressed spliceosome components in growth hormone (GH)-secreting pituitary tumors and investigate their roles in pathogenesis.We performed transcriptome analysis of 20 somatotroph adenomas and 6 normal pituitary tissues to select dysregulated spliceosome components. Clinical characteristics were analyzed based on gene expression in 64 patients with acromegaly. GH secreting pituitary adenomas were confirmed by 75 g oral glucose tolerance and immunohistochemical staining. Proliferation, invasion, and hormonal activity of GH secreting pituitary adenoma cells were investigated after modulating gene expression.TCERG1 expression was significantly higher in somatotroph adenomas than in normal cells (log2 fold change 0.59, adjusted P=0.0002*). Genotype-phenotype analysis revealed that patients with higher TCERG1 expression had lower surgical remission rates than those with lower expression (63.64% vs. 95.45%, P=0.009*). TCERG1 expression was significantly higher in groups with cavernous sinus (CS) invasion or Ki67 index over 1.5 (2.06 vs. 1.65, P=0.011*; 2.02 vs. 1.66, P=0.043*). TCERG1 overexpression led to a 16.91% increase in proliferation after 72 h (P&amp;lt;0.001*) and a 249.47% increase in invasion after 48 h in GH3 cells (P=0.026*). Conversely, TCERG1 silencing significantly decreased cell proliferation (10.15% at 72 h, P&amp;lt;0.001*) and invasion (96.87% at 48 h, P=0.029*). Vimentin was increased, but E-cadherin was decreased in both TCERG1 overexpressed GH3 cells and somatotroph adenomas. And TCERG1 silence reversed the expression of the genes (CDH2, SNAI1, ZEB2, and VIM) in GH3 cells. Additionally, GH secretion increased when TCERG1 was overexpressed in GH3 cells. Spliceosome machinery provide novel insights into the pathogenesis of GH-secreting pituitary tumor and highlight the potential role of TCERG1 as a therapeutic target. Presentation: 6/2/2024

Spliceosome component TCERG1 regulates the aggressiveness of somatotroph adenoma.

We aimed to identify differentially expressed spliceosome components in growth hormone (GH)-secreting pituitary tumors and investigate their roles in pathogenesis. We performed transcriptome analysis of 20 somatotroph adenomas and 6 normal pituitary tissues to select dysregulated spliceosome components. Clinical characteristics were analyzed based on gene expression in 64 patients with acromegaly. Proliferation, invasion, and hormonal activity of GH secreting pituitary adenoma cells were investigated. TCERG1 expression was significantly higher in somatotroph adenomas than in normal pituitaries (log2 fold change 0.59, adjusted P = 0.0002*). Genotype-phenotype analysis revealed that patients with higher TCERG1 expression had lower surgical remission rates than those with lower expression (63.64% vs. 95.45%, P = 0.009*). TCERG1 expression was significantly higher in groups with cavernous sinus (CS) invasion or Ki67 index over 3 (all P>0.05*). TCERG1 overexpression led to a 29.60% increase in proliferation (P<0.001*) and a 249.47% increase in invasion after 48h in GH3 cells (P = 0.026*). Conversely, TCERG1 silencing significantly decreased cell proliferation (25.76% at 72h, P<0.001*) and invasion (96.87% at 48h, P = 0.029*). E-cadherin was decreased, but vimentin was increased in both TCERG1 overexpressed GH3 cells and somatotroph adenomas. And TCERG1 silence reversed the expression of the genes (CDH2, SNAI1, ZEB2, and VIM) in GH3 cells. Spliceosome machinery provide novel insights into the pathogenesis of GH-secreting pituitary tumor and highlight the potential role of TCERG1 as a biomarker for tumor aggressiveness.

Community science can inform invasive species management: Melaleuca (Myrtaceae) in South Africa

Abstract Community science initiatives are revolutionising our ability to detect and respond to biological invasions. Non‐native trees and shrubs are among the world's most damaging invasive species and community science data can be used to inform protocols for managing these invasions. This study explores the utility of iNaturalist in informing management practices for the widely cultivated and naturalised genus Melaleuca L. (Myrtaceae; here including the genus Callistemon) in South Africa. We applied data from iNaturalist to assess the distribution and invasion ecology of Melaleuca species in South Africa. Melaleucas, first recorded in South Africa in 1882, have been widely used as garden ornamentals and street trees in the country for over 50 years. Naturalisation of melaleucas in South Africa was first reported in 1998 and the first records of naturalisation/invasiveness for other species are accumulating rapidly. Data on all Melaleuca species in South Africa were downloaded from iNaturalist and analysed using Geographic Information System software. In September 2023, iNaturalist had 3221 records of melaleucas across the country. After checking and filtering, and applying criteria to increase reliability, 2815 records remained, with confirmed identifications of 26 species. These species were recorded in a total of 138 quarter‐degree cells (QDCs) in South Africa (7% of the country); Research Grade (RG, wild‐growing) records occurred in 21 QDCs, records of cultivated plants in 75 QDCs, and 42 QDCs had records of both cultivated and wild‐growing plants. An Invasiveness Index was calculated for each species in the country, provinces, and municipalities, to show which species are already invasive or have substantial invasion debt. Thirty‐two percent of the filtered records were RG (naturalised). The municipality with the highest number of records is the City of Cape Town, with 43% RG records. iNaturalist provided useful information on the occurrence of five Melaleuca species for which no information was available before this study was undertaken. Case studies of invaded habitats highlight that melaleucas have the potential to alter ecosystems incurring substantial control costs. Practical implications: Our study highlights the value of community science data in the detection, monitoring, and management of invasive plant species.

Predictors for Vulnerable Plaque in Functionally Significant Lesions

BackgroundVulnerable plaque presents prognostic implications in addition to functional significance. ObjectivesThe aim of this study was to identify relevant features of vulnerable plaque in functionally significant lesions. MethodsIn this multicenter, prospective study conducted across 5 countries, including patients who had invasive fractional flow reserve (FFR) ≤0.80, a total of 95 patients with available pullback pressure gradient (PPG) and plaque analysis on coronary computed tomographic angiography and optical coherence tomography were analyzed. Vulnerable plaque was defined as the presence of plaque rupture or thin-cap fibroatheroma on optical coherence tomography. Among the 25 clinical characteristics, invasive angiographic findings, physiological indexes, and coronary computed tomographic angiographic findings, significant predictors of vulnerable plaque were identified. ResultsMean percentage diameter stenosis, FFR, and PPG were 77.8% ± 14.6%, 0.66 ± 0.13, and 0.65 ± 0.13, respectively. Vulnerable plaque was present in 53 lesions (55.8%). PPG and FFR were identified as significant predictors of vulnerable plaque (P < 0.05 for all). PPG >0.65 and FFR ≤0.70 were significantly related to a higher probability of vulnerable plaque after adjustment for each other (OR: 6.75 [95% CI: 2.39-19.1]; P < 0.001] for PPG >0.65; OR: 4.61 [95% CI: 1.66-12.8]; P = 0.003 for FFR ≤0.70). When categorizing lesions according to combined PPG >0.65 and FFR ≤0.70, the prevalence of vulnerable plaque was 20.0%, 57.1%, 66.7%, and 88.2% in the order of PPG ≤0.65 and FFR >0.70, PPG ≤0.65 and FFR ≤0.70, PPG >0.65 and FFR >0.70, and PPG >0.65 and FFR ≤0.70 (P for trend < 0.001), respectively. ConclusionsAmong low-FFR lesions, the presence of vulnerable plaque can be predicted by PPG combined with FFR without additional anatomical or plaque characteristics. (Precise Percutaneous Coronary Intervention Plan [P3] Study; NCT03782688)

Microvascular resistance reserve: impact on health status and myocardial perfusion after revascularization in chronic coronary syndrome.

The microvascular resistance reserve (MRR) is a novel invasive index of the microcirculation, which is independent of epicardial stenoses, and MRR has both diagnostic and prognostic implications. This study investigates whether MRR is associated with health status outcomes by revascularization in patients with moderate coronary stenoses. Consecutive patients with stable chest pain and moderate (30-90% diameter) stenoses on invasive coronary angiography (n=222) underwent invasive physiology assessment. Revascularization was performed by guideline recommendations. At baseline and follow-up, health status and myocardial perfusion were assessed by Seattle Angina Questionnaire (SAQ) and positron emission tomography. The primary endpoint was freedom from angina at follow-up with secondary endpoints including changes in health status by SAQ domains and myocardial perfusion by MRR and revascularization status. Low MRR was defined as ≤3.0. Freedom from angina occurred in 38/173 patients. In multivariate analyses, MRR was associated with freedom from angina at follow-up (odds ratio 0.860, 95% confidence interval 0.740-0.987). By MRR and revascularization groups, patients with normal MRR who did not undergo revascularization, and patients with abnormal MRR who underwent revascularization, improved health status of angina frequency (mean difference SAQ angina frequency score 8.5 [3.07-13.11] and 13.5 [2.82-23.16], respectively). For both groups, health status of physical limitation (mean difference in SAQ physical limitation score 9.7 [4.79-11.93] and 8.7 [0.53-13.88], respectively) and general health status (mean difference in SAQ summary score 9.3 [5.18-12.50] and 10.8 [2.51-17.28], respectively) also improved. Only patients with abnormal MRR who underwent revascularization improved myocardial perfusion. In patients with moderate coronary stenoses, MRR seems to predict symptomatic and perfusion benefit of revascularization.

Association of CT-DSA vascular assessment and perioperative outcomes in metastatic spinal surgery

IntroductionComputed tomography-digital subtraction angiography (CT-DSA) is a radiological method for assessing spinal metastatic tumor vascularity. The study aimed to investigate the association between CT-DSA results and perioperative outcomes in spinal metastatic surgery. Material and methodsPatients who underwent spinal metastatic operations with preoperative CT-DSA examinations at any time between January 2018 to December 2022. CT-DSA was classified into five grades ranging from grade 0 to grade 4. Grades 3 and 4 were indicative of hypervascularity. We analyzed the perioperative outcomes of intraoperative blood loss amount, massive hemorrhage (≥2500 ml) occurrence, blood transfusion status, operation time, hospital stay duration, and 30-day and 60-day mortality rates. Logistic regression analyses were conducted to identify factors affecting the likelihood of massive hemorrhage in conjunction with CT-DSA. ResultsData from 212 operations involving 209 patients were analyzed. In total, 30, 36, 66, 56, and 24 operations had CT-DSA grades from grade 0 to grade 4, respectively. Eighty (38 %) studies were indicative of hypervascularity. CT-DSA grade was positively correlated with the amount of operative blood loss, the occurrence of massive hemorrhage, and the amount of blood in blood transfusion (p < 0.05). However, CT-DSA grades was not significantly associated with operation duration or mortality rate. A multivariable analysis indicated that factors such as hemoglobulin, hypervascular pathology, and spinal instability neoplastic scores were positively correlated with CT-DSA grade. CT-DSA grade (odds ratio: 2.37, p = 0.02), spinal metastatic invasiveness index, and tumor size (≥50 mL) were found to be independent predictors in a multivariable logistic regression analysis where factors associated with massive hemorrhage were included. Hypervascular pathology type was not significantly associated with the likelihood of hemorrhage in the univariable and multivariable analyses. ConclusionsCT-DSA serves as an effective tool for assessing vascularity, and is associated with intra-operative blood loss and likelihood of experiencing massive hemorrhage. The predictive capability of CT-DSA surpasses that of traditional histopathology classifications, making it a useful method for preoperative planning in spinal metastatic surgeries.

Impact of Direct Acting Antivirals Therapy on Novel Fibrosis Index for Assessment of Hepatic Fibrosis in Comparison with AST to Platelet Ratio and Fibrosis-4 (FIB-4) Indices in Egyptian Patients with Chronic Hepatitis C Infection in Correlation with Fibroscan

Abstract Background Chronic viral infection causes multiple waves of inflammation and tissue repair which involves deposition of extracellular matrix resulting in scarring or progressive fibrosis over time and ultimately leading to liver cirrhosis. The introduction of DAAs has improved eradication rate of HCV and achievement of SVR. In addition to the high rates of sustained virological response (SVR), hepatic fibrosis may regress, and the risks of complications, such as hepatic failure and portal hypertension are reduced after SVRs, Stage of liver fibrosis in chronic HCV infection is a well-established factor that determines the severity of disease and associated complications. Numerous noninvasive fibrosis scores, imaging techniques and new serum fibrosis markers have been applied to evaluate the phases of liver fibrosis, and have mostly replaced liver biopsy Transient elastography (TE) is the most accurate method with high sensitivity and specificity for advanced fibrosis the aminotransferase (AST)/platelet ratio index (APRI) and the fibrosis-4 (FIB-4) scores are the most widely used in viral hepatitis C patients, particularly in those with significant fibrosis and cirrhosis. Objective The aim of this study is to evaluate Impact of Direct Acting Antivirals therapy on Novel fibrosis index for assessment of hepatic fibrosis in comparison with AST to Platelet ratio and fibrosis-4(FIB-4) indices in Egyptian patients with chronic hepatitis C infection in correlation with fibro scan. Patients and Methods This is a prospective Cohort clinical study performed on 100 Egyptian patients are ≥18 years of age who have chronic infection with hepatitis C who will be treated with combination of IFN-free DAAs (Sofosbuvir &amp; Daclatasvir ± Ribavirin) for 3 months. oral informed consent was taken from all patients included in the study. Results In the current study, there was significant regression of degree of fibrosis after treatment with DAAs in all patients achieving SVR by fibroscan, APR and fib4. novel fibrosis index is reliable and good tool in assessment of liver fibrosis in correlation to fibroscan, APRI and FIB4 especially significant fibrosis with the cut off value in prediction of hepatic fibrosis stage 4 was &amp;gt;3.1 and has sensitivity of 81.5% while the specificity was 74.1%. The positive predictive value was 66% while the negative predictive value was 86.8% Conclusion Novel fibrosis index has been found to be good reliable marker for assessment of liver fibrosis with high accuracy of predicting f4 fibrosis stage. There was significant marked reduction of fibrosis degree by fibroscan and non invasive indices (APRI &amp;FIB4) after treatment with directly acting antiviral in both cirrhotic and non cirrhotic patients regardless the treatment regimen used with improved overall liver function tests especially albumin level, liver enzymes, hemoglobin level and platelet count in patients who reached SVR.

Diagnostic Role of Serum Chitinase 3 Like Protein 1 as Potential Marker for Fibrosis Assessment in Patient with Chronic Hepatitis B Infection

Abstract Objectives The main objective of this research was to study to evaluate the diagnostic accuracy of serum chitinase-3 like protein-1 (CHI3L1) in comparison with transient elastography (TE) and non- invasive indirect serum indices (Fib-4 and APRI) for the prediction of significant hepatic fibrosis in patients with chronic HBV infection. Methods The current cross-sectional was carried out on 30 individuals with CHB who attended the viral hepatitis unit outpatient clinic, Faculty of Medicine, Ain Shams University, from Aug-2021 to Mar-2022. The primary outcome measures are the correlation of CHI3L1 level to TE, Fib-4, and APRI and calculating the sensitivity and specificity. Results The mean age of CHB cases enrolled was 41.60 ± 11.68 years. Male accounted for 21(70%) of cases. The serum level of CHI3L1 was statistically significantly higher in the enrolled patients' group (CHB) median (IQR): 317.5 (300 – 380) ng/ml than healthy control group 28 (25 – 35) with a p-value &amp;lt;0.001. The results of the current study showed a highly significant (p &amp;lt; 0.001) positive correlation (r = +0.702) between CHI3L1 and TE. However, no statistically significant correlations have been found between the level of CHI3L1 and either Fib-4 or APRI. CHI3L1 levels were significantly higher in CHB patients with significant hepatic fibrosis than in those without significant fibrosis in our study. ROC curve shows that CHI3L1 at the cut-off &amp;gt; 307.5 can differentiate between patients with significant fibrosis and patients with no or mild fibrosis according to TE with a sensitivity of 85.5%, specificity of 62.5%, and area under the curve (AUC) of 0.80 (95% CI: 0.64-0.96). Our study showed that significant fibrosis had been found more in older age. The higher the CHI3L1 serum levels, the higher the degree of hepatic fibrosis. Conclusion In conclusion, as the CHI3L1 levels were significantly higher in CHB patients with significant hepatic fibrosis than in those without significant fibrosis, the beneficial effect of CHI3L1 for the prediction of significant hepatic fibrosis in patients with chronic HBV infection has some evidence.

Can Frailty Predict 90-Day Postoperative Outcome in Elderly Patients with Degenerative Cervical Spine Pathology?

Abstract Background: Age and general health status are major points of concern in the decision-making process when it comes to cervical spine surgeries in the elderly. While there have been studies on the various frailty indices in their ability to predict outcomes in spine surgery, there have been few articles that have investigated the utility of the 5-point modified Frailty Index (mFI-5) for this purpose. Our study attempts to have a granular view of the problem of frailty in the elderly and study the correlation between the mFI-5 and American society of anesthesiologists (ASA) classes, and the 90-day surgical outcome of patients of 60 years and above, operated for degenerative cervical spine pathologies. Materials and Methods: This is a single-center retrospective study of prospectively collected data on 41 patients aged 60 years and above who were operated at our institute between January 1, 2017, and December 31, 2022. We studied the correlation of mFI-5, ASA class and the Spinal Surgical Invasiveness Index (SII) with various outcome variables like length of hospital stay, need for ICU stay, complications, severe adverse events (Clavien Dindo grade 4 and above), re-intubation, unplanned re-admission, and need for re-operation. Results: Statistical analysis showed a significant correlation between ASA class and mFI-5 scores (Chi square test, P value: 0.0401) and between ASA scores and the need for an ICU stay (Chi square test, P value: 0.0047). SII was found to correlate with length of hospital stay (Spearman rank test, P value: 0.0037) and with need for ICU care (Mann–Whitney U test, P value 0.0422). However, there was no significant correlation between the mFI-5 scores and the outcome variables. Conclusion: Although there was no significant correlation between mFI-5 and the 90-day surgical outcome, variables like ASA and SII had a bearing on it. Thus, it can be stated that the outcome of cervical spine surgery in the elderly is multifactorial. While frailty should put the healthcare team on alert while dealing with such patients, it should not discourage them from offering a surgical solution when required, as efficient peri-operative management by the surgical, anesthesia, and critical care teams can lead to favorable 90-day outcomes.

Squamous cell carcinoma of ear and temporal bone: A retrospective study on clinicopathological predictors.

Ear and temporal bone squamous cell carcinoma (ETBSCC) is a rare and aggressive malignant tumor with minimal clinicopathological studies. The object of this study was to retrospectively evaluate the predictive effect of clinicopathological variables on the 5-year overall survival (OS) rate of ETBSCC patients in a single tertiary medical center in Tianjin, China. A cohort of 44 patients with diagnosed ETBSCC from December 2012 to August 2022 were retrospectively studied. Univariate and multivariate analysis were, respectively, performed for the assessment of clinicopathological predictors, including sex, age, history of chronic suppurative otitis media (CSOM), lesion side, diameter, the choice of surgical approach, parotidectomy, neck dissection, adjuvant therapies, T stage, lymph node metastasis, tumor grade, margin, perineural invasion (PNI), and Ki-67 index. Seventeen females and 27 males were included, with the mean age of 65 years old, ranging from 36 to 89 years. The 5-year OS rate was 43% (mean 51 months, 95% confidence interval [CI] = 39-64). Significant prediction of a worse prognosis for 5-year OS rate was observed under univariate analysis for advanced T stage, positive margin, identified PNI, and higher Ki-67 index, respectively. Advanced T stage was confirmed to be an independent prognostic factor strongly affecting 5-year OS rate among this cohort of patients using a multivariate cox proportional hazard model. We found that clinicopathological parameters, especially postoperative pathological parameters, play a critical role in predicting the prognosis of ETBSCC patients.

Immunohistochemical Profile of Triple-Negative Breast Cancers: SOX10 and AR Dual Negative Tumors Have Worse Outcomes

Triple-negative breast cancer (TNBC) refers to an estrogen receptor–negative, progesterone receptor–negative, and HER2-negative breast cancer. Although accepted as a clinically valid category, TNBCs are heterogeneous at the histologic, immunohistochemical, and molecular levels. Gene expression profiling studies have molecularly classified TNBCs into multiple groups, but the prognostic significance is unclear except for a relatively good prognosis for the luminal androgen receptor subtype. Immunohistochemistry (IHC) has been used as a surrogate for basal and luminal subtypes within TNBC, but prognostication of TNBC using IHC is not routinely performed. We aimed to study immunophenotypic correlations in a well-annotated cohort of consecutive TNBCs, excluding postneoadjuvant chemotherapy cases. Tissue microarrays were constructed from a total of 245 TNBC cases. IHC stains were performed and consisted of luminal (AR and INPP4B), basal (SOX10, nestin, CK5, and EGFR), and diagnostic (GCDFP15, mammaglobin, GATA3, and TRPS1) markers. Survival analysis was performed to assess the significance of clinical-pathologic variables including age, histology, grade, lymphovascular invasion, Nottingham prognostic index category, American Joint Committee on Cancer (AJCC) stage, stromal tumor-infiltrating lymphocytes at 10% increment, CD8+ T-cell count, Ki-67 index, PD-L1 status, and chemotherapy along with the results of IHC markers. Apocrine tumors show prominent reactivity for luminal markers and GCDFP15, whereas no special-type carcinomas are often positive for basal markers. TRPS1 is a sensitive marker of breast carcinoma but shows low or no expression in apocrine tumors. High AJCC stage, lack of chemotherapy, and dual SOX10/AR negativity are associated with worse outcomes on both univariable and multivariable analyses. Lymphovascular invasion and higher Nottingham prognostic index category were associated with worse outcomes on univariable but not multivariable analysis. The staining for IHC markers varies based on tumor histology, which may be considered in determining breast origin. Notably, we report that SOX10/AR dual negative status in TNBC is associated with a worse prognosis along with AJCC stage and chemotherapy status.

AORTIC REGURGITATION INDEX IDENTIFIES SIGNIFICANT AORTIC REGURGITATION DURING IMPELLA SUPPORT FOR CARDIOGENIC SHOCK

Abstract Background Aortic regurgitation (AR) significantly hampers the unloading effect and the antegrade flow enhancement expected from the micro–axial flow pump Impella (Abiomed, Danvers). To date, no dedicated hemodynamic index is available to inform on the severity of AR during Impella support. Methods We included 100 patients receiving Impella support for CS with invasive hemodynamic assessment with pulmonary artery catheter (PAC). PAC measures were obtained 48 hours after Impella support initiation. AR grading was performed by either trans–thoracic or trans–esophageal echocardiography in the following strata: 0–none; 1–mild; 2–moderate; 3–moderate–severe; 4–severe. Study cohort was dichotomized according to AR severity≥2+. Several relevant hemodynamic indexes were validated against echocardiographic AR assessment to identify those mostly associated with significant AR (AR severity≥2+), including: AR index [ARI, calculated as (diastolic arterial pressure – pulmonary artery wedge pressure)/systolic arterial pressure, abbreviated in (DAP–PAWP)/SAP], diastolic pulse pressure (DPP, calculated as DAP–PAWP), MAP–adjuster ARI [ARIMAP calculated as (diastolic arterial pressure – pulmonary artery wedge pressure)/mean arterial pressure, abbreviated in (DAP–PAWP)/MAP)]. Results Significant AR (≥2+) was found in 31% patients. Patients with AR≥2+ had higher values of pulmonary artery wedge pressure (PAWP) after 48 hours from support initiation [15 (12, 21) vs 12 (10, 16) mmHg; p&amp;lt;0.021]. Several invasive hemodynamic indexes differentiated AR≥2+ vs AR&amp;lt;2 patients, including: ARI [0.42 (0.36, 0.51) vs 0.50 (0.44, 0.61); p&amp;lt;0.001], DPP [47 (37, 58) vs 57 (48.00, 68) mmHg; p=0.003] and ARIMAP [0.62 (0.54, 0.70) vs 0.70 (0.64, 0.75); p=0.005] (Figure 1). ARI demonstrated the strongest association and the greatest accuracy in identifying AR≥2+ (area under the curve 0.73; 95%CI: 0.61–0.85; p=0.002). The threshold of ARI 0.39 had excellent specificity (88.0%) and moderate sensitivity (62.9%), Figure 2. Conclusions The easy–to–use ARI metric [(DAP–PAWP)/SAP] accurately identifies patients with significant AR during Impella support, at the optimal cutoff of ARI 0.39. This index may be complementary to echocardiography in the assessment of AR during Impella support.

Endoscopic submucosal dissection versus surgery for T1b esophageal carcinoma: a single-center retrospective study

IntroductionEndoscopic submucosal dissection (ESD) is a preferred treatment option for superficial esophageal squamous cell carcinoma (SESCC). However, only few studies compared long-term survival outcomes of ESD with surgery, especially for T1b SESCC. This study compared the overall survival (OS), disease-free survival (DSS), recurrence-free survival (RFS), and complication rates of both, to evaluate the value of ESD in patients with T1b SESCC.MethodsWe reviewed patients who underwent ESD (n = 47) or surgery (n = 73) for T1b SESCC at Affiliated Hospital of Nanjing University of Chinese Medicine from 2009 to 2021. To increase the precision of our results interpretation, subgroups were analyzed according to the depth of tumor invasion and elderly people.ResultsIn the ESD and surgery groups, the overall mortality rates were 0/100 and 12.3/100 person years, incidence rates of recurrence were 2.13/100 and 11/100 person years, respectively. Kaplan–Meier survival analysis revealed no significant different in OS, DSS and RFS. Charlson comorbidity index (CCI) and depth of submucosal invasion were identified as risk factors for cancer recurrence in multivariate analysis. For elderly people, no significant differences were found in OS, DSS and RFS between different treatments.ConclusionESD are related to lower complication rates and shorter hospital stay than surgery in long-term outcomes for patients with pT1b SESCC. But in pT1b-SM2 patients, we still need long-term follow-up.

Assessment of dental and periodontal indices and Streptococcus mutans virulence in fragile X syndrome patients.

Fragile X syndrome (FXS) is the most common cause of hereditary genetic disorder in a single gene characterised by intellectual disability. Behavioural features such as autism, hyperactivity and anxiety disorder may be present. Biofilm development and pathogenicity of Streptococcus mutans may be altered because FXS renders the dental approach and oral hygiene more complex. The purpose of this study was to compare the levels of transcripts for VicRK and CovR of S. mutans isolated from FXS patients with the levels of transcripts for VicRK and CovR of standard strain ATCC, using a quantitative polymerase chain reaction (qPCR). The caries experience index was assessed by the International Caries Detection and Assessment System (ICDAS), Periodontal Condition Index (PCI) and Invasive Dental Treatment Need Index (INI). The clinical index findings revealed a high rate of caries cavities and bleeding on probing of FXS patients. When VicRK and CovR transcript levels were compared with the reference strain, Fragile X patients were found to have significantly higher values. The present study demonstrated that FXS patients have more adverse clinical conditions, with increased biofilm accumulation and virulence. When combined with behavioural abnormalities, these patients become even more vulnerable to dental caries.

Cytochrome c oxidase IV isoform 1 (COX4-1) regulates the proliferation, migration and invasion of trophoblast cells via modulating mitochondrial function

IntroductionSpontaneous miscarriage is a common complication of early pregnancy. Previous studies have shown that mitochondrial function plays an important role in establishment of a successful pregnancy. Cytochrome c oxidase subunit 4 isoform 1 (COX4I1), a component of electron transport chain complex Ⅳ, is required for coupling the rate of ATP production to energetic requirements. However, there is very limited research on its role in trophoblast biology and how its dysfunction may contribute to spontaneous miscarriage. MethodsPlacental villi (7–10 weeks gestational age) collected from either induced termination of pregnancy or after spontaneous miscarriage were examined for expression of COX4I1. COX4I1 was knocked down by siRNA transfection of primary isolates of EVT cells. Real-time cell analysis (RTCA) and 5-Ethynyl-2′-deoxyuridine (EdU) were used to detect changes in proliferation ability after COX4I1 knockdown of EVT cells. Migration and invasion indices were determined by RTCA. Mitochondrial morphology was observed via MitoTracker staining. Oxidative phosphorylation, ATP production, and glycolysis in COX4I1-deficient cells and controls were assessed by a cellular energy metabolism analyzer (Seahorse). ResultsIn placental villous tissue, COX4I1 expression was significantly decreased in the spontaneous miscarriage group. Knockdown of COX4I1 inhibited EVT cell proliferation, increased the migration and invasion ability and mitochondrial fusion of EVT cells. Mitochondrial respiration and glycolysis were impaired in COX4I1-deficient EVT cells. Knockdown of MMP1 could rescue the increased migration and invasion induced by COX4I1 silencing. DiscussionLow expression of COX4I1 leads to mitochondrial dysfunction in EVT, resulting in altered trophoblast function, and ultimately to pregnancy loss.

Cardiomyocyte Specific MLK3 Deletion Opposes LV Dysfunction and Cardiac Fetal Gene Re-Expression

Study Objective: To determine the cardiac myocyte (CM) and blood pressure-independent effects of Mixed lineage kinase 3 (MLK3) in the regulation of left ventricular (LV) function at baseline and in response to pathological stress. Background: MLK3 functions as a direct substrate effector of cGMP-dependent protein kinase 1α (PKG1α). Whole-body MLK3 deletion in mice increases cardiac dysfunction and remodeling after pressure overload and prevents the therapeutic effect of cGMP augmentation on LV function. However, MLK3 deletion also causes hypertension, which may confound these findings. Hypothesis: MLK3 opposes LV dysfunction through a blood pressure-independent function in the cardiac myocyte (CM). Methods: We generated mice harboring LoxP sites flanking the MAP3K11 gene encoding MLK3 (MLK3fl/fl) and crossed them with αMHC-Cre transgenic mice, enabling constitutive postnatal cardiac myocyte-specific MLK3 deletion (CMKO). Male and female 3- and 6-month-old MLK3 CMKO and control MLK3 intact (MLK3fl/fl Cre-) littermates were studied in the basal state. We also performed transaortic constriction (TAC) or sham surgery for 4 weeks on 3-month-old male mice. We assessed LV structure and function by organ mass, echocardiography, pressure volume loop analysis, qPCR, and immunoblot. In basal and TAC studies, we used age-matched αMHC-Cre x MLK3+/+ (non-floxed) mice as additional controls. Results: MLK3 gene excision in CMs was confirmed by PCR. By 6 months of age, MLK3 CMKO mice displayed: progressive reduction in LV ejection fraction; increase in LV internal diameter; and LV hypertrophy, indicating LV dysfunction and pathological remodeling, compared with littermate controls or with αMHC-Cre x MLK3+/+ non-floxed mice. This effect was more prominent in females than in males. LV fetal gene expression did not differ between genotypes at 3 months. At 6 months of age, however, the fetal genes nppa, RCAN, and CTGF were significantly upregulated in both male and female MLK3 CMKO mice, compared with MLK3 intact, indicating pathological remodeling. After 4-week TAC, MLK3 CMKO LVs developed more severe reduction in LV systolic function compared with MLK3 intact littermates as assayed by echocardiographic measures of LV ejection fraction; and invasive hemodynamic indices of preload recruitable stroke work, maximum LV pressure and LV developed pressure. The MLK3 CMKO LVs also demonstrated a more eccentric remodeling phenotype in which LV mass/tibia length, LV end diastolic and end systolic diameters increased more severely in CMKO mice, with corresponding reduced LV wall thicknesses. Finally, lung mass/tibia length was elevated in the MLK3 CMKO TAC mice compared to MLK3 intact TAC littermates, indicating overt heart failure. Conclusion: (1) MLK3 functions as a tonic inhibitor of LV dysfunction and pathological remodeling through a role in the CM, possibly through sex-specific mechanisms. (2) Intact MLK3 is required for normal LV compensation and concentric remodeling in response to pressure overload. These findings have important clinical implications, as drugs which activate PKG1 in heart failure improve outcomes but are limited by excess hypotension. As a myocardial PKG1 substrate which opposes pathological LV remodeling through blood pressure-independent mechanisms, MLK3 may represent a candidate therapeutic target for heart failure. NIH 1R01HL162919. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A new workflow for warning and controlling the water invasion

Warning and controlling the water invasion in water-driving reservoirs is significant because water invasion will seriously hamper well productivity and gas recovery. Unfortunately, there are few comprehensive methods to control water invasion. First, we establish and verify a water invasion model of reservoir scale. Then, a new workflow for warning and controlling the water invasion is proposed using the numerical simulation method. The workflow first judges the water invasion characteristics, determines the water invasion index based on the production data, and then controls the water invasion by finding and closing the perforation layer of serious water production. Finally, the optimal water control scheme is obtained by comparing water and gas production. The results show that the accuracy of the geological reserves of the established water invasion model is 99% and has a good pressure fitting result. The early warning chart for the gas reservoir in the west of Amu Darya B area is drawn, including the early warning pressure and the level 1, level 2, and level 3 early warning water–gas ratio, which is convenient for field application. For the water-driving wells west of area B, the early warning value of the water–gas ratio increases with the increase of gas production rate during fixed production and decreases with the increase of bottom hole pressure during constant pressure production. Closing the harmful perforation from the water-finding study will significantly reduce the water while retaining the gas production. After water control technology, water production decreased by 90.9%, while gas production decreased by only 9.7%.