Risk of cervical high-grade squamous intraepithelial neoplasia in cytologic negative and persistently high-risk human papillomavirus positive patients according to genotypes: a retrospective single center analysis.

In January 2020, a different cervical cancer screening program started in Germany. Women above the age of 35 are recommended to have a combined HPV and cytology swab every three years. Showing persistent high-risk human papillomavirus (hrHPV), cytologic negative cervical samples at baseline and after 12 months, patients are referred to colposcopy. Entailing considerable additional workload due to the required colposcopies, we analyzed the risk of high-grade cervical intraepithelial neoplasia (CIN 3) in cytologic negative and persistent hrHPV women according to their hrHPV genotypes.Methods In this single center retrospective study, patients with persistent hrHPV, cytology negative cervical samples from our certified Colposcopy Unit in 2020 and 2021 were analyzed. Patient demographics, hrHPV types, biopsy rates and histological reports were collected.Results During the study, 69 patients were enrolled. Most frequent hrHPV genotypes were: hrHPV other 72.5%; HPV 16, 20.3% and HPV 18, 7.2%. Colposcopy showed no or minor changes in 92.7% and major changes in 7.2%. CIN 3 was found in 7 patients (10.1%). Prevalence of CIN 3 by hrHPV genotypes was 27.3% for HPV16, 20.0% for HPV18 and 7.1% for HPVO. A statistically significant dependency between hrHPV and cervical intraepithelial neoplasia was demonstrated (p = 0.048).Conclusion Within this single center study of persistent hrHPV, cytologic negative samples, patients with HPV 16 were more likely to have high-grade disease compared to other hrHPV subtypes. Larger prospective randomized trials are needed to substantiate our results and obtain adjusted cervical cancer screening time intervals according to the hrHPV genotypes.

High-grade neuroendocrine head and neck cancer: Case series and review of the literature.

BACKGROUND: High-grade neuroendocrine cancers (NEC) of the head and neck (HN) are rare and aggressive, accounting for ≤1 % of all HN cancers, with a 5-year overall survival (OS) of ≤20 %. This case series examines clinical characteristics, treatments, and outcomes of patients diagnosed at a regional UK HN cancer centre over the last 23 years. METHODS: A retrospective review of medical records was conducted for all patients diagnosed with NEC HN from 1st January 2000 until 1st March 2023 at Velindre Cancer Centre. RESULTS: During the study period, 19 cases of NEC HN were identified, primarily affecting males (n = 15, 79 %). Median age of 67 years (range: 44-86). At diagnosis, 32 % of patients (n = 6) were smokers. The most common primary tumour sites were larynx (n = 5, 26.3 %) and sinonasal (n = 5, 26.3 %). Most patients presented with advanced loco-regional disease or distant metastasis, with stage IVA (n = 6, 32 %) and stage IVC (n = 6, 32 %) being the most common. The key pathology marker was synaptophysin, present in 100 % of the tested patients (n = 15). In the study, of the 12 patients with non-metastatic disease, 10 received a combination of treatments that included radiotherapy (RT). Some of these patients also received chemotherapy (CT) at the same time as their radiotherapy. Surgery alone was used in two patients with stage II disease. Seven subjects had complete responses, and one achieved a partial response. Among the seven metastatic patients, three received CT, and one underwent palliative RT, all achieving a partial response. In all cases, the CT used was carboplatin and etoposide. After a median follow-up of 11 months (range: 1-96), the median OS was 27 months for the overall population, 51 months for those treated radically, and three months for metastatic patients with palliative treatment. The 1-year OS for all patients was 54.3 %, the 2-year OS was 46.5 %, and the 5-year OS was 23.3 %. Among patients treated radically, these rates were 65.3 %, 52.2 %, and 26.1 %, respectively. For patients treated palliatively, the 1-year OS was 33.3 %. CONCLUSION: This case series contributes preliminary observations on the characteristics and management of non-metastatic NEC HN, suggesting potential benefits from multimodality treatment strategies. Given the small cohort size, these observations should be interpreted cautiously and seen as a foundation for further research.

The relationship between low levels of albuminuria and mortality among adults without major cardiovascular risk factors.

AIMS: The determine if elevated levels of albuminuria within the low range (urinary albumin-to-creatinine ratio, UACR <30 mg/g) are linked to cardiovascular death in adults lacking major cardiovascular risk factors. METHODS: The association between UACR and cardiovascular mortality was investigated among 12,835 participants in the 1999-2014 National Health and Nutrition Examination Survey using Cox proportional hazard models and confounder-adjusted survival curves. We excluded participants with baseline cardiovascular disease, hypertension, diabetes, pre-diabetes, estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2, currently pregnant, and those who had received dialysis in the last year. RESULTS: Over a median follow-up of 12.3 years, 110 and 621 participants experienced cardiovascular and all-cause mortality. In multivariable-adjusted models, each doubling of UACR was associated with a 36% higher risk of cardiovascular death [HR 1.36 (95% confidence interval (CI) 1.02-1.82)] and a 24% higher risk of all-cause mortality [HR 1.24 (95% CI 1.10-1.39)]. The 15-year adjusted cumulative incidences of cardiovascular mortality were 0.91%, 0.99%, and 2.1% for UACR levels of <4.18 mg/g, 4.18 to <6.91 mg/g, and ≥6.91 mg/g, respectively. The 15-year adjusted cumulative incidences of all-cause mortality were 5.1%, 6.1%, and 7.4% for UACR levels of <4.18 mg/g, 4.18 to <6.91 mg/g, and ≥6.91 mg/g, respectively. CONCLUSIONS: Adults with elevated levels of albuminuria within the low range (UACR <30 mg/g) and no major cardiovascular risk factors had elevated risks of cardiovascular and all-cause mortality. The risks increased linearly with higher albuminuria levels. This emphasizes a risk gradient across all albuminuria levels, even within the supposedly normal range, adding to the existing evidence.

In this study of 12,835 adults without major cardiovascular risk factors (such as hypertension, cardiovascular disease, diabetes, pre-diabetes, or chronic kidney disease), we investigated the association between higher albuminuria levels within the low range (urine albumin-to-creatinine ratio (UACR) <30 mg/g) and both cardiovascular and all-cause mortality. Our findings revealed a linear increase in excess risk for both outcomes with rising albuminuria among relatively healthy adults. Each doubling of albuminuria was associated with a 36% higher risk of cardiovascular death (HR 1.36, 95% CI 1.02-1.82) and a 24% higher risk of all-cause mortality (HR 1.24, 95% CI 1.10-1.39). Each 10 mg/g increase in albuminuria was associated with 66% higher risk of cardiovascular mortality (HR 1.66, 95% CI 1.20, 2.28) and 41% higher risk of all-cause mortality (HR 1.41, 95% CI 1.17-1.68). These results challenge the assumption that UACR values below 30 mg/g are non-prognostic in adults without major cardiovascular risk factors.

Proposal for an optimised definition of adverse pathology (unfavourable histology) that predicts metastatic risk in prostatic adenocarcinoma independent of grade group and pathological stage.

AIMS: Histological grading of prostate cancer is a powerful prognostic tool, but current criteria for grade assignment are not fully optimised. Our goal was to develop and test a simplified histological grading model, based heavily on large cribriform/intraductal carcinoma, with optimised sensitivity for predicting metastatic potential. METHODS AND RESULTS: Two separate non-overlapping cohorts were identified: a 419-patient post-radical prostatectomy cohort with long term clinical follow-up and a 209-patient post-radical prostatectomy cohort in which all patients had pathologically confirmed metastatic disease. All prostatectomies were re-reviewed for high-risk histological patterns of carcinoma termed 'unfavourable histology'. Unfavourable histology is defined by any classic Gleason pattern 5 component, any large cribriform morphology (> 0.25 mm) or intraductal carcinoma, complex intraluminal papillary architecture, grade 3 stromogenic carcinoma and complex anastomosing cord-like growth. For the outcome cohort, Kaplan-Meier analysis compared biochemical recurrence, metastasis and death between subjects with favourable and unfavourable histology, stratified by pathological stage and grade group. Multivariable Cox proportional hazards models evaluated adding unfavourable histology to the Memorial Sloan Kettering Cancer Center (MSKCC) post-prostatectomy nomogram and stratification by percentage of unfavourable histology. At 15 years unfavourable histology predicted biochemical recurrence, with sensitivity of 93% and specificity of 88%, metastatic disease at 100 and 48% and death at 100 and 46%. Grade group 2 prostate cancers with unfavourable histology were associated with metastasis independent of pathological stage, while those without had no risk. Histological models for prediction of metastasis based on only large cribriform/intraductal carcinoma or increasing diameter of cribriform size improved specificity, but with lower sensitivity. Multivariable Cox proportional hazards models demonstrated that unfavourable histology significantly improved discriminatory power of the MSKCC post-prostatectomy nomogram for biochemical failure (likelihood ratio test P < 0.001). In the retrospective review of a separate RP cohort in which all patients had confirmed metastatic disease, none had unequivocal favourable histology. CONCLUSIONS: Unfavourable histology at radical prostatectomy is associated with metastatic risk, predicted adverse outcomes better than current grading and staging systems and improved the MSKCC post-prostatectomy nomogram. Most importantly, unfavourable histology stratified grade group 2 prostate cancers into those with and without metastatic potential, independent of stage. While unfavourable histology is driven predominantly by large cribriform/intraductal carcinoma, the recognition and inclusion of other specific architectural patterns add to the sensitivity for predicting metastatic disease. Moreover, a simplified dichotomous model improves communication and could increase implementation.

Navigating Complexities: Vitamin D, Skin Pigmentation, and Race.

Vitamin D plays a critical role in many physiological functions, including calcium metabolism and musculoskeletal health. This commentary aims to explore the intricate relationships among skin complexion, race, and 25-hydroxyvitamin D (25[OH]D) levels, focusing on challenges the Endocrine Society encountered during clinical practice guideline development. Given that increased melanin content reduces 25(OH)D production in the skin in response to UV light, the guideline development panel addressed the potential role for 25(OH)D screening in individuals with dark skin complexion. The panel discovered that no randomized clinical trials have directly assessed vitamin D related patient-important outcomes based on participants' skin pigmentation, although race and ethnicity often served as presumed proxies for skin pigmentation in the literature. In their deliberations, guideline panel members and selected Endocrine Society leaders underscored the critical need to distinguish between skin pigmentation as a biological variable and race and ethnicity as socially determined constructs. This differentiation is vital to maximize scientific rigor and, thus, the validity of resulting recommendations. Lessons learned from the guideline development process emphasize the necessity of clarity when incorporating race and ethnicity into clinical guidelines. Such clarity is an essential step toward improving health outcomes and ensuring equitable healthcare practices.

Curcumin-loaded food-grade nano-silica hybrid material exhibiting improved photodynamic effect and its application for the preservation of small yellow croaker (Larimichthys polyactis).

Two types of curcumin-loaded food-grade nano-silica (F-SiO2) hybrid materials were successfully synthesized using the rotary evaporation method (F-SiO2@Cur) and the adsorption method (Cur@F-SiO2). The microstructure and spectral analyses confirmed that the curcumin in F-SiO2@Cur was loaded within the nanopores in a non-aggregate form rather than being adsorbed onto the surface (Cur@F-SiO2). Additionally, F-SiO2@Cur exhibited remarkable water solubility (1510 ± 50.33 µg/mL) and photostability (a photodegradation ratio of only 59.22 %). Importantly, F-SiO2@Cur obtained a higher capacity for the generation of singlet oxygen (1O2) compared to control groups. Consequently, F-SiO2@Cur-mediated photodynamic inactivation (PDI) group attained the highest score in sensory evaluation and the best color protection effect in PDI experiment of small yellow croaker (Larimichthys polyactis) at 4 °C. Moreover, F-SiO2@Cur could effectively controlled total volatile basic nitrogen (TVB-N) content, pH, and total viable count (TVC), thereby prolonging the shelf life. Therefore, F-SiO2@Cur-mediated PDI is an effective fresh-keeping technology for aquatic products.

Radiomic Prediction of CCND1 Expression Levels and Prognosis in Low-grade Glioma Based on Magnetic Resonance Imaging.

OJECTIVES: Low-grade glioma (LGG) is associated with increased mortality owing to recrudescence and the tendency for malignant transformation. Therefore, it is imperative to discover novel prognostic biomarkers as existing traditional prognostic biomarkers of glioma, including clinicopathological features and imaging examinations, are unable to meet the clinical demand for precision medicine. Accordingly, we aimed to evaluate the prognostic value of cyclin D1 (CCND1) expression levels and construct radiomic models to predict these levels in patients with LGG MATERIALS AND METHODS: A total of 412 LGG cases from The Cancer Genome Atlas (TCGA) were used for gene-based prognostic analysis. Using magnetic resonance imaging (MRI) images stored in The Cancer Imaging Archive with genomic data from TCGA, 149 cases were selected for radiomics feature extraction and model construction. After feature extraction, the radiomic signature was constructed using logistic regression (LR) and support vector machine (SVM) analyses. RESULTS: CCND1 was identified as a prognosis-related gene with differential expression in tumor and normal samples and plays a role in regulating both the cell cycle and immune response. Landmark analysis revealed that high-expression levels of CCND1 were beneficial for survival (P < 0.05) in advanced LGG. Four optimal radiomics features were selected to construct radiomics models. The performance of LR and SVM achieved areas under the curve of 0.703 and 0.705, as well as 0.724 and 0.726 in the training and validation sets, respectively. CONCLUSION: Elevated levels of CCND1 expression could impact the prognosis of patients with LGG. MRI-based radiomics, especially the AUC values, can serve as a novel tool for predicting CCND1 expression and understanding the correlation between elevated CCND1 expression and prognosis. AVAILABILITY OF DATA AND MATERIALS: The datasets analyzed during the current study are available in the TCGA, TCIA, UCSC XENA and GTEx repository, https://portal.gdc.cancer.gov/, https://www.cancerimagingarchive.net/, https://xenabrowser.net/datapages/, https://www.gtexportal.org/home/.

Clinical Outcomes of Splenic Artery Embolization Versus Splenectomy in the Management of Hemodynamically Stable High-Grade Blunt Splenic Injuries: A National Analysis.

INTRODUCTION: This study aims to compare the outcomes of splenic artery embolization (SAE) versus splenectomy in adult trauma patients with high-grade blunt splenic injuries. METHODS: This retrospective analysis of the American College of Surgeons Trauma Quality Improvement Program database (2017-2021) compared SAE versus splenectomy in adults with blunt high-grade splenic injuries (grade ≥ IV). Patients were stratified first by hemodynamic status then splenic injury grade. Outcomes included in-hospital mortality, intensive care unit length of stay (ICU-LOS), and transfusion requirements at four and 24 h from arrival. RESULTS: Three thousand one hundred nine hemodynamically stable patients were analyzed, with 2975 (95.7%) undergoing splenectomy and 134 (4.3%) with SAE. One thousand eight hundred sixty five patients had grade IV splenic injuries, and 1244 had grade V. Patients managed with SAE had 72% lower odds of in-hospital mortality (odds ratio [OR] 0.28; P = 0.002), significantly shorter ICU-LOS (7 versus 9 d, 95%, P = 0.028), and received a mean of 1606 mL less packed red blood cells at four h compared to those undergoing splenectomy. Patients with grade IV or V injuries both had significantly lower odds of mortality (IV: OR 0.153, P < 0.001; V: OR 0.365, P = 0.041) and were given less packed red blood cells within four h when treated with SAE (2056 mL versus 405 mL, P < 0.001). CONCLUSIONS: SAE may be a safer and more effective management approach for hemodynamically stable adult trauma patients with high-grade blunt splenic injuries, as demonstrated by its association with significantly lower rates of in-hospital mortality, shorter ICU-LOS, and lower transfusion requirements compared to splenectomy.

The impact of an online course on agreement rates of the certainty of evidence assessment using GRADE: a before-and-after study.

BACKGROUND/AIM: The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach is a systematic method for assessing the certainty of evidence (CoE) and strength of recommendations in healthcare. We aimed to verify the effects of an online-based GRADE course on multi-rater consistency in the evaluation of the CoE in systematic reviews (SRs) analysis. STUDY DESIGN AND SETTINGS: Sixty-five Brazilian methodologists and researchers participated in an online course over eight weeks. Asynchronous lessons and weekly synchronous meetings addressed the GRADE system in the context of CoE assessment. We asked participants to evaluate the CoE of random SRs (two before and another two after the course). Analyzes focused on the multi-rater agreement with a standard response, in the inter-rater agreement, and before-after changes in the proportion of participants that rated down the domains. RESULTS: 48 individuals completed the course. Participants presented improvements in the raters' assessment of the CoE using the GRADE approach after the course. The multi-rater consistency of indirectness, imprecision, and the overall CoE increased after the course, as well as the agreement between raters and the standard response. Furthermore, interrater reliability increased for risk of bias, inconsistency, indirectness, publication bias, and overall CoE, indicating progress in between-raters consistency. After the course, approximately 78% of individuals rated down the overall CoE to a low/very low degree, and participants presented more explanations for the judgment of each domain. CONCLUSION: An online GRADE course improved the consistency and agreement of the CoE assessment by Brazilian researchers. Online training courses have the potential to improve skills in guideline methodology development.

Exploring a distinct FGFR2::DLG5 rearrangement in a low-grade neuroepithelial tumor: A case report and mini-review of protein fusions in brain tumors.

We report the novel clinical presentation of a primary brain neoplasm in a 30-year-old man with a mass-like area in the anteromedial temporal lobe. Histopathological analysis revealed a low-grade neuroepithelial tumor with cytologically abnormal neurons and atypical glial cells within the cerebral cortex. Molecular analysis showed a previously undescribed FGFR2::DLG5 rearrangement. We discuss the clinical significance and molecular implications of this fusion event, shedding light on its potential impact on tumor development and patient prognosis. Additionally, an extensive review places the finding in this case in the context of protein fusions in brain tumors in general and highlights their diverse manifestations, underlying molecular mechanisms, and therapeutic implications.

Updated endometrial cancer FIGO staging: the role of MRI in determining newly included histopathological criteria.

PURPOSE: Endometrial cancer (EC) is among the prevalent malignancies in gynecology, showing an increasing occurrence and mortality rate. The updated 2023 FIGO staging integrates both histopathological and molecular analyses, which significantly impact the prognosis and treatment approaches. This research aims to examine the effectiveness of MRI in identifying essential histopathological tumor features, including histological subtype, grade, and lymphovascular space invasion. METHODS: A total of 106 patients diagnosed with EC from February 2018 to December 2023 underwent preoperative pelvic MRI. Surgical procedures followed ESMO guidelines, with histopathological assessments using FIGO 2009 criteria. Two radiologists independently evaluated MRI images, measuring maximum tumor size, minimum tumor ADC value (using a free-hand ROI technique), and ADC tumor/myometrium ratio. MRI findings were compared with histopathological data. RESULTS: Peritoneal implant presence and tumor size exhibited significant differences between endometrioid adenocarcinoma (EAC) and non-endometrioid endometrial carcinoma (NEEC), with p values of < 0.001 and 0.003, respectively. Significant differences in age, tumor size, ADC tumor, and ADC tumor/myometrium between low-grade and high-grade tumors were observed, with p values of < 0.001, 0.004, 0.006, and 0.011, respectively. Increased tumor size, reduced ADC tumor, ADC tumor/myometrium, and pelvic peritoneal implant presence were significantly associated with LVSI, with p values of < 0.001, 0.001, 0.002, and 0.001, respectively. The AUC values for tumor size, ADC tumor, and ADC tumor/myometrium were 0.842, 0.781 and 0.747, respectively, in distinguishing between low and high-grade endometrial tumors. Similarly, obtained AUC values for predicting LVSI were 0.836, 0.719, and 0.696, respectively. CONCLUSION: Our study emphasizes MRI's role in predicting tumor characteristics such as histological subtype, grade, and LVSI based on updated FIGO criteria. By highlighting the potential of MRI, this research contributes to our comprehension of improving diagnostic and clinical management for EC. Further multicenter studies are warranted to validate these findings and establish MRI's role in EC management.

Peripheral blood immune cell parameters in patients with high-grade squamous intraepithelial lesion (HSIL) and cervical cancer and their clinical value: a retrospective study.

Objective: The objective of this study was to delineate the profile of peripheral blood lymphocytic indices in patients afflicted with high-grade squamous intraepithelial lesions (HSIL) and cervical neoplasms, and to elucidate the correlation of these hematologic markers with the clinicopathological spectra in individuals diagnosed with cervical carcinoma. Methods: We adopted a retrospective case-control modality for this investigation. An aggregate of 39 HSIL patients and 42 cervical carcinoma patients, who were treated in our facility from July 2020 to September 2023, were meticulously selected. Each case of cervical malignancy was confirmed through rigorous histopathological scrutiny. Concomitantly, 31 healthy female individuals, who underwent prophylactic health evaluations during the corresponding timeframe, were enlisted as the baseline control group. We systematically gathered and analyzed clinical demographics, as well as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), from peripheral blood samples. Pearson's correlation coefficient was deployed to dissect the interrelation between peripheral NLR and PLR concentrations and the clinicopathological features in the cervical cancer group. Results: Inter-group comparative analysis unveiled statistically substantial variances in the PLR and NLR values among the tripartite clusters (F = 36.941, 14.998, P < 0.001, respectively). Although discrepancy in NLR (P = 0.061) and PLR (P = 0.759) measures between the groups of cervical carcinoma and HSIL was not statistically appreciable, these indices were markedly elevated in the cervical carcinoma faction as juxtaposed with the normative control group (t = 5.094, 5.927; P < 0.001 for both parameters). A discernible gradation in peripheral blood PLR and NLR concentrations was noted when stratified by clinical stage and the profundity of myometrial invasion in cervical cancer subjects (P < 0.001). The correlation matrix demonstrated a positive liaison between peripheral blood PLR and the clinical gradation, as well as the invasiveness of the neoplastic cells into the muscularis propria (P < 0.05); a similar trend was observed with the NLR values (P < 0.05). Conclusion: Augmented NLR and PLR levels in peripheral blood specimens are indicative of HSIL and cervical malignancy. These hematological parameters exhibit a pronounced interconnection with clinical staging and muscular wall penetration depth, serving as potential discriminative biomarkers for the diagnosis and prognosis of cervical cancer.

Mitochondrial RNA modification-based signature to predict prognosis of lower grade glioma: a multi-omics exploration and verification study.

Mitochondrial RNA modification (MRM) plays a crucial role in regulating the expression of key mitochondrial genes and promoting tumor metastasis. Despite its significance, comprehensive studies on MRM in lower grade gliomas (LGGs) remain unknown. Single-cell RNA-seq data (GSE89567) was used to evaluate the distribution functional status, and correlation of MRM-related genes in different cell types of LGG microenvironment. We developed an MRM scoring system by selecting potential MRM-related genes using LASSO regression analysis and the Random Survival Forest algorithm, based on multiple bulk RNA-seq datasets from TCGA, CGGA, GSE16011, and E-MTAB-3892. Analysis was performed on prognostic and immunological features, signaling pathways, metabolism, somatic mutations and copy number variations (CNVs), treatment responses, and forecasting of potential small-molecule agents. A total of 35 MRM-related genes were selected from the literature. Differential expression analysis of 1120 normal brain tissues and 529 LGGs revealed that 22 and 10 genes were upregulated and downregulated, respectively. Most genes were associated with prognosis of LGG. METLL8, METLL2A, TRMT112, and METTL2B were extensively expressed in all cell types and different cell cycle of each cell type. Almost all cell types had clusters related to mitochondrial RNA processing, ribosome biogenesis, or oxidative phosphorylation. Cell-cell communication and Pearson correlation analyses indicated that MRM may promoting the development of microenvironment beneficial to malignant progression via modulating NCMA signaling pathway and ICP expression. A total of 11 and 9 MRM-related genes were observed by LASSO and the RSF algorithm, respectively, and finally 6 MRM-related genes were used to establish MRM scoring system (TRMT2B, TRMT11, METTL6, METTL8, TRMT6, and TRUB2). The six MRM-related genes were then validated by qPCR in glioma and normal tissues. MRM score can predict the malignant clinical characteristics, abundance of immune infiltration, gene variation, clinical outcome, the enrichment of signaling pathways and metabolism. In vitro experiments demonstrated that silencing METTL8 significantly curbs glioma cell proliferation and enhances apoptosis. Patients with a high MRM score showed a better response to immunotherapies and small-molecule agents such as arachidonyl trifluoromethyl ketone, MS.275, AH.6809, tacrolimus, and TTNPB. These novel insights into the biological impacts of MRM within the glioma microenvironment underscore its potential as a target for developing precise therapies, including immunotherapeutic approaches.

The association between non-HDL cholesterol and high-grade pancreatic neuroendocrine neoplasms.

PURPOSE: High-density lipoprotein cholesterol (HDL-c) plays an important role in tumorigenesis in several endocrine-related cancers. Few studies have shown the effect of non-HDL-c in malignant tumors. The present study aimed to identify the association between non-HDL-c and high-grade pancreatic neuroendocrine neoplasms (PNENs). METHODS: A total of 197 PNEN patients who underwent surgery were analyzed retrospectively. Clinical and histopathological features, such as patients' age and sex, tumor location and size, tumor grade, the level of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and fasting plasma-glucose levels were obtained. Non-HDL-c was calculated as total cholesterol - HDL-c. The relationships between those features and high-grade PNENs were identified using logistic regression analysis. RESULTS: Among the 197 patients with PNENs, a lower HDL-c level was more common seen in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.05). The non-HDL-c/HDL-c ratio was greater in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.01). Similarly, a greater proportion of patients with a non-HDL-c/HDL-c ratio larger than 5 was found in patients with poorly differentiated PNENs than in those with well-differentiation PNENs (P < 0.01). Multivariate logistic analysis showed that the non-HDL-c/HDL-c ratio was positively associated with poorly differentiated PNENs (odds ratio (OR) = 1.45, 95% conference interval (CI):1.13-1.87). Similarly, the risk of poorly differentiated PNENs increased significantly in patients with a non-HDL-c/HDL-c greater than 5 (OR = 14.13, 95%CI: 2.98-66.89). The risk of high-grade PNENs increased in patients with a high non-HDL-c/HDL-c ratio (OR = 1.27, 95% CI: 1.04-1.55), and the risk also increased markedly when the ratio was greater than 5 (OR = 5.00, 95%CI: 1.28-19.49). CONCLUSIONS: A high ratio of non-HDL-c/HDL-c was associated with high-grade PNENs or poorly differentiated PNENs.

Exploring novel approaches in the systemic therapy of low-grade serous carcinoma of the ovary: a literature review.

By presenting a comprehensive analysis of low-grade serous carcinomas (LGSCs), a subset of epithelial ovarian cancers, this review delves into their distinct molecular characteristics, clinicopathological features and systemic therapy options, emphasizing their differences from high-grade serous carcinomas (HGSCs). Notably, LGSCs exhibit prevalent RAS/RAF/MEK/MAPK pathway activation, KRAS and BRAF mutations, and infrequent p53 mutations. While chemotherapy is commonly employed, LGSCs display lower responsiveness compared to HGSCs. Hormone therapy, particularly endocrine maintenance therapy, is explored due to the higher estrogen receptor expression. Novel therapeutic approaches involving CDK4/6 inhibitors, MEK inhibitors, and antiangiogenic agents like bevacizumab are also investigated. Ongoing clinical trials are striving to enhance LGSC treatment strategies, offering valuable insights for future therapeutic advancements in this challenging ovarian cancer subtype.

Awake Craniotomy for a Frontal Astrocytoma: A Case Report.

Awake craniotomy is a surgical procedure that has been gaining significance over the past decades. Neuronavigation is an intraoperative technology that locates tumors and monitors the brain cortex during awake craniotomy. The presence of cerebral low-grade gliomas in the frontal lobe creates a risk of affecting vital centers of the brain cortex during surgery. We present a clinical case of a 42-year-old male patient who entered the neurosurgery clinic with a clinical manifestation of headache for two months. MRI showed evidence of the recurrence of a left frontal glioma. Differential diagnoses of frontal gliomas include metastases, abscesses, and cysts. The pathophysiologic background of the disease is the mutation of neuroglial cells, which leads to an abnormal and uncontrollable proliferation. Under sleep-awake anesthesia, operative treatment was performed through left frontal awake craniotomy under neuronavigation. As a result, a total excision was achieved. Motor functions of the right limbs and speech have been preserved. The patient was mobilized on the day after the intervention. Surgery-related complications were not observed. The patient had relief from the symptoms and was discharged on the fifth day. Awake craniotomy combined with neuronavigation was the most efficient and the least harmful method for the excision of the tumor. For low-grade gliomas localized in the frontal area of the encephalon, awake craniotomy is the only secure option for surgery.

Clinical severity of aneurysmal subarachnoid hemorrhage over time: systematic review.

The incidence of aneurysmal subarachnoid hemorrhage (aSAH) is well studied. Yet, little is known about the trend of aSAH severity. This systematic review aims to analyze the distribution of aSAH severity over time. We performed a systematic review of the literature according to the PRISMA-P guidelines. We included studies from January 1968 up to December 2022. Studies were included if they either reported the severity of aSAH as single increments of the corresponding 5-point scale or as a binary measure (good grade 1-3, poor grade 4-5) on the Hunt and Hess (HH) or World Federation of Neurosurgical Societies (WFNS) scale. Studies with fewer than 50 patients, (systematic) reviews, and studies including non-aSAH patients were excluded. A total of 2465 publications were identified, of which 214 met the inclusion and exclusion criteria. In total, 102,845 patients with an aSAH were included. Over the last five decades the number of good-grade HH (0.741 fold, p = 0.004) and WFNS (0.749 fold, p < 0.001) has decreased. Vice versa, an increase in number of poor grade HH (2.427 fold, p = 0.004), WFNS (2.289 fold, p < 0.001), as well as HH grade 5 (6.737 fold, p = 0.010), WFNS grade 4 (1.235 fold, p = 0.008) and WFNS grade 5 (8.322 fold, p = 0.031) was observed. This systematic review shows a worldwide 2-3 fold increase of poor grade aSAH patients and an 6-8 fold increase of grade 5 patients, over the last 50 years. Whether this evolution is due to more severe hemorrhage, improvements in neuro-intensive care and prehospital management, or to a change in grading behavior is unknown. This study strongly emphasizes the necessity for an improved grading system to differentiate grade 4 and grade 5 patients for meaningful clinical decision- making.

Awake surgery for a deaf patient using sign language: A case report.

Background: Although awake surgery is the gold standard for resecting brain tumors in eloquent regions, patients with hearing impairment require special consideration during intraoperative tasks. Case Description: We present a case of awake surgery using sign language in a 45-year-old right-handed native male patient with hearing impairment and a neoplastic lesion in the left frontal lobe, pars triangularis (suspected to be a low-grade glioma). The patient primarily communicated through sign language and writing but was able to speak at a sufficiently audible level through childhood training. Although the patient remained asymptomatic, the tumors gradually grew in size. Awake surgery was performed for tumors resection. After the craniotomy, the patient was awake, and brain function mapping was performed using tasks such as counting, picture naming, and reading. A sign language-proficient nurse facilitated communication using sign language and the patient vocally responded. Intraoperative tasks proceeded smoothly without speech arrest or verbal comprehension difficulties during electrical stimulation of the tumor-adjacent areas. Gross total tumor resection was achieved, and the patient exhibited no apparent complications. Pathological examination revealed a World Health Organization grade II oligodendroglioma with an isocitrate dehydrogenase one mutant and 1p 19q codeletion. Conclusion: Since the patient in this case had no dysphonia due to training from childhood, the task was presented in sign language, and the patient responded vocally, which enabled a safe operation. Regarding awake surgery in patients with hearing impairment, safe tumor resection can be achieved by performing intraoperative tasks depending on the degree of hearing impairment and dysphonia.