High-grade serous carcinoma of the fallopian tube in a young woman with chromosomal 4q abnormality: A case report.

BACKGROUND: Few studies have reported an association between an increased risk of acquiring cancers and survival in patients with 4q deletion syndrome. This study presents a rare association between chromosome 4q abnormalities and fallopian tube high-grade serous carcinoma (HGSC) in a young woman. CASE SUMMARY: A 35-year-old woman presented with acute dull abdominal pain and a known chromosomal abnormality involving 4q13.3 duplication and 4q23q24 deletion. Upon arrival at the emergency room, her abdomen appeared ovoid and distended with palpable shifting dullness. Ascites were identified through abdominal ultrasound, and computed tomography revealed an omentum cake and an enlarged bilateral adnexa. Blood tests showed elevated CA-125 levels. Paracentesis was conducted, and immunohistochemistry indicated that the cancer cells favored an ovarian origin, making us suspect ovarian cancer. The patient underwent debulking surgery, which led to a diagnosis of stage IIIC HGSC of the fallopian tube. Subsequently, the patient received adjuvant chemotherapy with carboplatin and paclitaxel, resulting in stable current condition. CONCLUSION: This study demonstrates a rare correlation between a chromosome 4q abnormality and HGSC. UBE2D3 may affect crucial cancer-related pathways, including P53, BRCA, cyclin D, and tyrosine kinase receptors, thereby possibly contributing to cancer development. In addition, ADH1 and DDIT4 may be potential influencers of both carcinogenic and therapeutic responses.

Prediction of WHO grade and methylation class of aggressive meningiomas: Extraction of diagnostic information from infrared spectroscopic data.

Background: Infrared (IR) spectroscopy allows intraoperative, optical brain tumor diagnosis. Here, we explored it as a translational technology for the identification of aggressive meningioma types according to both, the WHO CNS grading system and the methylation classes (MC). Methods: Frozen sections of 47 meningioma were examined by IR spectroscopic imaging and different classification approaches were compared to discern samples according to WHO grade or MC. Results: IR spectroscopic differences were more pronounced between WHO grade 2 and 3 than between MC intermediate and MC malignant, although similar spectral ranges were affected. Aggressive types of meningioma exhibited reduced bands of carbohydrates (at 1024 cm-1) and nucleic acids (at 1080 cm-1), along with increased bands of phospholipids (at 1240 and 1450 cm-1). While linear discriminant analysis was able to discern spectra of WHO grade 2 and 3 meningiomas (AUC 0.89), it failed for MC (AUC 0.66). However, neural network classifiers were effective for classification according to both WHO grade (AUC 0.91) and MC (AUC 0.83), resulting in the correct classification of 20/23 meningiomas of the test set. Conclusions: IR spectroscopy proved capable of extracting information about the malignancy of meningiomas, not only according to the WHO grade, but also for a diagnostic system based on molecular tumor characteristics. In future clinical use, physicians could assess the goodness of the classification by considering classification probabilities and cross-measurement validation. This might enhance the overall accuracy and clinical utility, reinforcing the potential of IR spectroscopy in advancing precision medicine for meningioma characterization.

Simulation-based caregiving skills training for family members of high-grade glioma patients.

Background: Because family caregivers of patients with a high-grade glioma experience high levels of distress and feel unprepared to perform the complex caregiving tasks associated with the disease and its treatment, we pilot-tested a caregiving skills intervention that integrates hands-on caregiving with coping skill training. Methods: In this single-arm trial, caregivers participated in a 4-session research nurse-led intervention involving simulation-based caregiving skills training at the hospital and psychoeducation delivered via videoconference. We collected measures of patients' and caregivers' psychological symptoms; caregivers' caregiving self-efficacy and role adjustment; and patients' cancer-related symptoms (MDASI) at baseline and again postintervention. We tracked feasibility data. Results: We approached 29 dyads of which 10 dyads (34%) consented. All patients (mean age: 60 years, 89% male) and caregivers (mean age: 58 years, 80% female, 80% spouses) completed the baseline and 7 dyads completed the follow-up assessments (attrition was related to patient's hospice transfer). Seven caregivers completed all 4 sessions and rated the program as beneficial. Paired t-tests revealed a significant improvement in caregiving self-efficacy at 6 weeks postintervention (t = -3.06, P = .02). Although improvements in caregiver role adjustment and patient and caregiver symptoms were not observed, no decreases in symptom burden or role adjustment were found during the follow-up period. Conclusions: This novel supportive care program appears to be safe, feasible, acceptable, and perceived as useful for caregivers of patients with high-grade glioma. Based on feasibility indicators and a signal of intervention efficacy, a randomized controlled trial is warranted.

Pathologic characterization of precursors and cholangiocarcinoma referring to peribiliary capillary plexus: a new pathologic approach to bile duct neoplasm.

The peribiliary capillary plexus (PCP) regularly and densely lines the basal side of the lining epithelia of normal bile ducts. To determine the pathology of the PCP in high-grade biliary intraepithelial neoplasms (BilINs) and intraductal papillary neoplasms of the bile duct (IPNBs), a precursor of cholangiocarcinoma (CCA), and CCA. Seventy-six cases of surgically resected high-grade BilIN and 83 cases of IPNB were histopathologically examined using endothelial immunostaining of PCP; all cases of high-grade BilIN and 40 cases of IPNB were associated with invasive CCA. Invasive and preinvasive neoplasms were pathologically examined referring to a two-layer pattern composed of biliary lining epithelia and underlying PCP unique to the bile duct. All high-grade BilIIN cases had an underlying single layer of capillaries, similar to PCP (PCP-like capillaries). In 43% of the 83 cases of IPNB, these capillaries were regularly distributed in almost all stalks and intervening stroma of intraluminal neoplastic components, while in the remaining 57% of IPNB, capillaries were sparsely or irregularly distributed in intraluminal components showing cribriform or solid growth patterns composed of striking atypical neoplastic epithelia. Invasive carcinomas associated with high-grade BilIN and IPNB were not lined with capillaries. The loss of PCP-like capillaries underlying high-grade BilIN and in stalks or stroma of IPNB may be involved in the malignant progression of these precursors. Immunostaining of PCP could be a new pathological tool for the evaluation of malignant progression and vascular supply in CCA and its precursors.

Radiomics predict the WHO/ISUP nuclear grade and survival in clear cell renal cell carcinoma.

OBJECTIVES: This study aimed to assess the predictive value of radiomics derived from intratumoral and peritumoral regions and to develop a radiomics nomogram to predict preoperative nuclear grade and overall survival (OS) in patients with clear cell renal cell carcinoma (ccRCC). METHODS: The study included 395 patients with ccRCC from our institution. The patients in Center A (anonymous) institution were randomly divided into a training cohort (n = 284) and an internal validation cohort (n = 71). An external validation cohort comprising 40 patients from Center B also was included. Computed tomography (CT) radiomics features were extracted from the internal area of the tumor (IAT) and IAT combined peritumoral areas of the tumor at 3 mm (PAT 3 mm) and 5 mm (PAT 5 mm). Independent predictors from both clinical and radiomics scores (Radscore) were used to construct a radiomics nomogram. Kaplan-Meier analysis with a log-rank test was performed to evaluate the correlation between factors and OS. RESULTS: The PAT 5-mm radiomics model (RM) exhibited exceptional predictive capability for grading, achieving an area under the curves of 0.80, 0.80, and 0.90 in the training, internal validation, and external validation cohorts. The nomogram and RM gained from the PAT 5-mm region were more clinically useful than the clinical model. The association between OS and predicted nuclear grade derived from the PAT 5-mm Radscore and the nomogram-predicted score was statistically significant (p < 0.05). CONCLUSION: The CT-based radiomics and nomograms showed valuable predictive capabilities for the World Health Organization/International Society of Urological Pathology grade and OS in patients with ccRCC. CRITICAL RELEVANCE STATEMENT: The intratumoral and peritumoral radiomics are feasible and promising to predict nuclear grade and overall survival in patients with clear cell renal cell carcinoma, which can contribute to the development of personalized preoperative treatment strategies. KEY POINTS: The multi-regional radiomics features are associated with clear cell renal cell carcinoma (ccRCC) grading and prognosis. The combination of intratumoral and peritumoral 5 mm regional features demonstrated superior predictive performance for grading. The nomogram and radiomics models have a broad range of clinical applications.

The adjunctive use of antimicrobial photodynamic therapy, light-emitting-diode photobiomodulation and ozone therapy in regenerative treatment of stage III/IV grade C periodontitis: a randomized controlled clinical trial.

OBJECTIVES: To assess the short-term efficacy of multiple sessions of antimicrobial photodynamic therapy (aPDT), light-emitting-diode (LED) photobiomodulation, and topical ozone therapy applications following surgical regenerative treatments on clinical parameters, patient-centered outcomes, and mRNA expression levels of VEGF, IL-6, RunX2, Nell-1, and osterix in gingival crevicular fluid samples in patients with stage III/IV, grade C periodontitis. MATERIALS AND METHODS: Forty-eight systemically healthy patients were assigned into four groups to receive adjunctive modalities with regenerative periodontal surgical treatment. A 970 ± 15 nm diode laser plus indocyanine-green for aPDT group, a 626 nm LED for photobiomodulation group, and topical gaseous ozone were applied at 0, 1, 3, and 7 postoperative days and compared to control group. The clinical periodontal parameters, early wound healing index (EHI), and postoperative patients' morbidity were evaluated. The mRNA levels of biomarkers were assessed by real-time polymerase chain reaction. RESULTS: No significant difference in the clinical parameters except gingival recession (GR) was identified among the groups. For group-by-time interactions, plaque index (PI) and probing pocket depths (PD) showed significant differences (p = 0.034; p = 0.022). In sites with initial PD > 7 mm, significant differences were observed between control and photobiomodulation groups in PD (p = 0.011), between control and aPDT, and control and photobiomodulation groups in CAL at 6-month follow-up (p = 0.007; p = 0.022). The relative osterix mRNA levels showed a statistically significant difference among the treatment groups (p = 0.014). CONCLUSIONS: The additional applications of aPDT and LED after regenerative treatment of stage III/IV grade C periodontitis exhibited a more pronounced beneficial effect on clinical outcomes in deep periodontal pockets.

Effect of aquatic versus conventional physical therapy program on ankle sprain grade III in elite athletes: randomized controlled trial.

INTRODUCTION: Ankle sprains are the second most common sports injury after knee injuries, with about 85% of them affecting the lateral ankle ligaments. These injuries are particularly prevalent in sports like basketball and volleyball. PURPOSE: To investigate the effect of Aquatic therapy as an early rehabilitation protocol for elite athletes with acute lateral ankle sprain grade III on back-to-sport time, dynamic balance, pain, Athletic performance, and muscle power compared to land-based exercise training. METHODS: Thirty elite athletes have ankle sprain grade III with sprain onset from 1 to 7 days, their age ranges from 18-30 years old were recruited. All participants are professional athletes; mainly participating in above-head sports such as volleyball and basketball. The patients were randomly allocated into two treatment groups: Group I (control group): 15 patients received a conventional physical therapy program of structured therapeutic exercise program, manual therapy and land-based exercises, in addition to external support, and Group II (Aquatic therapy group): 15 patients received aquatic training. Visual Analog Scale (VAS) was used to measure the pain intensity, while the dynamic balance was measured by the Star Excursion Balance Test. Athletic performance was measured by HOP Tests (Single, Triple, 6-m, and Cross-over hops) aided by the Agility T-Test (ATT) and Illinois Agility Test (IAT). Muscle power was tested by a Single Leg Press. Finally, back to sports time was recorded for each participant in both groups. RESULTS: There was a significant interaction effect of Aquatic therapy and time for VAS (p < 0.001), single hop (p < 0.001), triple hop (p < 0.001), cross-over hop (p < 0.001), IAT (p = 0.019) and ATT (p < 0.001) of both affected and nonaffected. There was no significant interaction effect of Aquatic therapy and time for 6-MHT of affected (p = 0.923), and nonaffected (p = 0.140). There was a significant main effect of time for all dependent variables (p < 0.001) except for 6-MHT of affected (p = 0.939), nonaffected (p = 0.109), and IAT (p = 0.099). The Star excursion dynamic balance test (SEBT) and Single leg press revealed a significant difference between groups on affected and non-affected sides (p < 0.001*). Lastly and most importantly the back-to-sport time revealed a significant difference in the return-to-sport time in favor of the Aquatic therapy group who returned faster than the control group (p < 0.001*). CONCLUSION: Aquatic therapy is more effective than traditional protocols regarding early rehabilitation of acute ankle sprain grade III in Elite professional athletes for reducing pain intensity, improving dynamic balance and athletic performance and power and accelerating their return to sports time. Because aquatic therapy produces better outcomes, it is advised to be included in the rehabilitation programs of athletic patients with acute ankle sprains grade III.

Single cell spatial biology over developmental time can decipher pediatric brain pathologies.

Pediatric low grade brain tumors and neurodevelopmental disorders share proteins, signaling pathways, and networks. They also share germline mutations and an impaired prenatal differentiation origin. They may differ in the timing of the events and proliferation. We suggest that their pivotal distinct, albeit partially overlapping, outcomes relate to the cell states, which depend on their spatial location, and timing of gene expression during brain development. These attributes are crucial as the brain develops sequentially, and single-cell spatial organization influences cell state, thus function. Our underlying premise is that the root cause in neurodevelopmental disorders and pediatric tumors is impaired prenatal differentiation. Data related to pediatric brain tumors, neurodevelopmental disorders, brain cell (sub)types, locations, and timing of expression in the developing brain are scant. However, emerging single cell technologies, including transcriptomic, spatial biology, spatial high-resolution imaging performed over the brain developmental time, could be transformational in deciphering brain pathologies thereby pharmacology.

Perioperative imaging predictors of tumor progression and pseudoprogression: a systematic review.

In high-grade gliomas, pseudoprogression after radiation treatment might dramatically impact patient's management. We searched for perioperative imaging predictors of pseudoprogression in high-grade gliomas according to PRISMA guidelines, using MEDLINE/Pubmed and Embase (until January 2024). Study design, sample size, setting, diagnostic gold standard, imaging modalities and contrasts, and differences among variables or measures of diagnostic accuracy were recorded. Study quality was assessed through the QUADAS-2 tool. Twelve studies (11 with MRI, one with PET; 1058 patients) were reviewed. Most studies used a retrospective design (9/12), and structural MRI (7/12). Studies were heterogeneous in metrics and diagnostic reference standards; patient selection bias was a frequent concern. Pseudoprogression and progression showed some significant group differences in perioperative imaging metrics, although often with substantial overlap. Radiomics showed moderate accuracy but requires further validation. Current literature is scarce and limited by methodological concerns, highlighting the need of new predictors and multiparametric approaches.

Cytomorphological characteristics of low-grade papillary urothelial carcinoma in voided urine samples: Distinction from benign and high-grade papillary urothelial carcinoma.

OBJECTIVE: Given its frequent recurrence and the potential for high-grade transformation, accurate diagnosis of low-grade papillary urothelial carcinoma (LGPUC) in urine cytology is clinically important. We attempted to identify cytomorphologic features in urine samples, which could be helpful for the identification of LGPUC. METHODS: We conducted a retrospective review of voided urine specimens collected from patients with histopathologic diagnoses of LGPUC. Their cytomorphological features were compared with those from patients with benign conditions and high-grade papillary urothelial carcinoma (HGPUC). RESULTS: A total of 115 voided urine specimens were evaluated, including 30 benign, 41 LGPUC, and 44 HGPUC cases. In LGPUC, 18 cases (44%) were diagnosed as atypical, a proportion significantly higher than that observed in benign cases (4 cases, 13%), while the remaining 23 cases (56%) were diagnosed as negative. LGPUC urine samples tended to have higher cellularity than benign cases, but the difference was not statistically significant. Three cytological features, namely nuclear enlargement, higher nuclear-to-cytoplasmic (N/C) ratio, and presence of small cell clusters, were statistically more prevalent in LGPUC compared to benign cases, although the changes were relatively subtle. In contrast, cytomorphological distinction between LGPUC and HGPUC was evident, as high cellularity, nuclear enlargement, hyperchromasia, high N/C ratio, irregular nuclear membrane, and apoptosis were significantly more prevalent in HGPUC cases. CONCLUSIONS: Several cytomorphologic features in voided urine samples were more prevalent in cases with LGPUC, albeit not observed in all instances. Since these alterations were relatively subtle, meticulous attention to these cytomorphologic details is crucial to suggest the possibility of LGPUC.

Thymic Carcinoma Presenting as a Mediastinal Mass Resembling a Cardiac Tumor.

Thymoma and thymic carcinomas are a few of the rarest malignancies seen in humankind. They are mostly seen in the Asian population, many of which are reported in the Southeast Asia region like Japan, China, Vietnam, etc. They usually can be a sequela of other underlying conditions such as myasthenia gravis or some unknown mutations that express later in life.   Our patient is a young 41-year-male, a healthy and active individual who presented for evaluation of acute shortness of breath, two months after recovering from SARS-CoV-19 infection. His shortness of breath progressed while on oxygen and diuretics, a Point of Care Ultrasound (POCUS) showed cardiac tamponade and moderate pleural effusion. A Computerized Tomographic (CT) scan of the chest/abdomen/pelvis showed cardiomegaly, pleural effusion, and a mass abutting the heart. A pericardiocentesis revealed malignant cells. Thymic carcinoma was confirmed with a core biopsy and the patient was initiated on treatment rapidly to help improve symptoms and contain the growing mass.  .

Identification of TNFAIP6 as a reliable prognostic indicator of low-grade glioma.

Glioma is the most common primary malignant tumor in the brain, characterizing by high disability rate and high recurrence rate. Although low-grade glioma (LGG) has a relative benign biological behavior, the prognosis of LGG patients still varies greatly. Glioma stem cells (GSCs) are considered as the chief offenders of glioma cell proliferation, invasion and resistance to therapies. Our study screened a series of glioma stem cell-related genes (GSCRG) based on mDNAsi and WCGNA, and finally established a reliable single-gene prognostic model through 101 combinations of 10 machine learning methods. Our result suggested that the expression level of TNFAIP6 is negatively correlated with the prognosis of LGG patients, which may be the result of pro-cancer signaling pathways activation and immunosuppression. In general, this study revealed that TNFAIP6 is a robust and valuable prognostic factor in LGG, and may be a new target for LGG treatment.

A Comparative Review of Solidified Floating Organic Drop Microextraction Methods for Metal Separation: recent Developments, Enhanced co-Factors, Challenges, and Environmental Assessment.

The current work is devoted to a comparative analysis of enhanced co-factors in solidified floating organic drop microextraction methods (SFODME) and an environmental assessment. Also, the description of SFODME, with a focus on its applications in the determination of metals in different matrices, was explained. The impact of several parameters, developments, and greenness evaluations was introduced. Especially, the review provides a concise overview of the multiple approaches to SFODME, with an emphasis on environmentally friendly, supported co-factors. These mods include ultrasound, vortex, and air-assisted SFODME procedures. The selectivity and sensitivity increase when co-factors are added to SFODME. Lastly, the analysis also aims to select tools (Analytic GREEnness Metric Approach (AGREE), Red-Green-Blue (RGB12), and Blue Applicability Grade Index (BAGI)) that have been described as environmentally friendly. Additionally provide an explanation of the data collected, compare, and emphasize the advantages of certain characteristics in each tool. Furthermore, case studies and comparisons for three tools were shown.

Are Pre-clerkship Remediation, Grading, and Reporting Practices Equitable in the U.S.? A National Survey.

Phenomenon: With the proliferation of pass/fail grading practices in the pre-clerkship phase of undergraduate medical education, questions arise about the transparency and variability of grading and grade reporting practices, raising issues of equity in assessment, particularly regarding residency matching. The purpose of this survey was to determine the remediation and academic performance reporting practices of United States (U.S.) allopathic medical schools in the pre-clerkship phase of their curricula. Approach: After an extensive literature search and feedback from curriculum deans and learning experts, we developed a survey that we sent in the Spring of 2022 to pre-clerkship curriculum officials at all 154 accredited U.S. allopathic medical schools. It addressed curriculum content and structure; pre-clerkship remediation (e.g., course retakes) and reporting (e.g., permanency of transcript notation) practices; documentation and reporting of nonacademic competencies; and participant opinions and recommendations regarding reporting, transparency, and equity. We generated descriptive statistics and did manifest coding of open-ended responses. Findings: We had a response rate of 40% (62/155), with over 71% indicating mainly organ systems-based curricula. Depending on the situation, there were a wide range of remediation approaches for single- and multiple-course failures, including tutoring or learning support, re-exams, and referrals to a promotion board. Professionalism concerns were a top priority to report to residency directors, with significant variability in respondent opinions and practices in reporting remedial activities. Respondents were concerned about equity, both in terms of flexible grading practices and transparency of reporting practices. Insights: The variability in reporting practices across schools, while allowing holistic and individualized approaches to academic support, also creates potential inequities. More work is needed to understand how different reporting practices across institutions may disadvantage marginalized and minoritized student groups at different points in their preparation.

Global post­marketing safety surveillance of Tumor Treating Fields (TTFields) therapy in over 25,000 patients with CNS malignancies treated between 2011-2022.

BACKGROUND: Tumor Treating Fields (TTFields) are alternating electric fields that disrupt cancer cell processes. TTFields therapy is approved for recurrent glioblastoma (rGBM), and newly-diagnosed (nd) GBM (with concomitant temozolomide for ndGBM; US), and for grade IV glioma (EU). We present an updated global, post-marketing surveillance safety analysis of patients with CNS malignancies treated with TTFields therapy. METHODS: Safety data were collected from routine post-marketing activities for patients in North America, Europe, Israel, and Japan (October 2011-October 2022). Adverse events (AEs) were stratified by age, sex, and diagnosis. RESULTS: Overall, 25,898 patients were included (diagnoses: ndGBM [68%], rGBM [26%], anaplastic astrocytoma/oligodendroglioma [4%], other CNS malignancies [2%]). Median (range) age was 59 (3-103) years; 66% patients were male. Most (69%) patients were 18-65 years; 0.4% were < 18 years; 30% were > 65 years. All-cause and TTFields-related AEs occurred in 18,798 (73%) and 14,599 (56%) patients, respectively. Most common treatment-related AEs were beneath-array skin reactions (43%), electric sensation (tingling; 14%), and heat sensation (warmth; 12%). Treatment-related skin reactions were comparable in pediatric (39%), adult (42%), and elderly (45%) groups, and in males (41%) and females (46%); and similar across diagnostic subgroups (ndGBM, 46%; rGBM, 34%; anaplastic astrocytoma/oligodendroglioma, 42%; other, 40%). No TTFields-related systemic AEs were reported. CONCLUSIONS: This long-term, real-world analysis of > 25,000 patients demonstrated good tolerability of TTFields in patients with CNS malignancies. Most therapy-related AEs were manageable localized, non-serious skin events. The TTFields therapy safety profile remained consistent across subgroups (age, sex, and diagnosis), indicative of its broad applicability.

Longitudinal assessment of quality of life, neurocognition, and psychopathology in patients with low-grade glioma on first-line temozolomide: A feasibility study.

Background: The treatment timing and choice after neurosurgical resection in patients with newly diagnosed diffuse low-grade glioma (DLGG) remain controversial. Indeed, the effect of such treatments must be balanced with the possible side effects. This study evaluated the feasibility of longitudinal exhaustive quality of life (QoL) and neuropsychological assessments in patients with DLGG receiving first-line temozolomide. Methods: QoL, neurocognition, and psychological disorders were assessed prospectively until disease progression, using testing, clinician-reported, and self-reported questionnaires. The primary endpoint was the participation and adherence to this complete assessment at Baseline (before temozolomide initiation), months 6 and 12 of treatment, and month 6 post-treatment. The QoL and neuropsychological changes over time also were described. Results: Twenty-six of the twenty-nine eligible patients were enrolled (participation rate: 89.7%, 95% CI: 72.6-97.8). The adherence rate was 95.7% (95% CI: 78.1-99.9; n = 23 because 3 patients progressed in the first 12 months of treatment). Up to month 6 post-treatment, QoL and fatigue remained stable (EORTC QLQC30 and BN20, MFI-20); some specific symptoms were transitory. Both subjective (FACT-Cog) and objective (Z-scores of neurocognitive tests) neurocognitive outcomes remained stable or tended to improve. The percentage of patients with severe depression (BDI-II), anxiety (STAI-Y), or anger (STAXI-II) was stable over time. Conclusions: This prospective study demonstrated the feasibility of an exhaustive and longitudinal evaluation of QoL, neurocognition, and psychological disorders, with high acceptability by patients with DLGG undergoing chemotherapy. First-line temozolomide seems to have limited short-term effects on QoL and neurocognition. These findings must be confirmed in the long term and in a larger cohort.

Mortality Risk for Patients with Biopsy Gleason Grade Group 1 Prostate Cancer.

BACKGROUND AND OBJECTIVE: We investigated the association of clinical factors at presentation with the presence of unsampled high-risk prostate cancer (PC) and PC-specific mortality (PCSM) and all-cause mortality (ACM) following radical prostatectomy in patients with biopsy Gleason Grade Group (GGG) 1 PC. METHODS: The study population comprised 10228 patients treated for GGG1 PC diagnosed via transrectal ultrasound (TRUS)-guided systematic biopsy (SBx; n = 9248) or combined biopsy (CBx; SBx + TRUS/magnetic resonance image [MRI] fusion biopsy; n = 980) from a cohort study at a university hospital in Hamburg, Germany. We used logistic, Fine and Grays, and Cox multivariable regression methods to calculate the adjusted odds ratio (aOR) of adverse pathology and adjusted hazard ratios (aHRs) for early prostate-specific antigen (PSA) failure (≤18 mo), PCSM, and ACM in relation to each clinical factor. KEY FINDINGS AND LIMITATIONS: Irrespective of biopsy approach, percent positive biopsies (PPB) >50% and PSA >20 ng/ml were significantly associated with higher risk of adverse pathology (SBx: aOR 1.71 and 3.49; CBx: aOR 1.81 and 2.82, respectively) and early PSA failure (SBx: aHR 1.54 and 4.37; CBx: aHR 2.88 and 7.81, respectively). PPB >50% and PSA >20 ng/ml were also associated with higher risk of PCSM (aHRs 2.56 and 3.71) and ACM (aHRs 1.47 and 2.00) in the SBx group (all p ≤ 0.04). The study is limited by the single-institution cohort design. CONCLUSION AND CLINICAL IMPLICATION: Maintaining the "cancer" classification for patients with GGG1 and either PPB >50% or PSA>20 ng/ml and considering rebiopsy to identify unsampled high-grade disease may minimize the risk of mortality for this subgroup. PATIENT SUMMARY: For patients undergoing non-targeted prostate biopsy, approximately 1 in 12 with a biopsy result of grade group 1 prostate cancer may have more aggressive cancer than the result suggests. A very high PSA (prostate-specific antigen) level (>20 ng/ml) or the presence of grade group 1 cancer in more than 50% of the biopsy samples can identify patients at risk.

Integrated pan-cancer and scRNA-seq analyses identify a prognostic coagulation-related gene signature associated with tumor microenvironment in lower-grade glioma.

Cancer-associated thrombosis is a significant complication in cancer patients, leading to increased morbidity and mortality. The expression of coagulation/fibrinolysis genes, termed the "coagulome", plays a critical role in this process. Using the single-sample gene set enrichment analysis (ssGSEA), we identified seven cancer types with significantly activated coagulation pathways, focusing on lower-grade glioma (LGG) and stomach adenocarcinoma due to their predictive value for overall survival. Through 1000 iterations of the Least Absolute Shrinkage and Selection Operator (LASSO), we selected prognostic genes and constructed effective Cox regression models, particularly for LGG. Incorporating clinical characteristics, we constructed a nomogram for LGG, achieving an impressive area under the curve (AUCs) of 0.79, 0.82, and 0.81 at 1, 3, and 5 years in the test dataset, indicating strong potential for clinical application. Functional enrichment analysis between high-risk and low-risk LGG groups revealed significant enrichment of genes involved in the inflammatory response, interferon-gamma response, and epithelial-mesenchymal transition pathways. Combined with CIBERSORT and single-cell RNA sequencing analysis of LGG, our results demonstrated that the interplay between coagulation and the tumor microenvironment, particularly involving gliomas and myeloid cells, significantly influences tumor progression and patient outcomes.

Human peritoneal fluid exerts ovulation- and nonovulation-sourced oncogenic activities on transforming fallopian tube epithelial cells.

Secretory cells in the fallopian tube fimbria epithelium (FTE) are regarded as the main cells of origin of ovarian high-grade serous carcinoma (HGSC). Ovulation is the main cause of FTE oncogenesis, which proceeds through a sequence of TP53 mutations, chromosomal instability due to Rb/cyclin E aberration, in situ carcinoma (STIC), and metastasis to the ovary and peritoneum (metastatic HGSC). Previously, we have identified multiple oncogenic activities of the ovulatory follicular fluid (FF), which exerts the full spectrum of transforming activity on FTE cells at different stages of transformation. After ovulation, the FF is transfused into the peritoneal fluid (PF), in which the FTE constantly bathes. We wondered whether PF exerts the same spectrum of oncogenic activities as done by FF and whether these activities are derived from FF. By using a panel of FTE cell lines with p53 mutation (FT282-V), p53/CCNE1 aberrations (FT282-CCNE1), and p53/Rb aberrations plus spontaneous transformation, and peritoneal metastasis (FEXT2), we analyzed the changes of different transformation phenotypes after treating with FF and PF collected before or after ovulation. Similar to effects exhibited by FF, we found that, to a lesser extent, PF promoted anchorage-independent growth (AIG), migration, anoikis resistance, and peritoneal attachment in transforming FTE cells. The more transformed cells were typically more affected. Among the transforming activities exhibited by PF treatment, AIG, Matrigel invasion, and peritoneal attachment growth were higher with luteal-phase PF treatment than with the proliferative-phase PF treatment, suggesting an ovulation source. In contrast, changes in anoikis resistance and migration activities were similar in response to treatment with PF collected before and after ovulation, suggesting an ovulation-independent source. The overall transforming activity of luteal-phase PF was verified in an i.p. co-injection xenograft mouse model. Co-injection of Luc-FEXT2 cells with either FF or luteal-phase PF supported early peritoneal implantation, whereas co-injection with follicular-phase PF did not. This study, for the first time, demonstrates that PF from ovulating women can promote different oncogenic phenotypes in FTE cells at different stages of malignant transformation. Most of these activities, other than anoikis resistance and cell migration, are sourced from ovulation.

INFLA score: a novel inflammatory marker for assessing cardiometabolic disease risk in obese individuals.

BACKGROUND: The low-grade inflammation score (INFLA-score) is a composite index that assesses chronic inflammatory status using multiple inflammatory markers. However, its correlation with cardiometabolic diseases (CMDs) in obese populations remains unclear. METHODS: We conducted a prospective cohort study involving 79,160 participants with obesity (BMI ≥ 30 kg/m2) from the UK Biobank. The INFLA-score was calculated based on high-sensitivity C-reactive protein, leukocyte count, platelet count and granulocyte/lymphocyte ratio. We employed Kaplan-Meier survival curves, multivariable Cox regression, restricted cubic splines and accelerated time-to-failure models to analyse the association between the INFLA-score and CMDs risk, including coronary heart disease (CAD), stroke and type 2 diabetes mellitus (T2DM). RESULTS: Over a median follow-up of 161.41 months, we recorded 14,903 CMDs events, comprising 7184 CAD cases, 1914 strokes and 7924 T2DM cases. Cox regression analysis revealed that each unit increase in the INFLA-score corresponded to a 1.5%, 1.1%, 1.2% and 2.4% increase CMDs risk (HR: 1.015, 95% CI 1.013-1.018), CAD risk (HR: 1.011, 95% CI 1.007-1.015), stroke risk (HR: 1.012, 95% CI 1.004-1.020) and T2DM risk (HR: 1.024, 95% CI 1.020-1.028), respectively. Restricted cubic spline analysis indicated a non-linear relationship between cumulative INFLA-score and CMDs risk (P = 0.044). Subgroup analysis revealed interactions between sex, age, history of lipid-lowering drug use, and INFLA-score regarding CMDs risk. Sensitivity analysis corroborated the main findings. CONCLUSION: Our findings strongly support the close association between INFLA-score and CMDs risk, particularly notable in women, those aged < 55, and individuals with a history of lipid-lowering drug use. These findings offer new insights into the role of inflammation in obesity-related CMDs, suggesting potential applications for prevention and identification of high-risk populations.