Deep Angiomyxoma of the Knee: a Rare Case Report.

Background: Deep angiomyxoma (DAM) is a slow-growing benign tumor with high risk of local recurrence after surgical resection. Although DAM in a lower extremity is extremely rare, clinicians must be aware of its possible occurrence. Suspicion can be made based on clinical examination and radiological imaging but final diagnosis is confirmed on histopathological examination and immunohistochemistry. We intend to present an extremely rare case of DAM in the knee, managed successfully with marginal excision. Case Presentation: A 4-year-old male child presented with the complains of a painless, progressively increasing, soft, non-tender, and fluctuant swelling in his right knee. The plain radiograph showed a non-calcified soft-tissue swelling and MRI revealed a multi-loculated cystic lesion with multiple septations. A pre-operative diagnosis of a benign cystic lesion was made. It was managed by marginal excision of the tumor and a histological diagnosis of DAM was made. IHC staining showed positivity for SMA, CD34 and vimentin were focally positive, while desmin and calponin were negative. At 12 months of follow-up, the patient had a normal painless gait and full knee ROM, without any local recurrence. Conclusion: DAM is a rare tumor which is often misdiagnosed. In this report, we present a rare case of benign cystic lesion which turned out to be DAM on HPE of resected specimen. Marginal excision of this lesion revealed good outcomes with no recurrence until 12 months of final follow-up. With this, we conclude that surgical excision should be the gold standard in cases of DAM.

The Impact of Social Deprivation on Anterior Urethral Stricture Recurrence After Urethroplasty - A Trauma and Urologic Reconstructive Network of Surgeons (TURNS) Analysis.

INTRODUCTION AND OBJECTIVES: Several factors influence recurrence after urethral stricture repair. The impact of socioeconomic factors on stricture recurrence after urethroplasty is poorly understood. This study aims to assess the impact that social deprivation, an area-level measure of disadvantage, has on urethral stricture recurrence after urethroplasty. METHODS: We performed a retrospective review of patients undergoing urethral reconstruction by surgeons participating in a collaborative research group. Home zip code was used to calculate Social Deprivation Indices (SDI; 0-100), which quantifies the level of disadvantage across several sociodemographic domains collected in the American Community Survey. Patients without zip code data were excluded from the analysis. The Cox Proportional Hazards model was used to study the association between SDI and the hazard of functional recurrence, adjusting for stricture characteristics as well as age and body mass index. RESULTS: Median age was 46.0 years with a median follow up of 367 days for the 1452 men included in the study. Patients in the fourth SDI quartile (worst social deprivation) were more likely to be active smokers with traumatic and infectious strictures compared to the first SDI quartile. Patients in the fourth SDI quartile had 1.64 times the unadjusted hazard of functional stricture recurrence vs patients in the first SDI quartile (95% CI 1.04-2.59). Compared to anastomotic ± excision, substitution only repair had 1.90 times the unadjusted hazard of recurrence. The adjusted hazard of recurrence was 1.08 per 10-point increase in SDI (95% CI 1.01-1.15, P = .027). CONCLUSIONS: Patient social deprivation identifies those at higher risk for functional recurrence after anterior urethral stricture repair, offering an opportunity for preoperative counseling and postoperative surveillance. Addressing these social determinants of health can potentially improve outcomes in reconstructive surgery.

Tenofovir is associated with a better prognosis than entecavir for hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND AND AIMS: Whether tenofovir or entecavir has different effects on the prevention of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in secondary and tertiary preventive settings is still a matter of debate. This study aimed to compare the long-term prognosis of HCC between tenofovir and entecavir in patients with chronic hepatitis B (CHB). METHODS: CHB patients diagnosed with HCC between November 2008 and December 2018 and treated with either entecavir or tenofovir at a tertiary center in Korea were included. The effect of tenofovir compared to entecavir on the prognosis of HBV-related HCC was assessed using multivariable-adjusted Cox and propensity score (PS)-matched analyses. Various predefined subgroup analyses were conducted. RESULTS: During a median follow-up period of 3.0 years, the mortality rate for entecavir-treated patients (n = 3,469) was 41.2%, while tenofovir-treated patients (n = 3,056) had a mortality rate of 34.6%. Overall survival (OS) was better in the tenofovir group (adjusted hazard ratio [aHR], 0.79; P < .001), which were consistently observed in the PS-matched analysis. The magnitude of the risk difference in OS was more prominent 2 years after the diagnosis of HCC (aHR, 0.50; P < .001) than 2 years before (aHR, 0.88; P = .005), and it was more pronounced in patients with earlier HCC stages. In all subgroups, except for those with shorter life expectancy, such as those with compromised liver function, tenofovir was associated with better OS compared to entecavir. CONCLUSIONS: Among patients with HBV-related HCC, those treated with tenofovir had a better prognosis than those treated with entecavir, particularly among those with prolonged survival.

[Follow-up after urinary diversion]. / Nachsorge nach Harnableitung.

Radical cystectomy is currently the standard of care for muscle-invasive bladder cancer. Different parts of the small and large intestines can be utilized for continent and incontinent urinary diversion. The postoperative follow-up after urinary diversion should consider functional, metabolic and oncological aspects. The functional follow-up of (continent) urinary diversion includes stenosis, emptying disorders or incontinence. The oncological follow-up should focus on the detection of local, urethral and upper tract recurrences as well as distant metastases. As 90% of the tumor recurrences occur during the first 3 years, a close follow-up should be carried out during this period. Metabolic disturbances, such as vitamin B12 and bile acid deficits, acidosis and disorders of calcium metabolism can also occur during long-term follow-up. The metabolic follow-up should consider the metabolic consequences of the parts of the intestines utilized for the urinary diversion.

Stemness, invasion, and immunosuppression modulation in recurrent glioblastoma using nanotherapy.

The recurrent nature of glioblastoma negatively impacts conventional treatment strategies leading to a growing need for nanomedicine. Nanotherapeutics, an approach designed to deliver drugs to specific sites, is experiencing rapid growth and gaining immense popularity. Having potential in reaching the hard-to-reach disease sites, this field has the potential to show high efficacy in combatting glioblastoma progression. The presence of glioblastoma stem cells (GSCs) is a major factor behind the poor prognosis of glioblastoma multiforme (GBM). Stemness potential, heterogeneity, and self-renewal capacity, are some of the properties that make GSCs invade across the distant regions of the brain. Despite advances in medical technology and MRI-guided maximal surgical resection, not all GSCs residing in the brain can be removed, leading to recurrent disease. The aggressiveness of GBM is often correlated with immune suppression, where the T-cells are unable to infiltrate the cancer initiating GSCs. Standard of care therapies, including surgery and chemotherapy in combination with radiation therapy, have failed to tackle all the challenges of the GSCs, making it increasingly important for researchers to develop strategies to tackle their growth and proliferation and reduce the recurrence of GBM. Here, we will focus on the advancements in the field of nanomedicine that has the potential to show positive impact in managing glioblastoma tumor microenvironment. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Clinical characteristics and surgical outcomes of vertebral lesions associated with tumor-induced osteomalacia: report of 16 patients and review of the literature.

Vertebral tumors in patients with tumor-induced osteomalacia (TIO) have a low diagnostic rate and poor postoperative outcomes. The application of 68 Ga-DOTATATE-PET/CT significantly increased the detection rate. Compared with tumor curettage, segmental resection was recommended as the preferred surgical type due to its high recovery rate. PURPOSE: Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic osteomalacia, and surgery is the first-line therapy. Most TIO tumors are found in the bones of the appendicular skeleton, cranium, and paranasal sinuses but rarely in the vertebrae. Tumor curettage and segmental resection are the two main surgical options for vertebral TIO patients. However, research on the clinical characteristics and surgical prognosis of vertebral TIO patients is rare. In the present study, for the first time, we investigated the clinical characteristics of 16 vertebral TIO patients and compared the surgical outcomes of patients who underwent surgery via two different surgical methods. METHODS: This was a retrospective cohort study. In this study, we included 16 adult TIO patients with lesions in vertebrae from Peking Union Medical College Hospital (PUMCH), all of whom underwent surgery. Baseline laboratory data were collected through medical records review. Technetium-99 m octreotide scintigraphy (99Tcm-OCT) and 68gallium-DOTA-TATE-positron emission tomography/computed tomography (68 Ga-DOTATATE-PET/CT) were conducted at the Department of Nuclear Medicine of PUMCH. The tumor histopathology was confirmed by a senior pathologist at our center. RESULTS: Vertebral TIO patients had lower serum phosphorus and TmP/GFR and higher serum alkaline phosphatase (ALP), serum parathyroid hormone (PTH), and serum C-terminal cross-linked telopeptide of type I collagen (ß-CTX) levels than the normal range. The sensitivity of 68 Ga‒DOTATATE PET/CT was 100%, significantly greater than that of 99Tcm-OCT (40%). After comparing the outcomes between the two surgical methods, we found that the recovery rate after segmental resection (62.5%) was greater than that after tumor curettage (12.5%). In the thoracic and sacral vertebrae, segmental resection surgery had a good prognosis. CONCLUSION: 68 Ga-DOTATATE PET/CT could serve as the first diagnostic tool in patients with vertebral TIO, and segmental resection could be used as the preferred surgery. This study would raise awareness of the clinical features and management of these rare vertebral TIO patients.

Prognostic and predictive value of tertiary lymphoid structures in TURBT materials: Should it be seated in the routine pathological examination, and can it be used in deciding on the treatment method?

OBJECTIVE: This study aims to reveal the importance of tertiary lymphoid structures (TLS) in transurethral resection of bladder tumor (TURBT) materials with a practical and applicable method in which the effect of a certain threshold value on survival and treatment response can be implicated. METHODS: TURBT materials that had not previously received any treatment (chemotherapy, radiotherapy, or immunotherapy) and were diagnosed for the first time at Mardin Training and Research Hospital between 2014 and 2022 were included in the study. The maximum TLS per 4× magnification field (field diameter: 4.5 mm) was recorded. Grouping and statistical analysis of the TLS number were performed using threshold values of "≥1", "≥2", and "≥3". RESULTS: TLSs were more frequently found in high-grade tumors (P = 0.008) and showed a strong association with stage progression (P < 0.001). It was also significantly associated with many adverse histopathological parameters. Conversely, high TLS (≥1, ≥2, and ≥3) appeared to be associated with fewer recurrences (P = 0.032, P = 0.001, and P = 0.018, respectively), and cases with higher TLS showed longer recurrence-free survival (P = 0.089, P = 0.023, P = 0.037, respectively). TLS≥3 was found to be an independent parameter that was associated with favorable RFS (P = 0.019, HR = 0.401), and multifocality was found to be an independent risk factor for RFS (P = 0.023, HR = 2.302). CONCLUSION: This study is the first to demonstrate the relationship between the presence and specific thresholds of TLS in TURBT materials with prognostic parameters. Including this information in the routine pathological examination of TURBT materials will allow a more accurate approach to treatment and follow-up, especially in patients with non-muscle invasive bladder cancer (NMIBC).

Development and Validation of a Clinical Predictive Nomogram for Assessing the Risk of Recurrence of Acute Pancreatitis in Combined Hypertriglyceridemia.

BACKGROUND: The objective of this study is to develop and validate a new nomogram-based scoring system for anticipating the recurrence of acute pancreatitis (AP) in combined hypertriglyceridemia (HTG). METHODS: A total of 292 patients diagnosed with AP combined with HTG participated in this research. Among them, 201 patients meeting the inclusion criteria were randomly divided into training and validation sets at a ratio of 7:3. Clinical data were collected for all patients. In the training set, predictive indicators were chosen through backward stepwise multivariable logistic regression analysis. Subsequently, a nomogram was developed based on the selected indicators. Finally, the model's performance was validated in both the training and validation sets. RESULTS: By employing backward stepwise multivariable logistic regression analysis, we identified diabetes, gallstones, alcohol consumption, and triglyceride levels as predictive indicators. Subsequently, a clinical nomogram that incorporates these four independent risk factors was constructed. Model validation demonstrated an AUC of 0.726 (95% CI 0.644-0.809) in the training set and an AUC of 0.712 (95% CI 0.583-0.842) in the validation set, indicating a good discriminative ability. The Hosmer-Lemeshow test yielded P-values of 0.882 and 0.536 in the training and validation sets, respectively, suggesting good calibration. Calibration curves further confirmed good agreement. Ultimately, decision curve analysis (DCA) emphasized the clinical utility of our model. CONCLUSION: We have developed a nomogram for predicting the recurrence of AP combined with HTG in patients, and this nomogram demonstrates good discriminative ability, calibration, and clinical utility. This tool holds the potential to assist clinicians in offering more personalized treatment strategies for AP combined with HTG.

Is Perineural Invasion an Independent Prognostic Factor for Local Recurrence in Oral Squamous Cell Carcinoma?

Purpose: The purpose of this study was to analyse the independent prognostic significance of perineural invasion (PNI) on local recurrence (LR) in patients with oral squamous cell carcinoma (OSCC) managed primarily with surgery. Subjects and Methods: Clinical and histopathological data of 195 patients with OSCC were analysed retrospectively to identify risk factors associated with PNI and to evaluate its significant correlation with local recurrence, overall survival (OS) and recurrence free survival (RFS). Results: Patients were followed for a mean period of 39.5 ± 1.376 months and median 35 months. PNI was found in 57 patients (29.2%). PNI correlated with tongue subsite (p = 0.001), nodal metastasis (p < 0.000), depth of invasion (DOI) (p = 0.002), stage (p = 0.013) and adjuvant therapy (p < 0.001). Mean time to recurrence with PNI was significantly shorter (p = 0.002).Multivariate analysis did not establish significant relationship between PNI and LR. Kaplan-Meier curve did not show statistical significance with OS (p = 0.085) or RFS (p = 0.110). Conclusion: PNI remains an aggressive factor for nodal metastasis mandating neck management for regional control. Though PNI showed no statistical significance with LR, time to recurrence in PNI positive patients were significantly shorter. Hence, close follow-up regimen becomes necessary.

A novel methodology for emotion recognition through 62-lead EEG signals: multilevel heterogeneous recurrence analysis.

Objective: Recognizing emotions from electroencephalography (EEG) signals is a challenging task due to the complex, nonlinear, and nonstationary characteristics of brain activity. Traditional methods often fail to capture these subtle dynamics, while deep learning approaches lack explainability. In this research, we introduce a novel three-phase methodology integrating manifold embedding, multilevel heterogeneous recurrence analysis (MHRA), and ensemble learning to address these limitations in EEG-based emotion recognition. Approach: The proposed methodology was evaluated using the SJTU-SEED IV database. We first applied uniform manifold approximation and projection (UMAP) for manifold embedding of the 62-lead EEG signals into a lower-dimensional space. We then developed MHRA to characterize the complex recurrence dynamics of brain activity across multiple transition levels. Finally, we employed tree-based ensemble learning methods to classify four emotions (neutral, sad, fear, happy) based on the extracted MHRA features. Main results: Our approach achieved high performance, with an accuracy of 0.7885 and an AUC of 0.7552, outperforming existing methods on the same dataset. Additionally, our methodology provided the most consistent recognition performance across different emotions. Sensitivity analysis revealed specific MHRA metrics that were strongly associated with each emotion, offering valuable insights into the underlying neural dynamics. Significance: This study presents a novel framework for EEG-based emotion recognition that effectively captures the complex nonlinear and nonstationary dynamics of brain activity while maintaining explainability. The proposed methodology offers significant potential for advancing our understanding of emotional processing and developing more reliable emotion recognition systems with broad applications in healthcare and beyond.

Prognostic significance of invasive cribriform gland size and percentage in Gleason score 7 prostate adenocarcinoma.

OBJECTIVES: Cribriform glands are linked to poorer outcomes in prostate adenocarcinoma. We aimed to assess the prognostic role of the percentage of cribriform glands and the size of the largest invasive cribriform gland in Gleason score 7 prostate adenocarcinomas. METHODS: The presence, percentage, and size of the invasive cribriform glands were investigated and their association with prognostic factors were assessed in 177 Grade Groups 2 and 3 prostate adenocarcinomas. RESULTS: Biochemical recurrence-free survival was statistically significantly lower in cases with a cribriform gland percentage greater than 10% (P < .001) and in cases where the largest invasive cribriform gland size was greater than 0.5 mm (P < .001). Mean largest cribriform gland size and percentage were statistically significant associated with more advanced pT status, lymph node metastasis, biochemical recurrence, and higher preoperative prostate-specific antigen values. CONCLUSIONS: Our findings suggest that the presence of a cribriform pattern, increases in the percentage of such patterns, and increases in the size of the largest cribriform gland within a given tumor are associated with poor prognosis. We suggest that a more aggressive clinical approach may be needed in Grade Group 2 and 3 cases with invasive cribriform glands larger than 0.5 mm and a cribriform gland percentage greater than 10%, especially in prostate needle biopsy specimens.

Cerebrospinal Fluid Seeding Versus Inflammation in Setting of Ventriculoperitoneal Shunt as a Potential Cause for Distant Recurrence of Glioblastoma.

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults with a median survival of approximately 15 months, despite treatment, with most patients experiencing recurrence within 9 months of resection. The propensity of recurrence in GBM exemplifies the fatal course of the disease and remains an underlying area of study as novel instances of recurrence are encountered. The authors present a unique case of a 31-year-old male patient with a history of cerebellomedullary junction astrocytoma who later developed a supratentorial GBM followed by recurrence centered around a preexisting ventriculoperitoneal catheter and located in the hemisphere contralateral to his first GBM. Each of these lesions was initially thought to represent de novo glial neoplasms because of the absence of intervening T2 fluid-attenuated inversion recovery signal change between each lesion. However, next-generation sequencing using the GlioSeq™ platform revealed similar mutational profiles in both GBMs, suggesting an alternative method of migration of tumor cells to the shunt catheter site, and a local inflammatory environment likely triggering recurrence. This study concludes that in rare instances, in the presence of dormant glioma cells, intracranial foreign bodies may promote an inflammatory microenvironment that may activate tumorigenesis.

Malignant Transformation of Meningioma With TERT Promoter Mutation: A Case Report.

High-grade meningiomas make up a relatively minor proportion of meningiomas, which are one of the most common types of primary intracranial tumors in adults. Though rare, a considerable portion of high-grade meningiomas arise from malignant transformation of benign meningiomas. The 2021 World Health Organization (WHO) classification criteria introduced molecular markers in the diagnosis and grading of central nervous system (CNS) tumors and assigned certain genomic mutations to grade 3 meningiomas. We report a case of a 54-year-old male patient who underwent stepwise malignant transformation of meningioma from WHO grade 1 to grade 3 within 10 years, during the course of five surgeries followed by adjuvant stereotactic radiosurgery and radiotherapy. We performed next-generation sequencing (NGS) on the most recent grade 3 meningioma specimen and found that it carried a telomerase reverse transcriptase promoter (TERTp) mutation (c.-124C>T) in accordance with the 2021 WHO criteria for grade 3 meningiomas. We then retrospectively examined the previous grade 1 and 2 specimens and found them to have the same mutation. We reviewed the significance of molecular markers in the diagnosis of meningiomas, possible genetic alterations associated with their malignant transformation, and what measures could be taken to effectively manage meningiomas considering NGS findings.

Recurrences after nephron-sparing treatments of renal cell carcinoma: a competing risk analysis.

PURPOSE: To examine associations between ablative therapy (AT) and partial nephrectomy (PN) and the occurrence of local recurrence (LR), distant metastatic recurrence (DMR) and all-cause mortality in a nation-wide real-world population-based cohort of patients with nonmetastatic renal cell carcinoma (nmRCC). METHODS: Data on 2751 AT- or PN-treated nmRCC tumours diagnosed during 2005-2018, representing 2701 unique patients, were obtained from the National Swedish Kidney Cancer Register. Time to LR/DMR or death with/without LR/DMR was analysed using Cox regression models. RESULTS: During a mean of 4.8 years follow-up, LR was observed for 111 (4.0%) tumours, DMR for 108 (3.9%) tumours, and death without LR/DMR for 206 (7.5%) tumours. AT-treated tumours had a 4.31 times higher risk of LR (P < 0.001) and a 1.91 times higher risk of DMR (P = 0.018) than PN-treated, with no significant differences in risk of death without LR/DMR. During a mean of 3.2 and 2.5 years of follow-up after LR/DMR, respectively, 24 (21.6%) of the LR cases and 56 (51.9%) of the DMR cases died, compared to 7.5% in patients without LR/DMR. There were no significant differences between AT- and PN-treated regarding risks of early death after occurrence of LR or DMR. CONCLUSION: AT treatment of patients with nmRCC implied significantly higher risks of LR and DMR compared with PN treatment. To minimize the risks of LR and DMR, these results suggest that PN is preferred over AT as primary treatment, supporting the EAU guidelines to recommended AT mainly to frail and/or comorbid patients.

Predicting disease recurrence in patients with endometriosis: an observational study.

BACKGROUND: Despite surgical and pharmacological interventions, endometriosis can recur. Reliable information regarding risk of recurrence following a first diagnosis is scant. The aim of this study was to examine clinical and survey data in the setting of disease recurrence to identify predictors of risk of endometriosis recurrence. METHODS: This observational study reviewed data from 794 patients having surgery for pelvic pain or endometriosis. Patients were stratified into two analytic groups based on self-reported or surgically confirmed recurrent endometriosis. Statistical analyses included univariate, followed by multivariate logistic regression to identify risk factors of recurrence, with least absolute shrinkage and selection operator (Lasso) regularisation. Risk-calibrated Supersparse Linear Integer Models (RiskSLIM) and survival analyses (with Lasso) were undertaken to identify predictive features of recurrence. RESULTS: Several significant features were repeatedly identified in association with recurrence, including adhesions, high rASRM score, deep disease, bowel lesions, adenomyosis, emergency room attendance for pelvic pain, younger age at menarche, higher gravidity, high blood pressure and older age. In the surgically confirmed group, with a score of 5, the RiskSLIM method was able to predict the risk of recurrence (compared to a single diagnosis) at 95.3% and included adenomyosis and adhesions in the model. Survival analysis further highlighted bowel lesions, adhesions and adenomyosis. CONCLUSIONS: Following an initial diagnosis of endometriosis, clinical decision-making regarding disease management should take into consideration the presence of bowel lesions, adhesions and adenomyosis, which increase the risk of endometriosis recurrence.

Follow-up analysis and research of very low-risk and low-risk gastrointestinal stromal tumors after endoscopic resection.

Currently, due to limited long-term evidence, there remains some controversy surrounding the recommended postoperative monitoring strategy for primary low-risk gastrointestinal stromal tumors (GISTs). This study recruited a total of 532 patients diagnosed with very low-risk and low-risk GISTs who underwent endoscopic resection from 2015 to 2021, including 460 very low-risk patients and 72 low-risk patients. Descriptive statistical analysis was used to evaluate the clinical and pathological characteristics of GIST patients, and Kaplan-Meier methods were employed for survival analysis. The results showed that the 5-year recurrence-free survival rates for very low-risk and low-risk patients were 98.5% and 95.9%, respectively. The 5-year disease-specific survival rates for both groups were 100%. Additionally, the 5-year overall survival rates were 99.7% for very low-risk patients and 100% for low-risk patients (P = 0.69). Therefore, it is suggested that routine follow-up monitoring, including endoscopic surveillance and imaging, may not be necessary for very low-risk and low-risk GISTs after endoscopic resection.

Utility of 64Cu-Sarcophagine-Bombesin PET/CT in Men with Biochemically Recurrent Prostate Cancer and Negative or Equivocal Findings on 68Ga-PSMA-11 PET/CT.

Despite a high detection rate of 68Ga-prostate-specific membrane antigen (PSMA) PET/CT in biochemical recurrence (BCR) of prostate cancer, a significant proportion of men have negative 68Ga-PSMA-11 PET/CT results. Gastrin-releasing peptide receptor, targeted by the copper-chelated bombesin analog 64Cu-sarcophagine-bombesin (SAR-BBN) PET/CT, is also overexpressed in prostate cancer. In this prospective imaging study, we investigate the detection rate of 64Cu-SAR-BBN PET/CT in patients with BCR and negative or equivocal 68Ga-PSMA-11 PET/CT results. Methods: Men with confirmed adenocarcinoma of the prostate, prior definitive therapy, and BCR (defined as a prostate-specific antigen [PSA] level > 0.2 ng/mL) with negative or equivocal 68Ga-PSMA-11 PET/CT results within 3 mo were eligible for enrollment. 64Cu-SAR-BBN PET/CT scans were acquired at 1 and 3 h after administration of 200 MBq of 64Cu-SAR-BBN, with further delayed imaging undertaken optionally at 24 h. PSA (ng/mL) was determined at baseline. All PET (PSMA and bombesin) scans were assessed visually. Images were read with masking of the clinical results by 2 experienced nuclear medicine specialists, with a third reader in cases of discordance. Accuracy was defined using a standard of truth that included biopsy confirmation, confirmatory imaging, or response to targeted treatment. Results: Twenty-five patients were enrolled. Prior definitive therapy was radical prostatectomy (n = 24, 96%) or radiotherapy (n = 1, 4%). The median time since definitive therapy was 7 y (interquartile range [IQR], 4-11 y), and the Gleason score was 7 or less (n = 15, 60%), 8 (n = 3, 12%), or 9 (n = 7, 28%). The median PSA was 0.69 ng/mL (IQR, 0.28-2.45 ng/mL). Baseline PSMA PET scans were negative in 19 patients (76%) and equivocal in 6 (24%). 64Cu-SAR-BBN PET-avid disease was identified in 44% (11/25): 12% (3/25) with local recurrence, 20% (5/25) with pelvic node metastases, and 12% (3/25) with distant metastases. The κ-score between readers was 0.49 (95% CI, 0.16-0.82). Patients were followed up for a median of 10 mo (IQR, 9-12 mo). Bombesin PET/CT results were true-positive in 5 of 25 patients (20%), false-positive in 2 of 25 (8%), false-negative in 7 of 25 (28%), and unverified in 11 of 25 (44%). Conclusion: 64Cu-SAR-BBN PET/CT demonstrated sites of disease recurrence in 44% of BCR cases with negative or equivocal 68Ga-PSMA-11 PET/CT results. Further evaluation to confirm diagnostic benefit is warranted.

Predicting recurrent glioblastoma clinical outcome to immune checkpoint inhibition and low-dose bevacizumab with tumor in situ fluid circulating tumor DNA analysis.

OBJECTIVE: Most recurrent glioblastoma (rGBM) patients do not benefit from immune checkpoint inhibition, emphasizing the necessity for response biomarkers. This study evaluates whether tumor in situ fluid (TISF) circulating tumor DNA (ctDNA) could serve as a biomarker for response to low-dose bevacizumab (Bev) plus anti-PD-1 therapy in rGBM patients, aiming to enhance systemic responses to immunotherapy. METHODS: In this phase II trial, 32 GBM patients with first recurrence after standard therapy were enrolled and then received tislelizumab plus low-dose Bev each cycle. TISF samples were analyzed for ctDNA using a 551-gene panel before each treatment. RESULTS: The median progression-free survival (mPFS) and overall survival (mOS) were 8.2 months (95% CI, 5.2-11.1) and 14.3 months (95% CI, 6.5-22.1), respectively. The 12-month OS was 43.8%, and the objective response rate was 56.3%. Patients with more than 20% reduction in the mutant allele fraction and tumor mutational burden after treatment were significantly associated with better prognosis compared to baseline TISF-ctDNA. Among detectable gene mutations, patients with MUC16 mutation, EGFR mutation & amplification, SRSF2 amplification, and H3F3B amplification were significantly associated with worse prognosis. CONCLUSIONS: Low-dose Bev plus anti-PD-1 therapy significantly improves OS in rGBM patients, offering guiding significance for future individualized treatment strategies. TISF-ctDNA can monitor rGBM patients' response to combination therapy and guide treatment. CLINICAL TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT05540275.

Clinical manifestations and immune markers of non-HIV-related CMV retinitis.

BACKGROUND: Since the HIV epidemic in the 1980s, CMV retinitis has been mainly reported in this context. CMV retinitis in persons living with HIV is usually observed when CD4 + cells are below 50 cells/mm3. This study aims to describe the immune markers of non-HIV-related CMV retinitis as well as to describe its clinical manifestations and outcomes. METHODS: Retrospective chart review of consecutive patients with CMV retinitis not related to HIV seen at the uveitis clinic of Jules Gonin Eye Hospital between 2000 and 2023. We reported the clinical manifestations and outcomes of the patients. We additionally assessed immune markers during CMV retinitis (leukocyte, lymphocyte, CD4 + cell and CD8 + cell counts as well as immunoglobulin levels). RESULTS: Fifteen patients (22 eyes) were included. Underlying disease was hematologic malignancy in 9 patients, solid organ transplant in 3 patients, rheumatic disease in 2 patients and thymoma in one patient. The median time between the onset of underlying disease and the diagnosis of retinitis was 4.8 years. Lymphopenia was observed in 8/15 patients (mild = 3, moderate = 4, severe = 1), and low CD4 counts were observed in 9/12 patients, with less than 100 cells/mm3 in 4 patients. Hypogammaglobulinemia was detected in 7/11 patients. Retinitis was bilateral in 7/15 patients, and severe visual loss was frequent (5/19 eyes). Disease recurrence was seen in 7/13 patients at a median time of 6 months after initial diagnosis. No differences in immune markers were observed in patients with vs. without recurrence. CONCLUSION: CMV retinitis is a rare disorder that can affect patients suffering any kind of immunodeficiency. It is associated with a high visual morbidity despite adequate treatment. CD4 + cell counts are usually higher than those in HIV patients, but B-cell dysfunction is common.

Multiomics analysis of canine myocardium after circumferential pulmonary vein ablation: Effect of neuropeptide Y on long-term reinduction of atrial fibrillation.

Catheter ablation (CA) is an essential method for the interventional treatment of atrial fibrillation (AF), and it is very important to reduce long-term recurrence after CA. The mechanism of recurrence after CA is still unclear. We established a long-term model of beagle canines after circumferential pulmonary vein ablation (CPVA). The transcriptome and proteome were obtained using high-throughput sequencing and TMT-tagged LC-MS/LC analysis, respectively. Differentially expressed genes and proteins were screened and enriched, and the effect of fibrosis was found and verified in tissues. A downregulated protein, neuropeptide Y (NPY), was selected for validation and the results suggest that NPY may play a role in the long-term reinduction of AF after CPVA. Then, the molecular mechanism of NPY was further investigated. The results showed that the atrial effective refractory period (AERP) was shortened and fibrosis was increased after CPVA. Atrial myocyte apoptosis was alleviated by NPY intervention, and Akt activation was inhibited in cardiac fibroblasts. These results suggest that long-term suppression of NPY after CPVA may lead to induction of AF through promoting cardiomyocyte apoptosis and activating the Akt pathway in cardiac fibroblasts, which may make AF more likely to reinduce.