Hormone Receptor Expression and Activity for Different Tumour Locations in Patients with Advanced and Recurrent Endometrial Carcinoma.

BACKGROUND: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored the relationship between ER/PR-IHC expression and tumour location in EC. METHODS: Pre-treatment tumour biopsies from 6 different sites of 80 cases treated with hormonal therapy were analysed for ER/PR-IHC expression and classified into categories 0-10%, 10-50%, and >50%. The ER pathway activity score (ERPAS) was determined based on mRNA levels of ER-related target genes, reflecting the actual activity of the ER receptor. RESULTS: There was a trend towards lower PR-IHC (33% had PR > 50%) and ERPAS (27% had ERPAS > 15) in lymphogenic metastases compared to other locations (p = 0.074). Hematogenous and intra-abdominal metastases appeared to have high ER/PR-IHC and ERPAS (85% and 89% ER-IHC > 50%; 64% and 78% PR-IHC > 50%; 60% and 71% ERPAS > 15, not significant). Tumour grade and previous radiotherapy did not affect ER/PR-IHC or ERPAS. CONCLUSIONS: A trend towards lower PR-IHC and ERPAS was observed in lymphogenic sites. Verification in larger cohorts is needed to confirm these findings, which may have implications for the use of hormonal therapy in the future.

Influence of obesity on blood glucose control using continuous glucose monitoring data among patients with type 1 diabetes.

INTRODUCTION: The global increase in the prevalence rates of overweight or obesity has also affected patients with type 1 diabetes (T1D), where this disease had traditionally been associated with a lean phenotype. On the other hand, the effect of obesity on new glycemic control metrics obtained from continuous glucose monitoring (CGM) in T1D is poorly understood. We wanted to assess whether there is any relationship between BMI (body mass index) and the different CGM metrics or HbA1c. METHODS: Two hundred and twenty-five patients with T1D (47.1% ♀, mean age 42.9±14.7 years) with a CGM for a minimum of 6 months were analysed by downloading their CGM and collecting clinical and anthropometric variables. RESULTS: 35.1% (79/225) of the T1D patients had overweight and 17.3% (39/225) lived with obesity, while the remaining 47.6% had a normal weight. A negative correlation was found between GMI (glucose management indicator) and BMI (-0.2; p=0.008) and HbA1c (-0.2; p=0.01). In contrast, a positive correlation was observed between the total dose of insulin and the BMI (0.3; p<0.0001). No significant correlations were found between BMI and other CGM metrics. CONCLUSIONS: Overweight or obesity do not imply worse glycemic control in patients with T1D or less use of CGM. Possibly, and in order to achieve a good glycemic control, more units of insulin are necessary in these patients which, in turn, makes weight control more difficult.

"Vanishing" glioblastoma: A case report and review of the literature.

Contrast enhancement resolution induced by corticosteroids is a phenomenon primarily associated with primary central nervous system lymphoma, while malignant brain gliomas usually maintain a consistent radiological appearance during systemic steroid treatment. Although rare, a few primary and metastatic intracranial lesions have shown similar radiographic changes following corticosteroid therapy. In the case of glioblastomas, corticosteroid therapy is commonly used to alleviate pressure effects from peritumoral edema, but its impact on contrast enhancement is not well-established. A few reported cases in the literature describe reduced contrast enhancement in glioblastomas after corticosteroid treatment. We present a case of corticosteroid-induced regression on imaging of glioblastoma evaluated at our institutionwith the intention to explore the pathogenesis of this response and discuss the therapeutic and prognostic implications of this discovery.

Geographical and ecological factors affect microplastic body burden in marine fish at global scale.

Microplastic (MP) contamination has been identified as a worrisome environmental issue at the global level. Fish are the taxonomic group more extensively investigated to assess MP contamination in marine environment. A large variability in MP bioaccumulation (i.e., body burden) was reported in fish but to date there is a dearth of information concerning the drivers underlying this process. The present systematic review aimed at summarizing the results of the scientific literature on MP body burden in the digestive tract of marine fish to quantitatively shed light on the contribution of different geographical (i.e., latitudinal origin of the sample, distance from the coastline and field- or marked-collected) and ecological (i.e., trophic strategy, milieu, and body size) factors driving bioaccumulation. The mean (±SE) MPs/individual was 4.13 ± 2.87, and the mean MPs/ww (i.e., MPs/g) was 5.92 ± 0.94. Overall, MP abundance expressed as MPs/individual of fish from tropical areas was significantly higher compared to the other latitudinal bands, with species sampled close to the coastline that accumulated a larger number of MPs compared to those collected offshore. Neither the trophic strategy, nor the milieu and the market or field origin of fish explained the MP body burden. However, fish body size resulted as a determinant of MP body burden (as MPs/individual), with small fish accumulating a lower amount of MPs compared to larger ones. Qualitatively, but not statistically significant, similar results were generally obtained for MPs/ww, except for an opposite, and significant, variation according to species body size. Our findings showed that geographical, rather than ecological factors represent the main drivers of MP body burden in marine fish, suggesting that environmental variables and/or local pollution sources mainly contribute to explaining the large variability underlying the ingestion and bioaccumulation processes of these contaminants.

The endometrial transcriptome of infertile women with and without implantation failure.

INTRODUCTION: Implantation failure after transferring morphologically "good-quality" embryos in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) may be explained by impaired endometrial receptivity. Analyzing the endometrial transcriptome analysis may reveal the underlying processes and could help in guiding prognosis and using targeted interventions for infertility. This exploratory study investigated whether the endometrial transcriptome profile was associated with short-term or long-term implantation outcomes (ie success or failure). MATERIAL AND METHODS: Mid-luteal phase endometrial biopsies of 107 infertile women with one full failed IVF/ICSI cycle, obtained within an endometrial scratching trial, were subjected to RNA-sequencing and differentially expressed genes analysis with covariate adjustment (age, body mass index, luteinizing hormone [LH]-day). Endometrial transcriptomes were compared between implantation failure and success groups in the short term (after the second fresh IVF/ICSI cycle) and long term (including all fresh and frozen cycles within 12 months). The short-term analysis included 85/107 women (33 ongoing pregnancy vs 52 no pregnancy), excluding 22/107 women. The long-term analysis included 46/107 women (23 'fertile' group, ie infertile women with a live birth after ≤3 embryos transferred vs 23 recurrent implantation failure group, ie no live birth after ≥3 good quality embryos transferred), excluding 61/107 women not fitting these categories. As both analyses drew from the same pool of 107 samples, there was some sample overlap. Additionally, cell type enrichment scores and endometrial receptivity were analyzed, and an endometrial development pseudo-timeline was constructed to estimate transcriptomic deviations from the optimum receptivity day (LH + 7), denoted as ΔWOI (window of implantation). RESULTS: There were no significantly differentially expressed genes between implantation failure and success groups in either the short-term or long-term analyses. Principal component analysis initially showed two clusters in the long-term analysis, unrelated to clinical phenotype and no longer distinct following covariate adjustment. Cell type enrichment scores did not differ significantly between groups in both analyses. However, endometrial receptivity analysis demonstrated a potentially significant displacement of the WOI in the non-pregnant group compared with the ongoing pregnant group in the short-term analysis. CONCLUSIONS: No distinct endometrial transcriptome profile was associated with either implantation failure or success in infertile women. However, there may be differences in the extent to which the WOI is displaced.

Management of Uterine Fibroids and Sarcomas: The Palermo Position Paper.

BACKGROUND: Uterine fibroids are benign monoclonal tumors originating from the smooth muscle cells of the myometrium, constituting the most prevalent pathology within the female genital tract. Uterine sarcomas, although rare, still represent a diagnostic challenge and should be managed in centers with adequate expertise in gynecological oncology. OBJECTIVES: This article is aimed to summarize and discuss cutting-edge elements about the diagnosis and management of uterine fibroids and sarcomas. METHODS: This paper is a report of the lectures presented in an expert meeting about uterine fibroids and sarcomas held in Palermo in February 2023. OUTCOME: Overall, the combination of novel molecular pathways may help combine biomarkers and expert ultrasound for the differential diagnosis of uterine fibroids and sarcomas. On the one hand, molecular and cellular maps of uterine fibroids and matched myometrium may enhance our understanding of tumor development compared to histologic analysis and whole tissue transcriptomics, and support the development of minimally invasive treatment strategies; on the other hand, ultrasound imaging allows in most of the cases a proper mapping the fibroids and to differentiate between benign and malignant lesions, which need appropriate management. CONCLUSIONS AND OUTLOOK: The choice of uterine fibroid management, including pharmacological approaches, surgical treatment, or other strategies, such as high-intensity focused ultrasound (HIFU), should be carefully considered, taking into account the characteristics of the patient and reproductive prognosis.

Decoding the puzzle: A multidisciplinary systematic review of adult brainstem glioma.

Adult brainstem gliomas (BSGs) are a group of rare central nervous system tumors with varying prognoses and controversial standard treatment strategies. To provide an overview of current trends, a systematic review using the PRISMA guidelines, Class of evidence (CE) and strength of recommendation (SR), was conducted. The review identified 27 studies. Surgery was found to have a positive impact on survival, particularly for focal lesions with CE II SR C. Stereotactic image-guided biopsy was recommended when resective surgery was not feasible with CE II and SR B. The role of systemic treatments remains unclear. Eight studies provided molecular biology data. This review gathers crucial literature on diagnosis and management of adult BSGs. It provides evidence-based guidance with updated recommendations for diagnosing and treating, taking into account recent molecular and genetic advancements. The importance of brain biopsy is emphasized to optimize treatment using emerging genetic-molecular findings and explore potential targeted therapies.

Radioclinical Assessment of Posterior Tympanotomy Difficulties during Ordinary Cochlear Implantation: A Prospective Case-Series Study.

OBJECTIVES: This study proposes a preoperative radiologic scoring system for predicting posterior tympanotomy (PT) and mastoidectomy-associated difficulties during cochlear implantation (CI). STUDY DESIGN: It was a prospective case-series study. SETTINGS: The included CI surgeries were performed at tertiary referral institutions from October 2022 to April 2023. SUBJECTS: We included 73 CI candidates performed via the PT approach. INTERVENTION: The proposed radiologic score, composed of 13 items, was fulfilled and evaluated before each CI surgery. MAIN OUTCOME MEASURE: We correlated this score with the intraoperative difficulty and surgical duration. RESULTS: The operation was straightforward in 42 patients with a score of 3.87 ± 1.72 and challenging in 31 patients with a score of 10.66 ± 1.73. The radiologic score was strongly correlated with the surgical difficulty and duration (p < 0.0001). CONCLUSIONS: Our proposed radiologic score was a valid, reliable, and precise tool to predict intraoperative difficulty during cochlear implantation. Chorda-facial angle was the strongest predictor, significantly affecting the difficulty, surgical duration, and preoperative radiologic score. A score equal to or more than 7.5 was expected to be associated with surgical difficulty.

Extra-axial cranial nerve enhancement: a pattern-based approach.

Cranial nerve enhancement is a common and challenging MRI finding that requires a meticulous and systematic evaluation to identify the correct diagnosis. Literature mainly describes the various pathologies with the associated clinic-radiological characteristics, while the radiologist often needs a reverse approach that starts from the radiological findings to reach the diagnosis. Therefore, our aim is to provide a new and practical pattern-based approach to cranial nerve enhancement, which starts from the radiological findings and follows pattern-driven pipelines to navigate through multiple differential diagnoses, guiding the radiologist to reach the proper diagnosis. Firstly, we reviewed the literature and identified four patterns to categorize the main pathologies presenting with cranial nerve enhancement: unilateral linear pattern, bilateral linear pattern, unilateral thickened pattern, and bilateral thickened pattern. For each pattern, we describe the underlying pathogenic origin, and the main radiological features are displayed through high-quality MRI images and illustrative panels. A suggested MRI protocol for studying cranial nerve enhancement is also provided. In conclusion, our approach for cranial nerve enhancement aims to be an easy tool immediately applicable to clinical practice for converting challenging findings into specific pathological patterns.

Could transperineal interstitial laser ablation of the prostate be the right option for highly-comorbid patients with lower urinary tract symptoms due to benign prostatic obstruction? A preliminary single-center experience focusing on functional and safety outcomes.

In this paper, we aimed to highlight functional and safety outcomes of highly-comorbid patients undergoing transperineal laser ablation (TPLA) of prostate at a referral academic center. Patients undergoing TPLA from April 2021 and February 2023 with moderate to severe lower urinary tract symptoms (LUTS), prostate volume ranging from 30 to 100 mL, and an American Society of Anesthesiologists (ASA) Score ≥3 were included. All patients were evaluated as unfit for standard surgery. Procedures were performed in an outpatient setting using local anesthesia. Failure after the procedure was defined as the shift to other ultra-minimally invasive surgical treatment or the need for long-term indwelling catheter replacement. Overall, 23 patients were enrolled with a median age of 76 years. Median ASA Score and Charlson Comorbidity Index were 3 and 5, respectively. Of these, 11 (48%) were under antiplatelets, 4 (17%) under new oral anticoagulants (NOACs) and 3 (13%) under warfarin. Six (26%) patients had an indwelling catheter preoperatively. Median prostate volume was 42 mL. Median follow-up was 12 months. No Clavien-Dindo Grade ≥2 complications were recorded. Four/six (66%) patients with an indwelling catheter before TPLA achieved spontaneous micturition. Treatment failure occurred in 2 (8.5%) patients. Of the remaining 21 patients, 12/21 (57%) patients reported an improvement in International Prostate Symptoms Score (IPSS) symptoms class (i.e., severe to moderate, moderate to mild, etc.); all patients whose IPSS symptoms class remained stable (N.=8 [38%]) had a significant improvement of the IPSS score as compared to the preoperative period, while 1 (4.5%) patient reported worsening of LUTS. In conclusion, TPLA appears to be a safe and feasible ultra-minimally-invasive option for LUTS due to benign prostatic obstruction (BPO) in patients with significant comorbidities at high-risk for standard surgical options.

Interrater reliability of Brain Tumor Reporting and Data System (BT-RADS) in the follow up of adult primary brain tumors: a single institution experience in Italy.

Background: In 2018, a new system was proposed for classifying and reporting post-treatment adult brain tumor on magnetic resonance imaging, named as Brain Tumor Reporting and Data System (BT-RADS), that needs a validation by means of agreement studies. Methods: A retrospective study was designed with the aim of identifying contrast-enhanced magnetic resonance imaging (MRI) of adult patients on follow-up for primary brain tumor at Fondazione Policlinico Campus Bio-Medico. Four radiologists (2 radiology residents, 1 general radiologist, 1 neuroradiologist) read and scored each study using the BT-RADS scoring tool, blinded to the MRI original report. Interobserver agreement and Fleiss' k were calculated to assess the level of diagnostic agreement. It was assessed how many times the assignment of different scoring of BT-RADS would have led to a different patient management. Results: The total number of patients included in the study was 23 with 147 MRIs and a total of 588 BT-RADS scores retrospectively evaluated. The two most frequent tumor types were astrocytoma grade 4 (62%) and oligodendroglioma grade 3 (21%). The overall agreement rate for all 4 radiologists was 82% with a Fleiss' k of 0.70. The overall agreement rate between general radiologist and neuroradiologist was 91% with a Fleiss' k of 0.86. The overall agreement rate between 2 radiology residents and neuroradiologist was 80% with a Fleiss' k of 0.66. Astrocytoma grade 3 (k: 0.51) and oligodendroglioma grade 2 (k: 0.32) showed a poor agreement while higher values of agreement were found for astrocytoma grade 4 (k: 0.70), astrocytoma grade 2 (k: 0.78) and oligodendroglioma grade 3 (k: 0.78). All the radiologists agreed on BT-RADS assignment in 70% patients, three radiologists agreed in 17% and two radiologists agree in 13%. In no cases there was a complete disagreement among the readers. In 18% of cases the discrepancy in the estimated BT-RADS would have led to a different follow-up management. Conclusions: BT-RADS can be considered a valid tool for neuroradiologists and radiologists even with little experience in the interpretation of patients' images during follow-up for adult primary brain tumors supporting standardized interpretation, reporting and clinical management.

Surgical Management of Adult Brainstem Gliomas: A Systematic Review and Meta-Analysis.

The present review aims to investigate the survival and functional outcomes in adult high-grade brainstem gliomas (BGSs) by comparing data from resective surgery and biopsy. MEDLINE, EMBASE and Cochrane Library were screened to conduct a systematic review of the literature, according to the PRISMA statement. Analysis was limited to articles including patients older than 18 years of age and those published from 1990 to September 2022. Case reports, review articles, meta-analyses, abstracts, reports of aggregated data, and reports on multimodal therapy where surgery was not the primary treatment were excluded. The ROBINS-I tool was applied to evaluate the risk of bias. Six studies were ultimately considered for the meta-analysis. The resective group was composed of 213 subjects and the bioptic group comprised 125. The analysis demonstrated a survival benefit in those patients in which an extensive resection was possible (STR HR 0.59 (95% CI 0.42, 0.82)) (GTR HR 0.63 (95% CI 0.43, 0.92)). Although surgical resection is associated with increased survival, the significantly higher complication rate makes it difficult to recommend surgery instead of biopsy for BSGs. Future investigations combining volumetric data and molecular profiles could add important data to better define the proper indication between resection and biopsy.

Advances in the Application of Direct Injection Mass Spectrometry Techniques to the Analysis of Grape, Wine and Other Alcoholic Beverages.

Direct injection mass spectrometry (DIMS) entails the direct introduction of a gaseous sample into a mass analyser without prior treatment or separation. DIMS techniques offer the opportunity to monitor processes in time, with limits of detection as low as 0.5 parts per trillion in volume (for a 1 s measurement time) while providing results with high informational content. This review provides insight into current and promising future developments of DIMS in the analysis of grape, wine and other alcoholic beverages. Thanks to its unique characteristics, DIMS allows the online monitoring of volatile organic compounds (VOCs) released by grapes during fermentative bioprocesses or by wine directly from the glass headspace or during drinking. A DIMS-based approach can also be adopted to perform quality control and high-throughput analysis, allowing us to characterise the volatile profile of large sample sets rapidly and in a comprehensive fashion. Furthermore, DIMS presents several characteristic elements of green analytical chemistry approaches, catalysing an interest linked to the development of sustainable paths in research and development activities in the field of viticulture and oenology.

Giant serpentine aneurysm: Neuroradiological and neurosurgical management in a left-handed patient.

Giant serpentine aneurysms are rare huge and partially thrombosed aneurysms, with an eccentric tortuous intra-aneurysmal vascular channel. Surgical treatment is often necessary due to the great mass effect. We describe a case of a left-handed woman with a giant serpentine aneurysm of the left middle cerebral artery whose management was complex. The challenge was to exclude the aneurysm from circulation, reduce the mass effect, and, mostly, preserve the language function. Since the patient was left-handed the language dominance needed to be assessed; functional MRI (fMRI) and Wada test (WT) showed a right dominance. Surgical treatment was performed, as a complication, the patient developed left fronto-basal ischemia with a slight paresis of the right hand but without any language deficit. Our case shows the importance of a multidisciplinary team in patient management, with a pivotal role of neuroradiological functional tests in presurgical planning.

Radiosurgery for Brain Metastases: Challenges in Imaging Interpretation after Treatment.

Stereotactic radiosurgery (SRS) has transformed the management of brain metastases by achieving local tumor control, reducing toxicity, and minimizing the need for whole-brain radiation therapy (WBRT). This review specifically investigates radiation-induced changes in patients treated for metastasis, highlighting the crucial role of magnetic resonance imaging (MRI) in the evaluation of treatment response, both at very early and late stages. The primary objective of the review is to evaluate the most effective imaging techniques for assessing radiation-induced changes and distinguishing them from tumor growth. The limitations of conventional imaging methods, which rely on size measurements, dimensional criteria, and contrast enhancement patterns, are critically evaluated. In addition, it has been investigated the potential of advanced imaging modalities to offer a more precise and comprehensive evaluation of treatment response. Finally, an overview of the relevant literature concerning the interpretation of brain changes in patients undergoing immunotherapies is provided.

Intradural abscess: A challenging diagnosis. Case series and review of the literature.

Spinal intradural abscesses are extremely rare. To our knowledge, only a few cases have been described in the literature. We report 2 cases of spinal intradural abscesses in patients presenting to our institution with different symptomatology. Both cases involved the lumbar spine, with different etiologies: Case 1 was presumptively related to spondylitis phenomena, with surgery confirming the intradural localization of the abscess; case 2 was of probable iatrogenic nature (secondary to lumbar drain positioning). The aim of this report is to briefly discuss the clinical significance and pathogenesis of these cases.

Long-term treatment outcomes of temozolomide-based chemoradiation in patients with adult-type diffuse IDH-mutant grade 2 astrocytoma.

PURPOSE: To report the long-term outcomes in adult patients with grade 2 IDH-mutant astrocytoma treated with temozolomide (TMZ)-based chemoradiation. METHODS: One hundred and three patients with histologically proven grade 2 astrocytoma received radiation therapy (RT), 50.4-54 Gy in 1.8 Gy fractions, and adjuvant TMZ up to 12 cycles. Fifty-two patients received RT at the time of tumor progression and 51 in the early postoperative period for the presence of at least one high-risk feature (age > 40 years, preoperative tumor size > 5 cm, large postoperative residual tumor, tumor crossing the midline, or presence of neurological symptoms). Overall survival (OS) and progression-free survival (PFS) were calculated from the time of diagnosis. RESULTS: With a median follow-up time of 9.0 years (range, 1.3-15 years), median PFS and OS times were 9 years (95%CI, 6.6-10.3) and 11.8 years (95%CI, 9.3-13.4), respectively. Median PFS was 10.6 years in the early treatment group and 6 years in delayed treatment group (hazard ratio (HR) 0.30; 95%CI 0.16-0.59; p = 0.0005); however, OS was not significantly different between groups (12.8 vs. 10.4 years; HR 0.64; 95%CI 0.33-1.25; p = 0.23). Extent of resection, KPS, and small residual disease were associated with OS, with postoperative tumor ≤ 1 cc that emerged as the strongest independent predictor (HR: 0.27; 95%CI 0.08-0.87; p = 0.01). CONCLUSIONS: TMZ-based chemoradiation is associated with survival benefit in patients with grade 2 IDH-mutant astrocytoma. For this group of patients, chemoradiation can be deferred until time of progression in younger patients receiving extensive resection, while early treatment should be recommended in high-risk patients.