IRIS UniSR (’Università Vita-Salute San Raffaele)
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Diagnostic Accuracy of Fully Hybrid PET/MRI with [68 Ga]Ga-PSMA-11 and [68 Ga]Ga-RM2 in Detecting Primary Prostate Cancer: A Phase 2 Trial with Histology as Gold Standard
No full text: The primary aim of this study was to compare the diagnostic accuracy of [68Ga]Ga-PSMA-11 PET, [68Ga]Ga-RM2 PET, and multiparametric MRI (mpMRI) for the detection of primary prostate cancer (PCa) using histopathology as the reference. The secondary aims of the study were to assess the agreement among imaging modalities and identify noninvasive biomarkers for the diagnosis and risk stratification of patients. Methods: Forty-two patients with biopsy-confirmed, high-risk PCa were enrolled in this single-center, prospective, phase 2 clinical trial between September 2020 and May 2023 at San Raffaele hospital. All patients underwent [68Ga]Ga-PSMA-11 PET/MRI with mpMRI, and 36 had additional imaging with [68Ga]Ga-RM2 PET/MRI. All patients were included in the patient-level T staging analysis. Twenty-five patients were treated with radical prostatectomy with extended lymphadenectomy and considered for N staging analysis. Sixteen patients underwent all imaging and surgical procedures needed for coregistration between imaging and histology and were included in the lesion-based analysis for T staging. Two expert nuclear medicine physicians reviewed [68Ga]Ga-PSMA-11 and [68Ga]Ga-RM2 PET images with knowledge of the patients' available clinical and imaging information. mpMRI was interpreted as the standard of care by 2 expert radiologists using Prostate Imaging Reporting and Data System, version 2, criteria. Peripheral whole-blood samples were collected at the time of patient's enrollment to assess their association with lymph node involvement on histology. Results: In the patient-based analysis, [68Ga]Ga-PSMA-11 PET and mpMRI identified at least 1 intraprostatic lesion in all patients, whereas [68Ga]Ga-RM2 PET results were negative in 3 of 36 patients. The lesion-level analysis performed in 16 patients showed that, in this cohort, the dominant intraprostatic lesion was always detected by [68Ga]Ga-RM2 PET, whereas both [68Ga]Ga-PSMA-11 PET and mpMRI missed it, reporting a false-positive finding elsewhere. For N staging analysis, [68Ga]Ga-PSMA-11 PET had the highest sensitivity among the investigated imaging modalities (sensitivity, 0.375). Blood analysis showed that a higher fraction of polymorphonuclear-myeloid-derived suppressor cells (MDSCs) over monocytic MDSCs was significantly associated patients with lymph node involvement on histology (P = 0.0285). Conclusion: All imaging modalities showed high sensitivity for the preoperative detection of primary PCa, but only [68Ga]Ga-RM2 PET correctly identified the dominant lesion in all patients who underwent lesion-based subanalysis. The identification of lymph node involvement remains challenging, with [68Ga]Ga-PSMA-11 PET reaching a sensitivity of only 0.375. In this regard, the polymorphonuclear MDSC-to-monocytic MDSC ratio may represent a valuable biologic marker of lymph node involvement in patients with high-risk PCa and warrants further investigation
Mechanical asphyxia by hanging: A look back in search for evidence
No full textThe lack of pathognomonic findings to diagnose death by hanging is a well-known problem in forensic practice. This review examines the significance of signs that have been proposed over time as useful in forensic diagnosis, reporting the frequency of occurrence in the various published case histories. The analysis covered both internal and external signs, followed by an overview of potentially useful laboratory investigations. There is great variability in the frequency of occurrence of signs considered useful in forensic diagnosis. In addition, some of the signs that were considered historically valid must now be deemed not to be supported by sufficient scientific evidence as to their actual usefulness. There is a need for new case studies with overlapping methodologies and observed variables to enable effective and further comparisons
The Last Decade in Tricuspid Regurgitation: How Imaging Shaped a Field
No full textThe tricuspid valve has become a major focus of novel structural heart interventions, with the Conformité Européenne approval of 5 devices in Europe and the U.S. Food and Drug Administration approval of 2 devices in the United States. Multiple meta-analyses and large population-based registries have shown that although significant tricuspid regurgitation (TR) often accompanies left heart or pulmonary vascular diseases, it is associated with an increased risk of mortality and a reduced quality of life after adjusting for these comorbidities. Echocardiography remains the imaging modality of choice for diagnosing the etiology and assessing the severity of TR. However, advanced imaging techniques have played an essential role in the rapid advancement of the structural field and, in particular, transcatheter interventions for TR. Herein, we review the advances made in this field, focusing on the role that imaging has played in shaping a new field of study
Effect of Uptitration of Recommended Heart Failure Medications on Restricted Mean Survival Time in STRONG-HF
No full textA 24-week prospective, multicenter, real-world study on eptinezumab’s effectiveness and safety in migraine prevention (EMBRACE II)
Full text linkIntroduction: We evaluated the effectiveness, tolerability, and safety of eptinezumab in preventing high-frequency episodic migraine (HFEM) and chronic migraine (CM) over 24 weeks in real-world. We also assessed its impact during the first treatment week, in patients failing monoclonal antibodies targeting the calcitonin gene-related peptide (anti-CGRP mAbs), and the effects of dose escalation to 300 mg in patients requiring enhanced control. Methods: EMBRACE II is a multicenter (n = 22), prospective, 24-week, real-world study involving consecutive patients with HFEM or CM who had failed > 3 preventive treatments. Eptinezumab (100 mg, with the option for escalation to 300 mg at week 12) was administered quarterly. Primary endpoint: change in monthly migraine days (MMD), for HFEM or monthly headache days (MHD), for CM, between weeks 21-24 and baseline. Secondary endpoints: changes in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), Migraine Disability Assessment Scale (MIDAS), Migraine Interictal Burden Scale (MIBS-4), and responder rates. Results: Of the 215 participants who had received ≥ 1 eptinezumab dose, 74 were treated for ≥ 24 weeks and considered for effectiveness analysis. Eptinezumab significantly (p < 0.001) reduced MMD/MHD (- 10.5), MAI (- 15.6), NRS (- 2.2), HIT-6 (- 9.9), MIDAS (- 48.7), and MIBS-4 (- 4.3). ≥ 50% responders were 69%, ≥ 75% responders 39.2%, and 100% responders 4.1%. Comparing the first week with the last baseline week, a significant reduction in migraine days was observed (- 3.7; p < 0.001). Significant improvements were seen in patients failing anti-CGRP mAbs (32.4%) and in those escalating to 300 mg (33.8%). Half of the subjects reported being "very much improved" or "much improved". The adverse events were infrequent (2.8%). Conclusions: This real-world study documents that 24-week eptinezumab treatment is rapidly effective and well tolerated in migraine patients with multiple therapeutic failures (including anti-CGRP mAbs). One-third of patients escalated to 300 mg at week 12, achieving further significant migraine-related disability reduction
Associations of intraoperative end–tidal CO2 levels with postoperative outcome–secondary analysis of a worldwide observational study
No full textBackground: Patients receiving intraoperative ventilation during general anesthesia often have low end–tidal CO2 (etCO2). We examined the association of intraoperative etCO2 levels with the occurrence of postoperative pulmonary complications (PPCs) in a conveniently–sized international, prospective study named ‘Local ASsessment of Ventilatory management during General Anesthesia for Surgery’ (LAS VEGAS). Methods: Patients at high risk of PPCs were categorized as ‘low etCO2’ or ‘normal to high etCO2’ patients, using a cut–off of 35 mmHg. The primary endpoint was a composite of previously defined PPCs; the individual PPCs served as secondary endpoints. The need for unplanned oxygen was defined as mild PPCs and severe PPCs included pneumonia, respiratory failure, acute respiratory distress syndrome, barotrauma, and new invasive ventilation. We performed propensity score matching and LOESS regression to evaluate the relationship between the lowest etCO2 and PPCs. Results: The analysis included 1843 (74 %) ‘low etCO2’ patients and 648 (26 %) ‘normal to high etCO2’ patients. There was no difference in the occurrence of PPCs between ‘low etCO2’ and ‘normal to high etCO2’ patients (20 % vs. 19 %; RR 1.00 [95 %–confidence interval 0.94 to 1.06]; P = 0.84). The proportion of severe PPCs among total occurring PPCs, were higher in ‘low etCO2’ patients compared to ‘normal to high etCO2’ patients (35 % vs. 18 %; RR 1.16 [1.08 to 1.25]; P < 0.001). Propensity score matching did not change these findings. LOESS plot showed an inverse relationship of intraoperative etCO2 levels with the occurrence of PPCs. Conclusions: In this cohort of patients at high risk of PPCs, the overall occurrence of PPCs was not different between ‘low etCO2’ patients and ‘normal to high etCO2’ patients, but severe PPCs occurred more often in ‘low etCO2’, with an inverse dose–dependent relationship between intraoperative etCO2 levels and PPCs. Funding: This analysis was performed without additional funding. LAS VEGAS was partially funded and endorsed by the European Society of Anesthesiology and Intensive Care (ESAIC) and the Amsterdam University Medical Centers, location ‘AMC’. Registration: LAS VEGAS was registered at Clinicaltrials.gov (NCT01601223), first posted on May 17, 2012
Effectiveness of guselkumab in patients with facial and/or genital psoriasis: Interim analysis results at Week 12 from the GULLIVER study
No full textBackground: Facial (FP) and genital psoriasis (GP) significantly affect patients' quality of life. Despite the advances in treatments, limited data on efficacy and safety are available on these difficult-to-treat areas. Guselkumab is an interleukin (IL)-23 inhibitor which has been proven effective in treating patients with moderate-to-severe plaque psoriasis. Objectives: The aim of this interim analysis was to report the efficacy and safety of guselkumab in the treatment of patients with FP and/or GP. Materials and Methods: GULLIVER is a 52-week Italian observational study to evaluate the effectiveness and safety of guselkumab in a real-life setting in patients with FP and/or GP. Adult patients with facial and/or genital moderate-to-severe psoriasis (sPGA score ≥ 3) were included. The primary endpoint of this analysis was the percentage of patients achieving a facial or genital sPGA score of 0 (clear) or 1 (almost clear), at Week 12. The change in the score of the facial or genital sPGA components in patients with a score ≥3 for each sPGA component was assessed. PASI score in patients with a baseline PASI above or below 10 was evaluated. Results: Overall, 351 patients were included in the study; 83.3% of FP and 76.5% of GP patients achieved the primary endpoint. Similar response rates were observed for the facial or genital sPGA components in patients with a baseline facial or genital sPGA score ≥3 in each component. Among patients with a baseline PASI score >10, mean PASI score improved from 19.0 (SD 8.3) to 2.2 (SD 4.8). Forty-four AEs were observed in 32 patients; two mild and transient AEs (fatigue and nausea) were considered treatment related. No SAEs were observed. Conclusions: Guselkumab, showing to be effective and safe in treating FP and GP, may be a valid therapeutic option for patients with psoriasis localized in these difficult-to-treat areas
Incorporating Individual Early Response in the Dose-Effect Relationship of Complete Pathological Response Following Neoadjuvant Radiochemotherapy for Rectal Cancer
No full textPurpose: To develop and externally validate a model predicting pathological complete response (pCR) in patients with rectal cancer treated with neoadjuvant radiochemotherapy. The approach combines the classical logit dose-effect curve with individual early response assessed by magnetic resonance imaging during radiochemotherapy. Methods and materials: The dose-response model incorporating the early regression index (ERI) was derived from 2 published data sets. A population-averaged dose-response curve was obtained by fitting data from a recent meta-analysis. Then, an ERI-based model for pCR prediction was fit to 95 patients treated at San Raffaele Hospital; ERI was incorporated as a dynamic dose-modifying factor in the Hill model, based on Equivalent Uniform Dose to 2 Gy and including the time factor. The model was validated on an external cohort of 132 patients treated at Policlinico Gemelli with standard and dose-escalated schedules. Calibration plots, area under the curve, and average precision were used to assess performance. Recalibration refined predictions for the external cohort. Results: The final Hill model showed best-fit values of TD50 = 52.2 Gy, dynamic dose-modifying factor = (0.89 + 0.02 × ERI), and steepness k = 5.91 + 0.11 × ERI. The validation cohort had a pCR rate of 35.6%. Agreement between prediction and observed rates was high (offset, 0; slope, 0.84). Discriminative ability was robust (area under the curve, 0.77; average precision, 0.65 vs 0.356 for baseline). ERI-stratified dose-pCR relationships confirmed predictive value across 4 ERI categories: highly responsive (ERI, 1-6.9; pCR, 65%), moderately responsive (ERI, 6.9-13.1; pCR, 55%), poorly responsive (ERI, 13.1-36; pCR, 14% and 35%), and nonresponsive (ERI, >36; pCR, 0%). Predictions aligned with results using median ERI values per group. Conclusions: The ERI-dose model was validated on an external cohort with distinct radiation therapy regimens. Dose escalation of 8.5 Equivalent Uniform Dose to 2 Gy in moderate-to-good responders corresponds to an increase of approximately 20% in pCR, whereas no benefit was reported in nonresponders. These findings highlight the model's potential for personalizing radiation therapy protocols by optimizing dose escalation based on ERI