IRIS UniSR (’Università Vita-Salute San Raffaele)
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A machine learning-based analysis for the definition of an optimal renal biopsy for kidney cancer
No full textObjective: Renal Tumor biopsy (RTB) can assist clinicians in determining the most suitable approach for treatment of renal cancer. However, RTB's limitations in accurately determining histology and grading have hindered its broader adoption and data on the concordance rate between RTB results and final pathology after surgery are unavailable. Therefore, we aimed to develop a machine learning algorithm to optimize RTB technique and to investigate the degree of concordance between RTB and surgical pathology reports. Materials and methods: Within a prospectively maintained database, patients with indeterminate renal masses who underwent RTB at a single tertiary center were identified. We recorded and analyzed the approach (US vs. CT), the number of biopsy cores (NoC), and total core tissue length (LoC) to evaluate their impact on diagnostic outcomes. The K-Nearest Neighbors (KNN), a non-parametric supervised machine learning model, predicted the probability of obtaining pathological characterization and grading. In surgical patients, final pathology reports were compared with RTB results. Results: Overall, 197 patients underwent RTB. Overall, 89.8% (n=177) and 44.7% (n=88) of biopsies were informative in terms of histology and grading, respectively. The discrepancy rate between the pathology results from renal tissue biopsy (RTB) and the final pathology report following surgery was 3.6% (n=7) for histology and 5.0% (n=10) for grading. According to the machine learning model, a minimum of 2 cores providing at least 0.8 cm of total tissue should be obtained to achieve the best accuracy in characterizing the cancer. Alternatively, in cases of RTB with more than two cores, no specific minimum tissue threshold is required. Conclusions: The discordance rates between RTB pathology and final surgical pathology are notably minimal. We defined an optimal renal biopsy strategy based on at least 2 cores and at least 0.8 cm of tissue or at least 3 cores and no minimum tissue threshold. Patients summary: RTB is a useful test for kidney cancer, but it's not always perfect. Our study shows that it usually matches up well with what doctors find during surgery. Using machine learning can make RTB even better by helping doctors know how many samples to take. This helps doctors treat kidney cancer more accurately
Nausea and vomiting in an evolving anticancer treatment landscape: long-delayed and emetogenic antibody-drug conjugates
No full textNausea and vomiting are common, distressing side effects associated with chemotherapeutic regimens, resulting in reduced quality of life and treatment adherence. Appropriate antiemetic prophylaxis strategies may reduce/prevent chemotherapy-induced nausea and vomiting (CINV). Historically, investigators assessed antiemetics up to 120 hours after chemotherapy. However, CINV can extend beyond this time. Thus, the effect of antiemetics during the long-delayed period (>120 hours) requires investigation. Emerging treatment options, including certain antibody-drug conjugates (ADCs), are associated with high rates of acute and late-onset nausea and vomiting that can last for extended duration. With the increasing number of ADCs approved and in development, there is urgency to control nausea and vomiting in patients receiving these new therapies. In this narrative review, we present the emetogenic potential of ADCs and CINV in the long-delayed period along with antiemetic prophylaxis strategies used to date. We also discuss the promising role of the fixed-combination antiemetic NEPA ([fos]netupitant plus palonosetron) in controlling long-delayed nausea and vomiting, addressing characteristics that may contribute to its longer efficacy duration compared to other antiemetics. Finally, we highlight encouraging results with NEPA in patients receiving the ADCs trastuzumab deruxtecan or sacituzumab govitecan, which suggest NEPA may be an effective antiemetic prophylaxis in these settings
Remote pulmonary artery pressure-guided management of patients with heart failure: A clinical consensus statement of the Heart Failure Association (HFA) of the ESC
No full textEpisodes of worsening heart failure (HF) are a major cause of unplanned hospitalizations. Their onset is usually preceded by an early increase in intracardiac pressures with subsequent worsening of symptoms due to congestion. Implantable devices allowing daily remote pulmonary artery pressure (PAP) monitoring are useful to identify early haemodynamic changes so that medical therapy can be adjusted at an early stage, before symptom onset, and HF-related hospitalizations be prevented. Second, the use of these devices may help to maintain clinical stability keeping PAP in the target range on a day-to-day basis. The CardioMEMS system allows remote PAP monitoring, and PAP-guided medical therapy has reduced HF-related hospitalizations in prospective, randomized, controlled clinical trials in symptomatic patients with HF, independent of their left ventricular ejection fraction. The safety and feasibility of other devices, like the Cordella implantable PAP sensor, have also been demonstrated and clinical usefulness in larger patient populations is currently being assessed in several trials. Most of the studies testing remote PAP monitoring were reported after the 2021 European Society of Cardiology HF guidelines. An update of the clinical significance and potential implications for clinical practice of these systems seems therefore warranted. The aim of this clinical consensus statement is to summarize current knowledge on remote PAP-guided management of patients with HF, with a special focus on current evidence from clinical trials, potential impact on clinical practice and management aspects
miR-210 overexpression increases pressure overload-induced cardiac fibrosis
No full textAortic stenosis, a common valvular heart disease, can lead to left ventricular pressure overload, triggering pro-fibrotic responses in the heart. miR-210 is a microRNA that responds to hypoxia and ischemia and plays a role in immune regulation and in cardiac remodeling upon myocardial infarction. This study investigated the effects of miR-210 on cardiac fibrosis caused by pressure overload. Using a mouse model with inducible miR-210 over-expression, we subjected mice to transverse aortic constriction (TAC) to induce pressure overload. Mice with miR-210 over-expression developed eccentric hypertrophy, heightened expression of hypertrophic markers (Nppa and Nppb) and increased cross sectional area of cardiomyocytes, impacting the free wall of the left ventricle. These findings suggest that miR-210 worsens cardiac dysfunction. Furthermore, miR-210 over-expression led to a more robust and sustained inflammatory response in the heart, increased interstitial and perivascular fibrosis, and activation of myofibroblasts. miR-210 also promoted angiogenesis. In vitro, cardiac fibroblasts over-expressing miR-210 showed increased adhesion, wound healing and migration capacity. Our results demonstrate that miR-210 contributes to adverse cardiac remodeling in response to pressure overload, including eccentric hypertrophy, inflammation, and fibrosis
Role of low-frequency integrase strand transfer inhibitor resistance mutations on virological outcomes in antiretroviral therapy-naïve individuals initiating second-generation integrase inhibitors
No full textObjectives: This study investigated the role of low-frequency integrase strand transfer inhibitor (INSTI) resistance mutations, detectable by next-generation sequencing (NGS), at predicting virological rebound (VR) among people with HIV (PWH) starting second-generation INSTI-based first-line regimens. Methods: This case-control study compared PWH (retrieved from the ICONA cohort; www.icona.org) who experienced VR (cases) with those who maintained virological control (controls) under first-line regimens based on dolutegravir or bictegravir. NGS data obtained through the Illumina platform were interpreted using the HIVdb algorithm version 9.7. Major (MRM), accessory (ARM), and other (ORM) INSTI resistance mutations were analysed at 5%, 10%, and 20% NGS cut-offs, respectively. Conditional logistic regression was used to evaluate the association between INSTI resistance and risk of VR. Results: Among 266 PWH (90 cases, 176 controls), cases experienced VR with a median (interquartile range) viremia of 317 (93–6060) copies/mL after 15 (8–28) months from antiretroviral therapy start. The prevalence of MRM was low (NGS cut-off 5%, 10%, 20%: 1.9%, 0.8%, 0.4%, respectively), while it was moderate for ARM (7.5%, 7.1%, 6.4%) and high for ORM (50.0%, 44.7%, 42.1%). There was no evidence of a difference in prevalence of ≥1 MRM, ARM, or ORM between cases and controls. At 5% NGS cut-off, the prevalence of ≥2 ORM was higher in cases compared with controls. After adjusting for confounders, including HIV-1 subtype, ≥2 ORM detected as minority variants remained associated with VR risk. Conclusion: Our findings suggest that combinations of low-frequency ORM may increase the risk of VR in individuals starting dolutegravir or bictegravir-based regimens. Further studies are needed to better understand these findings
Minimally invasive rectal surgery: current status and future perspectives in the era of digital surgery
No full textOver the past two decades, minimally invasive approaches in rectal surgery have changed the landscape of surgical interventions, impacting both malignant and benign pathologies. The dynamic nature of rectal cancer treatment owes much to innovations in surgical techniques, reflected in the expanding literature on available treatment modalities. Local excision, facilitated by minimally invasive surgery, offers curative potential for patients with early T1 rectal cancers and favorable pathologic features. For more complex cases, laparoscopic and robotic surgery have demonstrated significant efficacy and provided precise, durable outcomes while reducing perioperative morbidity and enhancing postoperative recovery. Additionally, advancements in imaging, surgical instrumentation, and enhanced recovery protocols have further optimized patient care. The integration of multidisciplinary care has also emerged as a cornerstone of treatment, emphasizing collaboration among surgeons, oncologists, and radiologists to deliver personalized, evidence-based care. This narrative review aims to elucidate current minimally invasive surgical techniques and approaches for rectal pathologies, spanning benign and malignant conditions, while also exploring future directions in the field, including the potential role of artificial intelligence and next-generation robotic platforms
Molecular imaging targeting carbonic anhydrase 9 in clear-cell renal cell carcinoma: more than meets the eye
No full textTransplanted human striatal progenitors exhibit functional integration and modulate host circuitry in a Huntington’s disease animal model
No full textPreoperative mFOLFIRINOX versus PAXG for stage I–III resectable and borderline resectable pancreatic ductal adenocarcinoma (PACT-21 CASSANDRA): results of the first randomisation analysis of a randomised, open-label, 2 × 2 factorial phase 3 trial
No full textBackground Perioperative chemotherapy is a standard option for treatment of patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC). This study aimed to assess the superiority of PAXG (cisplatin, nab-paclitaxel, capecitabine, and gemcitabine) over mFOLFIRINOX (modified fluorouracil, leucovorin, irinotecan, and oxaliplatin) in this population. Methods CASSANDRA is a randomised, open-label, 2 × 2 factorial phase 3 trial, involving 17 Italian academic hospitals. Eligible patients were aged 18–75 years with pathologically confirmed resectable or borderline resectable PDAC. Randomisation was performed by a central web-based system using R-code lists with a computerised algorithm. The design adopted a 1:1 randomisation, with a block stratification by centre and carbohydrate antigen 19-9. Participants were first randomly assigned PAXG (total daily capecitabine dose of 1250 mg/m2 in a 625 mg/m2 twice a day dosage and intravenous cisplatin 30 mg/m2, nab-paclitaxel 150 mg/m2, and gemcitabine 800 mg/m2 every 14 days) or mFOLFIRINOX (intravenous fluorouracil 2400 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2, and oxaliplatin 85 mg/m2 every 14 days) for 4 months, followed by a second randomisation to 2 months of additional chemotherapy either before or after surgery. The primary endpoint was event-free survival (EFS) in the intention-to-treat population and the safety population included all patients who received at least one cycle of the assigned therapy. The results of the first randomisation are reported here. The trial, registered on ClinicalTrials.gov ( NCT04793932 ) and EudraCT (2020-003080-26 and 2024-519031-42-00), completed accrual and reached the necessary events for first randomisation primary analysis but follow-up of overall survival is ongoing. Findings Between Nov 3, 2020, and April 24, 2024, 132 eligible patients were assigned to PAXG and 128 to mFOLFIRINOX. In the PAXG group, the median age was 65 years (IQR 60–70), 68 (52%) of 132 patients were female, and 64 (48%) were male. In the mFOLFIRNOX group, the median age was 63 years (IQR 57–69), 62 (48%) of 128 patients were female, and 66 (52%) were male. All 260 patients received at least one assigned chemotherapy administration. PAXG prolonged the median EFS compared with mFOLFIRINOX (16·0 months [95% CI 12·4–19·8] vs 10·2 months [8·6–13·5]; hazard ratio 0·63 [0·47–0·84]; p=0·0018). At least one grade 3 or worse adverse event was observed in 87 (66%) of 132 patients in the PAXG group and in 78 (61%) of 128 patients in the mFOLFIRINOX group, including one fatal event. Interpretation PAXG significantly improved EFS compared with mFOLFIRINOX in resectable or borderline resectable PDAC. Preopertive PAXG could be considered a standard option for resectable or borderline resectable PDAC. Accordingly, preoperative PAXG should be considered as the standard comparator group for future trials in this setting. Funding MyEverest and Codice Viola