IRIS UniSR (’Università Vita-Salute San Raffaele)
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Microplastics and nanoplastics in healthcare: environmental persistence, health implications, and professional awareness
Get PDFMicroplastics (<5 mm) and nanoplastics (<1 μm) emerged as widespread and persistent environmental pollutants, raising growing concern for human health. These particles result from the fragmentation of larger plastic items or are directly manufactured and have infiltrated ecosystems, food, water, and air. This review examines the environmental persistence, global spread, and health implications of micro- and nanoplastics, with a particular focus on their relevance to healthcare. Special attention is given to dentistry and orthodontics, where plastic use is extensive. Microplastics have been detected in virtually all environments and even in human tissues. Although the long-term health consequences remain uncertain, emerging evidence suggests potential adverse effects, including inflammation, endocrine disruption, and toxicity, particularly from nanoplastics capable of penetrating biological barriers. The healthcare sector contributes significantly to plastic pollution through the widespread use of disposable materials. Dentistry and orthodontics generate considerable plastic waste and microplastic debris, notably from single-use items and clear aligners. However, awareness among healthcare providers remains limited, though preliminary studies indicate that education can significantly increase concern and engagement. Microplastic pollution represents a pressing environmental and public health issue. The healthcare community must acknowledge its dual responsibility, as both a contributor to and a potential mitigator of plastic pollution. Targeted education, sustainable practices, and research are urgently needed
How to Do Echo in a Multimodality Approach to Assess the Risk of Sudden Death: A Consensus Statement of the Italian Society of Echocardiography and Cardiovascular Imaging
No full textRisk stratification for sudden cardiac death (SCD) is a multiparametric process that integrates the data from family history, clinical evaluation, electrocardiographic findings, arrhythmic burden, and cardiovascular imaging. Echocardiography is the first-line imaging modality for both diagnosis and risk stratification of cardiovascular diseases associated with SCD. Advances in echocardiography and multimodality imaging have identified a number of parameters with proven prognostic value in SCD risk stratification. CMR = Cardiac magnetic resonance, CT = Computed tomography, ECG = Electrocardiogram, ECHO = Echocardiograph
Psychedelics and schizophrenia: a double-edged sword
No full text: Psychedelics have shown promising effects in several psychiatric diseases as demonstrated by multiple clinical trials. However, no clinical experiments on patients with schizophrenia have been conducted up to date, except for some old semi-anecdotal studies mainly performed in the time-span '50s-'60s. Notably, these studies reported interesting findings, particularly on the improvement of negative symptoms and social cognition. With no doubts the lack of modern clinical studies is due to the psychomimetic properties of psychedelics, a noteworthy downside that could worsen positive symptoms. However, a rapidly increasing body of evidence has suggested that the mechanisms of action of such compounds partially overlaps with the pathogenic underpinnings of schizophrenia but in an opposite way. These findings suggest that, despite being a controversial issue, the use of psychedelics in the treatment of schizophrenia would be based on a strong biological rationale. Therefore, the aim of our perspective paper is to provide a background on the old experiments with psychedelics performed on patients with schizophrenia, interpreting them in the light of recent molecular findings on their ability to induce neuroplasticity and modulate connectivity, the immune and TAARs systems, neurotransmitters, and neurotropic factors. No systematic approach was adopted in reviewing the evidence given the difficulty to retrieve and interpret old findings. Interestingly, we identified a therapeutic potential of psychedelics in schizophrenia adopting a critical point of view, particularly on negative symptoms and social cognition, and we summarized all the relevant findings. We also identified an eligible subpopulation of chronic patients predominantly burdened by negative symptoms, outlining possible therapeutic strategies which encompass very low doses of psychedelics (microdosing), carefully considering safety and feasibility, to pave the way to future clinical trials.Psychedelics have shown promising effects in several psychiatric diseases as demonstrated by multiple clinical trials. However, no clinical experiments on patients with schizophrenia have been conducted up to date, except for some old semi-anecdotal studies mainly performed in the time-span ‘50s-‘60s. Notably, these studies reported interesting findings, particularly on the improvement of negative symptoms and social cognition. With no doubts the lack of modern clinical studies is due to the psychomimetic properties of psychedelics, a noteworthy downside that could worsen positive symptoms. However, a rapidly increasing body of evidence has suggested that the mechanisms of action of such compounds partially overlaps with the pathogenic underpinnings of schizophrenia but in an opposite way. These findings suggest that, despite being a controversial issue, the use of psychedelics in the treatment of schizophrenia would be based on a strong biological rationale. Therefore, the aim of our perspective paper is to provide a background on the old experiments with psychedelics performed on patients with schizophrenia, interpreting them in the light of recent molecular findings on their ability to induce neuroplasticity and modulate connectivity, the immune and TAARs systems, neurotransmitters, and neurotropic factors. No systematic approach was adopted in reviewing the evidence given the difficulty to retrieve and interpret old findings. Interestingly, we identified a therapeutic potential of psychedelics in schizophrenia adopting a critical point of view, particularly on negative symptoms and social cognition, and we summarized all the relevant findings. We also identified an eligible subpopulation of chronic patients predominantly burdened by negative symptoms, outlining possible therapeutic strategies which encompass very low doses of psychedelics (microdosing), carefully considering safety and feasibility, to pave the way to future clinical trials
Safety of laparoscopic compared to open right hepatectomy after portal vein occlusion: results from a multicenter study
No full textBackground: Concerns have been expressed about the feasibility of laparoscopic right hepatectomy (Lap-RH) after portal vein occlusion (PVO), because of its technical difficulty. The aim of this study is to assess the safety and feasibility of lap-RH after PVO. Methods: Retrospective analysis of prospectively collected data from high-volume HPB centers was performed. The peri-operative outcomes of lap-RH were compared to open-RH. Propensity score matching (PSM) was used to mitigate the influence of selection bias. Both one-stage and two-stage procedures were considered. Results: Between 01/2010 and 12/2020, 284 patients underwent RH or extended RH after PVO. The laparoscopic approach was used in 63 (22%) cases. Overall, surgeries were mainly performed for colorectal metastases (68.6%). Two-stage procedures were required in one-third of the cases for both groups. After PSM, 126 patients of the open-RH group were matched with 63 patients of the lap-RH group. In the lap-RH group, compared to open-RH, median FLR% post-PVO was larger (39.4% vs 38.5%, p = 0.037), median operation time was longer (360 vs 264 min, p < 0.001), pedicle clamping was used more frequently (79.4% vs 38.9%, p > 0.001), and median blood loss was higher (250 cc vs 200 cc, p = 0.024). Severe intraoperative incidents seldom occurred in both groups (6.3% lap-RH vs 1.6% open-RH, p = 0.208). The overall and severe complication rates were comparable. ISGLS liver failure grade B/C was rare in both groups (3.2% lap-RH vs 4.8% open-RH, p = 0.721). 90-day mortality was 1.6% following either lap-RH or open-RH. Lap-RH allowed a shorter median hospital stay (6 vs 8 days, p = 0.001). R1 resection rate was lower after lap-RH (3.2% vs 16%, p = 0.008). Conclusion: Lap-RH after PVO is safe, although it is technically more demanding than open-RH. This study also suggests some potential benefits of the laparoscopic approach, in terms of a shorter hospital stay and increased rate of radical resections
Cardiac index-guided therapy to maintain optimised postinduction cardiac index in high-risk patients having major open abdominal surgery. Comment on Br J Anaesth 2024; 133: 277-87
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Pediatric, adult, and late onset multiple sclerosis: Cognitive phenotypes and gray matter atrophy
No full textObjectivesWe aim to investigate cognitive phenotype distribution and MRI correlates across pediatric-, elderly-, and adult-onset MS patients as a function of disease duration.MethodsIn this cross-sectional study, we enrolled 1262 MS patients and 238 healthy controls, with neurological and cognitive assessments. A subset of 222 MS patients and 92 controls underwent 3T-MRI scan for brain atrophy and lesion analysis. Multinomial probabilistic models identified likelihood of belonging to cognitive phenotypes ("preserved-cognition," "mild verbal memory/semantic fluency," "mild multi-domain," "severe attention/executive," and "severe multi-domain") and experiencing MRI abnormalities based on disease duration and age at onset.ResultsIn all groups, the likelihood of "preserved-cognition" phenotype decreased, whereas "mild multi-domain" increased with longer disease duration. In pediatric- and adult-onset patients, the likelihood of "mild verbal memory/semantic fluency" phenotypes decreased with longer disease duration, and that of "severe multi-domain" increased with longer disease duration. Only in adult-onset patients, the likelihood of "severe executive/attention" phenotype increased with longer disease duration. All groups displayed escalating probabilities of cortical, thalamic, hippocampal, and deep gray matter atrophy over disease course. Compared to adult, pediatric-onset patients showed lower probability of experiencing thalamic atrophy with longer disease duration, while elderly-onset showed higher probability of experiencing cortical and hippocampal atrophy.InterpretationAge at MS onset significantly influences the distribution of cognitive phenotypes and the patterns of regional gray matter atrophy throughout the disease course
Persistent Corneal Epithelial Defect Following Pars Plana Vitrectomy: A Narrative Review
No full textPurpose: Persistent corneal epithelial defects (PCEDs) following pars plana vitrectomy (PPV) represent a significant clinical challenge, potentially leading to corneal scarring, vision loss, and other severe complications. This review aims to summarize the prevalence, associated risk factors, and management strategies for PCEDs in the context of PPV, providing evidence-based guidance for clinicians. Methods: A comprehensive systematic review was conducted using PubMed and Embase databases, identifying English-language studies addressing PCEDs after PPV. Results: The prevalence of PCEDs post-PPV varied widely, from 0% to 78.37%, influenced by intrinsic factors such as diabetes mellitus, which impairs corneal nerve function and healing, and extrinsic factors like intraoperative tamponade with C3F8. Management strategies ranged from conservative options like bandage contact lenses to advanced treatments like topical insulin. Conclusion: PCEDs after PPV are multifactorial and demand individualized management. Advanced therapies, particularly serum-based treatments, and topical insulin, show promising outcomes. Further prospective research is warranted to refine these treatments
Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or Bendamustine/Rituximab in Covalent Bruton Tyrosine Kinase Inhibitor-Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321)
Get PDFPURPOSEPirtobrutinib, a noncovalent, Bruton tyrosine kinase inhibitor (BTKi), has shown clinical efficacy and a favorable safety profile. BRUIN CLL-321 was an open-label, randomized phase III study conducted exclusively in patients with R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) previously treated with cBTKi, and compared pirtobrutinib with investigator's choice (IC) of idelalisib/rituximab (IdelaR) or bendamustine/rituximab (BR).METHODSPatients were randomly assigned 1:1 to receive pirtobrutinib (200 mg once daily) or IC of IdelaR or BR, and were stratified by previous use of venetoclax and del(17p). The primary end point was independent review committee-assessed progression-free survival (PFS). Secondary end points included time to next treatment or death (TTNT), overall survival (OS), and safety. The primary PFS end point was met at the time of the primary analysis (August 29, 2023), and updated results are reported from the final OS analysis (August 29, 2024).RESULTSA total of 238 patients were randomly assigned to receive pirtobrutinib (n = 119) or IC (n = 119; IdelaR [n = 82], BR [n = 37]). The PFS hazard ratio (HR) was 0.54 ([95% CI, 0.39 to 0.75]; P =.0002), with a median PFS of 14 months (95% CI, 11.2 to 16.6) in the pirtobrutinib group and 8.7 months (95% CI, 8.1 to 10.4) with IC. The unadjusted OS HR was 1.09 ([95% CI, 0.68 to 1.75]; P =.7202), and 18-month OS rate was 73.4% (95% CI, 63.9 to 80.7) in the pirtobrutinib group and 70.8% (95% CI, 60.9 to 78.7) with IC. Median TTNT was 24 months (95% CI, 17.8 to 29.7) with pirtobrutinib versus 10.9 months (95% CI, 8.7 to 12.5) with IC (HR, 0.37 [95% CI, 0.25 to 0.52]). At a median follow-up of 17.2 months, grade ≥3 treatment-emergent adverse events (AEs) were lower with pirtobrutinib (57.7%) than IC (73.4%). Treatment discontinuation due to AE occurred in 20 (17.2%) patients receiving pirtobrutinib and 38 (34.9%) patients receiving IC.CONCLUSIONPirtobrutinib improved PFS and TTNT, and demonstrated favorable tolerability, versus IdelaR/BR in exclusively cBTKi pretreated patients with CLL/SLL
Negative impact of corticosteroid use on outcome in patients with advanced BTCs treated with cisplatin, gemcitabine, and durvalumab: A large real‐life worldwide population
Get PDFIn recent years, there has been increasing interest in the possible prognostic impact of concomitant medications in patients with cancer treated with immunotherapy combinations. This real-world analysis aims to evaluate the impact of concomitant medications on survival outcomes in patients with advanced biliary tract cancer (BTCs) treated with cisplatin, gemcitabine and durvalumab (CGD) therapy. The study cohort included patients with a diagnosis of advanced BTCs who were taking concomitant medications for their comorbidities before the start of CGD. The primary objectives were overall survival (OS) and progression-free survival (PFS). The initial population consisted of 666 patients, who were retrospectively collected from 41 sites in 12 countries. Data on concomitant medications were available for 493 patients. After a median follow-up of 8.8 months (95% CI: 7.8–9.8), patients who did not take steroids (prednisone >10 mg/day or equivalent) or nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, before the start of CGD, had longer OS and PFS in univariate analysis. The multivariate analysis confirmed longer OS for patients who did not take steroids. Patients who did not take steroids had an OS of 14.8 months (95% CI: 13.1–29.1) versus 5.0 months (95% CI: 2.14–11.32) of patients who took prednisone >10 mg/day or equivalent. No differences were reported in terms of overall response rate (ORR), disease control rate (DCR) (p = 1.0 and p =.16, respectively), and safety profile between the two groups. Our analysis suggests that patients who did not receive steroids before the start of GCD had longer survival and highlighted the relevance of balancing concomitant medications and chemoimmunotherapy