Perquisizioni.

SOMMARIO1. Nozione e presupposti. 2. Organi legittimati a disporre la perquisizione. 3. La richiesta di consegna come alternativa alla perquisizione. 4. Perquisizione personale. 5. Perquisizione locale e «mista». 6. Perquisizione domiciliare. 7. Perquisizione nel corso delle indagini preliminari: ad iniziativa della polizia giudiziaria. 8. (Segue) disposta dal pubblico ministero. 9. Perquisizioni negli uffici del difensore. 10. Sequestro a seguito di perquisizione. 11. La perquisizione nelle leggi speciali

Indagini difensive.

SOMMARIO1. Considerazioni generali. 2. I soggetti legittimati alle investigazioni. 3. I limiti temporali dell’attività di indagine: l’attività investigativa preventiva. 4. (Segue) L’attività suppletiva e integrativa di indagine. 5. Le attività tipiche di investigazione: l’acquisizione di notizie da fonti dichiarative. 6. (Segue) Gli avvertimenti alla persona contattata. 7. Le dichiarazioni indizianti. 8. Il rifiuto di rispondere: la richiesta di audizione o di incidente probatorio. 9. La documentazione delle dichiarazioni ed informazioni. 10. Il potere di segretazione del pubblico ministero. 11. La richiesta di documentazione alla pubblica amministrazione. 12. L’accesso ai luoghi. 13. Il fascicolo del difensore. 14. Utilizzabilità degli atti di investigazione

Predictors of Response to Hydroxyurea and Switch to Ruxolitinib in HU-Resistant Polycythaemia VERA Patients: A Real-World PV-NET Study

In polycythemia vera (PV), the prognostic relevance of an ELN-defined complete response (CR) to hydroxyurea (HU), the predictors of response, and patients' triggers for switching to ruxolitinib are uncertain. In a real-world analysis, we evaluated the predictors of response, their impact on the clinical outcomes of CR to HU, and the correlations between partial or no response (PR/NR) and a patient switching to ruxolitinib. Among 563 PV patients receiving HU for ≥12 months, 166 (29.5%) achieved CR, 264 achieved PR, and 133 achieved NR. In a multivariate analysis, the absence of splenomegaly (p = 0.03), pruritus (p = 0.002), and a median HU dose of ≥1 g/day (p < 0.001) remained associated with CR. Adverse events were more frequent with a median HU dose of ≥1 g/day. Overall, 283 PR/NR patients (71.3%) continued HU, and 114 switched to ruxolitinib. In the 449 patients receiving only HU, rates of thrombosis, hemorrhages, progression, and overall survival were comparable among the CR, PR, and NR groups. Many PV patients received underdosed HU, leading to lower CR and toxicity rates. In addition, many patients continued HU despite a PR/NR; however, splenomegaly and other symptoms were the main drivers of an early switch. Better HU management, standardization of the criteria for and timing of responses to HU, and adequate intervention in poor responders should be advised

Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP

Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 6410% at 3 months, 641% at 6 months, 640.1% at 12 months, 640.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 >10% at 3 and 6 months, >1% at 12 months, and >0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR

The SARS-CoV-2 viral load in COVID-19 patients is lower on face mask filters than on nasopharyngeal swabs.

Face masks and personal respirators are used to curb the transmission of SARS-CoV-2 in respiratory droplets; filters embedded in some personal protective equipment could be used as a non-invasive sample source for applications, including at-home testing, but information is needed about whether filters are suited to capture viral particles for SARS-CoV-2 detection. In this study, we generated inactivated virus-laden aerosols of 0.3-2 microns in diameter (0.9 µm mean diameter by mass) and dispersed the aerosolized viral particles onto electrostatic face mask filters. The limit of detection for inactivated coronaviruses SARS-CoV-2 and HCoV-NL63 extracted from filters was between 10 to 100 copies/filter for both viruses. Testing for SARS-CoV-2, using face mask filters and nasopharyngeal swabs collected from hospitalized COVID-19-patients, showed that filter samples offered reduced sensitivity (8.5% compared to nasopharyngeal swabs). The low concordance of SARS-CoV-2 detection between filters and nasopharyngeal swabs indicated that number of viral particles collected on the face mask filter was below the limit of detection for all patients but those with the highest viral loads. This indicated face masks are unsuitable to replace diagnostic nasopharyngeal swabs in COVID-19 diagnosis. The ability to detect nucleic acids on face mask filters may, however, find other uses worth future investigation

Ancient human bones studied and compared by near infrared spectroscopy, thermogravimetry and chemometrics

Near infrared spectroscopy and thermogravimetry have been coupled with chemometric exploratory methods in order to investigate ancient (pre-Roman/Roman) human bones from two different necropolises in Central-South Italy (Cavo degli Zucchi and Elea Velia). These findings have been investigated by principal component analysis and they have also been compared with ancient human bones from two Sudanese necropolises (Saggai and Geili). Samples coming from African and European necropolises, mainly differ in two aspects: the burial procedures and their historical period. The ritual applied in the European region involved cremation, while the one applied in the African necropolises did not. Bones from Italian sites (Cavo degli Zucchi and Elea Velia) are Pre-Roman/Roman while the others (from middle Nile) come from the Prehistoric, Meroitic, and Christian Sudanese age. Near infrared spectroscopy and thermogravimetric measures have been analysed either individually or by a mid-level data-fusion approach. Principal component analysis of the near infrared spectroscopy data allowed differentiation between burnt and unburnt samples, while from the scores plots extracted from the principal component analysis model based on the entire derived thermograms, it was possible to recognize the different clusters related to the various dating of samples. The data-fusion analysis led to considerations similar to those obtained from the model based on thermogravimetry data. Finally, instead of inspecting the entire thermogravimetry curves, principal component analysis was carried out on carbonates, total collagen and water losses only. In this case, the data-fusion approach has led to extremely interesting results; in fact, this model clearly shows that samples group in separate clusters in agreement with their age and the different burial rituals

Multiple Myeloma and Renal Failure

Renal failure (RF) occurs in approximately 20-30% of multiple myeloma (MM) patients at diagnosis and in more than 50% of patients with advanced disease. The pathogenesis of RF is related to the production of monoclonal light chains that can damage either the tubule (myeloma kidney) or the glomeruli (light chain deposition disease or amyloid light-chain amyloidosis). In the past, the prognosis of patients with MM and RF was considered poor due to the limited number of effective and non-nephrotoxic drugs that were available. At present, novel drugs acting both on MM clone and on bone marrow microenvironment have been introduced into clinical practice; among them, bortezomib-containing regimens have proved to be the most effective. High-dose myeloablative therapy followed by autologous stem cell rescue can also be proposed in younger patients with no other relevant comorbidities

UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA

Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achivng a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate