It is widely known that precipitation is a key variable of the hydrological cycle that is strongly affected by recent climate changes. Therefore, there is a growing interest in research activities ...focused on alteration of rainfall regime, as it conditions the planning of countermeasures against flood and landslide hazards. The available literature about precipitation tendencies over Italian peninsula offers a limited number of studies about recent changes of extreme events and precipitation intensity. This work aims at adding a contribution to fill this research gap, investigating the changes in rainfall regime observed over the 2002–2021 period in the Campania region (southern Italy). To pursue this aim, a dataset including daily precipitation records collected at 107 stations was analysed both through 11 indices developed by the Expert Team on Climate Change Detection and Indices and through the Standardized Precipitation Index in order to detect signals of changes in extreme events and to assess tendencies towards drier or wetter conditions. The Theil‐Sen method and the Mann–Kendall non‐parametric test were employed to evaluate the trends and their statistical significance. The main results emerging from this work are (i) an increasing tendency in precipitation intensity and in the frequency of occurrence of heavy rainfall events in autumn, mainly in the northern part of the region and in the mountainous areas, (ii) an upward trend of the duration of the longest wet spell in the coastal areas and (iii) an increasing trend of dry spells in spring and in summer in the Gulf of Salerno.
Recent changes in Campania (southern Italy) rainfall regime were analyzed through 11 extreme precipitation indices. The main results are:
an increasing trend in precipitation intensity and in the frequency of occurrence of heavy rainfall events in autumn season in the northern sector of region and in the mountainous areas,
a positive tendency of the duration of the longest wet spell on the coastal areas, and
an increasing trend of dry spells in spring and in summer in the Gulf of Salerno.
To assess the safety and efficacy of Stereotactic Ablative Radiotherapy (SABR) in oligometastatic patients from colorectal cancer.
82 patients with 1-3 inoperable metastases confined to one organ ...(liver or lung), were treated with SABR for a total of 112 lesions in an observational study. Prescription dose ranged between 48 and 75 Gy in 3 or 4 consecutive fractions. Primary end-points were local control (LC), overall survival (OS) and progression-free survival (PFS). Secondary end-point was toxicity.
Median follow-up was 24 months (range 3-47). One, two and three years LC rate was 90%,80% and 75% (85%,75% and 70% for lung and 95%, 90% and 85% for liver metastases; no statistically significance was found). The difference in LC between the subgroup of lesions treated with ≥ 60 Gy (n = 58) and those irradiated with <60 Gy (n = 52) was statistically significant, with a 1, 2 and 3 yrs LC of 97%,92% and 83% for the higher dose, compared to 85%,70% and 70% for the lower dose (p < 0.04). Median OS was 32 months. Actuarial OS rate at 1, 2 and 3 yrs was 85%,65% and 43%. Univariate analysis showed a correlation only between OS and cumulative GTV > 3 cm (p < 0.02). Median PFS was 14 months, with a PFS rate of 56% at 1 yr and 40% at 2-3 yrs, without correlation with the site and prescription dose (p < 0.48 and p < 0.56). No patients experienced radiation-induced liver disease or grade >3 toxicity.
SABR is a safe and feasible alternative treatment of oligometastatic colorectal liver and lung metastases in patients not amenable to surgery or other ablative treatments.
In recent years, the outcome of mantle cell lymphoma (MCL) has improved, especially in younger patients, receiving cytarabine-containing chemoimmunotherapy and autologous stem cell transplantation. ...Nevertheless, a proportion of MCL patients still experience early failure. To identify biomarkers anticipating failure of intensive chemotherapy in MCL, we performed target resequencing and DNA profiling of purified tumor samples collected from patients enrolled in the prospective
(high-dose chemoimmunotherapy followed by autologous transplantation and randomized lenalidomide maintenance). Mutations of
and disruption of
by deletion or mutation associated with an increased risk of progression and death, both in univariate and multivariate analysis. By adding
mutations and
disruption to the MIPI-c backbone, we derived a new prognostic index, the "MIPI-genetic" ("MIPI- g"). The "MIPI-g" improved the model discrimination ability compared to the MIPI-c alone, defining three risk groups: i) low-risk patients (4-year progression free survival and overall survival of 72.0% and 94.5%); ii) inter-mediate-risk patients (4-year progression free survival and overall survival of 42.2% and 65.8%) and iii) high-risk patients (4-year progression free survival and overall survival of 11.5% and 44.9%). Our results: i) confirm that
disruption identifies a high-risk population characterized by poor sensitivity to conventional or intensified chemotherapy; ii) provide the pivotal evidence that patients harboring
mutations share the same poor outcome as patients harboring
disruption; and iii) allow to develop a tool for the identification of high-risk MCL patients for whom novel therapeutic strategies need to be investigated. (
).
The resolution of fluorescence microscopy images is limited by the physical properties of light. In the last decade, numerous super-resolution microscopy (SRM) approaches have been proposed to deal ...with such hindrance. Here we present Mean-Shift Super Resolution (MSSR), a new SRM algorithm based on the Mean Shift theory, which extends spatial resolution of single fluorescence images beyond the diffraction limit of light. MSSR works on low and high fluorophore densities, is not limited by the architecture of the optical setup and is applicable to single images as well as temporal series. The theoretical limit of spatial resolution, based on optimized real-world imaging conditions and analysis of temporal image stacks, has been measured to be 40 nm. Furthermore, MSSR has denoising capabilities that outperform other SRM approaches. Along with its wide accessibility, MSSR is a powerful, flexible, and generic tool for multidimensional and live cell imaging applications.
Many patients with coronavirus disease 2019 (COVID-19) are critically ill and require care in the intensive care unit (ICU).
To evaluate the independent risk factors associated with mortality of ...patients with COVID-19 requiring treatment in ICUs in the Lombardy region of Italy.
This retrospective, observational cohort study included 3988 consecutive critically ill patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinating center (Fondazione IRCCS Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network from February 20 to April 22, 2020. Infection with severe acute respiratory syndrome coronavirus 2 was confirmed by real-time reverse transcriptase-polymerase chain reaction assay of nasopharyngeal swabs. Follow-up was completed on May 30, 2020.
Baseline characteristics, comorbidities, long-term medications, and ventilatory support at ICU admission.
Time to death in days from ICU admission to hospital discharge. The independent risk factors associated with mortality were evaluated with a multivariable Cox proportional hazards regression.
Of the 3988 patients included in this cohort study, the median age was 63 (interquartile range IQR 56-69) years; 3188 (79.9%; 95% CI, 78.7%-81.1%) were men, and 1998 of 3300 (60.5%; 95% CI, 58.9%-62.2%) had at least 1 comorbidity. At ICU admission, 2929 patients (87.3%; 95% CI, 86.1%-88.4%) required invasive mechanical ventilation (IMV). The median follow-up was 44 (95% CI, 40-47; IQR, 11-69; range, 0-100) days; median time from symptoms onset to ICU admission was 10 (95% CI, 9-10; IQR, 6-14) days; median length of ICU stay was 12 (95% CI, 12-13; IQR, 6-21) days; and median length of IMV was 10 (95% CI, 10-11; IQR, 6-17) days. Cumulative observation time was 164 305 patient-days. Hospital and ICU mortality rates were 12 (95% CI, 11-12) and 27 (95% CI, 26-29) per 1000 patients-days, respectively. In the subgroup of the first 1715 patients, as of May 30, 2020, 865 (50.4%) had been discharged from the ICU, 836 (48.7%) had died in the ICU, and 14 (0.8%) were still in the ICU; overall, 915 patients (53.4%) died in the hospital. Independent risk factors associated with mortality included older age (hazard ratio HR, 1.75; 95% CI, 1.60-1.92), male sex (HR, 1.57; 95% CI, 1.31-1.88), high fraction of inspired oxygen (Fio2) (HR, 1.14; 95% CI, 1.10-1.19), high positive end-expiratory pressure (HR, 1.04; 95% CI, 1.01-1.06) or low Pao2:Fio2 ratio (HR, 0.80; 95% CI, 0.74-0.87) on ICU admission, and history of chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.28-2.19), hypercholesterolemia (HR, 1.25; 95% CI, 1.02-1.52), and type 2 diabetes (HR, 1.18; 95% CI, 1.01-1.39). No medication was independently associated with mortality (angiotensin-converting enzyme inhibitors HR, 1.17; 95% CI, 0.97-1.42; angiotensin receptor blockers HR, 1.05; 95% CI, 0.85-1.29).
In this retrospective cohort study of critically ill patients admitted to ICUs in Lombardy, Italy, with laboratory-confirmed COVID-19, most patients required IMV. The mortality rate and absolute mortality were high.
Breast cancers (BCs) are solid tumors composed of heterogeneous tissues consisting of cancer cells and an ever-changing tumor microenvironment (TME). The TME includes, among other non-cancer cell ...types, immune cells influencing the immune context of cancer tissues. In particular, the cross talk of immune cells and their interactions with cancer cells dramatically influence BC dissemination, immunoediting, and the outcomes of cancer therapies. Tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs) represent prominent immune cell populations of breast TMEs, and they have important roles in cancer immunoescape and dissemination. Therefore, in this article we review the features of TILs, TAMs, and MDSCs in BCs. Moreover, we highlight the mechanisms by which these immune cells remodel the immune TME and lead to breast cancer metastasis.
Free hemoglobin (fHb) may induce vasoconstriction by scavenging nitric oxide. It may increase in older blood units due to storage lesions. This study evaluated whether old red blood cell transfusion ...increases plasma fHb in sepsis and how the microvascular response may be affected.
This is a secondary analysis of a randomized study. Twenty adult septic patients received either fresh or old (<10 or >15 days storage, respectively) RBC transfusions. fHb was measured in RBC units and in the plasma before and 1 hour after transfusion. Simultaneously, the sublingual microcirculation was assessed with sidestream-dark field imaging. The perfused boundary region was calculated as an index of glycocalyx damage. Tissue oxygen saturation (StO2) and Hb index (THI) were measured with near-infrared spectroscopy and a vascular occlusion test was performed.
Similar fHb levels were found in the supernatant of fresh and old RBC units. Despite this, plasma fHb increased in the old RBC group after transfusion (from 0.125 0.098-0.219 mg/mL to 0.238 0.163-0.369 mg/mL, p = 0.006). The sublingual microcirculation was unaltered in both groups, while THI increased. The change in plasma fHb was inversely correlated with the changes in total vessel density (r = -0.57 95% confidence interval -0.82, -0.16, p = 0.008), De Backer score (r = -0.63 95% confidence interval -0.84, -0.25, p = 0.003) and THI (r = -0.72 95% confidence interval -0.88, -0.39, p = 0.0003).
Old RBC transfusion was associated with an increase in plasma fHb in septic patients. Increasing plasma fHb levels were associated with decreased microvascular density.
ClinicalTrials.gov NCT01584999.
Background
Complete revascularization (CR) of nonculprit lesions (NCL) is strongly recommended in patients with ST‐elevation myocardial infarction (STEMI) and multivessel coronary artery disease ...(MVD), but no definitive evidence is available regarding which diagnostic strategy should be preferred. Instantaneous wave‐free ratio (iFR) has never been investigated in this setting. We aimed to describe clinical outcomes of a cohort of patients undergoing iFR‐guided CR.
Methods
Following primary percutaneous coronary intervention (PCI), consecutive patients with STEMI and intermediate NCL were enrolled and destinated to an iFR‐guided CR. NCL with iFR ≤ 0.89 underwent PCI while NCL with iFR > 0.89 were deferred. The primary endpoint was NC target lesion failure (NC‐TLF) and the secondary endpoint was major adverse cardiovascular events (MACE), at 1‐year follow‐up.
Results
Overall, 209 patients were enrolled (ischemic iFR = 83; nonischemic iFR = 126). Patients with ischemic iFR showed a higher prevalence of traditional cardiovascular risk factors and angiographically determined three‐vessel disease. In the entire cohort, NC‐TLF and MACE occurred in 6.7% and 10.5% of patients, respectively. Compared to the deferred group, patients with ischemic iFR experienced significantly higher rates of both NC‐TLF (3.2% vs. 12.1%; p = 0.021) and MACE (7.1% vs. 16.9%; p = 0.041). These results were mostly driven by increased rates of NC‐TLF PCI and further revascularizations in this latter group, while no differences were evident in terms of nonfatal myocardial infarction or death. At multivariable analysis, the strongest predictor of MACE was symptom onset to balloon time (HR = 1.17 95% CI: 1.04–1.31, p = 0.008).
Conclusions
In our study enrolling STEMI patients with MVD, iFR assessment was feasible and safe. PCI‐deferring according to iFR evaluation of NCL was associated with low rates of adverse events. Further randomized studies are needed to investigate the effectiveness of iFR‐guided revascularization compared to current practice in this setting.
Summary
Checkpoint inhibitors (CPIs) are routinely employed in relapsed/refractory classical Hodgkin lymphoma. Nonetheless, persistent long‐term responses are uncommon, and one‐third of patients are ...refractory. Several reports have suggested that treatment with CPIs may re‐sensitize patients to chemotherapy, however there is no consensus on the optimal chemotherapy regimen and subsequent consolidation strategy. In this retrospective study we analysed the response to rechallenge with chemotherapy after CPI failure. Furthermore, we exploratively characterized the clonal evolution profile of a small sample of patients (n = 5) by employing the CALDER approach. Among the 28 patients included in the study, 17 (71%) were primary refractory and 26 (92%) were refractory to the last chemotherapy prior to CPIs. Following rechallenge with chemotherapy, response was recorded in 23 (82%) patients experiencing complete remission and 3 (11%) patients experiencing partial remission. The tumour evolution of the patients inferred by CALDER seemingly occurred prior to the first cycle of therapy and was characterized either by linear or branching evolution patterns. Twenty‐five patients proceeded to allogeneic stem cell transplantation. At a median follow‐up of 21 months, median PFS and OS were not reached. In conclusion, patients who fail CPIs can be effectively rescued by salvage chemotherapy and bridged to allo‐SCT/auto‐SCT.
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