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Triple-negative breast cancer (TNBC) is a very aggressive disease even in its early stages and is characterized by a severe prognosis. Neoadjuvant chemotherapy is one of the milestones of treatment, and paclitaxel (PTX) is among the most active drugs used in this setting. However, despite its efficacy, peripheral neuropathy occurs in approximately 20–25% of cases and represents the dose-limiting toxicity of this drug. New deliverable strategies to ameliorate drug delivery and reduce side effects are keenly awaited to improve patients’ outcomes. Mesenchymal stromal cells (MSCs) have recently been demonstrated as promising drug delivery vectors for cancer treatment. The aim of the present preclinical study is to explore the possibility of a cell therapy approach based on the use of MSCs loaded with PTX to treat TNBC-affected patients. For this purpose, we in vitro evaluated the viability, migration and colony formation of two TNBC cell lines, namely, MDA-MB-231 and BT549, treated with MSC-PTX conditioned medium (MSC-CM PTX) in comparison with both CM of MSCs not loaded with PTX (CTRL) and free PTX. We observed stronger inhibitory effects on survival, migration and tumorigenicity for MSC-CM PTX than for CTRL and free PTX in TNBC cell lines. Further studies will provide more information about activity and potentially open the possibility of using this new drug delivery vector in the context of a clinical study.

Cognitive and motor performances decline with ageing, and this may be exacerbated in people with HIV (PWH) due to several factors. The study aimed to compare cognitive and fine motor performance between older adults with and without HIV. We conducted a cross-sectional study of participants ≥ 65 years in the GEPPO cohort using Mini-Addenbrooke's Cognitive Examination (MACE) and Grooved Pegboard Test (GPT). Quality of life, depression, anxiety, and sleep quality were also measured. PWH (n = 239) were younger (73.7 vs. 80.6 years) and more commonly males at birth (85 vs. 25%) than PWoH (n = 52). No significant differences in MACE scores were observed between groups (24 vs. 23, p > 0.900). Time to complete GPT was longer in PWoH (140 vs. 106 s, p = 0.004), with 56% exceeding normative GPT values vs. 24% in PWH (p < 0.001). In multivariate models, older age and lower education predicted worse MACE and GPT scores, whereas benzodiazepine/Z drug use predicted poorer fine motor skills. PWH reported lower quality of life but similar or better depression, anxiety, and sleep scores compared to PWoH. Older PWH show comparable cognitive but better fine motor performance than PWoH. Education and benzodiazepine use emerged as key modifiable or protective factors, underscoring the importance of targeted geriatric and mental health interventions.

Background Long-COVID symptoms remain incompletely defined due to a large heterogeneity in the populations studied, case definitions, and settings of care. The aim of this study was to assess, in patients accessing care for Long-COVID, the profile of symptoms reported, the possible clustering of symptoms and cases, the functional status compared to pre-infection, and the impact on working activity. Methods Multicentre cohort study with a collection of both retrospective and prospective data. Demographics, comorbidities, severity and timing of acute COVID, subjective functional status, working activity and presence of 30 different symptoms were collected using a shortened version of the WHO Post COVID-19 Case Report Form. The impact on working activity was assessed in multivariable logistic regression models. Clustering of symptoms was analysed by hierarchical clustering and the clustering of cases by two-step automatic clustering. Results The study evaluated 1297 individuals (51.5% women) from 30 clinical centres. Men and women had different profiles in terms of comorbidities, vaccination status, severity and timing of acute SARS-CoV-2 infection. Fatigue (55.9%) and dyspnea (47.2%) were the most frequent symptoms. Women reported more symptoms (3.6 vs. 3.1, p  < 0.001), with a significantly higher prevalence of memory loss, difficult concentration, cough, palpitation or tachycardia, dermatological abnormalities, brain fog, headache and visual disturbances. Dyspnea was more common in men. In the cluster analysis of the 19 more common symptoms, five aggregations were found: four two-symptom clusters (smell and taste reduction; anxiety and depressed mood; joint pain or swelling and muscle pain; difficult concentration and memory loss) and one six-symptom cluster (brain fog, equilibrium/gait disturbances, headache, paresthesia, thoracic pain, and palpitations/tachycardia). In a multivariable analysis, headache, dyspnea, difficult concentration, disturbances of equilibrium or gait, visual disturbances and muscular pain were associated with reduced or interrupted working activity. Clustering of cases defined two clusters, with distinct characteristics in terms of phase and severity of acute infection, age, sex, number of comorbidities and symptom profile. Conclusions The findings provide further evidence that Long-COVID is a heterogeneous disease with manifestations that differ by sex, phase of the pandemic and severity of acute disease, and support the possibility that multiple pathways lead to different clinical manifestations.

Short- and medium-term cardio-pulmonary sequelae after COVID-19 have been extensively studied. However, studies with longer follow-ups are required. This study aims to identify and characterise cardio-pulmonary sequelae, in patients hospitalised for SARS-CoV-2 pneumonia, at 24 months follow-up. This is a prospective, observational cohort study conducted on consecutive patients hospitalised for COVID-19 and acute respiratory failure. Patients were followed up at 24 months with complete pulmonary function tests (PFTs), 6-min walking test and a dyspnoea score (Modified Medical Research Council scale). A subgroup of patients with at least one clinical or functional sign suggestive of increased pulmonary pressures also underwent transthoracic echocardiography (TTE) to evaluate the presence of direct or indirect signs of pulmonary hypertension (PH). Ninety consecutive patients (74% men, median age 59.1 years) were enrolled in the study. In regard to PFTs, carbon monoxide diffusion capacity (DLCO) impairment was observed in 23 cases (26%), in all cases of mild entity. When considering the dyspnoea, 30 (34%) patients showed some degree of breathlessness. Forty patients underwent TTE. No patients had overt PH or chronic thromboembolic PH. However, all patients showed a hyperdynamic state of the right ventricle, and 8 (20%) patients had a decreased acceleration time on pulmonary valve, signs of increased pulmonary vasculature resistances and afterload elevation. At 24-month follow-up after severe COVID-19, DLCO and TTE prove to be the most sensitive tool to detect cardio-pulmonary sequelae. Dyspnoea is still present in about one-third of patients and requires a multidisciplinary approach.

Objectives To evaluate the inter-rater agreement of chest X-ray (CXR) findings in coronavirus disease 2019 (COVID-19) and to determine the value of initial CXR along with demographic, clinical, and laboratory data at emergency department (ED) presentation for predicting mortality and the need for ventilatory support. Methods A total of 340 COVID-19 patients who underwent CXR in the ED setting (March 1–13, 2020) were retrospectively included. Two reviewers independently assessed CXR abnormalities, including ground-glass opacities (GGOs) and consolidation. Two scoring systems ( Brixia score and percentage of lung involvement) were applied. Inter-rater agreement was assessed by weighted Cohen’s kappa ( κ ) or intraclass correlation coefficient (ICC). Predictors of death and respiratory support were identified by logistic or Poisson regression. Results GGO admixed with consolidation ( n = 235, 69%) was the most common CXR finding. The inter-rater agreement was almost perfect for type of parenchymal opacity ( κ = 0.90), Brixia score (ICC = 0.91), and percentage of lung involvement (ICC = 0.95). The Brixia score (OR: 1.19; 95% CI: 1.06, 1.34; p = 0.003), age (OR: 1.16; 95% CI: 1.11, 1.22; p < 0.001), PaO 2 /FiO 2 ratio (OR: 0.99; 95% CI: 0.98, 1; p = 0.002), and cardiovascular diseases (OR: 3.21; 95% CI: 1.28, 8.39; p = 0.014) predicted death. Percentage of lung involvement (OR: 1.02; 95% CI: 1.01, 1.03; p = 0.001) and PaO 2 /FiO 2 ratio (OR: 0.99; 95% CI: 0.99, 1.00; p < 0.001) were significant predictors of the need for ventilatory support. Conclusions CXR is a reproducible tool for assessing COVID-19 and integrates with patient history, PaO 2 /FiO 2 ratio, and SpO 2 values to early predict mortality and the need for ventilatory support. Key Points • Chest X-ray is a reproducible tool for assessing COVID-19 pneumonia. • The Brixia score and percentage of lung involvement on chest X-ray integrate with patient history, PaO 2 /FIO 2 ratio, and SpO 2 values to early predict mortality and the need for ventilatory support in COVID-19 patients presenting to the emergency department.

Rectal surgery after total neoadjuvant therapy is a standard of care for proficient mismatch repair or microsatellite stable (pMMR/MSS) stage II–III rectal cancer. In patients who have clinical complete response, non-operative management (avoidance or delay of surgery and intensive surveillance) offers a patient-centred opportunity. However, its effect on metastatic recurrence remains uncertain. This study aimed to determine whether non-operative management compromises distant relapse-free survival in patients with clinical complete response after total neoadjuvant therapy. NO-CUT was an investigator-driven, multicentre, single-arm, phase 2 trial across four participating cancer centres in Italy in patients aged 18 years and older with Eastern Cooperative Oncology Group performance status of 0–1, with stage II–III adenocarcinoma of the lower-to-middle rectum, and with treatment-naive disease. Patients received four cycles of capecitabine (1000 mg/m2 orally twice a day on days 1–14 every 3 weeks) and oxaliplatin (130 mg/m2 intravenously on day 1 every 3 weeks), followed by capecitabine (825 mg/m2 orally twice a day) concurrently with radiotherapy (50–54 Gy in 25 fractions during 5 weeks). Patients who had a clinical complete response according to modified Memorial Sloan Kettering Cancer Center criteria underwent non-operative management and patients without clinical complete response received surgery. The primary endpoint was 30-month distant relapse-free survival after non-operative management in the intention-to-treat population. This trial was registered on EudraCT (2017-003671-60) and is now complete. Between June 6, 2018, and Aug 22, 2023, 180 patients with stage II-III adenocarcinoma of the lower-to-middle rectum were enrolled and started treatment. 179 patients with pMMR/MSS rectal cancer were included in the intention-to-treat population, 165 (92%) of which completed total neoadjuvant therapy and 47 (26%) had a clinical complete response and entered non-operative management. After a median follow-up of 35 months (IQR 21–50), 30-month distant relapse-free survival was 95% (95% CI 88–100) in the non-operative management group and 74% (95% CI 68–82) in the overall population. Diarrhoea (eight [4%] of 180) and neutropenia (seven [4%] of 180) were the most common grade 3–4 adverse events, consistent with expected toxicity of this regimen. No treatment-related deaths occurred. In exploratory analyses, circulating tumor DNA positivity after TNT showed both predictive and prognostic value. In pMMR/MSS stage II–III rectal cancer, total neoadjuvant therapy followed by non-operative management allows organ preservation in some patients without compromising distant relapse-free survival, supporting non-operative management as a treatment option in clinical practice. Fondazione AIRC ETS, Fondazione Oncologia Niguarda ETS, Grande Ospedale Metropolitano Niguarda, Ministero Salute, and AIRC 5xMille 2018.

The nutria (Myocastor coypus), an invasive alien species, is widely spread in Europe. Pursuant to regulation (EU) no. 1143/2014, the nutria is subject to management programs to reduce its spread. Surgical fertility control is considered an acceptable method, particularly in urban circumstances, avoiding euthanasia. To maintain the hormonal patterns and the social and behavioral dynamics, surgical infertilization preserving the gonads (i.e., salpingectomy and vasectomy) is recommended. Mini-invasive surgery is an eligible choice when dealing with wildlife, allowing reduced captivation time. For these reasons, 77 free-ranging nutrias, captured in urban nuclei in Italy, underwent infertilization under general anesthesia; laparoscopic salpingectomy and vasectomy were performed on 32 animals and traditional surgery on the remainder, leaving the gonads in place. A three-port technique was used, with two paramedian trocars (5 mm) for the instruments and a median one for the telescope. Ablation was obtained through Onemytis® plasma device, allowing a rapid surgical time with no need to place visceral sutures; the skin was surgically closed. After recovery, the animals were released, and no overt complications were noted. No modification of the behavioral patterns was noted, and the population decreased during the following months.

Prone positioning is frequently used for non-intubated hypoxemic patients with COVID-19, although conclusive evidence is still lacking. The aim of the present study was to investigate whether baseline CT-scans could predict the improvement in oxygenation in COVID-19 related Acute respira-tory syndrome (ARDS) patients when pronated. Methods: A retrospective study of COVID-19 patients who underwent non-invasive ventilation (NIV) and prone positioning was conducted. Results: Forty-five patients were included. On average, 50% of the overall lung volume was affected by the disease, as observed in the CT-scans, with ground glass opacities (GGOs) and consolidations accounting for 44% and 4%, respectively. The abnormalities were mainly posterior, as demonstrated by posterior/anterior distribution ratios of 1.5 and 4.4 for GGO and consolidation, respectively. The median PaO2/FiO2 ratio during NIV in a supine position (SP1) was 140 [IQR 108–169], which improved by 67% (+98) during prone positioning, on average. Once supine positioning was resumed (SP2), the improvement in oxygenation was maintained in 28 patients (62% of the overall population, categorized as “responders”). We found no significant differences between responders and non-responders in terms of the extent (p = 0.92) and the distribution of parenchymal abnormalities seen in the baseline CT (p = 0.526). Conclusion: Despite the lack of a priori estimation of the sample size, considering the absence of any trends in the differences and correlations, we can reasonably conclude that the baseline chest CT-scan does not predict a gas-exchange response in awake prone-positioned patients with COVID-19 related ARDS. Physicians dealing with this category of patients should not rely on the imaging at presentation when evaluating whether to pronate patients.

Background Automated analysis of lung computed tomography (CT) scans may help characterize subphenotypes of acute respiratory illness. We integrated lung CT features measured via deep learning with clinical and laboratory data in spontaneously breathing subjects to enhance the identification of COVID-19 subphenotypes. Methods This is a multicenter observational cohort study in spontaneously breathing patients with COVID-19 respiratory failure exposed to early lung CT within 7 days of admission. We explored lung CT images using deep learning approaches to quantitative and qualitative analyses; latent class analysis (LCA) by using clinical, laboratory and lung CT variables; regional differences between subphenotypes following 3D spatial trajectories. Results Complete datasets were available in 559 patients. LCA identified two subphenotypes (subphenotype 1 and 2). As compared with subphenotype 2 (n = 403), subphenotype 1 patients (n = 156) were older, had higher inflammatory biomarkers, and were more hypoxemic. Lungs in subphenotype 1 had a higher density gravitational gradient with a greater proportion of consolidated lungs as compared with subphenotype 2. In contrast, subphenotype 2 had a higher density submantellar–hilar gradient with a greater proportion of ground glass opacities as compared with subphenotype 1. Subphenotype 1 showed higher prevalence of comorbidities associated with endothelial dysfunction and higher 90-day mortality than subphenotype 2, even after adjustment for clinically meaningful variables. Conclusions Integrating lung-CT data in a LCA allowed us to identify two subphenotypes of COVID-19, with different clinical trajectories. These exploratory findings suggest a role of automated imaging characterization guided by machine learning in subphenotyping patients with respiratory failure. Trial registration : ClinicalTrials.gov Identifier: NCT04395482. Registration date: 19/05/2020.

Recovery from acute COVID-19 may be slow and incomplete: cases of Post-Acute Sequelae of COVID (PASC) are counted in millions, worldwide. We aimed to explore if and how the pre-existing Socio-economic-status (SES) influences such recovery. We analyzed a database of 1536 consecutive patients from the first wave of COVID-19 in Italy (February-September 2020), previously admitted to our referral hospital, and followed-up in a dedicated multidisciplinary intervention. We excluded those seen earlier than 12 weeks (the conventional limit for a possible PASC syndrome), and those reporting a serious complication from the acute phase (possibly accounting for symptoms persistence). We studied whether the exposition to disadvantaged SES (estimated through the Italian Institute of Statistics's model - ISTAT 2017) was affecting recovery outcomes, that is: symptoms (composite endpoint, i.e. at least one among: dyspnea, fatigue, myalgia, chest pain or palpitations); Health-Related-Quality-of-Life (HRQoL, as by SF-36 scale); post-traumatic-stress-disorder (as by IES-R scale); and lung structural damage (as by impaired CO diffusion, DLCO). Eight-hundred and twenty-five patients were included in the analysis (median age 59 years; IQR: 50-69 years, 60.2% men), of which 499 (60.5%) were previously admitted to hospital and 27 (3.3%) to Intensive-Care Unit (ICU). Those still complaining of symptoms at follow-up were 337 (40.9%; 95%CI 37.5-42.2%), and 256 had a possible Post-Traumatic Stress Disorder (PTSD) (31%, 95%CI 28.7-35.1%). DLCO was reduced in 147 (19.6%, 95%CI 17.0-22.7%). In a multivariable model, disadvantaged SES was associated with a lower HRQoL, especially for items exploring physical health (Limitations in physical activities: OR = 0.65; 95%CI = 0.47 to 0.89; p = 0.008; AUC = 0.74) and Bodily pain (OR = 0.57; 95%CI = 0.40 to 0.82; p = 0.002; AUC = 0.74). We did not observe any association between SES and the other outcomes. Recovery after COVID-19 appears to be independently affected by a pre-existent socio-economic disadvantage, and clinical assessment should incorporate SES and HRQoL measurements, along with symptoms. The socioeconomic determinants of SARS-CoV-2 disease are not exclusive of the acute infection: this finding deserves further research and specific interventions.