Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario

Introduction: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time. Methods: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann\u2013Whitney U test for continuous variables. Results: A slight reduction ( 126.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop 1212% versus 123.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36). Conclusions: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts

Efficacy and safety of extracranial vein angioplasty in multiple sclerosis: A randomized clinical trial

Importance: Chronic cerebrospinal venous insufficiency (CCSVI) is characterized by restricted venous outflow from the brain and spinal cord. Whether this condition is associated with multiple sclerosis (MS) and whether venous percutaneous transluminal angioplasty (PTA) is beneficial in persons with MS and CCSVI is controversial. Objective: To determine the efficacy and safety of venous PTA in patients with MS and CCSVI. Design, Setting, and Participants: We analyzed 177 patients with relapsing-remitting MS; 62 were ineligible, including 47 (26.6%) who did not have CCSVI on color Doppler ultrasonography screening. A total of 115 patients were recruited in the study timeframe. All patients underwent a randomized, double-blind, sham-controlled, parallel-group trial in 6MS centers in Italy. The trial began in August 2012 and concluded in March 2016; data were analyzed from April 2016 to September 2016. The analysis was intention to treat. Interventions: Patients were randomly allocated (2:1) to either venous PTA or catheter venography without venous angioplasty (sham). Main Outcomes and Measures: Two primary end pointswere assessed at 12 months: (1) a composite functional measure (ie, walking control, balance, manual dexterity, postvoid residual urine volume, and visual acuity) and (2) a measure of new combined brain lesions on magnetic resonance imaging, including the proportion of lesion-free patients. Combined lesions included T1 gadolinium-enhancing lesions plus new or enlarged T2 lesions. Results: Of the included 115 patients with relapsing-remitting MS, 76 were allocated to the PTA group (45 female [59%]; mean [SD] age, 40.0 [10.3] years) and 39 to the sham group (29 female [74%]; mean [SD] age, 37.5 [10.6] years); 112 (97.4%) completed follow-up. No serious adverse events occurred. Flow restoration was achieved in 38 of 71 patients (54%) in the PTA group. The functional composite measure did not differ between the PTA and sham groups (41.7%vs 48.7%; odds ratio, 0.75; 95%CI, 0.34-1.68; P = .49). The mean (SD) number of combined lesions on magnetic resonance imaging at 6 to 12 months were 0.47 (1.19) in the PTA group vs 1.27 (2.65) in the sham group (mean ratio, 0.37; 95%CI, 0.15-0.91; P = .03: adjusted P = .09) and were 1.40 (4.21) in the PTA group vs 1.95 (3.73) in the sham group at 0 to 12 months (mean ratio, 0.72; 95%CI, 0.32-1.63; P = .45; adjusted P = .45). At follow-up after 6 to 12 months, 58 of 70 patients (83%) in the PTA group and 22 of 33 (67%) in the sham group were free of new lesions on magnetic resonance imaging (odds ratio, 2.64; 95%CI, 1.11-6.28; P = .03; adjusted P = .09). At 0 to 12 months, 46 of 73 patients (63.0%) in the PTA group and 18 of 37 (49%) in the sham group were free of new lesions on magnetic resonance imaging (odds ratio, 1.80; 95%CI, 0.81-4.01; P = .15; adjusted P = .30). Conclusion and Relevance: Venous PTA has proven to be a safe but largely ineffective technique; the treatment cannot be recommended in patients with MS

Síntese e caracterização térmica e química do copolímero poli(D,L-lactídeo-co-glicolídeo) Synthesis and thermal and chemical characterization of the poly(D,L-lactide-co-glycolide) copolymer

O copolímero poli(D,L-lactídeo-co-glicolídeo) apresenta-se como um dos polímeros de maior interesse para aplicação na área médica. O fato de ser biorreabsorvível, biocompatível, atóxico e ter uma cinética de degradação que pode ser modificada pela razão entre os monômeros na copolimerização justifica tal interesse. Neste trabalho, os copolímeros foram sintetizados a 175 ºC, por meio da abertura dos anéis dos dímeros cíclicos dos monômeros D,L-lactídeo e glicolídeo, na presença do iniciador octanoato de estanho e do co-iniciador álcool laurílico. O controle eficiente do vácuo no meio reacional, aliado à adequada agitação, foram fundamentais para o sucesso da síntese. Para caracterização dos copolímeros sintetizados foram empregadas as técnicas de calorimetria exploratória diferencial (DSC), termogravimetria (TG) e espectroscopia na região do infravermelho (FTIR). Foram analisados não somente os produtos de reação, mas também os monômeros de partida. A nova rota de síntese utilizada mostrou-se adequada, sendo os copolímeros poli(D,L-lactídeo-co-glicolídeo) obtidos com sucesso.Poly (D, L-lactide-co-glycolide) copolymer (PLGA) has attracted a great deal of interest due to their special characteristics as biomaterials since it is bioreabsorbable, biocompatible, nontoxic and the kinetics of degradation can be modified by the ratio of monomers in copolymerization. In this work, the copolymers were synthesized at 175 ºC, by opening the ring of cyclic dimers of D,L-lactide and glycolide monomers in the presence of tin(II) octanoate initiator and lauryl alcohol co-initiator. The efficient control of the vacuum in the medium combined with adequate stirring were essential to the success of the synthesis. Characterization of the copolymers samples was carried out by using differential scanning calorimetry (DSC), thermogravimetry (TG) and Fourier transform infrared spectroscopy (FTIR). We analyzed not only the products of reaction but also the initial monomers. The new synthesis route employed was appropriate and the poly(D, L-lactide-co-glycolide) was successfully obtained

Advanced Non-Clear Cell Renal Cell Carcinoma Treatments and Survival: A Real-World Single-Centre Experience

Simple Summary Non-clear cell renal cell carcinoma (nccRCC) represents about the 20% of all RCCs but recommendations on treatment lacks evidence since the clinical trials include only clear cell RCC (ccRCC). The aim of our retrospective studies was to evaluate the efficacy of TKI and immunotherapy-based combinations in this population. We confirmed that nccRCC are heterogeneous and have a poorer prognosis as compared to ccRCC. The introduction of immunotherapy increased the efficacy of the treatments and the survival outcomes. Prognostic factors such as IMDC score or NLR are valid also for nccRCC. We highlight the importance of a pathological review and the need for prospective randomized trials designed for the different subtypes.Abstract Background: Non-clear cell renal cell carcinoma (nccRCC) is a heterogeneous group of cancer. Treatment recommendations are extrapolated from ccRCC and lack solid evidence. Here, we review advanced nccRCC patients treated at our institute. Patients and methods: We collected retrospective data on all advanced nccRCC pts treated at the Istituto Oncologico Veneto from January 2008. We compared overall response rate (ORR), progression free survival (PFS) and overall survival (OS) according to histological subtypes and type of systemic treatments. Kaplan-Meier method, log-rank test and Cox regression were used to estimate and compare PFS and OS. Results: Of 1370 RCC patients, 289 had a diagnosis of nccRCC and 121 were eligible for the analysis. Fifty-three pts showed papillary histology (pRCC), 15 chromophobe; 37 unclassified RCC (NOS-RCC), 16 other histologies. Pts with chromophobe and other hystologies showed poorer survival rates compared to pRCC and NOS-RCC (mOS 10.7 vs. 20.7 vs. 30.7, p = 0.34). Pts treated with combination regimens achieved a better OS (30.7 vs. 13.7, p = 0.10), PFS (12.7 vs. 6.4, p = 0.10) and ORR (42.4% vs. 13.9%, p = 0.002) than those treated with monotherapy. IMDC and Meet-URO score retained their prognostic value. Conclusion: Our retrospective real-life cohort of advanced nccRCC patients shows that immunotherapy-based combinations could improve ORR, PFS and OS compared to TKI monotherapy. Prospective trials for nccRCC patients utilizing novel therapies are ongoing and their results eagerly awaited