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Background: Circulating tumor cells (CTCs) are a promising source of biological information in cancer. Data correlating PD-L1 expression in CTCs with patients’ response to immune checkpoint inhibitors (ICIs) in non–small-cell lung cancer (NSCLC) are still lacking. Methods: This is a prospective single-center cohort study enrolling patients with advanced NSCLC. CTCs were identified and counted with the CellSearch system. PD-L1 expression on CTCs was assessed with phycoerythrin-conjugated anti-human PD-L1 antibody, clone MIH3 (BioLegend, USA). Primary endpoint was the correlation between the CTCs PD-L1 expression and overall survival (OS). Among secondary objectives, we evaluated the correlation between PD-L1 expression on CTCs and matched tumor tissue and the correlation of CTC number and baseline tumor size (BTS). Results: Thirty-nine patients treated with anti-PD-1/PD-L1 agents as second- or third-line therapy were enrolled. Patients were divided into 3 groups: no CTC detectable (CTCnull, n = 15), PD-L1 positive CTC (CTCpos, n = 13), and PD-L1 negative CTC (CTCneg, n = 11). Median OS in patients with CTCneg was 2.2 months, 95% confidence interval (CI), 0.8-3.6 (reference) versus 3.7 months, 95% CI, 0.1-7.5 (hazard ratio [HR] 0.33; 95% CI, 0.13-0.83; P = .019) in patients with CTCpos versus 16.0 months, 95% CI, 2.2-29.8 (HR 0.17; 95% CI, 0.06-0.45; P< .001) in patients with CTCnull. No correlation was found between PD-L1 expression on CTCs and on tumor tissue. CTC number was correlated with BTS. Conclusion: PD-L1 expression on CTCs is a promising biomarker in patients with NSCLC treated with ICIs. Further validation as predictive biomarker is needed.

Introduction: Haemophilia management and patients’ quality of life significantly improved. However, data on current patients’, caregivers’ and clinicians’ satisfaction and limitations of treatments and haemophilia management are limited. Aim: Assessing the management satisfaction and unmet needs from the perspective of Italian patients with haemophilia (PWH) without inhibitors (or caregivers if children) and of specialist physicians. Methods: Surveys (for patients≥18 years, caregivers of children and haemophilia specialists) were developed by a multidisciplinary working group and conducted from November 2019 to June 2020. Results: Among 275 participants, 120 (43.6%) were PWH without inhibitors, 79 (28.7%) caregivers and 37 (13.4%) clinicians. Patients and caregivers perceived a higher control of the disease compared to clinicians. However, more than 40% of patients and caregivers reported to feel significantly conditioned by the risk of bleeding during their daily life. PWH reported a 6-month mean/median (range) of bleeds 2.3/.0 (0-24) and caregivers 1.3/.0 (0-16) in children. The treatment burden (frequency of administration) was not satisfactory for more than half adults and caregivers of children treated with prophylaxis. A good access to treatment, haemophilia centres and medical service was reported, with issues associated to the multidisciplinary approach and treatment at emergency department. Conclusions: This large national study provides an updated overview of haemophilia care in Italy from different points of views, highlighting positive aspects and unmet needs. This information can guide future interventions to improve haemophilia management and the assessment of impact of new treatment options.

Several novel androgen receptor (AR)-inhibitors have been introduced for nonmetastatic castration-resistant prostate cancer (nmCRPC) treatment, with the improvement of survival outcomes which need to be balanced against the risk of adverse events. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating enzalutamide, apalutamide and darolutamide in nmCRPC patients, to assess overall survival (OS), incidence and risk of adverse drug events, adverse-events-related death and adverse-events-related treatment discontinuation. We selected three RCTs (SPARTAN, PROSPER and ARAMIS). New hormonal agents administration resulted in better OS, despite the increased risk of several any grade and grade 3-4 adverse events. In the decision-making process, careful evaluation of expected adverse events, patients' comorbidities and maintenance of quality of life are mandatory.

Introduction: Immune checkpoint inhibitors (ICIs) have become the standard of care in the management of advanced non–small cell lung cancer (NSCLC). Nevertheless, only a small proportion of patients benefit from ICIs. The aim of the present study is to assess whether 2-deoxy-2-[18F]fluoro-D-GLUCOSE POSITRON EMISSION TOMOGRAPHY-COMPUTED TOMOGRAPHY ([18F]FDG-PET/CT)–derived parameters may be used as biomarkers in patients with advanced NSCLC receiving first-line pembrolizumab. Materials and methods: This is a monocentric retrospective cohort study including patients with advanced NSCLC (stage IV) and Programmed death-ligand 1 (PD-L1) expression ≥50% treated with pembrolizumab. A control group of patients treated with epidermal growth factor receptor (EGFR) inhibitors for EGFR-mutated NSCLC was also enrolled. Only patients with a positive [18F]18F-FDG PET/CT result within 60 days from treatment initiation were included.Total metabolic tumour volume (tMTV) was calculated for each lesion using a dedicated software (PET VCAR; GE Healthcare), which semiautomatically delineates the tumour's contours with a maximum standardised uptake value (SUVmax) threshold of 42% within the lesion. tMTV was obtained summing each lesion's MTV. Potential prognostic parameters for overall survival (OS) were analysed (tMTV, SUVmax, bone/liver metastasis, neutrophil:lymphocyte ratio ≥4, Eastern Cooperative Oncology Group performance status ≥2, lactate dehydrogenase above the upper limit of normal). Results: Overall, 34 patients treated with first line-pembrolizumab and 40 patients treated with EGFR tyrosine kinase inhibitors were included. In the pembrolizumab group, the median follow-up was 20.3, while the median OS was 4.7 months (95% confidence interval [CI] = 0.3–9.1) for patients with tMTV ≥75 cm3 vs not reached (NR) for patients with tMTV

Objectives: ICIs have been approved and are routinely administered regardless of performance status (PS), despite randomized clinical trials of ICIs alone or combined with chemotherapy or target therapy enrolled patients with ECOG PS 0 or 1, while patients with ECOG PS 2 or more were excluded. Materials and methods: We carried out a meta-analysis of available clinical studies exploring the prognostic impact of PS ≥ 2 on Overall Survival (OS), Progression Free Survival (PFS) or Overall Response Rate (ORR) in patients with non small cell lung cancer (NSCLC) treated with immunotherapy (any line). Results: We reviewed 19 studies, comprising 3600 NSCLC patients, 757 of whom with ECOG PS > 1 (average 21.0%, range 6.0–48.6%). In the overall population PS ≥ 2 resulted in worse OS, PFS and ORR (OS pooled hazard ratio of 2.72; 95% CI: 2.03–3.63; I2 72.70%, p < 0.001; PFS pooled hazard ratio of 2.39; 95% CI 1.81–3.15, p < 0.0001; I2 73.03%; ORR pooled odds ratio 0.25; 95% CI 0.11–0.56, p 0.001; I2 0.00%). Conclusion: ECOG PS ≥ 2 retains an important prognostic validity in patients treated with ICI similar, in terms of effect size, to that reported for chemotherapy in NSCLC. The high level of heterogeneity for OS and PFS analysis (but not for ORR), not completely explained by the different proportion of ECOG 3−4 patients (ranging from 0% to 50% of the PS ≥ 2 population), could be the result of both patient heterogeneity within the PS 2 population and the subjectivity of ECOG PS assessment. Whether poorer PS is also a predictor of lower immunotherapy efficacy remains still to be demonstrated.

Introduction: Substantial paradigm shifts have been recently registered in metastatic renal cell carcinoma (mRCC), with combination therapies including immunotherapy showing unprecedented results. We performed number needed to treat (NNT) and number needed to harm (NNH) analyses to evaluate these approaches in mRCC.Areas covered: Clinical data of mRCC patients enrolled in four phase III trials were collected. The rates at 6, 12, 18, and 24 months for overall survival (OS), duration of response (DoR), and progression-free survival (PFS) were considered. At 6 months, the number of patients that should be treated to prevent one death with sunitinib was 20 for both pembrolizumab-lenvatinib or axitinib, 14 for nivolumab-cabozantinib, and 50 for nivolumab-ipilimumab. NNT was 100 (at 6 months) or >100 (at 12 and 18 months) for nivolumab-ipilimumab. The combinations reported peculiar and not superimposable safety profiles at the NNH analysis.Expert opinion: Although our results should be interpreted with caution, the analysis provides useful insight into the increasingly compelling interpretation of clinical trials. Immune combinations present clinically meaningful differences in terms of efficacy, with some treatments reporting different results at the NNT and the NNH analyses.

Patients with haematopoietic disorders requiring long-term blood transfusions are at risk of iron overload. This study aimed to investigate the efficacy and safety of long-term deferasirox monotherapy in patients with transfusion-dependent anaemia in the routine clinical practice setting.This was a retrospective analysis of patients who commenced deferasirox therapy at the Hospital Bianchi Melacrino Morelli in Reggio Calabria, Italy. Data collected included cardiac and hepatic iron load (assessed by magnetic resonance imaging); left ventricular ejection fraction (LVEF). Patients were divided into two groups for analysis: group A (baseline information collected prior to deferasirox initiation) and group B (baseline information collected after deferasirox initiation).Forty-six patients were included (group A: n=25; group B: n=21). The overall population was 63% male, with a mean age of 33 years. The majority of patients (65%) had thalassaemia major. In the overall population, cardiac iron levels between the baseline and first follow-up visits improved in both groups A and B (29.2 vs. 32.5 ms; p=0.04 and 28.4 vs. 31.4 ms; p=0.038). Liver iron levels improved significantly from baseline to visit 1 in group A (7.2 vs. 12.1 ms; p0.004) and from baseline to visit 3 (6.9 vs. 10.7; p=0.049) in group B. Generally, there was no correlation between cardiac and liver iron levels. LVEF remained stable throughout the study period. Deferasirox was well tolerated and was not associated with significant adverse events.Long-term treatment with deferasirox is effective and safe in patients with transfusion-dependent haemoglobinopathies monitored in the clinical practice setting.

This multisite study was conducted to compare the efficacy and tolerability of combination treatment with clozapine plus aripiprazole versus combination treatment with clozapine plus haloperidol in patients with schizophrenia who do not have an optimal response to clozapine. Patients continued to take clozapine and were randomly assigned to receive daily augmentation with aripiprazole or haloperidol. Physicians prescribed the allocated treatments according to usual clinical care. Withdrawal from allocated treatment within 3 months was the primary outcome. Secondary outcomes included severity of symptoms on the Brief Psychiatric Rating Scale and antipsychotic subjective tolerability on the Liverpool University Neuroleptic Side Effect Rating Scale. A total of 106 patients with schizophrenia were randomly assigned to treatment. After 3 months, we found no difference in the proportion of patients who discontinued treatment between the aripiprazole and haloperidol groups (13.2% vs 15.1%, P = 0.780). The 3-month change of the Brief Psychiatric Rating Scale total score was similar in the aripiprazole and haloperidol groups (-5.9 vs -4.4 points, P = 0.523), whereas the 3-month decrease of the Liverpool University Neuroleptic Side Effect Rating Scale total score was significantly higher in the aripiprazole group than in the haloperidol group (-7.4 vs -2.0 points, P = 0.006). These results suggest that augmentation of clozapine with aripiprazole offers no benefit with regard to treatment withdrawal and overall symptoms in schizophrenia compared with augmentation with haloperidol. However, an advantage in the perception of adverse effects with aripiprazole treatment may be meaningful for patients.

Background One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study. Methods/Design The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome. Discussion The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia. Trial Registration Clincaltrials.gov Identifier: NCT00395915

After a brief analysis of the present epidemiological situation both international and of our country, on the possibility of early diagnosis on clinical and laboratory bases, the A.A. dwell upon the most frequent dental pathologies in case of AIDS and upon the possibilities of singling patients suffering from the so-called "spy-lesions" of the oral cavity, which are characteristic in most cases. The A.A. conclude by reporting the methodologies (materials and methods) which are to be used, from time to time, in order to carry out a careful and correct anti-AIDS prophylaxis in dentistry, either of individuals and medical personnel or of instruments and work-environments.

Giardia Lamblia is the flagellated protozoan of intestinal-tract more frequently diagnosed. This disease is well known all over the world, particularly in hot countries and under precarious hygienic-environmental conditions. In Italy the rate of infestation is around 8%. The giardiasis affects people of every age. The disease can be transmitted either by direct contagion or through the ingestion of food contaminated by cysts. Some A.A. believe that in the last years real epidemics in adults occurred, due to the current changing in the habits of life, in particular as regards food and the use of canteens. The italian law demands the competent sanitary authorities to prepare diagnostical procedures for sanitary checks, to be carried out for consignment and renewal of the employment card and for periodical checks on production, manipulation, transport and sale-staff. In a quadrenniale study (1985-1988) the A.A. estimate the incidence of the intestinal parasites and they evaluate the real danger and risks deriving from the contamination of food, by checking 160 canteen-men working in a know metal-mechanical industry in our country, through periodical parasitological stool examination. The parasitological stool exam was carried out bright and after enrichment by Ritchie's method. The Giardia Lamblia, that certainly is the ++intestinal parasite more often isolated in our country, has been observed with varying frequency during the examined period from 1.9% to 5.6%. In 4 years, 38% of these patients, even undergoing specific therapy, has shown relapsing and recurrent infestations both in the following year and later.(ABSTRACT TRUNCATED AT 250 WORDS)