Bevacizumab plus XELOX as first-line treatment of metastatic colorectal cancer: The OBELIX study

AIM: To confirm the efficacy and safety of bevacizumab/XELOX combination for the treatment of locally advanced or metastatic colorectal cancer (CRC) in Italy. METHODS: This multicentric, prospective, open-label study included patients with CRC previously untreated with chemotherapy. Patients were administered bevacizumab in combination with XELOX. The primary efficacy end-point was progression-free survival (PFS). Secondary end-points included time to overall response (TOR), duration of response (DOR), time to treatment failure (TTF) and overall survival (OS). The incidence and type of adverse events AEs and severe AEs were evaluated. Also, the mutational status of BRAF and KRAS was assessed by high resolution melting and direct sequencing, and quality of life (QoL) was measured by the EuroQoL EQ-5D questionnaire at baseline and at the last visit. RESULTS: The intention-to-treat population included 197 patients (mean age: 62.3 ± 9.9 years, 56.4% males). At baseline, 16/34 evaluable subjects (47.1%) harbored a KRAS and/or a BRAF mutation; the mean QoL index was 80.2 ± 14.3. First-line therapy was given for 223.7 ± 175.9 d, and after a mean follow-up of 387.7 ± 238.8 d all patients discontinued from the study mainly for disease progression (PD, 45.4%) and AEs (25.4%). Median PFS was 9.7 mo (95%CI: 8.4-10.5) and the median values for secondary end-points were: TOR = 3.9 mo (95%CI: 2.6-4.7), DOR = 8.5 mo (95%CI: 7.3-10.3), TTF = 6.7 mo (95%CI: 6.0-7.7) and OS = 23.2 mo (95%CI: 20.1-27.2). Patients carrying at least one lesion had a lower overall response rate (66.7% vs 88.9%) and a lower probability of achieving complete or partial response than those without mutations, but the difference in relative risk was not statistically significant (P = 0.2). Mean EQ-5D-3L raw index score significantly decreased to 74.9 ± 19.1 at the last visit (signed-rank test, P = 0.0076), but in general the evaluation on QoL perceived by patients was good. CONCLUSION: The efficacy of bevacizumab in combination with XELOX in terms of PFS in patients with aCRC or mCRC in Italy was confirmed, with acceptable toxicity

Religion and quality of democracy in Israel

This research aims to answer the following questions: How does religion (in particular Judaism) affect the quality of democracy in Israel? Why, historically, religion assumed this role? How the correlation between religion and democracy affects the life of the so called "dominant" Jewish group? Using the TODEM method for democratic deepening, the procedural dimensions are investigated. The dimensions are: rule of law, electoral and inter-institutional accountability, participation and competition. After analyzing of all of them, a strong influence of religion is found in rule of law, participation and competition. This influence is evident at the institutional as well as at the social level and deeply affects the quality of democracy. Although the research does not question the belonging of Israel to the democratic group, a label is created to underline the shaping influence of religion: Orthodemocracy. This term refers both to the institutional role of religion (all recognized religions in Israel are given this role) and, in a more specific acceptation, to the role of Orthodox Judaism. The legal validity of religious norms in Orthodemocracy creates paths of discrimination and inequality that greatly impact on the daily life of the citizens. Jewish citizens, that a popular ethnic approach portrays as dominant in the Israeli society are all but exempted from the discriminatory effects. The strong influence that religion plays has historical reasons: this research argues that the source of power, since the diffusion of the nationalistic ideology, was the need for the state-enterprise to be agreed upon among all Jews. Religious legitimization, especially at the international level, was an absolute necessity for the Zionist project. Benefiting from this very political need, the religious minority managed to achieve astounding victories in terms of autonomy and influence in the society. After the dominance of the Zionists political leadership extinguished, the power was maintained through a new political role that the religious parties acquired in the fragmented Israeli society: that of Kingmakers

“Bordeaux Neobladder”: First Evaluation of the Urodynamic Outcomes

Background: The intracorporeal orthotopic modified-Y “Bordeaux“ neobladder (iYNB) was first described in 2016. No urodynamic evaluation of this neobladder has yet been performed. Objective: To present the urodynamic features of the iYNB and incontinence-specific health-related quality of life (HRQoL) outcomes. Design, setting, and participants: We prospectively assessed 26 patients operated between September 2018 and November 2020. Surgical procedure: Robotic radical cystectomy for malignant disease of the bladder and iYNB, performed by a single surgeon, were used. Measurements: Three months after surgery and in November 2021, consenting patients underwent clinical evaluation and multichannel urodynamic study (UDS). The incontinence quality of life (I-QoL) questionnaire was used to evaluate HRQoL. Continence was classified into day- and nighttime, and clinically defined as the use of zero pads. A descriptive statistical analysis was performed. Results and limitations: The mean age at surgery was 65.4 yr. The mean follow-up period was 27 mo (12–38). The mean time for the neobladder reconstruction was 192 min (110–340). The mean maximum capacity was 431 cm3 (range 200–553). The mean postvoid residual was 101.6 ml (0–310), and the rate of clean intermittent catheterization was 17.6%. With the exception of a significant reduction in the volume of the first sensation of bladder fullness, no other statistically significant changes in the UDS parameters of both the storage and the voiding phase were observed over time. Day- and nighttime continence rates were 58.8% and 23.5%, respectively. The mean postoperative I-QoL score was 103.3 (89–110). Limitations include the small number of patients and short follow-up. Conclusions: The UDS evaluation of iYNB demonstrates that both the volumetric and the pressure characteristics are acceptable and may enhance quality of life. Prospective studies with larger numbers of patients and longer follow-up are needed to further evaluate the iYNB. Patient summary: The “Bordeaux“ neobladder provides acceptable urodynamic outcomes. It is associated with high levels of health-related quality of life and good rates of continence in patients

Is off-clamp robot-assisted partial nephrectomy beneficial for renal function? Data from the CLOCK trial

23noTo compare the functional outcomes of on- vs off-clamp robot-assisted partial nephrectomy (RAPN) within a randomized controlled trial (RCT).nonenoneAntonelli, Alessandro; Cindolo, Luca; Sandri, Marco; Veccia, Alessandro; Annino, Filippo; Bertagna, Francesco; Carini, Marco; Celia, Antonio; D'Orta, Carlo; De Concilio, Bernardino; Furlan, Maria; Giommoni, Valentina; Ingrosso, Manuela; Mari, Andrea; Nucciotti, Roberto; Olianti, Catia; Porreca, Angelo; Primiceri, Giulia; Schips, Luigi; Sessa, Francesco; Bove, Pierluigi; Simeone, Claudio; Minervini, AndreaAntonelli, Alessandro; Cindolo, Luca; Sandri, Marco; Veccia, Alessandro; Annino, Filippo; Bertagna, Francesco; Carini, Marco; Celia, Antonio; D'Orta, Carlo; De Concilio, Bernardino; Furlan, Maria; Giommoni, Valentina; Ingrosso, Manuela; Mari, Andrea; Nucciotti, Roberto; Olianti, Catia; Porreca, Angelo; Primiceri, Giulia; Schips, Luigi; Sessa, Francesco; Bove, Pierluigi; Simeone, Claudio; Minervini, Andre