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 included197 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 followup 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 endpoints 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.     

Drainage of pleural effusion in mechanically ventilated patients: Time to measure chest wall compliance?

Purpose

Pleural effusion (PE) is commonly encountered in mechanically ventilated, critically ill patients and is generally addressed with evacuation or by fluid displacement using increased airway pressure (P_AW). However, except when massive or infected, clear evidence is lacking to guide its management. The aim of this study was to investigate the effect of recruitment maneuvers and drainage of unilateral PE on respiratory mechanics, gas exchange, and lung volume.

Materials and methods

Fifteen critically ill and mechanically ventilated patients with unilateral PE were enrolled. A 3-step protocol (baseline, recruitment, and effusion drainage) was applied to patients with more than 400 mL of PE, as estimated by chest ultrasound. Predefined subgroup analysis compared patients with normal vs reduced chest wall compliance (C_CW). Esophageal and P_AWs, respiratory system, lung and C_CWs, arterial blood gases, and end-expiratory lung volumes were recorded.

Results

In the whole case mix, neither recruitment nor drainage improved gas exchange, lung volume, or tidal mechanics. When C_CW was normal, recruitment improved lung compliance (81.9 [64.8-104.1] vs 103.7 [91.5-111.7] mL/cm H₂O, P < .05), whereas drainage had no significant effect on total respiratory system mechanics or gas exchange, although it measurably increased lung volume (1717 vs 2150 mL, P < .05). In the setting of reduced C_CW, however, recruitment had no significant effect on total respiratory system mechanics or gas exchange, whereas pleural drainage improved respiratory system and C_CWs as well as lung volume (42.7 [38.9-50.0] vs 47.0 [43.8-63.3], P < .05 and 97.4 [89.3-97.9] vs 126.7 [92.3-153.8] mL/cm H₂O, P < .05 and 1580 vs 1750 mL, P < .05, respectively).

Conclusions

Drainage of a moderate-sized effusion should not be routinely performed in unselected population of critically ill patients. We suggest that measurement of C_CW may help in the decision-making process.     

Endogenous testosterone density is an independent predictor of pelvic lymph node invasion in high-risk prostate cancer: results in 201 consecutive patients treated with radical prostatectomy and extended pelvic lymph node dissection

International Urology and Nephrology - To evaluate the influence of endogenous testosterone density (ETD) on pelvic lymph node invasion (PLNI) in high risk (HR) prostate cancer (PCa) treated with...     

Predictors of vitamin B6 and folate concentrations in older persons: the InCHIANTI study

BACKGROUND: Low dietary intake and low serum concentrations of vitamin B6 and/or folate are associated with increased risk of vascular events, possibly because of their association with inflammation, which plays a crucial role in the pathogenesis of cardiovascular diseases. METHODS: Using data from 1320 participants in the population-based InCHIANTI study (586 men and 734 women; median age, 69 years; range, 21-102 years) for whom complete data on folate, vitamin B6, inflammatory markers, 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T sequence variant, and important covariates were available, we evaluated the association of inflammatory markers with circulating concentrations of vitamin B6 and folate, independently of dietary vitamin intake, circulating vitamin concentrations, and MTHFR C677T sequence variant. RESULTS: According to multiple linear regression analysis, C-reactive protein and interleukin-6 receptor were strongly and negatively associated with circulating vitamin B6 but not with folate concentrations, independent of age, sex, serum creatinine, serum albumin, total energy intake, smoking history, dietary nutrient intake, and circulating homocysteine and vitamin concentrations. Serum folate concentrations were related to MTHFR 677 TT genotype in persons with folate intake in the lowest tertile (< 221.2 microg/day). Vitamin C and retinol intakes were strongly and positively associated with serum folate concentrations independent of age, sex, serum creatinine, serum albumin, total energy intake, smoking history, homocysteine plasma concentrations, dietary nutrient intakes, serum vitamin B6 and vitamin B12 concentrations, and MTHFR C677T sequence variant. CONCLUSIONS: Low serum vitamin B6, but not serum folate, concentrations are independent correlates of the proinflammatory state, and both are influenced by antioxidant reserves.