Phase II study of panitumumab combined with capecitabine and oxaliplatin as first-line treatment in metastatic colorectal cancer patients: clinical results including extended tumor genotyping

This clinical trial assessed the efficacy and toxicity of panitumumab combined with oxaliplatin and capecitabine as first-line treatment in KRAS exon 2 wild-type metastatic colorectal cancer (mCRC) patients. Patients with exon 2 KRAS wild-type mCRC received panitumumab 9 mg/Kg, oxaliplatin 130 mg/m², and capecitabine 2000 mg/m² repeated every 3 weeks. The primary endpoint was objective response rate (ORR, minimum 42 responses). We retrospectively assessed mutations in genes implicated in CRC with massively parallel sequencing; ERBB2 and EGFR amplification with fluorescence in situ hybridization, and tumor-infiltrating lymphocyte density. Among 78 patients enrolled, 45 (57.7%) completed 6 cycles. Most common grade 3–4 toxicities were skin rash (19.2%), diarrhea (18%), and neuropathy (6.4%). Among 5 (6.4%) potentially treatment-related deaths, 2 (2.6%) were characterized toxic. Objective response occurred in 43 (55.1%) of the patients (complete 6.4% and partial response 48.7%; stable 17.9% and progressive disease 7.7%), while 3.8% were non-evaluable and 15% discontinued their treatment early. Additional mutations in KRAS/NRAS/BRAF were found in 11/62 assessable (18%) tumors. After 51 months median follow-up, median progression-free (PFS) was 8.1 and overall survival 20.2 months, independently of KRAS/NRAS/BRAF or PI3K-pathway mutation status. Patients with TP53 mutations (n?=?34; 55%), as well as those with left colon primary tumors (n?=?66; 85%), had significantly better PFS, also confirmed in multivariate analysis. Although the clinical trial met its primary endpoint, according to the current standards, the efficacy and tolerability of the drug combination are considered insufficient. Extended genotyping yielded interesting results regarding the significance of TP53 mutations.ClinicalTrials.gov identifier: NCT01215539, Registration date: Sep 29, 2010.     

Acute responses of breathing techniques in maximal inspiratory pressure

Purpose

The purpose of the present study was to examine the effect of three breathing techniques [normal breath (NB), breath holding (BH) and intermittent breath holding (IBH)] on finswimmers’ heart rate (HR), arterial oxygen saturation (SpO₂) and maximum inspiratory pressure (PI_max).

Methods

Ten young finswimmers (15.8 ± 0.5 years) performed 8 × 25 m freestyle leg kick trials under the three different breathing occasions (NB, BH and IBH). HR, SpO₂ and PI_max were recorded immediately after the end of each test.

Results

The results showed lower SpO₂ values immediately after the end of IBH technique in correlation with the other breathing techniques (IBH: 88 ± 0.9%; BH: 93.3 ± 0.7%; NB: 98.3 ± 0.3%; p < 0.001). Additionally, HR was higher after IBH compared to the other breathing techniques (IBH: 177 ± 4.2 bpm^?1; BH: 165.7 ± 7.9 bpm^?1; NB: 158.3 ± 2.2 bpm^?1, p < 0.001) and PI_max was also higher after the IBH compared to the other two techniques (IBH: 168.3 ± 5.3 cmH₂O; BH: 166 ± 11 cmH₂O; NB: 161.7 ± 11.4 cmH₂O; p < 0.05).

Conclusion

The data from the present study support that BH and even more so IBH training acutely increase the inspiratory muscles strength. This is an important training tool to improve the inspiratory muscle performance in athletes.

     

Fatal intoxication with antidepressants: a case with many culprits

Serotonin-specific reuptake inhibitors (SSRIs) are generally considered safe drugs but fatal adverse effects do sometimes occur, often as a consequence of interactions with other serotonin active drugs. Polypharmacy is usually a problem that the elderly encounter, but it can also have dire consequences for young people, especially when an underlying heart condition is present. Thus, failure to diagnose heart disease and the use of contraindicated medications can be a lethal combination, irrespective of age. Here we present a case of a young adult suffering from bipolar disorder who used a combination of two SSRIs (citalopram and fluoxetine) and a monoamine oxidase inhibitor (MAO; moclobemide) with tragic consequences. The deceased also suffered from undiagnosed hypertrophic cardiomyopathy and was carrier of a genotype that may have predisposed him to increased sensitivity to SSRIs. The apparent difficulty in establishing the manner of death in this case is also discussed.     

Dual tracer tau PET imaging reveals different molecular targets for <Superscript>11</Superscript>C-THK5351 and <Superscript>11</Superscript>C-PBB3 in the Alzheimer brain

Purpose

Several tau PET tracers have been developed, but it remains unclear whether they bind to the same molecular target on the heterogeneous tau pathology. In this study we evaluated the binding of two chemically different tau-specific PET tracers (¹¹C-THK5351 and ¹¹C-PBB3) in a head-to-head, in vivo, multimodal design.

Methods

Nine patients with a diagnosis of mild cognitive impairment or probable Alzheimer’s disease and cerebrospinal fluid biomarker evidence supportive of the presence of Alzheimer’s disease brain pathology were recruited after thorough clinical assessment. All patients underwent imaging with the tau-specific PET tracers ¹¹C-THK5351 and ¹¹C-PBB3 on the same day, as well as imaging with the amyloid-beta-specific tracer ¹¹C-AZD2184, a T1-MRI sequence, and neuropsychological assessment.

Results

The load and regional distribution of binding differed between ¹¹C-THK5351 and ¹¹C-PBB3 with no statistically significant regional correlations observed between the tracers. The binding pattern of ¹¹C-PBB3, but not that of ¹¹C-THK5351, in the temporal lobe resembled that of ¹¹C-AZD2184, with strong correlations detected between ¹¹C-PBB3 and ¹¹C-AZD2184 in the temporal and occipital lobes. Global cognition correlated more closely with ¹¹C-THK5351 than with ¹¹C-PBB3 binding. Similarly, cerebrospinal fluid tau measures and entorhinal cortex thickness were more closely correlated with ¹¹C-THK5351 than with ¹¹C-PBB3 binding.

Conclusion

This research suggests different molecular targets for these tracers; while ¹¹C-PBB3 appeared to preferentially bind to tau deposits with a close spatial relationship to amyloid-beta, the binding pattern of ¹¹C-THK5351 fitted the expected distribution of tau pathology in Alzheimer’s disease better and was more closely related to downstream disease markers.

     

Assessment of Depression and Anxiety in Breast Cancer Patients: Prevalence and Associated Factors

Introduction: Having breast cancer or receiving treatment has been seen as a traumatic experience for women dueto its impacts on their self-image and sexual relationship, and may lead to an psychological reactions such as denial,anger, or intense fear toward their disease and treatment process. Also many of breast cancer patients have psychiatricmorbidities such as depression and anxiety. Purpose: The purpose of this study was to assess the prevalence andassociated factors of depression and anxiety in breast cancer patients, in order to identify independent predictors of mentalhealth disorders risk. Material and Methods: A cohort of 152 breast cancer patients who were attending an outpatientoncology department was recruited. Data were collected with a structured questionnaire consisted by social, clinicaland demographic information and PHQ-2 and GAD-2 scales. Results: The mean age of the patients was 53.25 years(SD=12.10), 69.7% of the patients underwent mastectomy and 30.3% ongectomy. Chemotherapy received 46.1% ofpatients as adjuvant therapy, 15.8% radiotherapy and 38.2% received both chemotherapy and radiotherapy. A largepercentage found to be classified as depressed (38.2%) and anxious (32.2%) and factors that found to be associatedwere age, marital status, educational level, stage of cancer from univariate analyses and place of residence, religion,symptoms burden from multivariate analysis (for depression and anxiety). Conclusions: Breast cancer patients arein high risk for developing psychiatric disorders such as depression and anxiety. Being rural resident, non-OrthodoxChristian and experiencing extend symptom burden can be predicting factors associated with depression and anxietyin breast cancer patients.     

Mitoxantrone pleurodesis to palliate malignant pleural effusion secondary to ovarian cancer

Background  

Advanced ovarian cancer is the leading non-breast gynaecologic cause of malignant pleural effusion. Aim of this study was to assess the efficacy of mitoxantrone sclerotherapy as a palliative treatment of malignant pleural effusions due to ovarian cancer.     

Erratum to: Chlorhexidine for routine PD catheter exit-site care

International Urology and Nephrology -     

Role of regional aortic wall properties in the pathogenesis of thoracic aortic dissection

Objectives. The mechanisms of the location and extension of acute aortic dissection (AD) are only poorly understood. The aim of this study was to compare the cohesion of the non-coronary aortic sinus (NAS) and the ascending aortic wall (AA) using the Dissectometer – a new device for analyses of the mechanical properties of the aorta. Design. The properties of the aortic wall were analyzed with the “Dissectometer” (parameters P7, P8 and P9) in adult patients undergoing aortic root (AR) replacement in two different segments: NAS and AA. The aortic wall thickness (AWT) was measured with a micrometer. Results. Thirty-three adult patients (mean age 65?±?14 years, 80% male) were included in this study. The aortic wall of the NAS was significantly thinner than that of the AA (1.9?±?0.4 vs. 2.3?±?0.4, p?Conclusions. This study shows that the wall of the AR is characterized by a thin but stable wall, whereas AA was found to be weaker despite its greater thickness. This difference might be involved in the development and spreading of aortic dissections.