The prognosis of patients with metastatic colorectal cancer (mCRC) remain poor despite the impressive improvement of treatments observed over the last 20 years that led to an increase in median overall survival from 6 mo, with the only best supportive care, to approximately 30 mo with the introduction of active chemotherapy drugs and targeted agents. The monoclonal antibodies (moAbs) cetuximab and panitumumab, directed against the epidermal growth factor receptor (EGFR), undoubtedly represent a major step forward in the treatment of mCRC, given the relevant efficacy in terms of progression-free survival, overall survival, response rate, and quality of life observed in several phase III clinical trials among different lines of treatment. However, the anti-EGFR moAbs were shown only to be effective in a subset of patients. For instance, KRAS and NRAS mutations have been identified as biomarkers of resistance to these drugs, improving the selection of patients who might derive a benefit from these treatments. Nevertheless, several other alterations might affect the response to these drugs, and unfortunately, even the responders eventually become resistant by developing secondary (or acquired) resistance in approximately 13-18 mo. Several studies highlighted that the landscape of responsible alterations of both primary and acquired resistance to anti-EGFR drugs biochemically converge into MEK-ERK and PIK3CA-AKT pathways. In this review, we describe the currently known mechanisms of primary and acquired resistance to anti-EGFR moAbs together with the various strategies evaluated to prevent, overcame or revert them.

Recurrent wheezing 36 months after infant bronchiolitis was associated with rhinoviruses and blood eosinophilia.

More than 40% of cases of all lung cancers are diagnosed in patients over the age of 70 years. Elderly patients have more comorbidities and tend to be less tolerant to toxic medical treatments than their younger counterparts. Thus, clinical data obtained in a younger population cannot be automatically extrapolated to the great majority of nonselected elderly patients with non-small cell lung cancer (NSCLC). The bulk of prospective clinical data regarding chemotherapy and molecularly targeted therapy for elderly NSCLC patients come from studies in advanced disease. In elderly advanced NSCLC patients, single-agent chemotherapy with third-generation agents (vinorelbine, gemcitabine, taxanes) is to be considered the routine standard of care for unselected patients, based on phase II and III trials specifically designed for this special population. Cisplatin-based chemotherapy with cisplatin at attenuated doses has been demonstrated to be an active and feasible option in phase II trials. Among targeted therapies, the epidermal growth factor receptor tyrosine kinase inhibitors, erlotinib and gefitinib, have relevant phase II prospective data showing activity and good tolerability as first-line treatment in this population. Concerning the antivascular endothelial growth factor monoclonal antibody, bevacizumab, combined with chemotherapy, particular care must be taken for elderly patients because of the higher incidence of cardiovascular comorbidities. The lack of data on octogenarians suggest that clinicians should exercise caution when applying the existing data on chemotherapy and targeted therapies for patients aged 70-79 years to those aged >80 years. Further specifically designed clinical trials are needed to optimize medical treatment of NSCLC in elderly patients.

ABSTRACT

BackgroundPreliminary results suggest that pertussis infection might be considered in infants during a seasonal respiratory syncytial virus (RSV) outbreak.MethodsIn order to analyze clinical features and laboratory findings in infants with pertussis hospitalized for acute respiratory symptoms during a seasonal RSV outbreak, we conducted a retrospective single-center study on 19 infants with pertussis (6 boys; median age 72 days) and 19 matched controls (RSV-bronchiolitis), hospitalized from October 2008 to April 2010. B. pertussis and RSV were detected from nasopharyngeal washes with Real Time-PCR.ResultsInfants with pertussis were less often breastfeed than infants with RSV bronchiolitis (63.2% vs 89.5%; p <0.06). Clinically, significantly fewer infants with pertussis than controls had more episodes of whooping cough (63.2% vs 0.0%; p < 0.001) and also less frequently fever at admission (15.8% vs 68.4%; p <0.01), apnea (52.6% vs 10.5%; p <0.006), and cyanosis (52.6% vs 10.5%; p < 0.006). Infants with pertussis had more often no abnormal chest sounds on auscultation than infants with RSV bronchiolitis (0% vs 42,1%; p < 0.005). The absolute blood lymphocyte and eosinophil counts were higher in infants with B. pertussis than in controls with bronchiolitis (23886 ± 16945 vs 10725 ± 4126 cells/mm3, p < 0.0001 and 13.653 ± 10.430 vs 4.730 ± 2.400 cells/mm3, p < 0.001). The molecular analysis of 2 B. pertussis isolates for ptxA1, ptxP3, and prn2 genes showed the presence of gene variants.ConclusionsWhen infants are hospitalized for acute respiratory symptoms, physicians should suspect a pertussis infection, seek for specific clinical symptoms, investigate lymphocyte and eosinophil counts and thus diagnose infection early enough to allow treatment.

7% HS-HA is a safe and effective therapy in treating infants hospitalized for mild-to-moderate bronchiolitis.

No abstract

Even though bronchiolitis is a disease that has been recognized for many years, there are still few therapeutic strategies beyond supportive therapies. Bronchiolitis is the most frequent cause of hospital admission in children less than 1 year of age. The incidence is estimated to be about 150° million cases a year worldwide, and 2-3% of these cases require hospitalization. It is acknowledged that viruses cause bronchiolitis, but most of the studies focus on RSV. The RSV causes a more severe form of bronchiolitis in children with risk factors including prematurity, cardiovascular disease and immunodeficiency. Other viruses involved in causing bronchiolitis include RV, hMPV, hBoV and co-infections. The RV seems to be associated with a less severe acute disease, but there is a correlation between the early infection and subsequent wheezing bronchitis and asthma in later childhood and adulthood. The supportive therapies used are intravenous fluids and oxygen supplement administered by nasal cannula or CPAP in most complicated patients. Additional pharmacological therapies include epinephrine, 3% hypertonic saline and corticosteroids. The Epinephrine seems to have the greatest short-term benefits and reduces the need of hospital admission, whereas hypertonic saline and corticosteroids seem to reduce the length of hospital stay. As bronchiolitis is such a prevalent disease in children and RV seems to play an important role, perhaps more studies should center around the RV's contribution to the initial disease and following pathology.