Therapeutic options for HER-2 positive breast cancer: Perspectives and future directions

During the last 15 years we have witnessed an unprecedented expansion in the drugs developed to target human epidermal growth factor receptor-2 (HER-2) positive breast cancer. Trastuzumab, pertuzumab, ado-trastuzumab emtansine and lapatinib are currently food and drug administration (FDA)-approved for the treatment of breast cancer patients with HER-2 over-expressed. However, given the amount of information gathered from years of uninterrupted clinical research, it is essential to have periodic updates that succinctly recapitulate what we have learnt over these last years and help us to apply that information in our daily practice. This review will pursue that objective. We will summarize the most relevant and updated information related to the state of the art management of HER-2 positive breast cancer in all the clinical scenarios including the adjuvant, neoadjuvant and metastatic settings. But we will also critically appraise that literature in order to highlight some key clinical concepts that should not be overlooked. Lastly, this review will also point out some of the most promising strategies that are currently being tested and may soon become available.     

Effect of Probiotic Supplement on Cytokine Levels in HIV-Infected Individuals: A Preliminary Study

Inflammation persists in patients infected with HIV. Reduction of inflammatory cytokines and microbial translocation might be one way that this could be managed. Purpose: The anti-inflammatory properties of certain probiotic strains prompted us to investigate whether a probiotic could reduce the inflammatory index of HIV-infected patients. Methods: The study involved 30 HIV+ males on antiretroviral therapy, who were given one bottle of fermented milk Yakult Light^® containing Lactobacillus casei Shirota (LcS) twice a day for four weeks. Results: The probiotic LcS was associated with an increase of T lymphocytes and a significant increase of CD56+ cells (p = 0.04). There was also a significant decrease of mRNA levels of TGFβ, IL-10 and IL-12 (p < 0.001) and IL-1β expression (p < 0.001) and an increase of serum IL-23 (p = 0.03). In addition, decreased inflammation and cardiovascular risk were observed, as shown by a reduction of cystatin C (p < 0.001). Conclusions: These data provide preliminary evidence that probiotic supplementation may modulate certain immunological parameters and some of the cytokines that were analyzed. Thus, we propose that LcS may be an inexpensive and practical strategy to support the immune function of HIV+ patients.     

Moderately Hypofractionated Helical IMRT,FDG–PET/CT-guided,for Progressive Malignant Pleural Mesothelioma in Patients With Intact Lungs

Introduction

The objective of this study was to present the outcomes of moderately hypofractionated helical intensity-modulated radiation therapy (HT) with/without simultaneous integrated boost (SIB) on fluorodeoxyglucose-positron emission tomography (FDG-PET) positive areas (gross tumor volume [GTV]-PET) for patients with progressive malignant pleural mesothelioma (MPM) after previous treatments.

“There but not there”: Imagined bonds with siblings never known

Continuing a bond after a loved one’s death is considered typical and healthy. However, such a bond can continue symbolically only if it existed in the first place. What of indirect grievers, those who never knew the decedent? The authors describe bonds between individuals who did not have a living relationship to begin with, a concept referred to as imagined bonds. Forty-nine adults, who had a sibling die that they never knew, were interviewed. This article describes the bonds constructed between participants and the sibling they never knew. The authors compare and contrast the concepts of continuing bonds versus imagined bonds.     

Impact of a conjugate vaccine on community-wide carriage of nonsusceptible Streptococcus pneumoniae in Alaska

BACKGROUND: Streptococcus pneumoniae is a leading cause of invasive bacterial disease and pneumonia among children. Antimicrobial resistance among pneumococci has increased in recent years and complicates treatment. The introduction of heptavalent pneumococcal conjugate vaccine (PCV7) could reduce acquisition of antimicrobial-resistant pneumococci. METHODS: We obtained 1350 nasopharyngeal swabs for culture from 1275 children aged 3-59 months presenting at 3 clinics in Anchorage, Alaska, during the winters of 2000, 2001, and 2002, as PCV7 was being introduced into the routine immunization schedule. We recorded the frequency of use of antibiotics as well as the dates of doses of PCV7 for enrolled children. We used multivariate logistic regression modeling to identify independent risk factors for overall carriage of pneumococci and carriage of PCV7-type pneumococci, cotrimoxazole-nonsusceptible (COT-NS) pneumococci, or penicillin-nonsusceptible (PCN-NS) pneumococci. RESULTS: The proportion of children who were up-to-date for age, with respect to PCV7 vaccination, increased from 0% in 2000 to 55% in 2002. Carriage of PCV7-type pneumococci decreased by 43% (P<.0001). Risk of carriage of PCV7-type pneumococci was lower in 2002 than in 2000, independent of vaccination status, suggesting an indirect effect of vaccination. Carriage of COT-NS, but not PCN-NS, pneumococci also decreased (38%; P=.02), not only among vaccinated children but also among unvaccinated children without recent use of antibiotics. CONCLUSIONS: Introduction of PCV7 into the routine infant immunization schedule in a community with a high prevalence of antimicrobial-resistant pneumococci appears to reduce transmission of PCV7 vaccine serotypes and COT-NS pneumococci but has no impact on overall carriage of pneumococci or carriage of PCN-NS pneumococci.     

Clinical outcomes of dexamethasone-eluting stent implantation in ST-elevation acute myocardial infarction.

OBJECTIVES: The aim of our study was to evaluate the safety and midterm clinical results of dexamethasone-eluting stent (DexES) implantation in ST-segment elevation acute myocardial infarction (STEMI). BACKGROUND: Inflammation plays a pivotal role in both inestabilization of coronary atherosclerotic plaques and development of restenosis after stent placement. Antiinflammatory agents may attenuate those mechanisms and improve clinical outcomes. There is little information about clinical results of DexES and no data are available about their utilization during percutaneous coronary intervention (PCI) in STEMI. METHODS: Consecutive patients with STEMI that underwent primary or rescue PCI in our institution were treated with DexES. Clinical follow-up with routine realization of noninvasive test for detection of myocardial ischemia and coronariography if necessary, were performed. The objective of the study was to evaluate the rate of MACE (death, reinfarction, or target lesion revascularization) during midterm follow-up. RESULTS: The procedure was successful in 96.7% of cases. There were no in-hospital deaths or reinfarctions. One acute stent thrombosis occurred and no subacute thrombosis were observed. During a mean follow-up period of 384 days, cardiac-related death was 1.1%, there were no reinfarctions or late stent thrombosis and target lesion revascularization rate was 4.2%. CONCLUSION: We conclude that utilization of DexES for PCI in STEMI is safe and provides good midterm clinical outcomes.     

Hyperglycemia,Insulin, and Insulin Resistance in Sepsis

Critically ill patients frequently have hyperglycemia. This event may reflect severe stress with an imbalance between anabolic hormones and catabolic hormones. Alternatively, it may reflect alterations in either insulin levels or insulin function. Insulin is a pleiotropic hormone with multiple important metabolic effects. In patients with sepsis, insulin levels are increased but insulin sensitivity is decreased. However, there is variability in insulin sensitivity, and this creates variability in glucose levels and insulin requirements and increases the frequency of hypo- and hyperglycemia. The factors that influence insulin sensitivity are complex and include inhibition of tyrosine kinase activity of the beta subunit, increased proteolytic activity resulting in loss of receptors from the plasma membrane, and possibly the transfer of insulin receptors into the nucleus where they bind to gene promoters. Better understanding of the role of insulin in critically ill patients requires prospective studies measuring insulin levels in various patient groups and the development of a simple measure of insulin sensitivity.