Efficacy Of Current Agents Research Articles

Frontiers in cancer immunotherapy-a symposium report.

Cancer immunotherapy has dramatically changed the approach to cancer treatment. The aim of targeting the immune system to recognize and destroy cancer cells has afforded many patients the prospect of achieving deep, long-term remission and potential cures. However, many challenges remain for achieving the goal of effective immunotherapy for all cancer patients. Checkpoint inhibitors have been able to achieve long-term responses in a minority of patients, yet improving response rates with combination therapies increases the possibility of toxicity. Chimeric antigen receptor T cells have demonstrated high response rates in hematological cancers, although most patients experience relapse. In addition, some cancers are notoriously immunologically "cold" and typically are not effective targets for immunotherapy. Overcoming these obstacles will require new strategies to improve upon the efficacy of current agents, identify biomarkers to select appropriate therapies, and discover new modalities to expand the accessibility of immunotherapy to additional tumor types and patient populations.

Early Outcomes Using Hepatitis C-Exposed Donors for Cardiac Transplantation in the Era of Effective Direct-Acting Antiviral Treatments

The shortage of suitable donors for heart transplantation (HT) contributes to wait-list mortality and increased reliance on mechanical circulatory support. Considering this need, and the favorable drug profiles and efficacy of current agents used to treat Hepatitis C (HCV), our institution is now transplanting selected patients using HCV-exposed donors.

Early outcomes using hepatitis C–positive donors for cardiac transplantation in the era of effective direct-acting anti-viral therapies

Given the shortage of suitable donor hearts for cardiac transplantation, and the favorable safety and efficacy of current agents used to treat hepatitis C virus (HCV), our institution recently piloted transplantation of select patients using HCV-positive donors. Between September 2016 and March 2017, 12 HCV-naive patients and 1 patient with a history of treated HCV underwent heart transplantation (HT) using hearts from HCV-positive donors after informed consent. Patients who acquired HCV were referred to hepatology and treated with direct-acting anti-viral therapies (DAAs). Data collection and analysis were performed with institutional review board approval. At the time of HT, mean age of recipients was 53 ± 10 years, and 8 patients (61.5%) were on left ventricular assist device support. After consent to consider an HCV-positive heart, mean time to HT was 11 ± 12 days. Nine of 13 patients (69%) developed HCV viremia after transplant, including 8 who completed DAA treatment and demonstrated cure, as defined by a sustained virologic response 12 weeks after treatment. One patient died during Week 7 of his treatment due to pulmonary embolism. DAAs were well tolerated in all treated patients. In the era of highly effective DAAs, the use of HCV-positive donors represents a potential approach to safely expand the donor pool. Additional follow-up is needed to elucidate long-term outcomes.

Early Outcomes Using Hepatitis C-Positive Donors for Cardiac Transplantation in the Era of Effective Direct-Acting Antiviral Treatments

Introduction: The shortage of suitable donor hearts for cardiac transplantation contributes to wait list mortality. Given this need, and the favorable drug profiles and efficacy of current agents used to treat Hepatitis C (HCV), our institution recently piloted transplantation of selected patients using HCV-positive donors. Methods: Between September 2016 and March 2017, 11 HCV-naïve patients and 1 patient with a history of HCV that was treated and cured prior to listing, underwent heart transplantation from HCV-positive donors. Patients were treated per our standard immunosuppression protocol. Following transplant, patients were referred to hepatology for monitoring and treatment. Data collection and analysis were performed after obtaining informed patient consent and IRB approval. Results: Baseline characteristics: Mean age of recipients at time of transplant was 52.7 years (SD 9.9). Eight patients (66%) were male, eight patients (66%) were Caucasian, and eight patients (66%) were on left ventricular assist device support. Mean age of organ donors was 30.3 years (SD 4.3). All donors tested positive for antibodies to HCV; only ten had positive HCV nucleic acid testing. Time to transplant: Recipients' total wait list time varied prior to them consenting to receive an HCV-positive heart. Following consent, time to transplant was short (median 2.5 days [IQR 1.2–17]), even for patients with unfavorable blood groups, elevated panel reactive antibodies, or lower listing status. Hepatitis C testing and treatment: Nine of 12 patients (75%) who received hearts from HCV-positive donors developed HCV viremia. Three patients remain disease-free. Of the nine patients who developed HCV, seven patients have initiated or completed antiviral treatment, with a fixed dose combination of either sofosbuvir/ledipasvir or sofosbuvir/velpatasvir. All treated patients have undetectable viral loads (mean time from treatment initiation to viral suppression 53.3 days [SD 28.8]). The two remaining patients with HCV will soon initiate treatment. Tolerability and adverse events: Among patients who initiated HCV treatment and demonstrated suppression of viremia, one patient died due to a pulmonary embolism and one patient developed echocardiographic graft dysfunction of unclear etiology, which resolved spontaneously upon subsequent imaging. Conclusions: In the era of highly effective HCV pharmacotherapy, the use of HCV-positive donors represents a potential approach to safely expand the donor pool. This report represents the first and largest series to date and demonstrates that HCV treatment leads to rapid viral suppression early after transplant, despite immunosuppression. Additional follow-up is needed to elucidate long-term outcomes and assess for sustained virologic response.

Efficacy of current agents used in the treatment of Gram-positive infections and the consequences of resistance

The proportion of pathogens causing hospital-onset infections that are resistant to antimicrobial agents continues to increase worldwide. Inadequate antimicrobial therapy is an important factor in the emergence of resistance and is associated with increased mortality. In the USA in 2000, the National Nosocomial Infections Surveillance system reported that >50% of Staphylococcus aureus isolates collected from intensive care units were resistant to methicillin (MRSA). The emergence of community-acquired MRSA is a new concern. MRSA are associated with adverse clinical outcomes and increased hospital costs. The increasing prevalence of MRSA contributes to the use of glycopeptides; however, isolates with intermediate and full resistance to vancomycin and teicoplanin are now being reported. Newer agents, such as the oxazolidinone linezolid, are effective in the treatment of serious Gram-positive infections; however, linezolid-resistant isolates of Enterococcus faecium, Enterococcus faecalis and S. aureus have been reported. Therefore, there is an unmet clinical need for new agents with activity against Gram-positive pathogens. Daptomycin, a lipopeptide with a novel mode of action, was recently approved for the treatment of skin and soft tissue infections in the USA. The two case studies presented herein detail experience with the use of daptomycin in the USA.