Jad Chahoud

Ventilator-associated events prevention, learning lessons from the past: A systematic review

BACKGROUND Preventing Ventilator-associated events (VAE) is a major challenge. Strictly monitoring for ventilator-associated pneumonia (VAP) is not sufficient to ensure positive outcomes. Therefore, the surveillance definition was updated and a change to the broader VAE was advocated. OBJECTIVE This paper summarizes the scientific efforts assessing VAP preventive bundles and the recent transition in surveillance methods. METHODS We conducted a systematic review to identify lessons from past clinical studies assessing VAP prevention bundles. We then performed a thorough literature review on the recent VAE surveillance algorithm, highlighting its advantages and limitations. CONCLUSION VAP prevention bundles have historically proven their efficacy and the introduction of the new VAE definition aimed at refining and objectivizing surveillance methods. Randomized controlled trials remain vital to determine the effect of VAE prevention on patient outcomes. We recommend expanding beyond limited VAP prevention strategies towards VAE prevention bundles.

Updated results of rituximab pre- and post-beam with or without90Yttrium ibritumomab tiuxetan during autologous transplant for diffuse large b-cell lymphoma

Purpose: We evaluated the effect on long-term survival of adding rituximab (R) to BEAM (carmustine, etoposide, cytarabine, and melphalan) conditioning with or without yttrium-90 ibritumomab tiuxetan (90YIT) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) undergoing autologous stem cell transplant (ASCT). Experimental design: Patients were enrolled on three consecutive phase II clinical trials. Patients received two doses of rituximab (375 and 1,000 mg/m2) during mobilization of stem cells, followed by 1,000 mg/m2 on days +1 and +8 after ASCT with R-BEAM or 90YIT-R-BEAM (90YIT dose of 0.4 mCi/kg) conditioning. Results: One hundred thirteen patients were enrolled, with 73 receiving R-BEAM and 40 receiving 90YIT-R-BEAM. All patients had a prior exposure to rituximab. The median follow-up intervals for survivors were 11.8, 8.1, and 4.2 years in the three trials, respectively. The 5-year disease-free survival (DFS) rates were 62% for R-BEAM and 65% for 90YIT-R-BEAM (P = 0.82). The 5-year overall survival rates were 73% and 77%, respectively (P = 0.65). In patients with de novo DLBCL, survival outcomes of the germinal center/activated b-cell histologic subtypes were similar with 5-year OS rates (P = 0.52) and DFS rates (P = 0.64), irrespective of their time of relapse (<1 vs. >1 year) after initial induction chemotherapy (P = 0.97). Conclusions: Administering ASCT with rituximab during stem cell collection and immediately after transplantation induces long-term disease remission and abolishes the negative prognostic impact of cell-of-origin in patients with relapsed DLBCL. The addition of 90YIT does not confer a further survival benefit. Clin Cancer Res; 24(10); 2304–11. ©2018 AACR.

PREVALENCE OF DIABETES MELLITUS AMONG PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION.

OBJECTIVES This study evaluates the prevalence of diabetes mellitus (DM) among patients with arterial hypertension, and indirectly, the crucial impact of adopting screening for diabetes as a standard procedure for all patients diagnosed with arterial hypertension. MATERIALS & METHODS This cross-sectional study was performed on a sample of hypertensive patients recruited from three different university hospitals in Lebanon. Blood pressure and glycemic blood measurements were determined in all subjects. In addition, a complete clinical history and physical exam were performed. Data was entered and analyzed using SPSS 19.0. Frequencies for the different variables were calculated, and the chi-square and independent sample t-tests were conducted. RESULTS This study included 294 patients. Prevalence of diabetes was 27%, and 23% of diabetic patients were newly diagnosed. More than half of the subjects suffering from DM had uncontrolled blood pressure, contrasted with only one third of the non-diabetic subjects with uncontrolled hypertension. CONCLUSION The prevalence of DM in patients with essential hypertension was more than double that of the general population. Therefore, major recommendations would be to adopt strictly the diabetes screening requirements and aggressive management among hypertensive patients to minimize both the health and cost burdens associated with undetected DM.

Managing seminomatous and nonseminomatous germ cell tumors

Purpose of review In the present review, we summarize the recent developments in the management of germ cell tumors (GCTs). Recent findings Treatment-related acute and late-onset toxicity remains a key challenge in the management of GCTs, with recent evidence showing that the adverse health outcomes of etoposide and cisplatin for four cycles in comparison to bleomycin, etoposide, and cisplatin for three cycles appear to be similar. Recent data showed that multidisciplinary clinic approach and management in experienced academic centers were associated with improved overall survival in GCT patients. There are currently multiple conventional-dose chemotherapy options for salvage therapy in patients with refractory or recurrent disease. In addition, more efficacious high-dose chemotherapy regimens continue to be developed. The role of salvage conventional-dose chemotherapy versus high-dose chemotherapy is currently being investigated prospectively. Recent reports suggested that brentuximab vedotin could be a potential salvage option for cluster of differentiation 30 positive refractory GCTs. On the other hand the results of the first phase II clinical trial investigating pembrolizumab in refractory GCTs were disappointing showing no clinical activity. Finally, deep exploration of the immune profile of GCTs using immunohistochemistry and gene expression profiling has identified that advanced GCT stage was associated with decreased T-cell and Natural killer-cell signatures, whereas T regulatory, neutrophil, mast cell, and macrophage signatures increased with advanced stage. Even though these results indicated that activated T-cell infiltration correlated with seminoma histology and good prognosis, and could be used in the future as a biomarker, this approach needs to be validated in a large cohort. Summary Remaining challenges to be addressed include minimizing therapeutic toxicity, and improving outcomes in patients with refractory/recurrent GCTs.

Identification of Glypican-3 (GPC3) Expression in a Lethal Subgroup of Refractory Cisplatin-Resistant Testicular Germ-Cell Tumors

Cisplatin-resistant testicular germ-cell tumors (TGCT) have limited treatment options. Immunotherapy and targeted therapy trials have failed to show any benefit. Glypican-3 (GPC3) expression has not been previously evaluated in these tumors. We show that metastatic tumors with yolk sac tumor and choriocarcinoma components strongly expressed GPC3. This is the first case series to show that lethal, cisplatin-resistant TGCT have enhanced expression of GPC3. GPC3-targeted therapy could benefit these patients, and further investigation is of value.

The β-HPV Subtypes—Cornerstone of the Next-Generation Vaccine

On January 12, 2016, President Barack Obama, began his final year in office by announcing during his State of the Union Address to Congress a “moonshot” to cure cancer. During an era when physicians are called on for action to find a cure for cancer, we tend to forget that we have available at our disposal a human papillomavirus (HPV) vaccine that prevents multiple types of cancers. The first US president, George Washington, said “disorders are easier prevented than cured,” and that is how we today hope to prevent all HPV-related cancers. Human papillomavirus comprises a family of at least 125 viruses classified into 5 genera; α-HPV, β-HPV, γ-HPV, μ-HPV, and ν-HPV. The current vaccines provide coverage only against the sexually transmitted α-HPVs, essential etiological types in cervical, anal, penile, vaginal, vulvar, and some oropharyngeal cancers, but not against β-HPV types. The causal role of β-HPV in the development of cutaneous squamous cell carcinoma (cSCC) and oropharyngeal cancers (OPC) is established in immunocompromised patients. Growing evidence supports this association in the general population, as scientists clarify the β-HPV type-specific molecular pathways involved in oncogenesis and provide robust epidemiological evidence. Recently, published data by Agalliu et al and our group,1,2 highlighted the strong association of β-HPV types 5 and 38 with the development of OPC and cSCC in immunocompetent individuals. On January 27, 2016, the directors of 69 National Cancer Institute (NCI)-designated cancer centers in the United States recognized low rates of HPV vaccination as a public health problem and issued a call to action to improve vaccination rates. We believe that a nextgeneration vaccine is needed to improve uptake rates and broaden the coverage. Such an HPV vaccine protecting against β-HPV subtypes would offer children precise prevention without being type-restricted, to prevent cSCC and OPC as well. This Viewpoint highlights the major benefits and expected challenges of this nextgeneration HPV vaccine.