Implementation of a tier system for IVIG indications to address IVIG shortage at a tertiary care pediatric medical center.

BACKGROUND: Drug shortages are a common issue that healthcare systems face and can result in adverse health outcomes for patients requiring inferior alternate treatment. The United States recently experienced a national drug shortage of intravenous immunoglobulin (IVIG). Several reported strategies to address the IVIG and other drug shortages have been proposed; however, there is a lack of evidence-based methods for protocol development and implementation. OBJECTIVE: To evaluate the efficacy of introducing a multidisciplinary task force and tier system of indications and to minimize adverse effects during a shortage of IVIG. METHODS: Faculty members across disciplines with expertise in IVIG use were invited to participate in a task force to address the shortage and ensure adequate supply for emergent indications. A tier system of IVIG indications was established according to the severity of diagnosis, urgency of indication, and quality of supporting evidence. Based on inventory, indications in selected tiers were auto-approved. Orders that could not be automatically approved were escalated for task force review. RESULTS: Overall, there were 342 distinct requests for IVIG during the study period (August 1, 2019 to December 31, 2019). All Tier 1 indications were approved. Of all requests, only 2.6% (9) of requests were denied, none of which resulted in adverse effects based on retrospective chart review. Seven patients who regularly receive IVIG had possible adverse effects due to dose reduction or spacing of treatment; however, each complication was multifactorial and not attributed to the shortage or tier system implementation alone. CONCLUSION: Implementation of a multidisciplinary task force and tier system to appropriately triage high-priority indications for limited pharmaceutical agents should be considered in health institutions faced with a drug shortage.

The core concepts of core binding factor acute myeloid leukemia: Current considerations for prognosis and treatment.

Core binding factor acute myeloid leukemia (CBF AML), defined by t(8;21) or inv(16), is a subset of favorable risk AML. Despite its association with a high complete remission rate after induction and relatively good prognosis overall compared with other subtypes of AML, relapse risk after induction chemotherapy remains high. Optimizing treatment planning to promote recurrence free survival and increase the likelihood of survival after relapse is imperative to improving outcomes. Recent areas of research have included evaluation of the role of gemtuzumab in induction and consolidation, the relative benefit of increased cycles of high dose cytarabine in consolidation, the utility of hypomethylating agents and kinase inhibitors, and the most appropriate timing of stem cell transplant. Surveillance with measurable residual disease testing is increasingly being utilized for monitoring disease in remission, and ongoing investigation seeks to determine how to use this tool for early identification of patients who would benefit from proceeding to transplant. In this review, we outline the current therapeutic approach from diagnosis to relapse while highlighting the active areas of investigation in each stage of treatment.

Oncologic Outcomes for Robotic Vs. Open Radical Cystectomy Among Locally Advanced and Node-Positive Patients: Analysis of The National Cancer Database.

INTRODUCTION: Despite concerns of atypical recurrence following robotic-assisted radical cystectomy (RARC), utilization of the modality is increasing. The presumed mechanisms of peritoneal immunomodulation and pneumoperitoneum-induced tumor cell intravasation are especially relevant for higher stage, locally advanced disease, where intrinsic metastatic potential of tumor cells may be greater. This study aims to compare the oncologic outcomes and survival after RARC compared to open radical cystectomy (ORC) among patients with stage pT3-4 or node-positive muscle-invasive bladder cancer. PATIENTS AND METHODS: Retrospective cohort analysis of pT3-4N0-3 and pT(any)N1-3 patients who underwent RARC or ORC was performed using the National Cancer Database (2010-2016) to investigate perioperative and oncologic outcomes. RESULTS: 9,062 ORC cases and 2,544 RARC cases met inclusion criteria. The robotic approach was significantly associated with superior unadjusted survival compared to open as well as lower proportions of unadjusted 30- and 90-day mortality, lower positive margin status, and shorter surgical inpatient stay (all respective P<.05). However, after adjusting for confounding covariates, multivariable analysis revealed no difference in mortality hazard or odds of any of the above secondary outcomes with the exception of shorter inpatient stay and higher lymph node yield. Patients treated with RARC were more likely to have neoadjuvant chemotherapy. CONCLUSIONS: RARC is no less safe than ORC for patients with locally advanced bladder cancer on the basis of overall, 30- and 90-day survival. Unadjusted mortality and surgical outcomes demonstrate advantages to RARC, which are attenuated after multivariate analysis. Perioperative benefits may favor the robotic approach, consistent with previous randomized control studies.

Head and neck osteosarcomas: Analysis of treatment trends and survival outcomes in the United States (2004-2016).

BACKGROUND: Head and neck osteosarcoma (HNOS) is a rare primary bone tumor with limited data to guide treatment approaches. METHODS: The NCDB was used to identify patients diagnosed with HNOS. Kaplan-Meier and Cox multivariate regression were used to examine the impact of each treatment on overall survival (OS). RESULTS: We identified 821 patients diagnosed with HNOS. Utilization of neoadjuvant chemotherapy + surgery increased from zero cases in 2004 to 24% of cases in 2016. Among surgically treated patients, 5-year OS was 55.8% (CI: 51.7-60.1%). No difference was seen in OS between each treatment cohort on multivariate analysis. However, neoadjuvant chemotherapy + surgery + adjuvant chemotherapy had improved 18-month survival compared to surgery alone (95.8% vs. 78.5%, p = 0.031). CONCLUSIONS: Our study demonstrated no survival benefit in perioperative chemotherapy or radiation therapy; however, short-term survival improvement in patients receiving both neoadjuvant and adjuvant chemotherapy displays promise and requires further investigation.

High-Fidelity Surgical Middle Ear Simulator: A Pilot Study.

OBJECTIVES: To assess a middle ear simulator as a surgical training tool among a cohort of novice trainees. STUDY DESIGN: Prospective pilot study. SETTING: The George Washington University Hospital (tertiary care academic hospital). PARTICIPANTS: Twenty one medical students and physician assistant students completed the protocol. Each student produced four recordings over 10 attempts. The two raters were attending surgeons from the George Washington University Hospital. INTERVENTIONS: Stapedotomies performed on a high-fidelity middle ear simulator. Participants were assessed at baseline with a Purdue pegboard test and trained with video and a low fidelity middle ear simulator. MAIN OUTCOME MEASURES: Two experts rated recordings on scales based upon a validated objective skills assessment test (OSAT) format. RESULTS: Inter-rater reliability was strong across all stapedotomy skills scores and global rating scores. Participants demonstrated statistically significant improvement up to the third recording (seventh attempt), but the scores on the fourth recording (tenth attempt) were not significantly different from the third. One participant failed to improve in score over 10 attempts. Pegboard test performance was not correlated with score improvement. Low-fidelity trial time was significantly correlated to stapedotomy and global rating scores. CONCLUSIONS: This pilot study serves as the first investigation of this middle ear simulator amongst a cohort of trainees. A high-fidelity middle ear simulator may serve as a measurement tool to select future surgical trainees, customize training pathways, and assess surgical capacity before graduation.

The Use of Dornase Alfa in the Management of COVID-19-Associated Adult Respiratory Distress Syndrome.

OBJECTIVE: Currently, management of acute respiratory distress syndrome (ARDS) in COVID-19 infection with invasive mechanical ventilation results in poor prognosis and high mortality rates. Interventions to reduce ventilatory requirements or preclude their needs should be evaluated in order to improve survival rates in critically ill patients. Formation of neutrophil extracellular traps (NETs) during the innate immune response could be a contributing factor to the pulmonary pathology. This study suggests the use of dornase alfa, a recombinant DNAse I that lyses NETs, to reduce ventilatory requirements and improve oxygenation status, as well as outcomes in critically ill patients with ARDS subsequent to confirmed or highly suspected COVID-19 infection. DESIGN: A single-institution cohort study. Setting. Intensive care unit in a tertiary medical center. Patients. Adult patients with acute respiratory distress syndrome (ARDS) admitted to the ICU with confirmed COVID-19 infection. Intervention. Treatment with aerosolized dornase alfa. Measurements and Main Results. Of 39 patients evaluated, most patients had improvement in oxygenation measured by increase in the PaO2/FiO2 ratio, reduction in ventilatory support or other supportive oxygen requirements, and partial resolution of bilateral opacities visible on CXR, as well as improved outcome. CONCLUSIONS: Administration of inhalational dornase alfa via a filtered nebulizer medication system or through an adapter in a ventilator circuit should be considered in all COVID-19-positive patients with ARDS as early in the disease course as possible.

Transoral robotic surgery versus nonrobotic resection of oropharyngeal squamous cell carcinoma.

The aim of this study is to evaluate the impact of transoral robotic surgery (TORS) compared to nonrobotic surgery (NRS) on overall survival in oropharyngeal squamous cell carcinoma (OPSCC). We performed a retrospective study of patients with HPV+ and HPV- OPSCC undergoing TORS or NRS with neck dissection using the National Cancer Database from the years 2010-2016. Among patients with OPSCC in our cohort, 3167 (58.1%) patients underwent NRS and 2288 (41.9%) underwent TORS. TORS patients demonstrated better overall survival than NRS patients (HPV+ patients: aHR 0.74, p = 0.02; HPV- patients: aHR 0.58, p < 0.01). Subsite analysis showed TORS was correlated with improved survival in base of tongue (BoT) primaries for both HPV+ (aHR 0.46, p = 0.01) and HPV- (aHR 0.42, p = 0.01) OPSCC. Compared to NRS, TORS is associated with improved overall survival for HPV+ and HPV- OPSCC, as well as greater overall survival for BoT primaries.

Pediatric head and neck rhabdomyosarcoma: An analysis of treatment and survival in the United States (1975-2016).

INTRODUCTION: Rhabdomyosarcoma (RMS) is the most common soft tissue head and neck sarcoma in children. Stringent analysis of survival data is imperative to optimize treatment. METHODS: The National Cancer Database (NCDB, 2004-2016) and the Surveillance, Epidemiology, and End Results Program (SEER, 1975-2016) were queried for patients ages 0-19 with RMS of the head and neck. Survival trends were analyzed using univariable logistic regression and Chi-square pairwise comparisons. Survival by treatment was analyzed using log-rank tests, Kaplan Meier, and multivariable Cox-proportional hazards regression. RESULTS: 1147 (63.3% age <10 years, 54.3% male) and 459 (71.4% age <10 years, 53.6% male) patients were identified in NCDB and SEER, respectively. In NCDB, embryonal (n = 625, 54.5%) and alveolar (n = 300, 26.2%) were the most common histology and nonparameningeal/non-orbital (n = 634, 55.3%), followed by parameningeal (n = 303, 26.4%) and orbital (n = 210, 18.3%) the most common location. Five-year overall survival (OS) was 70.3% with lower mortality risk for embryonal histology (adjusted HR [aHR] = 0.69, p = 0.0038). Orbital tumors had greatest survival (5-year OS = 92.4%) of all sites, and their mortality risk was higher with chemotherapy and radiation compared to surgery and radiation (aHR = 6.27, p = 0.0302). SEER analysis showed average increased survival by 4% per year (p < 0.0001), but no significant 5-year OS difference when comparing 1976-1980 and 2006-2010 (p = 0.0843). CONCLUSIONS: Major prognostic factors for survival in childhood RMS of the head and neck were embryonal histology, orbital site, extent of disease, and use of SRT for orbital tumors. Larger population studies are required to demonstrate survival differences between treatment modalities for other sites.

Trends in Treatment Strategies and Comparison of Outcomes in Lymph Node Positive Bladder Cancer: An Analysis of the National Cancer Database.

OBJECTIVE: To utilize a national dataset to compare outcomes and demonstrate trends in treatment for lymph node positive bladder cancer (N+ BC). METHODS: The National Cancer Database (2006-2014) was queried for cT2-4N1-3M0 N+ BC patients treated with radical cystectomy alone (RC), neoadjuvant chemotherapy (NAC), adjuvant chemotherapy (AC), chemoradiation (CRT), chemotherapy alone (CT), or no definitive treatment (NT). Survival by treatment was analyzed using Kaplan-Meier and multivariable Cox-proportional hazards regression. Pathologic down-staging was analyzed using univariable and multivariable logistic regression models. A univariable logistic regression model of treatment by year identified treatment trends. RESULTS: Among 3241 patients (cN1, 46%; cN2, 44%; cN3 10%), the majority underwent combined chemotherapy and RC (NAC, 418; AC, 591; RC, 567; CRT, 392; CT, 1068; NT, 205). Overall survival did not differ between NAC and AC, but both had improved survival compared to RC. All other treatment groups had worse survival outcomes compared to NAC. Down-staging to pT0 (adjusted odds ratio = 26.39) and pN0 (adjusted odds ratio = 6.88) was higher for NAC than RC. Utilization of NAC has increased, AC and RC has declined, and CRT and NT is unchanged. CONCLUSION: Combined chemotherapy and RC demonstrates best survival outcomes for N+ BC, with complete pathologic response to pT0N0 after NAC associated with a 5-year overall survival rate of ∼85%. However, there is no significant difference between NAC and AC. CRT is associated with worse oncologic outcomes compared to RC with perioperative chemotherapy, but improved survival compared to RC or CT.

Analysis of ABCA1 and Cholesterol Efflux in HIV-Infected Cells.

Cholesterol is an essential component of the cellular membranes and, by extension, of the HIV envelope membrane, which is derived from the host cell plasma membrane. Depletion of the cellular cholesterol has an inhibitory effect on HIV assembly, reduces infectivity of the produced virions, and makes the cell less susceptible to HIV infection. It is not surprising that the virus has evolved to gain access to cellular proteins regulating cholesterol metabolism. One of the key mechanisms used by HIV to maintain high levels of cholesterol in infected cells is Nef-mediated inhibition of cholesterol efflux and the cholesterol transporter responsible for this process, ABCA1. In this chapter, we describe methods to investigate these effects of HIV-1 infection.