Single Regimen Research Articles

Balstilimab and other immunotherapy for recurrent and metastatic cervical cancer.

Recurrent and metastatic cervical cancer is generally treated by cisplatin, paclitaxel, and bevacizumab with limited benefit this constituting an unmet need. Immune checkpoint inhibitors, namely the inhibitors of programmed death 1 and programmed death ligand 1 have been proved to be efficacious in the treatment of patients with advanced cervical cancer. Recently, a PD-1 inhibitor, pembrolizumab was approvedfor such cancer. However, there is much scope of improvement of current outcome. Dual blockade of cytotoxic T lymphocyte-associated protein 4 and PD-1 is an attractive therapeutic approach. It is used in other cancers and is currently proposed for cancer cervix also. Search is on for single or combined regimen showing efficacy in multiple pathological conditions of cancer cervix irrespective presence of PD-L1 in malignant tissue. An effort to meet such unmet need has culminated in inventing new immune checkpoint inhibitors namely PD-1 inhibitor, AGEN2034 (Balstilimab) and CTLA-4 inhibitor, AGEN1884 (Zalifrelimab).They have shown meaningful and durable activity as single-agent therapy in previously treated patients with persistent R/M CC in a large phase II trial (NCT03104699) in PD-L1 + and PD-L1- tumour. Responses were found both in squamous cell carcinoma & adenocarcinoma cell types. Balstilimab plus zalifrelimab combination (NCT03495882) produced improved clinical benefit over monotherapy as evidenced by higher relative response rates and longer response duration, as well as a manageable safety profile. Interesting development of this combination and other immunotherapies in R/M CC are discussed in this ensuing review.

Comparison of toxicity following single versus tandem autologous transplant regimens for pediatric medulloblastoma.

Medulloblastoma outcomes have improved with craniospinal irradiation and chemotherapy, but such therapy has resulted in poor neurocognitive outcomes for young patients. Chemotherapy-only regimens with autologous transplant have been implemented with the intention of avoiding radiation. It is not yet known whether single or tandem transplantation is superior with respect to efficacy and/or safety. We performed a retrospective review of children with medulloblastoma treated at Dana-Farber Cancer Institute from 1996 to 2016 who received either single or tandem autologous transplantation after completion of induction chemotherapy. We compared safety and outcome data between the two groups. Among 23 patients, 12 received tandem transplants. Median follow-up was 6.4years (IQR=0.8-10.5). There was no statistically significant difference in 5-year EFS or OS between the single (70.7±14%, 80.2±13%) and tandem transplant groups (57.1±15%, 79.6±13%). Seven tandem transplant patients received subsequent radiation while only four required radiation in the single transplant group (p=.41). In the single transplant regimen, patients experienced longer antibiotic duration (p=.03) and LOS (p=.01) and a trend toward increased number of transfusions (p=.06). Four cases of veno-occlusive disease were reported in the single transplant group (p=.04). Outcomes were similar between regimens, but the single transplant regimen had more hepatic complications. These data suggest that tandem transplant regimens may have reduced toxicity compared to the single transplant regimen with similar outcome measures.

Risk Factors for Measles Non-Immunity in Previously Immunized Pregnant Patients

Measles immunity testing, unlike that for rubella, is not currently part of routine prenatal screening even though immunity to both is conferred by the measles-mumps-rubella (MMR) vaccine. Although endemic transmission of measles was declared eliminated in the U.S. in 2001 after widespread MMR vaccination programs, outbreaks have continued to occur. The MMR vaccine was a single dose regimen prior to 1989, leading to a potentially under-vaccinated cohort of pregnant individuals who were born before recommendations for a second dose to bolster MMR efficacy.

Comparative effects of 6-weeks progressive resistance exercise and moderate intensity aerobic exercise on CD4 count and weights of people living with HIV/AIDS in Alex-Ekwueme Federal University Teaching Hospital Ebonyi State.

Introduction:The most significant clinical challenges in people living with HIV/AIDS (PLWHA) are decline in CD4+ T helper cells and abnormal weight reduction. Consequently, PLWHA who are on Anti-Retroviral Therapy (ART) or Highly Active Anti-Retroviral Therapy (HAART) are usually predisposed to coronary artery diseases due to abnormal weight gain (lipohypertrophy), though with improved and unstable Cluster of Differentiation 4 (CD4) counts.The main aim of this study was to compare the effects of 6 weeks progressive resistance exercise (PRE) and moderate intensity aerobic exercise (MIAE) on CD4 count, and weight of PLWHA in Alex-Ekwueme Federal University Teaching Hospital Ebonyi State.Method:The study adopted quasi experimental research design. The population of the study was 60 Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome patients that attended HIV clinics at Alex-Ekwueme Federal University Teaching Hospital Abakaliki (AE-FUTHA) which formed 58 sample sizes for this study.Simple random sampling technique was adopted for the study and flow cytometry, Heel Densitometer (X-rite 331C), and Omron BF 400 were the instrument used for data collection of CD4 counts and weight respectively; and they are standardized hence not validated. Mean, standard deviation and Analysis of Co-variance (ANCOVA) were used to analyze the data obtained. The reliability coefficient obtained from the pilot study was 0.848 and 0.994 for CD4 and WEIGHT respectively.Results:The major findings revealed a significant difference after 6 weeks’ PRE and MIAE on CD4 and Weight of PLWHA.Conclusion:Health promotion policy maker's arm of the government and Healthcare givers should integrate and enforce the use of exercises either as a single regimen or combined exercises into the management plan of PLWHA for greater boost in absolute CD4 count bearing in mind that both have positive effects. Physiotherapist should be integrated in the managements of PLWHA for appropriate prescription and education of therapeutic exercises for body weight.

Renal Function Protection as an Important Component of a Comprehensive Approach to the Management of Patients with Atrial Fibrillation

The increase in the life expectancy of the population is accompanied by an increase in the prevalence of diseases for which old and senile age are risk factors. Atrial fibrillation (AF) and chronic kidney disease (CKD) are two diseases that can coexist in a patient. The risk of ac thromboembolic and hemorrhagic events in this case increases due to the mutual aggravating influence of these diseases. In addition, these patients have a high incidence of coronary events, and cardiovascular complications are the main cause of death in patients with AF and CKD. Consequently, such patients require an integrated approach to treatment, and their management is a complex clinical task. The direct oral anticoagulant rivaroxaban has been most studied in a population of comorbid AF and CKD patients and has proven a high efficacy and safety profile in these patients in randomized controlled trials. In addition, rivaroxaban has shown a significant reduction in the risk of myocardial infarction in various patients, as well as the possibility of preserving renal function to a greater extent compared with warfarin therapy, and a possible positive effect on reducing the risk of cognitive impairment. A single dosing regimen can improve adherence to treatment, which is one of the key conditions for achieving the above effects. Thus, these factors make it possible to achieve comprehensive protection of comorbid patients with AF and CKD.

Cyclin-Dependent Kinase 4/6 Inhibitors: A Potential Breakthrough Therapy for Malignancies of Gastrointestinal Tract

Cancer is the leading cause of death worldwide for which effective treatments remain limited. This article aimed to critically review and discuss the potential of targeting cell cycle machineries as a vital tool for cancer treatment. Cyclin dependent kinase (CDK) 4/6 inhibitors were originally approved by the United State Food and Drug Administration (US FDA) for advanced-stage breast cancer treatment. The nearly double-prolonged survival time in patients who received CDK4/6 inhibitors are superior to the conventional chemotherapy or endocrine therapy alone and, thus, these medications have been designated a breakthrough therapy by the US FDA. The requirement of CDK4/6 in the progression of cancer cells, but probably dispensable in normal cells, makes CDK4/6 a popular target for cancer treatment. The effects of CDK4/6 inhibitors in cancer may also involve the tumor microenvironment in which the therapeutic effects are synergistically pronounced. These emerging roles, hence, prompt investigations regarding their therapeutic potential in other cancers, including gastrointestinal cancer. Many preclinical and clinical studies of CDK4/6 inhibitors in gastrointestinal cancers are underway and, as a result, several new potentials are gradually reported. Contrariwise, the primary effect of this drug group is arresting the cell cycle rather than inducing cell death. The efficacy of using CDK4/6 inhibitors as a single regimen in clinical practice is then limited. In this article, the effects of CDK4/6 inhibitors on the progression of gastrointestinal cancers, at both preclinical and clinical levels are reviewed. The future directions for research and the possibility of CDK4/6 inhibitors being "breakthrough therapy" for gastrointestinal cancers are also discussed.

Efficacy and safety of delafloxacin, ceftaroline, ceftobiprole, and tigecycline for the empiric treatment of acute bacterial skin and skin structure infections: A network meta-analysis of randomized controlled trials

BackgroundThis review aimed to conduct an indirect comparison using a Bayesian network meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of delafloxacin versus other single antibiotic regimens for the empiric treatment of Acute Bacterial Skin and Skin Structure Infections. MethodA systematic search with no start date restrictions was conducted. The Cochrane Risk of Bias tool was used to assess the quality of included RCTs. ResultsOf the 577 studies initially identified, nine RCTs were included in the review. The network meta-analysis showed that ceftaroline, ceftobiprole, delafloxacin and tigecycline had similar efficacy in the indirect comparisons [Ceftaroline Odds Ratio (OR) = 1.2, 95% Crl = 0.46–3.6), ceftobiprole (OR = 1.3, 95% Crl = 0.34–3.0) and tigecycline (OR = 0.96, 95% Crl = 0.30–2.9)]. However, the ranking plot for the intention to treat (ITT) population showed that delafloxacin had a probability of 80.8% to be ranked first followed by ceftobiprole (13.1%). The analysis of the overall adverse events showed that ceftaroline (OR = 0.88, 95% Crl = 0.65–1.2), ceftobiprole (OR = 1.1, 95% Crl = 0.69–2.0), delafloxacin (OR = 0.88, 95% Crl = 0.57–1.3) and tigecycline (OR = 1.4, 95% Crl = 0.88–2.2) had similar safety profiles. ConclusionDelafloxacin did not show any statistically significant differences when compared to ceftaroline, ceftobiprole, and tigecycline in terms of efficacy and safety. However, the surface under the cumulative ranking curve (SUCRA) probability ranked delafloxacin as the first option for the ITT population.

Agryasangraha – A Cluster of Drugs, Diet & Deeds (Primordial & Quintessentials) as Envisioned in Ayurveda

The term ‘Agrya’ refers to leading or primary and „Sangraha‟ refers to collection, Agryasangraha literally translated applies to mean collection of leading or principal substances. Agryasangraha in fact comprises of single drugs, food articles or regimen which are either wholesome or unwholesome in the given context. The expression „Agrya’ was first coined by Charaka the ancient Ayurveda physician of great eminence. There is a detailed discriprition of Agryas in Charak Samhita, written around 1000 BC that has pioneered this concept of Agryasangraha. The text has discussed the concept in sutrasthana [the first section of the text] where in a number of primordial materials [Agrya] have been mentioned. Among the other Ayurveda texts only Ashtanga Sangraha and Ashtang Hridaya written around 3rd / 7 th century AD have conceived the concept and have made few additions to the collection of Charaka. Ashtang sangraha has mentioned it in 13th Chapter of sutrasthana whereas Ashtang Hridaya has mentioned it in uttarasthana 40th Chapter.

Preliminary trial of 24 vs 72 hour perioperative meropenem in patients with ESBL-producing Enterobacterales bacteriuria scheduled for urological procedures.

IntroductionAntimicrobial prophylaxis is an important issue in positive urine culture patients undergoing endourological procedures or extracorporeal shock wave lithotripsy (ESWL). It is especially recognized in asymptomatic bacteriuria patients of alarm pathogen etiology. We designed a preliminary study to determine optimal duration of antibiotic prophylaxis in patients undergoing endourological procedures or ESWL with asymptomatic bacteriuria caused by Enterobacterales with extended spectrum beta-lactamase positive (ESBL+) type resistance.Material and methodsA total of 60 patients with confirmed ESBL+ Enterobacterales bacteriuria were admitted for endourological procedures or ESWL. The patients were randomized into two groups – a one-day (n = 33) and a three-day (n = 27) period of perioperative antibiotic prophylaxis with meropenem. In both groups on the following day after the procedure (24 hours after the procedure) and 7 days after the procedure serum inflammation markers were assessed.ResultsValues of white blood count, C-reactive protein and procalcitonin prior to, 24 hours and seven days after the procedure clearly showed no statistically significant differences between groups that have received a one-day and three-day antibiotic regimen.ConclusionsIn patients with ESBL+ Enterobacterales asymptomatic bacteriuria undergoing endourological procedures or ESWL a 72-hour perioperative meropenem prophylaxis showed no superiority over a 24-hour regimen. Further studies will be carried out to establish optimal prophylaxis for specific endourological procedures and to test safety of a single dose regimen.

Community Intervention of Single Dose or 2-Dose Regimen of Bivalent HPV Vaccine in Schoolgirls in Thailand - Vaccine Effectiveness 2 Years after Vaccination

Community Intervention of Single Dose or 2-Dose Regimen of Bivalent HPV Vaccine in Schoolgirls in Thailand - Vaccine Effectiveness 2 Years after Vaccination

Application of Controlled Hypotension During Surgery for Spinal Metastasis.

With advances in tumor treatment, metastasis to bone is increasing, and surgery has become the only choice for most terminal patients. However, spinal surgery has a high risk and is prone to heavy bleeding. Controlled hypotension during surgery has outstanding advantages in reducing intraoperative bleeding and ensuring a clear field of vision, thus avoiding damage to important nerves and vessels. Antihypertensive drugs should be carefully selected after considering the patient's age, different diseases, etc, and a single or combined regimen can be used. Hypotension also inevitably leads to a decrease in perfusion of important organs, so the threshold of hypotension and the maintenance time of hypotension should be strictly limited, and the monitoring of important organs during the operation is particularly important. Information such as blood perfusion, blood oxygen saturation, cardiac output, and neurophysiological conduction potential changes should be obtained in a timely fashion, which will help to reduce the risk of hypotension. In short, when applying controlled hypotension, it is necessary to choose an appropriate threshold and duration, and appropriate monitoring should be conducted during the operation to ensure the safety of the patient.

Warfarin Compliance after Mechanical AVR in the Pediatric Population: Case Series from a Developing Country

Background and Aim: Mechanical prosthetic heart valves exert a lifelong thromboembolic complication requiring continuous antithrombotic therapy. Vitamin K antagonist is the recommended therapy of choice along with meticulous INR monitoring to achieve and maintain an INR of 2.0 - 3.0. The study aimed to assess the compliance of anticoagulant therapy in pediatric patients after AVR and to highlight the challenges faced during follow-ups. Methods: A retrospective study was conducted at NICVD Hospital in Karachi, Pakistan for a time frame of 2 years from 2020-2021 where 7 patients were selected. Data were collected using hospital medical records and then validated through a phone call mediated structured questionnaire-based interview. Results: 2 out of 7 patients in the case series were compliant to regular follow-ups and had their INR in the desired range owing to their higher education status and access to INR clinic for regular follow-up in urban setting. Younger patients in the case series were non-compliant. 4 out of 7 patients who were on dual anti-coagulant regimens including warfarin and aspirin were either closer or within the range than compared to those on single drug regimen. Conclusion: Compliance was observed in patients who had favorable demographics and higher education. Multiple recent trials including PROACT and PROACT XA are underway to develop novel treatment options apart from warfarin after mechanical aortic valve replacement. Home-based INR testing kits provide easy access to regular testing in remote areas. Multi-center studies are required for in-depth analysis regarding reasons of non-compliance in pediatric population.

Abstract PO-214: Cancer disparities and African American representation in clinical trials involving Accelerated Partial Breast Irradiation Therapy

Abstract Background Radiation therapy is a critical component in the multi-disciplinary care of many breast cancer patients, but traditionally, has necessitated daily treatment visits over several weeks. Accelerated partial breast irradiation (APBI) in appropriately selected patients affords clinical outcomes that rival those achieved with conventionally fractionated whole-breast radiation. In addition to exposing a smaller volume of breast to radiation, APBI also allows reduction in total number of radiation treatment fractions to 1-10. This regimen thus stands to particularly benefit minorities such as Black American patients, who suffer disproportionately from high rates of economic burden in the form of absence from work, lost wages, and transportation costs related to prolonged cancer treatments. Yet, Black Americans have been traditionally underrepresented in clinical trials, threatening the generalizability of new treatments like APBI. In this study, we evaluated the racial makeup of clinical trials evaluating ABPI and the inclusion of Black Americans in these studies. Methods We retrospectively reviewed all published manuscripts involving accelerated partial breast irradiation therapy and analyzed the demographics of their study populations. Studies reported from centers outside the United States were excluded. When race reporting was not available in the published results, this information, where available, was obtained through the NIH Clinical trials registry. Results A total of 130 APBI trials were identified by PubMed search. Out of these, 80 studies were based in the United States. A total of 20 studies investigating APBI provided demographics data, comprising 1735 total patients. Of these, 1488 patients were White (85.7%), 124 were Black (7.1%), 67 were Hispanic (3.9%), and 46 were Asian (2.7%), and 10 patients were classified as multiple or unknown (0.6%). This percentage is lower than the 2019 US Census estimate of 13.4% Black Americans. We compared these results to two APBI trials conducted at our institution investigating 5-fraction and single fraction APBI regimens. Out of a total of 104 patients treated, 17 patients (16.3%) were Black. The higher proportion of Black Americans in our trials is likely due to a unique partnership between Parkland Hospital, a county Hospital that serves a high proportion of minority patients, and UT Southwestern Medical Center, which provides access to technologically sophisticated treatments such as APBI. Conclusion Despite APBI being uniquely positioned to provide increased benefits to racial minorities, Black Americans are underrepresented in clinical trials evaluating APBI, mirroring the broader national trend in all clinical trials. Based on our institutional experience, partnership between academic medical centers, which often have access to novel treatment regimens and county hospitals, which serve a large proportion of minority patients, is needed to reduce racial disparities in clinical trial participation and to eventually narrow and eliminate the racial health disparity gap. Citation Format: Ev Kakadiaris, Brian K Lue, Sherry Gu, Jonathan C. Tyes, Prasanna Alluri. Cancer disparities and African American representation in clinical trials involving Accelerated Partial Breast Irradiation Therapy [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-214.

The current landscape of systemic therapy for recurrent glioblastoma: A systematic review of randomized-controlled trials.

Conduct a systematic review of the effectiveness of systemic therapies for adult recurrent glioblastoma (rGBM). We electronically searched for randomized controlled trials from three major databases and four conferences from 2009-Dec 2020. Two independent reviewers conducted screening, data extraction, and quality assessment. 48 randomized trials were identified. Outcome reporting was inconsistent: overall survival (OS) in 46 studies, progression free survival in 37 studies, 6-month PFS in 30 studies, objective response rate in 28 studies, and 6-month OS in 7 studies. Network meta-analysis was not feasible due to heterogeneity in outcome reporting and single-study linkages. Most studies compared lomustine (8 studies), bevacizumab (18), or temozolomide (8) with other treatments. The median OS across all studies ranged from 3 to 17.6 months. Based on level one evidence, there is no superior systemic regimen for rGBM. rGBM is a heterogeneous population with no single regimen demonstrating OS benefit. Registration number: CRD42020148512.

Single Dose Versus Multiple Dose Prophylactic Antibiotics in Cesarean Section in a Tertiary Care Hospital

Introduction: Choice of antibiotics as prophylaxis has become crucial factor for morbidity of women after delivery and neonatal complication associated thereafter. The purpose of this study was to compare the efficacy of single dose versus multiple dose of ceftriaxone in cesarean section (CS). Methods: A prospective experimental study was carried out in Universal College of Medical Sciences and Teaching Hospital, Tribhuvan University, Bhairahawa, from May 2015 to October 2016. One hundred patients who had undergone cesarean section were divided in two groups with fifty in each. Patients in group I were treated with single dose of ceftriaxone, whereas patients in group II were treated with multiple dose of ceftriaxone. The data were analyzed using independent "t" test, chi-square test as appropriate. A p-value of <0.05 was considered significant. Results: The distribution of Emergency CS and Elective CS were 72% and 28% in prophylactic single dose group and 88% and 12% in postoperative multiple dose regime and was statistically non-significant difference between single and multiple dose ceftriaxone. One wound infection was observed in multiple dose ceftriaxone treated women as compared to single dose ceftriaxone treated women. Febrile morbidity (8%) and urinary tract infections (2%) were observed in postoperative multiple dose regimen as compared to prophylactic single dose regimen. Conclusion: Prophylactic single dose of ceftriaxone was effective in reducing infective morbidity in patients with cost benefit, and also reduces chances of drug resistant in future.

529. Systematic Review and Meta-Analysis of Ivermectin Safety Profile in COVID-19 Trials

BackgroundThere is a continued and pressing need for safe and effective treatment of COVID-19. Significant survival benefits have been shown by dexamethasone, tocilizumab and sarilumab, however they are only recommended in hospitalised COVID-19 patients. Ivermectin is a well-established and readily available antiparasitic drug which may be suitable for treatment in mild and moderate disease stages. It recently demonstrated anti-viral properties in vitro and now over 80 clinical trials have been registered worldwide to test its effectiveness in COVID-19 patients. This meta-analysis aims to collect data on adverse events reported in new COVID-19 treatment trials for the use of ivermectin as a repurposed medication.MethodsData was extracted from randomised trials of COVID-19 treatment trials identified through systematic searches of PUBMED, EMBASE, MedRxiv and trial registries. The primary outcome of this meta-analysis is the frequency of adverse events. Key safety events included serious, gastrointestinal, neurological, cardiovascular and dermatological adverse events.ResultsOverall, 18 trials investigating ivermectin for COVID-19 in a total of 2496 participants reported safety data and were included. There was no significant difference in the proportion of all adverse events between ivermectin and the comparator. There were 371/1261 (29%) adverse events recorded in the ivermectin containing arms and 376/1284 (29%) in the control arms (RR 1.02 [95% CI 0.77 - 1.34]; p = 0.91). There was no significant difference in the rate of serious adverse events across treatment arms (RR 1.95 [95% CI 0.75 - 5.11]; p = 0.18). No significant differences between ivermectin and the control were seen across different subcategories of adverse events. Figure 1 shows a summary of the results for all adverse events. Forest plot comparing ivermectin and the control for all adverse events in COVID-19 trials, subdivided into single-day dosing trials and multi-day dosing trials.ConclusionThe results of recent COVID-19 trials show that overall, ivermectin is safe and well-tolerated. No significant difference in adverse event reporting was found across all subgroups in single and multi-day treatment regimens for the studies analysed. Safety reporting methodologies often varied across trials. Future and ongoing trials should be encouraged to collect and monitor safety data systematically.Disclosures All Authors: No reported disclosures

1365. Clinical and Financial Implication of Dalbavancin Utilization on Length of Stay Avoidance in Acute Bacterial Skin and Skin Structure Infection

BackgroundOur institution admits 650 patients annually for acute bacterial skin and skin structure infection (ABSSSI). These patients may require intravenous antibiotics, potentially complicated by social factors and loss to follow up. Dalbavancin is a long-acting lipoglycopeptide given as a single dose regimen for ABSSSI. A previous review conducted at our institution identified 117 potential avoidable hospital days over 4 months with outpatient dalbavancin use. The objective of this prospective study was to evaluate the clinical and financial impact of avoided admissions with outpatient dalbavancin use.MethodsThe Institutional Review Board approved this single-site, prospective study. All patients who presented to the emergency department (ED) with ABSSSI from December 15, 2020 to April 15, 2021 were included in the study. Dalbavancin eligibility criteria were given to providers. Eligible patients were given a single dose of dalbavancin and then discharged. The primary outcome was the difference between percentage of avoidable admissions from the ED with dalbavancin use in the retrospective cohort and prospective cohort. The secondary outcomes were estimated length of stay avoidance, percentage of treatment success without ED re-visit within 30 days, estimated hospital cost avoidance and drug cost reimbursement. The primary outcome was assessed using the Chi-square test. Descriptive statistics were used for the secondary outcomes.ResultsFourteen patients received dalbavancin and avoided hospital admissions. The percentages of admissions avoided in the retrospective and prospective cohorts were 16.02% and 6.67%, respectively (Figure 1). A difference of 9.35% was found to be statistically significant (p=0.01). The total estimated length of stay avoidance was 50 days. No patients re-visited the ED within 30 days with treatment failure. The total estimated hospital cost avoidance was &148,852 (Table 1). The net reimbursement for dalbavancin over drug cost was &5,100 (Table 2). ConclusionDalbavancin use decreased avoidable admissions. At our institution, annual hospital cost savings can reach &1,015,794 if dalbavancin was utlilized to all eligible patients.Disclosures All Authors: No reported disclosures

Imiquimod-gemcitabine nanoparticles harness immune cells to suppress breast cancer

Monotherapy with a single chemotherapeutic regimen has met with significant hurdles in terms of clinical efficacy. The complexity of cancer accentuates the need for an alternative approach with a combination of two or more therapeutic regimens to win the battle. However, it is still a challenge to develop a successful combination of drugs with high efficiency and low toxicity to control cancer growth. While gemcitabine monotherapy remains a choice of standard treatment for advanced breast cancer, the approach has not prolonged the median survival time of metastatic breast cancer patients. Here, we report a hyaluronic acid (HA)-based drug combination of gemcitabine (GEM) with imiquimod (IMQ) to stimulate immune cells for anticancer activity. Treatment of the drug combination (IMQ-HA-GEM) showed enhanced anticancer activity against 4T1 breast tumor cells in vitro. Our study with a microfluidics-based 3D, compartmentalized cancer model showed that infiltration of THP-1 monocytes occurred particularly at the site of cancer cells treated with IMQ-HA-GEM. Moreover, IMQ-HA-GEM significantly suppressed the volume of 4T1 breast tumor of mice in vivo. Flow cytometry study displayed a significantly higher activation of CD11b+ immune cells in the blood of mice treated with IMQ-HA-GEM, whereas immunohistochemistry study revealed greater prevalence of CD68+ tumor-associated macrophages in the tumor. Histological examination of isolated tumors of mice treated with IMQ-HA-GEM further confirmed the efficacy of drug combination on cancer cells. This study supports the conclusion that imiquimod potentiates the effect of gemcitabine by activating immune cells to suppress tumors in the form of combination nanoparticles.

Abstract 9481: Inhibition of Apoptosis and Ferroptosis Signaling Pathways Alleviates Myocardial Ischemia-Reperfusion Injury in Rats Through Modulation of Mitochondrial Function

Introduction: Apoptosis and ferroptosis have been implicated in cardiac ischemia/reperfusion (I/R) injury. Inhibitors of apoptosis (Z-VAD) and ferroptosis (FER-1) have been shown to protect the heart in several cardiovascular disorders. However, the impacts of Z-VAD, FER-1, and combined therapy during cardiac I/R injury have not been elucidated. Hypothesis: Z-VAD and FER-1 provide cardioprotection by reducing myocardial cell injury and improving cardiac function. The combined treatment exerts better benefits than either single regimen. Methods: Male rats (n=25) were equally divided into 5 groups: sham, vehicle, Z-VAD at 3.3 mg/kg, FER-1 at 2 mg/kg, and combined FER-1 and Z-VAD. All treatments were intravenously injected to the rats 15 min before ischemia. Left anterior descending coronary was ligated for 30 min, followed by 120-min reperfusion in all animals except the sham group. Left ventricular ejection fraction (LVEF), infarct size, mitochondrial reactive oxygen species (ROS) production, and protein expressions of apoptosis and ferroptosis were determined. Results: Cardiac I/R injury led to cardiac mitochondrial dysfunction and cell death, contributed to infarct size expansion and LV dysfunction (Fig 1A-D). Z-VAD, FER-1 and combined treatments markedly increased %LVEF, reduced ROS levels and infarct size (the %reduction is 42.9%, 41.4%, and 47.7%, respectively, compared with vehicle). Cleaved caspase 3 (apoptosis) and ACSL4 (ferroptosis) expression levels were also reduced in those rats. The combined treatment did not show a significant advantage, compared with either single regimen (Fig 1A-D). Conclusions: Inhibitors of either apoptosis or ferroptosis similarly reduced cardiac mitochondrial dysfunction, apoptosis and ferroptosis, resulting in decreased infarct size, and finally leading to improved LV function. These findings indicate that ferroptosis could be a novel therapeutic target for cardioprotection in cardiac I/R injury.

Comparison of Covid-19 IgG Anti-Spike Antibody Titer after Vaccination with Sputnik V in Seropositive and Naïve Vaccinees

Introduction: Immunity to SARS-CoV-2 has shown to reduce the risk of having a severe infection and initiate a good degree of disease protection. Studies assessing the antibody titer after vaccination can be very helpful to see whether previously infected individuals have better immunological response as compared to uninfected or antibody naïve individuals. 
 Aims & Objectives: Comparison of Anti-spike IgG antibody among vaccinees with or without previous exposure to COVID-19. To determine whether single dose regimen can produce significant antibody titer amongst previously infected cases and design vaccine dosage regimens accordingly.
 Place and duration of study: This study was conducted at Chughtai Institute of Pathology from April 2021 to June 2021.
 Material & Methods: Blood samples were collected from 83 adult male and female vaccinees at baseline, 3 weeks after the first dose and finally 7 days after the second dose. Previously infected individuals’ record was noted separately. Samples were immediately analyzed using Abbott SARS-CoV-2 IgG II quant two step immunoassay. Data was analyzed using SPSS 23.0. A p-value of <0.05 was considered significant.
 Results: Majority of the candidates (57 %) were females and on analysis it was found that 42% of the patients were seropositive whereas 58% of the patients were antibody naïve before receiving the first dose of vaccine. There was a significant difference between mean antibody titer of seropositive and seronegative study participants at day 0, day 21 and finally on day 28 (p value <0.001) with seropositive individuals having higher antibody titers even after first vaccine shot.
 Conclusion: Post vaccination immunological response was higher in seropositive individuals as compared to the antibody naïve and this finding can help the policy makers to design a single dose vaccine regimen for the former