Effective Interventions to Reduce the Increase In Elective Cesarean Sections In Low Risk Women

According to the Annals of Family Medicine, the amount of babies born via cesarean section has increased from 4.5% in 1965 to 26.1% in 2002 and nearly 40% of all cesarean sections are repeats. After an extensive literature review, results showed that patients need to be educated about the risks and benefits of vaginal delivery and cesarean delivery. It was also found that there needs to be policy changes to decrease the amount of cesarean sections done and increase the labor and delivery support without using interventions. Further study should be focused on morbidity and mortality very low birth weight neonates for women with previous cesarean sections that accounts for unplanned VBAC deliveries.https://scholar.dominican.edu/ug-student-posters/1035/thumbnail.jp

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Effects of Aligning Patients and Nurses from the Same Ethnicity and Cultural Background in Bringing Better Patients’ Clinical Outcome in Disease Management.

In the current healthcare system, it is important for a nurse to be culturally sensitive and recognize that cultural effects on the experiences of each individual that are directly or indirectly related to their health. Patient’s cultural and literary background have a massive influence on their beliefs and behaviors which leads to their understanding of the disease process and a better treatment outcome as a result. Consequently, it is important for the nurses and every healthcare professional to be sensitive and aware to their patient’s unique language and culture background, which are key in terms of recognizing the treatment plan based on their preference. Cultural competence in the healthcare system takes a very integral part in bringing out the best outcome in patient care. The root cause of most of cultural communication problems originates from lacking the deeper level of understanding of patient\u27s culture, values and it’s preferences in the treatment process

A Single Center Retrospective Study of Real World Relapsed/Refractory DLBCL Patients Eligible for CAR T-Cell Therapy: Patient Characteristics and Outcomes

Introduction: Patients with Diffuse large B-cell lymphoma (DLBCL) may experience excellent long-term outcomes after initial anthracycline containing therapy. However, patients with relapsed or refractory (R/R) DLBCL often have poor outcomes. Select R/R DLBCL patients may be treated with additional chemoimmunotherapy (CIT) followed by hematopoietic stem cell transplant (HSCT). However, as many as 50% of R/R DLBCL patients are unable to undergo HSCT due to lack of response to CIT or comorbidities (Gisselbrecht C, et al JCO 2010). Recent data reported in the SCHOLAR-1 study suggest a median overall survival (OS) of 6.3 months for these patients, with only 20% of patients alive at 2 years (Crump M, et al Blood 2017). Chimeric antigen receptor T-cell (CAR-T) therapy, a novel form of immunotherapy, offers improved outcomes for such patients with complete response rates of approximately 40% and 50% OS at 12 months or greater (Neelapu SS et al. NEJM 2017; Borchmann P et al, EHA 2018). Delivery of CAR-T therapy is specialized and remains limited to a small number of centers at present. The broad applicability of CAR-T therapy in a real world population of R/R DLBCL patients remains unknown. This retrospective study aimed to identify the characteristics and outcomes of a cohort of R/R DLBCL patients who would have been eligible for CAR-T cell therapy if available over a 4 year period at Swedish Cancer Institute (SCI). The SCI is a specialty cancer research center, based in a non-profit, non-university affiliated medical center. Methods: All patients with recorded diagnosis of DLBCL (ICD9/10) seen for an outpatient encounter in a SCI facility between the dates of 01/01/2014 and 01/01/2018 were identified from an electronic medical record database. Patients who had received anthracycline-based chemotherapy only at SCI as initial therapy and then subsequently received 2nd line or beyond therapy at SCI between January 2014 and January 2018 were included. This population was defined as the study cohort of R/R DLBCL patients and was then evaluated for would-be eligibility for CAR-T therapy by application of the defined Kite Zuma-1 clinical trial Inclusion/Exclusion (I/E) criteria. Patient characteristics for the CAR-T eligible population were obtained by retrospective medical record review. Overall survival of the potential CAR-T eligible population was assessed including stratification by receipt of HSCT at any time during the study period. Results: 486 patients with a diagnosis of DLBCL were seen during outpatient SCI encounters between Jan 2014 and Jan 2018. Of these, 60 patients received prior 1st line anthracycline therapy exclusively at SCI and then received 2nd line or beyond therapy at SCI between 2014 and 2018 for R/R DLBCL. The majority of patients, 82% (n=49), met all Zuma-1 I/E criteria for CAR-T therapy. Characteristics of these patients are identified in Table 1. Among all CAR-T eligible patients, OS was 37.1% at 24 months (Figure 1). Patients received a variety of 2nd line or beyond therapies, including 47% (n=23) who received HSCT. OS at 24 months for CAR-T eligible patients was significantly better for those receiving HSCT in 2nd line or beyond versus those who did not receive HSCT (61.6% vs 12.0%, respectively; p\u3c0.001; Figure 2). Conclusion: In a retrospective cohort of real-world R/R DLBCL patients treated between 2014 and 2018 at SCI, a non-university based specialty cancer research center, 49 of 60 patients (82%) would have been eligible for CAR-T therapy based on Zuma 1 I/E criteria. This suggests that the majority of the patients with R/R DLBCL in the real-world may have an opportunity to receive CAR-T. Moreover, while those who underwent a successful HSCT as part of 2nd line or beyond therapy had greatly improved outcomes, those patients who did not undergo HSCT had poor outcomes. For such patients not receiving HSCT, the availability of CAR -T may lead to significantly improved outcomes

Initial Safety Results from a Phase II Study of Acalabrutinib Plus RICE Followed By Autologous Hematopoietic Cell Transplantation and/or Acalabrutinib Maintenance Therapy for Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Background: Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) often have a poor prognosis despite therapies using second-line chemoimmunotherapy (CIT). Achievement of complete response (CR) with second-line therapy is associated with improved long-term outcomes. Unfortunately, only 25-35% of patients achieve CR with standard CIT regimens alone. The addition of novel targeted agents such as Bruton Tyrosine Kinase inhibitors (BTKi) to second-line therapy may offer improved treatment responses given the importance of B-cell receptor (BCR) signaling in DLBCL. BTK has been shown to be essential for BCR-mediated activation of the NF- κB/Rel family of transcription factors and BCR signaling has been recognized as a key pathway in the pathogenesis of DLBCL. Moreover, NF-κB activity relies upon chronic active BCR signaling in activated B-cell-like DLBCL, which can be potentially blocked by kinase inhibitors targeting BTK. In this study we examine the feasibility and efficacy of adding the BTKi, acalabrutinib (A), to standard second-line therapy to improve disease response in patients with R/R DLBCL. Here we present initial safety and tolerability data for the ongoing study. Study Design and Methods: This is an open-label, prospective phase II trial (NCT03736616). Cohort A is open to R/R DLBCL patients eligible for autologous hematopoietic transplantation (HCT). Cohort B is open to R/R DLBCL patients considered ineligible for autologous HCT. The primary endpoint for cohort A is to estimate the confirmed CR rate (RECIL 2017 criteria) prior to autologous HCT in patients undergoing second-line CIT. The primary endpoint for cohort B is defined as the estimate of one-year progression-free survival in patients undergoing second-line induction and maintenance acalabrutinib therapy. Cohort A receive 2 cycles of standard RICE salvage CIT in combination with acalabrutinib, 100mg BID days 1-21 of a 21-day cycle (RICE+A). After 2 cycles of therapy, patients undergo autologous stem cell mobilization and collection. Patients then receive a 3 rd cycle of RICE in combination with acalabrutinib. PET-CT (PET3) is to be performed on day 15 of cycle 3 to assess response. Patients with CR or partial response (PR) after PET3 proceed to autologous HCT with BEAM conditioning within 28-42 days of PET3. Post-HCT CR patients receive acalabrutinib 100mg BID as maintenance therapy for 12 additional months. Protocol amendment in May 2021 allows for PET assessment (C2D15) prior to autologous stem cell collection (after cycle 3). Cohort B receive 3 cycles of RICE+A in 21-day cycles followed by PET-CT (PET3) on day 15 of cycle 3. Patients without progressive disease at PET3 continue with acalabrutinib maintenance up to 12 additional cycles until disease progression or unacceptable toxicity. Patients demonstrating progressive disease are withdrawn from study treatment but followed for outcomes. Results: Here we report initial safety and tolerability data for the ongoing study with data cutoff July 28, 2021. Twenty-two patients have been screened and 20 patients have received at least 1 cycle of RICE+A. Patient characteristics are shown in Table 1. Fifteen patients (79%) have completed 3 cycles of RICE+A. One patient (5%) discontinued due to an adverse event (AE; recurrent appendicitis), 3 patients (16%) discontinued due to progressive disease, and 1 patient is receiving ongoing RICE+A as of data cutoff. Hematologic AE have been observed in 17 patients (89%) with 74% being Grade 3/4. Amongst these, neutropenia was the most common AE occurring in 47% with all being Grade 3/4, and thrombocytopenia occurring in 32% with all being Grade 3/4. All hematologic AE recovered to baseline or grade 1 in median 7 days. Amongst non-hematologic AE, diarrhea occurred in 21% and 0% were Grade 3/4, nausea 16% with 0% Grade 3/4, and headache in 16% with 0% Grade 3/4. Discontinuation of therapy due to AE occurred in 1 patient (recurrent appendicitis) and dose reduction occurred in 1 patient (Gr 4 neutropenia). Temporary (per protocol) dose holds of A occurred in 9 patients (45%), primarily for cytopenias during concurrent RICE+A. Median duration for dose holds of A was 5.5 days. Conclusion: RICE+A is feasible with manageable primarily hematologic AEs similar to those reported for RICE alone. Enrollment and follow up is ongoing for efficacy endpoints and further toxicity assessment

Acalabrutinib Plus RICE Followed By Autologous Hematopoietic Cell Transplantation and/or Acalabrutinib Maintenance Therapy for Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Background: Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) often have a poor prognosis despite therapies using second-line chemoimmunotherapy. Achievement of CR with second-line therapy is associated with improved long-term outcomes. Unfortunately, only 25-35% of patients achieve complete response (CR) with RICE chemotherapy alone. The addition of novel targeted agents such as Bruton Tyrosine Kinase inhibitors (BTKi) to second-line therapy may offer improved treatment responses given the importance of B-cell receptor (BCR) signaling in DLBCL. BTK has been shown to be essential for BCR-mediated activation of the NF- κB/Rel family of transcription factors and BCR signaling has been recognized as a key pathway in the pathogenesis of DLBCL. Moreover, NF-κB activity relies upon chronic active BCR signaling in activated B-cell-like DLBCL, which can be potentially blocked by kinase inhibitors targeting BTK. The goal of this study is to examine the feasibility and efficacy of adding the BTKi, acalabrutinib, to standard second-line therapy as a means to improve disease response. Establishing the feasibility of combining acalabrutinib with RICE chemotherapy in autologous hematopoietic cell transplantation (HCT) eligible and HCT ineligible patients with R/R DLBCL may provide the foundation for a larger study of efficacy and long-term outcomes of the combination therapy for patients with R/R DLBCL. Study Design and Methods: The primary objective of this phase 2 trial is to evaluate the tolerability, feasibility, and efficacy of combining acalabrutinib with RICE as second line therapy in R/R DLBCL patients. There are two study cohorts. Cohort A is open to R/R DLBCL patients who are eligible for autologous HCT. Cohort B is open to R/R DLBCL patients who are considered medically ineligible for autologous HCT. The primary endpoint for cohort A is to estimate the confirmed CR rate (RECIL 2017 criteria) prior to HCT in patients undergoing second-line therapy. The primary endpoint for cohort B is defined as the estimate of one-year progression-free survival in patients undergoing second-line induction and maintenance acalabrutinib therapy. Secondary endpoints include assessment of the proportion of patients completing 3 cycles of acalabrutinib with RICE and proceeding with HCT or 2 additional cycles of maintenance acalabrutinib for HCT ineligible patients, overall response rate, incidence of Grade 3/4 adverse events, and incidence of SAEs. Patients in cohort A receive 2 cycles of standard RICE salvage chemoimmunotherapy in combination with acalabrutinib, 100mg BID day 1-21 of a 21 day cycle. After 2 cycles of therapy, patients in cohort A undergo autologous stem cell mobilization and collection. Patients then receive a 3rd cycle of RICE in combination with acalabrutinib. PET-CT (PET3) is performed 14-21 days after day 1 of cycle 3 to assess response. Those patients with CR or partial response (PR) after PET3 proceed to autologous HCT with BEAM conditioning within 28-42 days of PET3. After adequate hematopoietic recovery, patients restart acalabrutinib 100mg BID as maintenance therapy for a period of 12 additional months. Patients in cohort B receive 3 cycles of RICE salvage chemoimmunotherapy in combination with acalabrutinib 100mg BID day 1-21 of a 21-day cycle followed by PET-CT (PET3) 14-21 days after start of Cycle 3. Patients without progressive disease at PET3 continue with acalabrutinib maintenance up to 12 additional cycles until disease progression or unacceptable toxicity. Patients demonstrating progressive disease are withdrawn from study treatment but their outcomes continue to be recorded and will be included in the final data analysis. Historical outcomes from completed, published prospective clinical trials using RICE chemoimmunotherapy serve as a reference for statistical calculations. This trial is currently ongoing and additional information can be found on clinicaltrials.gov NCT listing NCT0373661

Initial Efficacy and Safety of Acalabrutinib Plus RICE in Transplant Eligible Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Background: Patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) undergoing second-line chemoimmunotherapy (2L CIT) often have a poor prognosis with a minority achieving curative outcomes. Achievement of CR with 2L CIT is associated with favorable long-term outcomes in patients consolidated with autologous stem cell transplant (ASCT). Unfortunately, only 25-35% of patients achieve complete response (CR/CR unconfirmed) with RICE CIT (Gisselbrecht 2010). Addition of novel targeted agents such as Bruton Tyrosine Kinase inhibitors (BTKi) to 2L CIT may offer improved treatment responses given the importance of B-cell receptor (BCR) signaling in DLBCL. Here we report the feasibility and efficacy of combining acalabrutinib (acala) 100mg BID with RICE (A-RICE) chemotherapy in ASCT eligible pts with R/R DLBCL. Study Design and Methods: In a single-center, open-label, phase 2 trial (NCT03736616) we evaluate the feasibility, efficacy, and tolerability of combining acala with RICE as 2L CIT in R/R DLBCL pts. There are two study cohorts. Cohort A is open to R/R DLBCL pts who are eligible for 2L CIT followed by ASCT consolidation. Cohort B is open to R/R DLBCL pts considered medically ineligible for ASCT. The primary objective for cohort A is to estimate the confirmed CR rate (RECIL 2017 criteria) of A-RICE prior to HCT. Primary endpoint for cohort A is met if \u3e10 of maximum 24 enrolled patients achieve CR, which allows rejection of the null hypothesis that confirmed CR rate is ≤ 25% if true CR rate is 50% (one-sided α =0.05, power = 85%). The primary endpoint for cohort B is the estimate of one-year progression-free survival in patients undergoing 2L CIT followed by maintenance acala for up to 12 months. Secondary endpoints include overall response rate (ORR), incidence of Grade 3/4 adverse events (AEs), and incidence of serious AEs in both cohorts. Pts in cohort A received 2 cycles of A-RICE in a 21 day cycle. After 2 cycles A-RICE, response assessment via PET-CT (PET2) was completed with responding patients receiving a 3rd cycle of A-RICE followed by stem cell mobilization and collection. PET-CT was performed 14-21 days after day 1 of cycle 3 (PET3) to assess response to 2L CIT. Those patients with CR or partial response (PR) after PET3 proceeded to BEAM conditioned ASCT within 28-42 days of PET3. After hematopoietic recovery, patients may continue acalabrutinib 100mg BID as maintenance therapy for 12 months post ASCT. Minimal residual disease (MRD) is assessed using ctDNA (clonoseq) at time points pre-ASCT, post-ASCT, and during maintenance A. Results: Primary endpoint for Cohort A has been met and is reported here, while Cohort B has not yet met pre-specified enrollment or follow up maturity for efficacy analyses. Safety for both cohorts to date is reported. Twenty-six pts have been enrolled (19 cohort A, 7 cohort B). In Cohort A, 5 pts had refractory DLBCL, 7 pts were GCB, 10 non-GCB. Median age of Cohort A was 58, and median of Cohort B was 75 (Table 1). 19 Cohort A pts received at least 1 cycle of A-RICE, with 16 pts completing 3 cycles. One patient (4%) stopped A-RICE due to AE, 3 patients (13%) discontinued due to progressive disease (PD). All 19 pts in cohort A were considered response evaluable following initiation A-RICE: ORR was 74% (14 pts), with 53% CR (10 pts), 21% PR (4 pts). Thirteen pts (68%) underwent planned consolidative ASCT. See Figure 1 for response data. Safety data for all 26 cohort A and B patients who received at least 1 cycle A-RICE was assessed for the first three cycles of A-RICE. The most common treatment-related AEs were thrombocytopenia (All 50%, Gr 3/4 46%) and neutropenia (Gr 3/4 30%). SAEs were reported in 5 pts with 1 therapy related SAE of neutropenic fever, and 4 treatment unrelated SAEs. Of the 19 efficacy evaluable pts in cohort A, 10 pts interrupted 1 or more doses of acalabrutinib during a A-RICE cycle either due to patient error or protocol specified dose hold related to AE. Conclusions: A-RICE in ASCT eligible pts w/ R/R DLBCL demonstrated CR in 53% of response evaluable patients. Further, we observed a high ORR (74%) and high proportion of pts completing planned ASCT (68%). AEs with A-RICE were consistent with those expected for CIT. A-RICE warrants further investigation in pts w/ R/R DLBCL eligible for 2L CIT with intention to undergo ASCT. Further analyses of cohort A, including ctDNA based MRD dynamics, PFS, and OS are ongoing and will be updated at meeting