Higher Proportion Of Patients Research Articles

Bendamustine Bridging Versus Standard of Care Chemotherapy on Toxicity Profile for Multiple Myeloma Patients Undergoing CAR T Cell Therapy

Introduction Multiple myeloma (MM) remains an incurable malignancy arising from plasma cells, however great promise has been seen with the use of Chimeric Antigen Receptor (CAR) T cells. Autologous CAR-T products require bridging therapy, however little is known about different agents used in this manner. Some studies indicate decrease in disease burden is crucial, while others note an association with higher rates of toxicity and negative effect on survival. As commercial CAR T cell therapy is indicated after failure of at least 4 prior treatments, careful consideration of bridging therapy is crucial, particularly in patients with aggressive and high-risk disease. This study aims to compare the impact of bendamustine to standard of care (SOC) bridging therapy in MM patients undergoing CAR T cell therapy. Methods A single-center retrospective chart review of 19 adult patients with relapsed/refractory multiple myeloma treated with CAR T cells, who also received bridging therapy with either bendamustine (n=9) or SOC/Other (n=10) was conducted at Mount Sinai Hospital. Patient demographic information (gender, race, MM subtype, history of prior transplant) was collected and toxicity profiles (infection, pancytopenia, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS)) were compared. Descriptive statistics were used to analyze demographic characteristics and toxicity profiles between the two cohorts. Results Comparative analysis of demographics showed that both cohorts were predominantly males with IgG MM subtype, and varied in terms of race ( Figure 1a). The Other cohort had a higher proportion of patients with a history of autologous stem cell transplant (ASCT) (70%) compared to the bendamustine group. In the SOC group, two patients developed infections, whereas none were observed in the bendamustine cohort ( Figure 1b). Pancytopenia was observed in both groups, but interestingly, 100% of patients experienced it in the SOC cohort. CRS and ICANS were comparable between the two groups ( Figure 1b). Comparative statistics demonstrated no significant difference between the two groups ( Figure 1c). Conclusion Our study findings indicate that there was no significant difference in toxicity profiles between the two pre-conditioning therapy groups. Given our limited sample size, future studies with a larger are indicated to validate these results.

FORTITUDE: A Phase 2 Open-Label Study in Progress to Evaluate Etavopivat for the Treatment of Anemia in Patients with Lower-Risk Myelodysplastic Syndromes

Background: Most patients with lower-risk myelodysplastic syndrome (LR-MDS) develop anemia and a high proportion of patients become dependent on red blood cell (RBC) transfusions. MDS-related anemia is associated with low hemoglobin (Hb) levels, iron overload and poor quality of life. Erythropoiesis-stimulating agents and other drugs, including lenalidomide, luspatercept and imetelstat (an investigational product), can lead to RBC transfusion independence and improve Hb levels in many patients; however, responses are generally transient and novel treatments are needed for this population. Etavopivat is an investigational, once-daily, selective erythrocyte pyruvate kinase (PKR) activator in development for the treatment of sickle cell disease (SCD) and anemia in patients with LR-MDS. In a phase 1 study in adult and adolescent patients with SCD by Saraf et al. HemaSphere. (2022), etavopivat 400 mg once daily was considered well tolerated and showed sustained Hb increases up to 12 weeks for most patients. Additional studies in healthy volunteers and patients with SCD support an acceptable safety profile together with improved RBC health and function during continuous treatment with etavopivat. In patients with LR-MDS, ineffective hematopoiesis may be due, in part, to insufficient ATP production, leading to increased erythroid lineage apoptosis. By activating PKR, etavopivat may improve RBC health and function by stimulating energy production (increasing ATP levels), increasing Hb levels (decreasing anemia), and decreasing erythroid lineage apoptosis. Aims:Describe the design of a multicenter, open-label, phase 2 study (FORTITUDE; NCT05568225) evaluating hematologic improvements in patients with very low-, low- and intermediate-risk MDS during treatment with etavopivat. Study design:Key eligibility criteria include age ≥18 years; very low-, low- and intermediate-risk MDS per the Revised International Prognostic Scoring System; and anemia defined by mean Hb <10.0 g/dL and <3 RBC transfusions <16 weeks prior to first dose for non-transfusion-dependent (NTD) patients or ≥3 units of RBCs for anemia <16 weeks prior to first dose for transfusion-dependent (TD) patients. Key exclusion criteria include MDS associated with del 5q cytogenetic abnormality and known TP53 abnormality, history of acute myeloid leukemia, and an absolute neutrophil count <0.5 × 10 9/L. Additional exclusion criteria include prior treatment with azacitidine; decitabine; erythropoietin, other hematopoietic growth factor treatment or lenalidomide within 30 days of Day 1 or anticipated to be required during the study; and luspatercept within 30 days of Day 1 for NTD patients and within 16 weeks of Day 1 for TD patients. Patients will receive etavopivat 400 mg once daily for at least 48 weeks. Treatment may be continued beyond 48 weeks in patients demonstrating clinical benefit. The primary objective of the study is to assess hematologic improvements based on an erythroid response over any continuous period ≥8 weeks within 24 weeks on etavopivat treatment in patients with LR-MDS. The primary endpoint will be based on the combined incidence of: ≥1.5 g/dL increase in Hb from baseline maintained for ≥8 consecutive weeks for NTD patients; absence of any transfusion for ≥8 consecutive weeks for low transfusion-burden patients; and reduction by ≥50% of RBC units for ≥8 consecutive weeks for high transfusion-burden patients. Safety, tolerability, pharmacokinetic, and pharmacodynamic properties of etavopivat will be evaluated. FORTITUDE is open for enrollment in Canada, France, Germany, and the USA. Planned enrollment includes approximately 15 patients in each of the three transfusion requirement-based groups (Figure). Statistical analysis: The primary endpoint (pooled incidence) will be tested with a one-sided Fisher's exact test at the significance level of 0.025 where 0.2 is the assumed null proportion. Summary:Etavopivat is a novel, investigational, once-daily, selective PKR activator with the potential to improve RBC health and lifespan. This phase 2 study will assess the safety of etavopivat and its impact on Hb levels and RBC transfusion burden in patients with LR-MDS and anemia.

Impact of Frailty on Outcomes after CAR T-Cell Therapy for Patients with Relapsed/Refractory Multiple Myeloma

Introduction: Multiple myeloma (MM) is a disease of the elderly with a median age of 69 years at diagnosis. In addition to advanced age, many of these patients are frail with pre-existing comorbidities and have been historically excluded from clinical trials evaluating chimeric antigen receptor (CAR) T-cell therapy for relapsed refractory (RR) MM. It has been shown that chronologic age alone should not be a barrier towards effective treatment modalities including stem cell transplant and CAR T and that instead of age, frailty scores should be incorporated into CAR T screening and eligibility assessments. As there is limited literature on safety and efficacy of CAR T-cell therapy in frail patients, we conducted a multi-center retrospective study to evaluate clinical characteristics and outcomes of frail patients with RRMM who received standard of care CAR T-cell therapy in real-world practice. Methods: Three U.S. academic medical centers contributed data which included patients with RRMM who had received idecabtagene vicleucel (ide-cel) between 8/30/2021 and 05/31/2023. Frailty was defined using the simplified frailty index by Facon et al (score based on age + ECOG performance status + comorbidity index; frail = score ≥2). Descriptive statistics were used to analyze clinical characteristics such as age, performance status, and comorbidities. Response outcomes were evaluated using IMWG criteria. Adverse events were graded based on the ASTCT and CTCAE v5.0 criteria. Key data-points included incidence and severity of cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), infections, treatment-related mortality (TRM), overall response rates (ORR), partial response (PR), very good partial response (VGPR), complete response (CR), progression-free survival (PFS), and overall survival (OS). Results: Of the 104 patients analyzed (age range 41-81), 70 (67%) were considered frail at the time of CAR T-cell infusion. The frail group had a high proportion of patients with renal insufficiency (19% vs 6%), high-risk cytogenetics (46% vs 36%), extramedullary disease (54% vs 47%), performance status ≥2 (20% vs 3%), and worse comorbidity index (median 3 vs 1) but were otherwise similar to the non-frail group (Table 1). While patients in the frail group experienced less CRS (73% vs 88%) and more ICANS (34% vs 18%) when compared to the non-frail group, incidence of grade 3+ CRS and ICANS were similar between the two groups. Rates of infection were also similar between the groups with nearly one-third of the patients experiencing an infection within 6 months post CAR T. With a median follow up of 8 months, best ORR was 83% (37% sCR/CR, 30% VGPR, 16% PR) in the frail group vs 97% (53% sCR/CR, 35% VGPR, 9% PR) in the non-frail group. Median PFS was 6.6 months in the frail group vs 11 months (p=0.062) in non-frail group. Median OS was 14.4 months in the frail group and was not reached (p=0.086) in the non-frail group (Figure 1). TRM was observed in 3 (4%) patients in the frail group. There was no treatment related mortality observed in the non-frail group. Conclusion: A majority of patients treated with standard of care ide-cel for RRMM in this real-world experience were frail by simplified frailty index. While these patients had worse performance status and higher comorbidity burden at the time of CAR T infusion, they did not experience any excessive high-grade toxicities including TRM. When compared to the non-frail group, frail patients had numerically inferior but statistically similar depth and duration of response. This study supports the tolerable safety and reasonable efficacy of CAR T-cell therapy for frail MM patients in a real-world practice and highlights the need to study outcomes in this patient population in larger registry-based data as well as clinical trials.

Oral Anticoagulant (OAC) Use Among Medicare Patients Newly Diagnosed with Venous Thromboembolism (VTE): Factors Associated with Treatment Status

Introduction Clinical guidelines recommend initial treatment with OACs, such as direct-acting oral anticoagulants (DOACs; apixaban, dabigatran, edoxaban, rivaroxaban) or warfarin, for at least 3 months after an initial venous thromboembolism (VTE) event. Early OAC use is associated with improved clinical outcomes and helps prevent VTE recurrence. Purpose To estimate the proportion of Medicare beneficiaries newly diagnosed with VTE with and without OAC treatment within the month from first VTE and identify factors associated with being untreated in that period. Additionally, to identify factors associated with treatment with DOACs or warfarin among OAC-treated patients. Methods Data from 1/1/2014-12/31/2019 of Medicare beneficiaries aged ≥65 years with a new diagnosis of VTE in the inpatient or ambulatory (including emergency room [ER]) setting from 1/1/2015 to 12/31/2019 were included. Additional eligibility criteria included continuous Medicare Parts A, B and D enrollment ≥12 months before and ≥30 days after first VTE diagnosis (index VTE), no diagnosis for atrial fibrillation, inferior vena cava filter, pregnancy or cancer, and no OAC treatment prior to index VTE. VTE patients with ≥1 outpatient pharmacy claims for a DOAC or warfarin within 30 days from index VTE were considered OAC-treated; otherwise, they were classified as untreated. Patients in the OAC-treated cohort were further classified into the DOAC or warfarin subgroups based on the first OAC treatment observed from index VTE (index OAC). Factors associated with being untreated with OACs (vs. treated) and with receiving treatment with DOACs (vs. warfarin) were assessed using multivariable logistic regressions. Results A total of 169,928 patients (49.7% OAC-treated; 50.3% untreated) were identified. In the OAC-treated cohort, 62,528 (74.0%) had DOACs (mainly apixaban [51.9%] and rivaroxaban [46.9%]), and 29,324 (26.0%) warfarin as index OAC. Within the OAC-treated and untreated cohorts respectively, mean age was 76.2 and 77.3 years, 62.9% and 66.4% were female, 82.6% and 75.4% were Non-Hispanic White, mean CCI score was 2.0 and 3.0, 51.8% and 70.3% had DVT only, and 48.2% and 29.7% had PE. Factors associated with being untreated with OACs (odds ratio; 95% confidence interval) included Hispanic ethnicity (vs. White) (1.35; 1.29-1.42), congestive heart failure (1.44; 1.39-1.48), cerebrovascular disease (1.36; 1.32-1.39), anemia (1.25; 1.22-1.28), and peripheral vascular disease (1.22; 1.19-1.25). Having part D low-income subsidy was also associated with being untreated with OACs (1.14; 1.07, 1.20). Index VTE diagnosis setting being ER (vs. outpatient) (0.38; 0.36-0.39) and pulmonary embolism (vs. DVT) (0.45; 0.44-0.46) were associated with increased odds of being treated with OAC, as was being diagnosed by a radiologist (0.62; 0.60-0.64), emergency medicine physician (0.52; 0.49-0.56) or hematologist (0.56; 0.50-0.63) (vs. primary care) ( Figure 1). Among the OAC-treated cohort, factors associated with being treated with DOACs vs. warfarin included diagnosis in more recent years, VTE in ER setting (1.22; 1.15-1.30). VTE in inpatient setting (0.74; 0.70-0.78) and renal disease (0.73; 0.70-0.76) were associated with increased odds of being treated with warfarin, as were Northeast (0.79; 0.76-0.83), Midwest (0.52; 0.50-0.54), and West US census regions (0.56; 0.53-0.59), respectively ( Figure 2). Conclusions In this study of Medicare patients, nearly half of the patients with ICD codes for VTE were not treated with OAC in the first month from initial diagnosis. Among OAC-treated patients, a higher proportion of patients were treated with DOAC vs. warfarin, consistent with more recent guideline recommendation. Factors associated with being untreated might reflect challenges associated with VTE management among disadvantaged populations and in the presence of certain comorbidities.

Implementation of financial toxicity screening and a novel financial navigation program.

290 Background: “Financial Toxicity” is the financial burden and stress imposed on a patient due to a disease and its associated treatment. About 50% of patients with gynecologic cancer experience financial toxicity. The aim of the study is to evaluate implementation of financial toxicity screening and a novel financial navigation program for patients with gynecologic oncology. Methods: Patients presenting for initial consultation with a gynecologic oncology provider from July 2022 to January 2023 were included. A new financial navigation program began in July 2022. On October 17, 2022, a financial toxicity screening question was added to new patient intake forms. We quantified patient referrals to the navigator before and after screening implementation, along with needs identified, action taken by the navigator and institutional support services utilized. Results: We included 458 new patients, 49% before and 51% after introduction of screening. The majority were white (61%) and had private insurance (59%) followed by Medicare (31%); median age was 59 (IQR 47-69). Following screening, a higher proportion of patients were referred to the financial navigator (15%) than before screening (4%, p<0.001). Additionally, referrals to other hospital social support services decreased from 9% before screening to 3% after (p<0.001). Uterine and cervical cancers were more prevalent in the 29 patients (12%) who screened positive (31% and 14% respectively) compared to those who screened negative (17% and 1%) or did not respond (24% and 4%). Referrals to the navigator included 59% of those who screened positive, 8% who screened negative and 10% who did not respond. Over six months, 62 patients (new and follow-up) were referred to the navigator. The most common need was transportation (21%) followed by financial assistance (16%) and emotional support (16%). The navigator assisted 11% of patients with transportation and referred 13% to financial counseling/billing and 27% to other resources. Conclusions: Implementing a financial toxicity screening question on intake forms was feasible, and increased identification of patients with financial toxicity and referrals to our financial navigator. Further investigation is needed to understand screening barriers and evaluate the program.

Brief Report: Changing Characteristics Among In-Hospital HIV Deaths: An 11-Year Retrospective Review of a Regional Hospital in South Africa.

Elevated HIV-associated mortality persists, despite a notable decline with the expansion of antiretroviral therapy (ART). In South Africa, the relative majority of deaths occur in health facilities, providing an opportunity to track decedent characteristics. We analyzed data from 14,870 adult patients who died between 2008 and 2018 at Klerksdorp/Tshepong Hospital Complex in South Africa. Recorded data included demographics, causes of death, HIV status, ART, and tuberculosis (TB) history. We present summary statistics and results from linear, log-binomial, and multinomial regressions to quantify changes over time. Over the study period, the median age of decedents with HIV in the hospital increased from 39.3 to 43.4 years, and there was a switch to male predominance (46%-54%). Those who died at a younger age (<40 years) remained more likely to be HIV-positive than the older age group, despite the overall proportion of HIV-positivity decreasing over time. The proportion of decedents with HIV ever started on ART increased from 21% to 67%. The proportion of HIV patients dying from TB and AIDS-defining illnesses decreased from 31% to 22%. We noted a shift in deaths over time to more men and older individuals, whereas the burden of HIV was heaviest on the younger age groups. Advanced HIV disease remained an important cause of mortality. We also observed an increase in less-traditional opportunistic illnesses among those with HIV, including malignancy, cardiovascular disease, and kidney disease. The high proportion of patients on ART who died prematurely requires further research and interventions.

Ventriculostomy-Related Infections: Reduced Incidence by Terminating Cerebrospinal Fluid Screening

The external ventricular drain (EVD) is an important instrument in managing patients in neurointensive care (NICU). A frequent and sometimes severe complication is ventriculostomy-related infection (VRI). This study aimed to evaluate the effects of biweekly VRI screening by CSF sampling on the clinical course and rate of VRI. Patients with implanted EVDs were retrospectively identified and a cohort screened twice per week was compared with a cohort sampled only on clinical indication. VRI was defined either as a suspected case or a culture-confirmed case. Length of stay in the NICU and CSF shunt dependency were used as outcome parameters. A total of 562 patients were included. The overall proportion of patients treated for VRI was 22% and was not affected by screening (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.57-1.54). Screening was associated with a higher proportion of patients with culture-confirmed VRI (OR, 2.86; 95% CI, 1.36-6.73). The main risk factor for VRI was the number of days with EVD. Positive bacterial culture was associated with both a longer time in the NICU (β= 3.6; P < 0.01) and higher risk for shunt surgery (OR, 1.95; 95% CI, 1.04-3.64). Screening was associated with a higher number of culture-confirmed VRI cases. In addition, screening did not detect VRI at an earlier stage and was not associated with a reduction in the rate of permanent hydrocephalus. No clinical benefit of screening was found. Frequent CSF sampling might contribute to infection. Based on these findings, CSF screening for VRI cannot be recommended.

Is it cost-effective to request IgM oligoclonal bands against lipids in daily practice as a biomarker for poor prognosis in multiple sclerosis?

various prognostic factors of multiple sclerosis have been identified, including demographic, clinical, radiological, and laboratory factors. The aim was to analyze whether the presence of IgM oligoclonal bands against lipids is associated with disease progression. an individual-based, prospective, observational study was conducted at the Neurology Department of Hospital Universitari i Politècnic la Fe. Clinical, radiological, and laboratory variables were collected. Data analysis was divided into a descriptive phase and a subsequent analytical phase. a total of 116 patients were included. 81.9% of them had IgM oligoclonal bands against lipids, with phosphatidylcholine being the predominant type. A higher proportion of patients with IgM oligoclonal bands against lipids required treatment with a disease-modifying drug, started treatment at an earlier stage, showed poorer results in functional tests, and exhibited a higher increase in lesion burden, although these differences were not statistically significant. In our study, the presence of IgM oligoclonal bands against lipids was not found to be associated with other poor prognostic variables.

Diabetic Foot Ulcers and Their Surgical Management: Our Experience at Hayatabad Medical Complex, Peshawar.

Surgeons face a therapeutic challenge while treating diabetic foot ulcers (DFUs), particularly in underdeveloped nations with limited healthcare resources and a high proportion of patients who arrive at medical institutions with advanced foot ulcers. To assess the effectiveness of treatment in patients with DFUs and to demonstrate how early surgical intervention and appropriate bedside medical care can improve results. This prospective study was carried out at Hayatabad Medical Complex, Peshawar, Pakistan, to assess how DFUs changed over a period between November 2021 and December 2022 at the wards and at the outpatient department of endocrinology and general surgery. A diabetic patient's foot is first screened for ulceration in the endocrinology department, and only those with active ulcers are referred to the surgical department. According to the Wagner classification, there were six (13.6%) cases in grade I, 11 (25%) in grade 2, 10 (22.7%) in grade 3, 13 (29.5%) in grade 4, and four (9%) in grade 5. Among comorbidities, a family history of diabetes mellitus was noted in 25 (56.8%) patients, followed by tobacco chewing and alcohol in 10 (22.7%) and hypertension in nine (20.4%) patients. Diabetes foot ulceration is the most common reason for non-traumatic lower limb amputation in people with diabetes mellitus and is a significant cause of morbidity and mortality.

Perinatal Outcome in Overweight Women: An Audit.

Obesity in pregnancy is associated with a myriad of well-documented complications. However, the outcomes of pregnancy in overweight females, who are not classified as obese, have not been studied. The aim of the study was to assess foeto-maternal outcomes in primigravida who are overweight and compare them to normal-weight patients. This was a prospective observational cohort study and included primigravida with full-term gestation (between 38 and 42 weeks), with a single live foetus in vertex presentation, who were admitted for labour induction. Based on pre-pregnancy weight, patients were divided into normal weight (body mass index, BMI<23kg/m2) and overweight (BMI≥23kg/m2 and<25kg/m2) categories labelled as groups A and B, respectively. Data was collected for gestational age, demographics (age, education, occupation), and obstetric and labour-related parameters per pre-designed proforma. Parameters included were the reason for induction, number of doses of prostaglandin E2 (PGE2) gelused, duration of labour, induction to delivery interval, and mode of birth- operative/ non-operative. Data was also collected for peri-partum maternal complications, neonatal Apgar score, and need for Neonatal Intensive Care Unit (NICU) admissions. One hundred and fifty patients were recruited in the study and divided based on weight into two groups- 115 in Group A (normal weight) and 35 in Group B (overweight). Compared to Group A, a higher proportion ofpatients in Group B needed a third dose of PGE2 gel (n=24, 20.8%vs n=18, 51.4%). Also, more patients in Group B had an induction to delivery time of longer than 30 hours (n=7, 20% vs n=5, 4.3%)and had a higher incidence of failed induction needing caesarean section (n=9, 25.7% vs n=13, 11.3%).Neonates born to overweight mothers had a poor Apgar score at 1 min. However, on reassessment, Apgar improved at 5 minutes, and no statistically significant difference was seen for admission to NICU- 5.7% (n=2) in Group B vs 1.7% (n=2) in Group A Conclusion: Pregnancy in overweight females is associated with prolonged labour, higher instances of failed induction, and poor neonatal outcomes at initial assessment. Thus, perinatal counselling and management should focus on weight control while also planning appropriate strategies for monitoring and treating pregnancy-related complications if weight control measures fail. Although obesity is the main focus of research, we suggest including overweight but non-obese females in such studies as they have similar adverse outcomes and complications.

Camouflaged cardiac alert: Correlation of breast arterial calcification with carotid intima media thickness for evaluation of cardiac risk

Objectives: To determine the association between breast arterial calcification (BAC) and carotid intima-media thickness (C-IMT) and, in turn, predict the risk of cardiovascular events. To independently access its relationship with other co-morbidities like diabetes mellitus (DM), hypertension (HTN), and menopause with BAC. Material and Methods: A total of 540 patients (270 with BAC and 270 without BAC) in the age group of 40–60 years who underwent mammograms at our institution between April 2021 to October 2021 were included in the study. In addition, an ultrasound was performed to evaluate the intima-media thickness in bilateral common carotid arteries 1 cm proximal to the carotid bulb. The mean C-IMT between the two groups (patients with and without BAC) was compared to understand the relationship between C-IMT and BAC. The independent relationship of BAC was also evaluated with the risk of co-morbidities like DM, HTN, and menopause. Results: The median C-IMT was higher in the group with BAC (0.85 mm, interquartile range (IQR) = 0.2) than in the group without BAC (0.6 mm, IQR = 0.10), which is statistically highly significant with p &lt; 0.001. Further analysis among subgroups of age and DM also revealed IMT to be significantly higher in the group with BAC (0.85 mm, IQR = 0.20) compared to those without BAC (0.6 mm, IQR = 0.15) (p &lt; 0.001). The median age in patients with BAC was significantly higher (57 years, IQR = 10 years) than those without BAC (48 years, IQR = 11.8 years) (p &lt; 0.001). In the group with BAC, a higher proportion of patients were diabetics, hypertensives and had attained menopause, then in the subgroup without BAC. Conclusion: Patients with BAC had higher C-IMT, which in turn correlates with a higher risk of cardiovascular events. Hence, the presence of BAC can be used as a substitute marker for identifying patients with a higher risk of cardiovascular events and for ruling out co-morbidities such as DM and HTN.

Netupitant/palonosetron (NEPA; Akynzeo®) combination in prevention of the nausea and vomiting in patients with breast cancer receiving anthracyclinbased chemotherapy

Chemotherapy-induced nausea and vomiting is a common problem during cancer treatment, especially in breast cancer patients with anthracycline/cyclophosphamide (ас) chemotherapy. Netupitant/palonosetron (NEPA; Akynzeo®) is a fixed-dose combination of two drugs (netupitant, a neurokinin 1 receptor antagonist; and palonosetron, a serotonin 3 receptor antagonist) which target two diferent signalling pathways involved in the induction of vomiting. Approved for use in the prevention of acute and delayed chemotherapy-induced nausea and vomiting in adults, netupitant/palonosetron is given orally or via intravenous infusion as a single dose prior to chemotherapy. In clinical trials, high proportions of patients who received netupitant/palonosetron (used in combination with the corticosteroid dexamethasone) prior to chemotherapy reported no vomiting, no requirement for rescue medication, and no signifcant nausea in the 5 days post chemotherapy. Both the oral and intravenous formulations of the drug combination are well tolerated. Thus, netupitant/palonosetron is a simple, convenient and efective drug combination for the prevention of acute and delayed xhemotherapy-induced nausea and vomiting in patients receiving chemotherapy that has a moderate to high emetogenic potential.

Clinical Characteristics Analysis of Hospitalized Patients Infected with the Omicron Variant of the Novel Coronavirus

Objective: It’s to analyze the clinical characteristics of hospitalized patients infected with the Omicron variant of the novel coronavirus. Methods: This study retrospectively analyzed the clinical data of 374 Omicron-infected patients admitted to The Third People's Hospital of Wuhu City from January 1, 2022, to December 31, 2022. Clinical characteristics were analyzed. Results: The mean time to nucleic acid conversion was 10.93±3.55 days, with a median of 10 days. There was no statistically significant difference in the infection rate between females and males (P&gt;0.05). The highest proportion of patients was in the age group of 0-44 years (P&lt;0.05). Among patients, those without underlying diseases were more prevalent (P&lt;0.05). The majority of patients had no symptoms or mild symptoms (P&lt;0.05). Regarding vaccination status, most patients had completed the primary immunization or booster immunization (P&lt;0.05). The main symptoms were fever and respiratory symptoms (P&lt;0.05). In laboratory tests, some patients showed a decrease in lymphocyte count (31.82%), elevated C-reactive protein (21.93%), elevated alanine transaminase (18.18%), and elevated creatine kinase (12.30%). Most patients had no lesions on chest CT scans (P&lt;0.05). Traditional Chinese medicine was the primary treatment used (P&lt;0.05). The recovery rate was 100.00%. Conclusion: During this epidemic, the nucleic acid conversion for infected patients occurred around 10 days. Female patients had a higher infection rate, and the majority of cases were asymptomatic or mild. Most patients had completed either primary or booster immunization, indicating some resistance of the Omicron variant to vaccines. The main symptoms were fever and respiratory symptoms, and patients had significantly elevated white blood cell counts, neutrophil counts, and lymphocyte counts, indicating significant infection symptoms. Traditional Chinese medicine was the primary treatment used, and the recovery rate was 100.00%, suggesting that treatment with Traditional Chinese medicine was effective for the Omicron variant.

Predictive value of the neutrophil-to-lymphocyte ratio for treatment response in patients diagnosed with definite or probable autoimmune encephalitis/encephalopathy.

Autoimmune encephalitis/encephalopathy (AE) is a complex and heterogeneous disease, making it difficult to predict the prognosis. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a potential prognostic tool, but its usefulness remains a matter of debate. This study aimed to explore prognostic factors in cases of clinically definite or probable AE, including those with autoantibody-negative, or unknown status. Data on patients diagnosed with definite or probable AE, including those with autoantibody-negative, or unknown status, were retrospectively collected from the admission records of our department between January 2013 and December 2022. These patients were then categorized into either a good- or poor-response group, based on their short-term treatment response. Clinical characteristics, auxiliary examinations, and treatments were compared between the two groups. A multivariable logistic regression model was constructed to identify independent predictors of poor short-term treatment response by Akaike information criterion backward stepwise method. A total of 31 patients were included in the final analysis, with 18 of them included in the poor-response group. In the univariable analysis, the poor-response group had a higher proportion of patients with a modified Rankin Scale (mRS) high score upon admission, female, epileptic seizures, or NLRs of 3.93 or higher than the good-response group (all p < 0.10). Furthermore, the multivariable logistic regression analysis revealed that the mRS score upon admission [OR: 5.51, 95% confidence intervals (CI): 1.29-23.50, p = 0.02], epileptic seizures (OR: 10.01, 95% CI: 1.16-86.66, p = 0.04), and NLRs of 3.93 or higher (OR: 11.37, 95% CI: 1.12-114.68, p = 0.04) were significantly associated with poor short-term treatment response. The NLR may play a supplementary role in predicting the short-term treatment response in patients diagnosed with definite or probable AE, including those with autoantibody-negative, or unknown status.

P041 Audit findings of Bilevel Titrations performed in 2022 at a Public Sleep Laboratory

Abstract Introduction The aim of this audit was to benchmark and grade outcomes of NIV titrations for chronic hypercapnia as per the NPPV titration task force of the AASM. Methods All NIV studies performed in 2022 were included in the audit. Titration gradings of success were defined as per the NPPV titration task force. Each change in setting was reviewed for consistency with laboratory protocols based on task force guidelines. Results 50 of 72 NIV titrations have been audited to date. Patients were mean age (56.4 years +/-17.6), 59% male, with the following pathophysiology leading to chronic hypoventilation. 46% OHS, 35% neuromuscular disease, 16% lung disease, 2% brain or spinal injury. 81% of all setting changes were consistent with laboratory protocols. Protocols were most often not followed when adjusting rise (86.2%), EPAP (82%), and ti max/min (62%). Titration grading outcomes were optimal (43%), good (14%), adequate (0%) and unacceptable (43%). Suboptimal titrations were attributed to; lack of supine REM sleep (24%), lack of sleep or any REM sleep (18%), persistent asynchrony (10%), uncontrolled obstruction (10%), or tcCO2/SpO2 not responding to treatment (38%). Patients with a primary condition of a neuromuscular disease had less suboptimal titrations (36%) compared with OHS (46%), lung disease (43%) and other conditions (50%) however were not statistically significant. Discussion Despite local titration protocols, a high number of unacceptable titrations were identified along with a high proportion of patients not responding to treatment. Further analysis to identify reasons for titration protocol deviations and treatment non-responders is required.

Effect of Glucagon-Like Peptide-1 Receptor Agonists on Bowel Preparation for Colonoscopy.

Inadequate bowel preparation can result in decreased diagnostic accuracy and therapeutic safety of colonoscopy for colon cancer screening. The Boston Bowel Preparation Scale (BBPS) has been used to assess the quality of bowel preparation. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are commonly used medications for diabetes mellitus and obesity that are known to delay gastrointestinal motility. We hypothesized that the use of GLP-1RA would be associated with decreased quality of bowel preparation. We performed a retrospective cohort study of patients who underwent screening or surveillance colonoscopy at a large academic medical center between December 2021 and December 2022. We included patients taking any GLP-1RA for diabetes or obesity during colonoscopy defined as our cases, and patients who were prescribed GLP-1RA at one point but not within 3 months of colonoscopy defined as our controls. We excluded patients on any promotility or antimotility agents and those without BBPS recorded on their procedure report. Independent t test assessed statistical differences in the case and control groups to compare the quality of bowel preparation for continuous variables, and the χ 2 test was used for categorical variables. Multivariate linear regression including diabetes as a covariate was also performed for continuous variables, and multivariate logistic regression was performed for categorical variables. A total of 446 patients were included in the study, comprising 265 (59%) cases and 181 controls (41%). There were no statistically significant differences between groups at baseline except for the diagnosis of diabetes ( P = 0.001) with a higher proportion of patients with diabetes in the cases. The mean BBPS was significantly higher in controls (7.0 ± 1.9 vs 7.5 ± 2.4, P = 0.046) when controlling for diabetes. The percentage of patients with a total BBPS score of <5 was significantly higher in cases (15.5% vs 6.6%, P = 0.01). The proportion of patients who required a repeat colonoscopy due to poor bowel preparation was also significantly higher in cases (18.9% vs 11.1%, P = 0.041). The use of GLP-1RA was associated with a statistically significantly lower quality of bowel preparation, with additional clinical significance given a notable difference in the need for a repeat colonoscopy. It will be essential to understand the cumulative effect of medications that may delay gastric emptying on the quality of bowel preparation to better understand the appropriate measures and counseling that need to be taken before undergoing outpatient colonoscopies.

Dexmedetomidine Withdrawal Syndrome in Children in the PICU: Systematic Review and Meta-Analysis.

To systematically review literature describing the clinical presentation, risk factors, and treatment for dexmedetomidine withdrawal in the PICU (PROSPERO: CRD42022307178). MEDLINE/PubMed, Cochrane, Web of Science, and Scopus databases were searched. Eligible studies were published from January 2000 to January 2022 and reported clinical data for patients younger than 21 years old following discontinuation of dexmedetomidine after greater than or equal to 24 hours of infusion. Abstracts identified during an initial search were screened and data were manually abstracted after full-text review of eligible articles. The Newcastle-Ottawa Scale was used to assess study quality. Summary statistics were provided and Spearman rank correlation coefficient was used to identify relationships between covariates and withdrawal signs. A weighted prevalence for each withdrawal sign was generated using a random-effects model. Twenty-three studies (22 of which were retrospective cohort studies) containing 28 distinct cohorts were included. Median cumulative dexmedetomidine exposure by dose was 105.95 μg/kg (range, 30-232.7 μg/kg), median dexmedetomidine infusion duration was 131.75 hours (range, 20.5-525.6 hr). Weighted estimates for proportion (95% CI) of subjects experiencing withdrawal signs across all cohorts were: hypertension 0.34 (range, 0.0-0.92), tachycardia 0.26 (range, 0.0-0.87), and agitation 0.26 (range, 0.09-0.77). Meta-analysis revealed no correlation between dexmedetomidine exposure variables and withdrawal signs. A moderate negative monotonic relationship existed between the proportion of patients who had undergone cardiac surgery and the proportion experiencing hypertension (correlation coefficient, -0.47; p = 0.048) and tachycardia (correlation coefficient, -0.57; p = 0.008), indicating that in cohorts with a higher proportion of patients who were postcardiac surgery, there were fewer occurrences of hypertension and or tachycardia. On review of the 2000-2022 literature, dexmedetomidine withdrawal may be characterized by tachycardia, hypertension, or agitation, particularly with higher cumulative doses or prolonged durations. Since most studies included in the review were retrospective, prospective studies are needed to further clarify risk factors, establish diagnostic criteria, and identify optimal management strategies.

Characteristics of Anti-Measles Immunity in Lung Transplant Candidates.

Measles has not yet been eradicated; therefore, its outbreaks are still reported throughout the world. Like any infection, measles is dangerous for immunocompromised patients. Levels of anti-measles IgG antibodies were measured in 157 patients aged 17 to 72, who were placed on the lung transplant waiting list. Measurements were undertaken by enzyme-linked immunosorbent assay (ELISA) using the VectoMeasles-IgG kit (Russia). The proportion of patients seronegative for measles was 19% (30/157). Correlation was detected between patients' age and their levels of anti-measles antibodies, with higher proportions of patients having undetectable titers (25.5-28.9%) or low antibody levels (38.3-44.4%) in the young age groups (17-29 and 30-39 years old). There were no differences between male and female patients in levels of anti-measles antibodies or in the proportion of seronegative individuals. Analyses of antibody levels with regard to type of disease revealed the highest rate of seronegative results in cystic fibrosis patients (34.4%, 11/32). Overall, 19% of lung transplant candidates, mostly young people and cystic fibrosis patients, did not have protective immunity against measles.

Activated Prothrombin Complex Concentrates for the Treatment of Factor Xa Inhibitor-Associated Spontaneous Intracerebral Hemorrhage

Background: Anticoagulant-associated intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality. Despite approval of a specific reversal agent for factor Xa inhibitors, there is still much interest in nonspecific reversal agents, such as activated prothrombin complex concentrates (aPCCs). Objective: The objective of this study was to describe ICH expansion in a cohort of patients with factor Xa inhibitor-associated ICH who were treated with aPCC. Methods: This was a retrospective cohort study conducted at an academic medical center designated as a comprehensive stroke center. Consecutive patients admitted for ICH who reported use of apixaban or rivaroxaban prior to admission were considered for inclusion in the study. Patients were treated with 25 to 50 units/kg of aPCC. Intracerebral hemorrhage volume was measured before administration of aPCC and then again within 36 hours of aPCC administration. Results: A total of 40 patients were included in the final analysis. Overall, the cohort was predominantly male (24 [60%]), white (27 [67.5%]), and the mean age was 75.3 ± 10.5 years. Most patients reported taking apixaban prior to admission (31 [77.5%]) and a large proportion were also taking aspirin (13 [32.5%]). The mean change in ICH volume was 1.12 ± 6.03 mL ( P = 0.2475). Conclusions and Relevance: There was a nonsignificant change in mean ICH volume and no reported cases of thromboembolism. Due to the relatively high proportion of patients with significant hematoma expansion, more studies are needed on which patient population would best benefit from treatment with aPCC.

Left Atrial Remodeling Related to Disproportionately Low B-Type Natriuretic Peptide in Acute Heart Failure Patients with Atrial Fibrillation

The diagnostic performance of B-type natriuretic peptide (BNP) for acute heart failure (HF) is impaired in patients with atrial fibrillation (AF). Increased AF burden in HF is associated with left atrial (LA) remodeling. Recent studies have revealed that LA remodeling may affect LV filling. We hypothesized that LA remodeling affects BNP secretion in acute HF conditions. The study investigated the clinical impact of LA remodeling on admission BNP levels in acute HF patients with and without AF. Consecutive acute HF hospitalized patients (n=899) were divided into groups with (n=382) or without AF (n=507) and subdivided into disproportionately low BNP (LB) (≤200pg/ml), medium BNP (200 to 600pg/ml) and high BNP (≥600pg/ml) subgroups. The AF group had a higher proportion of patients with LB than the non-AF group (23.6% vs 16.6%, p=0.009). BNP levels in both groups were positively correlated with LV end-diastolic volume and negatively correlated with LV ejection fraction in both groups. In contrast, BNP was positively correlated with LA volume index in the non-AF group, but negatively correlated in the AF group. The survival rates were significantly higher in the LB group than in the other groups in non-AF. Conversely, there were no significant differences across all groups in AF patients. In conclusion, in patients with acute HF and AF, disproportionately low BNP levels are associated with LA structural remodeling and poor prognosis.