Failure Group Research Articles

Associations of Heart Failure Onset Age with All-Cause Mortality: The Kailuan Study

Objective: This study was aimed at investigating the correlations between heart failure onset age and all-cause mortality. Methods: The study examined 186,249 patients treated at Kailuan Group hospitals who underwent medical evaluations between 2006 and 2018. Biennial health assessments were conducted, and, as of December 31, 2020, 4022 heart failure instances were identified. For each patient with new-onset heart failure, four control participants were randomly selected, matched for age (within ±1 year) and sex. Cox regression models were used to calculate the hazard ratios of all-cause mortality across age groups. Results: The median follow-up duration was 5.25 (2.65, 8.63) years. All-cause mortality occurred in 1783 participants in the new-onset heart failure group and 2633 participants in in the control group. Refined multivariable Cox regression analysis revealed that patients with heart failure under 55 years of age had the highest relative mortality risk, with an HR (95% CI) 6.86 (4.42–10.64) with respect to their matched controls. Moreover, the relative mortality risk systematically decreased with increasing age of heart failure onset: HR (95% CI) 4.70 (3.73–5.92) for ages 55–64, HR (95% CI) 3.23 (3.73–3.81) for ages 65–74, and HR (95% CI) 1.69 (1.48–1.94) for 75 years or older. Conclusion: Heart failure significantly elevates the risk of all-cause mortality, and the risk is more pronounced with earlier manifestation of the condition.

Predictors of outcomes after the trans-obturator tape procedure in females with equal severity for stress and urge mixed urinary incontinence

Mixed urinary incontinence (UI) is common in women. This study aimed to assess the efficacy of anti-incontinence surgery in female patients with equally severe stress UI (SUI) and urge UI (UUI). All patients had equal severity of SUI and UUI. The postoperative cure rate was categorized into the cure group (CG) and failure group (FG). Postoperative satisfaction was categorized into the satisfaction group (SG) and the dissatisfaction group (DG). Statistical significance was set at <i>P</i><0.05. Ninety patients (SG, 73.3%; DG, 26.7%; CG, 93.3%; FG, 6.7%) were included in the study. In the univariate analysis, body mass index (BMI), total bladder capacity, and overactive bladder symptom score (OABSS) were significantly different between the SG and DG groups. Peak urinary flow, Valsalva leak point pressure (VLPP), and OABSS were significantly different between the CG and FG groups. In the multivariate analysis, OABSS (<i>P</i>=0.001) and BMI (<i>P</i>=0.032) were independent predictors of postoperative satisfaction. VLPP (<i>P</i>=0.023) was the only independent factor associated with the postoperative cure rate. In equal severity of SUI and UUI, VLPP was found to be the only independent factor associated with postoperative cure rates. Higher VLPP values were associated with higher cure rates. BMI and OABSS were identified as independent predictors of postoperative satisfaction, with lower BMI and OABSS associated with higher postoperative satisfaction.

A correlation study between prostate necrosis rate calculated by 3D Slicer software and clinical efficacy of prostatic artery embolization, along with an analysis of predictors of clinical success after prostatic artery embolization.

To analyze the correlation between the prostate necrosis rate at 1-month after prostatic artery embolization (PAE) and the clinical efficacy at 1-year after PAE, and to explore potential predictors of clinical success after PAE for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). The prostate magnetic resonance imaging data at 1-month after PAE were imported into 3D Slicer software for calculating the prostate necrosis rate and thus analyzing the relationship between the prostate necrosis rate at 1-month after PAE and the efficacy score ratio at 1-year after PAE. The 151 patients with PAE technical success were divided into a clinical success group (n = 126) and a clinical failure group (n = 25). Independent predictors of clinical success after PAE were analyzed by multifactorial logistic regression, and the predictive performance of each factor was evaluated by applying the receiver operating characteristic curve and the area under the curve (AUC). There was a linear negative correlation between the prostate necrosis rate at 1-month after PAE and the efficacy score ratio at 1-year after surgery (P < 0.001). In the clinical success group, both the initial prostate volume (PV) and the prostate necrosis rate at 1-month after PAE were significantly higher than in the clinical failure group (P < 0.001), and acute urinary retention (AUR) and adenomatous-dominant BPH were also associated with clinical success (P < 0.05). Multifactorial logistic regression analysis revealed that larger initial PV, a higher prostate necrosis rate at 1-month after surgery, and AUR were independent predictors of clinical success after PAE. The AUC values for these three indicators and their combination were 0.720, 0.928, 0.599, and 0.951, respectively, in which the prostate necrosis rate at 1-month after PAE demonstrating a high predictive value. The higher the prostate necrosis rate at 1-month after PAE, the better the clinical efficacy at 1-year after PAE is likely to be, and the prostate necrosis rate at 1-month after PAE is expected to become a predictor of clinical success after PAE.

Effect of comorbid heart failure assessed by plasma B-type natriuretic peptide level on the activities of daily living in patients with hospitalization-associated disability after aspiration pneumonia.

We investigated the effects of comorbid heart failure on rehabilitation outcomes in patients with hospitalization-associated disability after aspiration pneumonia(AP). This study included 134 patients with hospitalization-associated disability after AP. Patients were classified into heart failure (B-type natriuretic peptide (BNP) ≧100pg/ml, n = 39) and non-heart failure (BNP < 100pg/ml, n = 95) groups, and the rehabilitation outcomes of both groups were compared. Rehabilitation effectiveness was lower in heart failure group than in non-heart failure group (21.1 ± 22.6% vs 36.2 ± 30.8, p < 0.01). The rate of independent walking at discharge in heart failure group (28.2%) was significantly lower than in non-heart failure group (53.7%). Multiple linear regression analysis revealed that age, male, handgrip strength, quadriceps strength, functional oral intake scale, Mini Nutritional Assessment Short Form, and BNP were significantly associated with rehabilitation effectiveness. Results suggest that comorbid heart failure has a negative impact on rehabilitation outcomes in patients with hospital-associated disability after AP.

Association of Gender, Age, Physiological, and Biochemical Parameters among Chronic Renal Failure Patients at Zawia Kidney Hospital

Background and objectives. Chronic renal failure is a major problem and one of the main causes of morbidity and mortality in the world. kidneys maintain internal balance of water, salts and minerals by eliminating waste products from the body. This study conducted to evaluate the association of physiological and biochemical changes among patients with renal failure who undergo dialysis compared to healthy people. Also, to identify the incidence of CKD in males and females. Methods. This study was conducted from January 2020 to December 2020 at Zawia Kidney Hospital. It was including 114 patients with chronic renal failure and 75 healthy people. The biochemical variables which were examined in the blood serum include glucose, triglycerides and cholesterol, urea, creatinine, and electrolytes in patients with renal failure as well as the healthy people. Results. This study showed that patients aged over 31year had higher frequency of kidney failure. There was a statistically significant difference in the glucose levels between the patient’s group and the control group (p &lt; 0.001) with patients having higher average glucose levels compared to the control group. There were no statistically significant differences between the two groups in cholesterol levels (p˂0.904). However, there was a statistically significant difference in triglyceride levels between patients and controls (p-value =0.021) as patients having higher levels compared to the control group. Statistically significant differences observed in urea, creatinine, calcium, sodium, potassium and phosphate values among renal failure and control groups as (p˂0.001 for each). In the relationship between blood type patients and kidney disease, the results showed a significant association between blood type and kidney failure (p&lt;0.001). Also, our study revealed that there is a significant correlation between gender and chronic renal failure (p&lt;0.001). In addition, an odds ratio of 11.7 indicates that the odds of men developing kidney failure are 11.7 times higher than that of women. Conclusion. Older ages, male, and O blood group are risk factors for chronic renal failure. Clear difference in the level of biochemical parameters in chronic renal failure compared to healthy people.

ELMO CPAP: an innovative type of ventilatory support for COVID-19-related acute respiratory distress syndrome.

To assess whether the use of ELMO, a helmet for noninvasive ventilation created in Brazil, had a positive impact on the prognosis of patients with hypoxemic respiratory failure caused by severe COVID-19. This is a retrospective study of 50 critically ill COVID-19 patients. Epidemiological, clinical, and laboratory data were collected on ICU admission, as well as before, during, and after ELMO use. Patients were divided into two groups (success and failure) according to the outcome. ELMO use improved oxygenation parameters such as Pao2, Fio2, and the Pao2/Fio2 ratio, and this contributed to a gradual reduction in Fio2, without an increase in CO2, as determined by arterial blood gas analysis. Patients in the success group had significantly longer survival (p < 0.001), as determined by the Kaplan-Meier analysis, less need for intubation (p < 0.001), fewer days of hospitalization, and a lower incidence of acute kidney injury in comparison with those in the failure group. The significant improvement in oxygenation parameters, the longer survival, as reflected by the reduced need for intubation and by the mortality rate, and the absence of acute kidney injury suggest that the ELMO CPAP system is a promising tool for treating ARDS and similar clinical conditions.

Risk factors and prognosis of preoperative herat failure after hip fracture

To explore incidence, risk factors and the relationship between preoperative heart failure and prognosis in elderly patients with hip fracture. A retrospective analysis was performed on 1 569 elderly patients with hip fracture treated from January 2012 to December 2019, including 522 males and 1 047 females, aged 81.00 (75.00, 90.00) years old;896 intertrochanteric fractures and 673 femoral neck fractures. Patients were divided into heart failure and non-heart failure groups according to whether they developed heart failure before surgery, and heart failure was set as the dependent variable, with independent variables including age, gender, fracture type, comorbidities and hematological indicators, etc. Univariate analysis was performed at first, and independent variables with statistical differences were included in multivariate Logistic regression analysis. Independent risk factors for preoperative heart failure were obtained. The length of hospital stay, perioperative complications, mortality at 30 days and 1 year after surgery were compared between heart failure and non-heart failure groups. There were 91 patients in heart failure group, including 40 males and 51 females, aged 82.00 (79.00, 87.00) years old;55 patients with intertrochanteric fracture and 36 patients with femoral neck fracture. There were 1 478 patients in non-heart failure groups, including 482 males and 996 females, aged 81.00(75.00, 86.00) years old;841 patients with intertrochanteric fracture and 637 patients with femoral neck fracture. There were significant differences in age, sex, coronary heart disease, arrhythmia and dementia between two groups(P<0.05). Multivariate Logistic analysis of statistically significant factors showed that males(OR=1.609, P=0.032), age(OR=1.032, P=0.031), arrhythmia(OR=2.045, P=0.006), dementia (OR=2.106, P=0.014) were independent risk factor for preoperative heart failure. The 30-day and 1-year mortality rates were 9.9% and 26.4% in heart failure group and 3.6% and 13.8% in non-heart failure group, respectively;and had statistical significance between two groups (P<0.05). There were significant differences in pulmonary infection, cerebrovascular complications and cardiovascular complications between two groups (P<0.05). The duration of hospitalization in heart failure group was (16.21±10.64) d compared with that in non-heart failure group (13.26±8.00) d, and the difference was statistically significant (t=2.513, P=0.012). Male, old age, arrhythmia and dementia are independent risk factors for heart failure after hip fracture in elderly patients. Patients with preoperative heart failure have a higher incidence of postoperative pulmonary infection, cerebrovascular and cardiovascular complications, higher mortality at 30 d and 1 year after surgery, and longer hospital stay.

Predictors of Phosphodiesterase Type 5 Inhibitor Treatment Failure in Patients Diagnosed With Erectile Dysfunction.

Erectile dysfunction (ED) is a prevalent condition, especially in aging populations, with significant implications for quality of life. While phosphodiesterase type 5 inhibitors (PDE5Is) are the first-line treatment, a substantial percentage of patients do not respond satisfactorily. This study aimed to identify predictors of PDE5I treatment failure in ED patients. Data from January 2016 to January 2022 was reviewed for patients with ED who either failed PDE5I treatment or had a successful outcome. Demographic, medical, and laboratory data were collected and analyzed. Patients with contraindications or who did not complete the treatment were excluded. The treatment failure group comprised 288 patients, while 225 age-matched patients formed the control responder group. There were no significant differences in marriage duration, comorbidities, smoking, or BMI. However, HbA1c levels, free testosterone, and SHBG were significantly different between the two groups. This study found that high HbA1c levels, low free testosterone, and high sex hormone-binding globulin (SHBG) were associated with PDE5I treatment failure. Managing high HbA1c levels and addressing hormonal imbalances may enhance PDE5I treatment effectiveness in ED patients. However, further research is needed to explore other factors contributing to treatment outcomes.

Therapeutic effect of adipose-derived stem cells injected into pericardial cavity in rat heart failure.

There are few studies on the treatment of heart failure by injecting stem cells into the pericardial cavity. Can the cells injected into the pericardial cavity migrate through the epicardium to the myocardial tissue? Whether there is therapeutic effect and the mechanism of therapeutic effect are still unclear. This study investigated the therapeutic efficacy and evidence of cell migration of adipose-derived stem cells (ADSCs) injected into the pericardial cavity in rat heart failure. The aim of this study is to demonstrate the effectiveness and mechanism of treating heart failure by injecting stem cells into the pericardial cavity, laying an experimental foundation for a new approach to stem cell therapy for heart disease in clinical practice. The inguinal adipose tissue of male SD rats aged 4-6weeks was taken, ADSCs were isolated and cultured, and their stem cell surface markers were identified. Forty rats aged 6-8weeks were divided into sham operation group, heart failure group, and treatment group; there were 15 rats in the heart failure group and 15 rats in the treatment group. The heart failure model was established by intraperitoneal injection of adriamycin hydrochloride. The heart function of the three groups was detected by small animal ultrasound. The model was successful if the left ventricular ejection fraction<50%. The identified ADSCs were injected into the pericardial cavity of rats in the treatment group. The retention of transplanted cells in pericardial cavity was detected by small animal in vivo imaging instrument, and the migration of transplanted cells into myocardial tissue was observed by tissue section and immunofluorescence. Western blotting and immunohistochemical staining were used to detect brain natriuretic peptide (BNP), α-smooth muscle actin (α-SMA), and C-reactive protein (CRP). ADSCs express CD29, CD44, and CD73. On the fourth day after injection of ADSCs into pericardial cavity, they migrated to myocardial tissue through epicardium and gradually diffused to deep myocardium. The cell density in the pericardial cavity remains at a high level for 10days after injection and gradually decreases after 10days. Compared with the heart failure group, the expression of BNP and α-SMA decreased (P<0.05 and P<0.001, respectively), and the expression of CRP in the treatment group was higher than that in the heart failure group (P<0.0001). A small amount of BNP, α-SMA, and CRP was expressed in the myocardium of the sham operation group. After injection of ADSCs, interleukin-6 in myocardial tissue was significantly lower than that in heart failure myocardium (P<0.01). After treatment, vascular endothelial growth factor A was significantly higher than that of heart failure (P<0.01). Pericardial cavity injected ADSCs can penetrate the epicardium, migrate into the myocardium, and have a therapeutic effect on heart failure. Their mechanism of action is to exert therapeutic effects through anti-inflammatory, anti-fibrosis, and increased angiogenesis.

Failure of intravenous nifekalant cardioversion as an independent predictor for persistent atrial fibrillation recurrence after catheter ablation.

Nifekalant is a class III antiarrhythmic drug that exerts antiarrhythmic effects by inhibiting rapid rectifying potassium channels and extending the effective refractory period of cardiomyocytes. It has a high success rate in converting atrial fibrillation (AF) to sinus rhythm. Whether the failure of intravenous nifekalant cardioversion is an independent predictor for persistent AF recurrence after catheter ablation has not been reported. A total of 92 patients with drug-refractory persistent AF were retrospectively enrolled. After all ablations, intravenous nifekalant was administrated. Patients were assigned to the success group (group 1) and failure group (group 2) based on nifekalant cardioversion results and followed for 12 months to note any episode of atrial arrhythmia recurrence. Each group included 46 patients. After 12 months of follow-up, nine (19.6%) patients from group 1 and 23 (50.0%) patients from group 2 had a recurrence of atrial tachyarrhythmia (P = 0.002). AF duration and type 2 diabetes were strongly associated with failure of intravenous nifekalant cardioversion. Univariable Cox proportional hazard regression showed that failure of intravenous nifekalant cardioversion, AF duration, and type 2 diabetes were potential risk factors. Multivariable Cox proportional hazard regression showed that failure of nifekalant cardioversion was statistically associated with AF recurrence (adjusted RR = 2.257, 95% CI: 1.006-5.066, P = 0.048). Failure of intravenous nifekalant cardioversion could bring a positive effect on the prognostic differentiation when added into the multivariable model (0.767 ± 0.042 vs. 0.774 ± 0.045, P = 0.025). Failure of nifekalant cardioversion is an independent predictor for persistent AF recurrence after catheter ablation.

Early arteriovenous fistula failure associated with mortality and major adverse cardiovascular events in patients undergoing incident hemodialysis.

Arteriovenous fistula (AVF) patency is important for patients undergoing hemodialysis. The association between early AVF failure and the prognosis, including all-cause mortality and major adverse cardiovascular events (MACE), has not been fully investigated. The present study was performed to investigate the association between early AVF failure and 3-year mortality, cardiovascular disease (CVD) mortality, and MACE. We analyzed 358 patients who started hemodialysis in our institution from October 2008 to February 2020. We defined early AVF failure as cases requiring percutaneous transluminal angioplasty or reoperation within 1 year after AVF surgery. The patients were divided into two groups according to the presence or absence of early AVF failure, and the prognosis of each group was examined. The association between early AVF failure and outcomes (3-year all-cause mortality, CVD mortality, and MACE) was determined using Cox proportional hazards regression analysis. During the 3-year follow-up, 75 (20.9%) patients died (cardiovascular death: n = 39) and 145 patients developed MACE. According to the multivariable analysis, the early AVF failure group had a significantly higher risk of 3-year all-cause mortality (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.09-1.83; p = 0.009), CVD mortality (HR, 1.54; 95% CI, 1.29-2.08; p < 0.001), and MACE (HR, 1.68; 95% CI, 1.25-2.26; p < 0.001). When the patients were stratified by age, early AVF failure was associated with 3-year all-cause mortality in all groups except for the younger group (<65 years of age). Early AVF failure was associated with an increased risk of 3-year all-cause mortality, CVD mortality, and MACE.

Factors associated with extubation failure in an intensive care unit: a case-control study.

to investigate the factors associated with extubation failure of patients in the intensive care unit. unpaired, longitudinal, retrospective and quantitative case-control with the participation of 480 patients through clinical parameters for ventilator weaning. Data were analyzed by: Fisher's exact test or the chi-square test; unpaired two-tailed Student's t test; and Mann-Whitney test. Significant P values lower than or equal to 0.05 were admitted. of the patients, 415 (86.5%) were successful and 65 (13.5%) failed. Success group: the most negative fluid balance, APACHE II in 20 (14-25), weak cough in 58 (13.9%). Failure group: the most positive fluid balance, APACHE II in 23 (19-29), weak cough in 31 (47.7%), abundant amount of pulmonary secretions in 47.7%. positive fluid balance and the presence of inefficient cough or inability to clear the airway were predictors of extubation failure.

Efficacy of transarterial chemoembolization with drug-eluting beads combined with systemic chemotherapy and targeted therapy in colorectal cancer liver metastasis

BackgroundSystemic therapy is the standard treatment for unresectable colorectal cancer with liver metastasis (CRCLM). Transarterial chemoembolization with drug-eluting beads (DEB-TACE) is considered an effective treatment option for CRCLM. Few studies have investigated the combination of DEB-TACE, chemotherapy, and targeted therapy for CRCLM. In the present study, we evaluated the disease control rate (DCR), adverse events, and survival among patients with CRCLM who underwent the combination of DEB-TACE and chemotherapy/targeted therapy.MaterialsWe retrospectively reviewed 35 patients with CRCLM who were treated between January 2015 and January 2021. Standard systemic chemotherapy, targeted therapy, and 66 DEB-TACE procedures were administered. Data were collected on each DEB-TACE procedure, including chemotherapy agents, tumor burden of liver metastasis, number of DEB-TACE courses, and adverse events. Patients who received DEB-TACE after failure of first-line systemic therapy were categorized into the first-line failure group. Patients who received DEB-TACE after the failure of second-line, third-line, or fourth-line therapy were categorized into the other group. Subgroup analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between the two groups.ResultsIn total, 35 patients with CRCLM (34 patients with adenocarcinoma and 1 patient with neuroendocrine carcinoma) were enrolled. In total, 13 patients (37.1%) had extrahepatic metastases at initial diagnosis. In this study, 66 DEB-TACE procedures were performed. The DCR was 54.3%. The median OS period was 47.4 months, and the estimated 3-year OS rate was 59.5%. The median PFS period was 6.3 months, and the estimated 1-year PFS rate was 20.6%. The PFS period was longer in the first-line failure group than in the other group (7.2 vs. 6.3 months). No significant difference was observed in OS between the two groups. Four episodes (6.1%) of grade 3 intra-abdominal infection were observed.ConclusionThe combination of chemotherapy, targeted therapy, and DEB-TACE can lead to a favorable DCR and survival outcomes in patients with CRCLM. Early intervention with DEB-TACE (i.e., after the failure of first-line therapy) has the potential to extend the PFS period in patients with CRCLM. Severe adverse events were rare and manageable. Further prospective, randomized controlled studies are warranted to obtain more conclusive findings.

T1-Weighted, Dynamic Contrast-Enhanced MR Perfusion Imaging Can Differentiate between Treatment Success and Failure in Spine Metastases Undergoing Radiation Therapy.

Current imaging techniques have difficulty differentiating treatment success and failure in spinal metastases undergoing radiation therapy. This study investigated the correlation between changes in dynamic contrast-enhanced MR imaging perfusion parameters and clinical outcomes following radiation therapy for spinal metastases. We hypothesized that perfusion parameters will outperform traditional size measurements in discriminating treatment success and failure. This retrospective study included 49 patients (mean age, 63 [SD, 13] years; 29 men) with metastatic lesions treated with radiation therapy who underwent dynamic contrast-enhanced MR imaging. The median time between radiation therapy and follow-up dynamic contrast-enhanced MR imaging was 62 days. We divided patients into 2 groups: clinical success (n = 38) and failure (n = 11). Failure was defined as PET recurrence (n = 5), biopsy-proved (n = 1) recurrence, or an increase in tumor size (n = 7), while their absence defined clinical success. A Mann-Whitney U test was performed to assess differences between groups. The reduction in plasma volume was greater in the success group than in the failure group (-57.3% versus +88.2%, respectively; P < .001). When we assessed the success of treatment, the sensitivity of plasma volume was 91% (10 of 11; 95% CI, 82%-97%) and the specificity was 87% (33 of 38; 95% CI, 73%-94%). The sensitivity of size measurements was 82% (9 of 11; 95% CI, 67%-90%) and the specificity was 47% (18 of 38; 95% CI, 37%-67%). The specificity of plasma volume was higher than that of conventional size measurements, suggesting that dynamic contrast-enhanced MR imaging is a powerful tool to discriminate between treatment success and failure.

Rehabilitation complexity scale and reimbursement of in-hospital pulmonary rehabilitation.

The use of case-based reimbursement for medical rehabilitation is greatly discussed. The investigators explored the relationship between disability and reimbursement opportunities in individuals with respiratory diseases undergoing in-hospital pulmonary rehabilitation (PR), considering the correlation (if any) between the Rehabilitation Complexity Scale (RCS-E v13) scores used at admission and the actual reimbursement. This study is part of a larger prospective multicenter study conducted by eight Pulmonary Rehabilitation Units in Italy. Here, investigators considered only data from the Lombardy Region. On January 30th or February 28th, 2023, participants were allocated according to the main DRG into 4 groups [tracheostomized/ventilated (TX/V), chronic respiratory failure (CRF), COPD, and miscellaneous group]. We recorded anthropometrics, diagnosis, international outcome measures, and calculated admission and discharge RCS-E v13 scores and hospital stay reimbursement according to the healthcare system (HS). Three hundred and sixteen participants were evaluated. Patients were elderly, in the majority of cases with CRF, presenting comorbidities, disability, dyspnea, and reduced effort tolerance. At admission, RCS-E v13 showed an average moderate value of complexity. The median (IQR) HS reimbursement/stay was different among groups. RCSE v13 evaluated at admission was weakly (r=0.3471), but significantly related to the HS reimbursement/stay (p<0.0001) mainly due to TX/V and miscellaneous subgroups, while no relationship was found for COPD and CRF patients. After PR, all outcome measures improved significantly in all groups (p<0.001 for all). Higher RCS-E v13 scores at admission did not correspond to a proper amount of reimbursement, being this latter under- or over-estimated if compared to needs assessed by RCS-E v13. RCS-E v13 at discharge decreased for all subgroups (range from -6 to -11) reaching a low value of complexity. The RCS-E v13 disability score does not fully mirror the HS reimbursement for patients undergoing inhospital PR.

Achieving optimal doses in treatment of heart failure with reduced ejection fraction at Gia Dinh People's Hospital

Heart failure (HF) with reduced ejection fraction (HFrEF) is a complex clinical syndrome associated with high mortality, long hospital length of stay, high readmission rates, reduced exercise tolerance, and decreased quality of life, as well as requiring significant resources to support treatment and care 1. Currently, it is reported that approximately 50% of all heart failure cases are HFrEF. However, due to recent advancements in cardiovascular diagnostic imaging, earlier, and possibly more precise, detection of HFrEF is greatly enabled. Not only does this seemingly increase the incidence rate of HfrEF in the general population, but it also gives treatment facilities an advantage in improving the prognosis and average life expectancy for these newly rising cases of HFrEF 2. According to heart failure treatment guidelines by Heart Associations around the world, an effective, interdisciplinary, and coordinated care system needs to be applied to all heart failure patients, including the reduced ejection fraction heart failure group, in order to achieve optimal guidelinesrecommended therapy, reduce mortality and readmission. In addition, each patient needs to be provided with a detailed treatment plan, which comprises treatment goals, effective management of comorbidities, follow-up time, diet, and physical activity 6. Therefore, the critical role of HF management programs in improving symptoms and quality of life in both inpatient and outpatient settings has been well recognized and paid continuous attention for the last two decades, with regular updates on team-based healthcare systems and home-based patient care 8,9,10. Recent updates in treatment guidelines have highlighted the role of the treating physician in customizing and adjusting the therapeutic drugs’ doses, to match those recommended as target or optimal, which must also be well-tolerated by the patients, with the aim of improving clinical outcomes 12. Therefore, it could be deduced that not only the sheer application of the four evidence-based foundational treatment but also dose adjustment over time of each one, should be collectively recognized as the basis of treating patients with HFrEF. The operation of a highlyspecialized unit, solely dedicated to the management of HF, known as ‘Heart Failure Unit’, has proven its effectiveness, by means of optimization of medical therapy, irrespective of baseline EF, but most notably reduced EF. Therefore, patients’ symptoms and readmission rate in facilities with “Heart Failure Unit” has witnessed a noticeable reduction. In today’s Vietnam, many tertiary medical facilities have implemented such centralized heart failure care models, and the Cardiology Department of Nhan dan Gia Dinh Hospital is definitely not an exception. The Heart Failure Unit in our department has been established and operating with a soulful dedication to providing HF patients with utmost comprehensive care and guideline-recommended therapy.

Mutation of Epigenetic Regulators at Diagnosis Is an Independent Predictor of Tyrosine Kinase Inhibitor Treatment Failure: A Report from the Residiag Study

Introduction Additional mutations at chronic myeloid leukemia (CML) diagnosis have been shown to variably affect tyrosine kinase inhibitor (TKI) response and were inconstantly detected at loss of response. Contradictory observations may have resulted from difficulties in reliably inferring CML clonal architecture from mutations quantified by NGS, BCR::ABL1 by qRT-PCR, ABL1-TK by RNA-Seq. The RESIDIAG study was designed to identify at diagnosis molecular markers predictive of TKI treatment failure and analyze the clonal dynamics using asymmetric capture sequencing (aCAP-Seq). Methods DNA samples from 60 TKI responders (median follow-up: 7.1 years) were sequenced at diagnosis by aCAP-Seq, allowing quantification and breakpoint sequencing of genomic BCR::ABL1 fusion together with 43 myeloid genes, including ABL1 with a limit of detection of ~0.1% for BCR::ABL1 and 0.5-1% for SNVs and Indels. In parallel, CML patients who experienced treatment failure (ELN 2020) were sequentially analyzed at diagnosis and at failure (n=53), at diagnosis only (n=1), and at failure only (n=3). Small deletions and BCR::ABL1 breakpoints were analyzed to search for microhomology-mediated end-joining (MMEJ) repair signatures. Mutation analysis followed strict medical standards. Results The proportion of patients receiving imatinib at diagnosis wasn't statistically different (p=0.08; Pearson's Chi-square test) between responders (70%) and the failure group (56%). At diagnosis, the number of mutations was higher (p&amp;lt;0.001, t-test with Welch correction) in the failure group (0.9±0.1) as compared with responders (0.18± 0.05). ASXL1, DNMT3A, and TET2 were more frequently mutated at diagnosis in the failure group (38.6%, p&amp;lt;0.001; 10.5%, p=0.01, and 4.3%, p=0.025 respectively; Pearson's Chi²test) as compared with responders (6.7%, 0% and 0% respectively) and the presence of a mutation in one of these genes was highly associated with a reduced failure-free survival (p&amp;lt;0.001, Log-ranked test, Figure 1). An MMEJ signature at BCR::ABL1 breakpoints was more frequent (p=0.014, Pearson's Chi² test) in the failure group (29.1%) than in the responder group (9.1%). and was significantly associated with the ELTS score (p=0.005, Pearson's Chi² test) but not the Sokal score (p=0.017, Pearson's Chi² test). At first failure, 69% of patients had additional mutations in ASXL1 (39%), ABL1-TK (38%), DNMT3A (18%), or TET2 (15%), while other genes were rarely (&amp;lt;5%) mutated. ASXL1 mutations found at diagnosis were still detectable in 18/22 patients at failure and VAF suggested that double mutant BCR::ABL1/ ASXL1 clones were driving TKI failure with or without BCR:: ABL1 tyrosine kinase domain mutation (TKD). ASXL1 mutations disappearing upon treatment were mostly at low frequency &amp;lt;5% at diagnosis and thus possibly not clonally related to CML. Furthermore, a stepwise selection of variables followed by multivariate analysis with the Fine-Gray model identified the age of patients (sdHR [95% C.I.] = 0.99 [0.97-1.00]; p=0.08) and the presence of a mutation in epigenetics regulators at diagnosis as factors affecting the onset of TKD mutations (sdHR = 3.01 [1.76-5.15]; p&amp;lt;0.001). Intriguingly, co-occurring mutations in DNMT3A and TET2 were found in five patients at TKI failure. Their allelic frequency kinetics suggested that these belonged to the same clone driving CML relapse in 4/5 CML patients, while one patient also had a TKD mutation likely involved in CML relapse. Finally, multivariate COX regression analysis identified two independent predictors of TKI failure at diagnosis: a high-risk ELTS score (p=0.001; hazard ratio=3.42 [1.62-7.22] with low-risk as baseline) and a mutation in ASXL1, DNMT3A or TET2 (p=0.002; hazard ratio=2.87 [1.49-5.51]). Conclusion Altogether these results strongly point to the contribution of epigenetic regulator mutations in the emergence of TKI failure in CML and warrant further biological studies to better understand the underlying mechanisms

Evaluating Effectiveness and Safety of Flumatinib for Chronic Phase Chronic Myeloid Leukemia in (CML-CP) without Optimal Response (Warning, Failure) to Imatinib or/and Dasatinib

Introduction Flumatinib is a novel second-generation BCR-ABL1 targeted kinase inhibitors (TKI) with better efficacy and safety than first generation TKIs in first-line treatment of chronic myeloid leukemia in chronic phase (CML-CP). In the previous phase III study, newly diagnosed CML-CP patients receiving flumatinib achieved higher treatment responses and safety than imatinib. When it comes to the patients not achieving the optimal response to TKIs, flumatinib is potentially a better option, nonetheless the robust evidence is unavailable. This study reports the effectiveness and safety of switching to flumatinib in patients who have not achieved the optimal molecular response to imatinib or/and dasatinib. Methods This prospective, multicentre study enrolled Philadelphia Chromosome-Positive (Ph+) CML-CP patients aged ≥18 years and who failed to achieve the optimal response with imatinib or/and dasatinib between March 2021 to October 2022. All patients were treated with flumatinib 600 mg once a day and followed up to 24 months. The primary endpoint of the study was rate of major molecular response (MMR) at 12 months as defined by European LeukemiaNet 2020 recommendations (BCR-ABL1 transcript level ≤0.1% in peripheral blood on RT-PCR assay on International Scale [IS]) and safety was the secondary endpoint assessed with CTCAE 4.03 version. In addition, the optimal molecular response in either the warning or failure patients was evaluated at 3, 6 and 12 months respectively, after switching to flumatinib, and the difference in effectiveness was also analyzed from the available mutation subtypes. Results Overall, 94 patients with Ph+ CML-CP were included in the study. The median (range) age of the patients were 53 (19.0-84.0) years old and 61.7% of the patients were males. A total of 38 (40.4%) patients reported warning response from the previous TKIs whereas 56 (59.6%) of patients reported treatment failure to the previous TKIs. Seventy-seven (81.9%) patients have been treated with one TKI, either imatinib or dasatinib, and 17 (18.1%) have been treated with both prior to the study. Overall, 25 (54%) patients achieved MMR at 12-months follow-up compared to the baseline (Figure 1). The rates of optimal molecular response at 3- and 6-months were also improved compared to the baseline. The optimal molecular response was 76(88%) at 3 months, and 52(73%) at 6 months. Subgroup analysis with previous response to TKIs revealed that flumatinib improved the rates of optimal molecular response in both warning and failure groups. Switching to flumatinib from imatinib or/and dasatinib have been reported with an enhanced optimal molecular response in patients who experienced warning compared with those who had treatment failure after the TKIs with 38 (100%) vs 38 (79%), 29 (91%) vs 23 (59%) and 15 (68%) vs 10 (42%) at 3-, 6- and 12-months respectively (Figure 2). Similarly, the rates of optimal molecular response were improved in patients without mutations compared to those having mutations, 65 (90%) vs 9 (75%) at 3 months, 46 (77%) vs 5 (56%) at 6 months and 23 (59%) vs 1 (20%) at 12 months respectively. The most common adverse events (AEs) were diarrhea in 17 (18%), rash in 11 (12%), bloating in 11 (12%), and thrombocytopenia in 11 (12%) patients. Common hematological AEs of grade 3/4 were thrombocytopenia in 7 (7%), anemia in 3 (3%) and leucopenia in 1 (1%) patients. Conclusion For Ph+ CML-CP patients without the optimal molecular response in previous imatinib or/and dasatinib, flumatinib is a better alternative to the existing treatments. In addition, if the patients were switched to flumatinib earlier, the optimal response was achieved faster. The grade 3/4 AEs were mainly hematologically related, whereas the gastrointestinal events were mostly of grade 1-2.

Considering Older Patients As Candidates for Auto Stem Cell Transplants: A Comprehensive Study on Toxicities and Survival Analysis

Introduction: High-dose chemotherapy and autologous stem cell transplantation (ASCT) are commonly used for relapsed/refractory (R/R) Hodgkin (HL) and non-Hodgkin lymphoma (NHL). However, concerns about treatment-related mortality (TRM) and toxicity limit its use in older patients (pts). Existing evidence suggests higher rates of complications and inferior overall survival (OS) in older pts, but conflicting findings suggest that outcomes may be influenced by comorbidities rather than age ( Lahoud O, Curr Oncol Rep. 2015). Our study comparing ASCT outcomes and toxicities in lymphoma pts in younger and older age groups. Methods: In this retrospective study, we analyzed lymphoma pts who underwent ASCT at the Princess Margaret Cancer Centre from January 2015 to December 2019. After Institutional Review Board approval, clinical data was collected from institutional databases and patient charts. The hematopoietic cell transplantation comorbidity index (HCT-CI) and Charlson Comorbidity Index (CCI) were retrospectively calculated. Response assessment was done by Lugano 2014 classification. Grade 3-5 nonhematologic toxicities were collected from admission to day 100 using Common Terminology Criteria for Adverse Events version 5. Overall survival (OS) and progression-free survival (PFS) were calculated from date of transplant to death or disease progression. OS and PFS assessed via Kaplan-Meier; log rank tests and Cox regression performed. The patients were divided into two age groups: Group A (&amp;lt;65 years) and Group B (≥65 years). Results: There were 334 pts who underwent ASCT. 332 pts were analyzed; 2 pts were lost to follow-up and 16 pts were day 1 transfers, making acute toxicity data unavailable. The median age was 53 (range: 18-71), 17% of pts being aged ≥65. The majority of pts (69%) had NHL (table 1). The Eastern Cooperative Oncology Group (ECOG) performance status was ≤1 for 91%. Group B had a higher proportion of pts with ECOG score =2 (18% vs 7%, p &amp;lt; 0.001 ) and higher CCI (88% vs 27% , p &amp;lt; 0.001). NHL and mantle cell lymphoma (MCL) were more prevalent in Group B (93%, 23% vs 68%, 12% respectively, p&amp;lt; 0.001). Thirteen percent of NHL pts were transformed disease. Both groups had similar percentage of pts with central nervous system (CNS) lymphoma (~ 5%). Conditioning regimens varied based on lymphoma type: most of the HL/aggressive lymphomas: Etoposide+Melphalan (ML), CNS lymphoma: Thiotepa based regimen, and MCL Cytarabine + ML+/- Total Body Irradiation. The majority (83%) were treated for R/R disease, while 17% received it as first-line treatment. Prior to transplant, 76% of pts were in CR. Median follow-up was 38 months. Median OS was not reached for Group A, and 73 months for Group B. Five year OS were 82% and 74% respectively (p = 0.05). Median PFS was 75.2 months for Group A and 43.0 months for Group B, with 5-year PFS of 54% and 47% respectively (p = 0.2). Twenty percent of pts died during follow-up, with only 4% being NRM. From the entire cohort 3% of patients died within 100 days post-transplant, with no difference between groups. Three pts died within 100 days of ASCT with 2 deaths from sepsis (Group A) and 1 death from Respiratory failure (Group B). Common transplant-related toxicities did not differ significantly between groups (figure 1). Group B had significantly higher rates of Renal (7%vs 18%), Respiratory (16% vs 6%), and Metabolism abnormalities (14% vs 5%) (p = 0.021-0.028). Group B needed more blood product transfusions by 100 days post-transplant: Packed Cells (mean) 1.7 vs 1.1 units (p 0.08), Platelets (mean) 3 vs 1.9 units (p 0.002). Group B had a longer average length of stay 18 days vs. 14 days (p &amp;lt; 0.001). About 6% of pts required ICU admission, and 4% were discharged to rehabilitation/long-term care facilities, with no group differences. Conclusions: The study concludes that ASCT can be safely performed in appropriately selected elderly pts. TRM rates were not significantly higher in older compared to younger pts with lymphoma. However, older pts did experience higher rates of specific toxicities including renal failure, pulmonary complications, metabolism abnormalities, longer hospital stays, and increased transfusion requirements. In the multivariate analysis, older pts exhibited shorter OS, influenced by lymphoma type and treatment response. Further research is needed to develop risk stratification and geriatric assessments to improve toxicity prediction in elderly pts undergoing ASCT.

Attrition after Referral for Chimeric Antigen Receptor T-Cell (CAR-T) Products in Multiple Myeloma (MM)

Introduction: Chimeric antigen receptor T-cell (CAR-T) products have shown an impressive response in relapsed/refractory MM patients (pts). The pivotal KarMMa-3 (Otero-Rodriguez P et al, NEJM, 2023) and CARTITUDE-4 (San Miguel J, et al, NEJM, 2023) studies showed that infusion of idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) was superior to other standard of care therapies. However, some pts in these studies were unable to receive CAR-T even after being deemed eligible for apheresis. In KarMMa-3, 12/140 pts who completed apheresis did not receive their cells, 3 due to disease progression/death and 1 due to a true manufacturing failure. In CARTITUDE-4, 16/113 pts who completed apheresis did not receive their cells, with 9 dying prior to infusion and 0 having true manufacturing failures. Other studies have shown that factors like peripheral CD3 count (PCD3) affected the probability of a successful apheresis (Rytlewski et al, ASCO 2022). Known reasons for CAR-T attrition include lack of available spots, true manufacturing failures, death post-apheresis but prior to infusion (PAD; due to infection and/or disease progression), and cell product issues necessitating an expanded access program (EAP). This study aimed to find patient- and disease-specific variables associated with increased rates of CAR-T attrition. Methods: We retrospectively reviewed the medical records of all pts who were approved for either ide-cel or cilta-cel as standard of care (SOC) treatment for MM at MD Anderson between August 2021 and June 2023. The study was approved by the Institutional Review Board at MD Anderson. Pts were classified by CAR-T product received, and the number of apheresis procedures required to produce viable product. They were then classified based on need for EAP. Descriptive statistics including mean, standard deviation, median, and range for continuous variables such as age and lab measurements, and frequency counts and percentages for categorical variables such as stage, gender, comorbidity, treatment, and response were obtained. Fisher's exact test or Chi-square test was used to evaluate the association between two categorical variables. Wilcoxon rank sum test or Kruskal-Wallis test was used to evaluate the difference in a continuous variable between or among patient groups. Kaplan-Meier method was used to estimate overall survival and progression free survival for the pts who received CAR-T infusion. Statistical software SAS 9.4 (SAS, Cary, NC) and S-Plus 8.2 (TIBCO Software Inc., Palo Alto, CA) were used for all the analyses. Results: Data from 153 pts were included. High-risk features, defined as the presence of high-risk cytogenetics, extramedullary disease, or R-ISS stage III, were present in 125 (81.7%), and 84 (54.9%) were penta-refractory. CAR-T cells were infused successfully in 86 (56.2%) pts, including 5 who were infused via EAP. Of the 67 pts who did not get infused, 26 (38.2%) died prior to apheresis, 8 (11.9%) were PAD, 10 (14.9%) were treated with a bispecific agent due to lack of available manufacturing slots, and 3 (4.5%) had true manufacturing failures. Of the 8 patients that were PAD, 2 died due to progression of disease, 4 died from complications of inpatient bridging chemo, and 2 died from complications from lymphodepleting chemo. For all pts with manufacturing failures, their apheresis had a low dose, with 2 out of 3 having PCD3 &amp;lt; 5%. The mean absolute lymphocyte count (ALC) at apheresis was significantly higher in the EAP group (n=5) compared with the non-EAP group, but significantly lower in the manufacturing failures group (n=3) compared with the successful CAR-T manufacturing (n=86) group (Table 1). For the overall cohort of pts receiving CAR-T (n=86), the median progression-free (PFS) and overall survival (OS) rates were 11.7 and 18.8 months, respectively (Figure 1). Conclusion: The PFS and OS for all pts, including those who received their CAR-T through EAP, were excellent. ALC at the time of apheresis was a predictor of true manufacturing failure. Surprisingly, pts successfully treated on EAP had an increased ALC compared with those receiving SOC. Further comparative studies of pts with barriers to CAR-T are needed to identify other variables that increase adverse outcomes so that these can be addressed. Hopefully, with a better understanding of the barriers patients have, we can ensure that more pts get access to this efficacious treatment.