Clinical Outcome Data Research Articles

ERBB2/HOXB13 co-amplification with interstitial loss of BRCA1 defines a unique subset of breast cancers

BackgroundThe HOXB13/IL17RB gene expression biomarker has been shown to predict response to adjuvant and extended endocrine therapy in patients with early-stage ER+ HER2- breast tumors. HOXB13 gene expression is the primary determinant driving the prognostic and endocrine treatment-predictive performance of the biomarker. Currently, there is limited data on HOXB13 expression in HER2+ and ER- breast cancers. Herein, we studied the expression of HOXB13 in large cohorts of HER2+ and ER- breast cancers.MethodsWe investigated gene expression, genomic copy number, mutational signatures, and clinical outcome data in the TGGA and METABRIC breast cancer cohorts. Genomic-based gene amplification data was validated with tri-colored fluorescence in situ hybridization.ResultsIn the TCGA breast cancer cohort, HOXB13 gene expression was significantly higher in HER2+ versus HER2- breast cancers, and its expression was also significantly higher in the ER- versus ER+ breast cancers. HOXB13 is frequently co-gained or co-amplified with ERBB2. Joint copy gains of HOXB13 and ERBB2 occurred with low-level co-gains or high-level co-amplifications (co-amp), the latter of which is associated with an interstitial loss that includes the tumor suppressor BRCA1. ERBB2/HOXB13 co-amp tumors with interstitial BRCA1 loss exhibit a mutational signature associated with APOBEC deaminase activity and copy number signatures associated with chromothripsis and genomic instability. Among ERBB2-amplified tumors of different tissue origins, ERBB2/HOXB13 co-amp with a BRCA1 loss appeared to be enriched in breast cancer compared to other tumor types. Lastly, patients with ERBB2/HOXB13 co-amplified and BRCA1 lost tumors displayed a significantly shorter progression-free survival (PFS) than those with ERBB2-only amplifications. The difference in PFS was restricted to the ER- subset patients and this difference in PFS was not solely driven by HOXB13 gene expression.ConclusionsHOXB13 is frequently co-gained with ERBB2 at both low-copy number level or as complex high-level amplification with relative BRCA1 loss. ERBB2/HOXB13 amplified, BRCA1-lost tumors are strongly enriched in breast cancer, and patients with such breast tumors experience a shortened PFS.

Can Endovascular Repair of Unruptured Intracranial Aneurysms Be Safely Performed in an Outpatient Setting? Lessons Learned from Spine Outcome Control Groups.

The performance of select neurosurgical procedures is being transitioned to an outpatient setting rather than an inpatient setting to increase healthcare cost-effectiveness. Despite numerous technological advancements in the treatment of unruptured intracranial aneurysms (UIAs), the procedures are solely performed in an inpatient setting. We aimed to compare the rate of short-term outcomes associated with inpatient endovascular treatment of UIAs with those for established outpatient neurosurgical procedures, including anterior cervical discectomy and fusions (ACDFs) and lumbar discectomies. We performed a retrospective analysis on the data of healthy (Charlson Comorbidity Index ≤4) adult patients undergoing elective neurosurgical procedures including endovascular repair of UIAs, ACDF, and discectomy between January 1, 2012, and August 31, 2019, at a single tertiary facility. Clinical complications and outcomes data were collected and analyzed. The primary outcome variable was the 30-day readmission rate with subgroup analyses of readmission <48 hours and 48 hours to 30 days. A total of 586 patients and a total of 606 procedures were identified, comprising 205 endovascular UIA treatments, 201 ACDFs, and 200 discectomies. Fourteen UIA procedures were excluded from analysis (n = 191) on the basis of anatomic high-risk features. For the primary outcome, there was no statistically significant difference in 30-day readmission rates among the comparison groups (P = .36). For the subgroup analyses, there were no differences in readmission rates for <48 hours (P = .06) and 48 hours to 30 days (P = .71). In addition, there was no significant difference in intraprocedural complication rates among the groups (P = .19). Inpatient elective endovascular treatment of UIAs had similarly low rates of intraprocedural complications and short-term readmissions compared with the established outpatient spine procedures. We hope that our findings may serve as the foundation for future, prospective studies assessing the safety and utility of performing endovascular procedures for UIAs in an outpatient setting.

Outcomes following functionally aligned total knee arthroplasty in severe varus deformity

IntroductionTotal knee arthroplasty (TKA) in severe varus deformity still remains a challenge. Alternative alignment TKA aims to improve outcomes and satisfaction. The purpose of this study is to report on the outcomes of a functionally aligned TKA in severe varus deformity. MethodsThis is a retrospective review of single surgeon series. 92 patients with a varus deformity of >15⁰ on varus stress underwent a functionally aligned, TKA (Stryker Triathlon, Mahwah, New Jersey, USA) between 2016 and 2022. A control group, matched for age, gender and body mass index (BMI) from the same period was also identified with mild varus deformity (<10⁰). Intra-operative robotic data collected included gap measurements, bone resection depths, alignment, and rate of soft tissue releases. Clinical outcome data was collected as part of the prospective registry which included patient reported outcome measures (Forgotten Joint Score 12, Oxford Knee Score and Knee Injury and Osteoarthritis Outcome Score Joint Replacement), pain Visual analogue score (VAS), patient satisfaction and range of motion. We reported a minimum follow-up of 12 months. ResultsMedial soft tissue release was performed in 7.6 % of patients in the severe varus group. No soft tissue release was required in the control group. 96.7 % of TKAs achieved coronal balance in extension within 1 mm in the severe varus group. The varus stressed Hip knee ankle angle (HKA) was corrected by 8.5⁰ (95 % CI -9.4 to −7.6, p < 0.001). Patients in both group achieved excellent clinical outcomes scores and satisfaction (Severe varus: 91.9 % vs control: 92.7 %) at the final follow-up. ConclusionPatient with severe varus deformity (>15⁰) undergoing a functionally aligned TKA achieve a well-balanced TKA with excellent clinical outcomes and small rates of soft tissue release.

The implementation of preoperative optimization in British Columbia: a quality improvement initiative.

Surgical patient optimization is a proactive approach to improve postoperative outcomes. This article reviews the development of the Surgical Patient Optimization Collaborative, an initiative supporting preoperative optimization in British Columbia, Canada. The Collaborative facilitated optimization programs over two cohorts between 2019 and 2024. A "Change Package" offered screening, intervention, and measurement tools for the following 13 surgical risk factors: anemia, anxiety, body mass index (cohort 2 only), cardiac status, frailty, glycemic control, nutrition, sleep apnea, pain management, physical activity, smoking, social support, substance use, and venous thromboembolism (cohort 1 only). Monthly data submissions from participating sites included the number of patients undergoing optimization, National Surgical Quality Improvement Program-defined 30-day outcomes, length of stay, and patient-reported measures. Run charts were used to analyze the progress of optimization implementation across both cohorts. Fourteen sites participated in each cohort. In total, 9,686 patients were screened for optimization, with 7,100/7,505 (95%) patients receiving at least one optimization intervention. Improvement shifts in the number of patients screened were identified in the run charts across both cohorts. Most patients felt that their optimization improved their surgical experience and outcomes. Data for clinical outcomes were inconsistently reported from sites and precluded analyses. Barriers to implementation included project complexity and structural characteristics, and facilitators were knowledge and beliefs about the intervention, reflection, and evaluation. Preoperative optimization programs were successfully implemented across multiple sites in British Columbia. High-quality clinical outcome analyses are still needed to determine the impact of preoperative optimization on postoperative outcomes. The insight gained from the Collaborative's implementation process may help inform future multicentre preoperative optimization efforts.

Comparison of clinical outcomes and return to sport between unicortical versus bicortical button fixation techniques for subpectoral biceps tenodesis.

There is limited clinical outcome data comparing fixation methods for tenodesis of the long head of the biceps tendon (LHBT), particularly button fixation. The purpose of this study was to compare clinical outcomes, patient-reported outcomes, and return to sport (RTS) between patients undergoing LHBT with bicortical versus unicortical button technique. The authors hypothesized these fixation methods would be similar for all outcomes. Patients who underwent LHBT using unicortical or bicortical button fixation with minimum 2-year follow-up were identified. Postoperative outcomes were evaluated using the American Shoulder and Elbow Surgeons (ASES) questionnaire and visual analogue scale (VAS) pain score. A sports activity survey was collected to assess baseline sport participation and ability to return to pre-injury activities. Continuous variables were analyzed using the Mann-Whitney-U test. Categorical variables were analyzed using Chi-squared tests. Multivariable logistic and linear regression were performed to determine predictors of RTS and time to RTS. Sixty-four subjects (19 unicortical and 45 bicortical button fixation) were included (average follow-up 3.5 (range: 2.0-7.8) years). There were no significant differences found between button groups for VAS pain score (1.5 vs. 1.2; p = 0.876), VAS pain during sport score (1.6 vs. 1.1, p = 0.398), and ASES score (66 vs. 71; p = 0.294). There were no significant differences in rate of RTS (75.0 vs. 77.4%; p = 0.885) or average time to return to sport (11.7 ± 7.3 vs. 7.0 ± 4.0months; p = 0.081) between groups. There were no significant differences in clinical outcomes, pain, or return to sport between patients who underwent LHBT with unicortical or bicortical button fixation.

Burden of Respiratory Syncytial Virus–Associated Hospitalizations in US Adults, October 2016 to September 2023

Respiratory syncytial virus (RSV) infection can cause severe illness in adults. However, there is considerable uncertainty in the burden of RSV-associated hospitalizations among adults prior to RSV vaccine introduction. To describe the demographic characteristics of adults hospitalized with laboratory-confirmed RSV and to estimate annual rates and numbers of RSV-associated hospitalizations, intensive care unit (ICU) admissions, and in-hospital deaths. This cross-sectional study used data from the RSV Hospitalization Surveillance Network (RSV-NET), a population-based surveillance platform that captures RSV-associated hospitalizations in 58 counties in 12 states, covering approximately 8% of the US population. The study period spanned 7 surveillance seasons from 2016-2017 through 2022-2023. Included cases from RSV-NET were nonpregnant hospitalized adults aged 18 years or older residing in the surveillance catchment area and with a positive RSV test result. Laboratory-confirmed RSV-associated hospitalization, defined as a positive RSV test result within 14 days before or during hospitalization. Hospitalization rates per 100 000 adult population, stratified by age group. After adjusting for test sensitivity and undertesting for RSV in adults hospitalized with acute respiratory illnesses, rates were extrapolated to the US population to estimate annual numbers of RSV-associated hospitalizations. Clinical outcome data were used to estimate RSV-associated ICU admissions and in-hospital deaths. From the 2016 to 2017 through the 2022 to 2023 RSV seasons, there were 16 575 RSV-associated hospitalizations in adults (median [IQR] age, 70 [58-81] years; 9641 females [58.2%]). Excluding the 2020 to 2021 and the 2021 to 2022 seasons, when the COVID-19 pandemic affected RSV circulation, hospitalization rates ranged from 48.9 (95% CI, 33.4-91.5) per 100 000 adults in 2016 to 2017 to 76.2 (95% CI, 55.2-122.7) per 100 000 adults in 2017 to 2018. Rates were lowest among adults aged 18 to 49 years (8.6 [95% CI, 5.7-16.8] per 100 000 adults in 2016-2017 to 13.1 [95% CI, 11.0-16.1] per 100 000 adults in 2022-2023) and highest among adults 75 years or older (244.7 [95% CI, 207.9-297.3] per 100 000 adults in 2022-2023 to 411.4 [95% CI, 292.1-695.4] per 100 000 adults in 2017-2018). Annual hospitalization estimates ranged from 123 000 (95% CI, 84 000-230 000) in 2016 to 2017 to 193 000 (95% CI, 140 000-311 000) in 2017 to 2018. Annual ICU admission estimates ranged from 24 400 (95% CI, 16 700-44 800) to 34 900 (95% CI, 25 500-55 600) for the same seasons. Estimated annual in-hospital deaths ranged from 4680 (95% CI, 3570-6820) in 2018 to 2019 to 8620 (95% CI, 6220-14 090) in 2017 to 2018. Adults 75 years or older accounted for 45.6% (range, 43.1%-48.8%) of all RSV-associated hospitalizations, 38.6% (range, 36.7%-41.0%) of all ICU admissions, and 58.7% (range, 51.9%-67.1%) of all in-hospital deaths. In this cross-sectional study of adults hospitalized with RSV before the 2023 introduction of RSV vaccines, RSV was associated with substantial burden of hospitalizations, ICU admissions, and in-hospital deaths in adults, with the highest rates occurring in adults 75 years or older. Increasing RSV vaccination of older adults has the potential to reduce associated hospitalizations and severe clinical outcomes.

Abstract 4136136: Left Ventricular Global Longitudinal Strain: An Imaging Marker Associated with Improved Survival in Paradoxical Low-Flow, Low-Gradient Severe Aortic Stenosis

Background: The optimal clinical management and timing of intervention are less well defined in paradoxical low-flow, low-gradient severe aortic stenosis (PLFLG AS). Left ventricular global longitudinal strain (LV-GLS) has been shown to predict outcomes in high flow severe AS, but there is lack of data in patients with PLFLG AS. Given the exaggerated LV hypertrophy and remodeling pattern in PLFLG AS, LV-GLS may be a mechanistic imaging marker for worse outcomes. Hypothesis: In patients with PLFLG AS, LV-GLS is associated with adverse clinical outcomes by detecting subclinical myocardial fibrosis resulting from myocardial remodeling due to LV pressure overload. Methods: We examined patients with PLFLG AS defined as AVA &lt;1cm 2 , mean gradient &lt;40mmHg and preserved left ventricular ejection fraction (LVEF) ≥50%, with low-flow state defined as transvalvular flow rate (Q) ≤210 ml/sec. Exclusion criteria included moderate or greater mitral or aortic regurgitation and presence of atrial fibrillation at the time of echocardiogram. LV strain analysis was performed using 2D-strain imaging software (TomTec, Chicago, IL). Clinical outcome data were obtained via the electronic health record. The primary outcome was defined as all-cause mortality. Patients were stratified by LV-GLS above and below the median value. Results: A total of 198 patients were included in the analysis, with a median LV-GLS of -12.3% [IQR: (-9.8,-16.3)]. Over a median follow-up time of 1.2 years, 130 deaths (65.6%) were identified. Patients with less negative LV-GLS (n=101) had worse survival than those with more negative LV-GLS (n=97; 22 vs 38%; p=0.02) (Fig 1). After multivariable adjustment for potential confounders (stroke volume index, aortic valve mean gradient, relative wall thickness, age, sex, heart failure, hypertension, coronary artery disease, and diabetes), less negative LV-GLS was independently associated with adverse outcomes (HR 1.56; 95% CI (1.03-2.38); p=0.04). Conclusions: In patients with PLFLG AS as defined by a transvalvular flow rate (Q) ≤210 ml/sec, reduced LV-GLS is associated with increased all-cause mortality. LV-GLS may serve as an imaging marker to help guide clinical decision making in PLFLG AS.

CTNI-55. A PHASE 0/1B STUDY OF AZD1390 PLUS RADIOTHERAPY IN NEWLY DIAGNOSED, MGMT-UNMETHYLATED AND RECURRENT GLIOBLASTOMA PATIENTS

Abstract BACKGROUND ATM inhibition is hypothesized to potentiate the effects of radiation by preventing acute phase DNA damage repair. This Phase 0/1b study evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of AZD1390, a first-in-class ATM inhibitor, in combination with radiation in newly-diagnosed and recurrent GBM patients (NCT05182905). METHODS All patients received 3 days of AZD1390 prior to planned resection at 2-4, 4-6 or 23-25 hrs following the final dose (120/300mg for nGBM and 400mg for rGBM). Tumor tissue, cerebrospinal fluid (CSF), and plasma were collected. Total and unbound drug concentrations were measured using validated LC-MS/MS methods. ATM inhibition was assessed via ex vivo tissue radiation, quantifying pRAD50 levels compared to non-radiated control. A PK ‘trigger’ determined eligibility for Phase 1b and patients exceeding the PK threshold (2 nM unbound drug levels in Gd-non-enhancing tumor region) were eligible for therapeutic dosing of AZD1390 plus radiotherapy. RESULTS Thirty nGBM patients and twenty-nine rGBM patients were enrolled. Forty-eight out of the forty-nine evaluable patients exceeded the PK threshold and qualified for therapeutic dosing. The mean unbound concentrations of AZD1390 in Gd-nonenhancing tumors of both nGBM and rGBM patients were significantly above the threshold at all dose levels and time intervals. Following 5Gy ex vivo radiation of surgical specimens, pRAD50 expression was significantly suppressed in AZD1390-treated patients compared to untreated controls. To date, 6 MGMT-unmethylated nGBM patients and 15 rGBM patients were enrolled in the Phase 1b component of the study, with median clinical follow-up of 7.0 months. Median PFS and OS have not been reached in the nGBM population. Median OS for rGBM patients was 15.4 months. CONCLUSION AZD1390 is well-tolerated in both newly-diagnosed and recurrent GBM patients, achieving pharmacologically relevant concentrations in Gd-nonenhancing tumor tissue, and suppressing radiation-induced increase in pRAD50 levels. These data are the first to demonstrate AZD1390-mediated PD and PK responses in nGBM and rGBM patients. Clinical outcomes data are maturing and will be reported.

Implementing the Global Leadership Initiative on Malnutrition (GLIM) criteria in Crohn's disease: Prevalence of malnutrition and association with clinical outcomes

Background & AimsLimited data exist regarding the implementation of the Global Leadership Initiative on Malnutrition (GLIM) criteria for diagnosing malnutrition in Crohn’s disease (CD), and its association with CD prognosis. In the present study eighteen GLIM combinations and a combined one were implemented to identify differences in the prevalence of malnutrition and to investigate potential associations with clinical outcomes at 6 months. MethodsDifferent methodologies to diagnose malnutrition were used at baseline, namely the Subjective Global Assessment (SGA), eighteen different combinations of phenotypic and etiologic GLIM criteria and a combined version based on all GLIM combinations (GLIMcv) to test differences in the estimated prevalence and outcomes’ prognosis. At 6 months, data for clinical outcomes were collected (i.e. hospitalization, antibiotics use, intensification/change of biologic agent, initiation of biologic agent/corticosteroids, surgery, disease activity), and an overall adverse clinical outcome index was created. Results250 people with CD (54.8% males, mean age 41.2±14.1 years, 37.2% with active disease) were enrolled. Prevalence of malnutrition based on SGA and GLIMcv was 23% and 52%, respectively, and 5.8-63% based on different GLIM combinations. Malnutrition diagnosed with GLIMcv was associated with an increased likelihood of intensification/change of biologic agent [Odds ratio (OR): 1.82, 95% Confidence interval (CI): 1.00-3.42, p=0.05] and an overall adverse clinical outcome (OR: 2.18, 95% CI: 1.23-3.87, p=0.008) at 6 months, after adjustment for age, sex, disease location and duration. Malnutrition diagnosed through SGA was not associated with clinical outcomes at 6 months. ConclusionsBased on GLIMcv, half of the sample was diagnosed with malnutrition. Malnutrition significantly increased the likelihood of uncontrolled disease requiring treatment upgrading and leading to an overall adverse clinical outcome short term.

Impact of real-world off-label dose of Apixaban on long-term clinical outcomes in patients with atrial fibrillation and chronic kidney disease

Abstract Background Apixaban represent one of the cornerstone treatments to prevent cardioembolic events in patients with nonvalvular atrial fibrillation (NVAF). However, the choices of Apixaban dose guided by the decision-making process of the physician, which considers specific according to kidney functions are inconsistent in the real-world practice. Objective The objective of the present study is to evaluate the effects of real-world Off-label dose of Apixaban on long-term clinical outcomes in NVAF patients with chronic kidney disease (CKD). Methods Our database of AF patients diagnosed with CKD from 2018 to 2023 was used to obtain laboratory, echocardiography, electrocardiogram (ECG), and clinical outcomes data. Inclusion criteria were all AF patients with CKD using Apixaban. And we compared bleeding, systemic thrombotic events including stroke/systemic embolism and death according to off-label real -world dose of Apixaban. Results Among 635 patients with AF and CKD (76.9±10.4 years), 335 (52.8%) patients took off-label underdosed Apixaban. Difference in the baseline characteristics was not observed among patients including CHA2DS2 VASc score and HASBLED score. During the median 18-month follow-up, a lower incidence of bleeding events (P=0.001) was observed in the off-label underdosed Apixaban group compared to those with standard dose or off-label overdosed Apixaban. However, there was no significant difference of systemic thrombotic events including stroke/systemic embolism and death according to off-label real-world dose of Apixaban (off-label underdose vs. standard dose, P=1.000; off-label overdose vs. standard dose, P=1.000; off-label underdose vs. off-label overdose, P=0.609). In multivariate analysis, HASBLED score was independent risk factors for bleeding events (OR 9.650; CI 1.998-46.622; P=0.005). Conclusions Compared with standard or off-label overdose of Apixaban, off-label underdose of Apixaban was associated with a lower risk of bleeding in patients with AF and CKD, with no difference in the risk of stroke/systemic embolism or death, supporting the apixaban dosing tailored to specific clinical features and drug pharmacokinetics of the Asian patients.

A meta-analysis of randomised controlled trials comparing optical coherence tomography-guided against angiography-guided revascularisation

Abstract Optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) offers more in-depth assessment of plaque morphology, vessel sizing and post-PCI stent deployment characteristics than angiography guidance alone. Previous studies have demonstrated superiority of OCT-guided compared to angiography-guided PCI in stent implantation and expansion, with no difference in safety outcomes. Despite this, adoption of OCT-guided PCI remains low in clinical practice due to its increased procedural time, larger contrast volume, and added cost. Two large multicentre international randomised controlled trials (RCTs) were recently published. We therefore aimed to perform an up-to-date meta-analysis of RCTs comparing OCT-guided revascularisation against angiography-guided revascularisation on hard clinical outcomes. A comprehensive search of PubMed/MEDLINE and Ovid/Embase was performed, of which only RCTs were included. Two authors identified relevant articles and extracted the data independently. Any disagreements were resolved by a third author. Clinical outcome data was extracted from each study and then pooled to determine the overall risk ratio (RR) and confidence interval (CI) collectively. This was calculated with random-effects model using the Mantel-Haenszel method. All reported P values are two-sided, with significance set at P&amp;lt;0.05. A total of ten RCTs involving a total of 5062 patients were included. After an average follow-up of 20 months, there was no significant difference in the trial-defined composite endpoint between OCT-guided versus angiography guided revascularisation [6.8% versus 7.9%, RR 0.85, 95% CI (0.69 to 1.03), P=0.10, heterogeneity (I2)=0%]. There was also no significant difference in cardiac death [1.0% versus 1.6%, RR 0.61, 95% CI (0.36 to 1.02), P=0.06, heterogeneity (I2)=0%, Figure 1a], myocardial infarction [3.2% versus 3.7%, RR 0.86, 95% CI (0.65 to 1.15), P=0.31, I2=0%, Figure 1b] and target lesion or vessel repeat revascularisation [3.8% versus 4.1%, RR 0.95, 95% CI (0.72 to 1.25), P=0.70, I2=0%, Figure 1c] between the two arms. However, the OCT-guided revascularisation arm was associated with a significantly lower rate of stent thrombosis [0.8% versus 1.5%, RR 0.57, 95% CI (0.33 to 0.97), P=0.04, I2=0%, Figure 1d] than the angiography-guided revascularisation arm. The number-needed-to-treat (NNT) by OCT-guided revascularisation to reduce one additional stent thrombosis event was 143. In conclusion, our findings show the use of OCT-guided revascularisation led to a significant reduction in stent thrombosis compared to angiography-guided revascularisation, but there was no difference in cardiac death, myocardial infarction and repeat revascularisation. The NNT for stent thrombosis was 143 patients. Further research is needed to identity those subgroups most likely to benefit from OCT-guided revascularisation before it can be more widely adopted to significantly impact on clinical care.

Preliminary results from the Polish Infective Endocarditis Registry (POL-ENDO): time to change clinical approach?

Abstract Background/Aims: Infective endocarditis (IE) is a severe valve disease associated with high morbidity and mortality. The aim of this preliminary study was to evaluate the profile and treatment outcomes of IE in Poland based on the POL-ENDO registry. Methods A prospective cohort, multicenter, observational study - the POL ENDO registry - of IE patients from 134 hospitals in Poland recruited between August 2022 and August 2023 was performed. We evaluated demographic, clinical, imaging, and treatment outcome data. A comparison of the Polish patients with those assessed in the ESC-EORP EURO-ENDO registry was performed. Results Among a total of 880 IE patients, 622 were male (70.7%). The POL-ENDO participants were older (61.4±16.7 years vs. 59.25±18.03 years, p=0.001). Native valve IE (NVIE) occurred more often in Poland (82.3% vs. 56.6%, p &amp;lt;0.001). Transthoracic echocardiography (TTE) was performed more frequently in Poland (93.6% vs. 89.8% p&amp;lt;0.001). New imaging techniques (CT/MRI/PET/SPECT) were less frequently used in Poland (CT: 53.2% vs. 41.3%, p&amp;lt;0.001; MRI: 18.7% vs. 6.4%, p&amp;lt;0.001). Heart failure (HF) occurred more often in Poland as inhospital complication (31.4% vs. 14%, p&amp;lt;0.001). Surgical treatment was less performed in Poland (51.2% vs. 36.9%, p&amp;lt;0.001). Inhospital mortality was higher in Poland (21% vs. 17%, p=0.008). Conclusion Polish patients with IE were significantly older and more comorbid. New imaging techniques are less frequently used in Poland. Echocardiography was performed more frequently in Poland as the diagnostic mainstay. Surgical treatment was significantly less frequent in Poland. Inhospital mortality in Poland is greater. The change of clinical practice in Poland should be considered.

Impact of coronary revascularization on clinical outcomes of post-acute myocardial infarction patients with left ventricular thrombus

Abstract Background Left ventricular thrombus (LVT) is an uncommon, but dangerous complication seen in post-acute myocardial infarction (AMI). With advances in percutaneous coronary intervention (PCI) techniques, the incidence of post-AMI LVT has declined in the contemporary era. However, a minority of patients do not undergo coronary revascularisation due to medical contraindications or patient preference. This study aimed to evaluate the clinical characteristics and outcomes of post-AMI LVT patients treated with and without coronary revascularisation. Methods This was a retrospective study of 263 consecutive post-AMI patients diagnosed with LVT from November 2012 to January 2021, retrieved from a echocardiography database. Patients were stratified by the presence or absence of revascularisation treatment. Baseline clinical characteristics, treatment and outcomes data were collected and analysed. Results The median follow-up duration was 2.9 years (IQR: 0.9 – 4.7). A majority of post-AMI LVT patients underwent revascularisation via PCI (71.5%, n = 188), CABG (4.2%, n = 11) or thrombolysis (0.4%, n = 1). Unrevascularised patients (24.0%, n = 63) were older (p &amp;lt;0.001), more likely to be female (p &amp;lt;0.001), and had more co-morbidities such as previous stroke (p &amp;lt;0.001), heart failure (p = 0.001), chronic kidney disease (p = 0.020), and malignancy (p = 0.021). More unrevascularised patient had NSTEMI (p &amp;lt; 0.001), and significantly fewer were treated with triple therapy (p &amp;lt; 0.001). Incidence of LVT resolution was lower (p &amp;lt; 0.001) while all-cause mortality was higher (p &amp;lt; 0.001) for unrevascularised patients on univariate survival analyses. On multivariable Cox regression, revascularisation status was not an independent predictor of LVT resolution, bleeding, stroke, or all-cause mortality outcomes. Conclusion While unrevascularised post-AMI LVT patients had poorer outcomes compared to revascularised patients overall, revascularisation status itself was not independently associated with poorer clinical outcomes. Optimising medical therapy such as triple therapy remains a key treatment goal for post-AMI LVT patients.

Ten-year major clinical outcomes between first- and second-generation drug-eluting stents in hypertensive patients underwent percutaneous coronary intervention

Abstract Background There are very limited long-term clinical outcome data comparing first-generation (1G) versus second-generation (2G) drug-eluting stents (DES) in patients with hypertension. The authors sought to compare the efficacy and safety 2G-DES with 1G-DES in hypertension patients who underwent percutaneous coronary intervention (PCI) during ten-year clinical follow-up periods. Methods Finally, a total of 1,631 eligible hypertensive patients who underwent PCI with 1G-DES (paclitaxel-, sirolimus-eluting stent, n = 715) or 2G-DES (zotarolimus [endeavor, endeavor resolute]- or everolimus-eluting stent [promus element, xience], n = 916) were enrolled. The study endpoints were individual and composite clinical outcomes up to ten-year. Results After PSM, two propensity-matched (PSM) groups (452 pairs) were generated. During the ten-year follow-up period, the 2G-DES group had a lower incidence of target lesion revascularization (TLR; hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.35 – 0.82; p = 0.004), target vessel revascularization (TVR; HR, 0.66; 95% CI, 0.46 – 0.94; p = 0.022), any revascularization (HR, 0.65; 95% CI, 0.48 – 0.88; p = 0.006), total major adverse cardiac events (MACE; HR, 0.70; 95% CI, 0.55 – 0.90; p = 0.005), TLR MACE (HR, 0.69; 95% CI, 0.49 – 0.98; p = 0.037), and MACCE (HR, 0.69; 95% CI, 0.54 – 0.88; p = 0.002, table). Conclusion In our single-center, all-comer registry, 2G-DES had better efficacy especially repeat revascularization and MACE as compared with 1G-DES in hypertensive patients during 10-year follow-up periods.

Impact of body weight and body mass index on clinical outcomes of edoxaban therapy in atrial fibrillation patients included in the ETNA-AF-Global registry

Abstract Background In atrial fibrillation (AF) patients (pts) receiving non-vitamin K antagonist oral anticoagulant therapy, extreme body weights, both obesity and low body weight, may impact clinical outcomes. Purpose To determine the impact of body weight and body mass index (BMI) on clinical outcomes in AF pts receiving edoxaban from the Global ETNA program (Europe [NCT02944019], Japan [UMIN000017011], Korea/Taiwan [NCT02951039], Hong Kong [NCT03247582] and Thailand [NCT03247569]). Methods ETNA-AF-Global, a multinational, prospective, observational study collected demographic and clinical outcomes data for AF pts receiving edoxaban. In this subanalysis, pts were categorised into the following body weight groups: ≤60kg, &amp;gt;60 to 80kg (reference body weight), &amp;gt;80 to ≤100kg and &amp;gt;100kg; and BMI groups: &amp;lt;18.5kg/m², ≥18.5 to &amp;lt;25.0kg/m² (reference BMI), ≥25.0 to &amp;lt;30.0kg/m², ≥30.0 to &amp;lt;40.0kg/m² and ≥40.0kg/m². Clinical outcomes at 2-year follow-up were compared across body weight and BMI groups. Results 26,805 pts were included in this analysis. Mean ± standard deviation body weight was 72.2 ± 18.1kg and mean BMI was 26.4 ± 5.0kg/m². 43.7% of pts were categorised into the &amp;gt;60 to 80kg reference body weight group. [other groups: ≤60kg, 28.1%; &amp;gt;80 to ≤100kg, 21.7%; &amp;gt;100kg, 6.5%] and 40.0% of pts into the ≥18.5 to &amp;lt;25.0kg/m² reference BMI group [other groups: &amp;lt;18.5kg/m², 3.0%; ≥25.0 to &amp;lt;30.0kg/m², 37.3%; ≥30.0 to &amp;lt;40.0kg/m², 18.0%; ≥40.0kg/m², 1.7%]. Clinical outcomes are shown in Fig. 1 as unadjusted hazard ratios vs. reference group according to weight and in Fig. 2 according to BMI. Among body weight groups, pts weighing ≤60kg had the highest annualised rates of any stroke or systemic embolic event (SEE; 1.24%), ischemic stroke (0.97%), all-cause death (3.96%), major bleeding events (1.49%), and major bleeding or clinical-relevant non-major (CRNM) bleeding events (3.45%). Pts in the reference body weight group had the lowest annualised rates of all-cause death (2.81%). Annualised rates of major bleeding, major bleeding or CRNM bleeding events and any stroke or SEE were lowest in pts weighing &amp;gt;100kg. Among BMI groups, annualised rates of all effectiveness and safety outcomes were highest in pts with a BMI &amp;lt;18.5kg/m². Pts in the ≥25.0 to &amp;lt;30.0kg/m² BMI group had the lowest annualised rates of all-cause death (2.85%) and pts in the ≥18.5 to &amp;lt;25.0kg/m² BMI group had the lowest annualised rates of CV death (0.73%). Conclusions In the Global ETNA-AF program, clinical outcomes varied between different body weight and BMI subgroups. These findings highlight the need to consider the clinical implications of low body weight and/or low BMI, as AF pts who belong to these categories may be at higher risk of adverse outcomes during long-term anticoagulant treatment.Figure 1.Figure 2.

Favorable impact of FFRCT on myocardial revascularization outcomes: results from an observational real-world registry

Abstract Background Based on excellent clinical outcomes data, coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) is endorsed by guidelines to diagnose obstructive coronary artery disease (OCAD)(1). Dedicated outcome analyses in revascularized patients are essential to assess the additional value of FFRCT in revascularization. Purpose To assess the impact of FFRCT use on the postprocedural myocardial injury (PMI) and long-term outcomes of patients with OCAD undergoing myocardial revascularization. Methods Patients with suspected OCAD on CCTA (at least one stenosis of &amp;gt;50% in any vessel) were included from a 2013-2021 tertiary hospital registry. Propensity score adjusted Cox- regression and logistic regression analysis were used to assess the impact of FFRCT on the outcomes of OCAD patients post-revascularization. PMI was defined as cardiac troponin (cTn)&amp;gt;5 times the 99th percentile URL for percutaneous coronary intervention (PCI) and cTn&amp;gt;10 times the 99th percentile URL for coronary artery bypass graft (CABG) (2). Major adverse cardiovascular events (MACE) comprised all – cause mortality, acute myocardial infarction (AMI), stroke, hospitalization for heart failure (HHF) and new revascularization. Results From a registry of 7541 patients, suspected CCTA - derived OCAD was reported in 1601 cases. 559 OCAD patients were revascularized: 386(69.05%) by PCI, 166(29.7%) by CABG and 7(1.25%) by PCI and CABG. FFRCT was performed in 252(45.1%) patients. During a follow-up of 4.4±2.2 years, MACE occurred in 137(24.5%) patients: 43(7.7%) died, 21(3.8%) patients were hospitalized for AMI, 14(2.5%) patients had a stroke, 12 (2.1%) patients had HHF and 77(13.8%) patients had a new revascularization. Survival analysis indicated significant differences in MACE and all-cause mortality–rates between FFRCT use and no FFRCT use (log- rank p = 0.033 and 0.004, Fig 1). Multivariable propensity–adjusted Cox–regression analysis showed a non–significant trend towards reduced MACE risk by using FFRCT (HR 0.736, 95% CI 0.513-1.055, P=0.095) and a significant reduction in all-cause mortality risk (HR 0.476, 95% CI 0.230–0.985, P=0.046). Sub-analysis in the PCI and CABG groups showed no significant association between FFRCT and MACE. Among the 477 patients with available cTn values, 203 (42.5%) had PMI. In the CABG group, FFRCT use correlated with low PMI incidence (5.3% vs. 15.6%, p=0.044). However, multivariable Cox regression analysis revealed no significant association between FFRCT use and PMI(Fig 2). Conclusion This observational designed study reveals for the first time that FFRCT reduces post-myocardial revascularization MACE, primarily driven by reduced all-cause mortality. No clear reduction of PMI was observed suggesting that FFRCT value extends beyond procedural enhancements. Although derived from a large real-world registry, these promising observations need to be confirmed by randomized studies.Figure 1Figure 2

Biomarkers of microbial translocation and generalized inflammation are associated with frailty among people with HIV.

Frailty occurs at higher rates and younger ages among people with HIV (PWH) compared to the general population and is often attributed to chronic inflammation and subsequent immune exhaustion. We assessed how inflammatory biomarkers are associated with frailty among PWH. The Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort is comprised of adult PWH in care at 10 sites, and harmonizes demographic, clinical, and patient-reported outcomes (PRO) data. A panel of 13 inflammatory biomarkers was collected from a subset of virally suppressed PWH once per person between 2010-2018. Frailty was measured with a validated PRO phenotype, scored 0-4, from biomarker collection date through July 2022. With adjusted linear mixed models, we estimated longitudinal associations between standard deviation-scaled log2-transformed biomarkers and frailty score. Among 273 PWH, most were male (91%), average age at baseline was 45, 42% were non-Hispanic White while 35% were non-Hispanic Black, and average follow-up time was 5.5 years. Several biomarkers were associated with higher frailty, including those linked to microbial translocation (sCD14, LBP, KT ratio) and systemic inflammation (CRP, IL-6, suPAR, sTNFR1, sTNFR2). Higher IL-6 was associated with a 0.25-point higher frailty score (95%CI:0.12-0.39). Higher sTNFR1 (0.35 [0.13-0.56]), sCD14 (0.21 [0.11-0.31]), and suPAR (0.24 [0.11-0.36]) levels were also associated with higher frailty scores over follow-up. Higher levels of biomarkers linked to microbial translocation and systemic inflammation are associated with higher average frailty scores over time in a cohort of virally suppressed PWH, highlighting these pathways as potential interventional targets for mitigating frailty in PWH.

Results of an Integrated Phase I/II Prospective Clinical Trial (NEXIS) for Neoadjuvant Anti-PD-L1 (Durvalumab) and Anti-CTLA-4 (Tremelimumab) With Radiation for High-Risk Soft-Tissue Sarcoma of the Trunk and Extremities.

Background The current management of large, high-grade soft tissue sarcoma (STS) of the trunk and extremities includes radiation and surgical resection. The initial use of chemotherapy and targeted therapy are controversial and although most patients present with localized disease, many eventually develop incurable metastases. The results and analysis of the safety and antitumor activity of combined checkpoint inhibitor immunotherapy with neoadjuvant radiation for high-risk primary STS are presented here. Methods This was an integrated phase I/II prospective single-arm trial (Nutrition and Exercise in Critical Illness Trial (NEXIS) trial). Eligible patients were age ≥18 years with histologically confirmed intermediate or high-grade STS of the trunk or extremity ≥5 cm diameter and were Eastern Cooperative Oncology Group performance status 0-1. The treatment algorithm included neoadjuvant anti-PD-L1 (Durvalumab) and anti-CTLA-4 (Tremelimumab) for three cycles of four weeks/cycle along with external beam radiation for five weeks, followed by wide surgical resection, and adjuvant Durvalumab monotherapy for four cycles. High-grade toxicity was continually assessed for the first 12 patients in phase I and the primary endpoint for phase II was an excellent histological response (grade 0 or 1 score on a semi-quantitative assessment for tumor regression). This study was registered with ClinicalTrials.gov, number NCT03116529. Findings Between October 2017 and November 2021, 23 patients were enrolled. Five patients had progression of distant disease during neoadjuvant treatment and withdrew from the study before surgery. A total of 18 patients who completed at least the neoadjuvant immunotherapy, radiation and surgery were included for analysis. The most common tumor was undifferentiated pleomorphic sarcoma (n=9, 50%). The occurrence of any adverse event (AE) was recorded in 16 (88.9%)patients, and 3 (16.7%)patients had a serious AE. Eight out of 18 patients (44.4%) had disease-free survival at a median of 39.7 months. Four out of 18 patients (22.2%) were alive-with-disease at a median of 37.1 months from diagnosis of distant metastasis, and six out of 18 (33.3%) died of disease at a median of 20.8 monthsfrom diagnosis of distant metastasis. Local recurrence occurred in two patients (11.1%) and was concomitant with distant disease in each case. Based on Response Evaluation Criteria in Solid Tumors v1.1, a partial response was noted in five (27.8%) cases, stable disease in 10 (55.6%) cases, and progressive disease in three (16.7%) cases. Histological semiquantitative analysis revealed a "good" responsein eight (44.4%) patients, a "moderate" response in four (22.2%) patients, and a "poor" response in six (33.3%) patients. The mean patient-reported outcome measures regarding fatigue, physical function, or physical interference demonstrated no significant differences between various timepoints before, during, or after treatment. Conclusion Neoadjuvant combined immunotherapy and radiation for high-risk STS was relatively well-tolerated. The histological, radiologic, and clinical outcome data in this novel trial were relatively similar to historical literature for non-immunotherapy treatment regimens.

Long term outcome of Immunoglobulin M (IgM) Nephropathy of Children in National Institute of Kidney Diseases &amp; Urology (NIKDU), Dhaka, Bangladesh

Background: Immunoglobulin M nephropathy (IgMN) is a new clinicoimmunopathologic entity which present mainly as idiopathic nephrotic syndrome in both children and adults. The clinical manifestation of IgMN are highly variable presenting with isolated haematuria or asymptomatic proteinuria. About 6 to 23 percent of IgMN patient developed end stage kidney disease. Usually treated with immunosuppressive agents (cyclosporine/tacrolimus) along with corticosteroid has response rates up to 50%. In our institute last few years we have observed a surprisingly rise of IgM nephropathy in children. Objective: To see the response of IgMN children treated with tacrolimus or mycophenolate mofetil(MMF) and long term follow up to observe their outcome. Methodology : This was a prospective observational study done in the Department of Paediatric Nephrology, National Institute of Kidney Diseases &amp; Urology, Dhaka, starting from January/2014 to December/2017. The study population consists of 86 IgMN children, age ranges from 2 to 12 years. The study was approved by institutional ethical review committee and informed written consent was taken from every parents. Twenty seven patients(Group-I) were selected purposively and treated with MMF and 59 patients (Group- II) treated with tacrolimus for 2 years. Patients were followed up three monthly onward in a prescribed form including adverse effect of drugs. Clinical outcome data like remission, active disease, active disease with renal impairment and dependency on renal replacement therapy(RRT) were documented for statistical analysis. Results: Of 86 IgMN children most of them were older than &gt;8-12 years in both groups and the highest percentage were clinically diagnosed as frequently relapsing nephrotic syndrome. In Group I 43.48% children remain on remission, 13.04% have active disease, 30.43% are active disease with impaired renal function and 4.35 % went into RRT. In Group II 55.56% children remain on remission, 12.96 % have active disease, 16.67% are active disease with impaired renal function and 5.56% dependent on RRT. Conclusion: From above observations, the overall prognosis of IgMN children is not good. The clinical course and disease outcome did not differ significantly between two groups treated with mycophenolate mofetil and tacrolimus. BANGLADESH J CHILD HEALTH 2023; VOL 47 (1) : 34-38

A Clinical Outcomes Data Archive for a Comprehensive Fetal Diagnosis and Treatment Center

Introduction: Data on near- and long-term clinical outcomes are critical for the care of all maternal-fetal patients presenting to a fetal center. This is especially important since physiologic and neurodevelopmental attributes do not manifest until later childhood when multilevel (e.g., individual, family, policy) factors have a direct influence on health outcomes. Electronic health records (EHRs) create opportunity for efficient data collection. However, documentation structures are not designed for acquisition of key attributes, and changes over time and between-clinician differences can affect resultant output. Therefore, EHR derived datasets have limited ability to accurately characterize the clinical presentation and care trajectory of patients with congenital anomalies. In addition, in most systems, the fetus lacks a digital identity and requires relinking fetal attributes documented in the maternal chart to those from the pediatric EHR. This conundrum amplifies in the setting of multiple gestation, returning maternal patients, and pregnancies with fetal demise. Moreover, current data capture systems result in incomplete abstraction of variables that may confound, mediate, or moderate critical associations. Our objective was to develop and implement a prospective data capture platform to transform EHR data into an analytic-grade database for multipurpose use. Methods: A unified platform for longitudinal follow-up of maternal-child dyads cared for at our fetal center, named the Clinical Outcomes Data Archive (CODA), was constructed. CODA was designed using a data dictionary based on multidisciplinary and interprofessional expert input, a relational identity for each patient, fetus, and pregnancy, and a process by which EHR-sourced and chart-abstracted data are validated by a well-trained team. Descriptive analyses were performed for data acquired between July 2022 and July 2023, and a comparison of studies before and after implementation of CODA is presented. Conclusion: 5,394,106 data points were validated for 7,662 patients across 12 conditions. 2% of data points were found to be unreliable or undocumented. 91% of data points were sourced from the EHR. Eighty-five percent of condition-specific variables required manual chart abstraction. The study conducted with CODA was able to contribute to 18 other studies. CODA successfully merges EHR-sourced and manually abstracted documentation for longitudinal study of the maternal-child dyad.