Large Study Research Articles

Abstract 4123563: High Prevalence of Unrecognized Actionable Cardiac Arrhythmias in Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease

Background: Patients with chronic obstructive pulmonary disease (COPD) are at high risk for developing arrhythmias due to hypoxemia, right heart failure and use of beta-agonists inhalers. Symptoms related to arrhythmias can often be masked or confounded by symptoms related to COPD exacerbation and remain undiagnosed. Objective: To identify the incidence of actionable arrhythmias in patients with no prior cardiology follow-up and moderate–severe COPD with continuous monitoring. Methods: An automatic referral for electrophysiology (EP) consult was generated in patients with moderate-severe COPD if they answered yes to one of the following: palpitations, dizziness, abnormal ECG, near syncope. Upon consultation with EP specialist, implantation of loop reorder was discussed (ILR) with the patient. Patients were then monitored for 12 months via remote monitoring. Actionable arrhythmia was defined the arrhythmia that correlated with symptoms triggered by the patient, necessitated adjustment of medications (including initiation of anticoagulation), catheter ablation and implantation of implantable cardiac defibrillator (ICD) or permanent pacemaker (PPM). Results: Out of 62 patients referred 22 (35.5%) agreed to undergo ILR implantation. Of the 22 (50.0% female, 62 ± 9.5 years) patients implanted with an ILR, 15 (68.2%) had an actionable arrhythmia after a mean follow-up of 2.7± .3 months. These included 14 symptomatic events requiring medication adjustment (10 atrial tachycardias, 4 ventricular events), 7 cases of atrial fibrillation (requiring initiation of anticoagulation in all cases and catheter ablation in 1), 1 case of sinus node dysfunction requiring pacemaker implantation, and 1 episodes of sustained ventricular tachycardia requiring ICD implantation. Conclusion: Continuous monitoring had high yield in diagnosing significant arrhythmic events in patients with moderate-severe COPD. Awareness should be raised about the high arrhythmic risk of this population and the role of continuous monitoring should be sought in larger studies.

Abstract 4120657: A Personal Risk Assessment Device in Patients with Chest Pain

Introduction: Early prehospital chest pain assessment improves acute coronary syndrome (ACS) outcomes and can reduce unnecessary Emergency Room (ER) visits but requires medical personnel and electrocardiographic (ECG) equipment. Objective: To evaluate the feasibility of a personal credit-card sized chest pain self-assessment device (HeartBeam, Santa Clara, CA, USA) in diagnosing ACS. Methods: ACS risk was estimated by serial likelihood ratio analysis of 3 components: pre-existing coronary heart disease (CHD) risk (pre-calculated based on pooled ASCVD equation), chest pain characteristics (interactive proprietary questionnaire), and integrated near-orthogonal 3-lead self-recorded vectorcardiogram (VCG) with optional comparison to baseline using portable handheld HeartBeam recorder. Final ACS risk was graded High/Intermediate/Low by the cloud-based proprietary algorithm. High risk was considered positive for ACS. Results: 184 ER patients with chest pain (Age 57 +/- 7years, 90 Male, 43 (23%) ACS) comprised learning (n=96) and test (n=88) sets. ACS sensitivity was 28/28 (100%) in learning and 15/16 (94%) in test set with specificity of 43% and 42% respectively. In the subset of patients with pain-free portable VCG recorded 9 months later used as a “reverse baseline” (n=110) sensitivity was 17/17 (100%) and 11/12 (92%), specificity 54% and 58% in learning and test set, respectively (p>0.1 with no baseline). Single patient missed by the analysis had known coronary disease with usual anginal episode resulting in minor troponin leak. In “reverse baseline” analysis 41/110 (37%) patients were classified as Low risk compared to 18/184 (10%) without baseline (p<0.001), all negative for ACS. Based on the analysis of CHD risk factors, chest pain characteristics, and 12-lead ECG, a consensus of 3-member ER chest pain unit physicians panel had sensitivity/specificity of 94/54% for the whole and 93/48% for the “reverse baseline” groups (p>0.1 with HeartBeam device). Conclusion: HeartBeam chest pain self-assessment device provides accurate ACS detection comparable to expert ER physicians using 12 lead ECG. The presence of baseline recording reduces the number of false positive results. If confirmed in larger studies, it can be used to facilitate outpatient chest pain assessment and triage by remote physicians and patients themselves.

Abstract 4138281: Relationship of Collagen Metabolism Biomarkers, Left Atrial Fibrosis and Ablation Outcome in Atrial Fibrillation

Introduction: Inflammation and fibrinogenesis in the left atrium are hypothesized to play a major role in the development of atrial fibrillation (AF). We previously showed that collagen metabolism biomarkers (CMB) are significantly elevated in patients with AF compared to healthy controls. Objective: We sought to investigate the relationship between CMB, Left Atrial Fibrosis (LAF) and AF recurrence after ablation. Methods: Patients with AF undergoing ablation evaluation (N= 96) were prospectively enrolled between 2015 – 2020. Plasma samples were collected prior to ablation and analyzed for CMB using commercially available ELISA kits. Sixty-four patients underwent AF ablation and were followed for 6 months for AF recurrence. CMR was performed in 48 patients using cine and 3D high resolution, late gadolinium enhancement imaging on 3T MRI to measure LAF. Patients were classified into 2 groups dichotomized by the median LAF value. Results: Mean age was 60.3 ± 10.3 years, mean BMI 29.7 ± 4.9 kg/m2, mean CHA2DS2-VASc score 1.9 ± 1.4 and 27% were women. Paroxysmal AF was present in 52.5%. The median LAF score was 13.6% (IQR 9.8 – 21.7). High PINP, high CITP and low TIMP-2 were associated with high LAF score (Table 1). High CITP was also associated with recurrence of AF after ablation {4.26 ng/ml (IQR 3.22 - 4.65) vs 3.26 ng/ml (IQR1.92 - 4.25), P = 0.02}. Conclusion: Higher levels of PINP and CITP were significantly associated with higher LAF score in AF patients. TIMP-2 was associated with low LAF. Higher CITP was also associated with AF recurrence after ablation. Further larger studies are needed to better understand the relationship between collagen biomarkers, LA fibrosis and their clinical impact on rhythm control in AF.

Abstract 4132159: Dietary Intake of Niacin and Risk of Cardiovascular Mortality in The Golestan Cohort Study

Introduction: Recent studies have linked niacin metabolism with vascular inflammation and cardiovascular disease (CVD); however, the association is still inconclusive regarding dietary intake, and the findings may not be generalizable to various populations. In this longitudinal study within a Middle Eastern population, we aimed to assess the relationship between dietary intake of B vitamins, including niacin, and the risk of CVD mortality. Methods: Our study utilized data from the Golestan Cohort Study, which has tracked 50,045 participants aged 40-75 years since 2004. We excluded subjects who reported extreme total energy intake or had a positive history of cancer, CVD, or diabetes at baseline. Vitamin B intake estimations including thiamin, riboflavin, niacin, pyridoxamine, folate, and cobalamin intake were derived from the baseline food frequency questionnaire, noting that supplement use was uncommon in this cohort. To adjust for calorie intakes, we employed the nutrient density method. Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for cardiovascular mortality, using the lowest quintile of intake as the reference group for vitamins and adjusting for potential confounders. Results: We analyzed 42,456 subjects with a mean age of 51.5 ± 8.7 years at baseline. During 579,339 person-years of follow-up (median: 14.1 years), 3,065 CVD deaths were recorded. The median dietary intake of niacin was 25.3 mg/d (Recommended Dietary Allowance = 14-16 mg/d). We observed significant associations between niacin intake (HR Q5 vs. Q1 = 1.13, 95% CI = 1.01-1.26, P trend <0.05) and CVD mortality. When niacin was modeled as a continuous linear variable, it was associated with a greater risk of CVD mortality (HR = 1.05, 95% CI = 1.01-1.09) per 2 mg/1000Kcal/d increase. None of the other B vitamin intakes evaluated were associated with CVD mortality in this population. Conclusion: These findings suggest that among B vitamins, only dietary niacin intake was positively associated with CVD mortality. Further confirmation in larger studies is needed.

Abstract 4125300: Prognostic Value of NT-proBNP and the H 2 FPEF Score on Empagliflozin-associated Left Ventricular Remodeling: Insights from the EMPA-HEART and EMPA-HEART 2 CardioLink Trial

Background: NT-proBNP is a prognostic and diagnostic marker for heart failure while the H 2 FPEF score is used to aid in diagnosing heart failure with preserved ejection fraction. Aims: These post hoc analyses of the randomized controlled EMPA-HEART CardioLink-6 and EMPA-HEART 2 CardioLink-7 trials examined how baseline NT-proBNP and the H 2 FPEF score influenced empagliflozin-associated left ventricular (LV) remodeling in people with either type 2 diabetes and coronary artery disease or without diabetes but with cardiovascular risk factors. Methods: A total of 242 participants were assigned to either empagliflozin 10 mg QD (n=118) or placebo (n=124) for 6 months. NT-proBNP was measured and cardiac MRI performed at baseline and end-of-study. Two independent analyses were performed. One divided the participants into those with baseline NT-proBNP < and ≧125 pg/mL and the other into those with H 2 FPEF score ≦2 and ≧3. The relationships between empagliflozin-associated LV mass and functional changes with baseline NT-proBNP and H 2 FPEF scores were assessed with linear models that adjusted for baseline differences (ANCOVA). Results: Mean age of the pooled cohort was 60.6 years; 14.0% were females, 37.2% had type 2 diabetes. Mean (SD) LV ejection fraction (LVEF) was 58.0 (10.2) %; median (IQR) NT-proBNP 77.5 (33, 164) pg/mL; mean (SD) H 2 FPEF score 2.9 (1.4). Empagliflozin (vs placebo) did not significantly alter LV mass index (mean [SD] -1.35 g/m 2 [0.75]; P=0.07) and LV end-systolic volume index (LVESVi; mean [SD] -1.37 mL/m 2 [0.74]; P=0.07) but did improve LVEF (mean [SD] 2.08% [0.82]; P=0.01). The effect of empagliflozin based on the subgroups of baseline NT-proBNP and H 2 FPEF scores are shown in Figures 1 and 2, respectively. Conclusions: These post hoc analyses suggest that lower baseline NT-proBNP levels and H 2 FPEF scores may be associated with more favourable reverse LV remodelling by empagliflozin and should be validated in larger studies.

Interventions in women with type 2 diabetes mellitus in the pre-pregnancy, pregnancy and postpartum periods to optimise care and health outcomes: A systematic review.

Type 2 diabetes is a chronic condition affecting increasing numbers of women of reproductive age. Recent UK data show more severe adverse offspring outcomes (stillbirth, neonatal death) than in infants of those with Type 1 diabetes. This systematic review aimed to evaluate randomised controlled trials (RCTs) undertaken in the pre-pregnancy, pregnancy and the postpartum periods in women with Type 2 diabetes, to optimise care and health outcomes. Six electronic databases were searched for eligible studies from January 2000 to September 2023; eligibility included RCTs of behavioural components, supplementation, pharmacotherapy and/or medical devices. Studies were screened in duplicate, and data were extracted on outcomes including behavioural, anthropometry, clinical measures and maternal and offspring outcomes. A narrative synthesis was performed. Eleven trials (12 papers) were included (total 1356 women with Type 2 diabetes, n = 25-502). Ten interventions were conducted in pregnancy, and one in the postpartum period. No pre-pregnancy RCTs were identified. Interventions included pharmacotherapies and supplementation, a diabetes-specific antenatal programme, continuous glucose monitoring and postpartum exercise. We found a paucity of interventions limited by inadequate design, statistical power and poor reporting. The largest Type 2 diabetes pregnancy study to date demonstrated evidence of benefit for adding metformin to a standard insulin regimen compared to insulin alone. Other interventions need replication in larger studies among more diverse groups. This review identified few RCTs targeting women of reproductive age with Type 2 diabetes particularly lacking in the preconception and postpartum periods. Tailored pre-pregnancy, pregnancy and postpartum interventions for women with Type 2 diabetes to optimise care and health outcomes are urgently needed.

BIOM-32. GENOMIC DETERMINANTS OF DIFFUSELY INFILTRATIVE GLIOMATOSIS CEREBRI PATTERN

Abstract Gliomatosis cerebri (GC), though no longer a distinct pathological entity in WHO 2021, is a unique and aggressive phenotype of diffuse gliomas with extensive and widespread infiltration. GC can present as primary de novo or secondary after treatment. We aimed to study the genomic determinants of GC. We identified 72 GC cases from 2013-2023 at MD Anderson Cancer Center. Cases were confirmed by detailed radiographic review. This included 57 glioblastoma (79%), 13 IDH mutant astrocytoma (18%), 1 IDH mutant oligodendroglioma (1.4%), and 1 high-grade astrocytoma with piloid features (1.4%). 53/72 (73.6%) were primary and 19/72 (26.4%) were secondary GC. We used 40 patients without the GC pattern as controls. Among glioblastoma GC cases and in comparison with controls, mutations in PTEN and EGFR were significantly associated with the GC pattern: 18/57 (32%) vs 3/38 (7.9%), p-value=0.01 and 23/57 (40%) vs 6/38 (16%), p-value=0.013, respectively. This held true in primary but not secondary GC. Out of 20 most commonly mutated genes in GC, mutations in EGFR, TERT, and MDM4 were associated with worse PFS: p-value=0.004, p-value=0.007, p-value=0.013, respectively and mutations in TERT and MDM4, but not EGFR, were associated with worse OS: p-value=0.003, p-value=0.015, respectively. Secondary GC was associated with IDH mutation compared to control non-GC cases: 8/19 (42%) vs 2/40 (5%), p-value=0.001. As expected, IDH mutation was associated with improved PFS, p-value<0.001 and OS, p-value=0.003 in GC. No genes were significantly associated with laterality of GC. We found novel associations between PTEN and EGFR mutations and the GC phenotype and IDH mutation with the occurrence of secondary GC after treatment. While MDM4 is not associated with outcomes in gliomas, we show that MDM4 mutation is associated with poor survival in GC. These findings shed light into molecular basis of GC and need to be further validated in larger studies.

Neuropathological Correlates of White Matter Hyperintensities in Cerebral Amyloid Angiopathy.

White matter hyperintensities (WMHs) are frequently observed on magnetic resonance imaging (MRI) in patients with cerebral amyloid angiopathy (CAA). The neuropathological substrates that underlie WMHs in CAA are unclear, and it remains largely unexplored whether the different WMH distribution patterns associated with CAA (posterior confluent and subcortical multispot) reflect alternative pathophysiological mechanisms. We performed a combined invivo MRI-ex vivo MRI-neuropathological study in patients with definite CAA. Formalin-fixed hemispheres from 19 patients with CAA, most of whom also had invivo MRI available, underwent 3T MRI, followed by standard neuropathological examination of the hemispheres and targeted neuropathological assessment of WMH patterns. Exvivo WMH volume was independently associated with CAA severity (P=0.046) but not with arteriolosclerosis (P=0.743). In targeted neuropathological examination, compared with normal-appearing white matter, posterior confluent WMHs were associated with activated microglia (P=0.043) and clasmatodendrosis (P=0.031), a form of astrocytic injury. Trends were found for an association with white matter rarefaction (P=0.074) and arteriolosclerosis (P=0.094). An exploratory descriptive analysis suggested that the histopathological correlates of WMH multispots were similar to those underlying posterior confluent WMHs. This study confirmed that vascular amyloid β severity in the cortex is significantly associated with WMH volume in patients with definite CAA. The histopathological substrates of both posterior confluent and WMH multispots were comparable, suggesting overlapping pathophysiological mechanisms, although these exploratory observations require confirmation in larger studies.

Associations between iron status and psychosocial wellbeing among pregnant women in Cape Coast, Ghana: a longitudinal study.

To determine the associations among iron status, depressive/anxiety symptoms, and quality of life (QoL) throughout pregnancy. This longitudinal study recruited participants in their 1st trimester (< 13 weeks; n=116) and followed in their 2nd (n=71) and 3rd (n=71) trimesters. Sociodemographic, food security, anxiety, depressive symptoms, and QoL questions were collected. Hemoglobin (Hb), ferritin (Ft), and transferrin saturation (TSAT) were determined. Women were categorized as iron improvers or non-improvers based on changes in iron status. Associations were assessed using difference-in-difference analyses. Cape Coast, Ghana between October 2017 to September 2018. Pregnant women, 18-38 years. Improvement in Ft levels from the 1st to 2nd trimester were associated with reduced depressive symptoms (-2.96 vs -0.58, p=0.028), and higher overall QoL (13.99 vs 1.92, p=0.006) particularly role physical (23.32 vs -2.55, p=0.025) and role emotional (27.50 vs 10.06, p=0.025) subscales. Improvement in Hb levels during the same period were linked to less anxiety, particularly fear factor (-2.62 vs -0.51, p=0.020); and worsened physical health aspect of QoL (-21.80 vs -3.75, p=0.005). Improvement in TSAT levels from 2nd to 3rd trimester were associated with increased total anxiety (1.56 vs -0.64, p=0.030) and panic factor (0.45 vs -0.26, p=0.004) and decreased total QoL (-1.08 vs 7.94, p=0.017), specifically role physical (-10.98 vs 11.93, p=0.018). Increases in iron status from first to second trimester were related to improvements in psychosocial wellbeing, implying potential benefit of iron supplementation on affect in early pregnancy. Larger studies are needed to confirm these findings.

Association of Oral Tobacco-Free Nicotine Delivery Product with Acute Renal Tubular Necrosis

Usage of novel non-tobacco oral nicotine delivery products (ONDPs) has been increasing among adolescents in the United States. It is presumed that they are less toxic than their tobacco-containing counterparts, but that has not been examined in controlled studies. Most of the studies have focused on non-renal manifestations of tobacco consumption via different means. The renal manifestations of non-tobacco ONDPs are not very well known, especially in immunocompromised patients. A 19-year-old male transplant recipient presented with flank pain and a few days’ history of intake of ZYNR pouches. Immunosuppression was with tacrolimus, mycophenolate, and steroids. Baseline serum creatinine was 1.1–1.3 mg/dL. Laboratory evaluation showed elevated C-reactive protein, increased serum creatinine and blood urea nitrogen, leukocytosis, neutrophilia, and increased lactate dehydrogenase (LDH). Infectious disease work-up was negative. A kidney transplant biopsy showed severe acute tubular injury/necrosis (ATN) without evidence of rejection. Donor-specific antibodies were negative. Other etiologies of hemolysis were negative. He did not require renal replacement therapy. Kidney function and LDH improved gradually. The most recent follow-up eight months after presentation showed a serum creatinine level of 2.6 mg/dL with stable electrolytes, with eGFR of 35 mL/min/1.73 m2. Here, we describe a 19-year-old adolescent with a kidney transplant who sustained ATN leading to advanced chronic disease apparently following the usage of non-tobacco ONDP. Further larger studies are needed to study ATN as a possible renal manifestation of these next-generation products to raise awareness among the public.

Association Between an Enhanced Clinical Pharmacy Service and Patient Experience in Hospitalized Adults: A Cohort Study.

Purpose. To determine if implementation of an enhanced clinical pharmacy service (ECPS) at a community hospital could improve patient experience as measured by medication-related Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores. Methods. A cohort study of 260 patients at a community hospital was conducted. Patients in the intervention group received additional pharmacy services from the standard of care (SOC) group, including daily medication counseling, pharmacist-driven medication administration, discharge medication reconciliation and education, consistent offers to enroll in a bedside medication delivery program (BMDP), and a telephone call following discharge. The primary outcome of patient experience was assessed through patients' responses to a care transitions HCAHPS survey question regarding understanding of the purpose of taking medications following discharge. Results. Among patients in the ECPS cohort, 75.8% had a top-box response to the care transitions HCAHPS question, compared to 63.3% of patients in the SOC cohort (OR = 1.81; 95% CI [0.61-5.37]). Top-box responses increased for all assessed HCAHPS questions but were not statistically significant. The HCAHPS survey response rate was 29.3% in the SOC cohort and 29.9% in the ECPS cohort. Conclusion. Following an ECPS intervention, patient experience as determined by HCAHPS scores increased, but the results did not reach statistical significance. Further, larger studies are needed on this topic.

Urinary interferon-γ-induced protein-10/creatinine ratio as a predictor of severe paediatric infections: A prospective pilot study.

This prospective pilot study evaluated urinary interferon-γ-induced protein-10 (IP-10)/creatinine and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)/creatinine ratios as non-invasive biomarkers for distinguishing bacterial from viral infections and assessing disease severity in febrile children. The study involved 85 febrile children and 29 healthy controls, measuring urinary IP-10/creatinine and TRAIL/creatinine ratios to determine their diagnostic utility. Both ratios were significantly elevated in infected patients compared to controls. The IP-10/creatinine ratio effectively assessed disease severity in the overall cohort and subgroups (AUC: 0.7324, 0.7192, 0.7277; p < 0.05). Serum C-reactive protein showed limited discriminatory ability in viral infections (AUC = 0.5385, p = 0.7257). Differentiation between bacterial and viral infections using IP-10/creatinine approached significance (p = 0.082). No significant differences in biomarker levels were observed across pathogens. The urinary IP-10/creatinine ratio shows promise as a biomarker for assessing paediatric infection severity, particularly when traditional markers are less effective. Larger studies are needed to validate these results and improve its discriminatory accuracy in clinical practice.

Role of Nasopharyngeal Airway in Management of Craniofacial Syndrome-Associated Upper Airway Obstruction in Children.

Upper airway obstruction (UAO) management in children, particularly those with associated anatomical mid-face structural differences, poses a significant challenge. This study describes using a nasopharyngeal airway (NPA) in managing infants with severe upper airway obstruction. Infants discharged home from Queensland Children's Hospital with an NPA insitu for the management of upper airway obstruction were retrospectively evaluated for clinical and demographic parameters, underlying diagnoses and respiratory support, including NPA insertion details and comorbidities. Sixty-seven children (24 male) were included with a median age at NPA insertion of 24 (IQR 7-59) days and a median duration of NPA use of 229.1 (IQR 151.50-297.75) days. Fifty-two (77.6%) had Pierre Robin sequence. Other diagnoses included CHARGE syndrome, Treacher Collins syndrome, Stickler syndrome, Crouzon syndrome, Bohring-Opitz syndrome, isolated cleft palate, Beckwith-Wiedemann syndrome, Chromosome 3 deletion and VACTERL association. Four infants required tracheostomy, and no complications related to NPA use were reported. Those with oximetry and polysomnography data showed improving indices following NPA insertion [pre NPA median (IQR) SpO2: 95.9% (94.73-97.73), AHI: 51.40 (44.50-69.45), OAHI 65.9 (56.45-73.35) and TcCO2 (mmHg) 65.70 (61.95-67.30) vs. post-NPA median (IQR) SpO2: 97.1% (96.19-97.9), AHI: 12.20 (11.25-24.35), OAHI 10.20 (6.12-5.62) and TcCO2 (mmHg) 52.40 (47.90-58.40)]. Our findings highlight the effectiveness and safety of NPA as a noninvasive management option for severe upper airway obstruction in children, particularly in those with anatomical midface structural differences. Further research and larger studies are warranted to confirm these findings and optimise management strategies for these patients.

Demonstration of T-Cell Monotypia Using Anti-TCRbeta1/2 (TRBC1/2) Immunostaining as a Rapid and Cost-Effective Alternative to PCR-Based Clonality Studies for the Diagnosis of T-Cell Lymphoma

Background/Objectives: T-cell lymphomas are often histologically indistinguishable from benign T-cell infiltrates, and diagnosis typically relies on slow, complex, and expensive multiplexed PCR reactions, requiring significant training and experience to interpret them. We aimed to raise highly specific antibodies against the two alternatively used and very similar T-cell receptor beta constant regions, TCRbeta1 and TCRbeta2, encoded by the TRBC1 and TRBC2 gene segments, respectively. We sought to demonstrate the feasibility of detecting TCRbeta1 and TCRbeta2 immunohistochemically in routine clinical (formalin-fixed, paraffin-embedded (FFPE)) tissue sections as a novel diagnostic strategy for T-cell lymphomas. Methods: Recombinant rabbit antibodies were validated using Western blotting and FFPE immunostaining of T-cell leukemia lines. The immunostaining of FFPE tissue containing benign and lymphomatous T-cell populations was undertaken, with corroboration by BaseScopeTM high-sensitivity in situ hybridization and quantitative real-time PCR (Q-PCR). An additional Q-PCR literature review and analysis of publicly available RNAseq data was used to determine the TCRbeta2/TCRbeta1 ratio cut-off to separate benign and malignant T-cell populations. Results: Our TCRbeta1/TCRbeta2 antibody pair gave highly specific FFPE tissue staining. All benign samples analyzed (immunohistochemically, by BaseScopeTM, by Q-PCR, and by RNAseq data analysis) had TCRbeta1/TCRbeta2 or TRBC1/TRBC2 ranges well within the previously published flow cytometric benign range (TCRbeta2/TCRbeta1 = 0.18:1–5.7:1), while samples of T-cell lymphoma did not. One out of thirteen (7.7%) lymphoma samples showed some detectable TCRbeta1/TCRbeta2 protein co-expression, and 4 out of 13 (30.8%) T-cell lymphomas showed a TRBC1/TRBC2 transcript co-expression using BaseScopeTM. Conclusions: Analyzing T-cell monotypia immunohistochemically, analogous to B-cell monotypia (kappa: lambda ratio for B-cell and plasma cell neoplasms), could make the diagnosis of T-cell lymphomas cheaper, quicker, and more accurate. Larger studies are needed to validate our antibodies for clinical use.

Energy and protein nutrition adequacy in general wards among intensive care unit survivors: A systematic review and meta-analysis.

Adequate energy and protein provision is mandatory to optimize survival chances in critical illness, prevent loss of muscle mass, and reduce length of stay. Data are available concerning feeding adequacy in intensive care unit (ICU) participants, but little is known about the adequacy in post-ICU participants. This systematic review aimed to evaluate feeding adequacy in post-ICU participants and addressed causes of feeding interruption leading to suboptimal adequacy. For this systematic review, a bibliographic search was performed in PubMed, Scopus, and Web of Science. Randomized controlled studies, non-randomized controlled studies, and observational studies conducted between January 1990 and November 2023 fulfilling the inclusion criteria were withheld. Eight studies were included. Outcomes reported were energy and protein adequacy, barriers, and feeding routes. Energy and protein requirements were determined in various ways, including indirect calorimetry and standardized and weight-based formulas. Energy adequacy ranged from 52% to 102% and protein adequacy between 63% and 86%. Participants were mainly fed with enteral nutrition (EN) or a combination of oral nutrition and EN. The main barrier reported for inadequate nutrition intake was feeding tube removal. Next to different ways in calculating targets and reporting results, a wide range in energy and protein adequacy was observed, but with constant protein underfeeding. Participants fed with EN or a combination of EN and oral nutrition had the best adequacy; inappropriate tube removal is a common barrier leading to inadequate therapy. Standardized reporting and larger studies are needed to guide nutrition care for post-ICU participants.

Retromuscular, periprosthetic drainage after hernioplasty with sublay mesh reinforcement in ventral hernias results in less retromuscular fluid collections but longer hospital stay and analgetic use with unclear effect on clinical outcome - a randomized controlled trial

PurposeTo determine whether periprosthetic drain insertion for hernioplasty using sublay mesh augmentation influences retromuscular fluid collections (RFC) and the clinical course.MethodsForty-two patients with open repair of midline hernias (M2-4, W1, European Hernia Society classification) were allocated to groups with or without retromuscular drains. Subcutaneous drainages were used in both groups to avoid confounding from surgical site occurrences due to superficial, subcutaneous fluid collections. The participants underwent clinical and ultrasound assessments on postoperative days (POD) 14 and 30 to detect RFC, subcutaneous seromas, and wound complications. The sample size was estimated using the RFC of a test cohort with drainage; the assumed relevant volume (5 ml) was calculated comprising 84% (mean + 1 SD) of these patients.ResultsIn the retromuscular drainage group, the RFC median volume was reduced by 75.2% on POD 14, and by POD 30, no RFC were found [0.2 vs. 25.8 (p < 0.001) and 0 vs. 4.0 (p = 0.02) on PODs 14 and 30, respectively]. The number of patients with RFC ≥ 5 mL was also significantly lower in the drainage group [4 vs. 12 (p = 0.02) and 1 vs. 8 (p = 0.02) on PODs 14 and 30, respectively]. No surgical site infections occurred in either group, but retromuscular hematoseroma led to one revision surgery and one needle aspiration in the group without drainage. In the drainage group, a significantly longer hospital stay (6.5 days vs. 4 days; p = 0.01) and longer regular analgetic intake (6 vs. 3 days; p = 0.03) were observed. Multivariable regression revealed that retromuscular drainage usage was the only independent predictor of the RFC volume.ConclusionWe found that the use of retromuscular drains after hernioplasty with sublay hernia repair reduced periprosthetic fluid collections in our population but prolonged hospital stay. Whether the reduction of RFC can prevent SSO or revision surgery cannot be determined from our data, the relevance is therefore not assessable. Hence, further larger studies are required to determine the clinical relevance of drains.

Measurement of platelet thrombus formation in patients following severe thermal injury

Severe thermal injury significantly impacts upon hemostasis and is associated with classical changes to the circulating platelet count with a nadir followed by a rebound thrombocytosis at days ~3 and ~15 post-injury, respectively. To date, few studies have assessed platelet function following thermal injury as platelet tests often require large quantities of blood, are not representative of normal platelet pathophysiology, and are usually dependent on a normal platelet count. The purpose of this study was to measure platelet thrombus formation in vitro using a whole blood flow chip-based system following thermal injury and to study how platelet counts may impact upon the measurement. Adult (≥16 years) patients (N = 10) with ≥ 20% total burn surface area (TBSA) burn were recruited within 24 h of injury. Healthy controls (N = 25) were also recruited. Whole blood counts were measured using a hematology analyzer (Sysmex XN-1000). Platelet function was measured using the Total Thrombus-formation Analyzer System (T-TAS) within chips coated with tissue factor and collagen at shear rates of either 600 sec−1 (AR chips) or 1200 sec−1 (HD chips), the latter test being independent of platelet count. We confirmed the classical nadir in platelet counts following severe thermal injury at days 2, 3, 4 (p < 0.0001) and day 5 (p < 0.01) post-injury compared to healthy controls. Physiological platelet thrombus formation was significantly (p < 0.01) abnormal at day 3 post-injury using the AR chips but was related to the platelet count. However, although platelet dysfunction was not significant using HD chips, some of the results were independent of platelet count. A small number of samples, however, still gave abnormal results suggesting that there can be an underlying acquired platelet functional abnormality. Furthermore, the AR chip Area Under the Curve (AUC) was significantly lower on day 1 post-injury and negatively associated with severity of injury (TBSA, p < 0.05) and higher platelet function (AUC) positively associated with survival (p < 0.05). This study suggests that measuring platelet dysfunction within a more physiological in vitro test may have potential clinical utility. Larger studies are required to fully understand the impact of platelet dysfunction following severe thermal injury.

Erythrocytic α-Synuclein in Parkinson’s Disease and Progressive Supranuclear Palsy—A Pilot Study

Background/Objectives: The current research examines the accuracy of α-synuclein in RBCs as a diagnostic biomarker for PD and PSP, despite their distinct molecular etiologies. Methods: We used ELISA to measure total, oligomeric, and p129-α-synuclein levels in erythrocytes from 8 PSP patients, 19 PD patients, and 18 healthy controls (HCs). The classification performances of RBC α-synuclein levels were investigated by receiver operator characteristic (ROC) curve. We also evaluated a possible correlation between RBC α-synuclein level and the biological and clinical features of our cohorts. Results: RBC total α-synuclein was higher in PSP patients compared to both PD patients and HCs, achieving good classification performance (AUC: 0.853) in distinguishing PSP patients from PD patients, with a sensitivity of 100% and a specificity of 70.6%; moreover, the levels of this biomarker positively correlated with disease severity in PSP group. Regarding oligomeric α-synuclein and p129-α-synuclein, the latter was slightly increased in RBCs from PSP patients compared to HCs, but no correlations were detected. Conclusions: Although these findings need to be confirmed in larger studies, our pilot work suggests that RBC total α-synuclein may represent a potential molecular biomarker for the differential diagnosis and clinical staging of PSP.

Quality of Life in Children With Chronic Health Conditions and Its Contribution to Unmet Supportive Care Needs of Families.

While theoretical models have established the bidirectional relationship between health and wellbeing of parents and children with chronic health conditions (CHCs), previous work has predominantly emphasised the impact of parent functioning on child outcomes. This study examines how quality of life (QoL) domains in children with CHCs are associated with unmet supportive care needs (SCN) of their parents and explores whether these associations vary by health condition. Parents of children with congenital heart disease (CHD), type 1 diabetes (T1D) and cancer diagnosed before the age of 12 years and receiving treatment within the last 5 years were eligible. Parents recruited through charity organisations and social media platforms completed a secure, online survey via Qualtrics. The PedsQL examined child QoL across four dimensions: physical, emotional, social and school functioning. A 34-item survey assessed parents' unmet SCN in the previous month across six need domains (e.g., care and informational). Linear regressions examined associations between child QoL and unmet SCN domains and moderation analyses determined whether associations varied as a function of CHC. The study included 186 parents (age range 25-56 years) of children diagnosed with various CHCs (52% CHD; 27% T1D, 21% cancer). The child's emotional functioning was inversely related to all unmet SCN domains, social functioning was inversely related to three domains (physical and social; support; financial), school functioning was inversely related to two domains (physical and social; care), and child's physical functioning was not associated with any SCN domains. Only the association between child school functioning and unmet care needs was significantly moderated by CHC type (p < 0.05). Poorer emotional functioning in children with a CHC is a key factor in determining parents unmet SCN. Larger studies are required to replicate these findings and inform design of interventions addressing QoL and unmet SCN in families of children with common CHCs.

The benefit of automated sac volume measurements in postoperative endovascular aortic repair surveillance

Abdominal aortic aneurysm (AAA) shrinkage is considered a marker for success following endovascular aortic repair (EVAR). Although maximum diameter is widely used to assess sac behavior, research indicates that changes in AAA morphology do not always affect the maximum diameter. The aim of this study is to investigate if automated AAA sac volume measurements after EVAR can add more nuanced information on sac behavior compared with maximum diameter evaluation alone. A retrospective review of all patients treated for AAA with a standard or fenestrated EVAR at two tertiary referral centers was performed. Patients with a pre- and postoperative computed tomography angiography (CTA) ≥ two years after treatment were included. Data were collected using medical charts, radiologic institutional databases, and a deep learning based method called Augmented Reality for Vascular Aneurysm (ARVA). Volume and diameter assessments were automatically performed on CTAs using ARVA. Preoperative sac volumes and diameters were compared with those obtained at least two years after repair. Information on endoleaks (ELs) was collected. Continuous data were tested using t-test, and categorical data were tested using chi-square or Fishers test, depending on sample size. A total of 89 patients (standard EVAR n=46; fenestrated EVAR n=43) were included in this study. Of the 89 patients, 41 (46%) had sac diameter shrinkage, 38 (43%) had stable sac diameters, and 10 (11%) had diameter sac growth during follow-up. The distribution of sac volume behavior was different amongst these patients: 51 (57%) had volume shrinkage, only 9 (10%) had stable volumes, and 29 (33%) had volume growth. Significantly more patients had sac growth, and fewer had sac stability, when assessed with volume compared with diameter, p=.003 and p<.001, respectively. The increase in patients with volume-assessed sac shrinkage (57% vs 46%) was not statistically significant. Of the 18 (20%) patients with stable sac diameters and simultaneous volume growth, 13 (72%) had ELs (T2ELs: n=9, T1ELs, n=2, T3EL: n=1, and EL of undefined origin: n=1). This study found that volume-assessed sac behavior identifies more sac shrinkage or growth, and less sac stability than diameter does. If confirmed by larger studies, sac volume assessment should be performed routinely after endovascular repair.