Higher Median Research Articles

HOXA9 and CD163 potentiate pancreatic ductal adenocarcinoma progression

BackgroundThe role of HOXA9 requires investigations in pancreatic ductal adenocarcinoma (PDAC) as HOXA9 inhibitors are being developed. HOXA9 might attract CD163 expressed tumor associated macrophages (TAM) and could affect PDAC prognosis. This work aims to study the expression and relevance of HOXA9 and CD163 in PDAC progression.Materials and methodsSelected 98 PDAC and 98 adjacent non tumor tissues as a control group were immunostained with HOXA9 and CD163 antibodies.ResultsPDAC displayed highly significant higher HOXA9 staining intensity, percent and H score values than control group. HOXA9 staining of PDAC cases showed significant associations with poor prognostic indicators including larger tumor size, higher grade and advanced stage. PDAC showed highly significant differences regarding CD163 macrophage-specific staining intensity, percent and H score values than control group. CD163 showed significant higher expressions with larger tumor size, higher histological grade and advanced stage group. HOXA9 staining in PDAC showed highly significant direct correlations with CD163 positive macrophages. Follow up of PDAC cases revealed that high median H score of HOXA9 and CD163 were significantly associated with worse overall survival. CD163 was an independent prognostic marker of worse survival.ConclusionsIn conclusion, HOXA9 could potentiate PDAC progression by stimulating CD163 expressed TAM attraction in tumors. HOXA9 and CD163 could participate in PDAC therapy. HOXA9 and CD163 could be predictors of worse prognosis and shorter survival in PDAC.

The mass profiles of dwarf galaxies from Dark Energy Survey lensing

ABSTRACT We present a novel approach to extracting dwarf galaxies from photometric data to measure their average halo mass profile with weak lensing. We characterize their stellar mass and redshift distributions with a spectroscopic calibration sample. By combining the ${\sim} 5000\,\mathrm{deg}^2$ multiband photometry from the Dark Energy Survey and redshifts from the Satellites Around Galactic Analogs Survey with an unsupervised machine learning method, we select a low-mass galaxy sample spanning redshifts $z\lt 0.3$ and divide it into three mass bins. From low to high median mass, the bins contain [146 420, 330 146, 275 028] galaxies and have median stellar masses of $\log _{10}(M_*/\text{M}_\odot)=\left[8.52\substack{+0.57 -0.76},\, 9.02\substack{+0.50 -0.64},\, 9.49\substack{+0.50 -0.58}\right]$ . We measure the stacked excess surface mass density profiles, $\Delta \Sigma (R)$, of these galaxies using galaxy–galaxy lensing with a signal-to-noise ratio of [14, 23, 28]. Through a simulation-based forward-modelling approach, we fit the measurements to constrain the stellar-to-halo mass relation and find the median halo mass of these samples to be $\log _{10}(M_{\rm halo}/\text{M}_\odot)$ = [$10.67\substack{+0.2 -0.4}$, $11.01\substack{+0.14 -0.27}$, $11.40\substack{+0.08 -0.15}$]. The cold dark matter profiles are consistent with NFW (Navarro, Frenk, and White) profiles over scales ${\lesssim} 0.15 \, {h}^{-1}$ Mpc. We find that ${\sim} 20$ per cent of the dwarf galaxy sample are satellites. This is the first measurement of the halo profiles and masses of such a comprehensive, low-mass galaxy sample. The techniques presented here pave the way for extracting and analysing even lower mass dwarf galaxies and for more finely splitting galaxies by their properties with future photometric and spectroscopic survey data.

Transcutaneous carbon dioxide monitoring in children undergoing rigid bronchoscopy: a prospective blinded observational study.

Anesthetic management during rigid bronchoscopy in children can be challenging, and continuous end-tidal carbon dioxide (EtCO2) monitoring is often unachievable. Transcutaneous carbon dioxide (TcCO2) monitoring is strongly correlated with the partial pressure of carbon dioxide (PaCO2) and EtCO2. We aimed to investigate the incidence of hypercapnia in children undergoing rigid bronchoscopy. We enrolled patients aged < 18yr scheduled for rigid bronchoscopy in a prospective observational study. We recorded TcCO2 values from anesthesia induction to the postanesthesia care unit (PACU) stay. We ended monitoring when TcCO2 reached values ≤ 50mm Hg. The operating room (OR) team was blinded to the TcCO2. The outcome of primary interest was the incidence of hypercapnia (TcCO2 > 50mm Hg) in the OR. Other outcomes were the incidences of hypercapnia in the PACU and severe hypercapnia (TcCO2 > 90mm Hg), factors possibly related to hypercapnia (patient, surgery, or anesthesia factors), and the incidence of perioperative adverse events. A total of 30 patients were enrolled. The median [interquartile range (IQR)] age was 3.5 [1.5-8.0] yr. The incidence of hypercapnia was 100% in the OR and 60% in the PACU. Five cases (17%) presented with severe hypercapnia in the OR. The highest median [IQR] TcCO2 was 69 [61-79] mm Hg. The most common adverse event was oxygen desaturation (57%, 17/30). Patients with severe hypercapnia had long stays in the PACU. Hypercapnia was a frequent event in children undergoing rigid bronchoscopy and severe hypercapnia was associated with a long PACU stay. Further studies are needed to assess the utility of TcCO2 monitoring in guiding ventilatory interventions during these cases.

Current exposure to environmental pollutants in the general adult population of Kinshasa, Democratic Republic of Congo (DRC): A cross-sectional study

BackgroundEnvironmental pollution is a serious public health problem because of its adverse effects on both human health and biodiversity. In Western countries, many human biomonitoring (HBM) studies are conducted to assess population exposure to pollutants. In contrast, the number of HBM studies in Africa is very low. ObjectiveTo measure contamination by arsenic, lead, 4,4′-dichlorodiphenyldichloroethylene (4,4′-DDE) and polychlorobiphenyls (PCBs) in the adult population of Kinshasa and to identify the susceptible population. MethodsIn the present work, we measured the contamination by arsenic in urine and lead in blood and by 4,4′-DDE and polychlorobiphenyls (PCBs) in serum in samples collected from 151 volunteers recruited in Kinshasa, the capital of the Democratic Republic of Congo (DRC). ResultsThe PCBs 180, -153 and −138 were detected in most samples with median concentrations of 0.04, 0.05 and 0.04 ng/ml, respectively. The median concentration of 4,4′-DDE was 0.83 ng/ml and 12.7% of our population showed contamination above the threshold of 3.675 ng/ml, which is associated with a significantly higher risk of cancer. Arsenic concentrations were also high (median: 48.1 μg/L in urine). Finally, exposure to lead is problematic: the median blood concentration was 54.9 μg/L, which is above the thresholds proposed by the WHO and the US CDC (50 μg/L and 35 μg/L respectively) to initiate clinical intervention, and 12.6% of the population had a lead level above 100 μg/L, which is associated with several health outcomes. ConclusionsOur results highlight the need for further HBM studies in Africa and should encourage the authorities of the DRC to implement laws and regulations to reduce pollution and population exposure.

Comparison of intramuscular medetomidine versus medetomidine-vatinoxan sedation in bearded dragons (Pogona vitticeps)

ObjectiveTo assess sedation following intramuscular (IM) administration of medetomidine versus medetomidine-vatinoxan in bearded dragons. Study designProspective, randomized, experimental, crossover study. AnimalsA group of 10 (males; n = 5, females; n = 5) bearded dragons (mean mass ± standard deviation 172 ± 28 g). MethodsAll animals were given both medetomidine (0.2 mg kg -1) (MED) and medetomidine (0.2 mg kg -1)-vatinoxan (4 mg kg -1) (MED-VAT) IM, with a 14–16-day washout period between treatments. Sedation was assessed using an adapted version of a sedation scale for bearded dragons (scale range 0–12) before (T0), and every 5 minutes from 10 to 45 minutes after treatment administration (T10–T45). Sedation scores were compared i) between timepoints (within treatments) using a Friedman test and Dunn post hoc test; and ii) between treatments at each timepoint using a Wilcoxon paired test. Heart rate and respiratory rate (fR) were analyzed descriptively. At T45, atipamezole was given IM. ResultsCompared to T0, sedation scores were significantly higher at most timepoints for both treatments. Highest median (range) scores occurred at T30 for MED [T0; 0 (0–0), T30; 2.5 (1–5), p = 0.0001] and at T35 and T40 for MED-VAT [T0; 0 (0–0), T35; 2 (1–5), p = 0.002, T40; 2 (1–5), p = 0.001]. No significant differences in sedation scores were identified between treatments at any timepoint. The two protocols caused bradycardia and reduction in fR. All animals were active and ate 1 hour after reversal administration. Conclusions and clinical relevanceBoth medetomidine and medetomidine-vatinoxan caused similar mild sedation in bearded dragons (median < 3/12). Inclusion of vatinoxan did not enhance sedation in this species.

Transpulmonary Pressure-Guided Mechanical Ventilation in Severe Acute Respiratory Distress Syndrome in PICU: Single-Center Retrospective Study in North India, 2018–2021

Objectives: In this study, we have reviewed the association between esophageal pressure-guided positive end-expiratory pressure (PEEP) setting and oxygenation and lung mechanics with a conventional mechanical ventilation (MV) strategy in patient with moderate to severe pediatric acute respiratory distress syndrome (PARDS). Design: Retrospective cohort, 2018–2021. Setting: Tertiary PICU. Patients: Moderate to severe PARDS patients who required MV with PEEP of greater than or equal to 8 cm H2O. Interventions: Esophageal pressure (i.e., transpulmonary pressure [PTP]) guided MV vs. not. Measurements and Main Results: We identified 26 PARDS cases who were divided into those who had been managed with PTP-guided MV (PTP group) and those managed with conventional ventilation strategy (non-PTP). Oxygenation and lung mechanics were compared between groups at baseline (0 hr) and 24, 48, and 72 hours of MV. There were 13 patients in each group in the first 24 hours. At 48 and 72 hours, there were 11 in PTP group and 12 in non-PTP group. On comparing these groups, first, use of PTP monitoring was associated with higher median (interquartile range) mean airway pressure at 24 hours (18 hr [18–20 hr] vs. 15 hr [13–18 hr]; p = 0.01) and 48 hours (19 hr [17–19 hr] vs. 15 hr [13–17 hr]; p = 0.01). Second, use of PTP was associated with higher PEEP at 24, 48, and 72 hours (all p &lt; 0.05). Third, use of PTP was associated with lower Fio 2 and greater Pao 2 to Fio 2 ratio at 72 hours. Last, there were 18 of 26 survivors, and we failed to identify an association between use of PTP monitoring and survival. Conclusions: In this cohort of moderate to severe PARDS cases undergoing MV with PEEP greater than or equal to 8 cm H2O, we have identified some favorable associations of oxygenation status when PTP-guided MV was used vs. not. Larger studies are required.

Whole blood to total transfusion volume ratio in injured children: A national database analysis.

Whole blood (WB) resuscitation is increasingly common in adult trauma centers and some pediatric trauma centers, as studies have noted its safety and potential superiority to component therapy (CT). Previous analyses have evaluated WB as a binary variable (any versus none), and little is known regarding the "dose response" of WB in relation to total transfusion volume (TTV) (WB/TTV ratio). Injured children younger than 18 years who received any blood transfusion within 4 hours of hospital arrival across 456 US trauma centers were included from the American College of Surgeons Trauma Quality Improvement Program database. The primary outcome was 24-hour mortality, and the secondary outcome was 4-hour mortality. Multivariate analysis was used to evaluate associations between WB administration and mortality and WB/TTV ratio and mortality. Of 4,323 pediatric patients included in final analysis, 88% (3,786) received CT only, and 12% (537) received WB with or without CT. Compared with the CT group, WB recipients were more likely to be in shock, according to pediatric age-adjusted shock index (71% vs. 60%) and had higher median (interquartile range) Injury Severity Score (26 [17-35] vs. 25 [16-24], p = 0.007). Any WB transfusion was associated with 42% decreased odds of mortality at 4 hours (adjusted odds ratio [aOR], 0.58 [95% confidence interval, 0.35-0.97]; p = 0.038) and 54% decreased odds of mortality at 24 hours (aOR, 0.46 [0.33-0.66]; p < 0.001). Each 10% increase in WB/TTV ratio was associated with a 9% decrease in 24-hour mortality (aOR, 0.91 [0.85-0.97]; p = 0.006). Subgroup analyses for age younger than 14 years and receipt of massive transfusion (>40 mL/kg) also showed statistically significant survival benefit for 24-hour mortality. In this retrospective American College of Surgeons Trauma Quality Improvement Program analysis, use of WB was independently associated with reduced 24-hour mortality in children; further, higher proportions of WB used over the total resuscitation (WB/TTV ratio) were associated with a stepwise increase in survival. Prognostic and Epidemiological; Level III.

Invasive ventilation at the boundary of viability: A respiratory pathophysiology study of infants born between 22 and 24 weeks of gestation

BackgroundInvasive ventilation of infants born before 24 weeks of gestation is critical for survival and long-term respiratory outcomes, but currently there is a lack of evidence to guide respiratory management. We aimed to compare respiratory mechanics and gas exchange in ventilated extremely preterm infants born before and after 24 weeks of gestation. MethodsSecondary analysis of two prospective observational cohort studies, comparing respiratory mechanics and indices of gas exchange in ventilated infants born at 22–24 weeks of gestation (N=14) compared to infants born at 25–27 weeks (N=37). The ventilation/perfusion ratio (VA/Q), intrapulmonary shunt, alveolar dead space (VDalv) and adjusted alveolar surface area (SA) were measured in infants born at the Neonatal Unit of King’s College Hospital NHS Foundation Trust, London, UK. ResultsCompared to infants of 25–27 weeks, infants of 22–24 weeks had higher median (IQR) intrapulmonary shunt [18 (4 - 29) % vs 8 (2 – 12) %, p=0.044] and higher VDalv [0.9 (0.6 – 1.4) vs 0.6 (0.5 – 0.7) ml/kg, p=0.036], but did not differ in VA/Q. Compared to infants of 25–27 weeks, the infants of 22–24 weeks had a lower adjusted SA [509 (322- 687) vs 706 (564 - 800) cm2, p=0.044]. The infants in the two groups did not differ in any of the indices of respiratory mechanics. ConclusionVentilated infants born before 24 completed weeks of gestation exhibit abnormal gas exchange, with higher alveolar dead space and intrapulmonary shunt and a decreased alveolar surface area compared to extreme preterms born after 24 weeks of gestation.

Hypertrophy Determination of H9c2 Cardiomyoblast Cell Line Using Wright-Giemsa Staining: An Experience in Developing an Acceptable and Easy-to-handle In-vitro Protocol

Introduction Cell-size area (CSA) becomes the standard parameter routinely tested in vitro for cardiac hypertrophy studies. Thus, staining is an essential tool for this purpose. As reported in a previous study, immunofluorescence staining is an established method for CSA. However, because it is expensive and requires a specialized microscope, e.g., immunofluorescence or confocal microscope, it is not applicable in a laboratory with limited equipment. Wright-Giemsa staining is a standard procedure in hematology laboratories and is inexpensive and convenient. Here, we shared our experience developing a CSA determination protocol using Wright-Giemsa in H9c2 cardiomyoblast. Methods The viability tests were performed on H9c2 to determine the effective dosage of angiotensin II and Irbesartan (standard drug). The H9c2 were divided into three groups: the control group (without either angiotensin II or irbesartan), the negative control (with angiotensin II), and the positive control (with angiotensin II and Irbesartan), triplicate for each group. The cells then are acclimatized overnight, serum-starved for one day, and incubated with angiotensin and irbesartan for 48 hours. Lastly, Wright-Giemsa was observed using a light microscope in three fields. The CSA was determined by three independent observers blindly, statistically different if the p&lt;0.05 using ANOVA ways or Kruskal-Wallis. Results After the H9c2 induced by angiotensin-II 1 μM and Irbesartan 1μM, we found the CSA significantly differed among each group (p&lt;0,0001). The negative control has a higher median and interquartile range (IQR) CSA (10.78 (6.79) um2) compared to the control group (median (IQR) 7.27 (4.91) um2) and positive control (median (IQR) 7.849(5.31) um2). Conclusion It can be concluded that the Wright-Giemsa might help determine the CSA for in-vitro hypertrophic studies.

Early Dysglycemia Is Detectable Using Continuous Glucose Monitoring in Very Young Children at Risk of Type 1 Diabetes.

Continuous glucose monitoring (CGM) can detect early dysglycemia in older children and adults with presymptomatic type 1 diabetes (T1D) and predict risk of progression to clinical onset. However, CGM data for very young children at greatest risk of disease progression are lacking. This study aimed to investigate the use of CGM data measured in children being longitudinally observed in the Australian Environmental Determinants of Islet Autoimmunity (ENDIA) study from birth to age 10 years. Between January 2021 and June 2023, 31 ENDIA children with persistent multiple islet autoimmunity (PM Ab+) and 24 age-matched control children underwent CGM assessment alongside standard clinical monitoring. The CGM metrics of glucose SD (SDSGL), coefficient of variation (CEV), mean sensor glucose (SGL), and percentage of time >7.8 mmol/L (>140 mg/dL) were determined and examined for between-group differences. The mean (SD) ages of PM Ab+ and Ab- children were 4.4 (1.8) and 4.7 (1.9) years, respectively. Eighty-six percent of eligible PM Ab+ children consented to CGM wear, achieving a median (quartile 1 [Q1], Q3) sensor wear period of 12.5 (9.0, 15.0) days. PM Ab+ children had higher median (Q1, Q3) SDSGL (1.1 [0.9, 1.3] vs. 0.9 [0.8, 1.0] mmol/L; P < 0.001) and CEV (17.3% [16.0, 20.9] vs. 14.7% [12.9, 16.6]; P < 0.001). Percentage of time >7.8 mmol/L was greater in PM Ab+ children (median [Q1, Q3] 8.0% [4.4, 13.0] compared with 3.3% [1.4, 5.3] in Ab- children; P = 0.005). Mean SGL did not differ significantly between groups (P = 0.10). CGM is feasible and well tolerated in very young children at risk of T1D. Very young PM Ab+ children have increased SDSGL, CEV, and percentage of time >7.8 mmol/L, consistent with prior studies involving older participants.

Liver and Inflammatory Biomarkers Are Related to High Mortality in Hospitalized Patients with COVID-19 in Brazilian Amazon Region.

COVID-19 is a multisystem disease with many clinical manifestations, including liver damage and inflammation. The objective of this study is to analyze inflammation biomarkers in relation to the clinical outcome and respiratory symptoms of COVID-19. This is a retrospective cohort of patients with COVID-19 admitted to the Hospital Regional do Baixo Amazonas from 2020 to 2022. Data were collected from electronic medical records from admission to the 30th day of hospitalization and soon after hospital discharge. A total of 397 patients were included in the study. In the longitudinal follow-up of liver markers, a significant difference was found for AST on day 14, with a higher median in the death group. Among the hematological markers, lymphopenia was observed throughout the follow-up, with the death group having the most altered values. When comparing the evolution of biomarkers in the Non-Invasive Ventilation (NIV) and Invasive Mechanical Ventilation (IMV) groups, AST showed a significant difference only on day 14 and GGT on day 1, being greater in the IMV group, and indirect bilirubin on day 7 being more altered in the NIV group. In conclusion, death during hospitalization or a more severe form of COVID-19 was related to significant changes in liver and inflammatory biomarkers.

Clinical manifestations and treatment outcomes for patients with Pseudomonas endocarditis.

To investigate clinical outcomes of patients with Pseudomonas endocarditis and identify factors associated with treatment failure. Adult patients meeting definitive Duke's criteria for Pseudomonas endocarditis at 11 hospitals were identified between May 2000 and February 2024. Failure was defined as death or microbiological failure by day 42. First-line therapy consisted of cefepime, piperacillin/tazobactam, ceftazidime or ceftolozane/tazobactam alone or in combination. Forty-eight patients met inclusion criteria; 29% were persons who inject drugs and 13% were organ transplant recipients. Pseudomonas aeruginosa was the causative species in 98% of cases. Patients who experienced 42 day cure were more likely to be initially managed with first-line β-lactam agents compared with those who experienced clinical failure (97% versus 62%, P = 0.004). Treatment with first-line β-lactams was associated with shorter time to treatment initiation and a lower likelihood of infection due to MDR Pseudomonas spp. In the univariate model, patients who experienced 90 day mortality were more likely to have prosthetic valve endocarditis (57% versus 24%, P = 0.02), an intracardiac complication (36% versus 9%, P = 0.04) and a higher median (IQR) Pitt bacteraemia score [2.5 (2-3.8) versus 1 (0-2), P = 0.048]. Combination therapy did not improve clinical outcomes but did increase the rate of adverse effects resulting in drug discontinuation compared with monotherapy, (21% versus 0%, P = 0.08). This is the largest study of Pseudomonas endocarditis to date. We identified improved clinical outcomes when cefepime, piperacillin/tazobactam, ceftazidime or ceftolozane/tazobactam were used for initial treatment. We did not identify a clinical benefit for combination treatment.

Assessing the Performance of In silico Tools and Molecular Dynamics Simulations for Predicting Pharmacogenetic Variant Impact.

The ability of freely available in silico tools to predict the effect of non-synonymous single nucleotide polymorphisms (nsSNPs) in pharmacogenes on protein function is not well defined. We assessed the performance of seven sequence-based (SIFT, PolyPhen2, mutation accessor, FATHMM, PhD-SNP, MutPred2, and SNPs & Go) and five structure-based (mCSM, SDM, DDGun, CupSat, and MAESTROweb) tools in predicting the impact of 118 nsSNPs in the CYP2C19, CYP2C9, CYP2B6, CYP2D6, and DPYD genes with known function (24 normal, one increased, 42 decreased, and 51 no-function). Sequence-based tools had a higher median (IQR) positive predictive value (89% [89-94%] vs. 12% [10-15%], P < 0.001) and lower negative predictive value (30% [24-34%] vs. 90% [80-93%], P < 0.001) than structure-based tools. Accuracy did not significantly differ between sequence-based (59% [37-67%]) and structure-based (34% [23-44%]) tools (P = 0.070). Notably, the no-function CYP2C9*3 allele and decreased function CYP2C9*8 allele were predicted incorrectly as tolerated by 100% of sequenced-based tools and as stabilizing by 60% and 20% of structure-based tools, respectively. As a case study, we performed mutational analysis for the CYP2C9*1, *3 (I359L), and *8 (R150H) proteins through molecular dynamic (MD) simulations using S-warfarin as the substrate. The I359L variant increased the distance of the major metabolic site of S-warfarin to the oxy-ferryl center of CYP2C9, and I359L and R150H caused shifts in the conformation of S-warfarin to a position less favorable for metabolism. These data suggest that MD simulations may better capture the impact of nsSNPs in pharmacogenes than other tools.

High dimensional model representation median filter for removing salt and pepper noise

High dimensional model representation median filter for removing salt and pepper noise

Health-related quality of life in adults with hematological cancer: a 2023 cross-sectional survey from Qatar.

Hematological cancers impose a complex burden on individuals, affecting their physical health and mental and emotional well-being. This study evaluated the health-related Quality of Life (HRQOL) and its determinants among adults with hematological cancers in Qatar in 2023. A cross-sectional study used a validated structured questionnaire conducted among adult patients diagnosed with hematological cancers. All adult patients who attended The National Centre for Cancer Care and Research (NCCCR) in Qatar during the Data collection period (January to March 2023) and agreed to participate were included in the study. A total of 257 participants were enrolled in the study. The highest median (IQR) score of the HRQOL domain was observed in the functionating score of 90.6 (13.8), followed by the global health score of 83.3(25. 0). The median (IQR) of the symptoms burden score was 07.4(12.3). Gender significantly affects HRQOL, with males reporting better functioning and lower symptom burden than females. Employment status is positively associated with functioning scores. Regular exercise correlates with higher global health and functioning scores and lower symptom burden, while depressive symptoms are linked to poorer HRQOL outcomes. Patients experiencing cancer recurrence or active disease report lower global health and functioning scores and higher symptom burden. Treatment modalities such as chemotherapy and bone marrow transplant (BMT) timing also influence HRQOL, with recent treatment recipients showing lower global health and higher symptom burden scores. Depressive symptoms were the primary factor, lowering the global health score by 15.2%. Regarding the low functioning score predictors, female gender, depressive symptoms, and cancer recurrence emerged as significant predictors of the low functioning score. Furthermore, Regular exercise increased the functioning score by 03.4 units (p-value=0.018). Finally, Multiple linear regression analysis reinforced the significance of depressive symptoms, active disease status, and recurrence within the past five years as substantial predictors of higher symptom scores. The study emphasizes the profound impact of depressive symptoms on all aspects of Health-Related Quality of Life (HRQOL), mainly affecting global health. It highlights the positive role of regular exercise in enhancing global health, functioning, and symptom burden scores.

#3054 The hospital frailty risk score lacks service planning and decision-making utility in end stage kidney disease

Abstract Background and Aims Survival time for patients commencing dialysis is poor (median 2.0 years in our data) and treatment is invasive. While the age of patients commencing dialysis has increased significantly, the survival advantage diminishes with increasing comorbidity and frailty. The Hospital Frailty Risk Score (HFRS) is a recently-described score derived from ICD-10 codes which has been shown to correlate with outcomes in patients aged &amp;gt;75 years admitted to acute hospital settings. As part of a wider initiative to improve service planning and patient decision-making in the renal setting, we investigated the utility of the HFRS in modelling the survival time of dialysis patients with chronic kidney disease (CKD) both prior to reaching end-stage kidney disease (ESKD), and at dialysis start date. Method A secondary care dataset was obtained of all patients who attended pre-dialysis clinic at a single renal unit in the north of England between 2006–2019 (n = 2,573). Patients choosing dialysis and conservative management were included in the cohort; 1,081 eventually underwent dialysis including 329 patients who were aged ≥70 years when they commenced dialysis. 62.9% were male. Retrospective survival analysis was conducted using the HFRS prior to, and at, dialysis start date and estimates compared using the log-rank test. Results HFRS on dialysis start date was associated with survival time in patients aged ≥70 years (Low frailty Median = 2.5 years; CI = [2.1–3.0 years] vs. Intermediate frailty Median = 1.5 years; CI = [1.0–2.0 years] vs. High frailty Median = 1.3 years; CI = [0.2–2.2 years]; p = 0.005). No association was found between HFRS and survival in the same patients (aged ≥70 on dialysis start date), at any of 3 timepoints prior to dialysis: eGFR level of 20, 15, or 12 (p = 0.18, p = 0.63, p = 0.38 respectively). However, only 150/329 patients (46%) had HFRS recorded prior to eGFR level so sample size was limited. 60 patients’ HFRS had also worsened by dialysis start date (8 had improved). Additional analyses including all age groups found a weaker association between HFRS on dialysis start date and survival (Low frailty Median = 2.1 years; CI = [1.9–2.3 years] vs. Intermediate frailty Median = 1.7 years; CI = [1.5–2.0 years] vs. High frailty Median = 2.1 years; CI = [1.3–2.4 years]; p = 0.04). HFRS and survival were associated at eGFR 15 for all ages (p = 0.02) but not eGFR 20 or 12. Conclusion We identified issues with the HFRS and its implementation that present challenges to its utility for treatment decision-making or service planning in a renal setting. While the HFRS has previously been shown to be predictive of 30-day outcomes in an acute admissions unit, it performed poorly in our cohort of patients with CKD, a long-term condition where HFRS may worsen or improve between treatment choice and dialysis start. Although HFRS did predict outcome from dialysis start in patients aged ≥70 years, this is of limited use given the abundance of validated tools that predict outcome at ESKD. More work is needed to refine the HFRS for pre-ESKD decision-making in a renal setting.

#1920 The impact of kidney function on cardiac diastolic dysfunction trajectories: insights from a longitudinal study

Abstract Background and Aims Although the association between kidney dysfunction and cardiac diastolic dysfunction has been investigated in cross-sectional studies, we currently lack a complete understanding of how the diastolic dysfunction changes over time in individuals with different kidney functions. Exploring the diastolic dysfunction trajectories is crucial as it can provide valuable insights into how kidney function influences cardiac health and which patients are at the highest cardiovascular risk. E/e’ is an echocardiography measure that estimates left ventricular filling pressure and diastolic dysfunction. This study evaluates how kidney function impacts changes in E/e′ over time. Method We identified patients from the Utrecht Patient Oriented Database (UPOD) who visited the outpatient clinic of Utrecht University Medical Center between January 2012 and April 2022. Patients who had received at least three echocardiography reports with a minimum of 12 months between them and had recorded serum creatinine measurements in their electronic health records were included. The estimated glomerular filtration rate (eGFR [mL/min/1.73 m2]) was calculated using the CKD-EPI 2021 creatinine formula without ethnicity and categorized as follows: eGFR ≥ 90, eGFR ≥ 60 - &amp;lt;90, eGFR &amp;lt; 60. Linear mixed-effect models were utilized to determine the impact of kidney function on changes in E/e′ over time. Results A total of 436 patients were included of whom 34.7% were women. The total number of echocardiography examination was 1308. Overall, the median eGFR for all patients was 78.2 mL/min/1.73 m2 [IQR: 61.9, 90.7]. Among them, 26.6%, 51.4%, and 22.0%, had an eGFR ≥ 90, eGFR ≥ 60 - &amp;lt; 90, and eGFR &amp;lt; 60, respectively. Patients with an eGFR &amp;lt; 60 had a higher prevalence of hypertension (64.6%) and cardiovascular disease (84.4%) compared to those with an eGFR ≥ 90, where the prevalence of hypertension and cardiovascular disease was 49.1% and 67.2%, respectively. Additionally, patients with an eGFR &amp;lt; 60 had the lowest mean ejection fraction of 44.9% ± 18.5% and the highest median E/e′ of 12.84 [10.10, 16.16]. The linear mixed model analysis showed that the estimated change in E/e′ per year depended on the level of kidney function. For patients with eGFR ≥ 60 - &amp;lt;90, E/e′ did not significantly change per year (p-value: 0.927). However, for patients with eGFR &amp;lt; 60, a statistically significant (p = 0.014) increase in the E/e′ of 0.45 (0.09, 0.81) was observed per year. Hypertension, diabetes mellitus, and cardiovascular disease were found to affect the change in E/e′, with estimates of 0.95 (0.41, 1.49), 1.82 (0.82, 2.89), and 1.25 (0.54, 1.97), respectively. Conclusion The trajectory of changes in E/e′ over time was significantly affected by varying levels of kidney function. Patients with impaired kidney function (eGFR &amp;lt; 60) have a higher E/e’ compared to those with normal kidney function (eGFR ≥ 90) and presented a significant increase of E/e’ per year.

Correlation Between H-Index, M-Index, and Academic Rank in Urology

OBJECTIVESTo evaluate the h- and m-indices of academic urologists across all U.S. accredited urology residency programs to determine the relationship between these metrics and an author’s academic rank, academic degrees, and gender. METHODSA total of 136 urology residency programs with available faculty information on their websites were evaluated. The academic rank, academic degrees, and gender were recorded for each clinical and research faculty member. Each author’s h-index was determined using the Scopus database. The m-indices for each author were then calculated. Statistical analysis was performed using the Wilcoxon rank-sum test. RESULTSThis study demonstrated that the h- and m-indices positively correlate with an author’s academic rank. Among the 2,253 academic urologists evaluated, chairs/chiefs and professors had the highest median h- and m-indices (h-index 26, m-index 1.046 for chairs/chiefs; h-index 30, m-index 1.094 for professors). This was followed by associate professors (h-index 14, m-index 0.750), assistant professors (h-index 6, m-index 0.667), and clinical instructors (h-index 6, m-index 0.511). The median h- and m-indices were overall statistically higher for males than females. Faculty members with only a PhD were found to have the highest h- and m-indices followed by MD PhD, MD MBA, MD MPH, MD only, and DO only in descending order of index value. CONCLUSIONSThe h- and m-indices of academic urologists positively correlate with their academic rank. These metrics may serve as an additional tool in measuring an individual’s academic productivity in consideration of job hirings, positional promotions, societal memberships, achievement awards, research grants, and more.

Factor VIII and Incident Hypertension in Black and White Adults: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort.

Nearly half of all Americans have hypertension, and Black adults experience a disproportionate burden. Hypercoagulability may relate to hypertension risk, and higher levels of factor VIII increase thrombosis risk. Black adults have higher factor VIII and more hypertension than other groups. Whether higher factor VIII associates with incident hypertension is unknown. The Biomarkers as Mediators of Racial Disparities in Risk Factors (BioMedioR) study measured certain biomarkers in a sex-race stratified sample of 4,400 REGARDS participants who attended both visits. We included BioMedioR participants, excluding those with prevalent hypertension, missing factor VIII level, or covariates of interest. Modified Poisson regression estimated risk ratios (RR) for incident hypertension by higher log-transformed factor VIII level per SD (SD of log-transformed factor VIII, 0.33). Weighting was applied to take advantage of REGARDS sampling design. Among the 1,814 participants included (55% female, 24% Black race), the median follow-up was 9.5 years and 35% (2,146/6,138) developed hypertension. Black participants had a higher median (IQR) factor VIII level (105.6%; 87.1%-126.9%) than White participants (95.6%; 79.8%-115.9%; P < 0.001). The age- and sex-adjusted Black-White hypertension RR was 1.45 (95% CI 1.28, 1.63). Higher factor VIII was not associated with more hypertension (final model RR 1.01; 95% CI 0.94, 1.07). In a prospective study of Black and White adults without prevalent hypertension, factor VIII was not associated with greater hypertension risk.

Fatigue Affects Body Acceleration During Vertical Jumping and Agility Tasks in Elite Young Badminton Players.

Badminton is a sport demanding both high aerobic and anaerobic fitness levels, and fatigue can significantly impact game performance. However, relevant studies are limited, and none have employed a wearable inertial measurement unit (IMU) to investigate the effects of fatigue on athletic performance in the field. Overall performance and body acceleration in both time and frequency domains during the fundamental badminton skills of vertical jumping and changes of direction will be affected by fatigue. Cross-sectional study. Level 3. A total of 38 young badminton players competing at the Division I level participated. Body accelerations while performing vertical jump and agility-T tests before and immediately after undergoing a fatigue protocol were measured by an IMU, positioned at the L4 to L5 level. Jumping height decreased significantly by 4 cm (P < 0.01) after fatigue with greater downward acceleration (1.03 m/s2, P < 0.05) during the squatting subphase. Finishing time increased significantly by 50 ms only during the 10-m side-shuffling of the agility-T test (P = 0.02) after fatigue with greater peak and mean accelerations (3.83 m/s2, P = 0.04; 0.43 m/s2, P < 0.01), and higher median and mean frequency (0.38 Hz, P = 0.04, 0.11 Hz, P = 0.01). This study using a wearable IMU demonstrates the effects of fatigue on body acceleration in badminton players. The frequency-domain analysis further indicated that fatigue might lead to loss of voluntary control of active muscles and increased impacts on the passive elastic elements. The findings imply that fatigue can lead to diminished athletic performance and highlight the potential for an increased risk of sports injuries. Consequently, maintaining precision in monitoring fatigue is crucial for elite young badminton players.