Hazard Analysis Research Articles

Clinical Impacts of Urinary Neutrophil Gelatinase-Associated Lipocalin in Patients With Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention.

Chronic kidney disease (CKD) is associated with poor prognosis in patients undergoing percutaneous coronary intervention (PCI). Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker for renal injury. However, the association between urinary NGAL concentrations and renal and cardiovascular events in patients with CKD undergoing PCI has not been elucidated. This study investigated the clinical impact of urinary NGAL concentrations on renal and cardiovascular outcomes in patients with non-dialysis CKD undergoing PCI.Methods and Results: We enrolled 124 patients with non-dialysis CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) undergoing elective PCI. Patients were divided into low and high NGAL groups based on the median urinary NGAL concentration measured the day before PCI. Patients were monitored for renal and cardiovascular events during the 2-year follow-up period. Kaplan-Meier analyses showed that the incidence of renal and cardiovascular events was higher in the high than low NGAL group (log-rank P<0.001 and P=0.032, respectively). Multivariate Cox proportional hazards analyses revealed that urinary NGAL was an independent risk factor for renal (hazard ratio [HR] 4.790; 95% confidence interval [CI] 1.537-14.924; P=0.007) and cardiovascular (HR 2.938; 95% CI 1.034-8.347; P=0.043) events. Urinary NGAL could be a novel and informative biomarker for predicting subsequent renal and cardiovascular events in patients with CKD undergoing elective PCI.

Identifying patients with reduced risk of recurrences after ablation for persistent atrial fibrillation

Abstract Background Catheter ablation (CA) is a well-established treatment option for recurrent atrial fibrillation (AF), and has shown to outperform antiarrhythmic drugs in prevention of AF recurrences in numerous studies. However, up to 50% of patients with persistent AF (peAF) will experience recurrences after first-time CA. Improving treatment for these patients involves, choosing the right patients for the ablation procedure, optimizing the timing of the procedure, and using the most effective ablation strategy. This will benefit not only the patients, but also target recourse use in the healthcare system. Purpose To identify characteristics and comorbidities of patients with peAF associated with a reduced risk of recurrence after CA. Additionally, to investigate the optimal timing and ablation strategy. Methods This observational cohort study was conducted using real-life data from the Danish healthcare registries. All patients with peAF, &amp;gt;18 years of age, who were assigned to first-time AF ablation, were included within the study period from January 1st 2010 to December 31st 2018. A composite endpoint for AF recurrences was defined as either AF admission, electric cardioversion, use of antiarrhythmic drugs or re-ablation after a 3-month blanking period. We followed the patients in the registries for up to 5 years. A Cox proportional hazards analysis was performed to identify specific patient characteristics, comorbidities, timing of ablation and ablation strategy associated with reduced risk of AF recurrences after ablation. Results The study cohort consisted of 2,123 patients with peAF undergoing first-time CA. Median age was 63 years [IQR: 56.10;68.90], 77.7% were male, and mean BMI was 28.40 (SD: 4.97). Mean diagnosis-to-ablation-time (DAT) was 3.56 years (SD: 4.25) and mean follow-up time was 928.3 days (SD: 829.62). Most prevalent co-morbidities were hypertension (59.1%), ischemic heart disease (16.9%), and heart failure (HF) (27.7%) (Table 1). Patients characterized by male sex (HR: 0.80, 95% CI 0.69-0.93), age 60-70 (HR: 0.79, 95% CI 0.67-0.93), and absence of co-morbidities such as HF (HR: 0.81, 95% CI 0.70-0.94) and chronic obstructive pulmonary disease (COPD) (HR: 0.58, 95% CI 0.44-0-75), were observed with a significantly reduced relative risk of recurrent AF. Short DAT(&amp;lt;1 year) was associated with a 24% lower risk of recurrence compared to longer (&amp;gt;2 years). Furthermore, PVI Plus (additional ablation to PVI) was not significantly associated with a reduced risk of recurrences (HR: 1.10, 95% CI 0,92-1.31) (Figure 1). Conclusion To obtain rhythm control for patients with peAF is a great challenge. This observational study with more than 2,000 patients, identifies patients most likely to benefit from CA. Lower recurrence rates were observed in younger patients (&amp;lt;70 years), absence of especially HF and COPD, and early ablation (&amp;lt;1 year). Notably, PVI plus did not reduce the risk of recurrences.

Contamination, morphological and chemical characterization, and hazard risk analyses of microplastics in drinking water sourced from groundwater in a developing nation

Groundwater (GW) plays a crucial role as the primary source of potable water in numerous developing nations. However, the increasing presence of microplastics (MPs) represents a concealed danger, threatening activities that guarantee safe drinking water in these countries. Despite this, there is limited awareness about the widespread existence of MPs in these regions of the world. In this study, we investigated the contamination levels, distribution, morphological characteristics, chemical composition, and associated public health risk of MPs in groundwater samples from six coastal districts of Bangladesh using stereomicroscopy and Fourier transform infrared spectroscopy (FTIR). MPs were prevalent at all sampling stations, with average concentrations of 24.63 ± 16.13 items/L and a range of 4–75 items/L. The majority of MPs (97.6%) were fibers, indicating a likely origin from fabric disintegration during drying, washing, discarded fishing nets, personal care items, and municipal waste. Smaller-sized MPs (&amp;lt;0.5 mm), transparent and violet-colored, were predominantly observed. Additionally, FTIR confirmed the presence of plastic polymers, including low-density polyethylene (LDPE), high-density polyethylene (HDPE), ethylene vinyl acetate (EVA), and polyethylene terephthalate (PETE). Despite the high visibility observed or focus given for PETE, PE was found to be abundant. These are thought to have come from runoff from agricultural fields, seeping from landfills where plastic trash is disposed of, synthetic fabrics, and inappropriate plastic product disposal. Estimated dietary intake was recorded as 1.85 particles/person/day (i.e., 675 particles/year), suggesting the possible health risk to consumers. Hazard analyses based on the polymeric risk score revealed diverse risks associated with polymer levels, with PETE indicating a medium risk and other polymers, e.g., HDPE, LDPE, and EVA at 39%, 31%, and 17%, respectively, showing a minor risk to human health from drinking water from the studied sources. This is the first study from the regions, and the findings will be valuable for identifying sources, implementing control measures, shaping policies, and safeguarding public health against plastic pollution.

Right atrial endomysial fibrosis is associated with higher POAF-burden

Abstract Background Atrial endomysial fibrosis, rather than overall connective tissue content, determines the complexity of conduction in human atrial fibrillation (AF). Moreover, the AF-specific blood biomarker BMP10 is associated with atrial endomysial fibrosis, but not overall connective tissue content. It is unclear whether pre-operative atrial endomysial fibrosis predicts post-operative AF (POAF) incidence and burden. Objective To determine the predictive value of atrial fibrosis for early and late POAF burden. Methods Patients with and without AF history were included in the RACE V tissue bank study (n=134). Post-operative rhythm was monitored continuously for 2.5 years with implantable loop recorders. Late POAF-burden was investigated following a 90-day blanking period. Left (n=89) and/or right (n=92) atrial appendage biopsies (LAA/RAA) were snap-frozen and histologically investigated following WGA-staining. Results Logistic regression, corrected for age, sex and AF history, showed that left (st.β = 0.54 [0.23-0.85], p=0.001) and right (st.β=0.35 [0.07-0.64], p=0.017) atrial endomysial fibrosis were associated with early POAF burden in the blanking period. Only right atrial endomysial fibrosis, however, predicted late POAF-burden (st.β=0.44 [-], p=0.009). Adjusted Cox proportional hazards analyses indicated that patients in the highest tertile of right atrial endomysial fibrosis, in particular, are at risk for late POAF (HR T3 vs T1: 2.47 [1.18-5.17], p=0.016, Fig 1). Overall connective tissue content in both atria was not associated with POAF-burden. Conclusion Patients with higher levels of right atrial endomysial fibrosis are at risk for developing late POAF with a higher POAF-burden.Figure 1

#963 Discrepancy between actual and estimated urine creatinine excretion predicts mortality in chronic kidney disease: from the KNOW-CKD study

Abstract Background and Aims Urine creatinine excretion is a surrogate marker of muscle mass and low urine creatinine excretion is a predictor of poor clinical outcome. There are several methods to estimate urine creatinine excretion. However, little is known about the clinical implication of discrepancy between actual and estimated urine creatinine excretion in chronic kidney disease (CKD). The aim of this study is to investigate the association between actual and estimated urine creatinine excretion discrepancy and mortality in CKD. Method This study analysed 1805 participants from the KNOW-CKD cohort. They underwent 24-hr urine collection and measured urine creatinine excretion at baseline. Their estimated urine creatinine excretion was calculated by Joachim's method. Discrepancy between actual and estimated urine creatinine excretion (dUCr) was defined as actual urine creatinine excretion minus estimated urine creatinine excretion. Patients were divided into 3 groups according to their tertile of dUCr. The study endpoint was all-cause death. Results During a follow-up of 13 062 person-years (median 8.0 years), 151 patients (8.4%) died, with a corresponding death rate of 11.6 (95% CI 9.9-13.6) per 1000 patients-years. 86 (14.4%), 41 (6.8%) and 24 (3.4%) patients from each 1st to 3rd tertile of dUCr died (P &amp;lt; 0.001). In multivariate Cox proportional hazard analysis, there was a graded association of dUCr with all-cause mortality. The adjusted hazard ratios (95% CI) of 2nd and 3rd tertile were 0.58 (0.39-0.86) and 0.36 (0.22-0.58) compared with the 1st tertile. Conclusion Higher discrepancy between actual and estimated urine creatinine excretion is associated with lower risk of mortality in predialysis CKD patients. This association was independent of various conventional and CKD-related risk factors.

Modelling seismic ground motion and its uncertainty in different tectonic contexts: challenges and application to the 2020 European Seismic Hazard Model (ESHM20)

Abstract. Current practice in strong ground motion modelling for probabilistic seismic hazard analysis (PSHA) requires the identification and calibration of empirical models appropriate to the tectonic regimes within the region of application, along with quantification of both their aleatory and epistemic uncertainties. For the development of the 2020 European Seismic Hazard Model (ESHM20) a novel approach for ground motion characterisation was adopted based on the concept of a regionalised scaled-backbone model, wherein a single appropriate ground motion model (GMM) is identified for use in PSHA, to which adjustments or scaling factors are then applied to account for epistemic uncertainty in the underlying seismological properties of the region of interest. While the theory and development of the regionalised scaled-backbone GMM concept have been discussed in earlier publications, implementation in the final ESHM20 required further refinements to the shallow-seismicity GMM in three regions, which were undertaken considering new data and insights gained from the feedback provided by experts in several regions of Europe: France, Portugal and Iceland. Exploration of the geophysical characteristics of these regions and analysis of additional ground motion records prompted recalibrations of the GMM logic tree and/or modifications to the proposed regionalisation. These modifications illustrate how the ESHM20 GMM logic tree can still be refined and adapted to different regions based on new ground motion data and/or expert judgement, without diverging from the proposed regionalised scaled-backbone GMM framework. In addition to the regions of crustal seismicity, the scaled-backbone approach needed to be adapted to earthquakes occurring in Europe's subduction zones and to the Vrancea deep seismogenic source region. Using a novel fuzzy methodology to classify earthquakes according to different seismic regimes within the subduction system, we compare ground motion records from non-crustal earthquakes to existing subduction GMMs and identify a suitable-backbone GMM for application to subduction and deep seismic sources in Europe. The observed ground motion records from moderate- and small-magnitude earthquakes allow us to calibrate the anelastic attenuation of the backbone GMM specifically for the eastern Mediterranean region. Epistemic uncertainty is then calibrated based on the global variability in source and attenuation characteristics of subduction GMMs. With the ESHM20 now completed, we reflect on the lessons learned from implementing this new approach in regional-scale PSHA and highlight where we hope to see new developments and improvements to the characterisation of ground motion in future generations of the European Seismic Hazard Model.

#2415 Estimated glomerular filtration rate thresholds associated with poor long-term outcomes in older patients with diabetes

Abstract Background and Aims Considering the natural decline of GFR with renal senescence, an age-adjusted estimated glomerular filtration rate (eGFR)-based chronic kidney disease (CKD) definition was recently proposed, which has been supported by that mortality risks start to increase at GFR &amp;lt;45 mL/min/1.73 m2 in older adults (≥65 years). However, the eGFR threshold for mortality and kidney outcomes in older patients with diabetes was less understood. We aimed to evaluate eGFR levels that raise the risk of mortality or end-stage kidney disease (ESKD) in older patients with diabetes. Method Older adult patients (≥65 years) with type 2 diabetes who visited our outpatient diabetes center during 2009 were retrospectively identified and followed up until 2017. Patients were categorized into four groups per their CKD-EPI equation-based eGFR: ≥60, 45–59, 30–44, and 15–29 mL/min/1.73 m2. Cox proportional hazard analysis for all-cause mortality and competing-risk analysis for ESKD (with a competing event of pre-ESKD death) were performed. Results Among 3,065 patients, 19%, 8%, and 2% of patients had eGFR 45–59, 30–44, and 15–29 mL/min/1.73 m2 at baseline, respectively. After adjusting various clinical covariates, including blood pressure, diabetes duration, urine albumin/creatinine ratio, HbA1c, serum cholesterol levels, and major comorbidities, patients with eGFR 30–44 and 15–29 mL/min/1.73 m2 had 1.51-fold (95% confidence interval [CI] 1.17–1.95, P &amp;lt; 0.001) and 2.66-fold (95% CI 1.87–3.79, P &amp;lt; 0.001) higher risks of mortality, respectively, whereas patients with eGFR 45–59 mL/min/1.73 m2 had a comparable risk (1.18, 95% CI 0.96–1.45, P = 0.127) to those with eGFR ≥60 mL/min/1.73 m2. Substitution hazard ratios for ESKD were 2.29 (95% CI 1.41–3.71, P = 0.001), 5.25 (95% CI 3.27–8.41, P &amp;lt; 0.001), and 16.74 (95% CI 9.73–28.80, P &amp;lt; 0.001) in patients with eGFR 45–59, 30–44, 15–29 mL/min/1.73 m2, respectively. In a subgroup of patients 75 or older (n = 800), patients with eGFR 45–59 mL/min/1.73 m2 exhibited comparable risks for both ESKD and mortality. Conclusion Reduced eGFR &amp;lt; 60 mL/min/1.73 m2 predicted an increased risk of ESKD in older patients with diabetes, suggesting that the current traditional eGFR threshold appears feasible. Thus, some high-risk individuals may be missed if age-adapted eGFR criteria with a lower eGFR threshold than 60 mL/min/1.73 m2 are universally applied for older adults ≥65 years.

#619 Serum aldosterone to potassium ratio and hyperkalemia risk in patients with chronic kidney disease

Abstract Background and Aims Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have demonstrated efficacy in improving outcomes in patients with chronic kidney disease (CKD). However, these medications have also been associated with the development of hyperkalemia. The aim of this study was to evaluate the relation of serum aldosterone to potassium ratio to the risk of the development of hyperkalemia in CKD patients receiving ACEIs or ARBs. Method Between January 2017 and December 2021, 186 patients with CKD 3-4 (estimated glomerular filtration rate, eGFR, of 15-59 ml/min/1.73 m2) who were receiving an ACEI or an ARB for at least 3 months and had serum aldosterone and potassium measured simultaneously were analyzed. Serum aldosterone to potassium (Aldo/K) ratio was calculated (ng/ml per mmol/l) and patients were divided into two groups according to the median value of serum Aldo/K ratio above or below 2.42. Follow-up serum potassium concentrations were measured every 2 to 3 months. The primary outcome was the occurrence of hyperkalemia (defined as serum potassium level &amp;gt; 5.5 mEq/l). Incidence rates for hyperkalemic events were computed as the ratio of the total number of hyperkalemic events to the total patient-time at risk. In addition, the times from the index date to the first occurrence of hyperkalemia for were computed. Cox proportional hazards models were used to identify patients at the risk of the occurrence of hyperkalemia. Results During a median follow-up period of 3.1 years, 2505 times of serum potassium were measured (mean ± standard deviation number of annual potassium measurements per patient, 4.5 ± 1.7 measurements/year per patient). A total of 144 hyperkalemic events in 81 patients (43.5%) were identified, yielding an incidence rate of 24.6 per 100 person-years (95% confidence intervals [CIs] 20.4–28.8). The incidence of hyperkalemic events was significantly higher in patients with low serum Aldo/K ratio than in those with high serum Aldo/K ratio (35.8 events/100 patient-years, 95% CI 28.9‒42.7 events/100 patient-years vs. 12.9 events/100 patient-years, 95% CI 8.8‒17.0 events/100 patient-years, p &amp;lt; 0.001). In multivariate Cox proportional hazards analysis, diabetes mellitus (Hazard ratio [HR], 1.842; 95% CI, 1.046-3.243; P=0.034), prior history of hyperkalemia (HR, 2.288; 95% CI, 1.372-3.815; P=0.002), low baseline eGFR (HR, 0.973; 95% CI, 0.948-0.998; P=0.037) and a low serum Aldo/K ratio (HR, 3.654; 95% CI, 2.066-6.463; P &amp;lt; 0.001) were predictors of subsequent development of hyperkalemia. Conclusion This study revealed that low serum Aldo/K ratio ( &amp;lt; 2.42) was strongly associated with the occurrence of hyperkalemia in CKD patients receiving ACEIs or ARBs, suggesting that the identification of patients at a risk for subsequent hyperkalemia could be made by measuring serum aldosterone and potassium levels simultaneously on these drugs.

#2414 Hypertension resolution after kidney transplantation is associated with better kidney transplant outcomes in patients with pre-transplant hypertension

Abstract Background and Aims Hypertension is prevalent in patients with advanced chronic kidney disease (CKD), and kidney transplantation (KT) can potentially improve hypertension. Although hypertension is expected to be resolved after KT in many recipients with pre-transplant hypertension, little is known about the hypertension resolution rate and its prognostic role in KT outcomes. Method We retrospectively identified KT recipients (between 2006 and 2015) who had pre-transplant hypertension using Health Insurance Review &amp; Assessment Service and Korea National Health Insurance System. The recipients were categorized into two groups based on their post-KT hypertension status: “persistent hypertension” and “resolved hypertension”. Cox proportional hazard analyses were performed to assess the risk of death-censored graft failure and all-cause mortality with adjusting various clinical, immunological risk factors, and socioeconomic status. Results Among 11,342 KT recipients with pre-transplant hypertension, 8,233 (73%) remained hypertensive, while 3,109 (27%) experienced hypertension resolution after KT. Recipients with resolved hypertension had lower rates of delayed graft function and major comorbidities, including diabetes mellitus, ischemic heart disease, and stroke compared to recipients who remained hypertensive. After adjusting for multiple covariates, the resolved hypertension group had 0.59-fold (95% confidence interval [CI] 0.49–0.73) lower risk for graft failure and 0.59-fold (95% CI 0.48–0.73) lower risk for all-cause mortality compared to the persistent hypertension group. Subgroup analyses revealed that the protective effect of resolved hypertension on graft survival was more pronounced in females (P for interaction = 0.045), and on overall survival was weaker in recipients with diabetes (P for interaction = 0.033). Conclusion A significant proportion of patients experienced hypertension resolution after KT, which is associated with improved graft survival and overall patient survival. The post-KT hypertension status can be used as a prognostic indicator for predicting better outcomes in KT recipients with pre-transplant hypertension.

#2338 Potassium-competitive acid blocker use is associated with a lower risk of renal function deterioration compared to proton pump inhibitor use

Abstract Background and Aims Proton pump inhibitors (PPI) are commonly used drugs worldwide and have been linked to worsening renal function and incident chronic kidney disease. Recently, potassium-competitive acid blockers (P-CAB) have emerged as alternative gastric acid-reducing agents with a comparable effect as PPIs. However, little is known about the renal safety of P-CAB. We aimed to compare the renal outcomes of patients treated with P-CAB and those treated with PPI. Method We retrospectively identified all patients who were prescribed P-CAB (tegoprazan) or PPI (esomeprazole) for 30 days or more in outpatient clinics of a tertiary care center between 2019 and 2023. Longitudinal serum creatinine data and various demographic and clinical variables were collected. Renal outcomes were defined as creatinine doubling or decline in estimated glomerular filtration rate (eGFR) of 30%. Patients with baseline eGFR &amp;lt; 15 mL/min/1.73 m2 and those who do not have sufficient creatinine measures to assess renal outcomes were excluded. Cox proportional hazard analyses were performed for renal outcomes with adjustment of multiple clinical covariates. Results Among 8 436 patients with a mean followup of 21 months, 2 214 and 6 222 patients were treated with P-CAB and PPI, respectively, for esophageal and gastric diseases. P-CAB group showed lower rates of creatinine doubling (Log-rank P = 0.001) and decline of eGFR (Log-rank P = 0.001) compared to PPI group. P-CAB use was associated with a 0.50-fold (95% confidence interval [CI] 0.33–0.75) lower risk for creatinine doubling and 0.58-fold (95% CI 0.42–0.81) lower risk for eGFR decline in unadjusted analysis. After adjusting multiple covariates including baseline eGFR, prescription days, major comorbidities, and concomitant use of other medications, hazard ratios for creatinine doubling and eGFR decline were 0.64 (95% CI 0.42–0.98) and 0.73 (95% CI 0.53–1.02), respectively. Conclusion Use of P-CAB is associated with a lower risk for renal function deterioration compared to PPI. Given the renal safety concerns of PPIs, using P-CAB could be a relatively safer strategy for preserving kidney function in patients who need long-term gastric acid suppression. Further studies with a larger cohort incorporating other P-CABs are required to validate this finding.

#553 Renal tubular damage is an independent risk factor for all-cause and cardiovascular mortality in a community-based population: the Takahata Study

Abstract Background and Aims Renal tubulointerstitial damage is a risk for renal failure. However, the association between renal tubulointerstitial damage and all-cause and cardiovascular mortality in the general population remains unclear. In this prospective cohort study, we examined this point using urinary β2-microglobulin/creatinine ratio (UBCR) as a marker of renal tubulointerstitial damage in the general Japanese population. Methods We examined the association between UBCR values at entry and all-cause and cardiovascular mortality during the follow-up period (median 9.2 years) in 3 427 residents (mean age 62.5 years, 45.1% male, mean eGFR 81.6 ml/min/1.73 m², ≥1+ protein 4.4%) of Takahata Town in Japan. Results Study participants were divided into two groups (low &amp;lt; 300 μg/gCre, high ≥300 μg/gCre) based on UBCR at entry. Kaplan-Meier analysis showed a significantly higher incidence of all-cause and cardiovascular mortality in the high UBCR group (Log-rank P &amp;lt; 0.01). A multivariate Cox proportional hazards analysis adjusted for age, sex, eGFR, urinary protein level, comorbidities, smoking status, and other background factors showed a hazard ratio of 1.47 (95% CI 1.09-2.00, P = 0.01) for all-cause mortality and a hazard ratio of 1.82 (95% CI 1.06-3.12, P = 0.03) for cardiovascular death in the high-UBCR group. The addition of high UBCR to conventional risk factors, including eGFR and urinary protein level, significantly improved the net reclassification improvement (NRI) for all-cause and cardiovascular mortality (P &amp;lt; 0.01). Conclusions UBCR, a marker of tubulointerstitial damage, was identified as a risk factor for all-cause and cardiovascular mortality in the general population independent of eGFR and urinary protein levels.

Ground-motion models for inelastic response spectra using NGA-West2 database

This article presents ground-motion models (GMMs) for inelastic response spectra using the NGA-West2 database. The inelastic response spectra are defined in terms of constant ductility. The GMMs are used to observe the effect of event scenarios, site conditions, and oscillator properties on maximum displacement. Using a large database enabled us to quantify the magnitude scaling of inelastic response as compared to that for the traditional elastic GMMs. We observe that using the magnitude scaling of elastic GMM for hazard analysis of inelastic structural response can be unconservative for large magnitudes and large ductility ratios. To compare our models with models in the literature, we use the developed GMMs to compute the Reduction Factor due to inelasticity. Comparison of this model with models in the literature shows the importance of considering the effect of magnitude on the Reduction Factor. We also observe that the ratio of RotD100/RotD50 is larger for inelastic single-degree-of-freedom system than that for elastic system, and the ratio increases with increasing ductility.

Predictors of HIV Viral Load Suppression After Enhanced Adherence Counseling, Nekemte, Ethiopia.

Enhanced adherence counseling refers to the counseling intervention for Human Immunodeficiency Virus (HIV) patients with an elevated viral load result, a viral load of > 1000 copies/ml, on a routine or need-based viral load test. The Federal Ministry of Health, Ethiopia, has launched routine viral load testing and enhanced adherence counseling since 2016 for high-viral load people living with HIV, which is applicable throughout the country for all health facilities providing HIV care and treatment. Our study aimed to assess viral load suppression after enhanced adherence counseling and its predictors among high viral load people living with HIV who were on antiretroviral therapy. We conducted a health facility-based retrospective follow-up study among 352 HIV-infected high-viral load people enrolled in enhanced adherence counseling from July 2018 to June 2021 in Nekemte town public health facilities. Cox proportional hazard analysis was used to identify independent predictors. The overall 65.1% of 352 persons on antiretroviral treatment achieved HIV viral load suppression after enhanced adherence counseling, (15.01 per 100 person months (95% CI13.02-16.99)). The median time to viral load suppression was 5 months. Age ≥ 15 years (AHR = 1.99, 95% CI: 1.11-3.57), no history of opportunistic infection (AHR = 2.01, 95% CI: 1.18-3.41), and not using substances (AHR = 2.48, 95% CI: 1.19-5.14) were more likely to have viral load suppressed, while having an initial viral load count greater than 50,000 RNA copies/ml (AHR = 0.56, 95% CI: 0.37-0.85) were less likely to have viral load suppressed after enhanced adherence counseling. Age, history of opportunistic infections, substance use, and an initial viral load count > 50,000 RNA copies/mL were significant predictors of viral load suppression. Enrolling all high-viral-load patients in enhanced adherence counseling is recommended for viral load suppression.

Clinical Outcomes of Secondary Duodenal Self-Expandable Metallic Stenting for Duodenal Stent Dysfunction in Patients with Malignant Duodenal Obstruction: A Retrospective Multicenter Study.

Malignant duodenal obstruction has become more common with the development of palliative therapies.The outcomes of endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) are comparable to those of surgical gastrojejunostomy or duodenal stenting. However, EUS-GJ is technically challenging. Duodenal self-expandable metallic stent (SEMS) placement is popular; however, obstructions are common. Duodenal SEMS obstruction can be managed with the insertion of a second SEMS in a stent-in-stent manner. Therefore, we aimed to analyze the clinical outcomes of secondary duodenal SEMS placement in patients with malignant duodenal obstruction. We retrospectively analyzed the data of patients who underwent secondary duodenal stent insertion for duodenal stent dysfunction between January 2016 and December 2021. The primary outcome was stent patency. The secondary outcomes were clinical success, factors associated with dysfunction, patient survival, and adverse events. A total of 109 patients were included. The mean age was 64.4±11.2 years, and 63 patients (57.8%) were male. Ninety-two patients (84.4%) had pancreaticobiliary cancer. Clinical success was achieved in 94 cases (86.2%). Twenty-three patients experienced stent dysfunction with 231 days of median stent patency (95% confidence interval [CI], 169 to not available). After a multivariable Cox hazard analysis of stent patency, the Eastern Cooperative Oncology Group performance status (hazard ratio [HR], 2.13; 95% CI, 1.20 to 3.81; p=0.010) and the first stent patency ≥6 months (HR, 0.33; 95% CI, 0.11 to 0.95; p=0.050) remained significant associated factors. Adverse events occurred in five patients (4.6%). Secondary duodenal stent insertion is a viable option for first duodenal stent obstruction. Further comparative studies involving surgery or EUS-GJ for obstructed duodenal stents are warranted.

Site-specific probabilistic seismic hazard analysis in Nuweiba, Gulf of Aqaba, Egypt: Combining area source model and active faults

Gulf of Aqaba in Eastern Egypt is characterized by significant seismic activity and high deformation rate, making it a major source of destructive earthquakes in the region. While previous studies have produced probabilistic seismic hazard analysis (PSHA) maps for the region, they have not adequately accounted for active faults or site response in their calculations. This study introduces a newly developed seismic source model for the Gulf of Aqaba, considering area source, active fault source, and a combination of both models to improve seismic hazard assessment for the region. The study incorporates the previously measured average shear-wave velocity for the upper 30 m (Vs30), fundamental frequency (F0), and amplification factor (A0) at some selected sites in Nuweiba city. Accordingly, site-specific PSHA is carried out for the bedrock condition (Vs30 = 800 m/s, according to the Egyptian Building Code) and for the surface of soft sediments using F0, A0, and Vs30. Uncertainties in slip rate, maximum magnitude, and recurrence model are accounted during PSHA computation. Ground motion parameters such as peak ground acceleration (PGA) and spectral acceleration (SA) for various probabilities of exceedance in 50-year lifetime are calculated for both rock site conditions and soft sediments. The maximum calculated PGA and SA are 0.65 g and 1.25 g, respectively, for a 10% probability of exceedance over 50 years at bedrock conditions.

Rapid construction of double macrocycles, hierarchical covalent organic framework with size-sieving and host-guest recognition for selective adsorption and targeted analysis of mycotoxins in cereals

Covalent organic frameworks (COFs) show promising applications in the adsorption of chemical hazards. However, on-demand design for selective recognition remains a great challenge. It is important for food and environmental safety to make COFs into novel multifunctional adsorbents with selective recognition and hierarchical structure through functionalization and structural regulation. Here, calix[4]arene (CX4) and 5,10,15,20-tetrakis(4-aminophenyl)porphyrin (Tph) were used as building blocks for the rapid preparation of novel hierarchical CX4-Tph-COF with double macrocycles synergistic effects for the first time. CX4-Tph-COF exhibited monodisperse and regular spherical structure. The perfect fusion of double macrocycles and porous COFs enabled CX4-Tph-COF to exhibit excellent host–guest recognition, size-sieving and high adsorption capacity. Meanwhile, adsorption experiments and simulation calculations further verified the recognition mechanism. CX4-Tph-COF had successfully achieved efficient adsorption and detection of mycotoxins in cereals, showing ultra-high sensitivity (LODs of 0.18–21.32 ng/kg), satisfactory recovery (81.7–118 %) and good precision (0.9–9.2 %). This provides a new idea for the design of multifunctional COFs with customizable molecular recognition and has potential applications in the targeted analysis of hazards in food safety and environmental monitoring.

Triglyceride-glucose index predicts all-cause mortality, but not cardiovascular mortality, in rural Northeast Chinese patients with metabolic syndrome: a community-based retrospective cohort study

BackgroundMetabolic syndrome (MetS) includes a group of metabolic irregularities, including insulin resistance (IR), atherogenic dyslipidemia, central obesity, and hypertension. Consistent evidence supports IR and ongoing low-grade inflammation as the main contributors to MetS pathogenesis. However, the association between the triglyceride-glucose (TyG) index and mortality in people with MetS remains uncertain. The objective of this study was to examine the correlation between the baseline TyG index and all-cause and cardiovascular (CV) mortality in rural Northeast Chinese individuals with MetS.MethodsFor the Northeast China Rural Cardiovascular Health Study, 3918 participants (mean age, 55 ± 10; 62.4% women) with MetS at baseline were enrolled in 2012–2013 and followed up from 2015 to 2017. The TyG index was calculated using the equation TyG index = ln [fasting TG (mg/dL) × fasting glucose (mg/dL)/2] and subdivided into tertiles [Q1(< 8.92); Q2 (8.92–9.36); Q3 (≥ 9.36)]. Multivariate Cox proportional hazards models were developed to examine the correlations between mortality and the baseline TyG index.ResultsDuring a median of 4.66 years of follow-up, 196 (5.0%) all-cause deaths and 108 (2.8%) CV disease-related deaths occurred. The incidence of all-cause mortality was significantly different among TyG index tertiles of the overall population (P = 0.045). Kaplan–Meier analysis demonstrated a significantly increased risk of all-cause mortality in rural Chinese patients with a higher TyG index (log-rank P < 0.05). After adjusting for possible confounders, Cox proportional hazard analysis revealed that the TyG index could effectively predict all-cause mortality (HR for the third vs. first tertile of TyG was 1.441 [95% confidence interval, 1.009–2.059]), but not CV mortality, in rural Chinese patients with MetS.ConclusionsThe TyG index is an effective predictor of all-cause mortality in rural Chinese patients with MetS. This indicates that the TyG index may be useful for identifying rural Chinese individuals with MetS at a high risk of death.

Hsa_circ_0070440 mediates the prognosis and progress of human prostate cancer.

This study was designed to explore whether hsa_circ_0070440 was dysregulated in prostate cancer (PCa), and assess the effects of hsa_circ_0070440 alteration on PCa prognosis and cell function. The expression levels of hsa_circ_0070440 were assessed in PCa tissues and cell lines. After the classification of patients with PCa based on mean hsa_circ_0070440 level in 138 cases, Chi-square test and survival analyses (Kaplan-Meier method and multivariable Cox proportional hazards analysis) were performed to assess the predictive value of hsa_circ_0070440 in treatment failure (TTF), time to PSA progression (TTPP) and overall survival time. To examine the function of hsa_circ_0070440 in PCa cells, 22Rv1 and C4-2B cells were used for CCK-8 proliferation and Transwell migration assays. Hsa_circ_0070440- and TXNDC5-specific bindings with miR-382/383-5p were validated by bioinformatic analysis and luciferase gene reporter assay. An increased expression of hsa_circ_0070440 was found in PCA tissues and cell lines, associated with clinical T stage (p=0.021) and lymph node metastasis. Hsa_circ_0070440 predicted poor overall survival, TTPP, and TTF, acting as independent prognostic factors for overall survival, TTPP, and TTF in patients with PCa. Knockdown of hsa_circ_0070440 inhibited cell proliferation and migration in vitro. Furthermore, hsa_circ_0070440 could sponge miR-382/383-5p. TXNDC5 was a common target gene for miR-382/383-5p in PCa cells. This study demonstrated that hsa_circ_0070440 can predict the prognosis of PCa patients. Hsa_circ_0070440 can facilitate the proliferation and migration of PCa cells, possibly by sponging miR-382/383-5p.

Inter-relationships of risk factors and pathways associated with all-cause mortality in patients with chronic schizophrenia.

Of all psychiatric disorders, schizophrenia is associated with the highest risk of all-cause mortality. This study aimed to investigate independent risk factors for all-cause mortality in patients with chronic schizophrenia. In addition, the possible causal inter-relationships among these independent risk factors and all-cause mortality were also explored. We conducted an analysis of 1,126 patients with chronic schizophrenia from our psychiatric department from April 2003 to August 2022, and retrospectively reviewed their medical records. The study endpoint was all-cause mortality. Baseline clinical characteristics including sociodemographic data, biochemical data, lifestyle factors, comorbidities and antipsychotic treatment were examined with Cox proportional hazards analysis. The all-cause mortality rate was 3.9% (44 patients). Multivariate Cox regression analysis revealed that several factors were independently associated with all-cause mortality, including diabetes mellitus (DM), hypertension, heart failure, gastroesophageal reflux disease (GERD), peptic ulcer disease, ileus, underweight, fasting glucose, triglycerides, albumin, and hemoglobin. Structural equation modeling (SEM) analysis revealed that several factors had statistically significant direct effects on all-cause mortality. Heart failure, hypertension, underweight, age at onset, and ileus showed positive direct effects, while albumin and hemoglobin demonstrated negative direct effects. In addition, several factors had indirect effects on all-cause mortality. GERD indirectly affected all-cause mortality through ileus, and peptic ulcer disease had indirect effects through albumin and ileus. Ileus, underweight, DM, and hypertension also exhibited indirect effects through various pathways involving albumin, hemoglobin, and heart failure. Overall, the final model, which included these factors, explained 13% of the variability in all-cause mortality. These results collectively suggest that the presence of DM, hypertension, heart failure, GERD, peptic ulcer disease, ileus, and underweight, along with lower levels of albumin or hemoglobin, were independently associated with all-cause mortality. The SEM analysis further revealed potential causal pathways and inter-relationships among these risk factors contributing to all-cause mortality in patients with chronic schizophrenia.

Superiority of high sensitivity cardiac troponin I over NT-proBNP and adiponectin for 7-year mortality in stable patients receiving haemodialysis

Patients on haemodialysis (HD) have high mortality risk, and prognostic values of the major cardiovascular biomarkers cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), and adiponectin should be ascertained over longer follow-up periods using higher-sensitivity assays, which we undertook. In 221 HD patients, levels of high-sensitivity (hs)-cTnI, NT-proBNP, and adiponectin, were measured using high-sensitivity assays, and their associations with all-cause mortality (ACM) and cardiovascular mortality (CVM) were prospectively investigated for 7 years. Higher hs-cTnI and NT-proBNP levels were significant risk factors for ACM and CVM in the Kaplan–Meier analysis. Multivariate Cox proportional hazards analyses in a model including hs-cTnI and NT-proBNP identified log hs-cTnI, but not log NT-proBNP, as an independent risk factor for ACM (HR 2.12, P < 0.02) and CVM (HR 4.48, P < 0.0005). Stepwise analyses identified a high hs-cTnI tertile as a risk factor for ACM (HR 2.31, P < 0.01) and CVM (HR 6.70, P < 0.001). The addition of hs-cTnI to a model including age, CRP, DM, and NT-proBNP significantly improved the discrimination of ACM and CVM each over 7 years. Conclusively, hs-cTnI was superior to NT-proBNP and adiponectin in predicting ACM and CVM over 7 years in HD patients, suggesting the significance of baseline hs-cTnI measurements in long-term management.