Pulmonary vasodilators in patients with advanced chronic kidney disease and pre-capillary pulmonary hypertension-A case series.

Pulmonary hypertension (PH) is a prevalent complication among patients with chronic kidney disease (CKD). In these patients, pulmonary vasodilators may be useful but are underused. We describe a group of patients with precapillary PH and advanced CKD treated with pulmonary vasodilators. This was a case series of patients with CKD stage 4 and 5 and precapillary PH (isolated or combined) based on right heart catheterization (RHC) treated with pulmonary vasodilators from 2018 to 2023. Of 263 patients with isolated precapillary or combined PH and advanced CKD, only 17 (6%) were treated with pulmonary vasodilators; 53% (n = 9) with precapillary PH and 47% (n = 8) with combined PH. Most patients (94%, n = 16) received phosphodiesterase-5 antagonists, while 12% (n = 2) received endothelin receptor antagonists. Adverse clinical outcomes were seen in 35% of patients within a year. The use of pulmonary vasodilator did not prevent adverse outcomes in patients with precapillary PH and advanced CKD.

Clinical Characteristics and Outcomes Associated With Distinct Hemodynamic Patterns in End-stage Liver Disease: A Retrospective Cohort Analysis.

Introduction: Despite advances in the diagnosis and therapeutics strategies for pulmonary hypertension (PH) in patients with end-stage liver disease (ESLD), the impact of hemodynamic patterns among ESLD patients identified through right heart catheterization (RHC) on clinical outcomes remains poorly understood. Methods: This single-center retrospective cohort study identified patients diagnosed with ESLD who underwent RHC from August 2018 to June 2023. Demographic and clinical data, including comorbidities, transthoracic echocardiography, and RHC findings, were obtained. Our outcomes of interest were all-cause mortality and the chance of receiving orthotopic liver transplantation (OLT) within a year after RHC. Kaplan-Meier with log-rank test was employed to generate survival curves. Results: We identified 415 ESLD patients with the RHC results. The median (IQR) age was 59 years (52-66), and 62% were male. Caucasians accounted for 43%, followed by African Americans (30%). Up to 89% had a diagnosis of portal hypertension. Median MELD-Na score was 30 (19-36). The etiology of ESLD was mainly from alcohol use (55%). Patients were classified based on RHC results as pre-capillary PH (19%), post-capillary PH (28%), and non-PH (53%) groups. Overall, one-year mortality post-RHC was 22%, with no significant difference in mortality regardless of hemodynamic group. However, the pre-capillary PH group was less likely to receive OLT compared to other groups (P < 0.001). Conclusion: We observed no difference in all-cause mortality among hemodynamic groups. However, pre-capillary PH group were less likely to undergo OLT compared to others. Further investigations are necessary to determine how this should be addressed in clinical practice.

Association of arteriovenous fistulae with precapillary pulmonary hypertension - A single center retrospective analysis of invasive hemodynamic parameters.

BACKGROUND: Pulmonary hypertension (pH) is a well-known complication among patients with chronic kidney disease (CKD). Arteriovenous fistulae (AVF) have been associated with pH mainly by increasing cardiac output. However, the burden of precapillary pH in individuals with CKD and an AVF is unclear. OBJECTIVES: To better and more fully understand the mechanism and development of precapillary pH in patients with AVF, as well as the consequences of precapillary pH in these patients. METHODS: This was a large retrospective study of patients with CKD stage 4 or 5 who underwent right heart catheterization (RHC) from 2018 to 2023. The data were stratified according to the presence of AVF. To determine if AVF was independently associated with precapillary pH, we used a multivariable logistic regression analysis adjusting for demographics and potential comorbidities associated with precapillary pH, including diagnosis of chronic lung disease, obstructive sleep apnea, connective tissue disease, history of venous thromboembolism, chronic anemia, and heart failure. RESULTS: Of 651 patients with CKD4 or CKD5, 145 (22 %) had AVF and 506 (78 %) did not have AVF. Within the AVF group, the median age was 64 years (IQR 54-71), and they were predominantly males (61 %, n = 88) and African American (77 %, n = 111). A total of 31 % (n = 45) had evidence of precapillary pH, 30 % (n = 43) of combined pH, and 14 % (n = 20) of isolated postcapillary pH. Compared to the non-AVF group, precapillary pH was more likely in the AVF group (31% vs 17 %, p < 0.0001). On multivariable analysis, AVF was independently associated with precapillary pH (OR 2.47, CI 1.56-3.89; p < 0.0001). The median time from dialysis initiation to RHC date (and precapillary pH diagnosis) was 6 years (IQR 3-8). CONCLUSION: Based on RHC findings, almost one-third of patients with CKD and AVF had precapillary pH. The presence of AVF was independently associated with precapillary pH.

Association of mildly elevated pulmonary vascular resistance with major cardiovascular events in pulmonary hypertension and chronic kidney disease: A retrospective cohort analysis.

Pulmonary hypertension (PH) is associated with adverse outcomes in chronic kidney disease (CKD) patients. Our study suggests mildly elevated pulmonary vascular resistance ( > 2 to ≤ 3) is independently associated with major adverse cardiovascular events at 1-year follow-up. Early diagnosis of precapillary PH in CKD patients can potentially improve clinical outcomes.

Metformin in Systemic Lupus Erythematosus: Investigating Cardiovascular Impact and Nephroprotective Effects in Lupus Nephritis.

OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by widespread organ inflammation. Metformin, commonly used for diabetes mellitus type 2, has been explored for its anti-inflammatory potential in SLE. This study investigates the association of metformin use on renal and cardiovascular outcomes in patients with SLE. METHODS: This is a retrospective study. We used the multicenter research network (TriNetX) database from 88 health care organizations globally. Patients with SLE aged 18 and above, admitted between January 1, 2014, and April 21, 2024, were included. Propensity score matching compared patients with SLE on metformin with those not on metformin, considering demographics, laboratory results, comorbidities, and baseline medication use. The study assessed outcomes, including lupus nephritis (LN), chronic kidney disease (CKD), and major adverse cardiovascular events (MACEs) at one and five years after SLE diagnosis. RESULTS: We identified 9,178 patients with SLE on metformin and 78,983 patients with SLE not on metformin. After propensity score matching, patients with SLE on metformin had higher levels of hemoglobin A1C, whereas patients not on metformin had higher levels of urea nitrogen. When comparing both groups, the risk of developing LN (risk ratio [RR] = 1.70 [1.17-2.41]; P = 0.004), CKD (RR = 1.27 [1.07-1.52]; P = 0.007), and MACEs (RR = 1.21 [1.00-1.46]; P = 0.04) was significantly higher among patients not on metformin at one year after SLE diagnosis. After five years, the risk of LN and CKD was also higher in patients with SLE not on metformin. MACE risk was no longer significant after five years of diagnosis between both groups. CONCLUSION: Patients with SLE not on metformin have a higher risk of developing LN, CKD, and MACEs compared with patients treated with metformin. Metformin's anti-inflammatory potential offers promise as a complementary therapy for SLE. Nonetheless, further research and clinical trials are needed to clarify its mechanisms, optimal dosage, and long-term effects.

Outcomes with inpatient use of midodrine in patients with heart failure and kidney failure on maintenance dialysis.

BACKGROUND: Midodrine, an FDA-approved medication for orthostatic hypotension, is also used off-label to manage hypotension in dialysis patients, including those with heart failure. However, in patients with reduced ejection fraction (HFrEF) and/or right heart failure, midodrine is potentially harmful. No known studies examine the safety of midodrine in hospitalised kidney failure patients with HF. METHODS: The TriNetX database was queried for hospitalised kidney failure patients with HFrEF and/or right heart failure who experienced hypotension (SBP < 110 mm Hg or MAP < 70 mm Hg). Excluding those needing critical care or vasopressors, we compared cohorts based on midodrine use, matching for comorbidities. RESULTS: Analysis showed patients on midodrine had a higher 6-month mortality risk ratio (RR 1.53, 95% CI 1.037 to 2.246) and Hazard Ratio (HR 1.54, 95% CI 1.022 to 2.317) compared to those not on midodrine, indicating an association with increased mortality. CONCLUSION: This study illuminates the complexities in treating hospitalised patients with kidney failure and HF. Our findings, drawn from an exploratory analysis, indicate that inpatient midodrine use is associated with increased 6-month mortality. This may reflect deleterious effects from vasoconstriction and/or unmeasured confounders in this vulnerable population. This investigation, utilising TriNetX, was limited by access to deidentified aggregate data, preventing detailed exploration of specifics such as timing, dosage, and indications for midodrine use. Moreover, given its observational nature, cause-effect relationship cannot be established. Our findings indicate an increased mortality associated with midodrine use for hypotension, underscoring the need for further research and consideration of alternative strategies.

Cardiovascular outcomes of sodium-glucose Co-transporter 2 inhibitors use after myocardial infarction: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Patients who had acute myocardial infarction are at high risk of negative cardiac outcomes and previous SGLT2i landmark trials excluded these patients. It therefore remains unclear if SGLT2i is safe and confers beneficial cardiovascular outcomes after acute myocardial infarction. METHODS: We systematically reviewed randomized controlled trials that evaluated the outcomes of adding SGLT2i to conventional post-myocardial infarction care. Random-effects model meta-analysis via RevMan 5.4 was done on data extracted from pooled 11,204 patients. RESULTS: SGLT2i use after acute myocardial infarction was significantly associated with reduced heart failure hospitalization (OR: 0.77, 95%CI: 0.62-0.96, p=0.02), but was not associated with a reduction in all-cause mortality (OR: 1.05, 95%CI: 0.77-1.43, p=0.75), cardiac-related death (OR: 1.04, 95%CI: 0.83-1.30, p=0.76), or major adverse cardiac events (OR: 0.90, 95%CI: 0.77-1.05, p=0.18). CONCLUSION: SGLT2 inhibitor therapy after acute myocardial infarction is safe and is associated with a reduced risk of heart failure hospitalization, but not with all-cause mortality.

Nonlinear time effects of vegetation response to climate change: Evidence from Qilian Mountain National Park in China.

Vegetation responses to climate change are typically nonlinear with varied time effects, yet current research lacks comprehensiveness and precise definitions, hindering a deeper understanding of the underlying mechanisms. This study focuses on the mountain-type Qilian Mountain National Park (QMNP), investigating the characteristics and patterns of these nonlinear time effects using a generalized additive model (GAM) based on MODIS-NDVI, growing season temperature, and precipitation data. The results show that 1) The time effects of climate change on vegetation exhibit significant spatial variations, differing across vegetation types and topographic conditions. Accounting for optimal time effects can increase the explanatory power of climate on vegetation change by 6.8 %. Precipitation responses are mainly characterized by time-lag and time-accumulation effects, notably in meadows and steppes, while temperature responses are largely cumulative, especially in steppes. The altitude and slope significantly influence the pattern of vegetation response to climate, particularly in areas with high altitudes and steep slopes. 2) There is a significant nonlinear relationship between vegetation growth and both precipitation and temperature, with the nonlinear relationship between precipitation and vegetation being stronger than that with temperature, particularly in the western and central regions of the park. Different vegetation types exhibit significant variations in their response to climate change, with deserts and steppes being more sensitive to precipitation. 3) Precipitation is the primary driver of vegetation change in the QMNP, particularly for high-elevation vegetation and herbaceous vegetation. The complex temporal patterns of vegetation response to climate change in the QMNP not only deepen the understanding of the intricate relationship between regional vegetation and climate variability but also provide a methodological reference for global studies on vegetation responses to climate change.

[Tobacco cessation: one of the most effective medical measures]. / Tabakentwöhnung ­ eine der effektivsten medizinischen Maßnahmen.

Tobacco smoking is widespread in Germany. An increase in the number of teenagers and young adults that smoke has recently been a cause for concern. The high prevalence in Germany is contrasted by inadequate preventive measures compared to international standards. Smoking behavior should always be inquired about and documented in the same way as vital signs. All smokers, regardless of the reason for contact and motivation, should receive short, low-threshold advice, e.g. using the ABC approach (ask, brief advice, cessation). In addition to repeated advice and referral to further services, the use of nicotine replacement or drug therapy is essential for the success of quitting. The combination of long- and short-acting nicotine replacement products doubles the success rate. Electronic nicotine delivery systems are not recommended for smoking cessation.

Osteo-inductive effect of piezoelectric stimulation from the poly(l-lactic acid) scaffolds.

Piezoelectric biomaterials can generate piezoelectrical charges in response to mechanical activation. These generated charges can directly stimulate bone regeneration by triggering signaling pathway that is important for regulating osteogenesis of cells seeded on the materials. On the other hand, mechanical forces applied to the biomaterials play an important role in bone regeneration through the process called mechanotransduction. While mechanical force and electrical charges are both important contributing factors to bone tissue regeneration, they operate through different underlying mechanisms. The utilizations of piezoelectric biomaterials have been explored to serve as self-charged scaffolds which can promote stem cell differentiation and the formation of functional bone tissues. However, it is still not clear how mechanical activation and electrical charge act together on such a scaffold and which factors play more important role in the piezoelectric stimulation to induce osteogenesis. In our study, we found Poly(l-lactic acid) (PLLA)-based piezoelectric scaffolds with higher piezoelectric charges had a more pronounced osteoinductive effect than those with lower charges. This provided a new mechanistic insight that the observed osteoinductive effect of the piezoelectric PLLA scaffolds is likely due to the piezoelectric stimulation they provide, rather than mechanical stimulation alone. Our findings provide a crucial guide for the optimization of piezoelectric material design and usage.

Gastric Lipomas: A Case Series and Review of the Literature.

Introduction: The purpose of this case series was to review a rare subset of tumors known as gastric lipomas, which are typically found incidentally. The motivation for this study arose from the identification of 2 cases within our institution in a short period. Case Presentation: The study involved a review of the diagnosis and management of 2 patients presenting with gastric lipomas at our institution after symptoms of gastrointestinal bleeding. With the advent of new radiologic investigations such as computed tomography and magnetic resonance imaging and advances in endoscopy, there are new approaches to identifying and managing these tumors. On further evaluation of the literature, we found that despite the availability of minimally invasive endoscopic techniques such as mucosal resection and submucosal dissection in the setting of large tumors, most patients tend to have to resort to surgical management. Conclusion: This case series underscores the rarity of gastric lipomas and their often-incidental discovery. Further investigation into endoscopic approaches for managing these tumors is needed, and additionally, there is a need to explore a potential association between gastric lipomas and malignancy, as chronic inflammation of the overlying mucosa may play a significant role.

A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association.

A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.

Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association.

Cardiovascular-kidney-metabolic health reflects the interplay among metabolic risk factors, chronic kidney disease, and the cardiovascular system and has profound impacts on morbidity and mortality. There are multisystem consequences of poor cardiovascular-kidney-metabolic health, with the most significant clinical impact being the high associated incidence of cardiovascular disease events and cardiovascular mortality. There is a high prevalence of poor cardiovascular-kidney-metabolic health in the population, with a disproportionate burden seen among those with adverse social determinants of health. However, there is also a growing number of therapeutic options that favorably affect metabolic risk factors, kidney function, or both that also have cardioprotective effects. To improve cardiovascular-kidney-metabolic health and related outcomes in the population, there is a critical need for (1) more clarity on the definition of cardiovascular-kidney-metabolic syndrome; (2) an approach to cardiovascular-kidney-metabolic staging that promotes prevention across the life course; (3) prediction algorithms that include the exposures and outcomes most relevant to cardiovascular-kidney-metabolic health; and (4) strategies for the prevention and management of cardiovascular disease in relation to cardiovascular-kidney-metabolic health that reflect harmonization across major subspecialty guidelines and emerging scientific evidence. It is also critical to incorporate considerations of social determinants of health into care models for cardiovascular-kidney-metabolic syndrome and to reduce care fragmentation by facilitating approaches for patient-centered interdisciplinary care. This presidential advisory provides guidance on the definition, staging, prediction paradigms, and holistic approaches to care for patients with cardiovascular-kidney-metabolic syndrome and details a multicomponent vision for effectively and equitably enhancing cardiovascular-kidney-metabolic health in the population.

Proportional troponin changes and risk for outcomes with intervention strategies in non-ST-elevation acute coronary syndrome across kidney function.

AIMS: This analysis evaluates whether proportional serial cardiac troponin (cTn) change predicts benefit from an early versus delayed invasive, or conservative treatment strategies across kidney function in non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Patients diagnosed with NSTE-ACS in the Veterans Health Administration between 1999 and 2022 were categorized into terciles (<20%, 20 to ≤80%, >80%) of proportional change in serial cTn. Primary outcome included mortality or rehospitalization for myocardial infarction at 6 and 12 months, in survivors of index admission. Adjusted hazard ratio (HR) with 95% confidence Intervals (95% confidence interval [CI]) were calculated for the primary outcome for an early invasive (≤24 h of the index admission), delayed invasive (>24 h of index admission to 90-days postdischarge), or a conservative management. RESULTS: Chronic kidney disease (CKD) was more prevalent (45.3%) in the lowest versus 42.2% and 43% in middle and highest terciles, respectively (p < 0.001). Primary outcome is more likely for conservative versus early invasive strategy at 6 (HR: 1.44, 95% CI: 1.37-1.50) and 12 months (HR: 1.44, 95% CI: 1.39-1.50). A >80% proportional change demonstrated HR (95% CI): 0.90 (0.83-0.97) and 0.93 (0.88-1.00; p = 0.041) for primary outcome at 6 and 12 months, respectively, when an early versus delayed invasive strategy was used, across CKD stages. CONCLUSIONS: Overall, the invasive strategy was safe and associated with improved outcomes across kidney function in NSTE-ACS. Additionally, >80% proportional change in serial troponin in NSTE-ACS is associated with benefit from an early versus a delayed invasive strategy regardless of kidney function. These findings deserve confirmation in randomized controlled trials.

Impact of comorbid heart failure among hospitalized patients with sarcoidosis: A United States population-based cohort study.

Background: There is paucity of data regarding the impact of concomitant heart failure (HF) on the in-hospital outcomes among hospitalized sarcoidosis patients. We aim to investigate the factors associated with concomitant HF and its impact on in-hospital outcomes among hospitalized sarcoidosis patients. Methods: We utilized the 2018-2020 National Inpatient Sample (NIS) Database in conducting this study. Multivariable logistic and linear regression models were used to examine the factors associated with HF and hospital-associated outcomes among patients with sarcoidosis. Results: A total of 36,864 hospitalized patients with sarcoidosis were identified, of which 24.78 % (n = 9135/36,864) had concomitant HF. Factors associated with concomitant HF were age (aOR 1.03; 95 % CI: 1.02-1.03, p value ≤ 0.001), black race (aOR 1.74; 95 % CI: 1.47-2.05, p value ≤ 0.001), not being female (aOR 0.79; 95 % CI: 0.69-0.91, p value ≤ 0.001), and arrhythmias (aOR 2.50; 95 % CI: 2.10-2.98, p value ≤ 0.001) specifically atrial fibrillation and ventricular tachycardia. Comorbidities associated with concomitant HF in this population were hyperlipidemia, obesity, coronary artery disease, cardiac device implantation history, and chronic kidney disease stage 1-4. Concomitant HF was not an independent predictor of in-hospital mortality or length of stay (LOS). However, age (aOR 1.04; 95 % CI, 1.03-1.06; p ≤ 0.001) and arrhythmia burden (aOR 2.08; 95 % CI, 1.47-2.95; p ≤ 0.001), specifically ventricular tachycardia and fibrillation, were independently associated with in-hospital mortality among sarcoidosis patients. Conclusion: Traditional cardiovascular risk factors were associated with concomitant HF among hospitalized sarcoidosis patients. Moreover, concomitant HF among sarcoidosis patients was not significantly associated with in-hospital mortality or LOS.

Injectable and biodegradable piezoelectric hydrogel for osteoarthritis treatment.

Osteoarthritis affects millions of people worldwide but current treatments using analgesics or anti-inflammatory drugs only alleviate symptoms of this disease. Here, we present an injectable, biodegradable piezoelectric hydrogel, made of short electrospun poly-L-lactic acid nanofibers embedded inside a collagen matrix, which can be injected into the joints and self-produce localized electrical cues under ultrasound activation to drive cartilage healing. In vitro, data shows that the piezoelectric hydrogel with ultrasound can enhance cell migration and induce stem cells to secrete TGF-ß1, which promotes chondrogenesis. In vivo, the rabbits with osteochondral critical-size defects receiving the ultrasound-activated piezoelectric hydrogel show increased subchondral bone formation, improved hyaline-cartilage structure, and good mechanical properties, close to healthy native cartilage. This piezoelectric hydrogel is not only useful for cartilage healing but also potentially applicable to other tissue regeneration, offering a significant impact on the field of regenerative tissue engineering.