Chronic Complications Research Articles

Surgical Treatment for Chronic Anterior Dislocation of the Radial Head.

Background: Surgical correction of chronic anterior dislocation of the radial head in paediatric patients is challenging, and they may experience re-dislocation or subluxation even after corrective surgery. We have been performing a radial shortening osteotomy combined with reconstruction of the annular and lateral collateral ligaments, and a corrective osteotomy of the ulna. The aim of this article is to describe our technique and outcomes at mid-term follow-up. Methods: This retrospective review included 10 paediatric patients with chronic anterior dislocation of the radial head that were surgically treated at our unit from January 2016 to July 2022. The dislocations were congenital in two patients, resulted from neglected Monteggia fractures in seven patients, and was idiopathic in one patient. The average age at surgery was 8.3 years. All patients underwent radial shortening osteotomy combined with reconstruction of the annular and lateral collateral ligaments, and a corrective osteotomy of the ulna. Outcomes with regards to period of follow-up, complications, arc of motion and the Kim elbow performance score were assessed. Results: The reduction of the radial head was maintained at the final follow-up (mean: 55 months). No acute or chronic complications occurred. The mean arc of flexion-extension improved from 124° to 140° while the arc of prono-supination decreased from 124° to 113°. The Kim elbow performance score was excellent in eight patients, fair in one and poor in one. Conclusions: A combination of radial shortening osteotomy, reconstruction of the annular and lateral collateral ligaments and corrective osteotomy of the ulna was able to maintain a stable reduction of the radial head with satisfactory elbow motion in the mid-term in paediatric patients with chronic anterior dislocation of the radial head regardless of the underlying cause. Level of Evidence: Level IV (Therapeutic).

Self-reported lifetime Hepatitis B virus testing, and vaccination uptake among people who inject drugs in Iran: a nationwide study in 2020.

Hepatitis B virus (HBV) infection is a silent epidemic among people who inject drugs (PWID). HBV testing and vaccination are important for PWID to reduce the risk of infection, prevent chronic complications and contribute to public health efforts in addressing HBV transmission. Our objective was to assess the self-reported lifetime uptake of HBV testing and vaccination among PWID in Iran and their associated factors. This cross-sectional study was conducted among 2,684 PWID in 11 large cities from July 2019 to March 2020 using a respondent-driven sampling method. Participants were interviewed face-to-face and asked about their lifetime experience of HBV testing and vaccination uptake as the outcome. Logistic regression models were built to identify related factors for reporting HBV testing and vaccination uptake. The prevalence of HBV testing and vaccination uptake among PWID was 14.2% (95% confidence intervals [CI]: 12.8-15.6) and 16.4% (95% CI: 14.9-18.1), respectively. Shared needles, syringes, or equipment in the past 12 months decreased the odds of reporting lifetime HBV testing uptake (Adjusted odds ratio [AOR]:0.46, 95% CI: 0.29-0.72). However, having an academic education (AOR: 1.89, 95% CI: 1.09-3.30) and lifetime experience of homelessness (AOR: 1.58, 95% CI: 1.21-2.06) increased the odds of reporting lifetime HBV vaccination uptake. Our study highlighted the low prevalence of HBV testing and vaccination uptake among PWID in Iran. It is essential to understand and address the obstacles preventing PWID from getting tested and vaccinated for HBV. Addressing these barriers could significantly reduce the burden of HBV among this socio-economically marginalized population.

Managing emotional and physical stress in sickle cell anemia: a review of effective strategies and approaches

Sickle cell anemia (SCA) is a genetic blood disorder characterized by recurrent pain episodes, chronic complications, and significant emotional and physical stress. This review article explores effective strategies for managing both the emotional and physical aspects of stress in SCA patients. A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, and Google Scholar, using keywords such as “sickle cell anemia,” “stress management,” “psychological support,” and “pain management.” Emotional stress in SCA arises from chronic pain, frequent hospitalizations, and disease uncertainty, leading to conditions such as anxiety and depression. Effective management of emotional stress involves a combination of psychological counseling, cognitive-behavioral therapy (CBT), and support groups, which help patients develop coping strategies and address the mental health challenges of living with a chronic illness. This review evaluates various psychological interventions and their impact on patient outcomes, emphasizing the need for integrated mental health support in the management of SCA. Physical stress in SCA is primarily due to acute vaso-occlusive crises and chronic pain, which require effective pain management and preventive measures. The review explores pharmacological treatments, such as opioids and hydroxyurea, as well as non-pharmacological approaches, including physical therapy and lifestyle modifications. Additionally, the article discusses innovative therapies like gene therapy and stem cell transplantation, which hold promise for long-term disease management.

Review on understanding of Astha Sthoulya Doshas and Sthoulya Lakshanas

Sthoulya is one among Santarpanotta Vikara and it is caused by Kapha Pradhana and Medodhushti. All the Santarponotta Nidanas and Medodhushti which will lead for Sthoulya. Sthoulya mainly features Chala Sphik Sthanah Udara Lambanam and Atisweda, Dhourgandy, Dourbalya as associated symptoms and these are considered as Sthoulya Doshas. Sthoulya leads to Kshudra Swasa and Alpaprana. Which implies the effect of Sthoulya on Pranavaha Srotas i.e., impairment in respiratory function which indicates Sthoulya does changes in normal breathing pattern. Life style disease and non-communicable diseases are major concern of health in present era. Obesity and Overweight are the major health care challenge that occupies the first place among non-communicable diseases creating an enormous socioeconomic and public health burden in most countries and is a worldwide epidemic. The worldwide prevalence of obesity nearly tripled between 1975 and 2020. Involvement of Meda, Agni, Kapha and Vata make the vicious curve of Samprapthi leading to chronic symptoms and complications like Ashta Sthoulya Doshas. Involved Agni and Ama in different stages which will make complicity to manage the Stholya and holistic approach is needed to treat the comorbidities like Ashta Sthoulya Doshas.

Cardioprotective effects of liposomal resveratrol in diabetic rats: unveiling antioxidant and anti-inflammatory benefits

ABSTRACT As a consequence of chronic hyperglycemia, diabetes complications and tissue damage are exacerbated. There is evidence that natural phytochemicals, including resveratrol, a bioactive polyphenol, may be able to reduce oxidative stress and improve insulin sensitivity. However, resveratrol's limited bioavailability hampers its therapeutic effectiveness. By using liposomes, resveratrol may be better delivered into the body and be more bioavailable. The objective of this study was to assess the cardioprotective potential of liposome-encapsulated resveratrol (LR) in a streptozotocin-induced (STZ) diabetic rat model. Adult male Wistar rats were categorized into five groups: control, diabetic, resveratrol-treated (40 mg/kg), liposomal resveratrol (LR)-treated (20 mg/kg) and liposomal resveratrol (LR)-treated (40 mg/kg) for a five-week study period. We compared the effects of LR to those of resveratrol (40 mg/kg) on various parameters, including serum levels of cardiac markers, tissue levels of pro-inflammatory cytokines, nuclear transcription factor, oxidative stress markers, and apoptotic markers. LR treatment in STZ-diabetic rats resulted in notable physiological improvements, including blood glucose regulation, inflammation reduction, oxidative stress mitigation, and apoptosis inhibition. LR effectively lowered oxidative stress and enhanced cardiovascular function. It also demonstrated a remarkable ability to suppress NF-kB-mediated inflammation by inhibiting the pro-inflammatory cytokines TNF-α and IL-6. Additionally, LR restored the antioxidant enzymes, catalase and glutathione peroxidase, thereby effectively counteracting oxidative stress. Notably, LR modulated apoptotic regulators, including caspase, Bcl2, and Bax, suggesting a role in regulating programmed cell death. These biochemical alterations were consistent with improved structural integrity of cardiac tissue as revealed by histological examination. In comparison, resveratrol exhibited lower efficacy at an equivalent dosage. Liposomal resveratrol shows promise in alleviating hyperglycemia-induced cardiac damage in diabetes. Further research is warranted to explore its potential as a therapeutic agent for diabetic cardiovascular complications and possible cardioprotective effects.

Clinical Burden and Healthcare Resource Utilization Associated With Managing Transfusion-dependent β-Thalassemia in England

PurposePatients with transfusion-dependent β-thalassemia (TDT) have reduced levels of β-globin, leading to ineffective erythropoiesis and iron overload. Patients with TDT depend on regular red blood cell transfusions (RBCTs) and iron chelation therapy for survival and management of disease- and treatment-related clinical complications. This study describes the clinical and economic burden in patients with TDT in England. MethodsThis longitudinal, retrospective study linked the Clinical Practice Research Datalink (CPRD) database with secondary care data from the Hospital Episode Statistics database to identify patients with a diagnosis of β-thalassemia between July 1, 2008, and June 30, 2018. Included patients had a diagnosis of β-thalassemia prior to the index date, ≥8 RBCTs per year for ≥2 consecutive years, and ≥1 year of follow-up data available from the index date. Each eligible patient was exact matched with up to 5 controls in the CPRD. Proportions of deaths and rates of mortality, acute and chronic complications, and healthcare resource utilization (HCRU) were calculated during the follow-up period. FindingsOf 11,359 identified patients with β-thalassemia, 237 patients with TDT met the eligibility criteria and were matched with 1184 controls. The mean age at the index date was approximately 25 years in the patient and control groups. The proportion of deaths (7.17% vs 1.18%; P < 0.05) and mortality rate (1.19 deaths per 100 person-years vs 0.20 deaths per 100 person-years) were higher among patients with TDT compared to controls. Endocrine complications and bone disorders were the most prevalent complications among patients with TDT (58.23%) and included osteoporosis (29.11%), diabetes mellitus (28.27%), and hypopituitarism (28.27%). Patients with TDT had a mean of 13.62 RBCTs per patient per year (PPPY). HCRU was substantially higher among patients with TDT, wherein patients with TDT had higher rates of prescriptions recorded in primary care (24.09 vs 8.61 PPPY), outpatient visits (16.69 vs 1.31 PPPY), and inpatient hospitalizations (17.41 vs 0.24 PPPY) than controls. Inpatient hospitalizations were primarily <1 day, with 16.62 events PPPY lasting <1 day and 0.79 events PPPY lasting ≥1 day. Patients with TDT aged ≥18 years had increased rates of mortality, clinical complications, and HCRU than those aged <18 years. ImplicationsPatients with TDT in England have higher mortality than matched controls, substantial disease-related clinical complications, and substantial HCRU. High mortality and clinical complications highlight the need for additional innovative therapies for TDT.

Efficacy of Lisosan G (fermented wheat) on reactive hypoglycemia after bariatric surgery.

post-bariatric hypoglycemia (PBH) is considered a chronic complication after gastric bypass (RYGB) impacting roughly 30% of patients. Current treatments often focus on nutritional interventions to reduce the frequency of episodes. This prospective study evaluated the effectiveness of Lisosan G (LG), a fermented wheat-based supplement added to the diet, in mitigating PBH episodes and elucidating its mechanism of action on the gut-pancreas axis. twenty subjects with PBH, who had undergone RYGB between 2015 and 2018, were enrolled. Subjects underwent clinical examination, blood test, and a 3-hour oral glucose load test (OGTT). Then, they were monitored for 2-weeks on a free diet with continuous glucose monitoring (CGM), which was extended for another 2-weeks after introduction of LG supplementation (5g, twice daily) on the same diet. Finally, subjects repeated OGTT and blood test. PBH was defined as interstitial glucose ≤54mg/dl. after treatment, a marked reduction in PBH time was observed (75[23-113] vs 16 [0-33], minutes, p<0.001). During OGTT, there was an increase in glucose nadir (44±11 vs 56±10, mg/dl, p=0.038), and a significantly decrease in total GLP-1 AUC (7.6±4.1 vs 6.5±3.8, nmol/L*min, p=0.043), in potentiation factor ratio (p=0.037) and in total insulin AUC (57±12 vs 49±9, nmol/L*min, p=0.043). LG effectively reduces PBH frequency and duration, probably by attenuating GLP-1 concentrations and leading to a decrease in the second phase of insulin secretion in response to glucose. These findings underscore the promise of LG as a novel adjunct therapy for PBH, particularly when added to the diet, and emphasize the need for further exploration into its microbiota-modulating and anti-inflammatory effects.

Rational design and synthesis of novel N-benzylindole-based epalrestat analogs as selective aldose reductase inhibitors: An unexpected discovery of a new glucose-lowering agent (AK-4) acting as a mitochondrial uncoupler

Diabetes mellitus is one of the most frequent metabolic diseases associated with hyperglycemia. Although antidiabetic drugs reduce hyperglycemia, diabetic patients suffer from abnormal fluctuations in blood glucose levels leading to the onset of long-term complications. Aldose reductase inhibitors are considered a promising strategy for regulating the occurrence of diabetic-specific comorbidities. So far, epalrestat is the only drug being approved in Asian countries. In this paper, we ground our research in discovering novel epalrestat analogs that prevent chronic complications and normalize hyperglycemia. Herein, we describe the rational design and synthesis of four novel 4-thiazolidinone acetic acid derivatives (AK-1-4) being evaluated for their efficacy against aldose reductase from rat lenses and their specificity over the homologous enzyme from rat kidneys. AK-1-4 were also tested against human recombinant protein tyrosine phosphatase 1B as a key target in insulin sensitization and towards the closely related T-cell-derived enzyme. Docking analyses suggested possible binding modes on examined targets. The promising inhibitory profile of AK-4 sparked our interest in exploring its effect on the insulin-receptor signaling pathway and its ability to stimulate glucose uptake under ex vivo conditions. We further investigated the ability of AK-4 to target mitochondria acting as an uncoupling agent and impairing mitochondrial membrane potential. Herein, we report for the first time a new glucose-lowering agent (AK-4) that can combine alleviation for chronic diabetic complications without off-target adverse effects and antihyperglycemic efficacy through controlled mitochondrial uncoupling activity. Pharmacokinetic and toxicity studies in silico revealed optimal properties of AK-4 for oral administration without potential side effects.

A diverse hidradenitis suppurativa cohort: a retrospective cross-sectional study of 13,130 patients from a large US healthcare system database from 1995-2022

BackgroundMost epidemiological studies of hidradenitis suppurativa (HS) have described homogeneous patient populations. ObjectiveTo characterize demographics, modifiable health behaviors, and comorbidities of HS patients within a diverse cohort. MethodsA retrospective cross-sectional study of 13,130 HS patients within a healthcare system was conducted. ResultsA female sex bias of ∼3:1 in all racial/ethnic subgroups was observed. Black/African American (AA) patients had a lower age at HS diagnosis than White patients (37.1 years vs 39.4 years, P<0.001). A higher proportion of Black/AA females than White females with HS had BMI in the obese range (69.9% vs 56.5%; P=0.03). In contrast, fewer Black/African American males with HS had a BMI in the obese range compared to White males (51.4% vs. 61.0%; P<0.001). More Black/AA patients than White patients with HS had congestive heart failure (OR=2.10, CI=1.19-3.78; P<0.05), chronic pulmonary disease (OR=1.34; CI=1.02-1.78; P<0.05), diabetes with chronic complication (OR=1.73; CI=1.16-2.60; P<0.05), renal disease (OR=2.66; CI=1.67-4.34; P<0.05), and Charlson Comorbidity Index score ≥4 (OR=1.67; CI=1.09-2.58; P<0.05). Furthermore, male patients were more likely than female patients to have renal disease (OR=2.62; CI 1.66-4.14; P<0.05). LimitationsA single-center study. ConclusionSubgroups of HS patients had significant differences in demographics, risk factors, and comorbid conditions.

Aldose reductase with quinolone antibiotics interaction: In vitro and in silico approach of its relationship with diabetic complications

Aldose reductase (AR, EC1.1.1.21), a member of the aldo-keto reductase family, is critically implicated in the pathogenesis of chronic complications associated with diabetes mellitus, including neuropathy, nephropathy, and retinopathy. Hyperglycemia-induced AR overactivity results in intracellular sorbitol accumulation, NADPH depletion, and oxidative stress. Consequently, AR is recognized as a key mediator of oxidative and inflammatory signaling pathways involved in diverse human pathologies such as cardiovascular diseases, inflammatory disorders, and cancer. This has sparked renewed interest in developing novel AR inhibitors (ARIs) with enhanced therapeutic profiles. In this study, we evaluated the inhibitory potential of five quinolone antibiotics-gatifloxacin, lomefloxacin, nalidixic acid, norfloxacin, and sparfloxacin-as ARIs relevant to various physiological and pathological conditions. Through comprehensive in vitro and in silico analyses, we explored these antibiotics' binding interactions and affinities within the AR active site. Our findings reveal that these quinolones moderately inhibit AR at micromolar concentrations, with inhibition constants (KIs) ranging from 1.03 ± 0.13 μM to 4.12 ± 0.51 μM, compared to the reference drug epalrestat (KI of 0.85 ± 0.06 μM). The combined in vitro and in silico results underscore significant interactions between these drugs and AR, suggesting their potential as therapeutic agents against the aforementioned pathological conditions. Furthermore, these insights will aid in optimizing clinical dosing regimens and mitigating unexpected drug-drug interactions when these antibiotics are co-administered with other treatments.

Diabetic Peripheral Neuropathy and Glycemia Risk Index in Type 2 Diabetes: A Cross-Sectional Study.

Diabetic peripheral neuropathy (DPN) is a prevalent chronic complication of diabetes which is linked to chronic hyperglycemia and glycemic variability. This study aimed to investigate the association between the glycemia risk index (GRI) and DPN in patients with type 2 diabetes mellitus (T2DM) using continuous glucose monitoring (CGM) data. From 2019 to 2023, 862 adults diagnosed with T2DM were enrolled at a tertiary care diabetes center in Ningbo, China. The medical history and laboratory parameters were recorded. Neurophysiological examinations were performed to evaluate DPN. The CGM data were recorded for 14 days, and the GRI was calculated based on these data. Multivariate logistic regression analyses were conducted to assess the odds ratio (OR) for DPN with an increased GRI. The prevalence of DPN in the ascending GRI quartiles was 41.6%, 47.9%, 49.1%, and 59.5%, respectively (P for trend < 0.001). In the multivariable logistic analysis, the highest GRI quartile exhibited a 63% greater risk of DPN (OR 1.631, 95% CI: 1.071 to 2.484, P = 0.023) than the lowest quartile after adjusted for age, sex, body mass index, diabetes duration, blood pressure, creatinine, urinary albumin-to-creatinine ratio, lipid profile and glycated hemoglobin. High GRI levels, as measured by CGM, were associated with a greater likelihood of DPN in T2DM patients.

Two-year outcomes of Micra AV leadless pacemakers in the Micra AV CED study.

Leadless pacing is a safe and effective alternative to transvenous pacing for bradycardia. Micra AV is a leadless, single-device solution that provides atrioventricular synchronous ventricular pacing therapy. Early results from the Micra AV CED study showed reductions in short-term complications associated with the Micra AV leadless pacemaker among US Medicare patients. The objective of this study is to compare chronic complications, re-interventions, and all-cause mortality at 2 years between patients implanted with a Micra AV leadless pacemaker and a traditional dual-chamber transvenous (DC-TV) pacemaker. Patients implanted with a Micra AV leadless pacemaker (n = 7552) or a DC-TV pacemaker (n = 110 558) in 2020 and 2021 were identified using device registration-linked Medicare administrative claims data. Competing risk models compared the unadjusted and propensity score overlap weight-adjusted complication, re-intervention, and all-cause mortality rates of Micra AV and DC-TV patients at 2 years. Micra AV patients had significantly more comorbidities (end-stage renal disease 14.9 vs. 2.0%, P < 0.0001; renal dysfunction 47.9 vs. 34.2%, P < 0.0001; diabetes 46.2 vs. 38.3%, P < 0.001; congestive heart failure 41.4 vs. 30.6%, P < 0.0001). Two years post-implant, Micra AV patients had lower complication rates [adjusted 5.3 vs. 9.6%, hazard ratio (HR): 0.54, 95% confidence interval (CI) 0.49-0.61, P < 0.0001] and lower re-intervention rates (adjusted 3.5 vs. 5.6%, HR: 0.62, 95% CI 0.54-0.72, P < 0.0001) than DC-TV patients. Upgrades to cardiac resynchronization therapy were low in both groups (adjusted 1.6 vs. 1.7%, P = 0.40), as were Micra AV upgrades to a dual-chamber system (adjusted 1.4%). All-cause mortality rates remained higher in Micra AV than in DC-TV patients (unadjusted HR: 2.48, 95% CI 2.35-2.62, P < 0.0001; adjusted HR: 1.53, 95% CI 1.44-1.62, P < 0.0001). Patients implanted with Micra AV had lower complications and re-intervention rates at 2 years than patients implanted with a traditional DC-TV pacemaker. All-cause mortality remained higher in Micra AV patients, likely due to their higher comorbidity burden and other differences in baseline characteristics. ClinicalTrials.gov ID NCT04235491.

Health disparities in cirrhosis care and liver transplantation.

Morbidity and mortality from cirrhosis are substantial and increasing. Health disparities in cirrhosis and liver transplantation are reflective of inequities along the entire spectrum of chronic liver disease care, from screening and diagnosis to prevention and treatment of liver-related complications. The key populations experiencing disparities in health status and healthcare delivery include racial and ethnic minority groups, sexual and gender minorities, people of lower socioeconomic status and underserved rural communities. These disparities lead to delayed diagnosis of chronic liver disease and complications of cirrhosis (for example, hepatocellular carcinoma), to differences in treatment of chronic liver disease and its complications, and ultimately to unequal access to transplantation for those with end-stage liver disease. Calling out these disparities is only the first step towards implementing solutions that can improve health equity and clinical outcomes for everyone. Multi-level interventions along the care continuum for chronic liver disease are needed to mitigate these disparities and provide equitable access to care.

Development and Validation of an Educational Intervention Using a Mobile Social Networking for People With Diabetes: A Brazilian Experience

Introduction Type 2 Diabetes Mellitus is a metabolic disease with high morbidity and mortality rate and increasing prevalence, which leading to a significant decrease in quality of life. Objective To develop and validate a intervention program of non-pharmacological interventions for self-care and a healthy lifestyles using a mobile social networking for people diagnosed with type 2 diabetes assisted by a Primary Health Care service. Method Applied technological research with mixed methodology. The method chosen for the development of the set of interventions was the Contextualized Instructional Design (DIC), and the validation was carried out by the Delphi Method. Results In the developed program, patients received information through posts in a WhatsApp® group called “Routine in Day.” In this virtual environment, the content was transmitted and discussed through text messages, videos, audios and images about Diabetes Mellitus, healthy eating, physical activity, correct use of medications, sleeping habits, mental health, drug control and guidance on the reduction of chronic complications based on scientific evidence. With regard to validation, after two rounds of the Delphi method, the Content Validity Index was above the standard in the literature. Conclusion: The current intervention proposal proved to be a useful and accessible tool, with the objective of contributing to the control of Diabetes Mellitus, in addition to facilitating communication between the team and patients.

COMPLICAÇÕES CRÔNICAS DO DIABETES MELLITUS TIPO 2

Diabetes mellitus is defined as a chronic non-communicable disease (NCD), being a syndrome characterized by persistent hyperglycemia, resulting from metabolic disorders, which may occur due to the destruction of insulin-producing beta cells or resistance to insulin action. The increase in plasma glucose occurs due to defects in the secretion and/or action of insulin produced by the pancreas, and can be subdivided into three main types: Type 1 Diabetes mellitus (autoimmune), Type 2 Diabetes mellitus (insulin resistant) and Diabetes gestational mellitus. Diabetes is characterized by multiple complications, acute and chronic (divided into microvascular and macrovascular), which constitute an important cause of early mortality. Chronic microvascular complications are associated with specific injuries caused by difficulty in passing blood to the endothelium. This obstruction occurs due to chronic hyperglycemia that triggers endothelial inflammation, resulting in the production of advanced glycolysis products, leading to oxidative stress, inflammation and the appearance of microthrombi, making this passage difficult. Macrovascular complications, in addition to hyperglycemia, are also related to problems such as dyslipidemia, systemic arterial hypertension and smoking. Such factors can lead to stroke, acute myocardial infarction and peripheral arterial obstructive disease. This work proposes a critical review of the existing literature on the chronic complications of Type 2 Diabetes mellitus, highlighting screening, prevention and treatment measures. It is concluded that technical and clinical knowledge about the pathophysiology and alternative interventions is essential for the immediate and comprehensive care of patients with Type 2 Diabetes mellitus, as well as the prevention of its chronic complications.

Real-world evidence of implanting leadless pacemakers after transcatheter aortic valve implantation procedures

Abstract Background Conduction disturbances can be a complication of Transcatheter Aortic Valve Implantation (TAVI) procedures, for which transvenous pacemakers (TVPs) are recommended. Leadless pacemakers (LPs) are a safe alternative to TVPs in a pacemaker-indicated population, but little is known about their use for TAVI-related conduction disturbances. Purpose To examine rates of pacemaker implantation post-TAVI, compare complications, all-cause mortality, and ventricular pacing rates in LP vs. TVP patients, and assess pacemaker deactivations/upgrades in LP patients. Methods Data from Optum’s de-identified Clinformatics Data Mart Database linked to a device registry between 2016 and 2021 were used to identify patients with TAVI procedures that are subsequently implanted with an LP or a TVP. Claims data were used to assess complications and all-cause mortality; device-reported parameters were used to calculate VP rates and deactivations. Complication rates, all-cause mortality, ventricular pacing rates, and device deactivations were calculated for patients with a pacemaker implant between 7 days before and 90 days after TAVI. Chronic complication rates, defined as complications with the potential to occur outside the acute peri- or post-procedural period, were assessed at 1 year. Regressions were used to compare complications and all-cause mortality, adjusting for patient characteristics. Results In a cohort of 18,073 patients with a TAVI procedure, 11.7% were implanted with a pacemaker at 1 year post-TAVI; 76.7% of implants occurred within 7 days. LPs comprised 7.2% of the total pacemaker implants observed. Of those LPs in the registry, around 25% have VDD capability. LP patients were older (avg. 84 LP, 82 TVP, p=0.02) and were more likely to have atrial fibrillation, end-stage or chronic kidney disease, and ventricular arrhythmias. Of patients implanted with a pacemaker within 90 days post-TAVI (LP N=122, TVP N=1,779), there were no differences in 30-day complication rates (12.3% LP, 15.6% TVP, unadj. p=0.33, adj. p=0.27). LP had fewer chronic complications than TVP (0.8% LP, 9.4% TVP, unadj. p=0.02, adj p=0.02) though the sample size was small. LP patients had higher unadjusted 30-day all-cause mortality (4.1% LP, 1.0% TVP, unadj. p=0.01, adj. p=0.06), reflecting the higher acuity of LP patients. At both 30 days and 1 year post-implant, most patients (85.3% LP, 72.7% TVP) continued to receive pacing support (ventricular pacing &amp;gt;10%). TVP patients were more likely than LP patients to be pacing dependent (ventricular pacing ≥90%) at both 30 days (53.8% vs. 29.4%) and 1 year (44.7% vs. 35.7%) post-implant. There were no observed deactivations/upgrades in LP patients at 1 year. Conclusion LPs, when used concomitantly with TAVI procedures, show similar acute and lower chronic complication rates compared to patients treated with TVPs implanted with TAVI. Most patients who received a pacemaker post-TAVI continue to receive pacing support.Acute and Chronic complicationsVentricular pacing

Left atrial substrate modification for persistent atrial fibrillation and left atrial macro or microreentrant tachycardia using a single-shot pulsed field ablation system - a single centre case series

Abstract Background Pulsed field ablation (PFA) is a novel ablation technique for pulmonary vein isolation (PVI) in patients with paroxysmal and persistent atrial fibrillation. However, data for efficacy and safety of PFA for left atrial substrate modification in patients with long-standing persistent atrial fibrillation (AF) and macro- as well as microreentrant atrial tachycardia (AT) is scarce. Aim Here we provide a retrospective, single-centre case series regarding efficacy and safety of left atrial substrate modification, using a single-shot PFA system. Methods and Results Over a period of 6 months, 8 patients with long-standing persistent AF and AT underwent Re-PVI with left atrial substrate modification using a single-shot PFA system. Median age was 63 years (IQR 58 - 75), and 4/8 of patients were female. Time from first diagnosis of AF was 7 years (IQR 4 –10). All but 1 patient underwent previous PVI (IQR 1-3) with (5/7) or without (2/7) prior substrate modification using radiofrequency ablation. On transthoracic echocardiography, all patients showed severe left- and right-atrial enlargement, with LA volume of 58 ml/m2 (IQR 49.7–72) and RA diameter of 62 mm (IQR 55-75). In 8 patients, 9 ATs and 2 typical flutters were treated with PFA. Following PVI, additional posterior wall isolation was performed in 6/8 patients, roof in 6/8, and anterior wall (between superior mitral anulus and RSPV) in 4/8 patients. In addition, 2/8 patients had cavotricuspid isthmus ablation for typical atrial flutter. All patients received atropine prior to PVI, as well as bolus of nitro-glycerine prior to PFA of anterior wall and/or cavotricuspid isthmus. Acute success rate was 100% and all ATs as well as typical flutter terminated with PFA. After median follow-up time of 88 days (IQR 61-112), 3 patients had a documented recurrence of AF/AT, in 2 of which electrical cardioversion was necessary. We observed no acute and/or chronic complications following PFA, i.e. no pericardial effusion/tamponade, TIA/stroke, myocardial infarction, coronary artery spasm, AV-block, bleeding, or atrioesophageal fistula. Conclusion In this small, single-centre case series, left atrial substrate modification for long-standing persistent AF and AT using a single-shot PFA system was safe and showed an excellent acute success rate.

One-year risk of all-cause death and major cardiovascular events in patients presenting with hypertensive crisis. A report from a global federated research health network

Abstract Background Few data are available about the clinical course of patients presenting with hypertensive crisis who are discharged alive from hospital. Purpose To assess the long-term risk of adverse events in patients with hypertensive crises. Methods Retrospective study utilizing a research health network. Based on the ICD-10-CM codes recorded between 2000 and 2022, from 85 health care associations mainly located in the United States, patients with hypertensive crisis were subdivided into hypertensive urgencies (I16.0) and hypertensive emergencies (I16.1). In those with hypertensive emergencies, the type of target organ damage was reported, ie. central nervous system (ischemic stroke, hypertensive encephalopathy, intracerebral hemorrhages), cardiovascular (CVS: myocardial infarction (MI), heart failure (HF), aorta dissection (AD)), or renal (acute kidney failure). Primary outcomes were the one-year risks of all-cause death, and major cardiovascular events (MACE: MI, stroke, cardiac arrest, AD, and HF). Secondary outcomes were the risks for each type of MACE. Cox regression analysis after propensity score matching (PSM) 1:1 was used to produce hazard ratios (HRs) and 95% Confidence Intervals (95%CIs). Results Overall, we identified 25 294 patients with hypertensive emergency (age 62.4±15.7, 46.1% females) and 21,737 patients with hypertensive urgency (age 63.5±17.2, 55.5% females). Patients with hypertensive emergency were more likely males, Black or African American origin and showed a higher prevalence of chronic hypertensive-related complications, vs. those with hypertensive urgency. After PSM, patients with hypertensive emergency showed a higher risk of all-cause death (HR, 1.34, 95%CI 1.25-1.44) and MACE (HR 4.09, 95%CI 3.87-4.33), vs. those with hypertensive urgency. Of the secondary outcomes, patients with hypertensive emergency had increased risks of MI (HR 3.33, 95%CI 3.03-3.67), stroke (HR 4.73, 95%CI 4.33-5.17), cardiac arrest (HR 1.30, 95%CI 1.07-1.58), AD (HR 5.49, 95%CI 3.90-7.73), and HF (HR 3.01, 95%CI 2.74-3.14). All the different types of organ involvement during the hypertensive emergency were each associated with similar long-term risks of adverse events (Figure 1). Conclusion Patients with hypertensive emergency have a high long-term risk of MACE and all-cause death. Preventing the onset of target organ damage in patients with hypertensive crisis is crucial to mitigate their long-term risk of adverse events.

Assessment of the Therapeutic Potential of Enhancer of Zeste Homolog 2 Inhibition in a Murine Model of Bronchiolitis Obliterans Syndrome.

Bronchiolitis obliterans syndrome (BOS) is a chronic complication following lung transplantation that limits the long-term survival. Although the enhancer of zeste homolog 2 (EZH2) is involved in post-transplantation rejection, its involvement in BOS pathogenesis remains unclear. We aimed to investigate the therapeutic potential of EZH2 inhibition in BOS. 3-deazaneplanocin A (DZNep) was administered intraperitoneally to heterotopic tracheal transplant recipient model mice. Tracheal allografts were obtained on days 7, 14, 21, and 28 after transplantation. The obstruction ratios of the DZNep and control groups on days 7, 14, 21, and 28 were 15.1% ± 0.8% vs. 20.4% ± 3.6% (p = 0.996), 16.9% ± 2.1% vs. 67.7% ± 11.5% (p < 0.001), 47.8% ± 7.8% vs. 92.2% ± 5.4% (p < 0.001), and 60.0% ± 9.6% vs. 95.0% ± 2.3% (p < 0.001), respectively. The levels of interleukin (IL)-6 and interferon-γ on day 7 and those of IL-2, tumor necrosis factor, and IL-17A on days 14, 21, and 28 were significantly reduced following DZNep treatment. DZNep significantly decreased the number of infiltrating T-cells on day 14. In conclusion, DZNep-mediated EZH2 inhibition suppressed the inflammatory reactions driven by pro-inflammatory cytokines and T cell infiltration, thereby alleviating BOS symptoms.

Nontargeted urine metabolomic analysis of acute intermittent porphyria reveals novel interactions between bile acids and heme metabolism: New promising biomarkers for the long-term management of patients.

Acute intermittent porphyria is an inherited error of heme synthesis. The underlying pathophysiology, involving mainly hepatic heme synthesis, is poorly understood despite its occurrence, and the severity of acute porphyria attack is still difficult to control. A better understanding of the interactions between heme synthesis and global metabolism would improve the management of AIP patients. An untargeted metabolomic analysis was performed on the urine of 114 patients with overt AIP and asymptomatic carriers using liquid chromatography coupled to high-resolution mass spectrometry. The collected data were analyzed by combining univariate and multivariate analyses. A total of 239 metabolites were annotated in urine samples by matching chromatographic and mass spectral characteristics with those from our chemical library. Twenty-six metabolites, including porphyrin precursors, intermediates of tryptophan or glycine metabolism and, unexpectedly, bile acids, showed significant concentration differences between the phenotypic groups. Dysregulation of bile acid metabolism was confirmed by targeted quantitative analysis, which revealed an imbalance in favor of hydrophobic bile acids associated with changes in conjugation, which was more pronounced in the severe phenotype. Using a random forest model, the cholic acid/chenodeoxycholic acid ratio enables the differential classification of severe patients from other patients with a diagnostic accuracy of 84%. The analysis of urine samples revealed significant modifications in the metabolome of AIP patients. Alteration in bile acids provides new insights into the pathophysiology of chronic complications, such as primary liver cancer, while also providing new biomarker candidates for predicting the most severe phenotypes.