Risk Of Adverse Events Research Articles

Low subcutaneous adipose tissue and myosteatosis are prognostic factors after allogeneic hematopoietic stem cell transplantation

ObjectiveAllogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only curative treatment option for several hematological neoplasms. This study aimed to assess the parameters of body composition as predictors of posttransplant overall survival (OS) and adverse events in patients with leukemia, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPN). MethodsThis was a retrospective study of 122 adult patients who underwent their first allo-HSCT. The CT-based semi-automated measurement of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), visceral-to-subcutaneous fat ratio (VSR), sarcopenia in terms of skeletal muscle index (SMI), and myosteatosis based on the skeletal muscle radiation attenuation (SM-RA) was performed. Cox regression analysis was used to assess the association of body composition parameters with OS. ResultsIn the univariate analysis, low SAT and myosteatosis were associated with lower OS (hazard ratio [HR] 2.02, 95% confidence interval [CI] 1.16–3.51, p = 0.01) and (HR 2.50, 95% CI 1.48 – 4.25, p=< 0.001), respectively. This association remained significant after adjusting for relevant covariates, with HR 2.32, 95% CI 1.23 – 4.38, p=0.01 and HR 2.86, 95% CI 1.51 – 5.43, p=< 0.001, respectively. On the contrary, VAT, VSR, sarcopenia, and sarcopenic obesity were not statistically significant in OS. Severe post-transplant adverse events were more common in the low SAT group (odds ratio [OR] 3.12, 95% CI 1.32– 7.40, p=0.01) and OR 3.17, 95% CI 1.31 – 7.70, p=< 0.01 in the age- and sex-adjusted analysis. ConclusionLow SAT and myosteatosis may contribute to an increased risk of mortality, while low SAT appears to increase the risk of severe post-transplant adverse events.

Effects of a ketogenic diet on motor function and motor unit number estimation in aged C57BL/6 mice

ObjectivePathological, age-related loss of muscle function, commonly referred to as sarcopenia, contributes to loss of mobility, impaired independence, as well as increased risk of adverse health events. Sarcopenia has been attributed to changes in both neural and muscular integrity during aging. Current treatment options are primarily limited to exercise and dietary protein fortification, but the therapeutic impact of these approaches are often inadequate. Prior work has suggested that a ketogenic diet (KD) might improve healthspan and lifespan in aging mice. Thus, we sought to investigate the effects of a KD on neuromuscular indices of sarcopenia in aged C57BL/6 mice. DesignA randomized, controlled pre-clinical experiment consisting of longitudinal assessments performed starting at 22-months of age (baseline) as well as 2, 6 and 10 weeks after the start of a KD vs. regular chow intervention. SettingPreclinical laboratory study. Sample sizeThirty-six 22-month-old mice were randomized into 2 dietary groups: KD [n = 22 (13 female and 9 male)], and regular chow [n = 15 (7 female and 8 male)]. MeasurementsMeasures included body mass, hindlimb and all limb grip strength, rotarod for motor performance, plantarflexion muscle contractility, motor unit number estimations (MUNE), and repetitive nerve stimulation (RNS) as an index of neuromuscular junction transmission efficacy recorded from the gastrocnemius muscle. At end point, muscle wet weight and blood samples were collected to assess blood beta-hydroxybutyrate levels. Statistical analysisPrimary analyses were two-way mixed effects ANOVA (diet and time × diet) to determine the effect of a KD on indices of motor function (grip, rotarod) and indices of motor unit (MUNE) and muscle (contractility) function. ResultsBeta-hydroxybutyrate (BHB) was significantly higher at 10 weeks in mice on a KD vs control group (0.83 ± 0.44 mmol/l versus 0.42 ± 0.21 mmol/l, η2 = 0.265, unpaired t-test, p = 0.0060). Mice on the KD intervention demonstrated significantly increased hindlimb grip strength (diet, p = 0.0001; time × diet, p = 0.0030), all limb grip strength (diet, p = 0.0005; time × diet, p = 0.0523), and rotarod latency to fall (diet, p = 0.0126; time × diet, p = 0.0021). Mice treated with the KD intervention also demonstrated increased MUNE (diet, p = 0.0465; time × diet, p = 0.0064), but no difference in muscle contractility (diet, p = 0.5248; time × diet, p = 0.5836) or RNS (diet, p = 0.3562; time × diet, p = 0.9871). ConclusionKD intervention improved neuromuscular and motor function in aged mice. This pre-clinical work suggests that further research is needed to assess the efficacy and physiological effects of a KD on indices of sarcopenia.

The burden of cardiovascular disease and risk for subsequent major adverse cardiovascular events in survivors of childhood cancer: a prospective, longitudinal analysis from the St Jude Lifetime Cohort Study

The burden of cardiovascular disease and risk for subsequent major adverse cardiovascular events in survivors of childhood cancer: a prospective, longitudinal analysis from the St Jude Lifetime Cohort Study

Detectable troponin below the 99th percentile predicts survival in patients undergoing coronary angiography

BackgroundCardiac troponin I (cTnI) above the 99th percentile is associated with an increased risk of major adverse events. Patients with detectable cTnI below the 99th percentile are a heterogeneous group with a less well-defined risk profile. The purpose of this study is to investigate the prognostic relevance of detectable cTnI below the 99th percentile in patients undergoing coronary angiography. MethodsThe study included 14,776 consecutive patients (mean age of 65.4 ± 12.7 years, 71.3 % male) from the Essen Coronary Artery Disease (ECAD) registry. Patients with cTnI levels above the 99th percentile and patients with ST-segment elevation acute myocardial infarction were excluded. All-cause mortality was defined as the primary endpoint. ResultsDetectable cTnI below the 99th percentile was present in 2811 (19.0 %) patients, while 11,965 (81.0 %) patients were below detection limit of the employed assay. The mean follow-up was 4.25 ± 3.76 years. All-cause mortality was 20.8 % for patients with detectable cTnI below the 99th percentile and 15.0 % for those without detectable cTnI. In a multivariable Cox regression analysis, detectable cTnI was independently associated with all-cause mortality with a hazard ratio of 1.60 (95 % CI 1.45–1.76; p < 0.001). There was a stepwise relationship with increasing all-cause mortality and tertiles of detectable cTnI levels with hazard ratios of 1.63 (95 % CI 1.39–1.90) for the first tertile to 2.02 (95 % CI 1.74–2.35) for the third tertile. ConclusionsDetectable cTnI below the 99th percentile is an independent predictor of mortality in patients undergoing coronary angiography with the risk of death growing progressively with increasing troponin levels.

Eosinophilic esophagitis and risk of incident major adverse cardiovascular events: a nationwide matched cohort study.

Inflammatory diseases have been associated with an increased cardiovascular risk. However, data on incident major adverse cardiovascular events (MACE) from large population-based cohorts of patients with eosinophilic esophagitis (EoE) is lacking. This study included all Swedish adults with EoE without a record of previous cardiovascular disease (CVD) (1990-2017, N = 1546) with follow-up until 2019. Individuals with EoE were identified from prospectively recorded histopathology reports from all Swedish pathology departments (n = 28). EoE patients were matched at index date for age, sex, calendar year and county with up to five general population reference individuals (N = 7281) without EoE or CVD. Multivariable-adjusted hazard ratios (aHRs) for MACE (ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality) were calculated using Cox proportional hazards models. Full sibling comparisons and adjustment for cardiovascular medication were performed. During a median follow-up of 6.0years, we observed 65 incident MACE in patients with EoE (6.4/1000 person-years (PY)) and 225 in reference individuals (4.7/1000 PY). EoE was not associated with a higher risk of MACE (aHR = 1.14, 95% CI = 0.86-1.51) or any of its components. No differences between age, sex and follow-up time were observed. The results remained stable in sensitivity analyses, including when adjusting for relevant cardiovascular medications and a full sibling comparison. In this large population-based cohort study, patients with EoE had no increased risk of MACE compared to reference individuals and full siblings. The results are reassuring for patients with EoE.

Comparative Efficacy and Safety of Potassium-Competitive Acid Blockers vs. Proton Pump Inhibitors for Peptic Ulcer with or without Helicobacter pylori Infection: A Systematic Review and Network Meta-Analysis

Novel potassium-competitive acid blockers (P-CABs) have emerged as effective acid-suppressive drugs in recent years, replacing proton pump inhibitors (PPIs). We aim to compare the efficacy and safety of P-CABs versus PPIs in the treatment of peptic ulcers with or without Helicobacter pylori (H. pylori) infection. We searched in PubMed, Embase, WOS, Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang databases (all years up to January 2024). Efficacy and safety outcomes were evaluated using odds ratio (OR) and 95% confidence intervals (CI). The Surface Under the Cumulative Ranking (SUCRA) probabilities were used to rank each intervention. Among 14,056 studies screened, 56 studies involving 9792 participants were analyzed. Vonoprazan demonstrated the best efficacy in ulcer healing rate and H. pylori eradication rate (SUCRA = 86.4% and 90.7%, respectively). Keverprazan ranked second in ulcer healing rates (SUCRA = 76.0%) and was more effective in pain remission rates (SUCRA = 91.7%). The risk of adverse events was low for keverprazan (SUCRA = 11.8%) and tegoprazan (SUCRA = 12.9%), and moderate risk for vonoprazan (SUCRA = 44.3%) was demonstrated. Compared to lansoprazole, vonoprazan exhibited a higher risk of drug-related adverse events (OR: 2.15; 95% CI: 1.60–2.89) and serious adverse events (OR: 2.22; 95% CI: 1.11–4.42). Subgroup analysis on patients with H. pylori-positive peptic ulcers showed that vonoprazan was at the top of the SUCRA rankings, followed by keverprazan. Vonoprazan showed superior performance in peptic ulcers, especially for patients with H. pylori-positive peptic ulcers. However, the risk of adverse events associated with vonoprazan should be noted. Keverprazan has also shown good therapeutic outcomes and has performed better in terms of safety.

Percutaneous radiologic gastrostomy versus percutaneous endoscopic gastrostomy for enteral feeding: A systematic review and meta-analysis.

Percutaneous radiological gastrostomy (PRG) and percutaneous endoscopic gastrostomy (PEG) are minimally invasive gastrostomy techniques for individuals requiring prolonged enteral feeding. Recent meta-analyses concerning their efficacy and safety mainly included retrospective studies and yielded conflicting results. This meta-analysis of randomized controlled trials (RCTs) aimed to compare efficacy, safety, and procedure time between PRG and PEG for enteral feeding. MEDLINE, Embase, and the Cochrane Library were searched for eligible RCTs comparing PRG and PEG for enteral feeding through February 23, 2024. The primary outcome was technical success. The secondary outcomes were (1) adverse events (AEs), (2) mortality, and (3) procedure time. We used the random-effects model to calculate pooled risk ratio (RR) and mean difference (MD) with corresponding 95% CIs for dichotomous and continuous outcomes, respectively. Five RCTs with 544 patients (268 PRG and 276 PEG) were included. There was similar technical success (RR = 1.02; 95% CI = 0.98-1.05; I² = 35%; moderate certainty of evidence because of inconsistency), overall mortality (RR = 1.25; 95% CI = 0.63-2.47; I² = 47%; very low certainty of evidence because of inconsistency, indirectness, and imprecision), and overall AEs risk (RR = 1.06; 95% CI = 0.63-1.76; I² = 81%; low certainty of evidence because of inconsistency and imprecision) between the two groups. However, compared with PEG, the procedure time was longer in the PRG group (MD = 19.35 min; 95% CI = 0.95-37.75 min; I² = 98%; very low certainty of evidence because of inconsistency and imprecision). PRG and PEG demonstrate similar efficacy and safety; however, the endoscopic technique may boast a shorter procedure time.

Effect of sacubitril–valsartan on left ventricular remodeling in patients with acute myocardial infarction after primary percutaneous coronary intervention: a systematic review and meta-analysis

BackgroundSacubitril–valsartan has been widely reported for reducing the risk of cardiovascular death and improving left ventricular remodeling in patients with heart failure (HF). However, the effect of sacubitril–valsartan in patients with acute myocardial infarction (AMI) remains controversial. Therefore, we conducted this meta-analysis to investigate whether sacubitril–valsartan could reverse left ventricular remodeling and reduce cardiovascular adverse events in AMI patients after primary percutaneous coronary intervention (PPCI).Materials and methodsTwo researchers independently retrieved the relevant literature from PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wanfang database. The retrieval time was limited from inception to 1 June 2023. Randomized controlled trials (RCTs) meeting the inclusion criteria were included and analyzed.ResultsIn total, 21 RCTs involving 2442 AMI patients who underwent PPCI for revascularization were included in this meta-analysis. The meta-analysis showed that compared with the angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), sacubitril–valsartan treatment in AMI patients after PPCI significantly reduced left ventricular end-diastolic dimension (LVEDD) (weighted mean difference (WMD) −3.11, 95%CI: −4.05∼−2.16, p &amp;lt; 0.001), left ventricular end-diastolic volume (LVEDV) (WMD −7.76, 95%CI: −12.24∼−3.27, p = 0.001), left ventricular end-systolic volume (LVESV) (WMD −6.80, 95%CI: −9.45∼−4.15, p &amp;lt; 0.001) and left ventricular end-systolic dimension (LVESD) (WMD −2.53, 95%CI: −5.30–0.24, p &amp;lt; 0.001). Subgroup analysis according to the dose of sacubitril–valsartan yielded a similar result. Meanwhile, PPCI patients using sacubitril–valsartan therapy showed lower risk of major adverse cardiac events (MACE) (OR = 0.36, 95%CI: 0.28–0.46, p &amp;lt; 0.001), myocardial reinfarction (OR = 0.54, 95%CI: 0.30–0.98, p = 0.041) and HF (OR = 0.35, 95%CI: 0.26–0.47, p &amp;lt; 0.001) without increasing the risk of renal insufficiency, hyperkalemia, or symptomatic hypotension. At the same time, the change of LV ejection fraction (LVEF) (WMD 3.91, 95%CI: 3.41–4.41, p &amp;lt; 0.001), 6 min walk test (6MWT) (WMD 43.56, 95%CI: 29.37–57.76, p &amp;lt; 0.001) and NT-proBNP level (WMD −130.27, 95%CI: −159.14∼−101.40, p &amp;lt; 0.001) were statistically significant.ConclusionIn conclusion, our meta-analysis indicates that compared with ACEI/ARB, sacubitril–valsartan may be superior to reverse left ventricular remodeling, improve cardiac function, and effectively reduce the risk of MACE, myocardial reinfarction, and HF in AMI patients after PPCI during follow-up without increasing the risk of adverse reactions including renal insufficiency, hyperkalemia, and symptomatic hypotension.

Platelet-fibrin clot strength and platelet reactivity predicting cardiovascular events after percutaneous coronary interventions.

Platelet-fibrin clot strength (PFCS) is linked to major adverse cardiovascular event (MACE) risk. However, the association between PFCS and platelet reactivity and their prognostic implication remains uncertain in patients undergoing percutaneous coronary intervention (PCI). In PCI-treated patients (n = 2512) from registry data from January 2010 to November 2018 in South Korea, PFCS using thromboelastography and platelet reactivity using VerifyNow were measured. High PFCS (PFCSHigh) was defined as thromboelastography maximal amplitude ≥ 68 mm, and high platelet reactivity (HPR) was defined as >208 P2Y12 reaction units. Patients were stratified into four groups according to maximal amplitude and P2Y12 reaction unit levels: (i) normal platelet reactivity (NPR)-PFCSNormal (31.8%), (ii) HPR-PFCSNormal (29.0%), (iii) NPR-PFCSHigh (18.1%), and (iv) HPR-PFCSHigh (21.1%). Major adverse cardiovascular event (all-cause death, myocardial infarction, or stroke) and major bleeding were followed up to 4 years. High platelet reactivity and PFCSHigh showed an additive effect for clinical outcomes (log-rank test, P < .001). Individuals with NPR-PFCSNormal, NPR-PFCSHigh, HPR-PFCSNormal, and HPR-PFCSHigh demonstrated MACE incidences of 7.5%, 12.6%, 13.4%, and 19.3%, respectively. The HPR-PFCSHigh group showed significantly higher risks of MACE compared with the NPR-PFCSNormal group [adjusted hazard ratio (HRadj) 1.89; 95% confidence interval (CI) 1.23-2.91; P = .004] and the HPR-PFCSNormal group (HRadj 1.60; 95% CI 1.12-2.27; P = .009). Similar results were observed for all-cause death. Compared with HPR-PFCSNormal phenotype, NPR-PFCSNormal phenotype was associated with a higher risk of major bleeding (HRadj 3.12; 95% CI 1.30-7.69; P = .010). In PCI patients, PFCS and platelet reactivity demonstrated important relationships in predicting clinical prognosis. Their combined assessment may enhance post-PCI risk stratification for personalized antithrombotic therapy.

Comparing the risk of death, major adverse cardiac events, and relapse in bullous pemphigoid patients treated with systemic or topical corticosteroids.

According to current guidelines, systemic or topical corticosteroids are recommended as first-line treatments for bullous pemphigoid (BP). There is evidence suggesting that topical application may be associated with a lower risk of mortality. However, there is a lack of comprehensive large-scale data comparing mortality rates, as well as the risk of major adverse cardiac events (MACE), infections, and relapse, between systemic and topical corticosteroid treatments. To evaluate the risk of death, MACE, infections, and relapse in BP patients treated with systemic or topical corticosteroids. A population-based retrospective cohort study was performed in the TriNetX US Collaborative Network. As a measure against bias, propensity-score matching for age, sex, ten diseases and six medications, and three sensitivity analyses were conducted. All-time risk of death was increased in US BP patients exposed to any dose of systemic corticosteroids (n=2,917) compared to topical clobetasol propionate treated patients (n=2,932, hazard ratio [HR], 1.43, 95% confidence interval [CI] 1.28-1.58, p<0.0001). This was consistent in time-stratified analysis (1- and 3-year mortality rates), and in analysis contrasting prednisone (equivalent) does of 1-10 mg (low) or 30-100 mg (medium-high) systemic corticosteroid to topical treatment. The increased risk of death in US BP patients exposed to any dose of systemic corticosteroids compared to topical treatment was accompanied by increased risks for MACE (HR 1.33, CI 1.08-1.64, p=0.0075) and infections (HR 1.33, CI 1.15-1.54, p=0.0001). The risk of continued disease or relapse was decreased in patients treated with systemic as opposed to topical corticosteroid (HR 0.85, CI 0.77-0.94, p=0.0016). Results regarding mortality and continued disease or relapse persisted in three of three sensitivity analyses. Potential limitations are the retrospective data collection, bias for treatment selection and miscoding. Pending validation in prospective studies, where feasible, and despite the heightened risk of relapse, topical corticosteroid treatment may be advantageous compared to systemic corticosteroid treatment due to its significantly lower risk of death.

Safety outcomes following COVID-19 vaccination and infection in 5.1 million children in England.

The risk-benefit profile of COVID-19 vaccination in children remains uncertain. A self-controlled case-series study was conducted using linked data of 5.1 million children in England to compare risks of hospitalisation from vaccine safety outcomes after COVID-19 vaccination and infection. In 5-11-year-olds, we found no increased risks of adverse events 1-42 days following vaccination with BNT162b2, mRNA-1273 or ChAdOX1. In 12-17-year-olds, we estimated 3 (95%CI 0-5) and 5 (95%CI 3-6) additional cases of myocarditis per million following a first and second dose with BNT162b2, respectively. An additional 12 (95%CI 0-23) hospitalisations with epilepsy and 4 (95%CI 0-6) with demyelinating disease (in females only, mainly optic neuritis) were estimated per million following a second dose with BNT162b2. SARS-CoV-2 infection was associated with increased risks of hospitalisation from seven outcomes including multisystem inflammatory syndrome and myocarditis, but these risks were largely absent in those vaccinated prior to infection. We report a favourable safety profile of COVID-19 vaccination in under-18s.

Low skeletal muscle mass predicts melanoma-specific survival in melanoma patients treated with adjuvant immune checkpoint blockade

PurposeAdjuvant immunotherapy with immune checkpoint blockade(ICB) has greatly reduced the risk of recurrence and metastatic spread in early and advanced melanoma. However, not all patients benefit from adjuvant treatment: many patients show disease recurrence despite therapy, while those without recurrence harbor the risk for potentially irreversible adverse events. Biomarkers to select patients benefitting most from adjuvant therapy are currently lacking. As body composition assessment using CT images has shown promising results as a prognostic biomarker in stage IV melanoma, we aim to study the applicability of body composition parameters also in adjuvant melanoma treatment.MethodsWe analyze body composition features via CT scans in a retrospective cohort of 109 patients with resected stage IIB-IV melanoma receiving an adjuvant first-line treatment with ICB in our department. In this analysis, we focus on the impact of body composition, especially the presence of low skeletal muscle mass (LSMM), on patients’ survival and occurrence of adverse events (AEs).ResultsIn uni- and multivariate analyses, we identify an association between CT-measured LSMM and melanoma-specific survival in patients treated with adjuvant ICB. Furthermore, LSMM is associated with a lower risk for therapy-related AEs, especially hypothyroidism, fatigue, and xerostomia. Conventional serological biomarkers e.g. S100 and LDH and measures of adipose tissue compartments did not show a correlation with survival or the occurrence of AEs.ConclusionsLSMM constitutes a novel biomarker for melanoma-specific survival in patients treated with adjuvant ICB.

Safety of patients undergoing radical resection combined with paclitaxel-based hyperthermic intraperitoneal chemotherapy for locally advanced gastric cancer

Objective: To analyze the safety of paclitaxel-based, hyperthermic, intraperitoneal perfusion chemotherapy (HIPEC) after radical resection of locally advanced gastric cancer. Methods: This was a retrospective cohort study of clinicopathological data of 467 patients with locally advanced gastric adenocarcinoma who had been admitted to the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University between July 2019 and April 2021. Among these patients, 151 had undergone radical resection combined with post-operative paclitaxel-based HIPEC (surgery+HIPEC group) and 316 radical resection alone (surgery group). The adverse perioperative events in study patients were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0) published by the U.S. Department of Health and Human Services. Subgroup analysis was performed on patients in the surgery+HIPEC group according to the number of times HIPEC was administered and the incidence of adverse events was compared between subgroups using the χ2 test. Independent risk factors for paclitaxel-based HIPEC-associated adverse events were identified by applying a logistic model. Results: In the surgery+HIPEC group, there were 113 (74.8%) male and 38 (25.2%) female patients of median age 64 (55, 68) years, 18 (11.9%), 79 (52.3%), and 54 (35.8%) of whom had undergone one, two, and three paclitaxel-based HIPEC treatments, respectively, after surgery. The median maximum tumor diameter was 5.0 (3.6, 6.5) cm. In the surgery group, there were 244 (77.2%) male and 72 (22.8%) female patients of median age 63 (54, 68) and the median maximum tumor diameter was 4.0 (3.0, 5.5) cm. In the surgery+HIPEC group, 112 patients (74.2%) had 198 Grade 2 or higher adverse perioperative events, postoperative hypoalbuminemia being the commonest (85 cases, 56.3%), followed by postoperative anemia (50 cases, 33.1%). Compared with the surgery group, the incidences of postoperative hypoalbuminemia (56.3% [85/151] vs. 37.7% [119/316], χ2=14.420, P<0.001), anemia (33.1% [50/151] vs. 22.5% [71/316], χ2=6.030, P=0.014), abdominal pain [7.3% [11/151] vs. 1.6% [5/316], χ2=10.042, P=0.002) and abdominal distension (5.3% [8/151] vs. 1.3% [4/316], χ2=5.123, P=0.024) were all significantly higher in the surgery+HIPEC group. Analysis of the three HIPEC subgroups revealed significant differences in the incidences of postoperative hypoalbuminemia (13/18 vs. 67.1% [53/79] vs. 35.2% [19/54], χ2=12.955, P<0.001) and pulmonary infection (6/18 vs. 6.3% [5/79] vs. 1.9% [1/54], χ2=13.232, P<0.001) between them. Univariate analysis identified body mass index, Borrmann's type and number of HIPEC treatments as associated with perioperative adverse events in the surgery+HIPEC group (P<0.05). However, according to multifactorial logistic analysis, the above factors were not independent risk factors for perioperative adverse events in the surgery+HIPEC group (P>0.05). Conclusions: Paclitaxel-based HIPEC after radical resection significantly increases the risk of postoperative hypoalbuminemia, anemia, abdominal pain, and abdominal distension in patients who have undergone excision of locally advanced gastric cancer. However, increasing the frequency of HIPEC treatments did not significantly increase the risk of paclitaxel-based HIPEC-related adverse events. Moreover, univariate and multivariate analysis did not identify any independent risk factors for paclitaxel HIPEC-related adverse events.

Patient-reported treatment burden: comparison between vitamin-K antagonist and non-vitamin K antagonist oral anticoagulants

Abstract Introduction Treatment burden (TB) is defined as the overall workload that maintenance or improvement of their functioning and well-being poses on patients with chronic medical conditions. A high patient-reported TB has been associated with lower adherence to treatment and increased risk of major adverse events including death. We explored the differences in patient-reported TB value and prevalence of unacceptably high TB score (≥59 points) between patients receiving vitamin K antagonist oral anticoagulants (VKA) and non-vitamin K antagonist oral anticoagulants (NOAC). Furthermore, we explored contributory factors associated with TB and the relationship between TB and quality of life (QoL) in these patients. Methods A single-centre study included consecutive adult in- and outpatients on long-term oral anticoagulation, seen at a university clinical centre a from April to June 2019, who were willing to complete the Treatment Burden Questionnaire encompassing 13 items assessing the TB associated with taking medicine, self-monitoring, laboratory assessments, medical consultations, organisational and administrative requirements, adherence to dietary and physical activity recommendations, as well as the social repercussions of the treatment. Results Of 320 enroled patients, 206 (64.4%) were taking a VKA. Atrial fibrillation was the most common indication for long-term oral anticoagulation (n=299, 93.4%). The mean TB score was significantly higher in patients on VKA versus those taking a NOAC (48.8 ±26.5 vs. 41.8 ±19.7, P= 0.014), mostly owing to significantly higher TB values for questions related to self-monitoring, including the International Normalized Ratio (INR) control (3.85±3.32 vs. 1.62±1.38, P&amp;lt;0.001) and diet restrictions (3.98±3.43 vs. 2.48±2.49, P&amp;lt;0.001) in patients taking VKA (Figure 1). In addition, these patients significantly more often reported an unacceptably high TB of ≥59 points compared with those taking NOAC (30.1% vs 18.4%, P= 0.024). Multivariable regression analysis of predictors of TB in patients taking a VKA or NOAC are presented in Table 1. Conclusion In our study, patients receiving a VKA reported significantly higher TB compared to those using NOAC, especially regarding the questions about self-monitoring (including INR control) and diet restrictions. An unacceptably high TB was also more prevalent among patients receiving a VKA. Our findings suggest that prescribing NOACs in preference to VKAs could help in decreasing the self-reported TB in patients who need oral anticoagulant therapy.

Non-Invasive Assessment of Human Microvascular Function in Health and Disease using Incident Dark Field Microscopy.

Reduced peripheral microvascular reactivity is associated with increased risk for major adverse cardiac events (MACE). Tools for non-invasive assessment of peripheral microvascular function are limited and existing technology is poorly validated in both healthy populations and patients with cardiovascular disease (CVD). Here, we utilized a handheld incident-darkfield imaging tool (CytoCam) to test the hypothesis that compared to healthy individuals (no risk factors for CVD), subjects formally diagnosed with coronary artery disease (CAD) or those with ≥ 2 risk factors for CAD (Endothelial Dysfunction; ED) would exhibit impaired peripheral microvascular reactivity. A total of 17 participants (11 healthy, 6 ED) were included in this pilot study. CytoCam was used to measure sublingual microvascular total vessel density (TVD), perfused vessel density (PVD), and microvascular flow index (MFI) in response to topical application of acetylcholine (Ach) and sublingual administration of nitroglycerin (NTG). Baseline MFI and PVD were significantly reduced in the ED cohort compared to healthy individuals. Surprisingly, following application of acetylcholine and nitroglycerin, both groups showed a significant improvement in all 3 microvascular perfusion parameters. These results suggest that despite baseline reductions in both microvascular density and perfusion, human in vivo peripheral microvascular reactivity to both endothelial-dependent and -independent vasoactive agents remains intact in individuals with CAD or multiple risk factors for disease.

A novel predictive model for differentiating cardiac and non-cardiac syncope in syncope-admitted patients

Abstract Background Syncope due to cardiac causes presents a higher risk for mortality or other adverse events compared to those with non-cardiac causes. Thus, a critical focus in syncope management must be the early identification of these patients. Purpose This study sought to explore the predictive role of readily available clinical features for cardiac syncope and develop a diagnostic nomogram to facilitate its adoption in practice. Methods 877 patients who were hospitalized with syncope and had a confirmed cause were included in this retrospective study at a tertiary heart center. They were randomly divided into the training set and validation set and were categorized into two groups based on their underlying cause: cardiac syncope and non-cardiac syncope. A wide range of clinical features were analyzed and selected using LASSO regression. Subsequently, we utilized multivariable logistic regression analysis to identify independent predictors and construct a nomogram. The receiver operating characteristic (ROC) curves and the area under the curves (AUCs) were used to assess the predictive accuracy of the predictive model. Furthermore, calibration curves were used to measure the alignment between the predicted and actual observed probability, and decision curve analysis (DCA) was used to evaluate the clinical benefit of the nomogram. Results Within the entire cohort, 521 patients were diagnosed with cardiac syncope and 356 patients were diagnosed with non-cardiac syncope. Among 36 candidate variables, five independent predictors for cardiac syncope were selected using the LASSO logistic regression analysis, including BMI (OR 1.088; 95%CI 1.022-1.158), LVEF (OR 0.940; 95%CI 0.908-0.973), logarithmic NT-proBNP (OR 1.463; 95%CI 1.240-1.727), chest symptoms preceding syncope (OR 5.251; 95%CI 3.326-8.288), and abnormal electrocardiogram (OR 6.171; 95%CI 3.966-9.600). Subsequently, a nomogram based on the five independent predictors was developed, yielding AUC of 0.873 (95% CI 0.845–0.902) and 0.856 (95%CI 0.809-0.903) in the training set and the validation set, respectively. The calibration curves showcased the nomogram's strong calibration, and DCA curves revealed its potential as a highly effective tool in clinical practice. Conclusions This study has successfully developed and internally validated a novel predictive nomogram for distinguishing between cardiac and non-cardiac syncope, which holds a promise to serve as an effective tool to help facilitate early identification of such patients in clinical practice.ROC curves of the training and test setThe nomogram and web-based calculator

Outcomes of on-label reduced-dose edoxaban in octogenarian patients with atrial fibrillation

Abstract Background Non-vitamin K antagonist oral anticoagulants (NOACs) are effective in preventing thromboembolisms and reduce the risk of bleeding compared with warfarin. There are few reports on the outcomes of on-label reduced-dose NOACs. Purpose The aim of this study was to assess the safety and efficacy of on-label reduced-dose edoxaban in octogenarian patients with atrial fibrillation (AF). Methods This study is a multi-center, prospective, non-interventional study to evaluate the safety and efficacy of on-label reduced-dose edoxaban in patients with AF. We evaluated outcomes of major bleeding, stroke or systemic embolism, all-cause death, and composite clinical outcomes. Results A total of 2448 patients (mean age 75.0±8.3 years, 801 [32.7%] males) was included in the present study. 932 patients (38.1%) were octogenarians. Major bleeding events occurred at a rate of 1.69%/yr in octogenarian patients and 0.9%/yr in non-octogenarian patients. The event rate of strokes and systemic embolisms was 1.93%/yr in octogenarian patients and 0.66%/yr in non-octogenarian patients The overall net clinical outcomes occurred at a rate of 5.45%/yr in octogenarian patients and 2.24%/yr in non-octogenarian patients. Conclusions Reduced-dose edoxaban can be used safely in Asian patients with very elderly patients. Older age was associated with a higher risk of ischemic stroke and composite adverse events.

Ventricular arrhythmia burden during different physical activities in patients with arrhythmogenic right ventricular cardiomyopathy: preliminary analysis

Abstract Background Patients suffering from arrhythmogenic right ventricular cardiomyopathy (ARVC) should avoid intense endurance exercise to reduce the risk of adverse cardiac events and disease progression. While an active lifestyle would be preferable to a sedentary one, evidence for safe levels of physical activity in ARVC, however, is scarce. Purpose This study aimed to describe the ventricular arrhythmia burden experienced during exercise and immediate recovery - estimated as the prevalence of premature ventricular contractions (PVC) - of different exercise modalities and intensities on ARVC patients. Methods This preliminary analysis includes four (1F, 33±12 yrs, BMI 24±4 kg/m2) ARVC patients harboring a pathogenic plakophilin-2 variant and carrying an implantable cardioverter-defibrillator that performed different exercises while monitored via 12-lead ECG. The order of modalities was randomized and participants instructed to stop when surpassing perceived exertion of 15 on the Borg 6-20 scale. Resistance exercises included two-legged squats and single arm biceps curls (20 repetitions and 2 min duration). Endurance exercise included 5 min of treadmill walking and 3-min cycling bouts at heart rates (HR) of 80, 100 and 120 bpm, as well as cycling at 120 bpm with 2 additional min of active cool down. Blood lactate concentration was assessed after each cycling bout. Results No adverse cardiac event or early termination for medical reasons occurred. Figure 1 summarizes the relationship between HR, perceived exertion and PVC burden. During walking (HR 76 ± 8 bpm), PVC burden was 11 ± 6% (range 4 – 18%). Cycling at 82 ± 4 bpm induced a PVC burden of 7 ± 5% (range 3 – 14%), which increased to 13 ± 8% (range 3 – 21%) at 93 ± 2 bpm and increased further to 16 ± 16% (range 7 – 37%) at 105 ± 3 bpm. In all three intensities the PVC burden was higher in the first 3 min of recovery than during the activity itself. Adding a 2-min active cool down increased the PVC burden to 25 ± 16% (range 6 – 45%). 2-legged squats (HR 101 ± 15 bpm) had a PVC burden of 9 ± 12%, which increased to 19 ± 14% at recovery. One arm biceps curls (HR 75 ± 13 bpm) had a PVC burden of 4 ± 3% during the activity and 9 ± 5% during recovery. Perception of effort varied widely when cycling at 80 bpm (range 6 – 12) or 100 bpm (range 8 – 14), but less so at 120 bpm (range 13 – 15). Blood lactate concentration when cycling at 120 bpm ranged between 2.2 and 3.5 mmol/L, typically associated with exercise in the "heavy" intensity domain. Conclusions PVC burden was high and seemingly intensity-dependent during exercise and immediate recovery. The wide range of PVC burden for physiological or subjective markers of effort call for personalized recommendations on physical activity. Exercises with small muscle mass such as biceps curls seem to minimize the PVC burden, thus, training the different muscles separately could be an interesting avenue to maintain physical fitness in ARVC patients.

Physical activity change after early rhythm control after new-onset atrial fibrillation and major adverse cardiovascular event risk

Abstract Background There is paucity of information about major adverse cardiovascular event (MACE) related to physical activity change after early rhythm control (ERC) after new-onset atrial fibrillation (AF). We investigated the association between physical activity after ERC and clinical outcomes in new-onset AF patients. Methods This study was performed based on the Korean National Health Insurance Service database. We included adults with new-onset AF between 2009 and 2018. Patients who received national health screening examination before and after AF diagnosis within 2-year were finally included (n=161,379). Among these, 48,243 patients were received rhythm control within 2-year after AF diagnosis. Patients were categorized into 4 groups as follows: persistent non-exerciser, new exerciser (after AF diagnosis and ERC), exercise maintainer, and exercise quitter (after AF diagnosis and ERC). The primary outcome was MACE defined as the composite of ischemic stroke, myocardial infarction, and hospitalization for heart failure. Multivariable Cox analysis was performed. Results Among 48,243 patients receiving ERC, 63% (n=30,540) was persistent non-exerciser, 13% (n=6260) was new exerciser, 11% (n=5102) was exercise maintainer, and 13% (n=6341) was exercise quitter. After multivariable adjustment, compared to persistent non-exerciser, new exerciser and exercise maintainer with ERC showed lower risk of MACE by 10% and 19%, respectively (adjusted hazard ratio [aHR], 95% confidence interval [95% CI], 0.903 [0.802-0.994] for new exerciser, and 0.810 [0.725-0.906] for exercise maintainer) (Table 1). However, exercise quitter did not show significant benefit compared to persistent non-exerciser (Table 1). To assess the synergistic effect of ERC and starting or maintaining physical activity, we performed exploratory analysis including patients who did not receive ERC. Compared to persistent non-exerciser without ERC, persistent non-exerciser with ERC was associated with a significantly lower risk of MACE (0.832 [0.797-0.868], Table 2). Patients who received ERC and started or maintained physical activity with ERC showed greatest risk reduction for MACE by 27% and 36%, respectively (0.732 [0.668-0.802] for new exerciser and 0.641 [0.576-0.713] for exercise maintainer) (Table 2). Conclusion Even in context with beneficial effect of ERC in patients with new-onset AF, maintaining or starting regular physical activity after ERC might bring greater reduction on the risk of MACE. Physician should emphasize healthy lifestyle behavior with rhythm control in patients with new-onset AF.

Efficacy and Safety of Excision Combination Therapies for Earlobe Keloids: A Systematic Review and Meta-analysis.

Different combinations of excision and adjuvant therapies have been applied to improve outcomes for earlobe keloids, though evidence in this field is still lacking. This study sought to systematically investigate efficacy and safety of these treatments. We conducted a systematic search on PubMed, Embase, Web of Science, and Cochrane Library to find all relevant studies. Meta-analysis of recurrence rates (RRs) and adverse event rates with 95% confidence intervals, and individual participants data (IPD) were calculated for each intervention when possible. Otherwise, narrative syntheses were performed. A total of 85 articles, covering 23 treatments for earlobe keloids, were included, indicating a preference for multiple combination therapy. The estimated RRs for 6 interventions (i.e., excision monotherapy, combinations of excision with imiquimod, pressure therapy, radiotherapy, steroids, and steroids with pressure therapy) appeared to be comparable. Electron radiotherapy was found to have potential advantages over X-ray treatment, contributing to the observed heterogeneity. Further meta-analysis using IPD revealed that both combination therapies of excision plus steroid therapy (p=0.003) and excision plus radiotherapy (p=0.003) yielded better recurrence-free survival compared to excision alone. The median recurrence-free interval for combination therapy was 10months. Adverse event rates were similar among different intervention groups. This study suggests that combining excision with radiotherapy or perioperative steroid therapy has the potential to improve prognosis of earlobe keloids without increasing the risk of adverse events. Overall evaluation of patients' conditions and further studies with sufficient follow-up are warranted for clinical practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .