Aggressive Treatment Research Articles

Genomic instabilities in hepatocellular carcinoma: biomarkers and application in immunotherapies.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers. For patients with advanced HCC, liver function decompensation often occurs, which leads to poor tolerance to chemotherapies and other aggressive treatments. Therefore, it remains critical to develop effective therapeutic strategies for HCC. Etiological factors for HCC are complex and multifaceted, including hepatitis virus infection, alcohol, drug abuse, chronic metabolic abnormalities, and others. Thus, HCC has been categorized as a "genomically unstable" cancer due to the typical manifestation of chromosome breakage and aneuploidy, and oxidative DNA damage. In recent years, immunotherapy has provided a new option for cancer treatments, and the degree of genomic instability positively correlates with immunotherapy efficacies. This article reviews the endogenous and exogenous causes that affect the genomic stability of liver cells; it also updates the current biomarkers and their detection methods for genomic instabilities and relevant applications in cancer immunotherapies. Including genomic instability biomarkers in consideration of cancer treatment options shall increase the patients' well-being.

Pulmonary nodules and the psychological harm they can cause: A scoping review

More than 1.6 million pulmonary nodules are diagnosed in the United States each year. Although the majority of nodules are found to be benign, nodule detection and the process of ruling out malignancy can cause patients psychological harm to varying degrees. The present study undertakes a scoping review of the literature investigating pulmonary nodule-related psychological harm as a primary or secondary outcome. Online databases were systematically searched to identify papers published through June 30, 2023, from which 19 publications were reviewed. We examined prevalence by type, measurement, associated factors, and behavioral or clinical consequences. Of the 19 studies reviewed, 11 studies investigated distress, anxiety (n = 6), and anxiety and depression (n = 4). Prevalence of distress was 24.0 %-56.7 %; anxiety 9.9 %-42.1 %, and 14.6 %-27.0 % for depression. A wide range of demographic and social characteristics and clinical factors were associated with nodule-related psychological harm. Outcomes of nodule-related harms included experiencing conflict when deciding about treatment or surveillance, decreased adherence to surveillance, adoption of more aggressive treatment, and lower health-related quality of life. Our scoping review demonstrates that nodule-related psychological harm is common. Findings provide evidence that nodule-related psychological harm can influence clinical decisions and adherence to treatment recommendations. Future research should focus on discerning between nodule-related distress and anxiety; identifying patients at risk; ascertaining the extent of psychological harm on patient behavior and clinical decisions; and developing interventions to assist patients in managing psychological harm for better health-related quality of life and treatment outcomes.

Advancing prostate cancer detection: High-accuracy urine test distinguishes between high and low-risk cancers

Prostate cancer remains one of the leading causes of cancer-related deaths among men. The standard method for early detection involves measuring Prostate-specific antigen (PSA) levels in the blood, with elevated PSA levels prompting further diagnostic procedures, such as a prostate biopsy. While effective, biopsies can be painful and carry risks of complications such as fever and urinary tract infections. To reduce unnecessary biopsies, researchers have sought alternative diagnostic methods. In recent years, a urine test was developed for early-stage prostate cancer detection. However, this test struggled to differentiate between aggressive and slow-growing cancers, the latter of which often require minimal treatment and are managed through active surveillance. To address this limitation, scientists at Wunderkind University have significantly enhanced the urine test. By analysing the genomes of thousands of prostate cancer patients, they identified a panel of 16 genes detectable in urine that can effectively distinguish between high-risk and low-risk cancers. When applied to individuals with elevated PSA levels, this improved test demonstrated an impressive 97% accuracy in identifying advanced prostate cancer. This advancement holds great promise for reducing unnecessary biopsies and improving patient outcomes by accurately identifying those needing aggressive treatment versus those suitable for observation. This review paper will explore the development, validation, and clinical implications of this novel urine test, highlighting its potential to transform prostate cancer diagnostics and patient management.

Predictors of periprocedural myocardial infarction following percutaneous coronary intervenction in NSTEMI

Abstract Background Percutaneous coronary intervention (PCI) has demonstrated a significant positive prognostic impact on outcomes in patients with Non-ST-elevation myocardial infarction (NSTEMI). However, PCI is associated with an increased risk of periprocedural complications, among which periprocedural myocardial infarction (PMI). Although risk factors of periprocedural events are only well established in patients undergoing PCI for chronic coronary syndrome with normal baseline cardiac troponin (cTn) levels, evidence on predictors of additional post-PCI myocardial infarction in patients with acute coronary syndrome who present elevated cTn levels at baseline (pre-PCI) is missing. Purpose To identify the predictors of PMI in patients affected by NSTEMI undergoing PCI. Methods We prospectively evaluated all NSTEMI patients admitted to our coronary care unit from 2017 to 2022 who underwent PCI. NSTEMI patients were managed according to the current European guidelines criteria. The diagnosis of PMI (type 4a myocardial infarction) was based on the Fourth Universal Definition of Myocardial Infarction. We only enrolled patients with stable (≤ 20% variation) or falling pre-procedure baseline cTn values. A multivariable logistic regression analysis was performed to investigate the factors independently associated with the occurrence of PMI after PCI. For the analysis, we selected the main known predictors of PMI after elective PCI, specifically age, serum creatinine, GRACE score > 140, multivessel disease, coronary bifurcation PCI, left main or proximal left anterior descending PCI, multivessel PCI and stent length ≥ 60 mm. Results The final court of the study included 1412 patients. PMI was recognized in 240 patients (17.0%). Although the patients who developed PMI had a higher risk profile as documented by a higher mean age, a higher complexity of atherosclerotic disease, and thus a significant technical difficulty of PCI compared to other patients, according to the multivariable model, only age [OR: 1.02 (95% CI: 1.01-1.04); p=0.006], coronary bifurcation PCI [OR: 3.71 (95% CI: 2.70-5.10); p<0.001], and stent length ≥ 60 mm [OR: 1.87 (95% CI: 1.30-2.68); p=0.001] were independent predictors of PMI. Interestingly, despite previous studies have demonstrated a predictive role of procedural complexity features, this was not completely confirmed by our analysis, in which left main or proximal left anterior descending PCI [OR: 0.92 (95% CI: 0.66-1.26); p=0.596] and multivessel PCI [OR: 0.83 (95% CI: 0.56-1.23); p=0.357] were not associated with an increased risk of periprocedural ischemic complications. Conclusions Among NSTEMI patients undergoing PCI, age, coronary bifurcation PCI and stent length ≥ 60 mm represent independent predictive factors of type 4a MI. This finding may have important clinical implications for clinical practice, providing valuable insights for the identification of higher-risk patients that can benefit from a more aggressive treatment.

Differences in risk profiles and clinical outcomes according to age in patients with high-risk myocardial infarction: insights from the PARADISE-MI trial

Abstract Introduction Temporal declines in rates of rehospitalization and death after acute myocardial infarction (MI) have not been uniform across age groups. A better understanding of how risk profiles and clinical outcomes differ after MI by age may allow for targeted treatment and prevention strategies. Aims To investigate risk profiles and clinical outcomes following high-risk MI according to age in the Prospective ARNI vs ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI). Methods Adults without prior heart failure (HF) were randomized to sacubitril/valsartan versus ramipril within 0.5 to 7 days of a MI complicated by transient pulmonary congestion and/or left ventricular systolic dysfunction and additional risk-augmenting factors. Associations between age and clinical outcomes were analyzed using Cox proportional hazards regression models, which were additionally adjusted for baseline demographic and clinical covariates (Figure). Results The mean age of the 5,661 PARADISE-MI participants was 64 ± 11 years. Patients aged ≥75 years (n=1051) were more likely women, had more hypertension and atrial fibrillation and lower estimated glomerular filtration rate, were less likely to present with ST-segment elevation MI and regardless of type of MI were less likely to receive primary reperfusion and guideline-based medical therapy (Table). Age was significantly associated with all-cause death (HR 1.54 per 10-year increase; 95% CI, 1.41-1.68) and was more strongly associated with non-CV death (HR 2.09; 95% CI, 1.70-2.56) than with CV death (HR 1.43; 95% CI, 1.29-1.57). Age was also associated with incident HF (HR 1.37; 95% CI, 1.25-1.49) (Figure). Multivariable adjustment attenuated the risk relationship of age with recurrent fatal or non-fatal MI (HR 1.08; 95% CI, 0.96-1.21) and the coronary composite outcome (HR 1.01; 95% CI, 0.93-1.09). The relative treatment effect of sacubitril/valsartan versus ramipril on the primary composite outcome of CV death or incident HF was not significantly modified by age (p-interaction = 0.19). Conclusions Following high-risk MI, age was most strongly associated with subsequent non-CV death followed by CV death and incident HF, but was not independently associated with recurrent coronary events. The heightened risk of CV death and HF with advancing age was not explained by differences in clinical characteristics. Older patients may require closer surveillance and more aggressive treatment after MI to mitigate the elevated risk of CV death and HF.

The association between drugs and vaccines commonly prescribed to older people and bullous pemphigoid: a case-control study.

Bullous pemphigoid (BP) is an autoimmune skin disease that affects mainly older people. Numerous drugs have been previously associated with BP based on case series and small hospital-based studies. More reliable and precise estimates of associations between a broad selection of drugs/vaccines and BP will enable greater awareness of potential increased risk of BP following certain medicines and help identify clinical, histological and genomic characteristics of drug-induced BP for different types of culprit drugs. Greater awareness could lead to earlier recognition or suspicion of BP and referral to a dermatologist for diagnosis. Earlier diagnosis may lead to less aggressive treatment and improved well-being. To determine the association between drugs/vaccines commonly prescribed to older people and BP risk. We conducted a population-based nested case-control study between 1998-2021 using electronic primary care records from the Clinical Practice Research Datalink. We matched BP cases with up to 5 controls. Exposures were drugs/vaccines commonly prescribed to older people. We used multivariable conditional logistic regression adjusting for multiple drug use. For antibiotics, we considered prescriptions may be prescribed for undiagnosed symptoms of BP which resemble skin infection (protopathic bias) in a sensitivity analysis. Antibiotics were the therapeutic group associated with the highest risk of BP (OR: 4.60; 95%CI 4.40-4.80). However, after adjusting for protopathic bias, the OR reduced to 2.08 (95%CI 1.99-2.17). After adjusting for protopathic bias, of all antibiotic classes and subclasses, penicillins and penicillinase-resistant penicillins had the strongest associations with BP risk (OR: 3.44; 95%CI 3.29-3.60; sensitivity analysis OR; 1.74; 1.66-1.84 and OR: 7.56; 95%CI 7.15-8.00; sensitivity analysis OR: 2.64; 95%CI 2.45-2.85, respectively). Other drugs strongly associated with increased risk were gliptins (OR: 2.77; 95% CI 2.37-3.23), and second-generation antipsychotics (OR: 2.58; 95%CI 2.20-3.03). Healthcare professionals need to be aware of BP risk in older people particularly when prescribing penicillinase-resistant penicillins, gliptins, and second-generation antipsychotic drugs to recognise and manage BP early. Due to the low prevalence of disease, we do not suggest avoidance of drugs/vaccines to prevent BP. Further research should consider recency, dosage, and duration of antibiotic treatments.

Association of renal circulation at acute phase with decongestion level at discharge in patients admitted for acute decompensated heart failure

Abstract Background In patients admitted with acute decompensated heart failure (ADHF), renal hemodynamics may play an important role in the clinical course during hospitalization based on the close cardio-renal relationship. Superb Microvascular Imaging (SMI), distinguished by its advanced clutter suppression capabilities to reveal microflow details, holds promise for evaluating renal circulation. Consequently, our study aims to explore the association between renal circulation as assessed by SMI and the levels of brain natriuretic peptide (BNP) at discharge as an indicator of decongestion status. Methods In a prospective design, 45 ADHF patients were sequentially examined via renal ultrasound with SMI at discharge. The vascular index (VI) by SMI was calculated as the percentage of blood flow signal area in the region of interest. Then, the intra-renal perfusion index (IRPI) as an index of cyclic variation in VI, was calculated as the maximum VI minus the minimum VI within one cardiac cycle in the ROI divided by the Max.VI (Figure A). Results The values of IRPI were as follows: at 12h, 0.70±0.04; at 48h, 0.58±0.05; at 1W, 0.50±0.04; and at discharge, 0.61±0.04. The IRPI measured at 48h showed a stronger correlation with BNP at discharge (r = 0.57, p<0.001) than those at the other three points (Figure B). Patients with higher log BNP at discharge (> 2.31: determined by the median value) had significantly higher IRPI and age, and lower hemoglobin levels at 48h, however, there were no significant differences in estimated glomerular filtration rate, ejection fraction, or systolic pulmonary artery pressure at 48h. The area under the curve of IRPI at 48h for higher log BNP at discharge > 2.31 at discharge was 0.746 (sensitivity 100%, specificity 48%). Conclusion Early assessment of renal circulation by SMI around 48 hours after ADHF admission may predict congestion resolution at discharge. This underscores the potential utility of SMI in guiding more aggressive decongestive treatment strategies earlier in ADHF.

Infection and Inflammation in the Cystic fibrosis (CF) airway.

Cystic fibrosis (CF) airway disease is characterized by chronic infection and neutrophil-driven inflammation, leading to progressive airway damage and early mortality. Infection with Pseudomonas aeruginosa significantly impacts morbidity and mortality, requiring early detection and aggressive antibiotic treatment. Controlling inflammation remains difficult due to the limited availability of effective anti-inflammatory treatments. CFTR modulators show potential in reducing inflammation, but further research is needed. Effective management of CF lung disease requires a comprehensive approach addressing both infection and inflammation.

Undiagnosed impaired glucose tolerance/diabetes mellitus and relationship with aortic stiffness in patients with acute coronary syndromes

Abstract Background Patients admitted with an acute coronary syndrome (ACS) often have unknown cardiovascular risk factors, such as impaired glucose tolerance (IGT) or diabetes mellitus (DM). Detecting these conditions is crucial to intensify appropriate therapies. Increased aortic stiffness, assessed by aortic pulse wave velocity (PWV), is associated with higher mortality in patients at high cardiovascular risk. Purpose Estimating the prevalence of IGT and DM and their relationship with increased aortic stiffness in patients admitted with an ACS. Methods Seventy-five consecutive patients admitted for ACS (21% women, mean age 63.6±11.1 ys), with fasting plasma glucose (PG) and glycated hemoglobin (HbA1c) not diagnostic for diabetes mellitus, underwent a fully standardized oral glucose tolerance test. All patients were also evaluated with the Arteriograph device, which applies a brachial cuff-based oscillometric method for the estimation of aortic PWV and arterial pulse waveform features. The automated vascular studies and OGTTs were performed after patient stabilization, at least 96 hours after admission. Results Forty-one patients (55% of the total study population) showed an abnormal OGTT response: 14 patients had a 2-h PG-OGTT ≥ 200 mg/dL, uncovering a diagnosis of DM, and 27 patients had a 2-h PG-OGTT ≥ 140 mg/dL, uncovering a diagnosis of IGT. Patients with DM showed no differences in terms of age, cardiovascular risk factors, Framingham risk score, C-reactive protein values, whereas a significant difference was observed in the number of diseased coronary vessels (2.2±0.8 vs 1.6±0.9, p=0.016) and PWV values (10.0±1.3 vs 8.8±1.6 m/s, p=0.028). Similarly, when considering all patients with an abnormal OGTT, a significant difference was observed in PWV values compared to patients with a normal OGTT (9.5±1.5 vs 8.4±1.7 m/s, p=0.032), as well as in estimated glomerular filtration rate (78±18 vs 83±23 mL/min/1.73mq, p=0.05), and peak troponin values (3698±2905 vs 2124±2561 ng/ml, p=0.02). At follow-up (mean time 51.7 months), no patients had died, but 5 patients had a new major cardiovascular event. Aortic pulse wave velocity values were different between patients with and without events (10.6±2.3 vs 8.6±1.4 m/s, p=0.024), and PWV was a significant predictor of events at univariate regression analysis (hazard ratio 1.93; 95 confidence intervals 1.01-3.69, p=0.047). Conclusions An unknown diagnosis of DM and/or IGT is very frequent in patients with ACS. Undiagnosed dysglycemic conditions are linked to a higher prevalence of coronary multivessel disease and increased aortic stiffness, which is also predictive of future cardiovascular events. A systematic screening with OGTT may help identifying patients at even higher cardiovascular risk, and tailoring secondary prevention strategies through personalized aggressive therapeutic interventions.

Ethnic disparity in the care and management of non-ST-segment elevation myocardial infarction and its impact on short-term and long-term survival: a long-term study of a national registry

Abstract Background Previous examination of data from the United Kingdom indicates no apparent ethnic disparity in the treatment of patients hospitalised with non-ST-segment elevation myocardial infarction (NSTEMI). However, it remains uncertain whether this lack of disparity results in similar long-term survival outcomes among ethnic minority groups, particularly those with multiple underlying risk factors for coronary artery disease, when compared to White patients. Purpose To assess the impact of quality of care on short-term and long-term survival among NSTEMI patients while examining disparities based on ethnicity. Methods We analysed records of 252,964 individuals diagnosed with NSTEMI from the Myocardial Ischaemia National Audit Project database spanning 2005 to 2019, alongside Office of National Statistics data for mortality. Among them, 233,158 were identified as White patients, while 19,806 were categorised as belonging to ethnic minority groups (Asian, Black, and mixed ethnicity). Propensity score matching was used to compare average treatment effects between cohorts while survival was compared using Cox regression model. Results Ethnic minorities were younger (median age in years) (66 vs. 73, P < 0.001), predominantly male (70% vs. 63%, P < 0.001), and exhibited a higher prevalence of cardiovascular risk factors such as diabetes (52% vs. 24%, P < 0.001), hypertension (67% vs. 54%, P < 0.001), hypercholesterolemia (49% vs. 34%, P < 0.001), and chronic renal dysfunction (13% vs. 8%, P < 0.001). Ethnic minorities more frequently underwent invasive coronary angiography (80% vs. 68%, P < 0.001), percutaneous coronary intervention (53% vs. 44%, P < 0.001), and coronary artery bypass grafting (5% vs. 4%, P < 0.001). After conducting propensity score matching, both cohorts had no significant differences in in-hospital all-cause mortality [odds ratio (OR) 1.13, confidence interval (CI) 0.89 – 1.43; P = 0.268], cardiac mortality (OR 1.20, CI 0.89 – 1.54; P = 0.209), one-year mortality (OR 1.01, CI 0.89 – 1.13; P = 0.893) and major adverse cardiovascular events (OR 1.21, CI 0.95 – 1.48; P = 0.108). However, upon conducting a five-year survival analysis, ethnic minorities had better survival rates than their White counterparts (Hazard ratio (HR) 0.89, CI 0.86-0.92; P < 0.001). Conclusions Despite ethnic minorities being at a higher risk for coronary artery disease, our findings indicate that they experience better five-year survival rates than White patients. This suggests equitable access to care and potentially a more aggressive treatment approach in this relatively young patient cohort.

Prediction model for survival of younger patients with breast cancer using the breast cancer public staging database

Breast cancer (BC) is a major contributor to female mortality worldwide, particularly in young women with aggressive tumors. Despite the need for accurate prognosis in this demographic, existing studies primarily focus on broader age groups, often using the SEER database, which has limitations in variable selection. This study aimed to develop an ML-based model to predict survival outcomes in young BC patients using the BC public staging database. A total of 3,401 patients with BC were included in the study. Patients were categorized as younger (n = 1574) and older (n = 1827). We applied several survival models—Random Survival Forest, Gradient Boosting Survival, Extra Survival Trees (EST), and penalized Cox models (Lasso and ElasticNet)—to compare mortality characteristics. The EST model outperformed others in predicting mortality for both age groups. Older patients exhibited a higher prevalence of comorbidities compared to younger patients. Tumor stage was the primary variable used to train the model for mortality prediction in both groups. COPD was a significant variable only in younger patients with BC. Other variables exhibited varying degrees of consistency in each group. These findings can help identify high-risk young female patients with BC who require aggressive treatment by predicting the risk of mortality.

A matter of inflammation: CAR T-cell therapy and atrial fibrillation

Abstract Background Chimeric antigen receptor (CAR) T-cell therapy has been revolutionary in the treatment of blood cancers, but has been associated with arrhythmias such as atrial fibrillation (AF). Whether the incidence of AF has changed over time and if contributing risk factors are present remains to be defined. Methods Leveraging the Mayo Electronic Medical Record, we extracted a cohort of patients who underwent CAR T-cell therapy between 2016 and 2022. From this cohort, we identified those who had a diagnosis of AF at any point. We then defined the endpoint of interest as the first episode of new or recurrent AF during or after CAR T-cell infusion. Fine and Gray subdistribution hazard modeling was used to calculate the association of patient characteristics to the endpoint of interest. Variables with P<0.20 in univariate modeling were chosen for the multivariate model. Significance was defined as P<0.05. Results There were 328 patients who underwent CAR T-cell therapy between 2016 and 2022. Of this cohort, 27 (8.2%) patients had a pre-existing diagnosis of AF, of which 6 had recurrence of AF after CAR T (22.2%), while 21 (77.8%) did not. Of the 301 patients without a prior history of AF, 8 (2.7%) patients developed new-onset AF after CAR T. The majority of the 14 new or recurrent AF events (4.3% overall incidence) occurred within 30 days of receiving CAR T (N=10, 71.4%), the remainder after 180 days (Figure 1). No trend in declining incidence over time was noted. Prior AF, neurotoxicity, and inflammation (cytokine release syndrome and macrophage activating syndrome-like (MAS-L)) were strongly associated with the risk of developing new or recurrent AF (Table 1). Only presence of MAS-L remained an independent predictor in the multivariate model (HR 15.4, 95% CI 3.9-61.2, P<0.001). Conclusion AF is mainly seen early following CAR T-cell therapy, and mainly in association with severe inflammatory responses. Early and aggressive treatment of CRS and MAS-L may be recommendable for patients undergoing CAR-T therapy, especially for those with a prior history of AF.

Prevalance and impact of concomitant atrial fibrillation in patients undergoing percutaneous coronary intervention for acute myocardial infarction

Abstract Introduction Atrial fibrillation (AF) is a common cardiac arrhythmia associated with coronary artery disease (CAD) and myocardial infarction (MI). The prevalence of AF in patients following acute MI varies, with conflicting evidence on its impact on outcomes. Concomitant atrial fibrillation is associated with an adverse prognosis in patients with acute myocardial infarction (MI). However, it remains unclear whether this is due to a causal effect of AF, or whether AF acts as a surrogate marker for comorbidities in this population Also, there are limited data on whether coronary artery disease distribution impacts the risk of developing AF. Purpose This large cohort study aims to determine the prevalence of AF in acute MI patients treated with PCI, assess its independent prognostic value for MACCE, investigate the association of AF with CAD distribution patterns, and provide insights into the long-term outcomes of AF in this patient population. Methods A cohort of 1000 consecutive MI patients treated with PCI was retrospectively analyzed. Data on demographics, medical history, presentation, treatment, and outcomes was collected. Propensity score matching was used to adjust for baseline differences between AF and non-AF groups. CAD distribution, major adverse events, and MACCE were assessed using statistical analyses. Results Amongst the studied population, 6.5% people had AF (65/1000) and it was noted that those with AF had a worse outcome. However, on statistical analyses (both on multivariable cox and propensity matching) accounting for risk factors, outcomes were not significantly different between those with and without AF. Hence, this negated key baseline differences between AF and non-AF groups, with no significant differences in demographics or presentation. Patients with AF had a higher prevalence of severe CAD in the left main stem (LMS) and left circumflex artery (LCx). The association of AF with MACCE was not significant in the matched groups. Long-term follow-up revealed similar rates of MACCE between AF and non-AF groups. Discussion AF in acute MI patients undergoing PCI is associated with a higher prevalence of severe CAD in the LMS and LCx. AF appears to be a surrogate marker of other risk factors, rather than an independent risk factor for MACCE. The study highlights the need for tailored aggressive treatment for risk factor modification in AF patients with MI. Conclusions AF is associated with an increased risk of MACCE in acute MI patients undergoing PCI. However, this association is primarily driven by the burden of comorbidities associated with AF, emphasizing the importance of tailored treatment strategies for AF patients. Prospective studies with routine ambulatory monitoring are recommended to validate these findings and guide future practice.

Long-term risk of heart failure and postoperative atrial fibrillation following noncardiac surgery: not so different from non-surgical atrial fibrillation

Abstract Background Atrial fibrillation (AF) is associated with the development of heart failure (HF). However, it is unclear if postoperative AF (POAF) after noncardiac surgery differs from non-surgical AF in terms of the risk of HF. Objectives To investigate the long-term rate of incident HF in patients developing new-onset POAF after noncardiac surgery relative to patients with non-surgical nonvalvular AF (NVAF). Methods Using Danish nationwide registries, all patients aged ≥30 years who developed POAF following noncardiac, nonobstetric surgery from 1996 to 2020 were identified. These patients were matched in a 1:3 ratio by age, sex, selected comorbidities, and year of inclusion with patients with non-surgical NVAF. The primary outcome was incident HF. Secondary outcomes were HF hospitalization and all-cause mortality. Results A total of 1,846 patients with POAF were matched with 5,538 patients with non-surgical NVAF (median age: 76 years [25th-75th percentile: 67-83 years]; 53.1% females). The median follow-up was 7.6 years. Compared with patients with non-surgical NVAF, patients with POAF did not have a significantly different rate of incident HF (2.7 versus 3.0 events per 100 person-years; HR 0.89 [95% CI, 0.78-1.03]) or HF hospitalization (2.2 versus 2.4 per 100 person-years; HR 0.88 [95% CI, 0.76-1.03]), but they had a higher rate of all-cause mortality (10.0 versus 8.7 per 100 person-years; HR 1.27 [95% CI, 1.18-1.37]) (Figure 1). Conclusions Patients with new-onset postoperative atrial fibrillation did not have a significantly different rate of incident heart failure or heart failure hospitalization, but they had a higher associated rate of all-cause mortality compared to patients with non-surgical atrial fibrillation. This finding suggests that postoperative atrial fibrillation may be regarded as non-surgical atrial fibrillation in terms of the long-term risk of heart failure. This highlights the importance of increased awareness among physicians of the risk of adverse outcomes, including heart failure, in patients with postoperative atrial fibrillation after noncardiac surgery. Closer postoperative follow-up and monitoring, as well as aggressive treatment of cardiovascular risk factors, may be warranted to reduce the risk of adverse outcomes in these patients.

Postoperative atrial fibrillation following noncardiac surgery is associated with long-term heart failure: insights from a nationwide cohort

Abstract Background Atrial fibrillation (AF) is associated with the development of heart failure (HF). Whether postoperative AF (POAF) also confers a greater risk of HF is unclear. Purpose To investigate the long-term rate of incident HF in patients developing new-onset POAF after noncardiac surgery relative to patients who did not develop POAF after noncardiac surgery. Methods In this cohort study, the Danish nationwide registries were used to identify all patients aged ≥30 years who developed POAF following noncardiac, nonobstetric surgery from 1996 to 2020. These patients were matched in a 1:3 ratio by age, sex, type of surgery, selected comorbidities, and year of inclusion with patients without POAF after noncardiac surgery. The primary outcome was incident HF. Secondary outcomes were HF hospitalization and all-cause mortality. Results A total of 2,270 patients with POAF were matched with 6,810 patients without POAF (median age: 75 years [25th-75th percentile: 67-82 years]; 53.5% females). The median follow-up was 7.2 years. Compared with patients without POAF, those with POAF had a higher associated long-term rate of incident HF (2.6 versus 1.2 events per 100 person-years; HR 2.39 [95% CI 2.06-2.78]]), HF hospitalization (2.2 versus 1.0 events per 100 person-years; HR 2.33 [95% CI 1.97-2.74]), and all-cause mortality (9.8 versus 7.4 events per 100-person-years; HR 1.55 [95% CI 1.45-1.66]) (Figure 1). Conclusions Patients with new-onset postoperative atrial fibrillation following noncardiac surgery had a higher associated long-term rate of incident heart failure compared to those without postoperative atrial fibrillation following noncardiac surgery. These findings highlight the importance of increased awareness among physicians of the risk of adverse outcomes, including heart failure, in patients with postoperative atrial fibrillation after noncardiac surgery. Closer postoperative follow-up and monitoring, as well as aggressive treatment of cardiovascular risk factors, may be warranted to reduce the risk of adverse outcomes in these patients.

Endoplasmic Reticulum Stress in Bronchopulmonary Dysplasia: Contributor or Consequence?

Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity. Oxidative stress (OS) and inflammation are the major contributors to BPD. Despite aggressive treatments, BPD prevalence remains unchanged, which underscores the urgent need to explore more potential therapies. The endoplasmic reticulum (ER) plays crucial roles in surfactant and protein synthesis, assisting mitochondrial function, and maintaining metabolic homeostasis. Under OS, disturbed metabolism and protein folding transform the ER structure to refold proteins and help degrade non-essential proteins to resume cell homeostasis. When OS becomes excessive, the endogenous chaperone will leave the three ER stress sensors to allow subsequent changes, including cell death and senescence, impairing the growth potential of organs. The contributing role of ER stress in BPD is confirmed by reproducing the BPD phenotype in rat pups by ER stress inducers. Although chemical chaperones attenuate BPD, ER stress is still associated with cellular senescence. N-acetyl-lysyltyrosylcysteine amide (KYC) is a myeloperoxidase inhibitor that attenuates ER stress and senescence as a systems pharmacology agent. In this review, we describe the role of ER stress in BPD and discuss the therapeutic potentials of chemical chaperones and KYC, highlighting their promising role in future therapeutic interventions.

Fatal invasive Aspergillus infection in an elderly patient with hepatitis E: A case report and literature review.

Elderly patients with acute liver failure are highly susceptible to severe complications, such as invasive fungal infections, due to weakened immune systems and altered gut microbiota. A thorough understanding of liver failure and opportunistic infections is crucial for effective management. An 84-year-old male with acute liver failure from hepatitis E experienced worsening jaundice despite standard treatments. He also developed respiratory symptoms, including blood-streaked sputum, raising concerns about a potential fungal infection. The patient was diagnosed with acute liver failure secondary to hepatitis E and an invasive fungal infection caused by Aspergillus fumigatus. Initial treatments included artificial liver plasma exchange and antifungal prophylaxis. Further diagnostics, including bronchoscopy and next-generation sequencing of alveolar lavage fluid, confirmed the Aspergillus infection. Elderly liver failure patients are particularly prone to opportunistic infections, underscoring the need for vigilant monitoring and early intervention. Despite aggressive treatments, including antifungal therapy and artificial liver support, prognosis remains poor, highlighting the importance of prompt diagnosis and comprehensive management to enhance patient outcomes.

Interpretation of the key points of Regulation for Diagnosis and Treatment of Non-neonatal Tetanus (2024 Edition)

Non-neonatal tetanus is an acute, specific, toxic disease in patients over 28 days of age, characterized by continuous rigidity and paroxysmal spasms of the skeletal muscles throughout the body caused by the intrusion of Clostridium tetani through skin or mucosal membrane into the body and reproducing in anaerobic environments to produce exotoxins. The mortality rate of severe patients is close to 100% without medical intervention. Even with aggressive comprehensive treatment, the global mortality rate remains at 30%-50%, making it a potentially fatal disease. In order to standardize the diagnosis, treatment and prevention of non-neonatal tetanus, based on "Regulation for Diagnosis and Treatment of Non-Neonatal Tetanus (2019)", experts have revised this regulation according to clinical practice and recent research progress in this field to guide medical institutions in the prevention and control of non-neonatal tetanus. This article interprets the key points and basis for updating the 2024 edition regulation to guide clinical implementation and application.

Osteosarcoma with Pathological Fracture: A Rare Case Report

Introduction: Osteosarcoma is a primary malignant bone tumor originating from stem cells and is characterized by the proliferation of tumor cells that directly form immature bone or bone-like tissue. Osteosarcoma represents only 3% to 5% of all spinal malignancies. The aim of study is to discuss the importance of diagnostic investigation for a relatively rare case of spinal osteosarcoma. Case presentation: A 49 years old female came to the Emergency Unit, with a chief complaint of bilateral weakness of lower extremities for 1 year and worsening in 2 weeks. Upon examination, the initial diagnosis was mistaken for a spinal canal stenosis because metastatic bone disease from previous history of malignant melanoma. Subsequently, a decompression with stabilization fusion and biopsy is performed. Primary osteosarcoma was confirmed from histopathology results. Further chemotherapy is planned referring to confirmed primary osteosarcoma on histopathology. Discussion: Spinal osteosarcoma is very rare. Osteosarcoma occurs most frequently in the appendicular skeleton, especially the distal femur and proximal tibial metaphysis, which account for 90% of all cases. Primary osteosarcomas of the vertebral column are uncommon and occur dominantly in the vertebral body. Biopsy remains the gold standard of care for diagnosis. Conclusion: The performance of MRI and pathologic evaluation with immunohistochemistry is particularly important for the differential diagnosis of soft tissue tumors. Histopathologic analysis also plays an important role in differentiating from metastatic bone disease. An aggressive treatment plan and long-term follow-up are mandatory in managing this case. Keywords: osteosarcoma, spinal osteosarcoma, spinal canal stenosis, malignancy, pathological fracture, rare case.

Identifying Patients at Increased Risk for Poor Outcomes Among Poor-Grade Aneurysmal Subarachnoid Hemorrhage Patients: The IPOGRO Risk Model

Background: A subarachnoid hemorrhage due to an aneurysmal rupture (aSAH) is a serious condition with severe neurological consequences. The World Federation of Neurosurgical Societies (WFNS) classification is a reliable predictor of death and long-term disability in patients with aSAH. Poor-grade neurological conditions on admission in aSAH (PG-aSAH) are often linked to high mortality rates and unfavorable outcomes. However, more than one-third of patients with PG-aSAH may recover and have good functional outcomes if aggressive treatment is provided. We developed a risk model called Identifying POor GRade Outcomes (IPOGRO) to predict 6-month mRS outcomes in PG-aSAH patients as a secondary analysis of a previously published study. Methods: All consecutive patients in poor-grade neurological conditions (WFNS IV-V) admitted to our institute from 2010 to 2020 due to aSAH were considered. Clinical and neuroradiological parameters were employed in the univariable analysis to evaluate the relationship with a 6-month modified Rankin Scale (mRS). Then, a multivariable multinomial regression model was performed to predict 6-month outcomes. Results: 149 patients with PG-aSAH were included. Most patients were surgically treated, with only 33.6% being endovascularly treated. The 6-month mRS score was significantly associated with clinical parameters on admission, such as lowered Glasgow Coma Scale (GCS), leukocytosis, hyperglycemia, raised Systolic Blood Pressure (SBP), greater Simplified Acute Physiology Score (SAPS II score), increased initial serum Lactic Acid (LA) levels, and the need for Norepinephrine (NE) administration. Neuroradiological parameters on the initial CT scan showed a significant association with a worsening 6-month mRS. The IPOGRO risk model analysis showed an association between a WFNS V on admission and a poor outcome (mRS 4-5), while raised SBP was associated with mortality. Conclusions: Our IPOGRO risk model indicates that PG-aSAH patients with higher SBP at admission had an increased risk of death at 6-month follow-up, whereas patients with WFNS grade V at admission had an increased risk of poor outcome but not mortality.