A Cohort Study

[Posted 27/Jul/2022]

AUDIENCE: Internal Medicine, Cardiology

KEY FINDINGS: Postoperative AF after noncardiac surgery is associated with similar risk for thromboembolism compared with nonoperative AF. Our findings have potentially important implications for the early postsurgical and subsequent management of postoperative AF.

BACKGROUND: Postoperative atrial fibrillation (AF) after noncardiac surgery confers increased risks for ischemic stroke and transient ischemic attack (TIA). How outcomes for postoperative AF after noncardiac surgery compare with those for AF occurring outside of the operative setting is unknown. Purpose of this study is to compare the risks for ischemic stroke or TIA and other outcomes in patients with postoperative AF versus those with incident AF not associated with surgery.

DETAILS: Patients were categorized as having AF occurring within 30 days of a noncardiac surgery (postoperative AF) or having AF unrelated to surgery (nonoperative AF). The population consisted predominantly of White patients; caution should be used when extrapolating the results to more racially diverse populations. Of 4231 patients with incident AF, 550 (13%) had postoperative AF as their first-ever documented AF presentation. Over a mean follow-up of 6.3 years, 486 patients had an ischemic stroke or TIA and 2462 had subsequent AF; a total of 2565 deaths occurred. The risk for stroke or TIA was similar between those with postoperative AF and nonoperative AF (absolute risk difference [ARD] at 5 years, 0.1% [95% CI, -2.9% to 3.1%]; hazard ratio [HR], 1.01 [CI, 0.77 to 1.32]). A lower risk for subsequent AF was seen for patients with postoperative AF (ARD at 5 years, -13.4% [CI, -17.8% to -9.0%]; HR, 0.68 [CI, 0.60 to 0.77]). Finally, no difference was seen for cardiovascular death or all-cause death between patients with postoperative AF and nonoperative AF.

Copyright © American College of Physicians. All Rights Reserved.

Source: Siontis, K. C., Gersh, B. J., Weston, S. A., et al. (2022). Associations of Atrial Fibrillation After Noncardiac Surgery With Stroke, Subsequent Arrhythmia, and Death: A Cohort Study. Annals of Internal Medicine. Published: July 26, 2022. DOI: 10.7326/M22-0434.

[Posted 4/Nov/2025]

AUDIENCE: Oncology, Gastroenterology

KEY FINDINGS: In the phase II Pancreatic Adenocarcinoma Signature Stratification for Treatment-01 (PASS-01) trial population, PFS was similar between GnP and mFFX; however, OS and safety trends favored GnP. The second-line setting appears inadequate to offer precision choices, given the short survival observed.

BACKGROUND: Goal of this study is to assess modified folinic acid/leucovorin, fluorouracil, irinotecan, oxaliplatin (FOLFIRINOX [mFFX]) versus gemcitabine/nab-paclitaxel (GnP) in de novo metastatic pancreatic ductal adenocarcinoma (PDAC) and explore predictive biomarkers.

DETAILS: Patients were randomly assigned 1:1 to mFFX or GnP with exclusion of germline pathogenic variants in BRCA1/2 or PALB2. The primary end point was progression-free survival (PFS) between arms with 0.3 significance. The per-protocol (PP) population included patients who received one dose of chemotherapy. Pretreatment biopsies underwent whole-genome/transcriptome sequencing and patient-derived organoid (PDO) development, providing correlate recommendations at a molecular tumor board and outcomes assessed according to RNA signatures (basal-like v classical). Of 160 patients randomly assigned (80 mFFX, 80 GnP), 140 patients were in the PP population (71 mFFX, 69 GnP), with median follow-up of 8.3 months. The median PFS was 4.0 months for mFFX versus 5.3 months for GnP (hazard ratio [HR], 1.37 [95% CI, 0.97 to 1.92]; P = .069) in intention-to-treat. Median overall survival (OS) was 8.5 months with mFFX and 9.7 months with GnP (HR, 1.57 [95% CI, 1.08 to 2.28]; P = .017). Genomic data were generated in 94%, transcriptomes in 74%, and PDOs in 50%. The median PFS for those with basal-like was 3.0 (mFFX) and 5.5 (GnP) months (P = .17), and classical PDAC was 6.3 (mFFX) versus 5.4 (GnP) months (P = .36). The median OS in basal-like was 7.5 (mFFX) and 8.9 (GnP) months (P = .75) versus in classical OS was 9.7 (mFFX) and 13.9 (GnP) months (P = .047). Overall, 75 (54%) of patients received second-line treatment, 33/75 (44%) correlate-guided. The median time on second-line treatment was only 2.1 months with a median OS of 5.4 months for a correlate-guided choice versus 4.4 months on a standard chemotherapy approach (P = .45).

Copyright © American Society of Clinical Oncology. All rights reserved.

Source: Knox, J. J., O'Kane, G., King, D., et al. PASS-01: Randomized Phase II Trial of Modified FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel and Molecular Correlatives for Previously Untreated Metastatic Pancreatic Cancer. Journal of Clinical Oncology. 2025; 43(31):3325. Published: November, 2025. DOI: 10.1200/JCO-25-004.

[Posted 3/Nov/2025]

AUDIENCE: Internal Medicine, Cardiology

KEY FINDINGS: HDL_Lox levels are highest in patients with ACS. Patients with stable CAD have higher levels than healthy controls. Correspondingly, the parameters of HDL function measured in this study, which all indicate a loss of HDL's atheroprotective function, correlate with these findings. Our study establishes a novel mechanistic pathway linking oxidized HDL to the presence of an ACS.

BACKGROUND: High-density lipoprotein (HDL) function, rather than its concentration, plays a crucial role in the development of coronary artery disease (CAD). Diminished HDL antioxidant properties, indicated by elevated oxidized HDL (nHDL_Lox) and diminished paraoxonase-1 (PON-1) activity, may contribute to vascular dysfunction and inflammation. Data on these associations in CAD patients, including acute coronary syndrome (ACS), remain limited. The aim of this study is to assess the association of oxidized HDL with PON-1 activity, oxidized low-density lipoprotein (LDL), vascular cell adhesion molecule-1 (VCAM-1), IL-6 levels, and nitric oxide (NO) production as markers of vascular health.

DETAILS: Authors assessed HDL function in three groups: 90 CAD patients, 90 healthy controls, and 90 ACS patients. HDL antioxidant function was measured using a validated biochemical assay to quantify oxidized HDL (nHD_Lox). Plasma PON-1 activity, oxidized LDL, VCAM-1, IL-6, and NO production were also evaluated. ACS patients had nHDL_Lox levels 140% higher than healthy controls (p < 0.001). Higher nHDLox levels were significantly linked to vascular inflammation, reflected by elevated VCAM-1 levels. Additionally, a reduced PON-1 activity indicates an impaired antioxidant protection in ACS patients. Finally, oxidized LDL levels were elevated, and NO production was reduced, suggesting impaired vascular function.

Copyright © John Wiley & Sons, Inc. All rights reserved

Source: Sasko, B., Pagonas, N., Christ, M., et al. Oxidized High-Density Lipoprotein Associates with Cardiometabolic Dysfunction in Coronary Artery Disease and Acute Coronary Syndrome. Journal of Internal Medicine. 2025; 298(5): 464-477. Published: November, 2025. DOI: 10.1111/joim.70019.

[Posted 27/Oct/2025]

AUDIENCE: Infectious Disease, Microbiologists

KEY FINDINGS: Enhanced antibiotic performance observed in preclinical mouse models. Potential to improve treatment outcomes for multiple intracellular bacterial infections. Ongoing efforts include mechanism elucidation and patent development.

BACKGROUND: Antibiotic resistance has severely limited the effectiveness of conventional treatments against persistent bacterial infections. Some pathogens, such as Staphylococcus aureus, Mycobacterium tuberculosis, and Salmonella enterica, can survive inside immune cells, remaining dormant and shielded from antibiotic action. The increasing prevalence of such infections underscores an urgent need for alternative approaches that do not rely solely on developing stronger antibiotics.

DETAILS: Researchers at the University of North Carolina (UNC) School of Medicine, led by Dr. Brian Conlon and Dr. Kuan-Yi Lu, identified a novel small molecule that modifies immune cell behavior to enhance antibiotic performance. Instead of directly targeting bacteria, the molecule reprograms the host's immune cells to activate dormant pathogens, rendering them more susceptible to antibiotic killing.

The team screened approximately 5,000 small molecules through the UNC Small Molecule Screening Core. They used luminescent reporter strains of S. aureus to identify compounds that triggered bacterial activation. The most promising compound was subsequently tested in mouse models, where it significantly improved antibiotic efficacy when administered alongside standard treatments.

In animal models, the selected molecule substantially improved pathogen clearance for S. aureus, M. tuberculosis, and S. enterica when used in combination with existing antibiotics. This finding supports a new therapeutic concept: targeting the host cell environment can potentiate antibiotic activity and overcome intracellular bacterial persistence. The discovery presents an innovative direction for combating infections that evade standard therapy.

Copyright © UNC School of Medicine. All rights reserved.

Source: Conlon, B. and Kuan-Yi, L. UNC Researchers Discover Method to Combat Antibiotic Treatment Failure. UNC Health Newsroom. 2025; Published: October 14, 2025.

A Systematic Review and Meta-analysis.

[Posted 17/Oct/2025]

AUDIENCE: Gastroenterology, Internal Medicine, Oncology

KEY FINDINGS: ESD is a safe and effective option for managing RNDLs with a low recurrence rate. Adverse events such as postprocedural perianal pain, postprocedural bleeding, and anal stenosis seem to be more common compared with colorectal ESD done for more proximal lesions. However, these can typically be managed conservatively or with minimally invasive endoscopic techniques.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a superior, minimally invasive technique compared with other snare-based endoscopic resection techniques for rectal neoplasms extending to the dentate line (RNDLs). However, performing a successful ESD in the anal canal can be challenging due to vascularity and limited scope stability. In this meta-analysis, we aim to evaluate the safety and efficacy of ESD for RNDLs.

DETAILS: Authors performed a comprehensive electronic database search from January 2005 through January 2024 for studies evaluating outcomes of ESD performed for managing RNDLs. Pooled proportions were calculated using random-effect models. Heterogeneity was evaluated using I2 and Q statistics. Data were extracted from 11 studies comprising 496 patients. The pooled en bloc resection rates were 93.60% (95% CI = 90.70-95.70). The pooled R0 resection rate was 80.60% (95% CI = 70.50-87.80). The pooled recurrence rate was 4.00% (95% CI = 2.40-6.50). There was no evidence of significant heterogeneity calculated using the Q test and I2 statistic. The main adverse events were anal pain, postprocedural bleeding, and anal stricture with pooled rates of 20.20% (95% CI = 14.80-26.90), 8.20% (95% CI = 4.70-14.0), and 3.50% (95% CI = 2.10-5.70), respectively.

Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Source: Gopakumar, H., Dahiya, D., Draganov, P. V., et al. Safety and Efficacy of Endoscopic Submucosal Dissection for Rectal Neoplasms Extending to the Dentate Line: A Systematic Review and Meta-analysis. Journal of Clinical Gastroenterology. 2025; 59(10): 954-963. Published: November/December, 2025. DOI: 10.1097/MCG.0000000000002090.

A Cohort Study Investigating Adherence of Dose and Duration to UK Clinical Guidelines

[Posted 14/Oct/2025]

AUDIENCE: Psychiatry, Family Medicine

KEY FINDINGS: This study highlights how antipsychotic prescribing in dementia is discordant with current NICE guidelines on both duration and dose. More than half of those who discontinued their treatment then restarted treatment. These findings emphasise a persistent gap between clinical guidelines and real-world prescribing, underscoring the need for interventions that prioritise safety and person-centred dementia care.

BACKGROUND: In the UK, it is recommended by the National Institute for Health and Care Excellence (NICE) that if antipsychotics are initiated in people living with dementia, treatment should be at the lowest dose for the shortest time possible (1-3 months). In this study, authors aimed to investigate how dose and duration of antipsychotic medication adhere to UK clinical guidelines and explore treatment restart details in those who stop treatment.

DETAILS: Authors did a retrospective cohort study using longitudinal UK primary care data from the IQVIA Medical Research Database. Authors included people living with dementia aged 60-85 years who received their first antipsychotic prescription between Jan 1, 2000, and Dec 31, 2023. Individuals with any previous antipsychotic prescriptions in their records more than 1 year before a dementia diagnosis and those who had missing social deprivation information were excluded from the study. Duration of first and subsequent antipsychotic treatment episodes, medication dosage, and treatment discontinuation and reinitiation rates were investigated. Duration and discontinuation were defined by grouping consecutive prescriptions into treatment episodes using the waiting time distribution method (80% inter-arrival density, 59 days). Daily doses were derived from strength and frequency information and categorised as low or moderate or high based on established minimum effective dose equivalences. People with lived experience of dementia care contributed throughout this project, shaping the research question and advising on interpretation and dissemination strategies. In the dataset search, authors identified 108,910 people with a record indicating dementia at any time. In total, 99,091 cases were excluded (ie, individuals with no antipsychotic prescription between the ages of 60 and 85 years between 2000 and 2023, a previous history of antipsychotics, missing deprivation information, or only one eligible prescription). Authors included 9819 people living with dementia aged 60-85 years who received their first antipsychotic prescription between 2000 and 2023 in the study. 5310 (54.1%) were female and 4509 (45.9%) were male, with a mean age of 77.1 years (SD 5.6 years), and ethnicity data were not available. The first treatment episode lasted a median of 7 months (IQR 6.6-8.7), exceeding NICE guidelines of 1-3 months and 18.1% [95% CI 17.4-18.9]) were initiated on a prescription above the minimum effective dose (ie, low dose). Of the 1781 participants who started on a moderate or high dose, 519 (29.1%) had a moderate or high dose in all quarters of the first year of treatment. 1 year after treatment initiation, 5136 (78.3%) of 6559 eligible individuals remained on medication (48.9% [95% CI 47.7-50.1] on low dose, 14.8% [13.9-15.6] on moderate or high dose of haloperidol, olanzapine, quetiapine or risperidone; and 14.6% [13.8-15.5] on other antipsychotics). Of the 5547 individuals eligible to restart treatment after initial discontinuation, 3106 (56%) restarted with a median treatment duration of 2.6 months (IQR 0.0-9.9).

Copyright © Elsevier Ltd. All rights reserved.

Source: Smsith, H. C., Petersen, I., Hayes, J. F., et al. (2024). Antipsychotic Prescriptions in People With Dementia in Primary Care: A Cohort Study Investigating Adherence of Dose and Duration to UK Clinical Guidelines. The Lancet Psychiatry. 2025; 12(10): 758-767. Published: October, 2025. DOI: 10.1016/S2215-0366(25)00261-5.