Unselected Patient Population Research Articles

ATRIAL FIBRILLATION IN A CIED POPULATION: RESULTS FROM A TELEMONITORING FOLLOW–UP

Abstract Background Telemedicine has emerged as a crucial tool in managing patients with Cardiac Implantable Electronic Devices (CIED), addressing the common challenge of the Atrial Fibrillation (AF) in cardiology. The incidence of AF in CIED recipients varies widely (30–70%), influenced by implant indication, device type, and population characteristics. This study aims to evaluate AF in an unselected, real–world CIED population, considering patients’ characteristics and the remote follow–up. Methods and Results 808 consecutive CIED recipients were evaluated between 2021 and 2023 in two Italian Division of Cardiology by collecting patients’ baseline characteristics and the scheduled remote follow–up data. Mean age was 75.6±12.6 years, 42% were females. 16.7% of the population was working actively and 73% of individuals were assisted by at least one caregiver, reflecting a diminished quality of life (EQ–5D score 8.9±4.3). Over a median follow–up of 20.6 months, 8.9% of patients died. 68.8% of the patients received a pacemaker, 19.3% an ICD and 11.9% a loop recorder. History of AF was present in 40.1% of the population, with a prevalence of permanent AF (46.6%). Ongoing anticoagulant therapy was documented in 303 patients (37.5%), 71% of whom were taking direct oral anticoagulants. Baseline CHA2DS2–VASC score was ≥3 in 79.7%, and the median HAS–BLED score was 1. During the observation period, scheduled remote transmissions revealed 719 AF episodes (15.7 episodes/patient/year), causing 21% of the overall remote alarms. Among patients without AF history, 69 (14.3%) experienced AF episodes (4.8 episodes/patient/year). Notably, 21.8% of the AF episodes lasted less than 10 minutes. Conclusions The wide spreading of heart rhythm monitoring technologies reveals the challenge of the subclinical AF in healthcare systems. This study, encompassing an unselected CIED population of elderly and frail patients with high AF prevalence, highlights AF as a primary cause of remote alerts and a substantial burden in telemonitoring controls. Telemedicine facilitated new AF diagnoses in 14.3% of individuals without a prior AF history and resulted a valuable tool considering the significant cardioembolic risk in these patients. However, the initiation of anticoagulation therapy remains debatable, especially for episodes of brief duration which in our experience exceeded 20% of the cases.

Post Percutaneous Transluminal Coronary Angioplasty (PTCA) Coronary Aneurysm- A Case Report

Introduction Coronary aneurysm defined angiographically as luminal dilation 50% larger than that of the adjacent reference segment. (1) Drug-eluting stents (DES), which locally elute antiproliferative drugs, can dramatically inhibit neointimal growth. However, several pathological studies have indicated that DES may delay healing after vascular injury, and DES implantation may be theoretically associated with a risk of coronary artery aneurysm formation. Coronary aneurysms have been reported from 3 days to up to 4 years after DES implantation procedures, with varying clinical presentations. The incidence of coronary artery aneurysms after DES implantation is low within the first 9 months, with a reported incidence of 0.2% to 2.3%, a rate similar to that reported after bare-metal stent (BMS) implantation (0.3% to 3.9%) in the DES versus BMS randomized trials.(2) However, the true incidence of coronary aneurysms in an unselected patient population is still largely unknown. It can be congenital, or secondary to vasculitis (Kawasaki disease) or after percutaneous coronary intervention. Drug-eluting stents (DES), which locally elute antiproliferative drugs, can dramatically inhibit neointimal growth has become standard of care for routine coronary angioplasty. However, several pathological studies have indicated that DES may delay endothelial healing after vascular injury, and DES implantation may be theoretically associated with a risk of coronary artery aneurysm formation (3)

Family history as a major prerequisite for microsatellite instability screening in colorectal cancer is a poor selection tool.

Deficient mismatch repair (MMR) leading to microsatellite instability (MSI) in tumors is thought to be present in over 15% of colorectal cancer (CRC) cases. Testing CRC for MSI has traditionally been recommended following the fulfillment of clinical criteria. However, the performance of clinical criteria, especially the family history, as a selection tool for MSI screening in CRC is questionable. We retrospectively investigated the incidence of high degree MSI (MSI-H) tumors in an unselected population of CRC patients and compared its prevalence between individuals with and without family history of cancers within the spectrum of MSI-H tumors as defined in the revised Bethesda criteria. The study population included 274 patients, 70 with positive and 204 without family history of MSI-H tumors with complete data including findings from MSI analysis. The overall incidence of MSI-H CRC was 18.98%. There was no statistically significant difference in the incidence of MSI-H CRC amongst both groups. The sensitivity and specificity of family history with regard to the presence of an MSI-H tumor in this collective was 36.5% and 77.5%, respectively. A relevant number of cases with high MSI-H CRC may be missed secondary to screening based on clinical criteria like family history alone. Thus, systematic screening independent of clinical characteristics, especially family history of cancer should be recommended in all cases with CRC.

Efficacy of NSCLC Rechallenge with Immune Checkpoint Inhibitors following Disease Progression or Relapse.

Immune checkpoint inhibitors (ICIs) are at the forefront of advanced non-small-cell lung cancer (NSCLC) treatment. Still, only 27-46% of patients respond to initial therapy with ICIs, and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6-3.1 months and a Disease Control Rate (DCR) of 21.4-41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75-81%, according to post hoc analyses of several clinical trials. Future research on ICI rechallenge for NSCLC should focus on better patient stratification to reflect the underlying biology of immunotherapy resistance more accurately. In this review, we summarize evidence regarding rechallenge immunotherapy efficacy following NSCLC disease progression or relapse, as well as ongoing trials on immunotherapy rechallenge.

Clinical outcomes for previously treated patients with advanced biliary tract cancer: a meta-analysis.

Aim: A systematic review and meta-analysis were performed to evaluate the efficacy of treatments for previously treated advanced biliary tract cancer (BTC) patients. Materials & methods: Databases were searched for studies evaluating treatments for advanced (unresectable and/or metastatic) BTC patients who progressed on prior therapy. Pooled estimates of objective response rate (ORR), median overall survival (OS)and median progression-free survival(PFS)were calculated using random effects meta-analysis. Results: Across 31 studies evaluating chemotherapy or targeted treatment regimens in an unselected advanced BTC patient population, pooled ORR was 6.9%, median OS was 6.6monthsand median PFS was 3.2months. Conclusion: The efficacy of conventional treatments for previously treated advanced BTC patients is poor and could be improved by novel therapies.

Delayed Gadolinium Leakage in Ocular Structures on Brain MR Imaging: Prevalence and Associated Factors.

Gadolinium leakage in ocular structures (GLOS) is characterized by hyperintense signal in the chambers of the eye on FLAIR and has been reported in association with blood-ocular barrier breakdown in patients with ischemic strokes. The underlying mechanism of GLOS remains poorly understood; however, some studies suggest it may be part of a physiologic excretion pathway of gadolinium. This study aimed to determine the prevalence of GLOS in an unselected patient population. A retrospective analysis was conducted on 439 patients who underwent brain MR imaging within 7 days of receiving a gadolinium-based contrast agent injection for a prior MR imaging study. Clinical, imaging, and laboratory data were collected. Descriptive and logistic regression analyses were performed. GLOS was observed in 26 of 439 patients (6%). The occurrence of GLOS varied with time, with 3 (12%), 14 (54%), 8 (31%), and 1 (4%) patient showing GLOS within 24, 25-72, 73-120, and >120 hours after gadolinium-based contrast agent injection, respectively. Patients with GLOS were older (median age: 72 versus 55 years, P = .001) and had higher median serum creatinine levels (73 versus 64 µmol/L, P = .005) and a lower median estimated glomerular filtration rate (84 versus 101 mL/min/1.73 m2, P < .001). A shorter median time interval between gadolinium-based contrast agent injection and the index brain MR imaging was observed in the group positive for GLOS (62 versus 91 hours, P = .003). Multivariable regression analysis identified the estimated glomerular filtration rate (OR = 0.970; 95% CI, 0.049-0.992; P = .008) and time interval since gadolinium-based contrast agent injection (OR = 0.987; 95% CI, 0.977-0.997; P = .012) as independent factors associated with GLOS. GLOS was observed in only a small percentage of patients receiving gadolinium-based contrast agent within 7 days before brain MR imaging. This phenomenon was noted in patients with normal findings on brain MR imaging and those with various CNS pathologies, and it was associated with lower estimated glomerular filtration rates and shorter time intervals after gadolinium-based contrast agent injection. While GLOS may be a physiologic gadolinium-based contrast agent excretion pathway, the presence of ocular disease was not formally evaluated in the included population. Awareness of GLOS is nonetheless useful for appropriate radiologic interpretation.

UK Biobank imaging in a memory clinic population: associations between imaging‐derived phenotypes and cognition in the Oxford Brain Health Clinic

AbstractBackgroundSince August 2020, the Oxford Brain Health Clinic (BHC) has seen over 200 NHS memory clinic patients (O’Donoghue et al., 2022). In addition to high‐quality cognitive and lifestyle assessments and opportunities for research participation, patients receive a clinical MRI scan (T1‐weighted, T2‐FLAIR, and SWI) and can consent to additional research scans (diffusion MRI – dMRI, resting‐state functional MRI – rfMRI, and arterial spin labelling ‐ ASL) aligned to the UK Biobank (Griffanti et al., 2022). In this project, we aimed to automatically extract imaging‐derived phenotypes (IDPs) from the different imaging modalities acquired at the BHC and perform unimodal group‐level analyses to explore associations with cognition and diagnoses in this real‐world memory clinic population.MethodAs of January 2023, scans were analysed from 176 BHC patients, 101 of whom completed the additional research MRI scans. Cognitive scores (ACE‐III total score, N = 166) were available from the BHC appointment, and subsequent diagnoses (N = 118) were extracted from electronic healthcare records. Scans were processed using the UK Biobank pipeline (Alfaro‐Almagro et al., 2018), adapted to include previously described modifications (Griffanti et al., 2022). All IDPs were deconfounded for age, sex, and head size. We calculated Spearman correlations with ACE‐III cognitive scores and group comparisons (Kruskal‐Wallis tests) between 3 diagnostic groups: dementia, MCI, and no dementia‐related diagnosis. Results were corrected for multiple comparisons (false discovery rate with Benjamini‐Hochberg procedure; FDR‐adjusted p = 0.000016).Result11 IDPs significantly correlated with ACE‐III (Figure 1). Four voxel‐based morphometry temporal lobe measures, 3 FreeSurfer temporal lobe measures, FIRST left hippocampal volume, and SIENAX peripheral grey matter volume positively correlated with ACE‐III, in line with known dementia‐related atrophy patterns (Figure 2). dMRI mean diffusivity in the bilateral parahippocampal part of the cingulum negatively correlated with ACE‐III, highlighting white matter disruption (Figure 3). No FDR‐corrected differences were found between diagnostic groups.ConclusionUsing an unselected patient population, all of whom have a degree of memory problems, this work provides real‐world validation of associations that are well‐established in the research context. This represents a key step towards integrating research‐quality imaging in the memory clinic. Imaging and clinical variables are planned to be available through DPUK.

UK Biobank imaging in a memory clinic population: associations between imaging‐derived phenotypes and cognition in the Oxford Brain Health Clinic

AbstractBackgroundSince August 2020, the Oxford Brain Health Clinic (BHC) has seen over 200 NHS memory clinic patients (O’Donoghue et al., 2022). In addition to high‐quality cognitive and lifestyle assessments and opportunities for research participation, patients receive a clinical MRI scan (T1‐weighted, T2‐FLAIR, and SWI) and can consent to additional research scans (diffusion MRI – dMRI, resting‐state functional MRI – rfMRI, and arterial spin labelling ‐ ASL) aligned to the UK Biobank (Griffanti et al., 2022). In this project, we aimed to automatically extract imaging‐derived phenotypes (IDPs) from the different imaging modalities acquired at the BHC and perform unimodal group‐level analyses to explore associations with cognition and diagnoses in this real‐world memory clinic population.MethodAs of January 2023, scans were analysed from 176 BHC patients, 101 of whom completed the additional research MRI scans. Cognitive scores (ACE‐III total score, N = 166) were available from the BHC appointment, and subsequent diagnoses (N = 118) were extracted from electronic healthcare records. Scans were processed using the UK Biobank pipeline (Alfaro‐Almagro et al., 2018), adapted to include previously described modifications (Griffanti et al., 2022). All IDPs were deconfounded for age, sex, and head size. We calculated Spearman correlations with ACE‐III cognitive scores and group comparisons (Kruskal‐Wallis tests) between 3 diagnostic groups: dementia, MCI, and no dementia‐related diagnosis. Results were corrected for multiple comparisons (false discovery rate with Benjamini‐Hochberg procedure; FDR‐adjusted p = 0.000016).Result11 IDPs significantly correlated with ACE‐III (Figure 1). Four voxel‐based morphometry temporal lobe measures, 3 FreeSurfer temporal lobe measures, FIRST left hippocampal volume, and SIENAX peripheral grey matter volume positively correlated with ACE‐III, in line with known dementia‐related atrophy patterns (Figure 2). dMRI mean diffusivity in the bilateral parahippocampal part of the cingulum negatively correlated with ACE‐III, highlighting white matter disruption (Figure 3). No FDR‐corrected differences were found between diagnostic groups.ConclusionUsing an unselected patient population, all of whom have a degree of memory problems, this work provides real‐world validation of associations that are well‐established in the research context. This represents a key step towards integrating research‐quality imaging in the memory clinic. Imaging and clinical variables are planned to be available through DPUK.

External Validation of the OAC3-PAD Bleeding Score in a Nationwide Population of Patients Undergoing Invasive Treatment for Peripheral Arterial Disease

The OAC3-PAD score was developed to predict bleeding risk in patients with lower extremity peripheral arterial disease (PAD), but its performance in concomitant international cohorts is largely unknown. This study aimed to validate the OAC3-PAD score in an unselected nationwide population of patients undergoing invasive treatment for symptomatic PAD. This was a nationwide cohort study including all patients who underwent a first revascularisation procedure or major amputation for symptomatic PAD in Denmark from 2000 - 2021. The study population was stratified based on OAC3-PAD score, and the one year risk of major bleeding was assessed, accounting for the competing risk of death. The score performance was evaluated using calibration plots, C statistic, Brier score, and the index of prediction accuracy (IPA). A total of 52 016 patients were included (mean age 71 years, 43.8% female). The one year risk of major bleeding increased with higher OAC3-PAD score, ranging from 1.6% (95% confidence interval [CI] 1.4 - 1.8%) to 2.3% (95% CI 2.0 - 2.5%), 3.5% (95% CI 3.2 - 3.8%), and 5.2% (95% CI 4.8 - 5.6%) for patients with low, low moderate, moderate high, and high score, respectively. Using patients with low risk as reference, the OAC3-PAD score effectively categorised patients, demonstrating statistically significant differences in bleeding risk acrossstrata. However, the score showed modest discriminative performance, with a C statistic of 65% (95%CI 63 - 66%) and a Brier score of 2.6% (95% CI 2.5 - 2.7%). Nevertheless, it performed significantly better than the null model, as indicated by an IPA of 3.1%. Among patients who underwent invasive treatment for symptomatic PAD in routine care, the OAC3-PAD score was associated with greater risk of major bleeding with increasing score level. However, its discriminatory ability was modest, and the clinical utility remains to be determined.

Characteristics, Treatment Patterns and Survival of International Federation of Gynecology and Obstetrics Stage IV Epithelial Ovarian Cancer—A Population-Based Study

Background: The aim of the present study was to describe an unselected population of patients with diagnosis of FIGO stage IV OC. Methods: Data from 1183 patients were available for analysis. Results: The majority of patients (962/1183, 81.3%) received cancer-directed treatment. The median follow-up time was 3.8 years, and the median overall survival duration was 1.9 years. Notably, patients &gt;80 years had a low overall survival rate (HR of age &gt;80 years vs. ≤50 years was 3.81, 95%-CI [2.76, 5.27], p &lt; 0.0001). The survival rate was best in patients with HGSOC (p &lt; 0.0001). The highest overall survival rate was observed in patients in the group with surgical intervention followed by systemic treatment, with an unadjusted HR of 0.72, 95%-CI [0.59, 0.86], p = 0.007 vs. systemic treatment only. After adjustment for age and histology, survival differences between treatment schemes were smaller (HR 0.81, 95%-CI [0.66, 1.00], p = 0.12). Conclusions: In this cohort of patients with FIGO stage IV OC, more than 80% of the patients received cancer-directed treatment. Age and high-grade serous histology were determinants for survival. The highest overall survival rate was observed in patients who underwent surgery followed by systemic treatment.

DDX41-Low Expression Mimics Germline DDX41-Phenotype in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a complex disease characterized by diverse molecular pathogenesis. Genetic alterations, including germline and somatic variants in the DEAD box helicase 41 gene ( DDX41) located on chromosome 5 play an increasingly recognized role. Recent reports indicate that 5% of intensively treated adult AML patients harbor DDX41 germline mutations ( DDX41MutGL), and their precise impact remains incompletely understood. These studies suggest that DDX41MutGL may define a distinct biological subgroup, associated with e.g. older age, male gender, low blast, and low white blood cell count (WBC). To further elucidate the role of DDX41 in AML, we performed a retrospective analysis of 906 unselected adult AML patients from the AML Cooperative Group (AMLCG) registry (2015-2022), by targeted sequencing. As DDX41MutGL are typically “null mutations”, leading to reduced DDX41 expression, we additionally investigated whether DDX41 gene expression correlates or resembles the observed germline phenotype. Our analysis encompassed &amp;gt;1000 independent gene expression profiles (GSE37642, GSE14468, and GSE106291) of intensively treated adult AML patients. We identified a sub-cohort with low DDX41 ( DDX41-low) expression and re-analyzed them with next-generation sequencing to detect DDX41MutGL. Additionally, we correlated gene expression data with 198 DNA methylation profiles (from patients who had undergone both analyses) to identify potential epigenetic mechanisms underlying DDX41-low expression. Among the 906 patients (median age 61 years; range 18-98 years), we identified 11 unrelated individuals with suspected DDX41MutGL (VAF &amp;gt; 40%). Notably, the overall frequency of DDX41MutGL in the German unselected AML patient population was merely 1%, considerably lower than previously reported (p&amp;lt;0.0001 in comparison to Duployez et al. 2022). Characteristically, DDX41MutGL patients in this cohort were mostly male (73%), with a median age of 67 years displaying low WBC (average 1,3G/l) and a normal karyotype (80%) at initial diagnosis. Remarkably, our analysis of independent large gene expression cohorts revealed a pattern of phenotypic association in patients with decreased DDX41 expression ( DDX41-low) closely resembling those with DDX41MutGL. These associations were consistent across different datasets and included e.g. older age, low WBC, and low blast count. Furthermore, DDX41-low patients had poor overall survival. The DDX41-low subgroup constituted almost 10% of all AML patients, surpassing the reported frequencies of DDX41MutGL. In an exploratory pilot study, we screened 48 patients exhibiting the lowest DDX41 gene expression by sequencing the coding regions for DDX41 mutations but found none, suggesting alternative mechanisms, such as copy number changes, non-coding alterations or aberrant DNA methylation patterns that may replicate the phenotypic effects associated with DDX41MutGL. To further elucidate this mechanism, we correlated the gene expression of DDX41 with all DNA methylation loci (CpG sites covered by the EPIC array) on chromosome 5 using Spearman correlation analysis (GSE106291). We plotted the correlations against the sorted chromosome length, identifying a peak at a specific location corresponding to the PCDH (Protocadherin) cluster (Figure). Thus, DDX41-low was associated with reduced methylation at the PCDH loci and linked to higher PCDH gene expression. Across several data sets, we confirmed the association between higher PCDH cluster gene expression and low DDX41 expression. In summary, our study reveals that the frequency of DDX41MutGL in an unselected population of German AML patients is considerably lower than previously reported. Additionally, we found that apart from DDX41MutGL, DDX41-low exhibits a comparable clinical profile and is linked to specific methylation and gene expression patterns, with a notable emphasis on the PCDH complex located on chromosome 5. Understanding the functional implications of PCDH genes and their interaction with DDX41 in AML may significantly advance our knowledge of AML pathogenesis. Gaining insights into DDX41 alterations may open avenues for personalized therapeutic approaches and further prognostic stratification for AML patients with distinct molecular characteristics.

Prevalence of Sleep Disordered Breathing in Adult Sickle Cell Clinic Patients and Cardiovascular Correlates

Sleep disordered breathing (SDB) is strongly correlated with hypertension and cardiovascular disease in the general population, and especially in African Americans. In Sickle Cell Disease (SCD), the adverse effect of nocturnal hypoxemia is anticipated to have additional adverse effects with the sickling of red blood cells and microvascular thrombosis unique to the disease. Prospective data regarding the prevalence and consequences of SDB in this population are lacking. In an ongoing study, 27 adult subjects (age &amp;gt; 18 years), with homozygous HbSS genotype, presenting to the Howard University Sickle Cell Center for routine follow up have been recruited irrespective of the presence of sleep symptoms. Exclusion criteria include previous diagnosis or treatment of a sleep disorder or requirement for supplemental oxygen. Testing occurs when subjects are in a stable phase of disease, with no hospitalizations or medication changes for 4 weeks. In addition to clinical history and questionnaires, participants are assessed with blood work, 6 minute walk testing, pain and sleep diaries during 1 week actigraphy, transthoracic echocardiography and overnight in lab polysomnography with capnography. At the time of this interim analysis, the mean age is 42 (range 29-71, +/- std dev 11) and male:female distribution is 17:10. The mean BMI is 20.4 (+/- 4.5). Mean Hgb is 9.1 g/dl (+/- 1.8) and mean LDH is 325 iu/L (+/- 163). Polysomnography scoring utilized a 3% desaturation criterion for hyponeas as per American Academy of Sleep Medicine Scoring Manual Chapter VIII, 1A. Mean sleep efficiency is 77% ( std dev +/- 4.2%). 48% of subjects demonstrate some degree of sleep disordered breathing as defined by an AHI &amp;gt; 5 events/hour (33% mild, 4% moderate, 11% severe). 70% of subjects demonstrate an RDI &amp;gt; 5 events/hour (40% mild, 19% moderate, 11% severe). Twelve participants (44%) exhibit more than 5 minutes sleep duration at saturations &amp;lt;89% (mean = 187 minutes). Hypercapnia is not suggested as an important component of SDB with the mean ET CO2 = 40.7 mm Hg (range 30-46 mm Hg). Echocardiographic values (LVPWd, Lad, MV E/A, PVV, and RVSP) do not correlate with any indices of sleep disordered breathing other than minutes &amp;lt;89% saturation correlating with RVSP. In summary, this interim analysis of sleep in a population of unselected Sickle Cell Clinic patients demonstrates a striking frequency of sleep disordered breathing. This is despite a generally low BMI for these patients which is typically considered one of the most important risk factor for sleep apnea. Ongoing recruitment is planned to confirm these findings. Correlation with clinical outcomes and potential response to therapeutic interventions will be important future research questions.

Influence of heart failure and chronic kidney disease on cardiovascular outcome in patients with atrial fibrillation - insights from a cohort study of 7,412 patients

Abstract Background Heart failure (HF) and chronic kidney disease (CKD) form a vicious circle, reinforcing each other’s disease development and progression and causing higher rates in both morbidity and mortality. Here, we aimed to investigate the relationship between these two prevalent and interrelated diseases in an unselected patient population with AF. Methods This analysis includes patients with known AF, treated at a tertiary center between 07/2000 and 07/2019. The primary combined endpoint was hospitalization for heart failure (HHF) or cardiovascular (CV) death. We used cox regression models adjusted for age, sex, diabetes, coronary artery disease, hypertension, BMI and CRP-levels. Results We examined 7412 patients with AF and followed them over a median of 5.3 years. The median age was 70 years (IQR 61 to 78 years) and 2,945 (39.7%) were female. 434 (5.0%) patients had known CKD, 1,296 (17.5%) patients had HF, and 372 (5.4%) patients had both CKD and HF. There was a significant stepwise increase in event rates for the composite of CV death/HHF among patients without CKD or HF (KM event rate at 5 years: 23%), patients who had HF but no CKD (KM event rate at 5 years: 61%), patients with CKD but no HF (KM event rate at 5 years: 63%), and those who had both, HF and CKD (KM event rate at 5 years: 82%; P-logrank &amp;lt;0.001; Figure 1A). After multivariable adjustment, both CKD (with an adjusted hazard ratio of 2.22 and a 95% confidence interval of 1.87 to 2.63) and HF (with an adjusted hazard ratio of 2.53 and a 95% confidence interval of 2.26 to 2.84) were significantly associated with CV death/HHF and exerted a similar magnitude of the relationship. Patients with concomitant disease had the highest risk of the primary endpoint (with an adjusted hazard ratio of 3.96 and a 95% confidence interval of 3.34 to 4.68; Figure 1B). Conclusion AF patients with CKD and HF are at very high risk of CV death/HHF. Commonly used risk scores usually focus on stroke as the most dreaded complication in patients with AF. These findings suggest that the influence of CKD and HF expand beyond the risk of stroke to CV death/HHF in an unselected AF patient population.Figure 1

Short-stem total hip arthroplasty is equivalent to a standard-length stem procedure in an unselected population at mid-term follow-up.

Limitations of standard-length femoral stems persist, including proximal-distal mismatch, non-ideal load transfer, loss of bone tissue, and perioperative fracture. Symbol® (Dedienne Santé, France) is a metaphyseal-engaging short-stem implant designed to address these issues in total hip arthroplasty (THA). While short stems have been well studied in selected and younger patients, it is unclear whether they offer advantages in an unselected population. We hypothesized that short femoral stems offer similar mid-term survivorship at fiveyear minimum follow-up and function score to standard-length femoral stems, in an unselected patient population. We retrospectively reviewed a continuous unselected cohort of patients who undergone THA by one surgeon with a standard-length stem between November 2013 and October 2015, and a short stem between November 2015 and March 2017. We compared modified Harris Hip Score and Oxford Scores with a minimum follow-up of five years and procedural factors that could be associated with worse results with a short stem design. There was no difference in survival rate between the two groups. Average Harris Hip Score and Oxford Scores at the last follow-up were comparable. A multivariate linear regression was performed to assess the relationship between modified Harrys Hip Score at five years post-operatively and the explanatory variables: age, body mass index, physical status score ASA (American Society of Anesthesiologists), and HHS pre-op. None was associated with the standard-length stem but for the short stem. Short-stem implants provide good survival rate at mid-term; nevertheless, a steep learning curve is necessary to optimize the metaphyseal filling of the implant, especially for osteoporotic bone.

Can 24 h of ambulatory ECG be used to triage patients to extended monitoring?

Access to long-term ambulatory recording to detect atrial fibrillation (AF) is limited for economical and practical reasons. We aimed to determine whether 24 h ECG (24hECG) data can predict AF detection on extended cardiac monitoring. We included all US patients from 2020, aged 17-100 years, who were monitored for 2-30 days using the PocketECG device (MEDICALgorithmics), without AF ≥30 s on the first day (n = 18,220, mean age 64.4 years, 42.4% male). The population was randomly split into equal training and testing datasets. A Lasso model was used to predict AF episodes ≥30 s occurring on days 2-30. The final model included maximum heart rate, number of premature atrial complexes (PACs), fastest rate during PAC couplets and triplets, fastest rate during premature ventricular couplets and number of ventricular tachycardia runs ≥4 beats, and had good discrimination (ROC statistic 0.7497, 95% CI 0.7336-0.7659) in the testing dataset. Inclusion of age and sex did not improve discrimination. A model based only on age and sex had substantially poorer discrimination, ROC statistic 0.6542 (95% CI 0.6364-0.6720). The prevalence of observed AF in the testing dataset increased by quintile of predicted risk: 0.4% in Q1, 2.7% in Q2, 6.2% in Q3, 11.4% in Q4, and 15.9% in Q5. In Q1, the negative predictive value for AF was 99.6%. By using 24hECG data, long-term monitoring for AF can safely be avoided in 20% of an unselected patient population whereas an overall risk of 9% in the remaining 80% of the population warrants repeated or extended monitoring.

Poly (ADP-Ribose) Polymerase Inhibitors in Patients With Urothelial Cancer.

Poly ADP-ribose polymerase inhibitors (PARPis) have clinical activity in several cancers. The rationale of their therapeutic use in urothelial cancer (UC) resides in the high homologous-recombination repair (HRR) deficiency (HRD) prevalence and potential cross-sensitivity with platinum-based chemotherapy (PBCT). This review aims to summarize and analyze trials exploring the activity of PARPis in UC, focusing on patients who may benefit from those agents, the best clinical setting for the treatment and the benefit of the association with immune-checkpoint inhibitors (ICIs). We included all the available trials analyzing the activity of PARPis in UC in neoadjuvant, adjuvant, first or subsequent lines, and maintenance setting. We included PARPis in monotherapy and in association with other agents. The results in the maintenance setting are intriguing: ATLANTIS trial showed signals of improved progression-free survival in patients with known HRR aberrations, although the Meet-URO12 trial, with its negative results, suggested the failure of clinical selection based on platinum sensitivity only. Single-agent PARPis in pretreated patients showed discouraging results in an unselected population of chemo-refractory patients. Concerning the association of PARPis with ICIs, several trials are exploring their role in platinum-naïve setting; the results in the advanced setting were globally negative. Prior selection of HRD status is essential to identify patients who might benefit from PARPis. The ideal clinical settings seem to be the maintenance treatment and the combination with ICIs in platinum-naïve patients. Definitive results of ongoing and further trials will delineate the position for PARPis, if any, in UC therapy.

What predicts survival in glioblastoma? A population-based study of changes in clinical management and outcome.

Glioblastoma is the most common and most aggressive primary brain tumor in adults. Despite multimodal treatment, the median survival time is 15-16 months and 5-year survival rate 5%-10%. The primary goal of this study was to identify prognostic factors for survival in an unselected population of patients operated for glioblastoma. The secondary goal was to explore changes in outcome and the clinical management of this patient group over time. We identified 222 consecutive adults operated for glioblastoma between November 2012 and June 2016 at the Department of Neurosurgery, Sahlgrenska University Hospital in Gothenburg, serving a health care region in the western part of Sweden with 1.900.000 inhabitants. Clinical variables were identified and tested as predictors for prognosis in extended Poisson regression models. The results were compared with a previously published cohort from 2004 to 2008, before current standard of care based on molecular tumor diagnosis was fully implemented. Median overall survival was 1.07 years, which was significantly longer than in the 2004-2008 cohort (1.07 vs. 0.73 y, age- and sex adjusted HR = 1.89, p < 0.0001). Variables associated with longer survival in the multivariable model were MGMT promoter hypermethylation, non-central tumor location, complete resection of enhancing tumor, WHO performance status 0-1, unilateral tumor location, fewer lobes involved, younger age and no comorbidities. The median survival for patients with glioblastoma treated according to current standard treatment has moderately but significantly increased, with MGMT promoter hypermethylation as the strongest predictor for survival.

Apparently Resistant Hypertension in Polish Hemodialyzed Population: Prevalence and Risk Factors.

The aim of this study was to assess the prevalence, characteristics, and determinants of apparent treatment-resistant hypertension (aTRH) in an unselected large population of patients with end-stage kidney disease (ESKD) treated with hemodialysis (HD) throughout the country. A database of 5879 patients (mean age 65.2 ± 14.2 years, 60% of males receiving hemodialysis) was obtained from the biggest provider of hemodialysis in the country. Hypertension and aTRH were defined using pre- or/and post-dialysis BP values. Patients with and without aTRH (non-aTRH) were compared. Using pre- and post-dialysis criteria, hypertension was diagnosed in 90.7% and 89.1% of subjects, respectively. According to pre- and post-dialysis blood pressure criteria, aTRH incidences were 40.9% and 38.4%, respectively. The hypertensive patients with aTRH versus non-aTRH were younger, had a higher rate of cardiovascular disease, lower dialysis vintage, shorter time on dialysis, higher eKt/V, higher ultrafiltration, higher pre- and post-dialysis BP and HR, and higher use of antihypertensive drugs. Factors that increase the risk of aTRH according to both pre- and post-dialysis BP criteria were age-OR 0.99 [0.98-0.99] and 0.99 [0.98-0.99], the history of CVD 1.26 [1.08-1.46] and 1.30 [1.12-1.51], and diabetes 1.26 [1.08-1.47] and 1.28 [1.09-1.49], adjusted OR with 95% CI. In the real-life world, as much as 40% of HD patients may have aTRH. In ESKD HD patients, aTRH seems to be multifactorial, influenced by patient-related rather than dialysis-related factors. Various definitions of aTRH preclude easy comparisons between studies.

Outcomes with atezolizumab in metastatic urothelial cancer: real-world data from a single institution.

Immune checkpoint inhibitors (ICIs) have been incorporated in the treatment of metastatic urothelial carcinoma (mUC) upon platinum-based chemotherapy according to the positive results of large clinical trials. Nevertheless, results from unselected populations reflecting real-world data (RWD) are highly informative to the clinician. We reviewed daily clinical practice outcomes in patients with mUC who received atezolizumab in our institution. Here we evaluated the clinical activity and safety of atezolizumab in an unselected population of mUC patients who received atezolizumab between 2018 and 2022 reflecting RWD. Efficacy and safety information were retrospectively collected. A total of 63 patients were included. The mean age was 68years and the objective response rate was 14.3%. The median progression-free survival was 3months and the median overall survival 6months. At 1year, 42% of the patients were alive. ECOG (0 vs 1) and neutrophil-lymphocytes ratio < 2 at the start of ICI were positive prognostic factors that discriminated between long vs short survivors. Overall tolerance was good with no new safety signals. Fivepatients (17%) had treatment-related adverse events grade ≥ 2 that required corticosteroids. In this retrospective study, atezolizumab was an effective and tolerable treatment option for patients with mUC after progression to platinum-based chemotherapy. Yet, patient selection remains critical to improve outcomes.

Arthroscopic posterior capsulolabral repair grants adequate outcomes in shoulders with posterior instability without glenoid cartilage lesions.

Posterior capsulolabral repair (posterior Bankart) is effective to restore shoulder stability and relieve pain, though a recent meta-analysis reported recurrent instability in 9.5% of patients, and that only 62.7% were able to resume sports. The purpose of this study was to assess the outcomes of arthroscopic posterior capsulolabral repair in a population of unselected patients, in terms of recurrence of instability, clinical scores, and return to sports. The authors retrospectively studied a consecutive series of 22 patients that underwent posterior capsulolabral repair between 2009 and 2019. Patients were assessed before posterior capsulolabral repair and at a minimum follow-up of 24months, in terms of subjective shoulder value (SSV), Western Ontario Shoulder Instability Index (WOSI), as well as level of sport. Following surgery, all complications, reoperations or episodes of instability were noted. The cohort comprised 21 men (95%) and 1 woman (5%), aged 38.8 ± 12.5years (range 17-61) at index surgery. Of the 20 patients that performed sports, only 2 (10%) stopped sports after surgery, while 18 resumed their main sport (90%). At a follow-up of 65.4 ± 34.8months (range 25-146), the SSV was 85.1 ± 14.7, pain on VAS was 1.9 ± 2.1, and the Constant-Murley score was 71.6 ± 17.9. Five patients had subjective instability without dislocation (23%). Nine patients (41%) had no pain (0 points), 6 patients (27%) had mild pain (1-2 points), 4 patients (18%) had moderate pain (3 points), while 3 patients (14%) had severe pain (5-8 points). Arthroscopic posterior capsulolabral repair prevented recurrent dislocation in patients with posterior shoulder instability at a minimum follow-up of 2years, despite persistent pain in 32%, and subjective instability in 23%. These complications were mainly observed in patients with work-related accidents and glenoid cartilage lesions. III, case series.