Longer and better lives for patients with atrial fibrillation: the 9th AFNET/EHRA consensus conference.

AIMS: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). METHODS AND RESULTS: Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF. CONCLUSIONS: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF.

Multitarget Stool RNA Test for Noninvasive Detection of Colorectal Neoplasias in a Multicenter, Prospective, and Retrospective Cohort.

INTRODUCTION: Effective colorectal cancer (CRC) prevention and screening requires sensitive detection of all advanced neoplasias (CRC and advanced adenomas [AA]). However, existing noninvasive screening approaches cannot accurately detect adenomas with high sensitivity. METHODS: Here, we describe a multifactor assay (RNA-FIT test) that combines 8 stool-derived eukaryotic RNA biomarkers, patient demographic information (smoking status), and a fecal immunochemical test (FIT) to sensitively detect advanced colorectal neoplasias and other non-advanced adenomas in a 1,305-patient, average-risk, prospective cohort. This cohort was supplemented with a 22-patient retrospective cohort consisting of stool samples obtained from patients diagnosed with AA or CRC before treatment or resection. Participants within these cohorts were evaluated with the RNA-FIT assay and an optical colonoscopy. RNA-FIT test results were compared with colonoscopy findings. RESULTS: Model performance was assessed through 5-fold internal cross-validation of the training set (n = 939) and by using the model on a hold out testing set (n = 388). When used on the hold out testing set, the RNA-FIT test attained a 95% sensitivity for CRC (n = 22), 62% sensitivity for AA (n = 52), 25% sensitivity for other non-AA (n = 139), 80% specificity for hyperplastic polyps (n = 74), and 85% specificity for no findings on a colonoscopy (n = 101). DISCUSSION: The RNA-FIT assay demonstrated clinically relevant detection of all grades of colorectal neoplasia, including carcinomas, AAs, and ONAs. This assay could represent a noninvasive option to screen for both CRC and precancerous adenomas.

Dynamic risk assessment to improve quality of care in patients with atrial fibrillation: the 7th AFNET/EHRA Consensus Conference.

AIMS: The risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes. METHODS AND RESULTS: This article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence. CONCLUSION: The remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.

A Case of Squamous Cell Carcinoma of the Anterior Urethra in a Man.

Squamous cell carcinoma (SCC) of the anterior urethra in men is rare, comprising less than 1% of all urologic cancers. The mean age at diagnosis is 60 years and it is nearly twice as common in black men compared with white men. We detail a case of SCC of the anterior urethra in a man presenting with an inguinal mass, meatal stenosis, and balanitis.

Prostate Biopsy Characteristics: A Comparison Between the Pre- and Post-2012 United States Preventive Services Task Force (USPSTF) Prostate Cancer Screening Guidelines.

To compare prostate cancer (PCa) characteristics diagnosed by prostate biopsy (Pbx) in the 3 years before and after the 2012 United States Preventive Services Task Force (USPSTF) recommendations for PCa screening, we completed a retrospective comparative analysis of 402 sequential PCa patients diagnosed from 2010 to 2012 (3 years) with 552 PCa patients diagnosed from 2015 to 2017 (3 years). Data was collected on patient age, race, total number of biopsies performed, prostate specific antigen (PSA), Gleason sum score (GSS), and digital rectal examination (DRE). The data was analyzed to determine whether the 2012 USPSTF screening recommendations affected PCa characteristics. Two study groups were defined, Group A and Group B, prior to and after the 2012 USPSTF screening recommendations, respectively. In Group A (pre- 2012 USPSTF recommendations), 567 patients/year underwent a Pbx versus Group B, 398 patients/year, a 30% reduction post-USPSTF. The annual positive Pbx rate for Group A is 134/year versus Group B 184/year, a 37.3% increase post-USPSTF. Group A had high-grade PCa (GSS 7-10) in 51.5% versus Group B in 60.1%, an 8.6% increase post-USPSTF. In Group B, the total number of positive biopsies was increased by 100%. This study shows that in Group B, the Pbx rate decreased by 30% but the annual PCa detection rate increased by 37%. High-grade GSS (7-10) PCa increased by 8.6%. Despite a reduction in the total number of prostate biopsies by 30%, there was a 100% increase in the total number of positive prostate biopsies.

Prostate biopsy characteristics: A comparison between pre- and post- United States Preventive Service Task Force Prostate Cancer Screening Guidelines of 2012.

This article compares prostate cancer (PCa) characteristics diagnosed by prostate biopsy in the years before and after the 2012 United States Preventative Service Task Force (USPSTF) recommendations against PCa screening. We completed a retrospective comparative analysis of 402 sequential PCa biopsy-diagnosed patients in 2010 to 2012 (3 years) with 269 PCa patients diagnosed in 2015 to 2016 (18 months). Data were collected on patient age, total number of biopsies performed, prostate-specific antigen level, Gleason sum score, and digital rectal examination results. The data were analyzed to determine whether the 2012 USPSTF screening recommendations affected PCa characteristics.

Smart detection of atrial fibrillation†.

AIMS: Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice, and its paroxysmal nature makes its detection challenging. In this trial, we evaluated a novel App for its accuracy to differentiate between patients in AF and patients in sinus rhythm (SR) using the plethysmographic sensor of an iPhone 4S and the integrated LED only. METHODS AND RESULTS: For signal acquisition, we used an iPhone 4S, positioned with the camera lens and LED light on the index fingertip. A 5 min video file was recorded with the pulse wave extracted from the green light spectrum of the signal. RR intervals were automatically identified. For discrimination between AF and SR, we tested three different statistical methods. Normalized root mean square of successive difference of RR intervals (nRMSSD), Shannon entropy (ShE), and SD1/SD2 index extracted from a Poincaré plot. Eighty patients were included in the study (40 patients in AF and 40 patients in SR at the time of examination). For discrimination between AF and SR, ShE yielded the highest sensitivity and specificity with 85 and 95%, respectively. Applying a tachogram filter resulted in an improved sensitivity of 87.5%, when combining ShE and nRMSSD, while specificity remained stable at 95%. A combination of SD1/SD2 index and nRMSSD led to further improvement and resulted in a sensitivity and specificity of 95%. CONCLUSION: The algorithm tested reliably discriminated between SR and AF based on pulse wave signals from a smartphone camera only. Implementation of this algorithm into a smartwatch is the next logical step.

Validation of a New Heart Rate Measurement Algorithm for Fingertip Recording of Video Signals with Smartphones.

INTRODUCTION: This study investigates the accuracy of a heart rate (HR) measurement algorithm applied to a pulse wave. This was based on video signals recorded with a smartphone. The results of electrocardiographic HR and standard linear heart rate variability (HRV) analysis were used for reference. MATERIALS AND METHODS: On a total of 68 subjects, an electrocardiogram (ECG) and the pulse curve were simultaneously recorded on an Apple iPhone 4S. The HR was measured using an algorithm developed by the authors that works according to a method combining the detection of the steepest slope of every pulse wave with the correlation to an optimized pulse wave pattern. RESULTS: The results of the HR measured by pulse curves were extremely consistent (R > 0.99) with the HR measured on ECGs. For most standard linear HRV parameters as well, high correlations of R ≥ 0.90 in the analysis were achieved in the time and frequency domain. CONCLUSION: In conclusion, the overall accuracy of HR and HRV indices of pulse wave analysis, based on video signals of a smartphone, with the developed algorithm was sufficient for preclinical screening applications.

Technique for reliable sentinel node biopsy in squamous cell carcinomas of the floor of mouth.

BACKGROUND: Applicability of sentinel node biopsy (SNB) for tumors of the floor of mouth (FOM) is controversial. METHODS: Prospective evaluation of the accuracy of gamma-probe-guided superselective neck dissection of the preglandular triangle of level I for SNB in FOM squamous cell carcinoma (SCC) after preoperative lymphoscintigraphy and single photon emission CT (SPECT)/CT. RESULTS: In total, 22 sentinel lymph nodes were harvested in level I. Eight of 22 (36%) were seen on lymphoscintigraphy and 11 (50%) on SPECT/CT. Eleven sentinel lymph nodes (50%) were only detected intraoperatively. In unilateral tumors, 20% were contralateral, and, in midline tumors, 93% showed bilateral level I sentinel lymph nodes. The false-negative rate was 8.3%, the negative predictive value was 96.4%, and the false-omission rate was 3.6%. The ultimate neck control rate, including salvage treatment, was 100%. CONCLUSION: SNB in FOM can be reliably performed using the presented surgical technique. Level I exploration, bilaterally in midline tumors, is mandatory irrespective of the visualization of sentinel lymph nodes in other levels. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1367-1372, 2016.

Tactile Corpuscle-like Bodies in Gastrointestinal-type Mucosa: A Case Series.

Tactile corpuscle-like bodies (TCLB) are microscopic Schwannian structures that simulate the superficial mechanoreceptors of the peripheral nervous system (Wagner-Meissner corpuscles). They have been described nearly exclusively in peripheral nerve sheath tumors, namely diffuse neurofibromas, and schwannomas but also in cellular nevi. There are rare reports of these structures in the gastrointestinal tract (predominantly the lower tract), with the presumption that they are incidental reactive neural proliferations. We compiled 9 cases showing this rare phenomenon in gastrointestinal-type mucosa in nonsyndromic patients to further characterize its features. There were 6 men and 3 women (age range, 39 to 79 y, mean 56 y) with lesions involving esophagus/gastro-esophageal junction (n=7), sigmoid colon (n=1), and gastric heterotopia of the cricopharynx (n=1). Endoscopic examination was abnormal in 6 of the 7 cases (including changes consistent with Barrett esophagus and polypoid/nodular mucosa) and normal in 1 of 7 cases for which this information was available. The histologic features were similar in all cases, with unencapsulated clusters of lamellated and concentrically arranged spindle cells in the lamina propria. The foci of TCLB ranged in size from <0.1 to 1.5 mm in the greatest dimension. Abnormal histopathologic findings were identified in the background mucosa in 6 of 9 cases (including Barrett esophagus, active and inactive chronic gastritis, enterochromaffin-like cell hyperplasia, and gastric intestinal metaplasia). None of the patients showed signs of neurofibromatosis type 1, multiple endocrine neoplasia type 2B, Cowden syndrome, or other inherited syndrome. No morbidity related to TCLB was reported for the patients with available follow-up.

PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.

BACKGROUND: Somatic mutations have the potential to encode "non-self" immunogenic antigens. We hypothesized that tumors with a large number of somatic mutations due to mismatch-repair defects may be susceptible to immune checkpoint blockade. METHODS: We conducted a phase 2 study to evaluate the clinical activity of pembrolizumab, an anti-programmed death 1 immune checkpoint inhibitor, in 41 patients with progressive metastatic carcinoma with or without mismatch-repair deficiency. Pembrolizumab was administered intravenously at a dose of 10 mg per kilogram of body weight every 14 days in patients with mismatch repair-deficient colorectal cancers, patients with mismatch repair-proficient colorectal cancers, and patients with mismatch repair-deficient cancers that were not colorectal. The coprimary end points were the immune-related objective response rate and the 20-week immune-related progression-free survival rate. RESULTS: The immune-related objective response rate and immune-related progression-free survival rate were 40% (4 of 10 patients) and 78% (7 of 9 patients), respectively, for mismatch repair-deficient colorectal cancers and 0% (0 of 18 patients) and 11% (2 of 18 patients) for mismatch repair-proficient colorectal cancers. The median progression-free survival and overall survival were not reached in the cohort with mismatch repair-deficient colorectal cancer but were 2.2 and 5.0 months, respectively, in the cohort with mismatch repair-proficient colorectal cancer (hazard ratio for disease progression or death, 0.10 [P<0.001], and hazard ratio for death, 0.22 [P=0.05]). Patients with mismatch repair-deficient noncolorectal cancer had responses similar to those of patients with mismatch repair-deficient colorectal cancer (immune-related objective response rate, 71% [5 of 7 patients]; immune-related progression-free survival rate, 67% [4 of 6 patients]). Whole-exome sequencing revealed a mean of 1782 somatic mutations per tumor in mismatch repair-deficient tumors, as compared with 73 in mismatch repair-proficient tumors (P=0.007), and high somatic mutation loads were associated with prolonged progression-free survival (P=0.02). CONCLUSIONS: This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab. (Funded by Johns Hopkins University and others; ClinicalTrials.gov number, NCT01876511.).

Comparison of cardiogoniometry and ECG at rest versus myocardial perfusion scintigraphy.

BACKGROUND: Cardiogoniometry (CGM) is a novel resting electrocardiac method based on computer-generated three-dimensional data derived from cardiac potentials. The purpose of this study was to determine CGM's and electrocardiography's (ECG) accuracy for detecting myocardial ischemia and/or lesions in comparison with stress/rest myocardial perfusion scintigraphy (single photon emission computer tomography [SPECT]). METHOD: A cohort of consecutively enrolled patients (n = 100) with suspected or known coronary artery disease (mean age 67.8 years, 52% female) were examined by CGM and resting ECG before stress/rest myocardial scintigraphy. RESULTS: Pathological scintigraphy findings at adenosine stress perfusion (ASP) and/or rest were conclusively identified in 21 patients. Diagnostic sensitivity was 71% for CGM and 24% for ECG, specificity was 70% for CGM and 95% for ECG. Reversible ischemia was diagnosed in 16 of 21 patients with pathological scintigraphy results. In this subgroup, sensitivity was 67% for CGM and 25% for ECG. CONCLUSIONS: At rest, the sensitivity of a CGM significantly surmounts that of a standard 12-lead ECG for detection of isolated myocardial ischemia or myocardial lesions revealed by scintigraphy/SPECT; specificity is in a reasonable range. CGM's ease of use and its considerable agreement with the results of myocardial scintigraphy, suggests a possible role for patient screening in the primary care setting.

The neural representation of emotionally neutral faces and places in patients with panic disorder with agoraphobia.

BACKGROUND: Panic disorder with agoraphobia (PD-A) has been associated with abnormal neural activity for threat-related stimuli (faces, places). Recent findings suggest a disturbed neural processing of emotionally neutral stimuli at a more general level. METHODS: Using functional magnetic resonance imaging (fMRI) we investigated the neural processing of emotionally neutral faces and places in PD-A. Fifteen patients with PD-A and fifteen healthy subjects participated in the study. RESULTS: When they perceived neutral faces and places, the patients with PD-A showed significantly less brain activity in the fusiform gyrus, the inferior occipital gyrus, the calcarine gyrus, the cerebellum, and the cuneus compared with the healthy controls. However, the patients with PD-A showed significantly more brain activity in the precuneus compared with controls subjects. LIMITATIONS: It was not possible to distinguish the agoraphobia-associated effects from possible contributions due to general anxiety induced by fMRI. For future investigations, an additional clinical control group with patients suffering from panic disorder without agoraphobia would be of interest. In addition, the psychopathology concerning the agoraphobic symptoms needs to be investigated in more detail. CONCLUSIONS: The findings suggest altered neural processing of emotionally neutral faces and places in patients with PD-A. Reduced neural activity in different brain regions may indicate difficulties in recognizing the emotional content in face and place stimuli due to anxiety-related hyper-arousal.

Canalicular adenoma--search for the cell of origin: ultrastructural and immunohistochemical analysis of 7 cases and review of the literature.

Canalicular adenoma (CA) is a rare, benign epithelial neoplasm of the salivary glands. Historically considered to be a variant of basal cell adenoma, this "monomorphic" adenoma has a distinct clinical, morphologic, and immunohistochemical profile. The putative cell of origin remains a topic of debate. A combination of morphology, immunohistochemistry, and ultrastructural analyses have been employed to determine histogenesis, but the interpretations of these studies have implicated multiple different cell types along the salivary gland duct as the cell of origin. The authors sought to further characterize CA using electron microscopy, immunohistochemistry, and special and immuno-stains on 7 cases. Their morphologic, immunohistochemical, and ultrastructural findings support a cell of origin demonstrating features of both the intercalated duct cells and the striated duct luminal epithelial cells.

Impact of chemotherapy for childhood leukemia on brain morphology and function.

OBJECTIVE: Using multidisciplinary treatment modalities the majority of children with cancer can be cured but we are increasingly faced with therapy-related toxicities. We studied brain morphology and neurocognitive functions in adolescent and young adult survivors of childhood acute, low and standard risk lymphoblastic leukemia (ALL), which was successfully treated with chemotherapy. We expected that intravenous and intrathecal chemotherapy administered in childhood will affect grey matter structures, including hippocampus and olfactory bulbs, areas where postnatal neurogenesis is ongoing. METHODS: We examined 27 ALL-survivors and 27 age-matched healthy controls, ages 15-22 years. ALL-survivors developed disease prior to their 11th birthday without central nervous system involvement, were treated with intrathecal and systemic chemotherapy and received no radiation. Volumes of grey, white matter and olfactory bulbs were measured on T1 and T2 magnetic resonance images manually, using FIRST (FMRIB's integrated Registration and Segmentation Tool) and voxel-based morphometry (VBM). Memory, executive functions, attention, intelligence and olfaction were assessed. RESULTS: Mean volumes of left hippocampus, amygdala, thalamus and nucleus accumbens were smaller in the ALL group. VBM analysis revealed significantly smaller volumes of the left calcarine gyrus, both lingual gyri and the left precuneus. DTI data analysis provided no evidence for white matter pathology. Lower scores in hippocampus-dependent memory were measured in ALL-subjects, while lower figural memory correlated with smaller hippocampal volumes. INTERPRETATION: Findings demonstrate that childhood ALL, treated with chemotherapy, is associated with smaller grey matter volumes of neocortical and subcortical grey matter and lower hippocampal memory performance in adolescence and adulthood.

18F-FDG PET/CT in a rare malignant extraskeletal osteosarcoma.

Extraskeletal osteosarcoma (EO) is a rare malignancy and its FDG PET/CT imaging is seldom reported. We present staging and restaging images of a FDG PET/CT imaging in an EO originating from paraspinous musculature. Initial staging FDG PET/CT scan showed increased metabolism of a mass in the right paraspinous region without nodal or distant metastasis. The patient underwent tumor resection and radiation therapy with a pathological diagnosis of EO. Restaging FDG PET/CT imaging demonstrated postsurgical changes without nodal or distant metastasis. This case demonstrates the clinical relevance of FDG PET/CT imaging for staging and restaging EO.

Functional imaging during recognition of personally familiar faces and places in Alzheimer's disease.

Alzheimer's disease (AD) patients show better everyday functioning in a familiar setting, but they have a reduced ability to access contextual details and episodes associated with a familiar person or environment. This suggests a dysfunction in the neural networks associated with stimulus identification. Using functional magnetic resonance imaging, we investigated the neural activity during the recognition of personally familiar and unfamiliar faces and places among AD patients and elderly controls. We did not find a group difference in the neural activity within brain areas important for perceptual familiarity recognition. Patients showed reduced activation for familiar stimuli in prefrontal brain areas known to be important for retrieving contextual information for a stimulus when compared with controls. These changes may contribute to how AD patients experience a personally familiar face or place.

Allograft pathology in patients transplanted for idiopathic dilated cardiomyopathy.

There are few morphologic studies on idiopathic dilated cardiomyopathy (CM) treated with transplant. We prospectively correlated gross, histologic, and clinical findings pertaining to hearts explanted in a 5-year period from patients with a clinical diagnosis of nonischemic CM and also correlated left ventricular diameter with preoperative echocardiographic reports. Of 64 patients with a clinical diagnosis of dilated cardiomyopathy (DC), 42 were men (age, 51 ± 13 y) and 22 were women (age, 42 ± 18 y). The pathologic diagnosis was idiopathic (dilated) cardiomyopathy (DC) in 55 patients (86%) and features of specific CM in 9 patients (14%). Specific diagnoses were fibrofatty change consistent with arrhythmogenic right ventricular cardiomyopathy (n=6), amyloidosis (n=2), and sarcoidosis (n=1), none of which were suspected clinically. The 55 hearts with idiopathic DC had a mean heart weight of 508 (range, 220 to 980) g. Pathologic subsets of the DC group included 4 hearts without enlargement, cavity dilatation, or significant histologic findings (minimal DC); 3 hearts with histologic evidence of healed myocarditis; and 5 hearts with mildly noncompacted left ventricle with hypertrabeculation. Five patients had prior mitral or tricuspid valve replacement/repairs to manage heart failure. There were 7 postpartum DC cases, 1 with a histologic pattern of healed myocarditis and 1 alcoholism-associated DC. Familial DC comprised 16% (9 of 55) of patients. In patients without prior assist device placement, pathologic left ventricular cavity diameter correlated with echocardiographic end-diastolic volume (r , 0.8, P<0.0001). Morphologically, DC is a heterogeneous group. Areas of fibrofatty change and features of noncompaction are not uncommon. Left ventricular measurement at explant correlates well with echocardiographic findings, with a relatively consistent underestimation of the diameter.