Mutant IDH inhibitors induce lineage differentiation in IDH-mutant oligodendroglioma.

A subset of patients with IDH-mutant glioma respond to inhibitors of mutant IDH (IDHi), yet the molecular underpinnings of such responses are not understood. Here, we profiled by single-cell or single-nucleus RNA-sequencing three IDH-mutant oligodendrogliomas from patients who derived clinical benefit from IDHi. Importantly, the tissues were sampled on-drug, four weeks from treatment initiation. We further integrate our findings with analysis of single-cell and bulk transcriptomes from independent cohorts and experimental models. We find that IDHi treatment induces a robust differentiation toward the astrocytic lineage, accompanied by a depletion of stem-like cells and a reduction of cell proliferation. Furthermore, mutations in NOTCH1 are associated with decreased astrocytic differentiation and may limit the response to IDHi. Our study highlights the differentiating potential of IDHi on the cellular hierarchies that drive oligodendrogliomas and suggests a genetic modifier that may improve patient stratification.

Brain dynamics predictive of response to psilocybin for treatment-resistant depression.

Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here, we leveraged the differential outcome in responders and non-responders to psilocybin (10 and 25 mg, 7 days apart) therapy for depression-to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used large-scale brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a healthy one. Binarizing the sample into treatment responders (>50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-hydroxytryptamine 2a and 5-hydroxytryptamine 1a, which psilocin, the active metabolite of psilocybin, has an appreciable affinity for, and where it acts as a full-to-partial agonist. Serotonergic transmission has long been associated with depression, and our findings provide causal mechanistic evidence for the role of brain regions in the recovery from depression via psilocybin.

NAB2::STAT6 fusions and genome-wide DNA methylation profiling: Predictors of patient outcomes in meningeal solitary fibrous tumors.

Meningeal solitary fibrous tumors (SFT) are rare and have a high frequency of local recurrence and distant metastasis. In a cohort of 126 patients (57 female, 69 male; mean age at surgery 53.0 years) with pathologically confirmed meningeal SFTs with extended clinical follow-up (median 9.9 years; range 15 days-43 years), we performed extensive molecular characterization including genome-wide DNA methylation profiling (n = 80) and targeted TERT promoter mutation testing (n = 98). Associations were examined with NAB2::STAT6 fusion status (n = 101 cases; 51 = ex5-7::ex16-17, 26 = ex4::ex2-3; 12 = ex2-3::exANY/other and 12 = no fusion) and placed in the context of 2021 Central Nervous System (CNS) WHO grade. NAB2::STAT6 fusion breakpoints (fusion type) were significantly associated with metastasis-free survival (MFS) (p = 0.03) and, on multivariate analysis, disease-specific survival (DSS) when adjusting for CNS WHO grade (p = 0.03). DNA methylation profiling revealed three distinct clusters: Cluster 1 (n = 38), Cluster 2 (n = 22), and Cluster 3 (n = 20). Methylation clusters were significantly associated with fusion type (p < 0.001), with Cluster 2 harboring ex4::ex2-3 fusion in 16 (of 20; 80.0%), nearly all TERT promoter mutations (7 of 8; 87.5%), and predominantly an "SFT" histologic phenotype (15 of 22; 68.2%). Clusters 1 and 3 were less distinct, both dominated by tumors having ex5-7::ex16-17 fusion (respectively, 25 of 33; 75.8%, and 12 of 18; 66.7%) and with variable histological phenotypes. Methylation clusters were significantly associated with MFS (p = 0.027), but not overall survival (OS). In summary, NAB2::STAT6 fusion type was significantly associated with MFS and DSS, suggesting that tumors with an ex5::ex16-17 fusion may have inferior patient outcomes. Methylation clusters were significantly associated with fusion type, TERT promoter mutation status, histologic phenotype, and MFS.

Left Anterior Descending Coronary Artery Mimic: A Case of Coronary Artery to Pulmonary Artery Fistula.

Coronary artery fistulas (CAFs) are rare coronary anomalies involving the communication of an epicardial coronary artery and another cardiovascular structure. CAFs are usually easily distinguished from nearby coronary arteries. Here, we report a unique case of CAF that mimics the size, branching pattern, and appearance of a native epicardial left anterior descending artery.

Antimicrobial Activity of Synthetic Enterocins A, B, P, SEK4, and L50, Alone and in Combinations, against Clostridium perfringens.

Multidrug-resistant Clostridium perfringens infections are a major threat to the poultry industry. Effective alternatives to antibiotics are urgently needed to prevent these infections and limit the spread of multidrug-resistant bacteria. The aim of the study was to produce by chemical synthesis a set of enterocins of different subgroups of class II bacteriocins and to compare their spectrum of inhibitory activity, either alone or in combination, against a panel of twenty C. perfringens isolates. Enterocins A, P, SEK4 (class IIa bacteriocins), B (unsubgrouped class II bacteriocin), and L50 (class IId leaderless bacteriocin) were produced by microwave-assisted solid-phase peptide synthesis. Their antimicrobial activity was determined by agar well diffusion and microtitration methods against twenty C. perfringens isolates and against other pathogens. The FICINDEX of different combinations of the selected enterocins was calculated in order to identify combinations with synergistic effects. The results showed that synthetic analogs of L50A and L50B were the most active against C. perfringens. These peptides also showed the broadest spectrum of activity when tested against other non-clostridial indicator strains, including Listeria monocytogenes, methicillin-resistant Staphylococcus aureus, Streptococcus suis, Streptococcus pyogenes, Enterococcus cecorum, Enterococcus faecalis, as well as Gram-negative bacteria (Campylobacter coli and Pseudomonas aeruginosa), among others. The selected synthetic enterocins were combined on the basis of their different mechanisms of action, and all combinations tested showed synergy or partial synergy against C. perfringens. In conclusion, because of their high activity against C. perfringens and other pathogens, the use of synthetic enterocins alone or as a consortium can be a good alternative to the use of antibiotics in the poultry sector.

Altered dynamical integration/segregation balance during anesthesia-induced loss of consciousness.

In recent years, brain imaging studies have begun to shed light on the neural correlates of physiologically-reversible altered states of consciousness such as deep sleep, anesthesia, and psychedelic experiences. The emerging consensus is that normal waking consciousness requires the exploration of a dynamical repertoire enabling both global integration i.e., long-distance interactions between brain regions, and segregation, i.e., local processing in functionally specialized clusters. Altered states of consciousness have notably been characterized by a tipping of the integration/segregation balance away from this equilibrium. Historically, functional MRI (fMRI) has been the modality of choice for such investigations. However, fMRI does not enable characterization of the integration/segregation balance at sub-second temporal resolution. Here, we investigated global brain spatiotemporal patterns in electrocorticography (ECoG) data of a monkey (Macaca fuscata) under either ketamine or propofol general anesthesia. We first studied the effects of these anesthetics from the perspective of band-specific synchronization across the entire ECoG array, treating individual channels as oscillators. We further aimed to determine whether synchrony within spatially localized clusters of oscillators was differently affected by the drugs in comparison to synchronization over spatially distributed subsets of ECoG channels, thereby quantifying changes in integration/segregation balance on physiologically-relevant time scales. The findings reflect global brain dynamics characterized by a loss of long-range integration in multiple frequency bands under both ketamine and propofol anesthesia, most pronounced in the beta (13-30 Hz) and low-gamma bands (30-80 Hz), and with strongly preserved local synchrony in all bands.

Convenient route to Fmoc-homotyrosine via metallaphotoredox catalysis and its use in the total synthesis of anabaenopeptin cyclic peptides.

Herein, we report the first solid-phase total synthesis of the natural cyclic peptide anabaenopeptin F and the use of metallaphotoredox catalysis to overcome the key challenges associated with the preparation of the non-proteinogenic amino acid homotyrosine contained in these peptides. Starting from L-homoserine, enantiopure Fmoc-protected homotyrosine was prepared in a straightforward manner by metallaphotoredox catalysis with N-Fmoc-(S)-2-amino-4-bromobutanoic acid and 4-tert-butoxybromobenzene partners. The prepared protected amino acid was used in solid-phase peptide synthesis to achieve the total synthesis of anabaenopeptin F and establish the stereochemistry of the isoleucine residue. Protease inhibition studies with the synthesized anabaenopeptin F showed inhibitory activities against carboxypeptidase B in the low nanomolar range. The high convergency of the synthetic methodologies paves the way for the rapid access to N-Fmoc-protected non-proteinogenic and unnatural amino acids and the total synthesis of complex bioactive peptides containing these amino acids.

Variation of corticospinal excitability during kinesthetic illusion induced by musculotendinous vibration.

Despite being studied for more than 50 years, the neurophysiological mechanisms underlying vibration (VIB)-induced kinesthetic illusions are still unclear. The aim of this study was to investigate how corticospinal excitability tested by transcranial magnetic stimulation (TMS) is modulated during VIB-induced illusions. Twenty healthy adults received vibration over wrist flexor muscles (80 Hz, 1 mm, 10 s). TMS was applied over the primary motor cortex representation of wrist extensors at 120% of resting motor threshold in four random conditions (10 trials/condition): baseline (without VIB), 1 s, 5 s, and 10 s after VIB onset. Means of motor-evoked potential (MEP) amplitudes and latencies were calculated. Statistical analysis found a significant effect of conditions (stimulation timings) on MEP amplitudes (P = 0.035). Paired-comparisons demonstrated lower corticospinal excitability during VIB at 1 s compared with 5 s (P = 0.025) and 10 s (P = 0.003), although none of them differed from baseline values. Results suggest a time-specific modulation of corticospinal excitability in muscles antagonistic to those vibrated, i.e., muscles involved in the perceived movement. An early decrease of excitability was observed at 1 s followed by a stabilization of values near baseline at subsequent time points. At 1 s, the illusion is not yet perceived or not strong enough to upregulate corticospinal networks coherent with the proprioceptive input. Spinal mechanisms, such as reciprocal inhibition, could also contribute to lower the corticospinal drive of nonvibrated muscles in short period before the illusion emerges. Our results suggest that neuromodulatory effects of VIB are likely time-dependent, and that future work is needed to further investigate underlying mechanisms.NEW & NOTEWORTHY The modulation of corticospinal excitability when perceiving a vibration (VIB)-induced kinesthetic illusion evolves dynamically over time. This modulation might be linked to the delayed occurrence and progressive increase in strength of the illusory perception in the first seconds after VIB start. Different spinal/cortical mechanisms could be at play during VIB, depending on the tested muscle, presence/absence of an illusion, and the specific timing at which corticospinal drive is tested pre/post VIB.

Multiple Mycobacterium abscessus O-acetyltransferases influence glycopeptidolipid structure and colony morphotype.

Mycobacterium abscessus causes severe lung infections. Clinical isolates can have either smooth (S) or rough (R) colony morphotypes; of these, S but not R variants have abundant cell wall glycopeptidolipids (GPL) consisting of a peptidolipid core substituted by a 6-deoxy-α-L-talose (6-dTal) and rhamnose residues. Deletion of gtf1, encoding the 6-dTal transferase, results in the S-to-R transition, mycobacterial cord formation, and increased virulence, underscoring the importance of 6-dTal in infection outcomes. However, since 6-dTal is di-O-acetylated, it is unclear whether the gtf1 mutant phenotypes are related to the loss of the 6-dTal or the result of the absence of acetylation. Here, we addressed whether M. abscessus atf1 and atf2, encoding two putative O-acetyltransferases located within the gpl biosynthetic locus, transfer acetyl groups to 6-dTal. We found deletion of atf1 and/or atf2 did not drastically alter the GPL acetylation profile, suggesting there are additional enzymes with redundant functions. We subsequently identified two paralogs of atf1 and atf2, MAB_1725c and MAB_3448. While deletion of MAB_1725c and MAB_3448 had no effect on GPL acetylation, the triple atf1-atf2-MAB_1725c mutant did not synthetize fully acetylated GPL, and the quadruple mutant was totally devoid of acetylated GPL. Moreover, both triple and quadruple mutants accumulated hyper-methylated GPL. Finally, we show deletion of atf genes resulted in subtle changes in colony morphology but had no effect on M. abscessus internalization by macrophages. Overall, these findings reveal the existence of functionally redundant O-acetyltransferases and suggest that O-acetylation influences the glycan moiety of GPL by deflecting biosynthetic flux in M. abscessus.

Should an elective contralateral neck dissection be performed in midline-reaching squamous cell carcinomas of the oral cavity and oropharynx?

OBJECTIVE: to compare the rate of occult contralateral neck metastases (OCNM) in oral and oropharyngeal squamous cell carcinomas (SCC) reaching or crossing the midline and to identify risk factors for OCNM. MATERIALS AND METHODS: we conducted a single-center retrospective study of oral and oropharyngeal SCC with contralateral cN0 neck. The cohort was divided into a midline-reaching (MR; approaching the midline from up to 10 mm) group and a midline-crossing (MC; exceeding the midline by up to 10 mm) group. Clinical N-status was assessed by a radiologist specializing in head and neck imaging. All patients underwent contralateral elective neck dissection (END). RESULTS: A total of 98 patients were included in this study, 59 in the MR group and 39 in the MC group. OCNM were present in 17.3% of patients, 20.3% in the MR group and 12.8% in the MC group (p = 0.336). In multivariable analysis, MR/MC status as well as distance from the midline (in mm) were not identified as risk factors for OCNM. Conversely, oropharyngeal primary and clinical N-status above N1 were significantly associated with a higher risk of OCNM, with odds ratios (OR) of 3.98 (95% CI = 1.08-14.60; p = 0.037) and 3.41 (95% CI = 1.07-10.85; p = 0.038) respectively. CONCLUSION: in patients with oral and oropharyngeal SCC extending close to or beyond the midline, tumor origin and clinical N-status should carry the most weight when dictating the indications for contralateral END, rather than the midline involvement in itself.

The Cardiovascular Manifestations of COVID-19.

The Coronavirus 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus, has resulted in unprecedented morbidity and mortality worldwide. While COVID-19 typically presents as viral pneumonia, cardiovascular manifestations such as acute coronary syndromes, arterial and venous thrombosis, acutely decompensated heart failure (HF), and arrhythmia are frequently observed. Many of these complications are associated with poorer outcomes, including death. Herein we review the relationship between cardiovascular risk factors and outcomes among patients with COVID-19, cardiovascular manifestations of COVID-19, and cardiovascular complications associated with COVID-19 vaccination.

Within-Session Test-Retest Reliability of Pressure Pain Threshold and Mechanical Temporal Summation in Chronic Low Back Pain.

OBJECTIVES: To determine the absolute and relative within-session test-retest reliability of pressure pain threshold (PPT) and temporal summation of pain (TSP) at the low back and the forearm in individuals with chronic low back pain (CLBP) and to test the impact of different sequences of measurements on reliability metrics. MATERIALS AND METHODS: Twenty-eight adults with CLBP were recruited. Relative (intraclass correlation coefficient [ICC] and coefficient of variation) and absolute reliability (standard error of measurement and minimal detectable changes) were quantified at 4 sites (back: sacrum and lumbar erector spinae; wrist: hand dorsum and wrist flexors) for PPT and 2 sites (hand and low back) for TSP, for various sequences of measurements. RESULTS: Systematic differences were found between within test and retest for most PPT sequences at the lumbar erector spinae site and 1 TSP sequence (1-2-3) at back and hand sites, precluding reliability analyses for these data. Within-session PPT relative reliability was excellent at low back (ICC = 0.83 to 0.94) and wrist (ICC = 0.88 to 0.97) sites, whereas TSP showed good to excellent reliability at hand (ICC = 0.80 to 0.90) and low back (ICC = 0.73 to 0.89). In general, 2 and 3 measurements optimized absolute and relative reliability for TSP and PPT, respectively. DISCUSSION: Within-session reliability was generally excellent for PPT and TSP at the low back and hand sites among individuals with CLBP. We recommend using 3 measurements for PPT and 2 for TSP to optimize reliability. Caution is recommended when testing PPT of the painful lower back area since a systematic difference was present between the test and retest.

Atretic cephalocele and encephalocele: A single-institution clinicopathological study.

BACKGROUND: Encephaloceles are neural tube defects characterized by herniation of meninges, neural tissue and cerebrospinal fluid, while atretic cephaloceles denote a rudimentary connection to the intracranial space with absence of herniated neural tissue and represent an infrequent dermatopathologic diagnosis. Limited reports of these entities confound the challenge in their histopathologic distinction. Accurate classification is important given associated anomalies and neurologic manifestations that impact prognosis. METHODS: We describe the clinicopathological and immunohistochemical [glial fibrillary acidic protein (GFAP), S100, epithelial membrane antigen (EMA), and somatostatin receptor subtype 2A (SSTR2A)] features in a retrospective series encountered at a single institution between 1994 and 2020. RESULTS: We identified 13 cases classified as atretic cephalocele (n = 11) and encephalocele (n = 2). Hamartomatous changes and multinucleated cells were unique to atretic cephaloceles while myxoid areas were unique to encephaloceles. At least focal staining for SSTRA was seen in all atretic cephaloceles with the majority (87.5%) staining for EMA; negative staining for GFAP and S100 confirmed absence of neural tissue. Encephaloceles were GFAP and S100 positive, and negative for SSTR2 and EMA. Atretic cephaloceles had a favorable prognosis compared to encephaloceles, with severe morbidity present in both encephalocele cases. CONCLUSION: Our study raises awareness of atretic cephalocele and encephalocele among dermatopathologists and reveals a mutually exclusive immunophenotype that facilitates their distinction for prognostication and management.

Distinctive phases and variability of vibration-induced postural reactions highlighted by center of pressure analysis.

BACKGROUND: The vibration-induced postural reaction paradigm (VIB-PR) offers a unique way for investigating sensorimotor control mechanisms. Measures of VIB-PR are usually calculated from the whole VIB period, yet recent evidence proposed that distinctive mechanisms are likely at play between the early vs. later phases of the postural reaction. OBJECTIVES: The present work verified if spatiotemporal analyses of center of pressure (COP) displacements can detect differences between these early/later phases of VIB-PR. Also, we further characterized the intra/inter-individual variability of COP measurements, since the underlying variability of VIB-PR remains largely unexplored. METHODS: Twenty young volunteers realized two experimental conditions of bipodal stance with eyes closed: (i) bilateral VIB of tibialis anterior (TIB) and (ii) Achilles' (ACH) tendons. Each condition consisted of five trials and lasted 30 s as follows: 10 s baseline, 10 s VIB and 10 s post-VIB. Linear COP variables (antero-posterior (AP) amplitude & velocity) were computed for both VIB and post-VIB periods using the following time-windows: early 2 s, the later 8 s and the whole 10 s duration. Intra- and inter-individual variability were respectively estimated using the standard error of the measurement and the coefficient of variation. Both variability metrics were obtained using five vs. the first three trials. RESULTS: Significant contrasts were found between time-windows for both VIB and post-VIB periods. COP variables were generally higher during the early 2 s phase compared to the later 8 s phase for both TIB [mean difference between 8 s- 2 s phases: Amplitude AP = -1.11 ± 1.14 cm during VIB and -2.99 ± 1.31 during post-VIB; Velocity AP = -1.17 ± 0.86 cm/s during VIB and -3.13 ± 1.31 cm/s during post-VIB] and ACH tendons [Amplitude AP = -0.37 ± 0.98 cm during VIB and -3.41 ± 1.20 during post-VIB; Velocity AP = -0.31 ± 0.59 cm/s during VIB and -3.89 ± 1.52 cm/s during post-VIB]. Most within- and between-subject variability scores were below 30% and using three instead of five trials had no impact on variability. VIB-PR patterns were quite similar within a same person, but variable behaviors were observed between individuals during the later phase. CONCLUSION: Our study highlights the relevance of identifying and separately analyzing distinct phases within VIB-PR patterns, as well as characterizing how these patterns vary at the individual level.

Assessment of exercise-induced hypoalgesia in chronic low back pain and potential associations with psychological factors and central sensitization symptoms: A case-control study.

INTRODUCTION: Exercise is the most recommended treatment for chronic low back pain (CLBP) and is effective in reducing pain, but the mechanisms underlying its effects remain poorly understood. Exercise-induced hypoalgesia (EIH) may play a role and is thought to be driven by central pain modulation mechanisms. However, EIH appears to be disrupted in many chronic pain conditions and its presence in people with CLBP remains unclear. As people suffering from chronic pain often exhibit psychological factors and central sensitization symptoms influencing pain perception, EIH might be associated with these factors. OBJECTIVE: The aim of this study is to compare the level of EIH between participants with and without CLBP following back and wrist exercises and to assess the associations between EIH, psychological factors, and symptoms of central sensitization (using the central sensitization inventory - CSI) in CLBP. METHOD: Twenty-eight participants with CLBP and 23 without pain were recruited. Pressure pain thresholds (PPT) were measured at 4 sites (2 bony sites = capitate, S1|2 muscle sites = wrist flexors, lumbar erector spinae) before and after each of two exercises (wrist flexion and lumbar extension). Exercise-induced hypoalgesia was defined as percent change in PPT from pre- to post-exercise. Participants with CLBP also completed questionnaires to measure psychological factors (e.g., kinesiophobia, catastrophizing, anxiety, and self-efficacy) and symptoms of central sensitization (CSI), and correlations with EIH were calculated. RESULTS: After wrist exercise, EIH measured at the muscle sites was lower in the CLBP group compared with the pain-free group (p = 0.047) but no differences were found at bony sites (p = 0.49). No significant differences for EIH were observed following back exercise at muscle sites (p = 0.14) or at bony sites (p = 0.65). Exercise-induced hypoalgesia was not correlated with any psychological factors or with the CSI score. CONCLUSION: The lower EIH following wrist exercises may represent an alteration in pain modulation control in CLBP. However, psychological factors and central sensitization symptoms may not explain the differences observed.

Dynamic sensitivity analysis: Defining personalised strategies to drive brain state transitions via whole brain modelling.

Traditionally, in neuroimaging, model-free analyses are used to find significant differences between brain states via signal detection theory. Depending on the a priori assumptions about the underlying data, different spatio-temporal features can be analysed. Alternatively, model-based techniques infer features from the data and compare significance from model parameters. However, to assess transitions from one brain state to another remains a challenge in current paradigms. Here, we introduce a "Dynamic Sensitivity Analysis" framework that quantifies transitions between brain states in terms of stimulation ability to rebalance spatio-temporal brain activity towards a target state such as healthy brain dynamics. In practice, it means building a whole-brain model fitted to the spatio-temporal description of brain dynamics, and applying systematic stimulations in-silico to assess the optimal strategy to drive brain dynamics towards a target state. Further, we show how Dynamic Sensitivity Analysis extends to various brain stimulation paradigms, ultimately contributing to improving the efficacy of personalised clinical interventions.

Vibration-induced postural reactions: a scoping review on parameters and populations studied.

Objective: Mechanical vibration is an effective way for externally activating Ia primary endings of the muscle spindles and skin mechanoreceptors. Despite its popularity in proprioception and postural control studies, there is still no review covering the wide variety of vibration parameters or locations used in studies. The main purpose of this scoping review was thus to give an overview of general vibration parameters and to identify, if available, the rationale for justifying methodological choices concerning vibration parameters. Methods: Three databases (Pubmed, CINHAL, and SPORTDiscus) were searched from inception to July 2022. Included articles were to focus on the study of muscle spindles and skin mechanoreceptors vibration in humans and assess postural control. Following inclusion, data regarding demographic information, populations, vibration parameters and rationale were extracted and summarized. Results: One hundred forty-seven articles were included, mostly targeting lower extremities (n = 137) and adults (n = 126). The parameters used varied widely but were most often around 80 Hz, at an amplitude of 1 mm for 10-20 s. Regarding rationales, nearly 50% of the studies did not include any, whereas those including one mainly cited the same two studies, without elaborating specifically on the parameter's choice. Conclusion: This scoping review provided a comprehensive description of the population recruited and parameters used for vibration protocols in current studies with humans. Despite many studies, there remain important gaps of knowledge that needs to be filled, especially for vibration amplitude and duration parameters in various populations.

Preadmission Oral Anticoagulation for Atrial Fibrillation/Flutter and Death or Thrombotic Events During COVID-19 Admission.

Atrial fibrillation/flutter (AF) and COVID-19 are associated with an elevated risk of arterial and venous thrombosis. Whether preadmission oral anticoagulation (OAC) for AF reduces the incidence of in-hospital death or thrombotic events among patients with COVID-19 is unknown. We identified 630 patients with pre-existing AF and a hospitalization diagnosis of COVID-19 and stratified them according to preadmission OAC use. Multivariable logistic regression was employed to relate preadmission OAC to composite in-hospital mortality or thrombotic events. Unadjusted composite in-hospital mortality or thrombotic complications occurred less often in those on than not on preadmission OAC (27.1% vs 46.8%, p <0.001). After adjustment, the incidence of composite in-hospital all-cause mortality or thrombotic complications remained lower with preadmission OAC (odds ratio 0.37, confidence interval 0.25 to 0.53, p <0.0001). Secondary outcomes including all-cause mortality (16.3% vs 24.9%, p = 0.007), intensive care unit admission (14.7% vs 29.0%, p <0.001), intubation (6.4% vs 18.6%, p <0.001), and noninvasive ventilation (18.6% vs 27.5%, p = 0.007) occurred less frequently, and length of stay was shorter (6 vs 7 days, p <0.001) in patients on than those not on preadmission OAC. A higher CHA2DS2-VASc score was associated with an increased risk of thrombotic events. In conclusion, among patients with baseline AF who were hospitalized with COVID-19, those on preadmission OAC had lower rates of death, arterial and venous thrombotic events, and less severe COVID-19.

The Cardiovascular Manifestations of COVID-19.

The Coronavirus 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus, has resulted in unprecedented morbidity and mortality worldwide. While COVID-19 typically presents as viral pneumonia, cardiovascular manifestations such as acute coronary syndromes, arterial and venous thrombosis, acutely decompensated heart failure (HF), and arrhythmia are frequently observed. Many of these complications are associated with poorer outcomes, including death. Herein we review the relationship between cardiovascular risk factors and outcomes among patients with COVID-19, cardiovascular manifestations of COVID-19, and cardiovascular complications associated with COVID-19 vaccination.