Citations

ABSTRACT Background The optimal long‐term antithrombotic strategy after apparently successful catheter ablation of atrial fibrillation (AF) remains uncertain, particularly in patients who meet conventional guideline thresholds for oral anticoagulation (OAC). Objectives To compare continuation versus cessation strategies of long‐term OAC after successful AF ablation and to quantify net clinical benefit (NCB) integrating thromboembolic and bleeding outcomes. Methods We searched PubMed, Cochrane CENTRAL, and Embase from inception through February 2026 for randomized and comparative observational studies evaluating long‐term OAC continuation versus cessation (no OAC and/or switch to aspirin) after successful AF ablation. Risk of bias was assessed using RoB2 for randomized trials and a modified Newcastle–Ottawa Scale (NOS) for observational studies. Random‐effects meta‐analyses used a restricted maximum likelihood estimator with Hartung–Knapp adjustment. NCB was calculated as: thromboembolic event rate − (1.5 × major bleeding rate). Results Six studies met the inclusion criteria (four randomized trials and two observational cohorts). Stroke/transient ischemic attack (TIA) events were reported in six studies and were not significantly different between OAC continuation and cessation strategies (OR 0.69; 95% CI 0.24–1.99; p = 0.49). Systemic embolism (three studies) did not differ between groups ( p = 0.12). Major bleeding (five studies) was numerically higher with continued OAC but not statistically significant (OR 2.07; 95% CI 0.88–4.86; p = 0.09). In NCB analysis, continued OAC yielded more negative or near‐neutral NCB values, whereas, the cessation strategies were less negative or marginally positive; the fixed‐effect risk difference in NCB (continued OAC vs cessation) was +0.00067 (95% CI −0.00279 to +0.00413). Conclusion This meta‐analysis suggests that after successful AF ablation, continuing OAC does not significantly reduce stroke risk compared to cessation or switching to aspirin, but it may increase major bleeding. While NCB trends favor cessation, the low absolute event rates and the risk of silent AF recurrence necessitate caution.

ABSTRACT Background Factor XI/XIa inhibitors are emerging anticoagulants with potential to reduce bleeding complications in atrial fibrillation (AF) patients. This meta‐analysis evaluated their efficacy and safety compared to direct oral anticoagulants (DOACs) and explored dose optimization. Methods A systematic search of PubMed, Cochrane, and Embase was conducted through March 2025 following PRISMA guidelines. Randomized controlled trials (RCTs) comparing Factor XI/XIa inhibitors with DOACs in AF patients were included. Outcomes assessed were major bleeding, stroke, systemic embolism, all‐cause and cardiovascular mortality and serious adverse events. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a Mantel‐Haenszel random‐effects model. Heterogeneity was evaluated with the I² statistic, and evidence certainty assessed by the GRADE approach. Trial Sequential Analysis (TSA) was performed. Results Three RCTs including 16,772 patients (mean age 73 years, CHA₂DS₂‐VASc 3.9–5) were analyzed. Factor XI/XIa inhibitors significantly reduced major bleeding (RR: 0.41, 95% CI: 0.36–0.46, I² = 0%) compared to DOACs. However, stroke risk was increased (RR: 3.42, 95% CI: 2.62–4.46), particularly with asundexian 50 mg (RR: 4.02). No significant differences were observed in all‐cause mortality (RR: 0.82) or cardiovascular death (RR: 1.05). Systemic embolism risk was higher (RR: 4.26), while serious adverse events were comparable (RR: 0.95). TSA indicated encouraging safety outcomes but highlighted the need for further large‐scale studies. Conclusion Factor XI/XIa inhibitors lower major bleeding risk in AF patients but increase stroke and systemic embolism rates without impacting mortality.

Abstract Systemic amyloidosis is a rare, multisystem disorder that is often challenging to diagnose due to vague and nonspecific symptoms that frequently overlap with other disorders. By the time patients are diagnosed, irreversible organ impairment from amyloid deposition occurrs, contributing to substantial morbidity and mortality. Although developing the American Society of Hematology (ASH) guidelines on systemic amyloidosis, we identified a critical knowledge gap in the recognition of the clinical presentation of its most common subtypes. Therefore, we conducted a scoping review of 117 studies following PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) guidelines to identify clinical “red flags” for light chain (AL) and transthyretin (ATTR; wild-type [ATTRwt] and hereditary [ATTRv]) amyloidosis. Studies were identified from the comprehensive systematic review through the ASH amyloidosis diagnosis guideline panel, data mining, and gray literature review. Data were extracted and synthesized by systems to characterize the earliest and most frequently overlooked clinical red flags for the different types of amyloidosis. Shortness of breath and fatigue, the earliest symptoms of AL amyloidosis, contrast with the carpal tunnel syndrome occurring years before ATTRwt cardiac amyloidosis is diagnosed. Weight loss, unexplained abdominal pain, and early satiety were overlooked red flags for AL amyloidosis, compared to the preceding arrhythmias often missed in evaluation for ATTRwt amyloidosis. Sensory loss was the predominant neuropathic presentation for AL amyloidosis compared to the painful length-dependent neuropathy of ATTRv amyloidosis. Awareness of the early symptoms and distinct patterns across subtypes can enhance cross-specialty awareness and support earlier diagnosis and intervention of AL and ATTR amyloidosis.

Background Light chain (AL) amyloidosis is a rare disease caused by the misfolding of immunoglobulin light chains produced by a plasma cell dyscrasia. Patients can present with involvement of many organs, including the heart, kidneys, liver, nerves, and other sites, resulting in a high symptom burden. Timely and accurate diagnosis is important to prevent organ failure and improve patient survival. Objective These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients and clinicians in the timely and effective diagnosis of AL amyloidosis. Methods ASH formed a multidisciplinary guideline panel that included 22 individuals representing various medical specialties (academic and community hematology, nephrology, neurology, cardiology, internal medicine, and pathology) as well as 1 patient representative. The group was balanced to minimize potential bias from conflicts of interest. The University of Kansas Medical Center supported the guideline development process, including updating or performing systematic evidence reviews (up to 6 March 2023). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results The panel agreed on 12 recommendations. Conclusions The use of serum immunofixation, urine immunofixation, and serum free light chains enhances the clinical suspicion of AL amyloidosis. The diagnosis of AL amyloidosis can be made effectively through surrogate biopsies, which require both a bone marrow biopsy and fat-pad sampling; however, target organ biopsies may be favored in certain clinical situations.

ABSTRACT Introduction Desmoplastic small round cell tumor (DSRCT) is a rare malignant mesenchymal neoplasm of polyphenotypic differentiation, characterized by EWSR1‐WT1 gene fusion. Despite multimodality therapy, the tumor carries poor prognosis. We report cytomorphological, immunohistochemical (IHC) and molecular features of seven cases of DSRCT from four patients. Materials and Methods A retrospective review of cytology smears, biopsies and molecular features of cases diagnosed as DSRCT at Department of Pathology, Henry Ford Health System, and Indiana University, USA between 2016 and 2022 were performed. A total of seven cases of DSRCT from four patients were included in this study. The cytological findings were correlated with concurrent or subsequent biopsy findings. Results All patients were male, with age ranging from 21 to 29 years. Two patients had primary tumor in the abdomen, one in the retroperitoneum, and one in the inguinal region. The tumors measured from 7.5 to 17 cm in size. Six out of seven cases showed typical hypercellular smears of small round cells with inconspicuous nucleoli, scant cytoplasm, and rare nuclear molding. The cytomorphology in Case no. 1 was unusual, showing discohesive pleomorphic tumor cells with large irregular nuclei, prominent nucleoli, occasional binucleation, and frequent mitotic activity. A subset of tumor cells demonstrated rhabdoid features. The tumor cells were positive for keratins (dot‐like), desmin, WT‐1, and CD15. In Case no. 4, the immunohistochemistry for desmin and WT‐1 was unusually negative reflecting the variability of the staining pattern. Three cases were positive for EWSR1 rearrangement by fluorescence in situ hybridization (FISH) and one positive for EWSR1‐WTI gene fusion by reverse transcriptase‐polymerase chain reaction (RT‐PCR). All seven cases had concurrent/subsequent surgical pathology diagnosis consistent with DSRCT. Conclusion Cytologic diagnosis for DSRCT is challenging but can be achieved with appropriate cytomorphology, IHC profiles, molecular studies, and demographic information. Rare rhabdoid differentiation can occur in DSRCT and can be present in effusion cytology.

Abstract Bone marrow is the primary immune organ responsible for stem cell maintenance and hematopoiesis. However, the contribution of the bone marrow niche for the generation of adaptive immune responses is less well-understood. We therefore assessed the capacity of virus antigen-specific CD8 T cells to be generated and expanded in bone marrow following acute neurotropic virus infection. Intracranial infection with the neurotropic Theiler’s Murine Encephalomyelitis Virus (TMEV) results in an acute infection in the C57BL/6 mouse which is cleared within 4 weeks post infection due to the generation of an antigen-specific CD8 T cell response against the immunodominant epitope VP2 121-130 . We determined that 1-10% of CD8 T cells present in the femoral, and sternal bone marrow were virus antigen-specific 5-7 days after intracranial TMEV infection. We determined that antigen-specific CD8 T cells were generated in the bone marrow with similar kinetics to that of conventional responses in the secondary lymphoid organs. Importantly, continuous treatment with FTY720, which sequesters T cells outside of the blood, did not eliminate antigen-specific CD8 T cells in the bone marrow compartment indicating generation within the bone marrow niche. Similarly, injection of Poly I:C admixed with fluorescently labeled ovalbumin into the brain generated a similar antigen-specific CD8 T cell response in the bone marrow indicating these responses occur following various brain insults. This model also identified the likely antigen presenting cell (APC) responsible for scavenging antigens from the brain and trafficking into the bone marrow as a migratory myeloid-derived APC. Moreover, following clearance of TMEV infection, CD8 T cells in the bone marrow established durable memory. Antigen-specific memory CD8 T cells in the bone marrow reactivated and expanded upon cognate antigen reencounter. Antigen-specific reactivation of memory CD8 T cells within the bone marrow caused a concurrent increase in Lineage-, Sca-1+, c-Kit+ (LSK) and CD11b+ MHCII+ myeloid cells. This increase in the LSKs and myeloid cells in the bone marrow niche was abrogated with CD8 T cell depletion. We conclude that brain viral infections induce in situ effector and memory T cell responses within the bone marrow compartment. Memory recall CD8 T cell responses induce niche dysregulation by expanding LSK cells and lead to an influx of MHCII+ myeloid cells. Our data pave the way for crucial studies of bone marrow resident antigen-specific CD8 T cells in health and diseases.

Abstract Objective Constipation is a common gastrointestinal concern in children, often prompting screening for celiac disease (CeD), particularly in refractory cases. However, limited data exist on the clinical course of constipation in children with CeD following treatment with a gluten‐free diet. Methods We reviewed electronic health records from the Mayo Clinic between 1994 and 2024 for children (<18 years) who presented with constipation and then diagnosed with CeD. Children were classified into groups based on the symptoms at the time of presentation. Constipation outcome was considered resolved by the documentation of improvement on a gluten‐free diet without ongoing laxative use, while unresolved cases required continued laxative therapy. A sub‐analysis was performed for children with encopresis. Results We identified 248 children with CeD, 177 (71%) had biopsy‐confirmed CeD, and 56 (23%) were diagnosed with serology‐only criteria. The mean age at diagnosis was 7.8 years (±4.98), with most being White (99%) and female (68%). Constipation was the main presenting symptom, but most children also exhibited additional symptoms at the time of diagnosis. Over an average of 5.3 years (±2.1) of follow‐up, constipation was resolved in 32% of children, while 68% required ongoing laxatives, in the subgroup of children with encopresis, only 29% had documented resolution. Tissue transglutaminase antibody normalization was slower in children with unresolved constipation. Trends were observed toward a higher prevalence of anxiety, depression (42% vs. 30%) and thyroid disorders (13% vs. 9%) in the unresolved group. We also noticed a trend to a higher likelihood of constipation resolution in children with type 1 diabetes mellitus (14% vs. 4%), but none reached statistical significance. Conclusion Many children with CeD continue to experience persistent unresolved constipation despite adherence to a gluten‐free diet. Comorbidities are associated with a lower rate of constipation resolution.

Abstract Background Streptococcus agalactiae (group B Streptococcus [GBS]) may cause pneumonia or may colonize the respiratory tract, making its clinical significance uncertain when detected in respiratory specimens. This study aimed to assess whether clinicians interpreted GBS detected by the BIOFIRE Pneumonia Panel (BF-PP) as a pathogen implicated in pneumonia. Methods This retrospective cohort study included adult patients hospitalized with suspected pneumonia at Mayo Clinic, Rochester, between September 2020 and February 2025. Cases were independently classified into pathogen and nonpathogen groups by 2 infectious diseases (ID) specialists, with a third reviewer resolving disagreements. Clinical characteristics and outcomes of both groups were recorded. A subgroup analysis of patients who had an ID consultation was performed. Results A total of 109 cases were included. GBS was considered a pneumonia pathogen in 47.7% of cases and a nonpathogen in 52.3%. ID consultation was performed in 33.0% of cases, with GBS considered a pathogen in 30.6% of those. Common comorbid conditions included pulmonary, gastrointestinal, neurologic, and cardiovascular disease and obesity. Rates of endotracheal intubation were similar in the pathogen and nonpathogen groups (51.9% vs 50.9%, respectively), with the in-hospital mortality rate being numerically but not significantly higher in the former versus the latter (21.2% vs 14.0%; P = .33); findings were similar in the ID-assessed subgroup. In 76.1% of GBS detections, other microorganisms—most commonly Staphylococcus aureus—were codetected. Only 10.2% of BF-PP GBS-positive specimens were culture positive for GBS. Conclusions While GBS is not an uncommon pneumonia pathogen, the clinical significance of its detection by BF-PP is uncertain in many cases.

Introduction Lactating physicians face considerable challenges in achieving lactation goals due to inflexible schedules and a lack of break time. While federal mandates have outlined the necessity of lactation breaks, the frequency and duration of breaks are unspecified. The objective of this study was to fill this gap by designing and implementing an outpatient neurology resident clinic schedule with protected lactation breaks, ensuring support and quality of trainees’ educational experience. Methods This quality improvement study began with developing a prototype schedule with input from lactating physicians, a lactation consultant, and neurology residency program leadership. Neurology residents and fellows with prior lactation experience were surveyed to determine if the proposed schedule would have fit their individual needs. The clinic schedule with protected lactation break time was then implemented, and lactating neurology residents were surveyed regarding their experience. Results Eleven previously lactating neurology residents and fellows who were surveyed about the proposed schedule agreed that the prototype schedule would suffice for their personal lactation needs. The clinic schedule was implemented for 5 neurology residents returning from maternity leave in 2022 to 2023, and 4 residents completed a survey of their experience. There was unanimous agreement that protected lactation breaks helped residents achieve their lactation goals and strongly benefited work/life balance and overall well-being. Despite this intervention, 75% of respondents stopped breastfeeding earlier than intended, and 100% of respondents experienced complications perceived to be related to inadequate pumping, such as diminished milk supply. Ongoing barriers to achieving breastfeeding goals included work interrupting lactation breaks, lack of lactation rooms, and lack of computer workstations in lactation rooms. Conclusions Inclusion of protected lactation breaks in outpatient clinic schedules helped neurology residents achieve their lactation goals as well as promoted work/life balance and overall well-being. However, more work is needed to address other barriers to achieving lactation goals.