Personalized data-driven interventions for depression are much needed. Here, we leveraged N-of-1 machine learning (ML) to optimally target behavioral lifestyle interventions for depression. 50 individuals with mild-to-moderate depression enrolled in the single-arm, open-label Personalized Mood Augmentation (PerMA) pilot clinical trial (NCT05662254). Participants completed a two-week digital monitoring phase using smartphone-based ecological momentary assessments (EMAs, 4×/day) plus smartwatch tracking of mood and lifestyle factors (sleep/exercise/diet/social connection). Personalized ML models were generated from these data to identify lifestyle factors most predictive of individual mood, and results were translated to individualized mood augmentation plans (iMAPs) implemented by participants for six weeks with once-a-week health coach guidance. Intervention completers (n = 40) showed significant reduction in depression symptoms (primary outcome self-rated PHQ9 -3.5 ± 3.8, Cohen's d = -0.89, CI [-1.25 -0.53], p < 0.001; clinician-rated HDRS -7.2 ± 6.8, d = -1.03, CI [-1.41 -0.65], p < 1E-6) with benefits sustained up to 12-week follow-up. Co-morbid anxiety was also significantly reduced (GAD7: d = -0.85, CI [-1.2, -0.49], p < 0.001) and quality of life improved (d = 0.68, CI [0.33, 1.02], p < 0.001). Additionally, objective cognitive measures impacted in depression including selective attention (d = 0.51, CI [0.18, 0.84], p < 0.001), interference processing (d = 0.53, CI [0.2, 0.85], p < 0.01) and working memory (d = 0.66, CI [0.31, 0.99], p < 0.001) showed significant enhancement. EMA tracking confirmed that improvement in depressed mood was specifically predicted by improvement in individually targeted lifestyles (β = 0.4 ± 0.09, p < 0.0005). Finally, decision algorithms and a large-language-model (LLM) could match human coach-led iMAP assignment with up to 95% accuracy. The PerMA trial presents a personalized lifestyle intervention approach for depression and merits scale-up and RCT testing to establish clinical efficacy. PERMA was registered with ClinicalTrials.gov under registry number NCT05662254.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare, aggressive subtype of peripheral T-cell lymphoma. Whole population studies of AITL are infrequent and often grouped along with other T-cell lymphomas. We undertook a population-based study using ICD-O3-coded cases of AITL diagnosed 2013-2019 in order to establish AITL epidemiology in England, along with survival outcomes and associated diagnoses. We identified 993 cases, with a median age of 71 years. Overall incidence was 2.57 cases/million person-years (95% CI 2.41-2.74). The incidence increased with age, ranging from 0.24 cases/million person-years at 0-49 years (CI 0.19-0.31) to 11.56 in ≥ 70 years (CI 10.62-12.55), and was lower in females (incidence rate ratio [IRR] 0.74, CI 0.66-0.84). One and 3-year overall survival (OS) were 58% and 37% respectively. 151 patients received auto-SCT, with a 1-year and 3-year OS from transplant of 78.9% and 65.8%. In multivariable analysis, gender (hazard ratio [HR] in females = 0.77, 95% CI 0.66-0.90) and age (HR in ≥ 80 years = 4.41, CI 2.86-6.79) impacted OS. 142 patients developed an associated B-cell lymphoma or Hodgkin lymphoma (14.3%). A diagnosis of autoimmune hemolytic anemia (AIHA) was reported in 56 patients (5.6%), and immune thrombocytopenic purpura (ITP) in 14 (1.4%). Our study defines AITL incidence for the first time in England, confirms OS in an unselected population, and describes rates of autoimmune disease and B-cell lymphomas. Gender and age are the primary characteristics that influence outcomes.

LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency belonging to the spectrum of common variable immunodeficiency disorders, frequently associated with immune dysregulation, autoimmunity, and lymphoproliferation. Its clinical presentation is highly heterogeneous, ranging from isolated autoimmune cytopenias to severe multisystem involvement. Here, we report five cases of LRBA deficiency from five Moroccan families, highlighting the broad clinical variability of this condition. The first patient presented with chronic immune thrombocytopenic purpura (ITP) as the initial and predominant manifestation, associated with hypogammaglobulinemia. The second patient developed ITP complicated by a hemorrhagic syndrome and significant lymphoproliferation, including splenomegaly and hepatomegaly. The third patient initially presented with autoimmune hemolytic anemia (AIHA), followed by splenomegaly. The fourth patient exhibited a complex clinical course, beginning with bicytopenia and progressing to enteropathy, arthritis, pneumopathy, and type 1 diabetes mellitus, associated with splenomegaly, hepatomegaly, and lymphadenopathy. Finally, the fifth patient initially presented with ITP and subsequently developed bilateral panuveitis, arthritis, and recurrent respiratory infections. Targeted next-generation sequencing identified homozygous pathogenic variants in the LRBA gene in all five patients, consistent with a loss-of-function mechanism. These included the nonsense variants c.3811C>T (p.Arg1271*) and c.5692G>T (p.Glu1898*), a large deletion encompassing exons 30 to 34, the frameshift variant c.5060_5067delACATACCA (p.Asn1687Serfs*21), and an extended deletion involving part of exon 4 (c.476_549 + 580del). All patients required immunosuppressive therapy and/or immunoglobulin replacement. LRBA deficiency should be considered in children presenting with autoimmune cytopenias, lymphoproliferation, and multisystem autoimmunity. The marked heterogeneity of clinical manifestations underscores the importance of early molecular diagnosis to guide therapeutic decision-making. In our experience, prompt recognition and the initiation of targeted therapies, such as abatacept or early hematopoietic stem cell transplantation, may improve patient outcomes.

Amegakaryocytic thrombocytopenia is a rare hematological disorder that is characterized by absent or near-absent megakaryocytes without evidence of other hematological abnormalities. The disease can either be congenital or acquired. Given that less than a hundred cases of acquired amegakaryocytic thrombocytopenia (AAMT) have been reported in the literature, its pathophysiology and treatment remain poorly understood. Various treatments have been proposed for AAMT, including glucocorticoids and other immunosuppressive agents, such as cyclosporine, antithymocyte globulin, and rituximab. To date, there are limited data on the role of thrombopoietin receptor agonists (TPO-RAs) for the treatment of AAMT. We present the case of a patient who initially presented with ecchymoses, purpura, and petechiae and was ultimately diagnosed with AAMT. He was treated with eltrombopag and had an increase in platelets with decreased bleeding after approximately 6 months of eltrombopag therapy. He did not experience any side effects from eltrombopag or require any platelet transfusions during follow-up. Treatment overlapped with cyclosporine and prednisone, but these were discontinued due to adverse effects. Our case demonstrates that TPO-RAs can be effective novel therapeutic agents and improve patient outcomes for this rare condition.

Immune thrombocytopenic purpura (ITP) is a rare autoimmune condition characterized by isolated thrombocytopenia in the absence of an identifiable secondary cause. While most cases respond to first-line therapy, relapsed or refractory forms, particularly in patients with coexisting autoimmune disorders, pose significant diagnostic and treatment challenges. Recent reports have identified rare instances of autoimmune cytopenias following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination, raising concern for potential immune reactivation in predisposed individuals with prior immune dysregulation. We present the case of a 68-year-old male with a history of ITP and autoimmune hemolytic anemia who developed a severe relapse of thrombocytopenia, epistaxis, and suspected gastrointestinal hemorrhage shortly after coronavirus disease 2019 (COVID-19) vaccination. Despite initial treatment with corticosteroids, intravenous immunoglobulin, and platelet transfusions, the patient experienced a second relapse requiring escalation of care with additional immunosuppressive therapy and close hematologic follow-up. Ultimately, his condition improved with a multimodal approach and coordinated outpatient management. This case is clinically significant due to its temporal association with COVID-19 vaccination and the relapsing nature of ITP in the setting of systemic autoimmunity. It underscores the importance of early recognition, timely intervention, and vigilant monitoring in preventing life-threatening complications. The report adds to a growing body of literature highlighting the need for individualized care strategies and post-vaccine surveillance in patients at heightened risk of autoimmune reactivation.

Thrombotic thrombocytopenic purpura (TTP), an insidious and often devastating thrombotic microangiopathy, represents one of the few true hematologic emergencies. Since the identification of the von Willebrand factor (VWF) cleaving protease ADAMTS13 in the early 21st century, tremendous advances have been made in the diagnosis and treatment of the disease. However, as with many areas of science, new knowledge begets new questions about the pathophysiology of both congenital and immune TTP, which identify gaps in our understanding of the mechanistic effects of ADAMTS13 and its inhibitors. Improvements in the clinical management of patients that have-or are suspected to have-TTP requires further advances in diagnostic testing and identification of clinically relevant biomarkers. In this review, we discuss ADAMTS13-related diagnostic testing in TTP, identify the underlying assumptions that guide the field, and explore avenues of research that promise to improve the lives of patients with the disease.

Helicobacter pylori (H. pylori), a helical, flagellated Gram-negative bacterium, exhibits remarkable adaptability within the human gastric niche, enabling survival under acidic, nutrient-limited, and oxidative stress conditions. Beyond its established role in gastritis, peptic ulcer disease, and gastric adenocarcinoma, accumulating evidence implicates H. pylori in a spectrum of hematologic disorders. Iron deficiency anemia (IDA), vitamin B12 deficiency, immune thrombocytopenic purpura (ITP), and gastric mucosa-associated lymphoid tissue (MALT) lymphoma represent the most substantiated associations. Pathogenesis is multifactorial, encompassing chronic inflammation, cytokine dysregulation, molecular mimicry, impaired micronutrient absorption, and virulence factor-mediated disruption of host cellular processes, notably through CagA, VacA, SabA, and BabA components. In IDA and vitamin B12 deficiency, H. pylori-induced hypochlorhydria, altered gastric ascorbate levels, and hepcidin upregulation compromise systemic iron and cobalamin homeostasis. In contrast, in ITP, cross-reactivity between bacterial antigens and platelet epitopes triggers the production of autoantibodies and accelerates platelet clearance. Chronic antigenic stimulation and epigenetic modifications underpin lymphomagenesis in gastric MALT lymphoma, with treatment response modulated by strain-specific virulence, host genetics, and somatic translocations affecting NF-κB signaling. Clinical evidence demonstrates that targeted eradication therapy, often in combination with micronutrient supplementation, significantly restores hematologic parameters and mitigates systemic sequelae, yet patient-specific variability necessitates individualized management strategies. This review integrates current mechanistic and clinical insights into H. pylori-associated hematologic manifestations, highlighting the bacterium's systemic impact, elucidating therapeutic implications, and identifying critical gaps for future research aimed at optimizing diagnostic precision, intervention efficacy, and prognostic outcomes in affected populations.

Difficulties in complex daily activities are a hallmark of dementia syndromes. We examined neural signatures of complex daily activity using electroencephalography in forty-five older adults performing a dual-task walking paradigm. Participants were stratified by risk of cognitive impairment (CI). Brain activation linked to gait-related and cognitive events was recorded during single- and dual-task conditions. We hypothesized that a higher risk of CI is associated with poorer performance and distinct fronto-parietal activation during dual-task walking. Cognitive performance declined during walking, with individuals at higher risk of CI performing worse. Increased brain activity during the cognitive task was associated with a lower risk of CI. Both groups showed increased gait-related activation of sensorimotor and fronto-medial cortices during dual-task walking; however, greater sensorimotor activation was observed in individuals at higher risk of CI. Neural signatures of complex daily activity may help identify early signs of cognitive decline and inform prevention strategies.