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Olanzapine is a frequently used second-generation antipsychotic, often considered to have a favorable hematological safety profile than clozapine. We report a rare case of recurrent pancytopenia associated with olanzapine rechallenge in a 46-year-old woman with acute psychotic episode. She had previously responded well to olanzapine but developed moderate hematological decline, which resolved on discontinuation. During current psychotic episode, olanzapine was re-initiated, and serial blood counts suggested progressive pancytopenia, which was confirmed on peripheral smear. Alternative causes including nutritional deficiencies and autoimmune disorders were ruled out. Olanzapine was discontinued and replaced with aripiprazole, following which all three cell lines normalized subsequently. This case demonstrates a clear temporal challenge-dechallenge-rechallenge association, confirming olanzapine as the causative agent. Clinicians should maintain a high degree of suspicion for hematological adverse effects even with olanzapine, especially in patients with prior cytopenic episodes. In such patients, baseline and serial hematological monitoring is advised and rechallenge is contraindicated. RésuméL’olanzapine est un antipsychotique de deuxième génération fréquemment utilisé, souvent considéré comme ayant un profil de sécurité hématologique plus favorable que la clozapine. Nous rapportons un cas rare de pancytopénie récurrente associée à la réintroduction de l’olanzapine chez une femme de 46 ans présentant un épisode psychotique aigu. Cette patiente avait auparavant bien répondu à l’olanzapine, mais avait développé une baisse hématologique modérée, résolutive à l’arrêt du traitement. Lors de l’épisode psychotique actuel, l’olanzapine a été réintroduite et des numérations sanguines successives ont suggéré une pancytopénie progressive, confirmée par un frottis sanguin périphérique. D’autres causes, notamment des carences nutritionnelles et des maladies auto-immunes, ont été exclues. L’olanzapine a été arrêtée et remplacée par l’aripiprazole, après quoi les trois lignées cellulaires se sont normalisées. Ce cas illustre une association temporelle claire entre l’introduction, l’arrêt et la réintroduction de l’olanzapine, confirmant son rôle causal. Les cliniciens doivent rester vigilants quant à la possibilité d’effets indésirables hématologiques, même avec l’olanzapine, en particulier chez les patients ayant des antécédents d’épisodes cytopéniques. Chez ces patients, une surveillance hématologique initiale et sérielle est recommandée et la réintroduction du traitement est contre-indiquée.

Systemic amyloid light-chain (AL) amyloidosis is a rare plasma cell disorder characterized by extracellular deposition of misfolded immunoglobulin light chains, resulting in progressive organ dysfunction. Although hepatic involvement is recognized in AL amyloidosis, it is often clinically silent or presents with hepatomegaly (liver enlargement) and cholestatic liver enzyme abnormalities. Severe cholestatic jaundice as the initial and dominant manifestation is uncommon, particularly in the absence of hepatomegaly or radiographic biliary obstruction. We report a 63-year-old woman with limited prior healthcare engagement who presented with persistent left ankle pain after a minor twisting injury and was incidentally found to have painless progressive jaundice. Initial laboratory evaluation showed a marked cholestatic pattern of liver injury, including alkaline phosphatase greater than 2300 U/L, total bilirubin of 11.8 mg/dL, direct bilirubin of 8.7 mg/dL, and gamma-glutamyl transferase of 1152 U/L, with disproportionately lower transaminase elevation. Imaging showed cholelithiasis but no biliary obstruction, ductal dilation, focal hepatic lesion, or hepatomegaly. Serologic evaluation for common hepatobiliary causes was unrevealing. Liver biopsy demonstrated amyloidosis predominantly around the portal veins, canalicular and chronic cholestasis, periportal fibrosis, and focal bridging fibrosis. Hematologic evaluation revealed an IgG lambda monoclonal protein, lambda-predominant free light-chain elevation, and bone marrow involvement by a lambda-restricted plasma cell neoplasm, establishing systemic AL amyloidosis with hepatic involvement. Despite initiation of attenuated daratumumab, bortezomib, and dexamethasone therapy, the patient developed rapidly progressive hepatic dysfunction, decompensated heart failure, acute kidney injury, refractory volume overload, and anuric renal failure. She ultimately elected comfort-focused care and was discharged to hospice. This case highlights hepatic AL amyloidosis as an important diagnostic consideration in unexplained cholestatic jaundice, even without hepatomegaly or biliary obstruction. Early recognition is essential, as severe hepatic dysfunction with multisystem involvement carries a poor prognosis.

To evaluate the impact of cancer treatment on the health-related quality of life (HRQoL) of children and adolescents. HRQoL self-perception was assessed using the Pediatric Quality of Life Inventory 3.0 Cancer Module (PedsQL), applied to 103 children and adolescents aged 1 to 18 years, recruited from a hematology and oncology unit of a Brazil public hospital and a support house. Sociodemographic and health data were collected through structured questionnaires, and a dental examination was conducted to assess dental caries. Data were analyzed using SPSS, including descriptive and Chi-square tests. Most participants were male (54.4%), aged 1-7 years (55.3%), with a primary diagnosis of hematologic and lymphatic cancer (85.4%). Family income was up to one minimum wage (55.3%), and 70.9% of mothers had at least 8 years of education. Children aged 1-7 scored lower in "Procedural Anxiety" (45.14 &#xb1; 40.37) than adolescents (66.67 &#xb1; 36.30). Adolescents scored lower in "Nausea" (55.11 &#xb1; 30.06) and "Worry" (56.34 &#xb1; 38.69) than children. HRQoL scores were associated with age (p < 0.001), maternal education (p = 0.022), brushing frequency (p = 0.046), and decayed teeth (p = 0.001). In the final model, self-reported HRQoL among children and adolescents aged 8 to 18 years (OR = 4.28; 95% CI: 1.07-17.12) was associated with lower HRQoL. Anxiety, nausea, and worry negatively impact the health-related HRQoL of pediatric cancer patients, and sociodemographic factors, such as the child's age, also influence this perception, highlighting the importance of individualized and integrated approaches to care.

The increasing importance of the issue of endogenous hyperandrogenism in women (which is found in polycystic ovary syndrome (PCOS), congenital adrenal hyperplasia (CAH), and differences of sex development (DSDs)) for both sports medicine and the regulation of female competitive athletics has made it necessary to examine whether high natural levels of androgens can improve exercise ability in women. It has been clearly demonstrated that exogenously administered androgens produce a physiologic benefit for athletes; however, little information exists regarding the physiologic benefits of endogenously elevated androgen levels. Androgens, specifically testosterone, could potentially impact several systems involved in physical activity, including bone formation and muscle hypertrophy, red blood cell production, and oxygen delivery to tissues, all of which would result in a potential physiologic advantage for certain types of athletes. Therefore, this review will discuss the existing literature examining the association between endogenously elevated androgen levels in women and their exercise capabilities (specifically muscle strength, aerobic capacity, hematologic parameters), while also evaluating the methodologic quality of the available literature. A comprehensive search of the medical literature using PubMed/MEDLINE and Google Scholar, along with manual reference screening, was conducted to identify relevant literature, including peer-reviewed articles. Current evidence suggests that excessive endogenous androgen levels are associated with greater amounts of lean body mass, higher hemoglobin concentrations, and better aerobic capacity compared to nonhyperandrogenemic women. The greatest amount of consensus was observed among women with DSDs. However, the data obtained from women with PCOS&#xa0;and&#xa0;CAH&#xa0;have been inconsistent. Thus, based upon the currently available evidence, there may be a physiologic advantage resulting from endogenous hyperandrogenism in select groups of women. However, the extent of the effect varies by condition. Additional research using appropriately designed studies will be needed to further define these relationships and provide direction for clinical practice decisions and regulatory policies.

Pulmonary embolism is a common and potentially life-threatening acute condition encountered in clinical practice. Neuroendocrine tumors are heterogeneous neoplasms characterized by diverse biological behaviors, and patients with poorly differentiated or advanced neuroendocrine tumors may have an increased risk of developing venous thromboembolism. We report the case of a 60-year-old female who experienced acute chest discomfort and was diagnosed with pulmonary embolism. Comprehensive evaluation revealed no evidence of lower limb thrombosis, autoimmune or hematologic disorders, or other identifiable causes. The emboli resolved following anticoagulant therapy. Seventeen months later, the patient developed upper abdominal pain and underwent a colonoscopy, which revealed a lesion approximately 20&#x2005;cm proximal to the terminal ileum. Histopathological and immunohistochemical analyses confirmed a grade-1 neuroendocrine tumor. 18F-octreotide positron emission tomography-computed tomography demonstrated increased tracer uptake in the terminal ileum and multiple hepatic foci, consistent with an ileal neuroendocrine tumor with liver metastases. The patient received intramuscular octreotide acetate microspheres (20&#x2005;mg every 4 weeks) and remained clinically stable during follow-up. This case underscores the importance of considering occult malignancy in older patients presenting with unprovoked pulmonary embolism. Small intestinal neuroendocrine tumors may remain clinically silent for extended periods and should be included in the differential diagnosis when common etiologies have been excluded.

Inflammation suppresses erythropoiesis, leading to non-regenerative anemia in dogs. Currently, clinical evidence of this inhibitory effect remains limited. This study provides important clinical insight by demonstrating a negative correlation between C-reactive protein (CRP) concentration and reticulocyte count over time in dogs with inflammatory anemia. This study aimed to leverage inflammatory anemia as a model to examine the longitudinal relationship between CRP levels and reticulocyte counts in dogs. Medical records of 23 dogs diagnosed with various inflammatory conditions and persistently non-regenerative erythropoiesis were retrospectively reviewed. Serial results of hematological and serological parameters were analyzed using linear mixed-effects models to account for intra- and inter-individual variation. Reticulocyte counts in anemic dogs with resolving underlying inflammatory conditions were significantly negatively correlated with CRP levels (standardized &#x3b2; = -0.53, 95% confidence interval (CI) -0.68 to -0.37; P<0.001). Moreover, cross-sectional analysis revealed that higher CRP levels were significantly associated with lower reticulocyte counts, suggesting that the severity of inflammation may be linked to reduced reticulocyte counts (Pearson's r = -0.5; P=0.01). Similarly, erythropoietic responses to darbepoetin alfa appeared to be attenuated in dogs with elevated CRP concentrations. In these dogs, whose mean CRP concentration was 6.15 mg/dL, the onset of reticulocytosis was delayed approximately twofold, and the increase in peak reticulocyte count was approximately 38% lower than that in dogs with normal CRP concentrations. This study provides clinical evidence supporting an association between systemic inflammation and reduced or delayed reticulocytosis in dogs, highlighting the clinical utility of concurrently monitoring CRP and reticulocyte levels to assess disease progression and inflammatory recovery.

Amomi Fructus (Amomum villosum Lour.)-processed Rehmanniae Radix (Rehmannia glutinosa Libosch.) is a traditional Chinese herbal preparation used to tonify blood and improve digestive tolerance. It is considered a rational processing method to enhance the efficacy of Rehmanniae Radix (RR) in blood deficiency syndrome (BDS). This study investigated the therapeutic effects of Amomi Fructus -processed Rehmanniae Radix (AR) on BDS and explored its underlying mechanisms using a multi-omics approach. A rat model of BDS was established using cyclophosphamide and acetylphenylhydrazine. Rats were treated with AR or RR. Hematological parameters, spleen histopathology, TUNEL staining, bone marrow apoptosis by flow cytometry, transcriptomics, spleen metabolomics, and gut microbiota profiling were performed. AR significantly improved RBC, WBC, HGB, and HCT levels and alleviated spleen pathological injury in BDS rats. Transcriptomic analysis showed that the PI3K/Akt, and MAPK signaling pathway was significantly enriched among differentially expressed genes. AR reduced phosphorylation of PI3K, Akt, ERK, JNK, and p38, and markedly suppressed apoptosis in the spleen and bone marrow. Metabolomic profiling indicated that AR restored BDS-induced metabolic disturbances, while gut microbiota analysis showed that AR modulated microbial composition. Overall, AR produced more pronounced effects than RR. AR alleviated BDS in rats, potentially by inhibiting PI3K/Akt/MAPK-mediated apoptosis and restoring metabolic and microbial homeostasis. These findings support the traditional use of AR as a blood-tonifying herbal preparation.

Osteopetrosis is a genetic disorder characterized by impaired osteoclast function, leading to diffuse osteosclerosis, brittle bones, and hematologic abnormalities. Herein, we report the case of a 55-year-old woman diagnosed with adult-onset osteopetrosis at age 33 after imaging demonstrated dense and marbled long bones, sclerotic medullary canals, vertebral endplate thickening, and hepatosplenomegaly. Bone marrow biopsy revealed preserved megakaryocytes, yet she experienced recurrent episodes of thrombocytopenia that responded to oral steroids and ultimately resolved following splenectomy, supporting an immune-mediated etiology of thrombocytopenia clinically managed as immune thrombocytopenic purpura. The clinical course was further complicated by multiple periprosthetic fractures, highlighting both the diagnostic and management challenges of this condition.

Leukemia represents a heterogeneous and refractory hematological malignancy, with current clinical therapies, including conventional chemotherapy, targeted therapy, and hematopoietic stem cell transplantation, still limited by drug resistance, off-target toxicity, and poor efficacy against high-risk subtypes. Indole/azaindole is a privileged heterocyclic scaffold in medicinal chemistry with versatile structural modification potential and inherent antileukemic bioactivity. Rational hybridization of indole/azaindole with diverse pharmacophores has become a core strategy for developing novel antileukemic agents, thereby enabling synergistic efficacy, reversal of drug resistance, and reduced toxicity. This review systematically summarizes the research progress of indole-based hybrids and closely related indole bioisosteres (azaindole hybrids) with antileukemic activity from 2021 to the present. Distinct from previous descriptive reviews, we stratified all candidate compounds by evidence hierarchy: in vitro antiproliferative activity, molecular mechanistic validation, and in vivo preclinical efficacy. This work focuses on structure-activity relationships (SARs), multi-target mechanisms, and preclinical pharmacological characteristics of indole- and azaindole-based antileukemic hybrids, aiming to provide targeted guidance for the rational design and clinical translation of novel indole- and azaindole-based antileukemic drugs.

Rhupus syndrome is a rare disease that presents with features of both rheumatoid arthritis and systemic lupus erythematosus. It is typically characterized by a rheumatoid arthritis pattern of symmetric, polyarticular small joint pain and swelling along with features of lupus such as photosensitive skin rashes and hematologic abnormalities. The disease is rare and inclusion criteria are mixed, but diagnosis is generally based on clinical features in conjunction with positive serologic lab results for both diseases. Severity can vary from benign to severe manifestations, rarely including anterior scleritis. We describe a case of a 20-year-old female with recently diagnosed inflammatory arthritis who presented with severe bilateral anterior scleritis and lupus nephritis, who achieved complete remission following treatment with high-dose intravenous glucocorticoids.

Ginsenoside Rg3, a rare protopanaxadiol-type saponin enriched during the heat processing of Panax ginseng, has attracted increasing attention as a multitarget anticancer agent. This systematic review examines the anticancer potential of Rg3 through comprehensive searches of the PubMed and Web of Science databases, with a focus on peer-reviewed preclinical and clinical studies. The therapeutic efficacy of Rg3 is critically influenced by its stereochemical configuration, concentration-dependent bidirectional regulation, and pharmacokinetic constraints, including poor oral bioavailability, rapid clearance, and gut microbiota-mediated metabolism. Nanocarrier-based and targeted delivery systems have substantially improved its pharmacokinetic profile and tumor accumulation, supporting its further development for anticancer applications. Within this pharmacological context, Rg3 exhibits broad-spectrum anticancer activity across multiple solid tumors, including hepatocellular carcinoma, melanoma, lung, ovarian, breast, colon, gastric, and prostate cancers, as well as osteosarcoma, renal cancer, lung adenocarcinoma, glioblastoma, gallbladder, nasopharyngeal, cervical, and pancreatic cancers, and the hematological malignancy multiple myeloma. Mechanistically, Rg3 suppresses cancer progression through coordinated regulation of proliferation, apoptosis, autophagy, ferroptosis, angiogenesis, epithelial-mesenchymal transition, cancer stemness, immune evasion, and redox homeostasis, primarily involving the PI3K/AKT/mTOR, NF-[Formula: see text]B, MAPK, Wnt/[Formula: see text]-catenin, EGFR, and p53 pathways. These effects reflect transferable network-level mechanisms rather than tumor type-restricted actions. Moreover, Rg3 demonstrates synergistic effects with chemotherapy, radiotherapy, targeted therapy, and immunotherapy, while reversing drug resistance and attenuating treatment-related toxicity in multiple cancer models and clinical settings. Overall, this review systematically integrates current evidence on the pharmacokinetics, anticancer spectrum, molecular mechanisms, synergistic combinations, immunomodulatory effects, and clinical applications of Rg3, providing a concise framework for the rational development of Rg3-based combination strategies in precision cancer therapy.

VEXAS syndrome is a recently identified adult-onset autoinflammatory disorder caused by somatic mutations in the UBA1 gene, leading to systematic inflammation and hematological dysfunctions. We present the case of a 71-year-old man with a prolonged history of cutaneous lesions and inflammatory arthritis that is refractory. Despite the treatment with multiple immunosuppressive therapies, his symptoms persisted alongside macrocytic anemia and thrombocytopenia. Genetic testing confirmed a UBA1 mutation, which established the diagnosis of VEXAS syndrome. A subsequent bone marrow biopsy revealed myelodysplastic syndrome. This case highlights the importance of early recognition of VEXAS syndrome, particularly in patients with multisystemic involvement and treatment-refractory disease. Therapies such as JAK inhibitors may provide effective disease control in patients who are not candidates for hematopoietic stem cell transplantation.

Relapsed or refractory extranodal natural killer/T-cell lymphoma (R/R NKTCL) remains a highly lethal disease, particularly after failure of PD-1 blockade-based therapy. Preclinical data suggest that inhibition of exportin-1 (XPO1) may enhance antitumor immunity and synergize with PD-1 blockade. We conducted a multicenter, open-label phase 1&#x2009;b study (TOUCH, Arm C) evaluating selinexor plus tislelizumab in patients with R/R NKTCL previously treated with L-asparaginase-containing regimens. A standard 3&#x2009;+&#x2009;3 dose-escalation design was followed by dose expansion. Seventeen patients were enrolled; 16 had prior checkpoint inhibitor (CPI) exposure and comprised the efficacy population. No dose-limiting toxicities were observed. Grade &#x2265;3 treatment-emergent adverse events occurred in 52.9% of patients; hematologic toxicities were the most common. Among patients with prior CPI exposure, the overall response rate was 75.0% (12/16), including complete responses in 43.8% (7/16). Responses were observed in patients with primary CPI-refractory disease. With a median follow-up of 21.7&#x2009;months, median progression-free survival was 6.1&#x2009;months (95% CI, 2.9-not estimable), and the 2-year progression-free survival rate was 37.5%. Median overall survival was not reached; the 2-year overall survival rate was 73.4%. Selinexor plus tislelizumab demonstrated manageable toxicity and substantial activity in patients with relapsed/refractory NKTCL previously treated with CPI, supporting further evaluation of nuclear export inhibition as a strategy to re-engage antitumor immunity after failure of PD-1 blockade. NCT04425070.

RUNX1 familial platelet disorder with associated myeloid malignancy (RUNX1-FPDMM) is an autosomal dominant disease that mimics immune thrombocytopenia (ITP). We report a case of a woman diagnosed with ITP who exhibited isolated megakaryocytic dysplasia in the bone marrow and a poor response to prednisolone and intravenous immunoglobulin. Ten years later, the patient was correctly diagnosed following her report of hematologic abnormalities across three generations, which prompted genetic testing. This case highlights that ITP should remain a diagnosis of exclusion throughout follow-up, and atypical findings or a suggestive family history should prompt reconsideration of inherited thrombocytopenia.

Anemia is a significant global public health issue with substantial health consequences, particularly affecting children and women of reproductive age. This study analyzes the global burden and epidemiological trends of anemia in these specific populations from 1990 to 2021 and projects its trajectory to 2040. Using data from the Global Burden of Disease (GBD) study 2021, we assessed the age-standardized prevalence rates (ASPRs), years lived with disability (YLDs), and estimated annual percentage changes (EAPCs) of anemia. Nordpred models were used to project prevalence and YLDs for anemia from 2021 to 2040. In 2021, 599 million children under 15 years old and 657 million women of reproductive age globally had anemia. The most common cases were mild and moderate anemia. Mild and moderate anemia accounted for most prevalent cases, while moderate anemia contributed the largest share of YLDs. Nutritional deficiencies remained the leading cause of anemia-related YLDs, followed by other non-communicable diseases. Population growth, especially in lower Socio-Demographic Index regions, significantly influenced the rise in YLDs. Projections suggested that the age-standardized prevalence rate of anemia would increase among women of reproductive age from 16,722.91 per 100,000 population in 2021 to 17,585.71 per 100,000 population in 2040, whereas that among children would slightly decrease from 8,682.60 to 8,558.84 per 100,000 population during the same period. Anemia remains a major health burden, necessitating urgent and effective strategies to address its diverse challenges.

Targeted therapies, including Bruton tyrosine kinase (BTK) inhibitors and venetoclax, have substantially improved clinical outcomes for patients with chronic lymphocytic leukemia (CLL). However, the increasing prevalence of polypharmacy in the predominantly older CLL population has emerged as a major challenge to the safe and effective delivery of these treatments. Multiple concomitant medications, particularly potentially inappropriate medications (PIMs), are associated with frailty, treatment-related toxicity, hospitalization, poor adherence, and inferior survival. These risks are further exacerbated by clinically significant drug-drug interactions with BTK inhibitors and venetoclax, as well as age-related pharmacokinetic changes. Integrating medication stewardship into routine CLL care-including medication reconciliation, interaction screening, adherence assessment, use of geriatric prescribing tools, and deprescribing of unnecessary or high-risk medications-may improve the safety and effectiveness of targeted therapies while reducing preventable treatment-related complications. Although current recommendations are largely extrapolated from geriatric oncology rather than CLL-specific studies, they may provide a practical framework for optimizing pharmacotherapy in this population.

For adults with newly diagnosed acute myeloid leukemia (AML) aged &#x2265; 75 years or considered unfit for intensive induction therapy, the combination of venetoclax (VEN) and hypomethylating agents (HMAs) has become the standard of care. However, real-world data on demographic disparities in treatment uptake among Medicare beneficiaries remain limited. We conducted a retrospective cohort analysis using Medicaire fee-for-service claims to identify factors influencing the receipt of AML-directed therapy. The study included 12,154 patients with newly diagnosed AML who were either &#x2265; 75 years and/or unfit for intensive induction chemotherapy. Overall, 5,647 patients received treatment, while 6,507 remained untreated. Treatment utilization increased over time. Untreated patients were older than treated patients (81.2 vs 77.9 years). Females were more likely to be untreated than males. Patients diagnosed in 2019 or later were more likely to receive therapy, and among those, 67.3% received VEN-based therapy. No significant differences in treatment receipt were observed by race or geographic residence. These findings suggest that factors extending beyond disease biology, such as age and sex, influence AML treatment uptake in the Medicare population. Management of AML demands a conscious effort to ensure equitable access to treatment and fair representation in clinical trials.