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Off-target anti-leukemic effects of antibiotics: mechanisms and therapeutic insights.3 weeks agoAntibiotics are among the transformative advances in medicine, but many interact with mammalian cellular targets and pathways beyond their antimicrobial activity. A clinically important expression of these off-target effects is hematologic toxicity, including immune-mediated cytopenias and direct bone marrow suppression. This narrative review examines whether the same biology that injures normal hematopoietic cells can, in selected contexts, reveal therapeutically exploitable vulnerabilities in leukemia. We synthesize molecular, clinical, and preclinical evidence and organize it into an integrative framework linking mitochondrial translation inhibition, mitonuclear imbalance, oxidative phosphorylation failure, reactive oxygen species generation, DNA/topoisomerase stress, autophagy and lysosomal-flux blockade, and apoptosis modulation with both hematotoxicity and antileukemic activity. The strongest preclinical evidence supports selected tetracyclines, macrolides, and oxazolidinones, whereas evidence for beta-lactams, glycopeptides, polymyxins, rifamycins, fluoroquinolones, and folate-pathway agents remains more limited or largely hypothesis-generating. Importantly, antibiotic-induced cytopenia should not be interpreted as proof of leukemia selectivity: immune-mediated toxicity, supratherapeutic in vitro exposure, normal progenitor injury, pharmacokinetic constraints, microbiome effects, and resistance mechanisms all narrow the translational window. Overall, antibiotic hematotoxicity is best viewed as a biologically informative signal that can guide mechanism-based repurposing and combination strategies, but clinical development requires rigorous pharmacokinetic/pharmacodynamic validation, normal hematopoietic comparators, and biomarker-driven patient selection.CancerCare/Management
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Fish-shaped erythrocytes and pincer cells co-occur in distinct hematological disorders and are associated with anemia severity.3 weeks agoRed blood cell (RBC) morphology in peripheral blood smears (PBS) remains essential for the differential diagnosis of anemia and other hematologic disorders. As yet unclassified poikilocytes, fish-shaped RBCs and pincer (mushroom-shaped) cells are rarely observed but have been described as "bizarre erythrocytes" and linked to hereditary spherocytosis. This study aimed to investigate their relevance across a spectrum of hematologic diseases and provide a basis for future morphological standardization.
Peripheral blood smears from 251 specimens were systematically reviewed, including cases of iron deficiency anemia (IDA), β-thalassemia minor (BTM), sickle cell disease (SCD), microangiopathic hemolytic anemia (MAHA), autoimmune hemolytic anemia (AIHA), hereditary spherocytosis (HS), hereditary elliptocytosis (HE), vitamin B12/folate deficiency, myelodysplastic neoplasms (MDS), primary myelofibrosis (PMF), malaria, liver disease (LD), and healthy controls. Abnormal RBC morphologies were quantified as cells per 20 high-power fields at 1,000 × magnification. Group comparisons used the Mann-Whitney U test and correlations were assessed by Spearman's rank correlation.
Numbers of fish-shaped and pincer cells were significantly increased in IDA, BTM, MDS, HE, PMF, and vitamin B12/folate deficiency with a strong positive intercorrelation (p<0.01) in most of these diseases. Pincer cells were also elevated in HS and hemoglobin levels were negatively correlated with both fish and pincer cells across all disorders studied (p<0.0001).
Fish-shaped RBCs and pincer cells represent abnormal erythrocyte morphologies associated with a range of hematologic disorders and correlate with severity of anemia. Their strong intercorrelation suggests a shared pathophysiologic mechanism or may reflect different stages of a common morphological process.CancerCare/Management -
When the appendix hides: the radiologist's guide to appendix variants and mimics.3 weeks agoThe identification of the appendix often presents a diagnostic challenge due to its significant anatomical variability, compounded by the frequency with which appendiceal pathologies manifest as atypical clinical presentations that mimic diverse abdominal and pelvic conditions. Beyond acute appendicitis, a wide spectrum of inflammatory, infiltrative, and neoplastic processes can involve the appendix, necessitating the rigorous recognition of their distinct imaging signatures. This pictorial essay reviews the normal anatomy of the appendix, its positional variations, and the spectrum of diseases that may affect it, including acute appendicitis, endometriosis, epiploic appendagitis, appendiceal diverticulitis, mucocele, and primary tumors. While computed tomography (CT) remains the gold standard for primary diagnostic evaluation, magnetic resonance imaging (MRI) serves as a critical complementary modality in specific clinical scenarios, providing superior soft-tissue characterization and improving diagnostic confidence in challenging cases. Recognition of anatomical variants and the primary mimics of the appendix is essential for the accurate interpretation of abdominal imaging studies.CancerCare/Management
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Multimodality staging of renal cell carcinoma-pearls & pitfalls.3 weeks agoAccurate staging of renal cell carcinoma (RCC) is critical because small differences in imaging interpretation can alter operative planning, systemic treatment decisions, and prognosis. This educational review highlights the practical role of multimodality imaging in RCC staging, with emphasis on common interpretive pitfalls and reporting strategies that improve clinical decision-making. Contrast-enhanced CT and MRI remain the foundation of local staging, enabling assessment of tumour size, renal sinus and perinephric extension, venous tumour thrombus, and spread beyond the perinephric fascia. However, several features are prone to overcall or undercall, particularly renal sinus invasion, perinephric invasion, inferior vena cava wall involvement, and adjacent organ invasion, with direct implications for management. Regional and distant staging are likewise imperfect. Nodal assessment remains limited by the overlap between reactive enlargement and metastatic disease, while indeterminate pulmonary nodules, marrow-based bone metastases, and atypical metastatic sites may all complicate interpretation. Selected technical considerations, including the potential value of arterial phase imaging in suspected clear cell RCC and the problem-solving role of MRI in equivocal local staging, may help reduce understaging. The role of PET and emerging targeted tracers remains selective rather than routine. Throughout, emphasis is placed on management-relevant imaging findings, modality-specific strengths and weaknesses, and practical pearls derived from experience. A structured reporting approach is also proposed to improve completeness, consistency, and communication with the multidisciplinary team.CancerCare/Management
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ADRENAL GLAND LESIONS IN AFRICAN PAINTED DOGS (LYCAON PICTUS) OF THE ASSOCIATION OF ZOOS AND AQUARIUMS SPECIES SURVIVAL PLAN® POPULATION.3 weeks agoAfrican painted dogs (Lycaon pictus; APD) are an endangered canid species with sophisticated behaviors and social structure. In the United States, there are approximately 160 individuals housed at institutions accredited by the Association of Zoos and Aquariums, where health and disease are monitored, and breeding and management strategies are implemented according to the Species Survival Plan®. From 1996 to mid-2025, 350 APD >1 yr old died or were euthanized and pathology reports were available for 188 (54%) individuals. Of the 81 with adrenal glands submitted for histologic evaluation, lesions were reported in 52 individuals, including 30 (58%) males and 22 (42%) females, 38 (73%) of which were intact. Common histologic lesions included nodular cortical hyperplasia (n = 24; 45%), cortical adenoma (n = 11; 21%), cortical carcinoma (n = 6; 11%), and pheochromocytoma (n = 8; 15%). There were two cases of metastatic neoplasia affecting the adrenal glands and two medullary thromboses/hematomas. Six dogs had more than one adrenal lesion. Nodular cortical hyperplasia was predominantly found in older adults (median age, 12 yr) and more so in males than females (1.4:1). Cortical carcinomas and pheochromocytomas were diagnosed in APD with several concurrent lesions, including other malignant neoplasms. Of dogs with malignant adrenal neoplasms, the median age was 12 yr and 42 (84%) were related as siblings or offspring. Although nodular cortical hyperplasia is considered an age-related process, malignant adrenal neoplasms may involve additional factors, thus warranting further investigation.CancerCare/Management
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A bibliometric analysis of the most-cited studies on robotic nephrectomy versus laparoscopic nephrectomy: Citation trends and scientific influence.3 weeks agoRobotic nephrectomy has emerged as an alternative to laparoscopic nephrectomy, offering enhanced surgical precision, reduced blood loss, and faster recovery. However, its clinical effectiveness and cost-efficiency remain debated. This study aims to perform a bibliometric analysis of the 100 most-cited publications comparing robotic and laparoscopic nephrectomy, focusing on clinical, technological, and economic aspects. A bibliometric search was conducted in the Scopus database on July 26, 2025, using the keywords "robotic nephrectomy" AND "laparoscopic nephrectomy" AND "human". Articles were sorted by citation count and screened based on clinical relevance. The top 100 most-cited studies were selected, and data on authorship, institutions, countries, journals, and keywords were extracted. A total of 435 publications from 43 countries were identified, with the United States leading in publication count (n=110) and citations (n=2,497), followed by China and Italy. The studies showed comparable oncologic outcomes (positive surgical margin, 1.6%-5.4%; 3-year disease-free survival, up to 94.9%), with robotic-assisted partial nephrectomy (RAPN) associated with improved perioperative outcomes, including shorter warm ischemia time, lower blood loss, and fewer complications (odds ratio, 0.55). Functional outcomes favored RAPN, particularly in complex tumors (estimated glomerular filtration rate, 96% vs. 90%), though robotic approaches were more costly. Robotic nephrectomy offers perioperative and functional advantages with comparable oncologic outcomes to laparoscopic approaches, though at higher cost. This bibliometric analysis provides clinical implications for decision-making and highlights the growing support for RAPN, emphasizing the need for high-quality prospective studies to guide future research.CancerCare/Management
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Small Molecules, Big Impact: Structural Innovations Driving PD-L1 Checkpoint Modulation.3 weeks agoCancer immunotherapy enhances the body's ability to recognize and eliminate tumor cells, mainly by modulating immune checkpoints such as PD-1/PD-L1 and CTLA-4. Monoclonal antibody inhibitors targeting PD-1 or PD-L1 have transformed cancer care, but their high cost, IV administration, and immune-related toxicities have encouraged the development of small-molecule alternatives. Early PD-L1 small-molecule inhibitors, pioneered by Bristol Myers Squibb, block PD-1/PD-L1 interactions by occupying hydrophobic pockets on PD-L1, and SAR studies continue to refine their potency and selectivity. This review focuses on how the structural scaffolds of small-molecule PD-L1 inhibitors determine their mechanisms of action, protein interactions, and biological performance. We examine how different chemotypes influence dimerization of PD-L1, disruption of PD-1 binding, or engagement of additional immune-modulatory pathways. Special attention is given to scaffolds capable of acting through more than one mechanism, as these may offer broader or more durable immunomodulatory effects. We also compare how scaffold design correlates with activity across in vitro assays, co-culture immune models, and in vivo tumor systems, highlighting the physicochemical features that enable or limit translatability. Finally, we discuss emerging clinical efforts, the challenges underlying trial failures, and how refined structural design may guide the next generation of small-molecule PD-L1 inhibitors.CancerCare/Management
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2025 Update of the Taiwan Expert Consensus on Hormone Receptor-Positive Metastatic Breast Cancer Management.3 weeks agoHormone receptor-positive metastatic breast cancer remains a major clinical burden and is characterized by sequential endocrine resistance over the disease course. In 2023, the Taiwan Breast Cancer Society (TBCS) published an expert consensus to support real-world decision-making in Taiwan. Subsequently, rapid advances in biomarker-informed strategies (e.g., estrogen receptor 1 and PI3K/AKT pathway alterations), endocrine partners, estrogen receptor (ER)-targeting agents (including oral selective ER degraders and emerging protein degraders), and the expanding role of antibody-drug conjugates based on human epidermal growth factor receptor 2 expression categories have materially increased the complexity of treatment selection and sequencing. Therefore, TBCS convened an expert panel to update the previous consensus while preserving its foundational framework and eight-chapter structure: risk evaluation and biomarker testing (I/II), first-line treatment selection (I/II), second-line treatment selection (I/II), and treatment options other than endocrine-based approaches (I/II). A multidisciplinary panel conducted a systematic literature review and iterative discussions using a modified Delphi process to identify the key clinical questions, update and refine statements where new evidence was practice-changing, and maintain continuity with the 2023 Consensus. The panel formulated updated recommendations, assigned levels of evidence and strengths of recommendations, and the key updates were integrated into practical treatment algorithms reflecting Taiwan's practice considerations. This updated consensus provides a continuity-based, yet evidence-responsive framework to facilitate the integration of emerging therapies into clinical practice in Taiwan and the Asia-Pacific region.CancerCare/Management
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Ovarian Function Suppression in Premenopausal Hormone Receptor-Positive Early Breast Cancer: A Comprehensive Review.3 weeks agoHormone receptor-positive (HR+) breast cancer in premenopausal women presents unique therapeutic challenges owing to persistent ovarian estrogen production and aggressive biological features. Although tamoxifen has long been the standard of care, the integration of ovarian function suppression (OFS) has transformed adjuvant management. This review synthesizes landmark clinical trial data, biological rationales, and emerging evidence to guide personalized treatment strategies. The hypothalamic-pituitary-ovarian axis remains the primary source of estrogen in premenopausal women and drives tumor proliferation. Landmark trials, including Suppression of Ovarian Function Trial, Tamoxifen and Exemestane Trial, Addition of Ovarian Suppression to Tamoxifen in Young Women with Hormone-Sensitive Breast Cancer who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy, and Hormonal Bone Effects, have established the superiority of OFS combined with aromatase inhibitors or tamoxifen over tamoxifen monotherapy in high-risk populations. However, the benefits must be weighed against toxicities such as bone loss, menopausal symptoms, and sexual dysfunction. Special subgroups, including young women, patients with invasive lobular carcinoma, and BRCA mutation carriers, derive distinct benefits from OFS. The phenomenon of ovarian escape and the potential of OFS to facilitate chemotherapy de-escalation are emerging as critical considerations. Suppression of ovarian function is the cornerstone of adjuvant therapy for high-risk premenopausal HR+ breast cancers. Optimal management requires a nuanced, risk-stratified approach that balances oncologic efficacy with long-term survivorship, integrating genomic tools and individualized duration strategies.CancerCare/Management
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Enigmatic Case of Adult-Onset Langerhans Cell Histiocytosis with Aggressive Bony Involvement.3 weeks agoLangerhans cell histiocytosis (LCH) is a rare hematologic neoplasm predominantly affecting children, with adult-onset cases being exceedingly uncommon. Neurological presentations, including spinal cord compression and cranial neuropathies, represent atypical manifestations that often lead to diagnostic delays. We present a 20-year-old previously healthy female who presented with progressive back pain, bilateral lower extremity weakness, and left-sided hearing loss. Imaging revealed a thoracic epidural mass causing severe spinal stenosis with additional diffuse osteolytic lesions. Initial biopsies showed nonspecific lymphoplasmacytic infiltrates. The patient subsequently developed cranial nerve palsies and dysphagia over several months. Definitive diagnosis required three biopsies, with the final petrous bone specimen demonstrating characteristic LCH histology and positive immunostaining for CD1a, S100, and Langerin. Treatment with zoledronic acid failed; subsequent therapy with cytarabine followed by cladribine plus hydroxyurea achieved partial radiographic and clinical improvement, though complicated by treatment-related sepsis. This case highlights the diagnostic and therapeutic challenges of adult LCH, given its rarity, variable presentation, and limited treatment guidelines. Multiple tissue samples with appropriate immunohistochemical staining may be required for diagnosis. Adult LCH treatment remains empirical, often extrapolated from pediatric data, with systemic therapies carrying significant toxicity risks. Greater awareness and adult-specific clinical trials are urgently needed.CancerCare/Management