Search Results (12,407)

Intravenous thrombolysis with recombinant tissue-type plasminogen activator (tPA) remains a keystone of acute ischemic stroke treatment but in a subset of patients is complicated by angioedema, a potentially life-threatening adverse event largely mediated by bradykinin signaling. The unpredictable and idiosyncratic nature of this reaction has long suggested an underlying genetic contribution, yet its molecular architecture has remained poorly characterized. We hypothesized that alteplase-associated angioedema represents a multigenic susceptibility phenotype, arising from the convergence of rare genetic variants across multiple interacting physiological systems rather than from a single causal variant. To explore this hypothesis, we performed clinical exome sequencing in a cohort of 11 patients who developed angioedema following alteplase administration. Rather than identifying a shared pathogenic variant, we observed distinct yet convergent patterns of genetic vulnerability, allowing patients to be grouped according to dominant, but overlapping, biological axes. These included alterations affecting bradykinin regulation (e.g., ACE, SERPING1, XPNPEP2), endothelial structure and hemostasis (e.g., VWF, COL4A1), neurovascular and calcium signaling (e.g., SCN10A, RYR1), and vascular repair or remodeling pathways (e.g., PSEN2, BRCA2). Notably, many of the identified variants were classified as Variant of Uncertain Significance (VUS) or likely benign significance in isolation. However, when considered within an integrated, pathway-based framework, these variants can be interpreted as capable of contributing cumulatively to system level fragility, a phenomenon best described as “contextual pathogenicity”. Under the acute biochemical and proteolytic stress imposed by thrombolysis, this reduced physiological reserve may allow otherwise compensated vulnerabilities to become clinically manifest. Together, these findings support a model in which severe alteplase-associated angioedema appears as an emergent property of interacting genetic networks, rather than a monogenic disorder. This systems level perspective underscores the limitations of gene centric interpretation for adverse drug reactions and highlights the potential value of pathway informed, multi-genic approaches to risk stratification. Such frameworks may ultimately contribute to safer, more personalized thrombolytic decision, while providing a conceptual foundation for future functional and translational studies. Full article

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by extracellular matrix (ECM) breakdown, inflammation, and pain-associated functional impairment. Current pharmacological treatments primarily provide symptomatic relief without preventing cartilage degeneration. Kaempferia parviflora extract (KPE), rich in polymethoxyflavonoids, has been reported to have anti-inflammatory properties; however, its in vivo effects on cartilage homeostasis in OA remain incompletely defined. Methods: A monosodium iodoacetate (MIA)–induced rat model of knee OA was used to evaluate the therapeutic effects of KPE. Following OA induction, rats received oral KPE at low, medium, or high doses for 19 days. Pain-associated functional impairment was assessed by static weight-bearing analysis. Cartilage integrity was evaluated histologically, serum inflammatory and cartilage degradation biomarkers were quantified, and expression of matrix-degrading enzymes and their endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), was analyzed in articular cartilage. Results: MIA injection induced marked joint dysfunction, including an approximately 50% reduction in weight bearing on the affected limb. While KPE did not significantly reduce acute knee swelling, all KPE doses significantly improved weight-bearing imbalance compared with MIA controls. Histological analysis demonstrated preservation of cartilage structure and proteoglycan content in KPE-treated groups. Serum CTX-II levels were significantly reduced across all KPE doses, indicating attenuation of collagen degradation. Systemic inflammatory markers showed differential modulation: significant reductions in serum CRP and COX-2 at medium and high doses, while PGE2 showed a consistent downward trend that did not reach statistical significance. In articular cartilage, KPE treatment restored TIMP-1 expression, whereas modulation of individual MMPs was modest and variable. Conclusions: KPE alleviates OA-associated functional impairment and cartilage degeneration in an experimental OA model. The therapeutic effects are associated with reinforcement of TIMP-1–mediated matrix homeostasis and modulation of inflammatory pathways, supporting the potential of KPE as a natural adjunct candidate for OA management. Full article

Background and Clinical Significance: Acute aortic dissection is the most common and most severe manifestation of acute aortic syndrome. An isolated dissecting aneurysm of the abdominal aorta is defined as a dissecting aneurysm distal to the diaphragm and is an extremely rare disease. Detection of an intimal flap between two lumens using different imaging methods is a definitive diagnostic sign of aortic dissection. A number of studies have validated ultrasound, including point-of-care ultrasound, as the standard initial imaging modality for the diagnosis of aortic dissection. Case Presentation: We present a 39-year-old patient who was sent to our institution under the suspicion of renal colic. The clinical findings revealed pale discoloration of the skin with sweating and abdominal pain. An emergency ultrasound showed an abdominal aortic aneurysm with an intimal flap, as well as free perirenal fluid on the left side. Multislice computed tomography aortography was then performed and the findings indicated rupture of a dissecting aneurysm of the abdominal aorta with a large retroperitoneal hematoma. The patient was then sent to a tertiary institution where he underwent emergency surgery and successfully recovered. Conclusions: Isolated abdominal aortic dissection is a rare condition with often non-specific clinical presentation, making imaging crucial for diagnosis. Ultrasound plays an important role as an initial imaging modality, as the detection of direct or indirect signs of dissection enables timely referral for CT aortography, confirmation of the diagnosis, and initiation of appropriate treatment. Full article

Background: recently, regenerative medicine has introduced a new branch of science that facilitates the repair of damaged tissues and organs in acute myocardial infarction. This study explores the role of the C-type natriuretic peptide (CNP) system in myocardial infarction (MI) and its modulation by Apelin-13 functionalized patches (A-13p). Methods: using an experimental rat model of ischemia/reperfusion, the rats were divided into four groups: Sham, Infarct, Sham with A-13p, and Infarct with A-13p. Cardiac tissue from the infarct, border, and remote zones was analyzed for CNP and its receptors’ mRNA expression via Real-Time PCR. Results: histological analysis, 4 weeks post A-13p implantation, showed no damage from A-13p implantation in either MI or Sham groups, with reduced left ventricle wall thinning in the Infarct group treated with A-13p. CNP mRNA expression was higher in the infarcted groups (p = ns), especially in the border/infarct zone (BZ + IZ), compared to the Sham group (p = 0.05). NPR-B receptor expression was higher in the RZ than in (BZ + IZ), both in the absence (p = 0.02) and presence of patches (p = 0.01), while NPR-C expression was lower. No significant differences were observed in VEGF mRNA levels across the groups. Conclusions: the findings suggest that the CNP system is involved in MI and that A-13p modulates CNP expression, highlighting CNP as a potential target for therapeutic strategies aimed at regulating vascular remodeling and angiogenesis in MI treatment. Full article

Background/Objectives: Malnutrition is highly prevalent in patients with acute leukemia and is frequently underrecognized at diagnosis. Traditional screening tools based on anthropometry often fail to identify early nutritional deterioration. This study aimed to evaluate the prognostic utility of a comprehensive morphofunctional assessment—including bioelectrical impedance vector analysis (BIVA), handgrip strength (HGS), and muscle ultrasound—conducted at diagnosis and after induction therapy, to evaluate the prognostic association with 12-month mortality. Methods: In this prospective cohort study, 52 adult patients with newly diagnosed acute leukemia were enrolled between November 2022 and November 2024 at two tertiary hospitals in Málaga, Spain. Nutritional status was determined using GLIM criteria. Morphofunctional assessment included BIVA-derived phase angle (PhA), HGS via dynamometry, and rectus femoris ultrasound. A second evaluation was performed prior to haematopoietic stem cell transplantation. Mortality at 12 months was the primary outcome. Logistic regression and ROC analysis were used to assess prognostic associations. Results: At baseline, 65.4% of patients were classified as malnourished. After three months, patients showed significant declines in PhA (−0.55°, p < 0.001), body cell mass (−3.15 kg, p < 0.01), skeletal muscle mass (−1.66 kg, p < 0.01), and rectus femoris cross-sectional area (−0.36 cm², p = 0.011). Baseline malnutrition (OR = 6.88; 95% CI: 1.17–40.38; p = 0.033) and PhA decline ≥ 0.90° were both independently associated with higher 12-month mortality. Conclusions: Early morphofunctional assessment using GLIM criteria, BIVA, and muscle ultrasound identifies patients at nutritional and functional risk. PhA decline during treatment was associated with higher 12-month mortality, supporting the need for early, personalized nutritional intervention in leukemia care. Full article

The mechanisms underlying wound healing mediated by cannabinoid receptor 1 (CB1)—known for its neuromodulatory functions—remain incompletely understood. Therefore, we investigated the impact of activating CB1 using specific agonists, both in vitro and in vivo, with a focus on wound healing. In the in vitro study, fibroblasts were isolated and cultured from the dermis of human skin and treated with a CB1 agonist, 2-arachidonyl glyceryl ether (2-AGE). In the in vivo study, a mouse acute wound model was created using a skin biopsy punch and treated with the CB1 agonist arachidonoyl 2′-chloroethylamide (ACEA). The in vitro study revealed that 2-AGE increased cell proliferation and differentiation, upregulated the expression of alpha-smooth muscle actin (α-SMA), N-cadherin, and vimentin, and enhanced cell migration as well as the synthesis of type I and III collagen and fibronectin in normal human dermal fibroblasts. The CB1 antagonist AM251 abolished 2-AGE-induced expression of α-SMA, type I collagen, and fibronectin. In vivo, ACEA treatment accelerated wound closure, increased expression of α-SMA, type I collagen, and fibronectin, and ultimately increased epidermal and dermal thickness. Overall, these findings suggest that the activation of CB1 promotes wound healing and provides evidence for the therapeutic potential of CB1 agonists in wound treatment. Full article

Objectives: Thoracic endovascular aortic repair (TEVAR) is rarely indicated on an urgent or emergent basis soon after open surgical repair of type A aortic dissection (TAAD), and systematic data on clinical outcomes are therefore missing. In the present study, we analyze a contemporary case series regarding the outcome after urgent and emergent endovascular treatment of the downstream thoracic aorta, following open surgery for TAAD. Methods: The study was conducted as a retrospective observational analysis. From January 2024 until April 2025, seven patients (four male, aged 56.8 ± 5.6 years) were treated with TEVAR on an urgent or emergent basis within 48 h after open surgical repair of TAAD at our institution. In all seven patients, the initial dissection extended from the ascending to the abdominal aorta. All seven patients had previously received emergent open surgical repair by ascending aortic repair combined with hemiarch replacement (five patients) or total arch replacement, utilizing the frozen elephant trunk (FET) technique (two patients). Results: In four patients, the indication for urgent TEVAR was due to true lumen collapse (TLC) of the downstream aorta with resulting visceral or peripheral malperfusion symptoms. Three patients were treated on an emergent basis, due to rupture of the descending thoracic aorta with a resulting hemorrhage. Technical success of the TEVAR procedure was 100%. Thirty-day mortality was 0% in the TLC cases but 66% in the ruptured cases, where two of three patients died postoperatively due to the consequences of severe hemorrhagic shock. Within the surviving patients, no subsequent aortic events occurred during follow-up. Late mortality was 0%. The follow-up period was 15.7 ± 2.0 months. Conclusions: In our case series, mortality of urgent or emergent TEVAR soon after open surgical repair for TAAD is substantial, especially in patients that were treated due to acute rupture of the descending thoracic aorta and consecutive hemorrhagic shock. On the other hand, true lumen collapse with resulting malperfusion was successfully treated by instant TEVAR application in all patients without late aortic complications by the midterm follow-up. Full article

Background: Not all ambulance missions result in patient transport, often referred to as non-conveyance. However, in some cases, patients discharged at the scene may require further examination and treatment. Patient sex, age, and psychiatric disease seem to be factors associated with non-conveyance. This study aimed to identify and characterise patients not transported following an urgent ambulance mission, and to examine subsequent hospital admission and mortality rates. In addition, we wanted to examine their reasons for calling the Emergency Medical Communication Centre (EMCC). Methods: This retrospective study was conducted for the emergency medical system of Norway’s second-largest city. Data, including information from non-conveyed patients involved in acute or urgent ambulance missions over 1 year, were obtained from the EMCC. The frequency of non-conveyance, patient demographics, and incidence of hospital admissions within 72 h were analysed. Furthermore, the 30-day mortality, predictive factors, and reasons for contacting the EMCC were determined. Results: Out of a total of 22,183 ambulance missions, 7.3% of patients were not conveyed, of whom 5.8% were admitted to hospital within 72 h. The 30-day mortality rate among all non-conveyed patients was 2.4%, whereas 2.1% of hospitalised patients died within 30 days. Psychiatric conditions were frequently observed in both groups. The mortality rate increased significantly with age but was not associated with the number of ambulance requests. Furthermore, 30-day mortality was not significantly associated with sex, time of day, day of the week, or rurality. Conclusions: Our data suggests that there is no difference between the short-term outcomes of non-conveyed and conveyed patients; both groups are equally likely to come to harm. Therefore, the factors influencing non-transportation decisions warrant further investigation. Subsequent events following patient discharge should be routinely collected by ambulance services and monitored for learning and to improve the quality of patient care. Full article

Background: Catheter ablation is a validated treatment for ventricular arrhythmias (VA), but conventional radiofrequency (RF) energy may cause collateral injury due to non-selective thermal damage. Pulsed Field Ablation (PFA), a non-thermal modality based on irreversible electroporation, offers myocardial tissue selectivity and enhanced safety. While PFA is widely adopted for atrial arrhythmias’ ablation, its application in the ventricles remains an evolving frontier. Methods: We report a single-center experience using the Centauri PFA system integrated with a focal, contact-force sensing irrigated catheter (Tacticath™ SE, Abbott Laboratories, St. Paul, MN, USA) in four consecutive patients with drug-refractory VA. Two patients presented with frequent premature ventricular complexes (PVC) arising from the right and left ventricular outflow tract, respectively, while two had ischemic cardiomyopathy with recurrent scar-related ventricular tachycardia (VT). All procedures were guided by high-density mapping using the EnSite X system (Abbott Laboratories, St. Paul, MN, USA). Procedural safety, acute efficacy, and early follow-up outcomes were assessed. Results: All ablations achieved acute procedural success without complications. In both PVC cases, PFA led to immediate and complete suppression of ectopy, with a ≥95% reduction in arrhythmic burden at 12- and 9-months follow-up, respectively. In the VT cases, the arrhythmogenic substrate was effectively modified, rendering the clinical VT non-inducible. ICD interrogation during a 9-month follow-up showed complete absence of recurrent sustained VT. No coronary spasm, atrioventricular block, pericardial effusion, or other adverse events occurred. Conclusions: In this initial experience, focal PFA using a contact-force sensing catheter appeared feasible and effective for both focal and scar-related VA. This system provides an intuitive workflow similar to RF ablation. While our data suggest a favourable safety profile, larger studies are required to definitively confirm safety margins near critical structures. Full article

Introduction: Massage therapy delivers structured mechanosensory input that can influence brain function, yet the central mechanisms and potential for neuroplastic change have not been synthesized across neuroimaging modalities. This mechanistic review integrates evidence from electroencephalography (EEG), functional MRI (fMRI), and functional near-infrared spectroscopy (fNIRS) to map how massage alters human brain activity acutely and over time and to identify signals of longitudinal adaptation. Materials and Methods: We conducted a scoping, mechanistic review informed by PRISMA/PRISMA-ScR principles. PubMed/MEDLINE, Cochrane Library, Google Scholar, and ResearchGate were queried for English-language human trials (January 1990–July 2025) that (1) delivered a practitioner-applied manual massage (e.g., Swedish, Thai, shiatsu, tuina, reflexology, myofascial techniques) and (2) measured brain activity with EEG, fMRI, or fNIRS pre/post or between groups. Non-manual stimulation, structural-only imaging, protocols, and non-English reports were excluded. Two reviewers independently screened and extracted study, intervention, and neuroimaging details; heterogeneity precluded meta-analysis, so results were narratively synthesized by modality and linked to putative mechanisms and longitudinal effects. Results: Forty-seven studies met the criteria: 30 EEG, 12 fMRI, and 5 fNIRS. Results: Regarding EEG, massage commonly increased alpha across single sessions with reductions in beta/gamma, alongside pressure-dependent autonomic shifts; moderate pressure favored a parasympathetic/relaxation profile. Connectivity effects were state- and modality-specific (e.g., reduced inter-occipital alpha coherence after facial massage, preserved or reorganized coupling with hands-on vs. mechanical delivery). Frontal alpha asymmetry frequently shifted leftward (approach/positive affect). Pain cohorts showed decreased cortical entropy and a shift toward slower rhythms, which tracked analgesia. Somatotopy emerged during unilateral treatments (contralateral central beta suppression). Adjuncts (e.g., binaural beats) enhanced anti-fatigue indices. Longitudinally, repeated programs showed attenuation of acute EEG/cortisol responses yet improvements in stress and performance; in one program, BDNF increased across weeks. In preterm infants, twice-daily massage accelerated EEG maturation (higher alpha/beta, lower delta) in a dose-responsive fashion; the EEG background was more continuous. In fMRI studies, in-scanner touch and reflexology engaged the insula, anterior cingulate, striatum, and periaqueductal gray; somatotopic specificity was observed for mapped foot areas. Resting-state studies in chronic pain reported normalization of regional homogeneity and/or connectivity within default-mode and salience/interoceptive networks after multi-session tuina or osteopathic interventions, paralleling symptom improvement; some task-based effects persisted at delayed follow-up. fNIRS studies generally showed increased prefrontal oxygenation during/after massage; in motor-impaired cohorts, acupressure/massage enhanced lateralized sensorimotor activation, consistent with use-dependent plasticity. Some reports paired hemodynamic changes with oxytocin and autonomic markers. Conclusions: Across modalities, massage reliably modulates central activity acutely and shows convergent signals of neuroplastic adaptation with repeated dosing and in developmental windows. Evidence supports (i) rapid induction of relaxed/analgesic states (alpha increases, network rebalancing) and (ii) longer-horizon changes—network normalization in chronic pain, EEG maturation in preterm infants, and neurotrophic up-shifts—consistent with trait-level recalibration of stress, interoception, and pain circuits. These findings justify integrating massage into rehabilitation, pain management, mental health, and neonatal care and motivate larger, standardized, multimodal longitudinal trials to define dose–response relationships, durability, and mechanistic mediators (e.g., connectivity targets, neuropeptides). Full article

The main objective of this study was to preliminarily analyze the major flavonoid and phenolic acid components of the ethanolic extract of Gerbera delavayi Franch (E-GDF), and to evaluate its anti-inflammatory and antioxidant properties in lipopolysaccharide (LPS)-stimulated murine macrophage RAW264.7 cells and systemic inflammation mouse models. Results indicated that E-GDF was rich in flavonoids (16.35 ± 0.19 mg RT/g d.w. Plant Material) and polyphenolic compounds (36.15 ± 0.20 mg GAE/g d.w. Plant Material). LC-MS analysis of E-GDF revealed that its major flavonoid components included kaempferol glycosides, luteolin, and their glycosylated derivatives, while its phenolic acids were predominantly chlorogenic acid, caffeic acid, ferulic acid, and their corresponding glycosides. E-GDF exhibited good antioxidant activities, including the scavenging of DPPH, ABTS, ^•OH, and O₂^•− radicals. E-GDF treatment significantly inhibited the production of ROS and inflammatory mediators (NO, IL-6, TNF-α) in LPS-stimulated macrophages (RAW 264.7), while concurrently down-regulating the mRNA expression of COX-2, IL-1β, Casp1, and GSDMD-1. In addition, in vivo experiments revealed that E-GDF treatment effectively reduced the serum LPS, AST levels, as well as hepatic TNF-α, IL-6 levels in mice with LPS-induced acute liver injury. Furthermore, E-GDF significantly ameliorated LPS-induced liver pathological damage. These results provide a basis for G. delavayi as a potential antioxidant, anti-inflammatory, and hepatoprotective herbal medicine. Full article

Diffusion-weighted imaging (DWI) has been increasingly utilized in the emergent evaluation of acute ischemic stroke (AIS) patients. DWI enhances sensitivity and specificity and enables the use of delayed reperfusion treatments in selected cases. However, DWI is not devoid of limitations. DWI-negative AIS is not uncommon in clinical practice and is reported in up to 1 of 4 AIS patients. We reviewed the relevant literature and searched the PubMed and Google Scholar databases for studies reporting on DWI-negative AIS prevalence during the 2021–2025 time period. Additionally, we included cases from our practice to highlight key points. DWI-negative AIS prevalence was 16% in one meta-analysis and ranged from 6.9% to 23.2% in identified studies that met our inclusion criteria. The biological, pathophysiological, technical, epidemiological and clinical factors that contribute to DWI-negative stroke are presented in detail. Overall, the application of diffusion imaging modalities for stroke is not bereft of blind spots despite enhanced sensitivity. Over-reliance on advanced neuroimaging and unfamiliarity with its limitations predispose DWI to errors in AIS assessment. Awareness of the predisposing factors, treatment effect, and prognosis guides appropriate decision-making, promoting good outcomes. Prospective appropriately designed trials should address the lingering questions identified, such as the association between time of imaging and DWI negativity. Full article

Background/Objectives: The underlying molecular mechanisms of deep vein thrombosis (DVT), which continues to be a major global public health concern, remain unclear. A key component of anticoagulant therapy, heparin (HP) interacts with heparin-binding growth factors including pleiotrophin (PTN) and midkine (MK), both of which have basic amino acid-rich domains that have a strong affinity for HP. The purpose of this study was to determine if changes in the levels of circulating HP, MK, and PTN are linked to the onset of acute DVT. Methods: Thirty patients diagnosed with acute DVT by venous Doppler ultrasonography (VDU) and 28 healthy controls with normal VDU findings were enrolled. Serum HP, MK, and PTN concentrations were measured using ELISA. In DVT patients, blood samples were obtained before and after routine subcutaneous low-molecular-weight heparin treatment; controls provided a single blood sample. ROC curve analysis was used to assess diagnostic performance. Results: Prior to treatment, patients with acute DVT exhibited significantly lower serum HP levels (p < 0.05) and significantly higher MK and PTN levels compared with healthy controls (both p < 0.05). Following heparin administration, serum HP levels increased significantly (p < 0.05), while MK and PTN levels showed a decreasing trend that did not reach statistical significance (p > 0.05). ROC curve analysis demonstrated limited diagnostic performance for HP (sensitivity 10.3%, specificity 68.8%), PTN (62.1%, 54.2%), and MK (82.8%, 35.4%). Conclusions: Decreased circulating HP and increased MK and PTN levels are characteristics of acute DVT that may indicate endogenous HP sequestration through binding to these growth factors. This imbalance could lead to less free HP being available, which would encourage the formation of thrombus. Therapeutic approaches that target MK- and PTN-mediated HP interactions may constitute a unique approach for the therapy of acute DVT, as evidenced by the partial normalization seen after exogenous heparin delivery. Full article

The search for new therapeutic principles is essential for treating relapsed/refractory (r/r) acute myeloid leukemia (AML). Novel principles include genome-agnostic differentiation induction, controlling AML-triggering inflammation, potentiating the immune response and ‘normalizing’ AML metabolism. This review summarizes data from a phase I study (10 patients, pts) and three case reports reporting 7 pts on the treatment of r/r AML by reprogramming AML hallmarks using APA, low-dose azacitidine, pioglitazone (PPARα/γ agonist) and all-trans retinoic acid. APA reprograms the r/r AML phenotype in patients with clinically and molecularly/genetically unfavorable risk profiles (17 pts, 16 refractory, one relapsed) in a genome-agnostic manner, restoring the plasticity of AML hallmarks, thereby improving immune surveillance, attenuating inflammation-triggered promotion of AML and distant microbial inflammation (healing of fungal pneumonia during induction of complete remission (CR) with APA), while normalizing leukemia metabolism (restoring phagocytosis and ROS production in leukemic neutrophils). APA induces CR in 10 pts (59%), with only modest hematotoxicity following CR induction. This allows treatment to be carried out in an outpatient setting, including for elderly and comorbid patients. Triple transcriptional modulation, facilitated by epigenetic modelling with azacitidine, targets reprogramming of non-oncogene addiction networks in AML, re-establishing functionally active, closely interrelated myeloid hallmarks and AML cell death genome-agnostically. Full article

Newborn screening (NBS) for sickle cell disease (SCD) has been performed in the United States (US) for decades, significantly reducing infant morbidity and mortality. A landmark clinical trial demonstrated that early identification of SCD enabled timely and life-saving prophylactic penicillin; this led to recommendations for universal NBS across the US. Early use of hydroxyurea as a safe and effective treatment for SCD further improved clinical outcomes by preventing acute and chronic disease complications. These advances add to the importance of early diagnosis through NBS, providing an opportunity for early treatment intervention. In recent years, high-resource countries—including those in Europe, the UK, and Canada—have adopted NBS for SCD using diverse strategies. Simultaneously, pilot programs in lower-resource settings such as Africa, Brazil, and India have demonstrated local feasibility and impact through implementation efforts. An overarching equity gap for achieving global NBS for SCD is the variable access to simple, accurate, and affordable testing. Other challenges include timing of NBS testing, targeted populations, laboratory methods, and parental education with genetic counseling. Questions remain about the equitable enrollment of affected infants worldwide into comprehensive care to ensure early treatment. These challenges raise concerns about sustainability, underscore the need for long-term funding and a strategic plan, and highlight persistent inequities from the lack of global NBS standards. Full article