Papilledema is a potentially vision-threatening finding in children, often diagnosed during routine ophthalmological evaluation in asymptomatic subjects, which requires prompt diagnostic evaluation to exclude intracranial pathology. The available literature suggests that a significant proportion of cases with confirmed idiopathic intracranial hypertension (IIH) may present without headache or other manifestations of increased intracranial pressure. Current diagnostic criteria for pediatric IIH include lumbar puncture (LP) as a mandatory step following neuroimaging. However, the invasive nature of this procedure raises critical questions regarding the identification of patients who truly require this investigation. Indeed, the challenge of distinguishing true papilledema from pseudopapilledema represents the critical diagnostic prerequisite, requiring an expert pediatric neuro-ophthalmologist to ensure appropriate patient selection and avoid unnecessary tests. Evidence regarding the management of asymptomatic IIH is limited. Most published cohorts report treatment with acetazolamide despite the absence of symptoms, probably based on concerns regarding potential visual deterioration rather than prospective data. Currently, data from pediatric populations characterizing the natural history of untreated patients are lacking, and there is no consensus regarding treatment duration, tapering strategies, or long-term follow-up for this group. This narrative review summarizes the current literature on the diagnostic and therapeutic strategies for asymptomatic pediatric papilledema. It focuses on the role of lumbar puncture, the importance of differentiating papilledema from pseudopapilledema, and the uncertainties surrounding treatment decisions. Nevertheless, significant knowledge gaps persist regarding the optimal management of these patients, highlighting the need for prospective studies.

All-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) is the standard of care for acute promyelocytic leukemia (APL), including high-risk disease. Secondary intracranial hypertension (SIH), historically termed pseudotumor cerebri (PTC), is a recognized but uncommon and potentially therapy-limiting complication of retinoid exposure, reported predominantly in pediatric and young-adult patients and most frequently during induction. We report a 31-year-old man with high-risk microgranular APL in whom SIH was diagnosed during the first ATRA/ATO consolidation cycle. The clinical course included progressive headache, ocular pain, pulsatile tinnitus, focusing difficulties, visual deterioration, and diplopia. Ophthalmological assessment demonstrated bilateral papilledema with marked peripapillary retinal nerve fiber layer thickening despite preserved central visual acuity. Magnetic resonance imaging showed bilateral optic nerve sheath distension, prominent optic nerve heads, mild pituitary flattening, and bilateral transverse sinus stenosis. Lumbar puncture demonstrated an opening pressure of 32 cm H2O with otherwise unremarkable cerebrospinal fluid; removal of approximately 30 mL resulted in immediate symptomatic improvement. Management consisted of temporary ATRA interruption, therapeutic lumbar punctures, acetazolamide, and individualized ATRA rechallenge and dose titration. Repeated attempts at dose escalation reproduced symptoms, and ATRA was ultimately maintained at a maximally tolerated dose of 30 mg/m[2]/day while full-dose ATO was continued. Molecular remission was achieved after the first consolidation cycle and remains sustained at 18-month follow-up. This case highlights the importance of recognizing ATRA-associated SIH throughout the treatment course and illustrates a pragmatic strategy for preserving ATRA exposure when standard-dose treatment is limited by neurological toxicity. However, the oncological equivalence of reduced-dose ATRA cannot be inferred from a single case.

FDA-approved carbonic anhydrase inhibitors (CAIs) have shown robust efficacy in reducing amyloid-β (Aβ) pathology, neurodegeneration, and cerebrovascular dysfunction in Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) models, highlighting carbonic anhydrase (CAs) as a promising, previously untapped therapeutic target for AD and vascular contribution to dementia. We have recently shown that Aβ aggregates disrupt neuro-signaling and deplete neurotrophic factors (particularly BDNF) in the heart of AD mouse models and human subjects. In this study, we present the first in-depth examination of CAI therapy (acetazolamide-ATZ) in Tg2576 mice, a well-established model of AD and CAA. We confirm that progressive cardiac fibrosis and Aβ deposition in 13-month-old mice severely impair the cardiac neuro-signaling system, marked by a drastic decrease in BDNF and reductions in adrenergic fibers and regenerating nerve endings (TH and GAP-43 markers), leading to significant declines in ejection fraction and fractional shortening compared to age-matched WT littermates. Critically, this study demonstrates that long-term ATZ treatment in Tg2576 mice significantly reduces cardiac Aβ burden, prevents adverse neuro-signaling remodeling, and restores heart physiological function, as assessed via speckle tracking strain echocardiography. These in vivo findings were corroborated in human cardiomyocytes, in which CA inhibition reduced human Aβ40 oligomer-dependent disruption of CREB signaling, thus preserving BDNF expression. Together, these results reveal a previously unrecognized cardio-neuroprotective role for CAIs in preventing Aβ-induced cardiovascular remodeling and neuro-signaling disruption in the Tg2576-AD model. Given the established benefits of CAIs on cerebrovascular function and cognition, our findings further support advancing repurposing efforts into clinical trials. CAIs such as ATZ could offer a dual-action therapy approach, addressing both the central nervous system and cardiac pathologies associated with AD and, potentially, the systemic effects of amyloidosis.

Loop diuretics remain the cornerstone of decongestion in acute heart failure, yet their use in heart failure with reduced ejection fraction (HFrEF) is obscured by two competing errors: undertreating congestion because serum creatinine rises, and continuing or escalating diuretics after euvolaemia. This narrative review integrates established evidence and contemporary guidance into a phase-based cardiorenal decision framework. Congestion is framed as a continuum generated by sodium retention, redistribution of stressed blood volume, vascular and ventricular compliance, right-sided pressure, and renal sodium avidity-not as a binary distinction between pressure and volume overload. During acute decompensation, intravenous loop diuretics remain first-line therapy; early urine output and spot urinary sodium can identify inadequate response and support protocolized escalation. Acetazolamide or a thiazide-type diuretic can improve decongestion when loop response is insufficient, although renal and electrolyte surveillance is essential. Sodium-glucose cotransporter 2 inhibitors should be initiated for disease modification after stabilization, but their context-dependent natriuretic effect does not replace loop diuretics in marked congestion. A creatinine rise during effective decongestion should be interpreted with residual congestion, haemodynamics, urine output, electrolytes, and evidence of kidney injury rather than through a universal threshold. After stabilization, implementation of foundational HFrEF therapy and reassessment of the minimum effective loop dose become priorities. Studies suggest that dose reduction or withdrawal is feasible in stable, euvolaemic patients, but event-powered evidence and validated outpatient biomarkers are lacking. Diuretics and disease-modifying therapy therefore have complementary, time-dependent roles: remove sodium when congestion is present, protect the kidney while recognizing hypoperfusion and intrinsic kidney injury, and de-escalate only after euvolaemia.

Radiotherapy resistance in tumors driven by metabolic adaptations within acidic microenvironments involves the upregulation of both carbonic anhydrase IX (CA IX) and the pentose phosphate pathway (PPP) as well as the functional crosstalk between them. To overcome this, we developed a polyvinylpyrrolidone (PVP)-modified gadolinium acetazolamide (PGA) nanoradiosensitizer. PGA simultaneously inhibits CA IX to trigger intracellular acidification and tumor cell acidosis, suppresses PPP through regulation of glucose-6-phosphate dehydrogenase (G6PD), and depletes key radioresistance-sustaining metabolites, such as NADPH, lipids, and nucleotide precursors. In addition, the high-Z element Gd endows PGA with potent radiosensitizing properties by enhancing X-ray absorption and DNA damage. In orthotopic and metastatic triple-negative breast cancer (TNBC) mouse models, PGA combined with radiotherapy markedly improves the therapeutic efficacy. Mechanistically, this metabolic reprogramming amplifies radiation-induced apoptosis and immunogenic cell death (ICD) while inhibiting metastasis-associated matrix metalloproteinases (MMPs) and the epithelial-mesenchymal transition (EMT) process. Consequently, PGA effectively overcomes radioresistance and suppresses TNBC lung metastasis through the coordinated disruption of tumor metabolism and remodeling of the tumor immune microenvironment. This work advances the frontier of metabolism-targeted nanomedicine for precision cancer therapy, offering a promising strategy to combat radiotherapy resistance in aggressive breast cancer.

Carbonic anhydrase IX (CAIX) is a well-established biomarker of tumor hypoxia and an attractive target for molecular imaging. Despite the development of small-molecule CAIX-targeting positron emission tomography (PET) probes, most exhibit high normal-organ uptake and suboptimal tumor-to-background contrast. Moreover, their application in hypoxic tumors remains insufficiently explored. Herein, we reported four 68Ga-labeled CAIX-targeting probes based on the acetazolamide (AAZ) scaffold, employing distinct conjugation strategies, including amide coupling and maleimide-thiol ligation. All probes demonstrated detectable tumor uptake in vivo. Among them, [68Ga]Ga-SMIC-2607 displayed the highest tumor uptake (14.67 ± 3.06 %ID/g) and tumor-to-kidney ratio (1.69 ± 0.41) at 1 h in subcutaneous OS-RC-2-bearing mice, along with high tumor uptake in HT-29-bearing mice (2.98 ± 0.28 %ID/g at 1 h). Overall, [68Ga]Ga-SMIC-2607 demonstrates favorable imaging characteristics, with high tumor uptake and high tumor-to-normal organ ratios, representing a promising candidate for imaging CAIX-overexpressing tumors and supporting clinical translation.

BackgroundIntracranial steno-occlusive disease (SOD) assessment benefits from hemodynamic imaging, but comprehensive evaluation often relies on contrast- or radiation-based techniques. Arterial spin labeling (ASL) provides a non-invasive alternative for quantifying tissue-level perfusion and cerebrovascular reactivity, yet does not capture upstream arterial flow dynamics. As a result, non-invasive assessment of macrovascular hemodynamics for SOD remains limited. This study evaluates whether quantitative 4D-MRA provides complementary arterial information beyond established ASL-derived metrics.MethodsTwelve SOD patients (7 women; age 42.3±25.8 years) underwent multi-delay ASL and 4D-MRA before and after acetazolamide. Cerebrovascular reactivity (CVR), arterial transit time (ATT), macrovascular ATT (mATT), and labeled blood volume (LBV) were quantified. Associations and vasodilatory responses were assessed using linear mixed-effects models.ResultsAt baseline, mATT correlated with ATT (β=0.66±0.08, p<0.001). Both decreased following acetazolamide (mATT: 1.07±0.03s to 1.01±0.03s, p=0.029; ATT: 1.63±0.07s to 1.40±0.07s, p<0.001). However, changes in mATT and ATT were not associated with CVR. In contrast, CVR was positively associated with ΔLBV (β=8.84, SE=2.43, p=0.01). Case analyses further demonstrated artery-level delayed inflow and vascular steal.ConclusionQuantitative 4D-MRA provides complementary macrovascular information to ASL in SOD. ΔLBV more consistently reflects cerebrovascular reactivity than transit-based metrics and is sensitive to artery-level delayed inflow and vascular steal.

Acetazolamide is recommended for the prevention of acute mountain sickness, but its effects on endurance performance at prophylactic doses remain unclear. Twelve male physical education students completed a randomized, double-blind, placebo-controlled crossover trial with a 1-week washout. Acetazolamide was administered as three 125-mg doses within 24 hours before testing. Following 30 minutes of seated normobaric hypoxia (FiO2=0.13; ~3,800 m simulated altitude), participants performed constant-load cycling at 60% of peak power output under normobaric hypoxia until exhaustion. Time to exhaustion and mean rating of perceived exertion were analyzed using linear mixed models accounting for treatment, period, and sequence. Time to exhaustion was lower with acetazolamide than with placebo (249.6±36.2 vs. 364.7±71.8 s; p<0.001). Mean rating of perceived exertion was higher with acetazolamide (14.50±1.64 vs. 11.81±1.57; p=0.002). Peripheral oxygen saturation was higher with acetazolamide during resting hypoxia, exercise, and at exhaustion (all p≤0.001), whereas the heart rate was higher with acetazolamide only during exercise (p=0.049). No period or sequence effects were detected for time to exhaustion or perceived exertion. Acetazolamide reduced endurance performance and increased early perceived exertion despite higher peripheral oxygen saturation during acute normobaric hypoxia.

Primary myelofibrosis (PMF) is a rare myeloproliferative neoplasm that typically affects older adults but may present aggressively in younger patients. Thromboembolic complications are well recognized, though arterial occlusions are uncommon in this age group. Ocular ischemia associated with systemic inflammatory conditions such as Sweet's syndrome is exceedingly rare. A 22-year-old female with PMF, diagnosed 18 months earlier and managed initially with ruxolitinib, presented with sudden, complete loss of vision in her left eye. She also had a history of Sweet's syndrome managed with oral corticosteroids and had received multiple blood transfusions. Ophthalmic evaluation revealed no light perception in the left eye, a pale retina with attenuated vessels, and a cherry-red spot. Optical coherence tomography (OCT) showed hyperreflectivity of the inner retinal layers, and OCT angiography demonstrated markedly reduced perfusion in all vascular plexuses. Carotid Doppler, echocardiography, and ECG excluded embolic sources. Despite ocular massage, anterior chamber paracentesis, acetazolamide, and anticoagulation with apixaban, vision did not recover. One week later, she developed anterior uveitis, keratic precipitates, and elevated intraocular pressure. Fundus showed Amalric's sign of choroidal infarction and Elschnig spots, confirmed on fluorescein angiography. Inflammation responded to topical and systemic corticosteroids, with normalization of intraocular pressure. This is the first documented case of combined central retinal artery occlusion and posterior ciliary artery occlusion with anterior uveitis in a young PMF patient with Sweet's syndrome. The case underscores the multifactorial contribution of hypercoagulability, systemic inflammation, and transfusion-related factors in ocular ischemia.

We present a case of a 65-year-old female with choroidal melanoma, who developed an orbital hematoma following ruthenium-106 ([106]Ru) plaque implantation. The patient, with a history of recurrent ipsilateral subconjunctival hemorrhages and arterial hypertension, experienced intense coughing immediately following the completion of surgery and extubation. Subsequently, she developed an orbital hematoma (confirmed by B-scan ultrasonography). Conservative management, including oral steroids and acetazolamide, was adopted. Plaque removal was challenging due to hematoma-induced restricted eyelid opening, but post-operative recovery was uneventful. Although potential suboptimal dosimetry raises concerns for long-term tumor control, short-term local tumor stability was observed at 6 months. To the best of our knowledge, this is the first report of such complication, highlighting the importance of vigilant post-operative monitoring to optimize treatment outcomes for [106]Ru brachytherapy.

Chronic intracranial venous hypertension (CIVHS) comprises a heterogeneous group of disorders characterized by impaired cerebral venous outflow and symptoms related to elevated intracranial pressure. Although venous sinus stenting is increasingly used for venous sinus stenosis with elevated trans-stenotic pressure gradients, venous sinus stenosis is an imaging phenotype rather than a single diagnosis. We retrospectively reviewed 13 consecutive patients with CIVHS who underwent clinical, imaging, and hemodynamic evaluation, including conventional neuroimaging, MR or CT venography, digital subtraction angiography, venous manometry when indicated, and selective high-resolution MRI. All patients initially presented to ophthalmology and had papilledema. Patients were classified according to presumed mechanisms of venous outflow impairment, and treatment was tailored to the anatomical substrate, hemodynamic findings, and clinical context. Six etiological categories were identified: intrinsic transverse sinus stenosis, extrinsic transverse-sigmoid sinus compression, shunt dependency syndrome, jugular foramen stenosis related to chronic organized thrombus, JAK2 V617F mutation-positive essential thrombocythemia with suspected microvascular venous congestion, and dialysis catheter-related central venous stenosis. An additional chronic cerebral venous sinus thrombosis case was included as an illustrative secondary comparator but was not classified as idiopathic intracranial hypertension. Treatments included venous sinus stenting, shunt-related management, hematologic-directed therapy, anticoagulation, acetazolamide, weight control, and conservative management. Among the 13 cohort patients with available follow-up, symptoms improved or remained clinically stable; Case 14 was lost to follow-up. No stent failure was documented during short-term follow-up, but long-term surveillance data were unavailable. These findings support an etiology-oriented, multimodal approach to chronic intracranial venous hypertension.