Search Results (212)

Background: Glaucoma is a progressive optic neuropathy marked by retinal ganglion cells (RGCs), apoptosis, vascular insufficiency, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. While intraocular pressure (IOP) reduction remains the primary intervention, many patients continue to lose vision despite adequate pressure control. Emerging neuroprotective agents—citicoline, coenzyme Q10 (CoQ10), pyruvate, nicotinamide, pyrroloquinoline quinone (PQQ), homotaurine, berberine, and gamma-aminobutyric acid (GABA)—target complementary pathogenic pathways in experimental and clinical settings. Methods: This literature review synthesizes current evidence on glaucoma neuroprotection, specifically drawing on the most relevant and recent studies identified via PubMed. Results: Citicoline enhances phospholipid synthesis, stabilizes mitochondrial membranes, modulates neurotransmitters, and improves electrophysiological and visual field outcomes. CoQ10 preserves mitochondrial bioenergetics, scavenges reactive oxygen species, and mitigates glutamate-induced excitotoxicity. Pyruvate supports energy metabolism, scavenges reactive oxygen species, and restores metabolic transporter expression. Nicotinamide and its precursor nicotinamide riboside boost NAD⁺ levels, protect against early mitochondrial dysfunction, and enhance photopic negative response amplitudes. PQQ reduces systemic inflammation and enhances mitochondrial metabolites, while homotaurine modulates GABAergic signaling and inhibits β-amyloid aggregation. Berberine attenuates excitotoxicity, inflammation, and apoptosis via the P2X7 and GABA-PKC-α pathways. Preclinical models demonstrate synergy when agents are combined to address multiple targets. Clinical trials of fixed-dose combinations—such as citicoline + CoQ10 ± vitamin B3, citicoline + homotaurine ± vitamin E or PQQ, and nicotinamide + pyruvate—show additive improvements in RGCs’ electrophysiology, visual function, contrast sensitivity, and quality of life without altering IOP. Conclusions: A multi-targeted approach is suitable for glaucoma’s complex neurobiology and may slow progression more effectively than monotherapies. Ongoing randomized controlled trials are essential to establish optimal compound ratios, dosages, long-term safety, and structural outcomes. However, current evidence remains limited by small sample sizes, heterogeneous study designs, and a lack of long-term real-world data. Integrating combination neuroprotection into standard care holds promise for preserving vision and reducing the global burden of irreversible glaucoma-related blindness. Full article

Dry powder inhalers (DPIs) are the mainstay in the treatment of obstructive pulmonary diseases. However, the performance of DPI formulations is highly dependent on the used inhaler device and the patient’s inspiratory effort. This study aimed to evaluate and compare the aerosolization behavior of three commercially available capsule-based DPI medications—formoterol (Foradil^®), glycopyrronium (Seebri^® Breezhaler), and tiotropium (Spiriva^®)—delivered using three different capsule-based inhalers (Aerolizer, Breezhaler, and Handihaler), under varying flow conditions. Methods: The aerodynamic performance of each formulation–inhaler combination was assessed using the Next-Generation Impactor (NGI) and Dosage Unit Sampling Apparatus (DUSA) methodology. Fine particle dose (FPD) and aerodynamic particle size distribution (APSD) were determined at fixed flow rates of 15, 30, 60, and 100 L/min, as well as at inhaler-specific flow rates corresponding to a 4 kPa pressure drop. Chromatographic quantification of active ingredients was performed using validated HPLC methods specific to each drug. Results: The FPD values increased consistently with higher flow rates across all tested formulations and inhalers. At a 4 kPa pressure drop, Aerolizer and Breezhaler achieved significantly higher FPDs compared to Handihaler. Notably, in some instances, non-dedicated inhalers produced greater respirable fractions than the originally intended devices. APSD profiles revealed that drug deposition shifted toward smaller NGI stages at higher inspiratory flows, supporting enhanced deep lung delivery potential under optimal conditions. Conclusions: Device resistance, capsule orientation, and piercing mechanics substantially influence drug aerosolization. Although non-dedicated inhalers may offer improved FPDs in vitro, clinical use should adhere to approved drug–device combinations, as these have been validated for efficacy and safety under real-world conditions. Full article

In recent years, there has been growing interest in using wood biomass for energy production, which has led to an increase in post-processing waste in the form of wood biomass ash (WBA). Due to the rich composition of WBA, its fertilising potential should be considered. In the conducted studies, WBA was used both alone and in combination with digestate (DG). The WBA was obtained from the Municipal Heat Energy Company and the DG from the Agricultural Biogas Plant in the form of unseparated liquid digestate (ULD), separated solid digestate (SSD) and separated liquid digestate (SLD). The studies included four series: (1) WBA, (2) WBA + ULD, (3) WBA + SSD and (4) WBA + SLD. In each series, WBA was introduced in three increasing doses (0.5, 1.0 and 1.5, expressed in hydrolytic acidity units (HACs) and determined based on the general alkalinity of the material). The digestates (DGs) were applied in fixed doses, which were balanced with respect to the nitrogen introduced into the soil. The test plant was the maize (Zea mays L.) variety Garantio, which was grown in a vegetation hall. The obtained results indicate that the combined use of WBA and DGs (especially ULD and SLD) had a positive effect on the plant height, leaf greenness index (SPAD), and thus, maize yield and dry matter content. In the series with DG addition, the maize yield ranged from 615.5 g (WBA + SSD) to 729.6 g pot⁻¹ (WBA + SLD), which was 28–52% higher than in the series with WBA alone. In turn, the application of increasing doses of WBA alone did not significantly affect the biomass yield but significantly increased the content of N (34%), K (60%), Mg (56%), Ca (60%) and Na (4%). In the series with WBA and DGs, the increase in the content of the above-mentioned macronutrients depended on the type of DG and the dose of WBA. The exception among the macronutrients was P, whose content generally decreased (by 4–23%) with an increasing WBA dose, regardless of the test series. The most favourable results in terms of the chemical composition, excluding the P content, were observed following the combined application of WBA and liquid forms of DG (ULD and SLD). Full article

Background/Objectives: Pain is a growing public health concern worldwide, and the use of combinations of drugs can improve their analgesic effects while minimizing their adverse effects. Drugs such as metformin (antidiabetic) and melatonin (sleep regulator) have analgesic potential in combination. In this study, we evaluated the pharmacological interaction between metformin and melatonin when orally administered in a rat model, using the formalin test. Methods: Female Wistar rats (220–350 g) were injected with 50 µL of 1% formalin in the dorsal surface of the right hind paw. Formalin produces pain-related flinching behavior, and antinociception was evaluated as the reduction in this response. The percentage of the antinociceptive effect was determined after the oral administration of metformin (30–1000 mg/kg), melatonin (10–150 mg/kg), and their combination (MMC). To establish the nature of the interaction, isobolographic analysis was performed in a fixed-dose ratio (0.5:0.5), based on the effective dose 50 (ED₅₀) values for each drug: metformin (947.46 ± 242.60 mg/kg) and melatonin (126.86 ± 37.98 mg/kg). To evaluate the mechanism of action, the receptor antagonist for metformin compound C (dorsomorphin) for AMPK inhibition, MT1 and MT2 melatonin receptor antagonists (4-P-PDOT, luzindole), and an opioid antagonist (naloxone) were employed. The rotarod test was used to evaluate the safety profile of the combination. Results: The metformin–melatonin combination significantly reduced the number of flinches in the second phase of the formalin test. The theoretical ED₅₀ for the combination (ED₅₀ T) was 537.15 ± 122.76 mg/kg. Experimentally, the ED₅₀ (ED₅₀ E) was significantly lower (360.83 ± 23.36 mg/kg), indicating a synergistic interaction for the combination involving opioidergic pathways, MT2 receptors, and AMPK activation. Conclusions: Oral metformin–melatonin coadministration could provide a therapeutic alternative for inflammatory pain. Full article

Background: Fixed-dose combinations have advanced in many therapeutic areas, including otorhinolaryngology, where hearing disorders are increasingly prevalent. Objectives: The present study focuses on developing and evaluating a new capsule combining nicergoline (NIC), piracetam (PIR), and hawthorn extract (HE) for the management of sensorineural hearing loss. Methods: The first phase methodology comprised preformulation studies (DSC, FTIR, and PXRD) to assess compatibility among active substances and excipients. Subsequently, four formulations were prepared and tested for flowability, dissolution behavior in acidic and neutral media, and stability under oxidative, thermal, and photolytic stress. Quantification of the active substances and flavonoids was performed using validated spectrophotometric and HPLC-UV methods. Results: Among the tested variants, the F1 formulation (4.5 mg NIC, 200 mg PIR, 50 mg HE, 2.5 mg magnesium stearate, 2.5 mg sodium starch glycolate, and 240.5 mg monohydrate lactose per capsule) displayed optimal technological properties, superior dissolution in acidic media, and was further selected for evaluation. The antioxidant activity of the formulation was confirmed through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, Trolox Equivalent Antioxidant Capacity (TEAC), and iron chelation tests, and was primarily attributed to the flavonoid content of the HE. Acute toxicity tests in mice and rats indicated a high safety margin (LD₅₀ > 2500 mg/kg), while ototoxicity assessments showed no adverse effects on auditory function. Conclusions: The developed formulation displayed good stability, safety, and therapeutic potential, while the applied workflow could represent a model for the development of future fixed-dose combinations. Full article

Background: Fixed-dose combinations of rosuvastatin and ezetimibe are increasingly used in clinical practice, but real-world data on their effectiveness and safety in large populations remain limited. Methods: This prospective, single-group, open-label, non-interventional observational study was conducted in the Republic of Korea to evaluate the effectiveness and safety of Rovazet^® (a fixed-dose combination of rosuvastatin and ezetimibe). Patients were prospectively enrolled from 235 institutions (50 general hospitals and 185 private clinics) as part of routine clinical practice over a five-year period. Lipid profiles and medication compliance questionnaire results were collected at baseline, 12 weeks, and 24 weeks of treatment. Results: A total of 5527 patients with dyslipidemia, the majority were men (53.0%), and the mean age was 60.4 years. Rovazet^® significantly reduced low-density lipoprotein cholesterol (LDL-C) by 23.5% at 12 weeks (from 117.47 ± 50.65 mg/dL to 81.14 ± 38.20 mg/dL; p < 0.0001) and by 27.4% at 24 weeks (from 117.47 ± 50.65 mg/dL to 74.52 ± 33.36 mg/dL; p < 0.0001). Total cholesterol was significantly reduced by 17.7% at 12 weeks and by 19.8% at 24 weeks. Rovazet^® treatment reduced triglycerides by 4.1% at 12 weeks and by 7.2% at 24 weeks. High-density lipoprotein cholesterol increased by 4.5% at 12 weeks and by 7.9% at 24 weeks following Rovazet^® treatment. These changes in lipid profiles were consistent, regardless of cardiovascular risk profiles. By 24 weeks of treatment with Rovazet^®, 91.8% of patients had reached their target LDL-C goals. Adverse drug reactions were reported in 2.81% of patients, most of which were minor, indicating that Rovazet^® was well tolerated. Conclusions: Rovazet^® was effective in improving lipid profiles and well tolerated in Korean adults with dyslipidemia. Full article

Background and Objectives: This study aimed to investigate the anticancer effects and potential synergistic interactions of quercetin (Q) and doxorubicin (Dox) on the MG-63 osteosarcoma (OS) cell line. Specifically, the effects of these agents on cell viability, apoptosis, reactive oxygen species (ROS) generation, antioxidant defense, and the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt1) signaling pathway were evaluated. Material and Methods: MG-63 cells were cultured and treated with varying concentrations of Q and Dox, both individually and in combination (fixed 5:1 molar ratio), for 48 h. Cell viability was assessed using an MTT assay, and IC₅₀ values were calculated. Synergistic effects were analyzed using the Chou–Talalay combination index (CI). Apoptosis was evaluated via Annexin V-FITC/PI staining and caspase-3/7 activity. ROS levels were quantified using DCFH-DA probe, and antioxidant enzymes (SOD, GPx) were measured spectrophotometrically. Gene expression (Runx2, PI3K, Akt1, caspase-3) was analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results: Q and Dox reduced cell viability in a dose-dependent manner, with IC₅₀ values of 70.3 µM and 1.14 µM, respectively. The combination treatment exhibited synergistic cytotoxicity (CI < 1), especially in the Q50 + Dox5 group (CI = 0.23). Apoptosis was significantly enhanced in the combination group, evidenced by increased Annexin V positivity and caspase-3 activation. ROS levels were markedly elevated, while antioxidant enzyme activities declined. RT-qPCR revealed upregulation of caspase-3 and downregulation of Runx2, PI3K, and Akt1 mRNA levels. Conclusions: The combination of Q and Dox exerts synergistic anticancer effects in MG-63 OS cells by inducing apoptosis, elevating oxidative stress, suppressing antioxidant defense, and inhibiting the PI3K/Akt1 signaling pathway and Runx2 expression. These findings support the potential utility of Q as an adjuvant to enhance Dox efficacy in OS treatment. Full article

Cyanobacteria-based bioinoculants represent a sustainable solution for enhancing soil fertility and crop productivity. This research assessed the biofertilizing potential of two indigenous nitrogen-fixing cyanobacteria strains (Nostoc punctiforme Har. and Anabaena cylindrica Lemmerm.) on tomato growth and yield. A greenhouse experiment was conducted to study their effects on soil properties, plant growth and physiology, and fruit yield/quality. The strains were applied individually, as a consortium, or combined with organic or mineral fertilizers at half the standard dose (50%). All bioinoculants improved soil fertility, plant growth, and fruit yield/quality compared to the control. The most significant improvement was observed in the consortium amended with 50% of conventional fertilizer (compost or NPK), compared with individual strains. Correlation analysis revealed strong positive associations between photosynthetic pigments, plant productivity, and fruit biochemical traits, indicating coordinated physiological responses under the applied treatments. The results demonstrated that the consortium of diazotrophic terrestrial cyanobacteria possesses tomato biofertilizer properties that can be efficiently used in crop production. These findings suggest that such formulations offer a cost-effective approach to tomato cultivation and present a sustainable alternative for integrated and optimized fertilizer management. Full article

This study proposes a data-driven optimization framework to enhance emission control performance in diesel engine selective catalytic reduction (SCR) systems under transient operating conditions. A one-dimensional SCR model was constructed in GT-Power, and simulation datasets were generated using experimentally measured inputs from the World Harmonized Transient Cycle (WHTC), with representative emission responses obtained by varying fixed ammonia-to-NOx (A/N) ratios. Building on these datasets, a hybrid prediction model combining Long Short-Term Memory (LSTM) networks and multi-head attention mechanisms was developed to accurately forecast SCR outlet NH₃ leakage and NOx emissions. The model exhibited high predictive accuracy, achieving R² values exceeding 0.977 and low RMSE across training, validation, and test sets. Based on the model predictions, a constrained dynamic multi-objective optimization strategy was implemented to adaptively adjust ammonia dosing, aiming to simultaneously minimize NH₃ leakage and NOx emissions. The optimized NH₃ injection profiles were validated through reapplication in the GT-Power simulation environment. Compared to the baseline fixed-ratio control strategy, the proposed approach reduced NH₃ leakage and NOx emissions by 34.40% and 11.15%, respectively, as determined for the transient segment of the WHTC cycle. These results demonstrate the effectiveness of integrating physics-based simulation, deep learning prediction, and dynamic optimization for improving aftertreatment adaptability and emission compliance in real-world diesel engine applications. All reported values are based on a single simulated WHTC cycle without statistical uncertainty analysis. Full article

Objectives: The aim of the present study was to evaluate the efficacy and safety of etoricoxib–tramadol 120 mg/100 mg (Eto-Tr) in acute moderate-to-severe pain. Methods: Eto-Tr once a day (n = 29) or naproxen 220 mg + tramadol 50 mg (Nap-Tr) every 12 h (n = 28) were administered after a third molar extraction for three days. Pain intensity difference at 4 h (PID4) was determined as the primary outcome. In addition, total pain relief (TOTPAR), trismus control, and adverse events were addressed. Results: The population PID4 score was 0 mm (Nap-Tr IQR 13 mm; Eto-Tr IQR 35 mm; p = 0.182). No differences for PID scores were observed (1 h to 72 h). TOTPAR increased gradually from 35.71% (Nap-Tr) and 39.39% (Eto-Tr) at 4 h to 67.86% (Nap-Tr) and 58.62% (Eto-Tr) at 72 h. Sustained pain relief over time and clinically meaningful trismus reduction was also observed (Nap-Tr: 4 mm [IQR 28.10] vs. Eto-Tr: 9.8 mm [IQR 12.3], p = 0.175). Common adverse events were notified [Nap-Tr (n = 5, 19%); Eto-Tr (n = 8, 27%)]. Conclusions: The once-daily administration of Eto-Tr 120 mg/100 mg showed similar efficacy and safety to conventional treatment in moderate-to-severe acute pain. The once-daily regimen together with a multimodal analgesia represents a suitable patient-centered alternative for pain management. Full article

Background: Tuberculosis remains a significant global health issue, and the rise of drug-resistant strains is becoming increasingly concerning. Currently, treatment options are limited to systemic regimens; however, developing topical drug delivery systems could offer advantages for treating cutaneous tuberculosis (CTB) when applied directly to the lesions. We developed topical emulsions using the self-emulsification mechanism that combine fixed doses of isoniazid (INH) and rifampicin (RIF) using a quality-by-design approach. Methods: Preformulation studies pertaining to drug solubility in various solvents, the construction of pseudoternary diagrams to identify self-emulsification regions for each tested excipient combination, and the preparation of checkpoint formulations were conducted and visually examined. Formulations displaying no physical instabilities were subsequently exposed to characterization experiments, including droplet size determination, zeta potential, size distribution, viscosity, pH, self-emulsification, cloud point, robustness to dilution, and thermodynamic stability assessment. Three selected formulations were consequently subjected to membrane release experiments, followed by skin diffusion studies, and INH and RIF stability in these emulsions was determined, because these drugs have a known interaction. Conclusions: While incorporating essential oils in a topical formulation improved RIF solubility, it also resulted in several instabilities. RIF exhibited greater susceptibility to degradation under higher temperatures and lower pH conditions. However, drug release from all formulations tested was confirmed. Notably, olive oil microemulsions demonstrated the most favorable characteristics for dermal drug delivery; nonetheless, drug diffusion into and through the skin (which was not desired) could not be quantified. Despite these challenges, the findings indicate that topical drug delivery systems using the self-emulsification process can facilitate the direct treatment of CTB. Full article

Background/Objectives: Fixed-dose combinations (FDCs) offer significant advantages for patients and healthcare systems by improving adherence and reducing pill burden. However, developing multi-drug formulations remains challenging due to complexities in drug compatibility, stability, and dissolution behavior. The COVID-19 pandemic has necessitated innovative therapeutic approaches. This study aims to develop and evaluate an FDC containing FR (an antiviral drug) and RT (a PDE4 inhibitor) for potential COVID-19 treatment. Methods: The proposed dual-layer FDC was formulated to achieve immediate release of RT using Klucel EXF and controlled release of FR using a combination of Klucel HXF and Compritol ATO888. Critical quality attributes, including drug–excipient compatibility, solid-state properties, tablet uniformity, and dissolution kinetics, were assessed. RT and FR quantification methods were developed and validated per international guidelines. Compatibility studies were conducted by combining excipients in fixed ratios with APIs, followed by stability testing. Results: No degradation or adverse interactions were observed between APIs and excipients. RT exhibited rapid dissolution within 30 min, while FR release was effectively controlled through a gel-forming matrix and lipid barrier. Bulk powder and tablet physical parameters met pharmacopeial standards, and content uniformity between layers was maintained. The formulation demonstrated a stable dissolution profile for both drugs, ensuring consistent drug release. Conclusions: The novel FDC of RT and FR exhibits favorable physicochemical properties, a stable dissolution profile, and potential for improved treatment efficacy in COVID-19 patients. By optimizing drug release mechanisms and ensuring formulation stability, this FDC could serve as a pharmaco-economically viable alternative to existing therapies, enhancing patient compliance and treatment outcomes. Full article

Background and Objectives: Elevated blood sugar poses an increasingly significant challenge to healthcare systems worldwide. We aimed to assess the efficacy of the SGLT-2i class in achieving metabolic control in patients with T2DM within a real-world standard-of-care regimen. Material and Methods: A prospective analysis was conducted over 6 months including individuals receiving care in an outpatient department, with baseline assessments and follow-ups at 3 and 6 months. Results: A total of 280 patients were assessed, with a mean age of 63.69 ± 9.16, 53.9% of which were males, with a mean DM duration of 9.06 ± 5.64 years, and a DM duration varying from 6 months to 24 years. Discussion: Real-world evidence bridges the gap between guidelines and practice. It emphasizes the need to overcome clinical inertia in order to optimize patient outcomes and contributes to the body of evidence supporting the efficacy of fixed-dose SGLT-2i combinations in managing T2DM and associated comorbidities. Conclusions: We demonstrate the significant clinical and therapeutic impact of SGLT-2i in T2DM patients in a real-world setting. This class of medication not only positively influences glycemic and weight control but also reduces CV risk factors and visceral adiposity. Full article

Background/Objectives: Using a combination of analgesics allows for the use of lower doses of each, therefore, lowering risk of side effects. The study aims to estimate the bioavailability (pharmacokinetics of enantiomers and metabolites, as well as linearity and sex-related effects) of fixed doses combinations of Ibuprofen/Tramadol via an intravenous (IV) vs. oral route, and it is interesting to bridge the gap of equipotent doses by different routes. Methods: This was a randomized, open-label, crossover, five-period pharmacokinetics clinical trial, in which a single dose of each formulation [four different strengths of Ibuprofen 400 mg/Tramadol HCl (30, 31.5, 33, 37.5 mg), intravenous; Ibuprofen/Tramadol HCl 400 mg/37.5 mg, granules for oral solution], were administered to healthy volunteers. Enantiomers of Ibuprofen, of Tramadol, and of its main active metabolite O-desmethyl-Tramadol (M1) were measured, and pharmacokinetic parameters (maximal concentration (Cmax) and area under the concentration curve (AUC)) were estimated. Given the exploratory nature of the study, the sample size was small to provide sufficient power for comparisons of differences across all subgroups. The study was registered at Spanish register of clinical trials (REec), EudraCT code: 2017-001303-77. Results: Twelve subjects were recruited. Different patterns of rate and amount of the studied analytes are shown for oral and the several strengths of IV drugs tested. Ibuprofen, with an absolute oral bioavailability of 91%, showed an equivalent AUC of oral and IV administration. Tramadol showed an absolute oral bioavailability of 80%. Conclusions: Intravenous administration of Tramadol produces higher bioavailability (Cmax and AUClast) of the parent drug and lower of M1, than oral route. Dose normalized Cmax and AUClast of Tramadol and M1 were into the bioequivalence interval. Upon our pharmacokinetics study results, the intravenous dose of Tramadol should not be reduced when switching from oral dosing. No significant differences attributable to sex, once corrected by weight, were found. Full article

Background: Accurate reconstruction and quantification in the post-therapy SPECT/CT imaging of ¹⁶⁶Ho microspheres for hepatic malignancies is crucial for treatment evaluation. This present study aimed to explore the impact of the OSEM reconstruction parameters on SPECT/CT image features for dose distribution determination, using Hybrid Recon™ (Hermes Medical Solutions AB) and full Monte Carlo (MC) collimator modeling. Methods: Image quality and activity quantification were assessed through two acquisitions of the Jaszczak phantom using a Siemens Symbia Intevo Bold SPECT/CT system. The datasets were reconstructed using the OSEM method, with variations in the number of iterations for 15 and 8 subsets, both with and without full MC collimator modeling. Contrast recovery coefficient (${\mathrm{Q}}_{\mathrm{H}}$), coefficient of variation (CV), contrast-to-noise ratio (CNR), calibration factor (CF), and activity recovery coefficient (ARC) were calculated and used to evaluate image quality and activity quantification. Results: Reconstructions with 5 iterations and 15 subsets, as well as 10 iterations and 8 subsets, were selected as the most suitable for ¹⁶⁶Ho imaging, as they provided higher ${\mathrm{Q}}_{\mathrm{H}}$ and ARCs. Incorporating full MC collimator modeling in both reconstructions led to significant improvements in image quality and activity recovery. The CFs remained consistent for a fixed value of 15 and 8 subsets, with values of (14.9 ± 0.5) cps/MBq and (14.6 ± 0.5) cps/MBq, respectively. However, when applying full collimator modeling, the CF values decreased to a range between 10.9 and 12.1 cps/MBq. Conclusions: For ¹⁶⁶Ho SPECT/CT imaging, OSEM (with either 5 iterations and 15 subsets or 10 iterations and 8 subsets) combined with full MC collimator modeling yielded superior image quality and quantification results. Full article