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An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous quantitation of doxorubicin (DOX) and sorafenib (SOR) in rat plasma. Chromatographic separation was performed using a reversed-phase column C18 (1.7 μm, 1.0 × 100 mm Acquity UPLC BEH™). The gradient mobile phase system consisted of water containing 0.1% acetic acid (mobile phase A) and methanol (mobile phase B) with a flow rate of 0.40 mL/min over 8 min. Erlotinib (ERL) was used as an internal standard (IS). The quantitation of conversion of [M + H]+, which was the protonated precursor ion, to the corresponding product ions was performed using multiple reaction monitoring (MRM) with a mass-to-charge ratio (m/z) of 544 > 397.005 for DOX, 465.05 > 252.03 for SOR, and 394 > 278 for the IS. Different parameters were used to validate the method including accuracy, precision, linearity, and stability. The developed UPLC–MS/MS method was linear over the concentration ranges of 9–2000 ng/mL and 7–2000 ng/mL with LLOQ of 9 and 7 ng/mL for DOX and SOR, respectively. The intra-day and inter-day accuracy, expressed as % relative standard deviation (RSD%), was below 10% for both DOX and SOR in all QC samples that have drug concentrations above the LLOQ. The intra-day and inter-day precision, expressed as percent relative error (Er %), was within the limit of 15.0% for all concentrations above LLOQ. Four groups of Wistar rats (250–280 g) were used to conduct the pharmacokinetic study. Group I received a single intraperitoneal (IP) injection of DOX (5 mg/kg); Group II received a single oral dose of SOR (40 mg/kg), Group III received a combination of both drugs; and Group IV received sterile water for injection IP and 0.9% w/v sodium chloride solution orally to serve as a control. Non-compartmental analysis was used to calculate the different pharmacokinetic parameters. Data revealed that coadministration of DOX and SOR altered some of the pharmacokinetic parameters of both agents and resulted in an increase in the Cmax and AUC and reduction in the apparent clearance (CL/F). In conclusion, our newly developed method is sensitive, specific, and can reliably be used to simultaneously determine DOX and SOR concentrations in rat plasma. Moreover, the results of the pharmacokinetic study suggest that coadministration of DOX and SOR might cause an increase in exposure of both drugs.

Background: Epilepsy is a common global neurological disorder. About 30% of epileptic patients are managed with anti-epileptic Drugs (AEDs). Since 2000, Levetiracetam (LEV) has been marketed around the world as an AED under the brand name Keppra, and recently more generics are found in the Saudi market as cheaper alternatives. The objective of this study is to evaluate the bioequivalence of LEV brand and generics available in the Saudi market in mice. Methods: Pharmacokinetics (PK), liver function test, and behavioral studies were conducted for LEV brand and generic in different groups of Blab/c mice. Results: PK results show a significance difference in PK parameters mostly evidenced with generic 3, then generic 2. The only significant different between Keppra and generic 1 was in T1/2. In addition, Keppra did not significantly increase liver enzymes in comparison to other generics. On the other hand, other generics showed less favorable results in increasing liver enzymes. Keppra reduced the number and intensity of epileptic attacks, had no mortality rate due to epilepsy, and was associated with less sever seizures attacks. Conclusion: Keppra, the brand form of LEV, has better safety and efficacy profiles in mice compared to 3 generics found in the Saudi market. Therefore, we recommend evaluating the same parameters tested in this study in patients utilizing similar generics and brand to establish the existence of bioequivalence between LEV brand and generics.

Background: The Saudi Food and Drug Authority (SFDA) requires marketing authorization holders to submit a PIL in both Arabic and English language. However, the readability of imprinted and disseminated Patient information leaflets (PILs) was not assessed extensively in Saudi Arabia. This study aims to assess the readability of PIL of antihypertensive drugs in both Arabic and English languages. Method: This study was a descriptive quantitative analysis conducted in Saudi Arabia in August 2021. PILs of all oral antihypertensive medications in Saudi Arabia were included in the study. The Arabic and English PILs were extracted from the Saudi Drugs Information System (SDI) and pharmaceutical companies' registration documents. The study used Flesch-Kincaid grade level to assess the readability of English and sentence length to assess the Arabic texts. Descriptive analyses were used to assess the readability scores and the mean differences. Results: It was found that almost 88% of English PILs were above recommended readability level compared to 79% of Arabic PILs. About 89% of English PILs of generic and 86% of brand-name medications were above the readability cutoff point compared with 83% of Arabic PILs of generic and 68% of brand-name medications. The means of grade level for readability of PILs for the widely used antihypertensive medications including angiotensin II receptor blockers (ARBs), antiadrenergic, diuretics, Beta-blockers (BBs), calcium channel blockers (CCBs), and combination antihypertensive medications, and CCBs were higher than the recommended readability level (p < 0.05). The highest mean grade level for readability among English PILs was for combinations of antihypertensive agents (9.35 ± 1.38, p 0.01) and among Arabic PILs was for ARBs (6.15 ± 1.62, p < 0.01). Conclusions: The majority of PILs of antihypertensive medications were above the recommended readability level that can be understood by the majority of the public, especially among generic medications and the most widely used antihypertensive medications. The study findings highlight the need of implementing guidelines to improve the readability of information imprinted in PILs and adopt new regulations requiring readability assessment for manufactures before submitting the PILs to the SFDA.

الملخص: أهداف البحث: دراسة العلاقة بين مقدار معامل زاوية ''كوب'' ومختلف كثافات العظم لدى المرضى الإناث المصابات بجنف العمود الفقري لدى اليافعات في السعودية، وقياس مدى كثافة العظام في مختلف مناطق أجسامهن. طرق البحث: استخدم البحث نموذج دراسة مقطعية كمية بعدد مناسب من المشاركات. شملت العينة المدخلة ٥٤ مريضة بجنف العمود الفقري لدى اليافعات تراوحت أعمارهن بين ١٠-٢٠ عاما. تم تسجيل معامل زاوية كوب ودرجات ''زد'' في مقياس امتصاص الأشعة السينية ثنائي البواعث لكل من عظمة الفخذ وعظمة الفقرة القطنية، وتم جمعها بين الأعوام ٢٠٠٨-٢٠١٨. النتائج: من بين ٥٤ مريضة، ٤١ منهن كان معامل زاوية كوب لديهن يتراوح بين ٤٠°-٧٠°، و١٣ بمعامل زاوية كوب ٧٠° مقارنة بالمرضى اللاتي معامل زاوية كوب 70°. The mean lumbar bone, right femur, and left femur BMDs were markedly higher in those with Cobb angles ≤70° compared with BMDs in those with Cobb angles >70°. Of the group with Cobb angles ≤70°, six (14.6%) and nine (22.0%) exhibited low BMD according to their lumbar and femoral Z-scores, respectively. Of the group with Cobb angles >70°, eight (61.5%) and nine (69.2%) exhibited low BMD according to their lumbar and femoral Z-scores, respectively. Conclusions: Female AIS patients with greater higher Cobb angles exhibited a significantly higher frequency of low BMDs.

Background/Introduction: Despite advances in the diagnosis and management of breast cancer (BC), it is still associated with high mortality rates. New biomarkers are being developed for the diagnosis, treatment, and prediction of responses of BC. Ceramide (CER), a bioactive sphingolipid, has emerged recently as a useful diagnostic tool in several types of tumors. In this study, we evaluated CER expression in invasive BC and assessed its relation to the molecular subtypes of BC. Materials and methods: The clinical data and histopathological slides of 50 patients with invasive ductal carcinoma were retrieved and reviewed. The cases were then stained with a mouse monoclonal anti-ceramide antibody. Pearson correlation was used to assess the correlation between CER percentage and intensity and other clinical and pathological variables. Results: CER expression showed a direct relationship with estrogen and progesterone receptors Allred scores. However, it showed an inverse relation with tumor grade, HER2/neu status and Ki-67 index. Conclusions: CER expression is likely to be associated with luminal BC molecular subtypes. However, more research is needed to confirm these results and to explore its relation to the different clinical outcomes, including response to treatment and prognosis.

First described by Green in 1832, persistent sciatic artery (PSA) is a rare anomaly classified into 2 types, namely complete and incomplete. We report the case of bilateral PSAs diagnosed by computed tomography angiography (CTA) in a 45-year-old female who presented with a 2-week history of pain and numbness in the left lower limb. Specifically, the CTA showed an incomplete PSA of the right lower limb and a complete PSA of the left lower limb complicated by an aneurysm. Complications of PSA, including aneurysmal rupture, occlusive thrombosis, and distal embolization, are critical as they impose serious hazards to the viability of the lower limbs. Asymptomatic patients with PSA require close surveillance for early detection and proper management of PSA-related complications, as they are prone to early atheromatous degeneration and aneurysm formation.

The present study involves the development of Dipivefrin hydrochloride (DV) containing Poloxamers (P407 and P188)-Carbopol-934 (CP) based thermoresponsive-gels for the management of elevated intraocular pressure (IOP). Optimal formulation was evaluated for gelation temperature (Tgel), physicochemical and viscoelastic properties, in-vitro gel dissolution and drug release studies. The in-vivo safety, precorneal retention, ocular pharmacokinetics and efficacy in reducing IOP were also evaluated. Tgel of DV-containing thermoresponsive-gels were between 35.1 and 38.9 °C and it was Poloxamers and CP concentrations dependent. The optimal formulation (F8), composed of 20% P407, 5% P188 and 0.15% CP (w/v), had a Tgel of 35 °C. Its viscosity indicated good flow at room temperature and ability to convert to gel at ocular temperature and the rheology studies revealed favorable characteristics for its ocular use. In precorneal retention experiment, F8 indicated significantly higher area under concentrations curves as compared to DV-aqueous suspension (DV-AqS). In-vivo ocular pharmacokinetics indicated a significant improvement in ophthalmic bioavailability of epinephrine (active form of DV). F8 was non-irritant to the eyes and showed a successful, continuous and superior ability to reduce IOP compared to DV-AqS in rabbits. In conclusion, our developed system could be an appropriate substitute to the conventional DV eye preparations in the management of elevated IOP.

Itraconazole (ITZ) is a highly effective antifungal agent. However, its oral application is associated with systemic toxicity and poor topical use. The present study aims to improve the antifungal activity of ITZ by loading it into bioadhesive niosomes. This approach is considered to enhance the ocular permeation of ITZ, thereby boosting its efficacy against fungal infections. Therefore, it was encapsulated into niosomes (F1) and subsequently coated with hyaluronic acid (HA; F2), chitosan (CS; F3), or a bilayer of CS/HA (F4). In addition, they were further incorporated into pH-sensitive in situ gels. This dual approach is expected to increase the amount of corneal-permeated ITZ, facilitating more effective management of ocular fungal infection.Firstly, the niosomes were prepared by hydrating proniosomes using span 60, cholesterol, and phospholipid. ITZ-niosomes showed an increase in vesicle size from 165.5 ± 3.4 (F1) to 378.2 ± 7.2 nm (F3). The zeta potential varied within −20.9 ± 2.1 (F1), −29.5 ± 3.1 (F2), 32.3 ± 1.9 (F3), and 22.6 ± 1.3 mV (F4). The high EE% values ranged from 78.1 ± 2.2 % to 86.6 ± 2.9 %. Regarding ITZ release, F1 demonstrated a high release profile, whereas bioadhesive niosomes showed sustained release patterns. Furthermore, in situ gels containing niosomes displayed excellent gelling capacity and viscosity. Remarkably, F3 laden-in situ gels (F3-ISG) demonstrated the highest ex vivo corneal permeability of ITZ and antifungal activity with a safety effect. These results indicate that F3-ISG presents a promising strategy for boosting the ocular delivery of ITZ, that could help in treating ocular fungal infections.

الملخص: أهداف البحث: يصاب حوالي شخص واحد من كل مليون شخص بالهيموفيليا المكتسبة. يعد التشخيص في الوقت المناسب أمرا بالغ الأهمية لإدارة المرض بطريقة مناسبة والوقاية من المضاعفات التي تهدد الحياة. قد يلجأ هؤلاء المرضى في البداية إلى أطباء غير متخصصين وقد يبقون غير مشخصين لسنوات عدة. يهدف هذا الإجماع إلى توفير إرشادات لجميع الممارسين في المملكة العربية السعودية لتشخيص وإدارة الهيموفيليا المكتسبة. طرق البحث: تعكس هذه البيانات الإجماعية الآراء التي تم صياغتها بواسطة مجموعة من أخصائيي أمراض الدم باستخدام عملية منهجية صريحة لتحديد مجالات الاتفاق والاختلاف. النتائج: يمكن استخدام هذا البيان الإجماعي كدليل لجميع الممارسين في المملكة العربية السعودية فيما يتعلق بتشخيص المظاهر السريرية، والعلاقة، وخصائص أعراض النزيف، وإدارة هذه الحالات، مع توجيه خاص للأخصائيين غير المتخصصين. سوف يناقش الإجماع جميع جوانب الإدارة، من التشخيص إلى أساليب العلاج. الاستنتاجات: قد يلجأ مرضى الهيموفيليا المكتسبة في البداية إلى أطباء يفتقرون إلى الخبرة المناسبة في تشخيص وإدارة هؤلاء المرضى. يوفر هذا البيان الإجماعي وثيقة مفصلة لتشخيص وإدارة الهيموفيليا المكتسبة، بتوجيه من أفضل الخبراء في المرض في المملكة العربية السعودية. Abstract: Objectives: Acquired hemophilia affects approximately one in 1 million people. Timely diagnosis is key to appropriate disease management and the prevention of life-threatening complications. Patients with this condition may initially be seen by inexperienced physicians and remain underdiagnosed for several years. This consensus statement is aimed at providing guidelines for all practitioners in the Kingdom of Saudi Arabia (KSA) to diagnose and manage acquired hemophilia A. Methods: This consensus statement reflects the opinions drafted by a group of hematology specialists, who used an explicit systematic process to identify areas of agreement and disagreement. Results: This consensus statement provides a guide for all practitioners in the KSA regarding the diagnosis of clinical presentation, relevance, characteristics of bleeding symptoms, and case management; it additionally provides guidance for non-specialists. All management aspects, including diagnosis and treatment modalities, are discussed. Conclusions: Patients with acquired hemophilia may initially be seen by physicians who lack appropriate expertise in diagnosing and managing this condition. This consensus statement from the premier experts on the disease in the KSA provides details for diagnosing and managing acquired hemophilia.

This study aimed to present findings on a paclitaxel (PTX)-loaded polymeric micellar formulation based on polycaprolactone-vitamin E TPGS (PCL-TPGS) and evaluate its in vitro anticancer activity as well as its in vivo pharmacokinetic profile in healthy mice in comparison to a marketed formulation. Micelles were prepared by a co-solvent evaporation method. The micelle's average diameter and polydispersity were determined using dynamic light scattering (DLS) technique. Drug encapsulation efficiency was assessed using an HPLC assay. The in vitro cytotoxicity was performed on human breast cancer cells (MCF-7 and MDA-MB-231) using MTT assay. The in vivo pharmacokinetic profile was characterized following a single intravenous dose of 4 mg/kg to healthy mice. The mean diameters of the prepared micelles were ≤ 100 nm. Moreover, these micelles increased the aqueous solubility of PTX from ∼0.3 μg/mL to reach nearly 1 mg/mL. While the PTX-loaded micelles showed an in vitro cytotoxicity comparable to the marketed formulation (Ebetaxel), drug-free PCL-TPGS micelles did not show any cytotoxic effects on both types of breast cancer cells (∼100% viability). Pharmacokinetics of PTX as part of PCL-TPGS showed a significant increase in its volume of distribution compared to PTX conventional formulation, Ebetaxel, which is in line with what was reported for clinical nano formulations of PTX, i.e., Abraxane, Genexol-PM, or Apealea. The findings of our studies indicate a significant potential for PCL-TPGS micelles to act as an effective system for solubilization and delivery of PTX.

Preterm labor is a growing health problem that causes newborn death, and safe and effective therapy is significantly needed. Arabin pessaries and progesterone are preventive and therapeutic approaches that can be applied to managing the short cervix; hence, reducing the risk of preterm labor. The main goal of current work is to fabricate a novel nanofiber formulation based on polycaprolactone (PCL) and loaded with progesterone to coat for Arabin pessaries to be used as dual preventive and therapeutic approaches for local vaginal delivery. Several important criteria were considered in this study to assess the prepared nanofibers (i.e.; nanofiber diameter, progesterone loading efficiency, progesterone release profiles and in vitro cytotoxicity assessment). The results showed a dimeter of 397 ± 88 nm, drug loading of 142 ± 3 µg/mg and encapsulation efficiency of 99 ± 2 % for the progesterone-loaded nanofibers. Approximately, 17 % of progesterone was released from the nanofibers after 90 days. The in vitro assessment showed that the application of progesterone is safe upon 24 and 48-hours incubation on HFF-1 cell line at concentrations ≤ 32 µg/mL and within 72-hours at a dose of ≤ 8 µg/mL. To conclude, the data recommended that progesterone-loaded nanofibers can coat the Arabin pessaries with the potential of being a safe and effective dual preventive and therapeutic tool for preterm labor.

The goal of this research was to prepare and characterize nanonized particles of the antifungal drug, fluconazole (FLZ) using antisolvent precipitation nanonization technique to improve its ocular permeation. The impact of various concentrations of different stabilizers, namely Pluronic F-127 (PL F 127), Kollicoat IR (KL), hydroxypropyl methylcellulose E3 (HPMC), xanthan gum (XG), polyvinyl pyrrolidone K30 (PVP), and sodium lauryl sulfate (SLS) upon the resulting nanoparticles was investigated. Additionally, the ex vivo release of the FLZ nanonized particles from ophthalmic gel bases was studied by using goat cornea, and the ocular pharmacokinetics of appropriate ophthalmic gel base containing optimized drug nanoparticle formula compared to the untreated drug were studied in rabbits. FLZ nanoparticles were successfully prepared with different concentrations of stabilizers. However, the effects of these stabilizers on nanoparticle size and zeta potential values varied according to the concentration and type of stabilizer used. Based on differential scanning calorimetry, the drug was in its amorphous state in the tested nanoparticle formulations. The results of ex vivo ocular diffusion of the FLZ nanoparticle gel formulations revealed an improvement compared to that with the FLZ untreated gel. Nanoparticle formula (F3) prepared by using 5% PL F127 showed small particle size (352 ± 6.1 nm) with zeta potential value of −18.3 mV with highest ex vivo release rate from goat cornea (100% after 6 h). Moreover, the AUC0-8h from ocular application of FLZ from sodium alginate gel containing nanoparticle formula F3 was 1.4-fold higher than that after its administration in the untreated formula. Based on our findings, the ophthalmic gel formulations containing FLZ nanoparticles enhanced drug corneal permeation and improved the ocular pharmacokinetic parameters.

Objectives: Purchasing medicinal products from the internet has become more popular in the last three decades. Understanding consumers’ use and perception of the safety of medicinal products obtained online is essential. Therefore, this study aims to evaluate the extent of medicines purchased from the internet in Saudi Arabia, types of products, sources of information, the satisfaction, the motivational factors, and estimate consumers’ vigilance and tendency to report ADRs if occurred. Design: A prospective cross-sectional study using a custom-designed questionnaire was conducted among community adults in Saudi Arabia, age ≥ 18. Setting: Evaluation of community subjects' perception towards buying medicinal products was done through the internet in Saudi Arabia from 1st July 2020 until the end of August 2020. Main outcome measure(s): The main outcome of the study was purchasing medicinal products from the internet (Yes, No). Results: Overall, 36% of the study participants (n = 643) have ever bought medicinal products from the internet (Table 2). Of those, the most obtained was herbal medicine, supplements, or cosmetics (61.3%). Motivational factors towards purchasing medicinal products from the internet were mostly positive, with the most commonly reported agreed motivational factors were lower cost (55.7%), easy online access (54.1%), a wide variety of products (52.6%), and more privacy (43.6%). Around 60.4% of participants believed that buying medicinal products from the internet can be safe. The most perceived risk was the difficulty of distinguishing between registered online pharmacies and other unlicensed commercial websites, with only 32.7% of the participants distinguishing between registered and unlicensed commercial websites. Conclusions: This study sheds light on the consumers’ use and perception of the safety and risks of medicinal products purchased from the internet. The study findings noticeably describe the great need to increase safety awareness about obtaining medicinal products from the internet among the Saudi community.

Introduction: Trigeminal schwannoma is a rare, benign, solitary tumor arising from the trigeminal nerve. Patients commonly present with symptoms such as facial pain and paraesthesia. Multiple approaches have been introduced to access the intracranial and infratemporal fossae. Case presentation: A 39-year-old female patient complains of a mild headache on the right side, with right vision and hearing loss, right facial weakness, and dysphagia. The CT and MRI indicated a large dumbbell-shaped mass extending across the right side of the skull base, from the middle cranial fossa to the infratemporal fossa. An endoscopic endonasal approach allows a more detailed view of the midline structures by drilling the pterygoid bone and dissecting the pterygoid muscle. Conclusion: The endonasal endoscopic approach is an excellent method for patients with trigeminal schwannoma in intracranial and infratemporal fossae. Familiarity with the microsurgical anatomy of the infratemporal fossa dissection techniques via anterior and lateral approaches helps provide the best results and achieve the goal of tumor removal with minimal morbidities.

Since the advent of antibiotics, major spontaneous tonsillar hemorrhage is extremely rare. The majority of the spontaneous tonsillar hemorrhage events is associated with acute or chronic tonsillitis, coagulopathies, or tonsillar cancer. Here, we report a very rare case of spontaneous tonsillar hemorrhage in a 7 year old girl managed by emergency tonsillectomy and IV antibiotic with no complications. Keywords: Pediatric spontaneous tonsillar hemorrhage, Emergency tonsillectomy, Bleeding tonsils

Summary: Steroid hormone receptors are simultaneously active in many tissues and are capable of altering each other’s function. Estrogen receptor α (ER) and glucocorticoid receptor (GR) are expressed in the uterus, and their ligands have opposing effects on uterine growth. In endometrial tumors with high ER expression, we surprisingly found that expression of GR is associated with poor prognosis. Dexamethasone reduced normal uterine growth in vivo; however, this growth inhibition was abolished in estrogen-induced endometrial hyperplasia. We observed low genomic-binding site overlap when ER and GR are induced with their respective ligands; however, upon simultaneous induction they co-occupy more sites. GR binding is altered significantly by estradiol with GR recruited to ER-bound loci that become more accessible upon estradiol induction. Gene expression responses to co-treatment were more similar to estradiol but with additional regulated genes. Our results suggest phenotypic and molecular interplay between ER and GR in endometrial cancer. : Estrogen receptor α (ER) and glucocorticoid receptor (GR) are expressed in the uterus and have differential effects on growth. Vahrenkamp et al. find that expression of both receptors is associated with poor outcome in endometrial cancer and that simultaneous induction of ER and GR leads to molecular interplay between the receptors. Keywords: estrogen receptor, glucocorticoid receptor, endometrial cancer

The current study was conducted to examine the rheological properties and the performance characteristics of polymer-modified asphalt binders at various temperatures. Different types and concentrations of polymers were used; including Styrene Butadiene Styrene (SBS) with or without a cross linker, Honeywell (HW) and polyphosphoric acid (PPA) which were added based on the total weight of different Performance Grade bitumen contents. Two methodologies (traditional Superpave and zero shear rate viscosity (ZSV)) were used for comparing binder viscosity and mixing and compaction temperatures. Theory of ZSV measurement was used to assess the rheological characteristics of the asphalt binder while a rotational viscometer device was used to measure the relation of viscosity changes with shear rate for neat and modified Iraqi asphalt binders. The Cross Williamson model was used for the simulation of the viscosity–shear rate dependency for each of the studied temperatures. From the results, there were changes in the rheological properties of the bituminous binders after the modification process. The neat bitumen showed improved rheological properties after mixing with the modifiers. It was noticed that increases in the percentage of polymer had no effect on the calculated mixing and compaction temperatures by ZSV; however, an increase of about 8% was observed with the traditional system. Furthermore, the two methods were observed to provide slightly different values for the viscosity when applied over a considerable range of test temperature. For the modified binders, they showed different mixing and compaction temperatures when ranked according to their Superpave grading protocol or their ZSV. The ZSV for mixing temperature was lower by about 42–54 °C compared to the Superpave method. Keywords: Zero Shear Viscosity, Polymers, Rheology, Modified Asphalt, Superpave Grading, Shear Rate

Background: Congenital fibrinogen deficiency is an ultra-rare disorder in which patients can experience severe and/or frequent bleeding episodes (BEs). Here, we present the largest prospective study to date on the treatment of this disorder., Methods: Hemostatic efficacy of human fibrinogen concentrate (HFC; FIBRYGA ® , Octapharma AG) for treatment of bleeding or surgical prophylaxis was assessed by investigators and adjudicated by an independent data monitoring and endpoint adjudication committee (IDMEAC) according to a four-point scale, using objective criteria. Thromboelastometry maximum clot firmness (MCF) was also determined., Results: Twenty-five afibrinogenemia patients were treated with HFC: 24 for on-demand treatment of 89 BEs, and nine as prophylaxis for 12 surgeries. For BEs, treatment success (rating of excellent or good) evaluated by investigators was 96.6% (90% confidence interval [CI], 0.92-0.99; two missing ratings, classified as failures) and by the IDMEAC was 98.9% (90% CI, 0.95-0.999). Mean ± standard deviation (SD) increase in MCF was 5.8 ± 2.5 mm one hour after the first HFC infusion (mean ± SD dose, 61.88 ± 11.73 mg/kg). For the 12 surgeries (median [range] HFC dose/surgery, 85.80 mg/kg [34.09-225.36]), intraoperative and postoperative treatment success were both rated 100% (90% CI, 0.82-1.00) by investigators and the IDMEAC. Three adverse events were possibly treatment related, including a moderate case of thrombosis. There were no deaths, no severe allergic or hypersensitivity reactions, and no clinical evidence of neutralizing antifibrinogen antibodies., Conclusions: Human fibrinogen concentrate was efficacious for on-demand treatment of bleeding and as surgical prophylaxis, with a favorable safety profile, in patients with congenital afibrinogenemia., (© 2020 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.)