Appropriate dose of tranexamic acid in the topical treatment of anterior epistaxis, 500 mg vs 1000 mg: A double-blind randomized controlled trial.

AIMS: Patients with epistaxis typically visit the emergency department for initial treatment. According to recent studies, tranexamic acid (TXA) is effective in the treatment of epistaxis. This study compared the therapeutic superiority of saline to that of 500 and 1000 mg doses of topical TXA for the treatment of anterior epistaxis. Materials and methods: This phase 4 clinical trial was a randomized, controlled, and double-blind trial. A total of 152 patients were divided into three groups. Group 1 was treated with 1000 mg TXA, Group 2 with 500 mg TXA, and Group 3 with saline. Results: Based on multinomial logistic regression analysis, the bleeding frequency at the 5th minute was 2.9 times and rebleeding status was 4.3 times less in Group 1 (1000 mg TXA) than in Group 3 (saline). There were no differences between the three groups in terms of side effects or salvage therapy. Conclusion: In addition to its superiority in treatment, 1000 mg of TXA is recommended because of the decreased rate of recurrent bleeding and low incidence of side effects.

Pomalidomide for Epistaxis in Hereditary Hemorrhagic Telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is characterized by extensive telangiectasias and arteriovenous malformations. The primary clinical manifestation is epistaxis that results in iron-deficiency anemia and reduced health-related quality of life. METHODS: We conducted a randomized, placebo-controlled trial to evaluate the safety and efficacy of pomalidomide for the treatment of HHT. We randomly assigned patients, in a 2:1 ratio, to receive pomalidomide at a dose of 4 mg daily or matching placebo for 24 weeks. The primary outcome was the change from baseline through week 24 in the Epistaxis Severity Score (a validated bleeding score in HHT; range, 0 to 10, with higher scores indicating worse bleeding). A reduction of 0.71 points or more is considered clinically significant. A key secondary outcome was the HHT-specific quality-of-life score (range, 0 to 16, with higher scores indicating more limitations). RESULTS: The trial was closed to enrollment in June 2023 after a planned interim analysis met a prespecified threshold for efficacy. A total of 144 patients underwent randomization; 95 patients were assigned to receive pomalidomide and 49 to receive placebo. The baseline mean (±SD) Epistaxis Severity Score was 5.0±1.5, a finding consistent with moderate-to-severe epistaxis. At 24 weeks, the mean difference between the pomalidomide group and the placebo group in the change from baseline in the Epistaxis Severity Score was -0.94 points (95% confidence interval [CI], -1.57 to -0.31; P = 0.004). The mean difference in the changes in the HHT-specific quality-of-life score between the groups was -1.4 points (95% CI, -2.6 to -0.3). Adverse events that were more common in the pomalidomide group than in the placebo group included neutropenia, constipation, and rash. CONCLUSIONS: Among patients with HHT, pomalidomide treatment resulted in a significant, clinically relevant reduction in epistaxis severity. No unexpected safety signals were identified. (Funded by the National Heart, Lung, and Blood Institute; PATH-HHT Clinicaltrials.gov number, NCT03910244).

Intelligent and biocompatible cellulose aerogels featured with high-elastic and fast-hemostatic for epistaxis and wound healing.

Nasal tamponade is a commonly employed and highly effective treatment method for preventing nasal bleeding. However, the current nasal packing hemostatic materials exhibit some limitations, such as low hemostatic efficiency, the potential for causing secondary injury when removed from the nasal cavity, limited intelligence in their design, and an inability to promote the healing of nasal mucosa wounds. Herein, we report the fabrication of a smart cellulose aerogel through the covalent cross-linking of carboxymethyl cellulose (CMC) macromolecules, while incorporating one-dimensional cellulose nanofibers (CNF) and two-dimensional MXene as reinforcing network scaffolds and conductive fillers. The abundant hydrogen and ether bonds in aerogels make them possess high elasticity in both dry and wet states, which can be compressed 100 times at 90 % deformation with a stress loss of <10 % under water. The highly elastic aerogels can be filled into the narrow nasal passages, pressuring the capillaries and reducing the amount of bleeding. Moreover, the strong interface between aerogels and blood can promote red blood cell aggregation, platelet adhesion and activation, activate intrinsic coagulation pathway and accelerate blood coagulation, resulting in excellent hemostatic ability. Furthermore, the aerogels exhibit excellent hemocompatibility and cytocompatibility, making them suitable for wound healing and capable of fully healing wounds within 15 days. Notably, the presence of MXene causes the aerogels to form a conductive network when exposed to blood, enabling them to perform real-time hemostatic monitoring without removing the dressing. This innovative biomedical aerogel, prepared from natural materials, shows excellent potential for applications in rapid nasal hemostasis.

The impact of different anticoagulants and antiplatelets regimens on acute epistaxis outcomes.

BACKGROUND: The impact of anticoagulants (AC) and antiplatelets (AP) on the management of acute epistaxis remains unclear. This study investigated the association between AC/AP therapy and treatment outcomes in patients with acute epistaxis. METHODOLOGY: A retrospective analysis of patients presented to the otolaryngology emergency room with acute epistaxis (2014-2022). Patients were categorized based on their regular medications: AP, dual AP therapy (DAPT), new oral anticoagulants (NOAC), vitamin K antagonists (VKA), or no regular AC/AP use (control group). Outcome measures included rates of minor interventions (chemical or electrical cautery, nasal tamponade), major interventions (endoscopic ligation, embolization), recurrent emergency department visits, admission rates, and duration. RESULTS: 786 patients were included with an average follow-up period of 52.56 ± 20.4 months. Compared to the control group, patients on AP, DAPT, or VKA had significantly higher rates of minor interventions (63.1% vs. 74.4%, 79.6%, and 77.3%, respectively, p < 0.05). DAPT users exhibited a higher rate of major interventions than the control (5.6% vs. 1.3%, p = 0.053). NOAC users showed no significant difference in minor interventions compared to control and required no major interventions. Both NOAC and VKA users had significantly higher rates of recurrent epistaxis events and prolonged hospitalization compared to the control (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: NOAC demonstrated more favorable outcomes than VKA in patients with acute epistaxis, and DAPT use was associated with an increased need for major interventions. These findings suggest a more conservative approach in NOAC users than other AC/AP agents.

Risk Factors and Management Outcomes in Pediatric Epistaxis at an Emergency Department.

BACKGROUND: Most cases of pediatric epistaxis are spontaneous and self-resolve. However, a subset of children may experience significant bleeding and require procedural or medical intervention. OBJECTIVE: We aim to identify risk factors associated with moderate and severe epistaxis in the emergency department (ED) and explore management outcomes. METHODS: We retrospectively reviewed all patients under 22 years old with epistaxis who presented to our ED between 2013 and 2022. Epistaxis severity was defined as mild (required nasal compression or intranasal medications), moderate (required cautery or packing), or severe (required factor replacement, transfusion, hospital admission, or surgery). We performed univariable and multinomial regression analyses, with risk factors and outcomes analyzed according to severity. RESULTS: Of 858 visits, 41 (5%) patients had moderate and 67 (8%) had severe epistaxis. Patients with moderate epistaxis were older than those with mild and severe epistaxis (median 15.6 vs. 8.3 vs. 10.7 years, p < 0.001). In regression analysis, moderate epistaxis was associated with older age, prior ED visit within 72 h, and antiplatelet medication use (p < 0.01). Severe epistaxis was associated with bleeding disorders, nasal procedures within 30 days, and anticoagulation medication use (p ≤ 0.001). Bleeding over 30 min prior to arrival was associated with both moderate and severe epistaxis (p < 0.05). Of the 67 patients with severe epistaxis, 10 (15%) required factor replacement, 28 (42%) required transfusion, 52 (77%) required hospital admission, and 5 (7%) underwent surgery. CONCLUSION: Epistaxis severity is associated with certain risk factors. However, most cases of pediatric epistaxis are mild and do not require intervention or ED evaluation.

Epistaxis and Facial Swelling Due to Nasal Blastomycosis in a Cat.

A 5 yr old castrated male domestic longhair was examined because of left-sided facial swelling and epistaxis. Head computed tomography with contrast identified a mass within the left nasal cavity and multifocal regions of nasal bone osteolysis. Histopathology of nasal mass biopsies and cytology of the facial swelling revealed pyogranulomatous inflammation due to Blastomyces dermatitidis. The cat experienced resolution of clinical signs following 8 mo of treatment with itraconazole. Although rare, clinicians should include blastomycosis on the differential diagnoses list of infectious causes for feline nasal disease if within an endemic area.

Apixaban versus no anticoagulation for the prevention of venous thromboembolism in children with newly diagnosed acute lymphoblastic leukaemia or lymphoma (PREVAPIX-ALL): a phase 3, open-label, randomised, controlled trial.

BACKGROUND: Paediatric patients with acute lymphoblastic leukaemia or lymphoma are at increased risk of venous thromboembolism resulting in increased mortality and morbidity. We hypothesised that apixaban, a direct oral anticoagulant, would safely reduce venous thromboembolism in this patient population. METHODS: PREVAPIX-ALL was a phase 3, open-label, randomised, controlled trial conducted in 74 paediatric hospitals in 9 countries. Participants aged 1 year or older to younger than 18 years with newly diagnosed acute lymphoblastic leukaemia (pre-B cell or T cell) or lymphoblastic lymphoma (B cell or T cell immunophenotype) and a central venous line in place throughout induction were randomly assigned 1:1 to standard of care (SOC, ie, no systemic anticoagulation) or weight-adjusted twice-daily apixaban during induction. Randomisation was performed centrally and stratified by age (those <10 years or those ≥10 years). Participants weighing 35 kg or less were administered 2·5 mg twice daily of apixaban as a 2·5 mg tablet, 0·5 mg tablets, or 0·4 mg/mL oral solution, while those weighing more than 35 kg were administered weight-adjusted prophylactic doses using 0·5 mg tablets or the 0·4 mg/mL oral solution twice daily. Primary outcomes were assessed by a blinded central adjudication committee. The primary efficacy outcome for the intention to treat population was the composite of symptomatic or clinically unsuspected venous thromboembolism, the primary safety outcome was major bleeding, and secondary safety outcomes included clinically relevant non-major (CRNM) bleeding. Patients were screened for venous thromboembolism by ultrasound and echocardiogram at the end of induction. The trial was registered with ClinicalTrials.gov (NCT02369653) and is now complete. FINDINGS: Between Oct 22, 2015, and June 4, 2021, 512 participants were randomly assigned and included in analyses (222 [43%] female and 290 [57%] male; 388 [76%] White, 52 [10%] Asian, 24 [5%] Black or African American, and 48 [9%] other races; and 122 [24%] Hispanic or Latino ethnicity). During a median follow-up period of 27 days (IQR 26-28), 31 (12%) of 256 patients on apixaban had a composite venous thromboembolism compared with 45 (18%) of 256 participants receiving SOC (relative risk [RR] 0·69, 95% CI 0·45-1·05; p=0·080). Two major bleeding events occurred in each group (RR 1·0, 95% CI 0·14-7·01; p=1·0). A higher incidence of CRNM bleeding, primarily grade 1 or 2 epistaxis, occurred in the apixaban group (11 [4%] of 256 participants) compared with the SOC group (3 [1%] of 256; RR 3·67, 95% CI 1·04-12·97, p=0·030). The most frequent grade 3-5 adverse events in both groups were thrombocytopenia (n=28 for the apixaban group and n=20 for the SOC group) or platelet count decreased (n=49 and n=45), anaemia (n=77 and n=74), febrile neutropenia (n=27 and n=20), and neutropenia (n=16 and n=17) or neutrophil count decreased (n=22 and n=25). Five deaths occurred, which were due to infection (n=3 in the SOC group), cardiac arrest (n=1 in apixaban group), and haemorrhagic cerebral sinus vein thrombosis (n=1 in the SOC group). There was one apixaban-related death (coagulopathy and haemorrhage after cardiac arrest of unknown cause). INTERPRETATION: PREVAPIX-ALL is, to our knowledge, the first trial assessing primary thromboprophylaxis using a direct oral anticoagulant in paediatric patients with acute lymphoblastic leukaemia or lymphoma. No statistically significant treatment benefit was identified in participants receiving apixaban. Major and CRNM bleeding were infrequent overall, but a higher incidence of CRNM bleeding (primarily epistaxis in younger children) occurred in participants receiving apixaban. For patients deemed to be at particularly high risk of thrombosis, PREVAPIX-ALL provides encouraging safety data for the use of apixaban in clinical settings in which the potential benefits are thought to outweigh the risk of bleeding. FUNDING: Bristol Myers Squibb-Pfizer Alliance.

[Iron deficiency anemia in a patient with hereditary hemorrhagic telangiectasia. Case report].

Rendu-Osler-Weber disease or hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease. It is characterized by vascular dysplasia with the formation of telangiectasias on the skin, mucous membranes of the respiratory and digestive tracts, arteriovenous malformations (AVMs) in the internal organs, which is manifested by bleeding. Diagnosis is based on Curacao criteria: recurrent and spontaneous nosebleeds, multiple telangiectases on the characteristic localizations, AVMs in one or more of the internal organs, a family history of HHT (i.e. first-degree relative who meets these same criteria for definite HHT). Therapy is aimed at preventing and stopping gastrointestinal, nosebleeds, correction of iron deficiency anemia. A promising method of therapy is the use of angiogenesis inhibitors, in particular bevacizumab. The article presents a description of a clinical case of HHT in a 49-year-old woman with telangiectisia on the mucous membrane of the tongue, gastrointestinal tract and liver AVMs.

Treatments of Epistaxis in Hereditary Hemorrhagic Telangiectasia: Systematic Review and Network Meta-Analysis.

PURPOSE OF REVIEW: To analyze and compare the effects of epistaxis treatments for Hereditary Hemorrhagic Telangiectasia (HHT) patients. RECENT FINDINGS: Of total of 21 randomized controlled trials (RCT), the data from 15 RCTs (697 patients, 7 treatments: timolol, propranolol, bevacizumab, doxycycline, tacrolimus, estriol/estradiol, and tranexamic acid) were pooled for the meta-analyses while the other 6 studies (treatments: electrosurgical plasma coagulation, KTP laser, postoperative packing, tamoxifen, sclerosing agent, and estriol) were reviewed qualitatively. When compared to placebo, propranolol offered the most improved epistaxis severity score, mean difference (MD), -1.68, 95% confidence interval (95%CI) [-2.80, -0.56] followed by timolol, MD -0.40, 95%CI [-0.79, -0.02]. Tranexamic acid significantly reduced the epistaxis frequency, MD -1.93, 95%CI [-3.58, -0.28]. Other treatments had indifferent effects to placebo. Qualitative analysis highlighted the benefits of tamoxifen and estriol. The adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol were significantly reported. Propranolol, timolol, tranexamic acid, tamoxifen, and estriol were effective treatments which offered benefits to HHT patients in epistaxis management. Adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol should be concerned.

Use of tranexamic acid-soaked NasoPore® in the emergency department, to reduce epistaxis admissions.

OBJECTIVES: The aim of this study was to assess the efficacy of a new emergency department (ED) intervention for the management of non-traumatic, anterior epistaxis in adult patients, aiming to reduce epistaxis admissions. DESIGN: A new epistaxis pathway was introduced for use by ED practitioners. This was disseminated in ED through an educational campaign by the ear, nose and throat team. A tranexamic acid (500 mg/5 mL)-soaked NasoPore® packing step was introduced for epistaxis which did not terminate following 10 min of simple first aid. The pathway was utilised for adult patients presenting with non-traumatic, anterior epistaxis. Pre- and post-implementation periods were defined, and all adults attending ED with non-traumatic, anterior epistaxis were included. Pre- and post-implementation epistaxis treatment interventions, admission rates and re-attendance rates were recorded by retrospective audit and compared. RESULTS: In the post-implementation group, epistaxis admissions were 51.7% (p < .05) lower than in the pre-implementation group, as a proportion of the total number attending ED with epistaxis during these periods. CONCLUSIONS: The significant reduction in epistaxis admissions demonstrates that this ED intervention is beneficial for patient outcomes.

A giant invasive macroprolactinoma with recurrent nasal bleeding as the first clinical presentation: case report and review of literature.

BACKGROUND: Giant prolactinoma (> 4 cm in dimension) is a rare disorder. Invasive macroprolactinoma has the potential to cause base of skull erosion and extend into the nasal cavity or even the sphenoid sinus. Nasal bleeding caused by intranasal tumor extension is a rare complication associated with invasive giant prolactinoma. We report a case of giant invasive macroprolactinoma with repeated nasal bleeding as the initial symptom. CASE PRESENTATION: A 24-year-old man with an invasive giant prolactinoma in the nasal cavity and sellar region who presented with nasal bleeding as the initial symptom, misdiagnosed as olfactory neuroblastoma. However, markedly elevated serum prolactin levels (4700 ng/mL), and a 7.8-cm invasive sellar mass confirmed the diagnosis of invasive giant prolactinoma. He was treated with oral bromocriptine. Serum prolactin was reduced to near normal after 6 months of treatment. Follow-up magnetic resonance imaging showed that the sellar lesion had disappeared completely and the skull base lesions were reduced. CONCLUSION: This case is notable in demonstrating the aggressive nature of untreated invasive giant prolactinomas which can cause a diagnostic difficulty with potential serious consequences. Early detection of hormonal levels can avoid unnecessary nasal biopsy. Early identification of pituitary adenoma with nasal bleeding as the first symptom is particularly important.

Rhinologist Use of Antibiotics With Nasal Packing for Epistaxis.

BACKGROUND: There is limited evidence supporting the usage of prophylactic antibiotics in the setting of nasal packing for epistaxis. It is unclear what current antiobiotic usage patterns are by otolaryngologists. OBJECTIVES: Characterize the antibiotic prescribing practices employed by otolaryngologists in the management of epistaxis patients treated with packing as well as the underlying rationale. Explore the impact of experience, geography, and academic affiliation on treatment decisions. METHODS: An anonymous survey of antibiotic prescribing patterns for patients with epistaxis requiring nasal packing was distributed to all physician members of the American Rhinologic Society. Responses to each question were descriptively summarized including 95% confidence intervals and were linked to demographics using Fisher's exact tests. RESULTS: One thousand one hundred and thirteen surveys were distributed with 307 responses (27.6%). Antibiotic prescription rates varied based on packing type, with 20.0% prescribing antibiotics for dissolvable packing compared to 84.2% to 84.6% for nondissolvable packing. The absorbance of nondissolvable packing does not impact the decision to prescribe antibiotics (P > .999). Precisely 69.7% (95% CI: 64.0%-74.8%) stop antibiotics immediately following packing removal. Precisely 85.6% (95% CI: 81.6%-89.9%) cite the risk of toxic shock syndrome (TSS) when prescribing antibiotics. Notable regional differences include greater utilization of amoxicillin-clavulanate in the Midwest (67.6%) and Northeast (61.4%) as compared with the South (42.1%) and West (45.1%) (P = .013). Further, years in practice were positively associated with several patterns including prescribing antibiotics for patients with dissolvable packing (P = .008), citing prevention of sinusitis as a rationale for antibiotic use (P < .001), and a higher likelihood of having treated a patient with TSS (P = .002). CONCLUSIONS: Antibiotic use in patients with epistaxis controlled with nondissolvable packing is common. Treatment patterns are influenced by geography, years in practice, and practice type. LEVEL OF EVIDENCE: 4.

The benefits and risks of non-steroidal anti-inflammatory drugs for postoperative analgesia in sinonasal surgery: a systematic review and meta-analysis.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) have emerged as an alternative to opioids for optimal postoperative pain management. However, the adoption of NSAIDs in sinonasal surgery has been impeded by a theoretical concern for postoperative bleeding. Our objective is to systematically review the efficacy and safety of NSAIDs for patients undergoing sinonasal surgery. METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, and the WHO International Clinical Trials Registry Platform were searched from inception to January 27, 2022. Randomized controlled trials (RCTs) and comparative observational studies in any language were considered. Screening, data extraction, and risk of bias assessment were performed in duplicate. Our outcomes were postoperative pain scores, requirement for rescue analgesia, and postoperative adverse events (epistaxis, nausea/vomiting). RESULTS: Out of 4661 records, 15 RCTs (enrolling 1210 patients) and two observational studies were included. Following endoscopic sinus surgery, there was no difference in pain scores between NSAIDs and non-NSAIDs groups (standardized mean differences [SMD] 0.44 units better, 95% CI -0.18 to 1.05). Following septorhinoplasty, NSAIDs decreased pain scores compared to non-NSAID regimens (SMD 1.14 units better, 95% CI 0.61 to 1.67 units better). Overall, NSAIDs reduced the need for rescue medication with a relative risk (RR) of 0.45 (95% CI 0.24 to 0.84). In addition, NSAIDs decreased the risk of nausea with an RR of 0.62 (95% CI 0.42 to 0.91) and did not increase the risk of epistaxis (RR 0.72, 95% CI 0.23-2.22). CONCLUSION: Among patients undergoing sinonasal surgery, NSAIDs are beneficial in postoperative pain management and avoidance of postoperative nausea without increasing the risk of postoperative epistaxis.

A Systematic Review and Meta-analysis of the Effects of Topical Tranexamic Acid versus Topical Vasoconstrictors on the Management of Epistaxis.

OBJECTIVE: We aimed to evaluate the effectiveness of topical tranexamic acid (TXA) versus topical vasoconstrictors in the management of epistaxis via a systematic review and meta-analysis. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were followed for the meta-analysis. We systematically searched Embase, Web of Science, Cochrane Library, CNKI, and PubMed for randomized controlled trials (from inception to August 2022; no language restrictions), comparing the effect of topical TXA and topical vasoconstrictors on the treatment of epistaxis. The Q test was used to evaluate heterogeneity, and funnel plots were utilized to identify bias. For the meta-analysis, the fixedeffects model was employed, and the t-test was utilized to determine significance. RESULTS: Of 1012 identified studies, 5 were found to be eligible for our analysis. In total, 598 patients were included; 297 of them received TXA and 301 received vasoconstrictors. Hemostasis was more likely to be achieved at the first re-assessment in patients treated with TXA. Subgroup analysis indicated patients treated with TXA to have less likelihood of bleeding recurrence, compared to patients treated with vasoconstrictors. The detected time interval of rebleeding was 10 min, between 24 h to 72 h, and after 7 days, respectively, and the differences were significant between the two groups of patients treated with TXA and vasoconstrictors. CONCLUSION: Topical TXA was associated with better post-treatment hemorrhagic arrest rates compared to topical vasoconstrictors in the management of epistaxis.

Tranexamic acid does not significantly lower postoperative bleeding after endoscopic sinus and nasal surgery.

BACKGROUND: Postoperative epistaxis is a known possibility following endoscopic sinonasal surgery. Tranexamic acid (TXA) has been shown to reduce intraoperative blood loss and improve the visual field. This study evaluated the clinical efficacy of TXA when given at end of surgery to reduce postoperative bleeding. METHODS: This randomized, double-blinded placebo-controlled trial was conducted from April to November 2021. Patients scheduled to undergo endoscopic sinus or nasal surgery were randomized to receive an intravenous dose of 1 g TXA or saline intraoperatively prior to extubation. A 10-in. visual analog scale (VAS) was used to query patients regarding postoperative bleeding each day for 1 week. The medical record was examined to determine the need for additional evaluations or interventions for epistaxis. RESULTS: Forty patients completed the study. The mean ± SD postoperative bleeding VAS for the TXA group on the day of surgery was not significantly different from the saline group (4.82 ± 2.18 in. vs. 5.03 ± 2.14 in., p = 0.8). There were no significant differences between treatment arms on any postoperative day through day 7 (0.67 ± 1.84 in. vs. 0.87 ± 0.99 in., p = 0.7), nor in the reduction in VAS compared to the respective baseline on the day of surgery. There were no significant differences in terms of additional interventions (e.g., additional evaluation in recovery, ED, or clinic, need for packing, or return to the operating room [OR]). CONCLUSION: Although TXA has previously demonstrated efficacy to reduce intraoperative bleeding during sinonasal surgery, when postoperative bleeding is already minimal at baseline, TXA does not appear to reduce it significantly further.

Sclerotherapy for Hereditary Hemorrhagic Telangiectasia-Related Epistaxis: A Systematic Review.

OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is a common inherited condition characterized by mucosal telangiectasias, recurrent epistaxis, and arteriovenous malformations. HHT results in detriment to quality of life. Morbidity and mortality result from severe anemia. Conventional interventions for HHT-related epistaxis include nasal packing, diathermy, lasers, coblation, microdebridement, bevacizumab (topical and systemic), as well as septodermoplasty and nasal closure. Sclerotherapy has been recently described in the literature as a novel approach to HHT-related epistaxis. We hypothesize that sclerotherapy is an effective treatment for HHT-related epistaxis and improves upon the current standard of care for this disease. METHODS: A systematic review was conducted to study sclerotherapy for treating HHT-related epistaxis. Ovid MEDLINE, Ovid EMBASE, Scopus, and Web of Science were searched. Articles were evaluated and excluded according to PRISMA guidelines and reviewed by 2 authors. Reported variables included number of injections, months of follow up, changes in Epistaxis Severity Score, previous treatments used to control epistaxis, and post-injection side effects. RESULTS: Seven studies with a total of 196 patients met inclusion criteria. Three studies reported significant improvement as measured by the Epistaxis Severity Score scale. One reported improvement through subjective patient surveys and others used the Bergler-Sadick scale to measure frequency and intensity of epistaxis. All studies reported improvement in HHT-related epistaxis. The lack of uniform reporting measures however precluded formal meta-analysis. CONCLUSIONS: Based on limited data, sclerotherapy appears to be effective for treating HHT-related epistaxis and offers promise for treating this recalcitrant condition. However, larger, prospective, multi-centered studies using universally validated instruments for epistaxis are needed to definitively evaluate outcomes from sclerotherapy.

Use of xylometazoline in hospitalised infants: is it safe? A retrospective cohort study.

OBJECTIVE: When infants suffer from nasal congestion, xylometazoline spray or drops can be effective to facilitate breathing and drinking. However, case reports on side effects have resulted in international warnings regarding use of xylometazoline in infants. Nevertheless, the incidence of these side effects in hospitalised infants is unknown. DESIGN: Retrospective cohort study. SETTING: Teaching hospital between 2017 and 2021. PATIENTS: Infants under 2 years of age. EXPOSURE: Receiving either saline-only (unlimited frequency, concentration 0.9%) or in combination with xylometazoline (maximum three times daily, concentration 0.025%). MAIN OUTCOME MEASURES: Predefined potential side effects (events), including among others apnoea, nausea, bradycardia, cyanosis and nosebleeds, were extracted from patient records, and the probability to be caused by saline only or xylometazoline-saline was determined using the ADR Probability Scale. RESULTS: We included 898 admitted children during 1285 treatment episodes who received saline with or without xylometazoline. 26 events occurred in the saline-only group (incidence 20.0/100 treatment episodes), and 117 events occurred in the xylometazoline saline group (incidence of 10.5/100 treatment episodes), which was significantly lower (OR 0.47 95% CI 0.29 to 0.75, p=0.002). No definite linked or life-threatening events were found. Three nosebleeds had a probable link to the use of xylometazoline-saline, and all other events could only possibly be linked to saline-only or xylometazoline saline use. The incidence of all events was higher in the saline-only group as compared with the xylometazoline saline group, except nausea, which had a similar occurrence (p=0.65). Results were very similar across (gestational) age groups, gender and reasons for admission. CONCLUSION: The use of low-dose xylometazoline seems to be safe in hospitalised infants.

Randomized, double-blind, placebo-controlled, crossover trial of oral doxycycline for epistaxis in hereditary hemorrhagic telangiectasia.

BACKGROUND: Vascular malformations in hereditary hemorrhagic telangiectasia (HHT) lead to chronic recurrent bleeding, hemorrhage, stroke, heart failure, and liver disease. There is great interest in identifying novel therapies for epistaxis in HHT given its associated morbidity and impact on quality of life. We aimed to measure the effectiveness of oral doxycycline for the treatment of epistaxis and explore mechanisms of action on angiogenic, inflammatory and pathway markers in HHT using a randomized controlled trial. METHODS: 13 HHT patients with epistaxis were recruited from the Toronto HHT Center at St. Michael's Hospital. Recruitment was stopped early due to COVID-19-related limitations. The study duration was 24 months. Patients were randomly assigned to the treatment-first or placebo-first study arm. We compared the change in weekly epistaxis duration and frequency, biomarkers, blood measurements, and intravenous iron infusion and blood transfusion requirements between treatment and placebo. RESULTS: There was no significant difference in the change in weekly epistaxis duration (p = 0.136) or frequency (p = 0.261) between treatment and placebo. There was no significant difference in the levels of MMP-9, VEGF, ANG-2, IL-6 or ENG with treatment. Hemoglobin levels were significantly higher (p = 0.0499) during treatment. Ferritin levels were not significantly different between treatment and placebo. There was no significant difference in RBC transfusions between treatment periods (p = 0.299). CONCLUSION: Overall, our study did not demonstrate effectiveness of doxycycline as a treatment for epistaxis in patients with HHT, though the study was underpowered. Secondary analyses provided new observations which may help guide future trials in HHT. Trial Registration ClinicalTrials.gov, NCT03397004. Registered 11 January 2018 - Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT03397004.

The Use of Beta-Blockers in Hereditary Hemorrhagic Telangiectasia-Related Epistaxis: A Systematic Review.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease affecting 1 in 5000 individuals. Epistaxis is seen in more than 90% of patients with HHT. Severe recurrent epistaxis can significantly decrease quality of life and may be resistant to standard treatment measures. Dysregulation of angiogenesis has been shown to cause the proliferation of abnormal blood vessels. As such, antiangiogenic treatments have been investigated including beta-blockers. OBJECTIVE: A systematic review of the efficacy of beta-blockers in topical treatment of epistaxis in patients with HHT based on epistaxis duration, frequency, and severity. METHODS: A systematic search was performed using the PubMed, Embase via Ovid, and Cochrane databases. The Preferred Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies that measured the efficacy of beta-blocker treatment of epistaxis in patients with HHT were included for qualitative analysis. RESULTS: Five studies (3 randomized controlled trials and 2 case series) with a total of 132 patients were included. Administration (systemically or topically via a spray or gel) of timolol and propranolol showed mixed evidence of improvement in epistaxis frequency, severity, and duration when compared with control groups. The evidence for propranolol appears more promising than timolol. CONCLUSION: There are significant limitations in the included studies, and further investigation with larger longitudinal or randomized prospective trials is recommended. The available evidence suggests that beta-blocker treatment may have a positive effect on HHT-related epistaxis.