Head and neck venous thrombosis secondary to pediatric otolaryngologic infection.

OBJECTIVES: Head and neck venous thrombosis is a rare but potentially devastating complication of childhood otolaryngologic infections. This study examines the presentation and management of this condition. METHODS: A retrospective chart review was performed on all pediatric patients with otolaryngologic infections complicated by cranial and cervical venous thrombosis at a tertiary children's hospital from 2007 to 2018. Patient demographics, presentation, site of infection, thrombosis location, implicated pathogen, length of hospital stay, need for surgery, and anticoagulant regimen were assessed. RESULTS: This study included 33 patients (mean age, 7.5 years; age range, 0.8-17 years; 19 [58%] male). The most common infection source was otologic (n = 20), followed by ophthalmic and sinonasal pathology (n = 9), and neck infections (n = 4). The most common site of thrombosis secondary to ear pathology was the sigmoid sinus. The ophthalmic veins were the most common site of thrombosis for ophthalmic/sinonasal infections. Nine CN VI palsies, one CN VII palsy, and one CN III palsy were observed. Twenty-six subjects (79%) required surgical intervention. All those who experienced a nerve palsy required surgery. Length of hospitalization significantly differed with the stay for a neck infection complicated by thrombosis longer compared to otologic and sinonasal infections (F[2,30] = 7.08, p = 0.003). Length of hospital stay was significantly correlated with admission temperature (r = 0.506, p = 0.003) and CRP (r = 0.400, p = 0.03) but not WBC (r = 0.181, p = 0.31). Culture growth predominantly isolated a single causative organism rather than polymicrobial involvement. Forty-eight species were identified, most (n = 41/48, 85%) being Gram-positive bacteria. Alpha-hemolytic Streptococcus was the most common isolate from children with vessel thrombosis secondary to ear infections, with Streptococcus pyogenes predominant in sinonasal infections and Staphylococcus aureus the most common in neck abscesses. There was significant variability in anticoagulation management within the patient population, but no bleeding complications were documented. Most patients had no evidence of underlying thrombophilia (n = 15); for those with positive hypercoagulability screens, the most common positive marker was the presence of lupus inhibitor (n = 6). CONCLUSION: Venous thrombosis resulting from adjacent otolaryngologic infection is a serious complication requiring proper recognition and management. The involved vasculature and cranial nerve findings are dependent on the anatomic location of the underlying infection. Cranial neuropathies in the presence of these infections should prompt evaluation for possible thrombosis.

Predicting Novel Therapies and Targets: Regulation of Notch3 by the Bromodomain Protein BRD4.

Systematic approaches for accurate repurposing of targeted therapies are needed. We developed and aimed to biologically validate our therapy predicting tool (TPT) for the repurposing of targeted therapies for specific tumor types by testing the role of Bromodomain and Extra-Terminal motif inhibitors (BETi) in inhibiting BRD4 function and downregulating Notch3 signaling in ovarian cancer.Utilizing established ovarian cancer preclinical models, we carried out in vitro and in vivo studies with clinically relevant BETis to determine their therapeutic effect and impact on Notch3 signaling.Treatment with BETis or siRNA-mediated BRD4 knockdown resulted in decreased cell viability, reduced cell proliferation, and increased cell apoptosis in vitro. In vivo studies with orthotopic mouse models demonstrated that treatment with BETi decreased tumor growth. In addition, knockdown of BRD4 with doxycycline-inducible shRNA increased survival up to 50% (P < 0.001). Treatment with either BETis or BRD4 siRNA decreased Notch3 expression both in vitro and in vivo BRD4 inhibition also decreased the expression of NOTCH3 targets, including HES1 Chromatin immunoprecipitation revealed that BRD4 was present at the NOTCH3 promoter.Our findings provide biological validation for the TPT by demonstrating that BETis can be an effective therapeutic agent for ovarian cancer by downregulating Notch3 expression.The TPT could rapidly identify candidate drugs for ovarian or other cancers along with novel companion biomarkers.

Effect of changing postoperative pain management on bleeding rates in tonsillectomy patients.

PURPOSE: To review rates of post-tonsillectomy hemorrhage (PTH) at a quaternary medical center, including the impact of narcotic versus nonsteroidal anti-inflammatory drug (NSAID) postoperative pain management. MATERIALS AND METHODS: A retrospective review was performed of tonsillectomies conducted at a single institution between 1/1/2013 and 1/1/2017. The rates of PTH and subsequent intervention were calculated. These were categorized into patients having surgery pre- and post-July 1, 2015, the former group receiving narcotics and the latter ibuprofen with acetaminophen. RESULTS: Of 1351 total tonsillectomies, 3.04% had PTH requiring return to the hospital. 0.74% required no further surgical intervention, whereas 2.30% required secondary surgical control. The bleed rate prior to July 2015 was 3.15%, with 1.05% non-surgical bleeds and 2.10% requiring surgery. Post-July 2015, the bleed rate was 2.92%, with 0.44% non-surgical bleeds and 2.49% requiring surgery. There were no statistically significant differences between the two groups with respect to overall, non-surgical, and surgical hemorrhage rates (p > 0.05). Of the total bleeds, the need for secondary surgery in the narcotic group was 66.7% and 85% in the NSAID group (p = 0.18). During the study period, 36 patients with PTH had their initial tonsillectomy performed at outside institutions; 53% required surgical intervention. CONCLUSIONS: Secondary hemorrhage remains a significant cause of morbidity in post-tonsillectomy patients, often requiring surgical intervention. This review found no increased bleeding risk associated with use of ibuprofen and acetaminophen as opposed to narcotic pain relief. LEVEL OF EVIDENCE: III.

Mycotic Pseudoaneurysm Associated with Skull Base Osteomyelitis Treated with Endovascular Embolization.

Pseudoaneurysms occur due to malformations in arterial wall uniformity, leading to blood collection between the outer arterial layers and resultant outpouching of the vessel. Unlike true aneurysms, pseudoaneurysms do not involve all layers of the blood vessel. Mycotic pseudoaneurysms can occur after associated vessel adventitia infection, leading to transmural dissection. Here we present a case of a 78-year-old man with a history of chronic otitis externa and osteomyelitis who presented with increasing right ear pain with bloody discharge and associated headache. Catheter angiography demonstrated a large pseudoaneurysm in the right middle meningeal artery (MMA) at the base of the skull. Based on the clinical findings and the patient's history, the patient was ultimately diagnosed with mycotic pseudoaneurysms of the MMA. The patient was subsequently treated with antibiotics as well as endovascular embolization and recovered without any complications.

Intracranial Ischemic Infarct Due to Blunt Force Trauma in a High School Football Player.

Ischemic stroke is an uncommon cause of death among teenagers and young adults; however, the etiologies differ when compared to ischemic strokes in older individuals. Large-vessel atherosclerosis and small-vessel disease causing ischemic stroke are rare for the teenage population, while cervicocerebral arterial dissections account for up to 20% of ischemic strokes. Here, we present the case of a 16-year-old male who developed internal carotid artery dissection (ICAD) after a head injury and subsequently developed ischemic stroke and seizures.