Acute and Delayed Intracranial Hemorrhage in Head-Injured Patients on Warfarin versus Direct Oral Anticoagulant Therapy.

INTRODUCTION: Direct oral anticoagulant (DOAC) use for thrombosis treatment and prophylaxis is a popular alternative to warfarin. This study compares rates of traumatic intracranial hemorrhage (ICH) for patients on anticoagulant therapies and the effect of combined anticoagulant and antiplatelet therapies. METHODS: A retrospective observational study of trauma patients was conducted at two level I trauma centers. Patients aged ≥18 years with preinjury use of an anticoagulant (warfarin, rivaroxaban, apixaban, or dabigatran) who sustained a blunt head injury within the past day were included. Patients were evaluated by head CT to evaluate for ICH. RESULTS: Three hundred and eighty-eight patients were included (140 on warfarin, 149 on a DOAC, and 99 on combined anticoagulant and antiplatelet therapies). Seventy-nine patients (20.4%) had an acute ICH, while 16 patients (4.1%) had a delayed ICH found on routine repeat CT. Those on combination therapy were not at increased risk of acute ICH (relative risk [RR] 0.90, confidence interval [CI]: 0.56-1.44; P > 0.5) or delayed ICH (RR 2.19, CI: 0.84-5.69; P = 0.10) compared to anticoagulant use only. Those on warfarin were at increased risk of acute ICH (RR 1.75, CI: 1.10-2.78, P = 0.015), but not delayed ICH (RR 0.99, CI 0.27-3.59, P > 0.5), compared to those on DOACs. No delayed ICH patients died or required neurosurgical intervention. CONCLUSION: Patients on warfarin had a higher rate of acute ICH, but not delayed ICH, compared to those on DOACs. Given the low rate of delayed ICH with no resultant morbidity or mortality, routine observation and repeat head CT on patients with no acute ICH may not be necessary.

Antiplatelet therapy is associated with a high rate of intracranial hemorrhage in patients with head injuries.

BACKGROUND: Antiplatelet agents are increasingly used in cardiovascular treatment. Limited research has been performed into risks of acute and delayed traumatic intracranial hemorrhage (ICH) in these patients who sustain head injuries. Our goal was to assess the overall odds and identify factors associated with ICH in patients on antiplatelet therapy. METHODS: A retrospective observational study was conducted at two level I trauma centers. Adult patients with head injuries on antiplatelet agents were enrolled from the hospitals' trauma registries. Acute ICH was diagnosed by head CT. Observation and repeat CT to evaluate for delayed ICH was performed at clinicians' discretion. Patients were stratified by antiplatelet type and analyzed by ICH outcome. RESULTS: Of 327 patients on antiplatelets who presented with blunt head trauma, 133 (40.7%) had acute ICH. Three (0.9%) had delayed ICH on repeat CT, were asymptomatic and did not require neurosurgical intervention. One with delayed ICH was on clopidogrel and two were on both clopidogrel and aspirin. Patients with delayed ICH compared with no ICH were older (94 vs 74 years) with higher injury severity scores (15.7 vs 4.4) and trended towards lower platelet counts (141 vs 216). Patients on aspirin had a higher acute ICH rate compared with patients on P2Y12 inhibitors (48% vs 30%, 18% difference, 95% CI 4 to 33; OR 2.18, 95% CI 1.15 to 4.13). No other group comparison had significant differences in ICH rate. CONCLUSIONS: Patients on antiplatelet agents with head trauma have a high rate of ICH. Routine head CT is recommended. Patients infrequently developed delayed ICH. Routine repeat CT imaging does not appear to be necessary for all patients. LEVEL OF EVIDENCE: Level III, prognostic.

Unusual clinical presentation of cutaneous angiosarcoma masquerading as eczema: a case report and review of the literature.

An unusual case of cutaneous angiosarcoma clinically mimicking eczema is described. A 98-year-old Caucasian male presented with a 6-month history of a flesh-colored, subcutaneous nodule on his left forehead with contralateral facial erythema and scaling that had been previously diagnosed as eczema. Despite treatments with topical steroids and moisturizers, the condition did not resolve. At our clinic, excisional biopsy of the forehead lesion and scouting biopsies from the contralateral cheek were performed which revealed cutaneous angiosarcoma. The described case illustrates that dermatitis-like features should be considered as a rare clinical manifestation of cutaneous angiosarcoma. It also demonstrates that these lesions may respond well to radiotherapy as a single modality.

Selectivity, directionality, and promiscuity in peptide processing from a Bacillus sp. Al Hakam cyclodehydratase.

The thiazole/oxazole-modified microcins (TOMMs) represent a burgeoning class of ribosomal natural products decorated with thiazoles and (methyl)oxazoles originating from cysteines, serines, and threonines. The ribosomal nature of TOMMs allows for the generation of derivative products from mutations in the amino acid sequence of the precursor peptide, which ultimately manifest in differing structures and, sometimes, biological functions. Employing a TOMM system for the purpose of creating new structures and functions via combinatorial biosynthesis requires processing machinery that can tolerate highly variable substrates. In this study, TOMM enzymatic promiscuity was assessed using a currently uncharacterized cluster in Bacillus sp. Al Hakam. As determined by Fourier transform tandem mass spectrometry (FT-MS/MS), azole rings were formed in both a regio- and chemoselective fashion. Cognate and noncognate precursor peptides were modified in an overall C- to N-terminal directionality, which to date is unique among characterized ribosomal natural products. Studies focused on the inherent promiscuity of the biosynthetic machinery elucidated a modest bias for glycine at the preceding (-1) position and a remarkable flexibility in the following (+1) position, even allowing for the incorporation of charged amino acids and bisheterocyclization. Two unnatural substrates were utilized as the conclusive test of substrate flexibility, of which both were processed in a predictable fashion. A greater understanding of substrate processing and enzymatic tolerance toward unnatural substrates will prove beneficial when designing combinatorial libraries to screen for artificial TOMMs that exhibit desired activities.