Bilateral Spontaneous Retrobulbar Hemorrhage due to Warfarin Misuse After Sinus Lavage.

While warfarin has historically played an important role in anticoagulation, direct oral anticoagulants have largely supplanted warfarin due to their improved safety profile and reduced need for monitoring. Herein, the authors report the case of a 64-year-old male who developed severe, bilateral retrobulbar hemorrhage following aggressive nasal lavage due to a supratherapeutic international normalized ratio from warfarin misuse. Visual acuity on arrival was hand-motion OD and no-light-perception OS. He underwent bilateral canthotomy with upper and lower lid cantholysis before transfer to a trauma center where his international normalized ratio was greater than 12. Reversal with vitamin K and prothrombin complex concentrate was initiated. Over the course of hospitalization, vision and swelling continued to improve and at 2-month follow-up his visual acuity was 20/20 OD and no-light-perception OS. This case outlines the risk of bleeding associated with warfarin misuse and advocates for the transition of patients to direct oral anticoagulants when possible.

Expression of LIM domain-binding 3 (LDB3), a striated muscle Z-band alternatively spliced PDZ-motif protein in the nervous system.

LIM domain-binding 3 (LDB3) is a member of the Enigma family of PDZ-LIM proteins. LDB3 has been reported as a striated muscle-specific Z-band alternatively spliced protein that plays an important role in mechanosensory actin cytoskeleton remodeling. This study shows that LDB3 is broadly expressed in the central and peripheral nervous system of human and mouse. LDB3 is predominantly expressed in the adult stages compared to early development and at a significantly higher level in the spinal cord than in the brain. As in skeletal muscle and heart, LDB3 is extensively alternatively spliced in the neurons. Three novel splice isoforms were identified suggesting splicing-dependent regulation of LDB3 expression in the nervous system. Expression of LDB3 in the motor cortex, cerebellum, spinal motor neuron, peripheral nerve, and neuromuscular junction in addition to skeletal muscle indicates important roles for this PDZ-LIM family protein in motor planning and execution. Moreover, expression in the hippocampal neurons suggests roles for LDB3 in learning and memory. LDB3 interactors filamin C and myotilin are also expressed in the spinal motor neuron, nerve, and neuromuscular junction, thereby providing the basis for neurogenic manifestations in myopathies associated with mutations in these so-called muscle proteins.

Myopathy associated LDB3 mutation causes Z-disc disassembly and protein aggregation through PKCα and TSC2-mTOR downregulation.

Mechanical stress induced by contractions constantly threatens the integrity of muscle Z-disc, a crucial force-bearing structure in striated muscle. The PDZ-LIM proteins have been proposed to function as adaptors in transducing mechanical signals to preserve the Z-disc structure, however the underlying mechanisms remain poorly understood. Here, we show that LDB3, a well-characterized striated muscle PDZ-LIM protein, modulates mechanical stress signaling through interactions with the mechanosensing domain in filamin C, its chaperone HSPA8, and PKCα in the Z-disc of skeletal muscle. Studies of Ldb3Ala165Val/+ mice indicate that the myopathy-associated LDB3 p.Ala165Val mutation triggers early aggregation of filamin C and its chaperones at muscle Z-disc before aggregation of the mutant protein. The mutation causes protein aggregation and eventually Z-disc myofibrillar disruption by impairing PKCα and TSC2-mTOR, two important signaling pathways regulating protein stability and disposal of damaged cytoskeletal components at a major mechanosensor hub in the Z-disc of skeletal muscle.

Don't blink: inattentional blindness in radiology report interpretation.

Objectives: Medical errors attributable to inattentional blindness (IAB) may contribute to adverse patient outcomes. IAB has not been studied in the context of reviewing written radiological reports. This cross-sectional, deception-controlled study measures IAB of physicians towards an unexpected stimulus while interpreting written radiological reports. Methods: Physicians and residents from multiple fields were asked to interpret four radiology text reports. Embedded in one was an unexpected stimulus (either an abnormally placed medical exam finding or a non-medical quote from the popular television show Doctor Who). Primary outcomes were differences in detection rates for the two stimuli. Secondary outcomes were differences in detection rates based on level of training and specialty. Results: The unexpected stimulus was detected by 47.8% (n = 43) of participants; the non-medical stimulus was detected more often than the medical stimulus (75.0% vs 21.7%, odds ratio 10.8, 95% confidence interval 4.1-28.7; p < 0.0001). No differences in outcomes were observed between training levels or specialties. Conclusion: Only a minority of physicians successfully detected an unexpected stimulus while interpreting written radiological reports. They were more likely to detect an abnormal non-medical stimulus than a medical stimulus. Findings were independent of the level of training or field of medical practice. Advances in knowledge: This study is the first to show that IAB is indeed present among internal medicine, family medicine, and emergency medicine providers when interpreting written radiology reports.

Transcatheter aortic valve replacement 24 years after cardiac transplantation.

As patient survival after cardiac transplantation has improved over the course of the last several decades, clinicians are now faced with late complications. This includes aortic stenosis which, traditionally, has been treated with reoperative sternotomy and aortic valve replacement. Transcather aortic valve replacement (TAVR) offers a minimally invasive alternative in this high-risk population. A small but growing number of cases of TAVR after heart transplantation in high-risk patients have been reported in the last 10 years; we now present a case of aortic valve replacement via a transcatheter approach 24 years after cardiac transplantation.

Oxytocin Reduces Ethanol Self-Administration in Mice.

BACKGROUND: Excessive ethanol (EtOH) consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces EtOH consumption. METHODS: Male C57BL/6J mice were given access to EtOH (20% v/v) using a model of binge-like drinking ("drinking in the dark") that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2-bottle choice drinking in the home cage. In addition, EtOH (12% v/v) and sucrose (5% w/v) self-administration on fixed- and progressive-ratio schedules were also evaluated. A wide range of systemically administered oxytocin doses were tested (0 to 10 mg/kg) in these models. RESULTS: Oxytocin (0, 0.3, 1, 3, or 10 mg/kg) dose dependently reduced EtOH consumption (maximal 45% reduction) in the binge drinking model, with lower effective doses having minimal effects on general locomotor activity. Oxytocin's effect was blocked by pretreatment with an oxytocin receptor antagonist, and the pattern of contacts (licks) at the EtOH bottle suggested a reduction in motivation to drink EtOH. Oxytocin decreased 2-bottle choice drinking without altering general fluid intake. Oxytocin also reduced operant responding for EtOH and sucrose in a dose-related manner. However, oxytocin decreased responding and motivation (breakpoint values) for EtOH at doses that did not alter responding for sucrose. CONCLUSIONS: These results indicate that oxytocin reduces EtOH consumption in different models of self-administration. The effects are not likely due to a general sedative effect of the neuropeptide. Further, oxytocin reduces motivation for EtOH at doses that do not alter responding for a natural reward (sucrose). While some evidence supports a role for oxytocin receptors in mediating these effects, additional studies are needed to further elucidate underlying mechanisms. Nevertheless, these results support the therapeutic potential of oxytocin as a treatment for alcohol use disorder.