Systemic bevacizumab to facilitate anticoagulation in antiphospholipid syndrome and bleeding gastrointestinal angiodysplasia.

Bleeding gastrointestinal angiodysplasia may occur in patients with vasculitis and can be challenging to treat. We describe the novel use of bevacizumab therapy to treat bleeding gastrointestinal angiodysplasia and severe anemia in a patient with eosinophilic granulomatosis with angiitis complicated by antiphospholipid antibody syndrome requiring indefinite warfarin therapy. Studies confirmed multiple bleeding jejunal angiodysplasias unamenable to endoscopic intervention, and the patient required ongoing support with iron infusions and blood transfusions to maintain a minimally acceptable hemoglobin. Given the severe anemia, need for continued, indefinite antiplatelet and anticoagulation therapy, and failure of standard treatment approaches, the patient was initiated on systemic bevacizumab therapy, on the basis of prior documented success of bevacizumab to manage gastrointestinal telangiectasias in patients with hereditary hemorrhagic telangiectasia. Bevacizumab was highly effective, with rapid resolution of bleeding, normalization of hemoglobin, liberation from hematologic support and no adverse events, including no thromboembolic events. Vascular endothelial growth factor (VEGF-A) rose paradoxically after initiation of bevacizumab and normalized after its discontinuation. Given these findings, use of systemic bevacizumab to manage bleeding angiodysplasia in patients with acquired vascular disorders merits further study.

Molecular Interactions between a Fluoride Ion Channel and Synthetic Protein Blockers.

Fluoride ion channels of the Fluc family selectively export F- ions to rescue unicellular organisms from acute F- toxicity. Crystal structures of bacterial Fluc channels in complex with synthetic monobodies, fibronectin-derived soluble ß-sandwich fold proteins, show 2-fold symmetric homodimers with an antiparallel transmembrane topology. Monobodies also block Fluc F- current via a pore blocking mechanism. However, little is known about the energetic contributions of individual monobody residues to the affinity of the monobody-channel complex or whether the structural paratope corresponds to functional reality. This study seeks to structurally identify and compare residues interacting with Fluc between two highly similar monobodies and subjects them to mutagenesis and functional measurements of equilibrium affinities via a fluorescence anisotropy binding assay to determine their energetic contributions. The results indicate that the functional and structural paratopes strongly agree and that many Tyr residues at the interface, while playing a key role in affinity, can be substituted with Phe and Trp without large disruptions.

Providing social support for inpatients: Insights from a virtual medical student initiative.

BACKGROUND: Although the COVID-19 pandemic increased social isolation among hospitalised patients given isolation precautions, visitor restrictions and curtailed interactions with healthcare teams, medical students had limited opportunities for involvement in the care of inpatients. APPROACH: We designed a humanistic and narrative medicine intervention to engage medical students in combating social isolation in hospitalised patients during the COVID-19 pandemic at a tertiary care teaching hospital. In our programme, medical students provided virtual social support to hospitalised patients via phone by providing assistance connecting with family members, having informal conversations and check-ins and writing up patient life narratives. EVALUATION: From April 2020 to March 2021, we received 126 referrals of potentially isolated patients from inpatient medical teams. Fifty patients accepted and received our intervention, including 26 who completed life narratives. Feedback was positive, demonstrating benefit to medical students in learning about humanism and connecting with patients through their life stories. In addition, patients and medical teams felt more supported. We share key operational lessons and resources to facilitate the implementation of this intervention elsewhere. IMPLICATIONS: Our intervention allows medical students to meaningfully contribute to the care of inpatients, support beleaguered inpatient teams and learn important lessons about humanism in medicine. This educational and patient care intervention holds promise in other settings, including beyond the COVID-19 pandemic.

Analysis of self-initiated visits for cervical trauma at urgent care centers and subsequent emergency department referral.

BACKGROUND: Following trauma involving the cervical spine (c-spine), patients often seek care at urgent care centers (UCCs) or emergency departments (EDs). PURPOSE: The purpose was to assess whether UCCs could effectively image acute self-selected c-spine trauma without referral to the ED as well as to estimate costs differences between UCC and ED imaging assessment. MATERIALS AND METHODS: This retrospective study identified patients receiving c-spine imaging at UCCs affiliated with a large academic hospital system from 5/1/-8/31/2021. Patients receiving c-spine X-rays with an indication of trauma following low acuity injury, at UCCs were compared to patients receiving any c-spine imaging in the main campus ED. Medical record numbers were cross-referenced to identify patients receiving imaging at both a UCC and ED within 24 h and within 7 days. Work relative value units (wRVUs) for each UCC and ED imaging type were calculated. For the hypothetical scenario of patients presenting to the ED in the absence of UCC, patients were assumed to receive c-spine computed tomography (CT) without contrast per "usually appropriate" designation by the American College of Radiology Appropriateness Criteria®. RESULTS: Among 143 self-selected, low acuity, patients who received c-spine X-rays at UCCs with an indication of trauma, one required referral to the ED within 24 h and two required referrals to the ED within 7 days. During the 4-month study period, 105.94 wRVUs ($3696.25) were saved by performing a c-spine X-ray in an UCC instead of a CT in the ED, extrapolated to 317.82 wRVUs ($11,088.74) per year. Using the average total costs of an UCC visit versus an ED visit, a total $145,976 was estimated to be saved during the study period or $437,928 per year. CONCLUSION: Offering access for patient-initiated visits at UCCs for low-acuity c-spine trauma may help reduce the need for an ED visit, reducing imaging and healthcare visit costs. SUMMARY STATEMENT: Urgent Care Centers (UCCs) reduced the need for an Emergency Department (ED) referral visit in nearly 100% of self-selected, low acuity, patients with cervical trauma.

Serum complement levels in immune thrombocytopenia: Characterization and relation to clinical features.

BACKGROUND: Complement may contribute to platelet destruction in immune thrombocytopenia (ITP), but serum complement levels of ITP patients are not well defined. This study characterized C3, C4, and CH50 levels from 108 ITP patients in comparison with 120 healthy subjects. METHODS: Results of complement testing performed using commercially available turbidimetric immunoassays were retrospectively analyzed. Mean complement levels in patients with ITP were compared with levels from a sample of 120 healthy subjects, and subgroups of ITP patients were compared. Regression analyses evaluated for relations between low complement levels and disease severity and response to ITP treatments. RESULTS: One hundred eight patients with ITP were included. Mean C3, C4, and CH50 were significantly lower in patients with ITP compared with healthy subjects, largely driven by the 32% of patients with ITP with substantial reductions in one or more assays. Patients requiring treatment had lower mean C4 (18.1 vs 23.1 mg/dL; P = .042) and CH50 (50.4 vs 63.0 mg/dL; P = .004). Mean C3 was higher in splenectomized versus nonsplenectomized patients (120.6 vs 101.0 mg/dL; P = .035). In multivariable analyses, reduced complement did not predict treatment response to corticosteroids, intravenous immunoglobulin, or thrombopoietin receptor agonists but low C4 levels did predict more severe ITP (relative to nonsevere disease, odds ratio for severe/refractory disease: 6.28; 95% confidence interval, 0.75-52.54; P = .090). Complement levels in patients with ITP were generally consistent over repeat measurements. CONCLUSIONS: Complement levels are reduced in one-third of patients with ITP and are associated with more severe disease. Additional study is needed to evaluate if hypocomplementemia is predictive of response to emerging complement-directed therapies.

Avatrombopag for the treatment of immune thrombocytopenia and thrombocytopenia of chronic liver disease.

Avatrombopag is an orally-administered small molecule thrombopoietin receptor agonist. It was the third thrombopoietin receptor agonist approved for the treatment of immune thrombocytopenia and the first approved to treat periprocedural thrombocytopenia in patients with chronic liver disease (thereby providing an alternative to blood transfusions for these patients). Unlike eltrombopag, avatrombopag does not require a 4 hr food-restricted window around its use and it has not been associated with hepatotoxicity in ITP patients or portal vein thrombosis in patients with chronic liver disease. In ITP patients it can often be dosed less frequently than once daily. It is overall well-tolerated with a side-effect profile similar to placebo in randomized clinical trials. This article will review the clinical development, efficacy, safety, and pharmacology of avatrombopag for use in patients with ITP and thrombocytopenia of chronic liver disease.