Facilitated Intravascular Ultrasound-Guided Balloon-Assisted Re-Entry Technique for Complex Lower-Extremity Chronic Total Occlusions: The FIBRE Technique.

PURPOSE: To examine the efficacy and safety of the facilitated intravascular ultrasound (IVUS)-guided balloon assisted-re-entry (FIBRE) technique in the treatment of complex, chronic total occlusion (CTO) peripheral arterial lesions. METHODS: A retrospective analysis of 150 patients undergoing peripheral intervention for lower extremity CTO was performed from 2014 to 2017 at two institutions. From the selected population, 10 patients with complex CTOs were identified using the FIBRE technique. Procedural success, 30 day and 6 month patency rates, ankle brachial index improvement, and complications were analyzed. RESULTS: Ten out of 150 patients had the FIBRE technique utilized to attempt revascularization of a complex CTO of a femoropopliteal artery. Technical success was achieved in all 10 patients (100%). There were no intra-operative or peri-procedural complications reported including vessel perforation, bleeding, distal embolization, infrapopliteal vessel compromise, or infection. Arterial studies were obtained at 30 days and 6 months to assess patency in 9/10 patients (90%), with 1 patient being lost to follow up. Of the 9 patients, all 9 (100%) had documented arterial patency at both 30 days and 6 months. All patients reported improvement in symptoms. There were also no reports of re-intervention, amputation, or death at 6-month follow up. CONCLUSIONS: The FIBRE technique is a safe and feasible strategy with excellent technical success in experienced hands for revascularization of complex lower extremity CTO when conventional modalities fail.

Hypochloraemia and 30 day readmission rate in patients with acute decompensated heart failure.

AIMS: Despite recent advances in guideline-directed therapy, rehospitalization rates for acute decompensated heart failure (ADHF) remain high. Recently published studies demonstrated the emerging role of hypochloraemia as a predictor of poor outcomes in patients with ADHF. This study sought to determine the correlation between low serum chloride and 30 day hospital readmission in patients with ADHF. METHODS AND RESULTS: We retrospectively reviewed electronic medical records of 1504 patients who were admitted to one 700 bed US tertiary care centre with the diagnosis of ADHF between June 2013 and December 2014. Of the 1504 reviewed records, 1241 were selected for further analysis. Hypochloraemia (either on admission or at discharge) was identified in 289 patients (23.3%) and was associated with significantly higher 30 day hospital readmission rate or death (42.2% vs. 33.7%, P = 0.008). This association persisted in multivariate analysis when controlling for serum sodium, weight loss, diuretic dose, adjunct thiazide use, serum blood urea nitrogen, and BNP levels (OR: 1.35, 95% CI: 1.02-1.77, P = 0.033); however, the predictive value of the overall model was low (Naglkerke R2 = 0.040). Hypochloraemia was also found to be associated with increased 12 month mortality in our cohort (31.4% vs. 20.2%, P = 0.015) that correlates with the results of previously published studies. CONCLUSIONS: Low serum chloride measured in patients admitted for ADHF is independently but weakly associated with increased 30 day readmission rate and demonstrated low predictive value as a potential biomarker in this cohort.

The utility of S100B level in detecting mild traumatic brain injury in intoxicated patients.

BACKGROUND: S100B is a serum protein known to elevate in patients with brain injury, but it is unknown whether it can predict intracranial pathology in intoxicated patients following mild traumatic brain injury (MTBI). We performed a systematic review and meta-analysis of the English language literature to address this question. MAIN OUTCOMES AND RESULTS: Four prospective cohort trials of serum S100B levels on acutely intoxicated patients with MTBI were included in this meta-analysis. Prevalence of intracranial pathology in the pooled cohort of the intoxicated MTBI patients was 10%, lower than the 15-30% reported in the literature for the general MTBI population. Standard mean difference of serum S100B levels between patients with and without intracranial pathology on CT was 0.73 µg/L (Z = 18.33, P < 0.001). Following sensitivity analysis and hierarchical summary receiver-operating characteristic models, three remaining articles were used for pooled estimates that found that S100B had a sensitivity of 0.96 (95% CI: 0.84-1.00, I2 = 0%) and specificity of 0.63 (95% CI: 0.58-0.68, I2 = 86.8%) with a high negative predictive value (100%, 95% CI: 95.14-100, I2 = 0%) and a negative LR of 0.06 (95% CI: 0.01-0.31). CONCLUSIONS: Serum S100B levels may have utility in ruling out intracranial pathology in intoxicated patients, however more study and comparison with other serum biomarkers of brain injury are necessary before this becomes the accepted standard of care.

AGEP overlap induced by hydroxychloroquine: a case report and literature review.

Acute Generalized Exanthematous Pustulosis (AGEP) is a rare drug reaction manifesting as pustular lesions with surrounding erythema following exposure. The disease is often self-limited and treatment is supportive. It may present in an atypical variant with vesicles that desquamate into erosions, which classifies the disease as an AGEP/SJS Overlap. This overlap syndrome can carry a substantial mortality rate and necessitate elevation in the level of care. Hydroxychloroquine has been implicated in cases of AGEP, and we present a case of AGEP/SJS overlap attributed to this common medication. Given the prevalence of drug eruptions, it is critical for the physicians to recognize and not overlook this rare and potentially fatal dermatological emergency.

Closed-Eye Visualizations in the Setting of Hyponatremia.

PURPOSE: To report a case of closed-eye visualizations and to clarify the different types of hallucinations and their etiologies. METHODS: Retrospective case report of a patient with closed-eye visualizations secondary to hyponatremia. Clinical findings, physical exam, laboratory assessment, treatment, and disease course from the patient's hospitalization were used in creating this report. Follow-up data after discharge were also obtained. RESULTS: Closed-eye visualizations were diagnosed as secondary to hyponatremia, as they did not occur with the eyes open, and potential alternate causes were excluded. Serum sodium nadir was 119 mEq/L. Symptoms resolved with correction of hyponatremia via fluid resuscitation and electrolyte replenishment. There has been no recurrence of the symptoms. CONCLUSION: This patient had hallucinations exclusively with the eyes closed, which must be differentiated from the release hallucinations seen with the eyes open in Charles Bonnet syndrome. This patient had no visual loss or retinal disease, which should be suspected in open eye hallucinations.

Effects of prophylactic anticholinergic medications to decrease extrapyramidal side effects in patients taking acute antiemetic drugs: a systematic review and meta-analysis.

OBJECTIVES: To determine the effectiveness of prophylactic anticholinergic medications in reducing extrapyramidal symptoms in patients taking acute antiemetics with a dopamine D2 receptor antagonist effect. METHODS: Systematic searches of all published studies through March 2017 were identified from PubMed, Cochrane library, Embase, Web of Science and Scopus. Only randomised controlled trials of patients receiving dopamine D2 antagonist antiemetic therapy for acute migraine in which an anticholinergic or placebo was compared were included. Pooled ORs were calculated for incidence of extrapyramidal symptoms and sedation. RESULTS: Four placebo-controlled randomised controlled trials consisting of 737 patients met the inclusion criteria for our meta-analysis. The effect of diphenhydramine differed depending on the method of administration of the antiemetic. When the antiemetic was delivered as a 2 min antiemetic bolus, the odds of extrapyramidal symptoms were significantly reduced in the diphenhydramine group compared with placebo (OR 0.42; 95% CI 0.22 to 0.81; P=0.01). However, when the antiemetic was given as a 15 min infusion, there was no significant difference in extrapyramidal symptoms with or without diphenhydramine (OR 1.06; 95% CI 0.58 to 1.91; P=0.85). The lowest incidence of extrapyramidal symptoms was observed in patients receiving a 15 min antiemetic infusion without diphenhydramine prophylaxis (9.8%). In two trials including 351 patients that dichotomously reported sedation scales, diphenhydramine had significantly higher rates of sedation (31.6%vs19.2%, OR 2.01, 95% CI 1.21 to 3.33; P=0.007). CONCLUSION: Prophylactic diphenhydramine reduces extrapyramidal symptoms in patients receiving bolus antiemetic therapy with a dopamine D2 antagonist effect, but not when it is given as an infusion. Because of significantly greater sedation with diphenhydramine, the most effective strategy is to administer the D2 antagonist antiemetic as a 15 min infusion without prophylaxis.

A case of probable Amiodarone-induced pancreatitis in the treatment of atrial fibrillation: a literature review and case report.

Amiodarone is an effective medication used in the treatment of several different arrhythmias. Its most well-known adverse effects include pulmonary fibrosis, thyroid dysfunction, and hepatotoxicity. A less common side effect is acute pancreatitis. A 67-year-old male being treated for atrial fibrillation in rapid ventricular response with Amiodarone developed acute epigastric abdominal pain 24 hours after initiation of therapy. He was diagnosed as having acute pancreatitis based on characteristic findings seen on an abdominal CT scan. Commonly encountered etiologies of pancreatitis were ruled out through a combination of the history, laboratory values, and imaging results. Based on the temporal association of the acute presentation and initiation of Amiodarone therapy, in conjunction with a lack of support for any other etiology, the diagnosis of Amiodarone-induced pancreatitis was made. Within 7 days following the cessation of Amiodarone therapy, the patient's symptoms had completely resolved. Amiodarone-induced pancreatitis is an often overlooked medication association and is one that has been infrequently reported throughout the literature. Given the substantial morbidity and mortality associated with acute pancreatitis, and the ease of treatment (withdrawing Amiodarone), this is a critical side effect that should be recognized in the appropriate clinical setting.

A ferritin-based label for cellular electron cryotomography.

Electron cryotomography provides nanometer resolution structural detail of thin biological specimens in a near-native state. Currently, its application is limited by the lack of a specific label for the identification of molecules. Our aim was to develop such a label, analogous to GFP used in fluorescence microscopy. Here, we demonstrate the use of Escherichia coli ferritin FtnA protein as a clonable label for electron cryotomography. Overproduced ferritin is visible in E. coli cells using cryotomography and fusing this label to a short membrane targeting sequence correctly directs the ferritin fusion to the membrane. Using two proteins with known subcellular localization patterns with this ferritin tag, also including GFP, we obtained essentially the same labeling patterns using electron cryotomography as compared with fluorescence light microscopy. Hence, the ferritin label localizes efficiently and faithfully and it will be a valuable tool for the unambiguous identification of molecules in cellular electron cryotomograms.

Structural analysis of the ParR/parC plasmid partition complex.

Accurate DNA partition at cell division is vital to all living organisms. In bacteria, this process can involve partition loci, which are found on both chromosomes and plasmids. The initial step in Escherichia coli plasmid R1 partition involves the formation of a partition complex between the DNA-binding protein ParR and its cognate centromere site parC on the DNA. The partition complex is recognized by a second partition protein, the actin-like ATPase ParM, which forms filaments required for the active bidirectional movement of DNA replicates. Here, we present the 2.8 A crystal structure of ParR from E. coli plasmid pB171. ParR forms a tight dimer resembling a large family of dimeric ribbon-helix-helix (RHH)2 site-specific DNA-binding proteins. Crystallographic and electron microscopic data further indicate that ParR dimers assemble into a helix structure with DNA-binding sites facing outward. Genetic and biochemical experiments support a structural arrangement in which the centromere-like parC DNA is wrapped around a ParR protein scaffold. This structure holds implications for how ParM polymerization drives active DNA transport during plasmid partition.

Concatenated metallothionein as a clonable gold label for electron microscopy.

Localization of proteins in cells or complexes using electron microscopy has mainly relied upon the use of heavy metal clusters, which can be difficult to direct to sites of interest. For this reason, we would like to develop a clonable tag analogous to the clonable fluorescent tags common to light microscopy. Instead of fluorescing, such a tag would initiate formation of a heavy metal cluster. To test the feasibility of such a tag, we exploited the metal-binding protein, metallothionein (MT). We created a chimeric protein by fusing one or two copies of the MT gene to the gene for maltose binding protein. These chimeric proteins bound many gold atoms, with a conservative value of 16 gold atoms per copy of metallothionein. Visualization of gold-labeled fusion proteins by scanning electron microscopy required one copy of metallothionein while transmission electron microscopy required two copies. Images of frozen-hydrated samples of simple complexes made with anti-MBP antibodies hint at the usefulness of this method.

Double-stranded DNA translocation: structure and mechanism of hexameric FtsK.

FtsK is a DNA translocase that coordinates chromosome segregation and cell division in bacteria. In addition to its role as activator of XerCD site-specific recombination, FtsK can translocate double-stranded DNA (dsDNA) rapidly and directionally and reverse direction. We present crystal structures of the FtsK motor domain monomer, showing that it has a RecA-like core, the FtsK hexamer, and also showing that it is a ring with a large central annulus and a dodecamer consisting of two hexamers, head to head. Electron microscopy (EM) demonstrates the DNA-dependent existence of hexamers in solution and shows that duplex DNA passes through the middle of each ring. Comparison of FtsK monomer structures from two different crystal forms highlights a conformational change that we propose is the structural basis for a rotary inchworm mechanism of DNA translocation.

Gold nanocluster formation using metallothionein: mass spectrometry and electron microscopy.

Clonable contrasting agents for light microscopy, such as green fluorescent protein, have revolutionized biology, but few such agents have been developed for transmission electron microscopy (TEM). As an attempt to develop a novel clonable contrasting agent for TEM, we have evaluated metallothionein, a small metal-binding protein, reacted with aurothiomalate, an anti-arthritic gold compound. Electro spray ionization and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry measurements show a distribution of gold atoms bound to individual metallothionein molecules. Unlike previous reports, these data show gold binding occurred as the addition of single atoms without retention of additional ligands. Moreover, under certain conditions, MALDI spectra show gold binding ratios of greater than 1:1 with the cysteine residues of metallothionein. Together, this may hint at a gold-binding mechanism similar to gold nanocluster formation. Finally, metallothionein-gold complexes visualized in the TEM show a range of sizes similar to those used as current TEM labels, and show the potential of the protein as a clonable TEM label in which the gold cluster is grown on the label, thereby circumventing the problems associated with attaching gold clusters.