The Need for a Coagulation Assay after Initiation of New Oral Anticoagulants in Patients with Renal Dysfunction: A Case Report

Background

Dabigatran etexilate, a new oral anticoagulant, was recently approved as an efficacious alternative to warfarin for the prevention of first and recurrent stroke in patients with nonvalvular atrial fibrillation. Limited data are available for dabigatran use in patients with a creatinine clearance rate (CrCL) of 15-30 mL/min. Furthermore, current guidelines do not recommend frequent blood monitoring after dabigatran use. We report herein a patient with severe renal dysfunction who exhibited profound coagulopathy after 2 days of dabigatran use.

Case Report

An 87-year-old woman was admitted for altered mental status and left-side weakness. She was diagnosed with right middle cerebral artery infarction. The baseline assessment revealed a serum creatinine concentration of 1.29 mg/dL and a CrCL of 27.2 mL/min. Dabigatran therapy was started 5 weeks after admission at a dosage of 110 mg twice daily. After 2 days of dabigatran use, the patient developed multiple bruises and evidence of upper-gastrointestinal bleeding. Laboratory tests demonstrated a severe coagulopathy, with a prothrombin time of 85.9 sec, an international normalized ratio of 11.36, an activated partial thromboplastin time of 119.2 sec, and a thrombin time of 230.8 sec. Serial assessment of the patient''s renal function revealed substantial fluctuation of the CrCL (range, 17.9-26.5 mL/min).

Conclusions

The present case emphasizes the need for frequent checking of renal function and assessment using coagulation assays after commencing dabigatran therapy in patients with moderate-to-severe renal impairment.     

New Metrics in High-Resolution and High-Definition Anorectal Manometry

Purpose of Review

To review recently published diagnostic methods that use high-resolution (HR-) or high-definition- (HD-) anorectal manometry (ARM) techniques.

Recent Findings

The integrated pressurized volume (IPV) is a new measure based on spatiotemporal plots obtained from HR-ARM. The IPV may be clinically useful for improving the prediction of abnormal balloon expulsion test in patients with constipation and for discriminating patients with anorectal disorders from asymptomatic controls. Combination of IPV parameters was superior to conventional manometric parameters in predicting the responsiveness to biofeedback therapy. Moreover, several novel parameters including the HR-ARM resting integral, HR-ARM squeeze profile, and anorectal asymmetry index may each be useful as predictive factors for identifying patients with fecal incontinence.

Summary

HR- and HD-ARM are increasingly performed worldwide for evaluation of anorectal function. Here, we describe new metrics whose clinical significance has not been fully established. Further standardization and validation of these metrics could provide clinically important new information and could help improve our understanding of the pathophysiology of anorectal disorders.

     

The effect of foot position on erector spinae and gluteus maximus muscle activation during sit-to-stand performed by chronic stroke patients

[Purpose] The aim of this study was to use surface electromyography (EMG) to investigate the effects of different foot positioning on bilateral erector spinae (ES) and gluteus maximus (GM) activation during sit-to-stand performed by individuals with stroke. [Subjects] Fifteen randomly selected participants with stroke were enrolled in this study. [Methods] All the participants were asked to perform sit-to-stand (STS) using three different strategies: (1) symmetric foot position, (2) unaffected foot placed behind the affected foot position (asymmetric-1), (3) affected foot placed behind the unaffected foot position (asymmetric-2). An EMG system was used to measure ES and GM muscle activities. The strategies were performed in a random order, and the mean values of five measurements were used in the analysis. One-way repeated measure ANOVA was used to determine the statistical significance of differences between the conditions. [Results] The affected ES muscle activity was significantly greater in asymmetric-2 (180.7±73.4) than in symmetrical foot placement (149.8±54.2). In addition, the affected ES, unaffected ES, and affected GM muscle activity were significantly greater in asymmetric-2 (180.7±73.4, 173.5±83.1, 98.3±90.3 respectively) than in asymmetric-1 foot placement (147.3±53.8, 151.2±76.5, 84.9±73.8 respectively). [Conclusion] Our results suggest that it may be more desirable for persons with stroke to place the affected foot behind the unaffected foot when performing STS to increase affected ES and GM muscle activation.Key words: Electromyography, Sit-to-stand, Stroke     

Effects of spiral taping applied to the neck and ankle on the body balance index

[Purpose] This study was performed to investigate the changes in the body balance index when spiral taping is applied to the neck and ankle. The findings are expected to serve as evidence of the usefulness of taping the neck instead of the ankle when ankle taping is not feasible in clinical practice. [Subjects and Methods] Twenty healthy male students at A university were enrolled in this study. Balance measurements were made under three conditions: no intervention, ankle intervention and neck intervention. Static balance was measured with subjects’ eyes open and closed, and dynamic balance was measured with subjects’ eyes closed. [Results] There were significant differences in dynamic balance assessed by the Overall Balance Index (OBI), and the Anteroposterior Balance Index (ABI) with subjects’ eyes open when ankle or neck taping was applied compared to no intervention. The static balance (OBI) of subjects with eyes open showed significant differences from the no intervention condition in both the ankle and neck intervention. The static balance (OBI) with subjects’ eyes closed also showed significant differences in both the ankle and neck interventions compared to the no intervention condition. [Conclusion] Our results indicate that neck taping stimulates the somatic senses around the neck and increase proprioception, resulting in balance improvement similar to that elicited by ankle taping. Further studies with larger sample sizes various experimental conditions should be performed to more systematically and objectively elucidate the effects of neck taping.Key words: Spiral taping, Balance, Balance index     

Case-Control Study of the Risk Factors for Acquisition of Pseudomonas and Proteus Species during Tigecycline Therapy

Tigecycline is an important agent in clinical practice because of its broad-spectrum activity. However, it has no activity against Pseudomonas or Proteus species. We conducted a case-control study to analyze risk factors for the acquisition of Pseudomonas or Proteus spp. during tigecycline therapy. Placement of suction drainage at infected wound sites, ICU stay, and neurologic disease were identified as independent risk factors for the acquisition of Pseudomonas and Proteus spp.     

A Comparison of Single-, Two- and Three-Port Laparoscopic Myomectomy

Background and Objective:

A recent FDA safety communication has discouraged the use of a power morcellator for myoma extraction and has called for a change in surgical techniques for myomectomy. The objective of this study was to compare surgical outcomes of laparoscopic single-, two-, and conventional three-port myomectomy and to evaluate the feasibility of contained manual morcellation for uterine myoma.

Methods:

This retrospective study was a review and analysis of data from 191 consecutive women who underwent single-, two-, or three-port myomectomy for the management of uterine myoma from January 1, 2009, through December 31, 2014.

Results:

The 3 study groups did not differ demographically. Apart from operative time, the single- and two-port groups showed operative outcomes comparable to those of the multiport group. The single-port group had significantly longer operative times (P = .0053) than the two- and three-port groups. However, in the latter half of the single-port cases, the operative time was similar to those in the three-port group. The two-port surgery group showed a consistent operative time without a learning period.

Conclusion:

Single- or two-port myomectomy with transumbilical myoma morcellation is feasible and safe, with outcomes comparable to those of three-port myomectomy. These results suggest the potential for minimally invasive management of symptomatic uterine myoma, without the use of a power morcellator.     

Preclinical Characterization and In Vivo Efficacy of GSK8853, a Small-Molecule Inhibitor of the Hepatitis C Virus NS4B Protein

The hepatitis C virus (HCV) NS4B protein is an antiviral therapeutic target for which small-molecule inhibitors have not been shown to exhibit in vivo efficacy. We describe here the in vitro and in vivo antiviral activity of GSK8853, an imidazo[1,2-a]pyrimidine inhibitor that binds NS4B protein. GSK8853 was active against multiple HCV genotypes and developed in vitro resistance mutations in both genotype 1a and genotype 1b replicons localized to the region of NS4B encoding amino acids 94 to 105. A 20-day in vitro treatment of replicons with GSK8853 resulted in a 2-log drop in replicon RNA levels, with no resistance mutation breakthrough. Chimeric replicons containing NS4B sequences matching known virus isolates showed similar responses to a compound with genotype 1a sequences but altered efficacy with genotype 1b sequences, likely corresponding to the presence of known resistance polymorphs in those isolates. In vivo efficacy was tested in a humanized-mouse model of HCV infection, and the results showed a 3-log drop in viral RNA loads over a 7-day period. Analysis of the virus remaining at the end of in vivo treatment revealed resistance mutations encoding amino acid changes that had not been identified by in vitro studies, including NS4B N56I and N99H. Our findings provide an in vivo proof of concept for HCV inhibitors targeting NS4B and demonstrate both the promise and potential pitfalls of developing NS4B inhibitors.     

Histone Acetylation Level and Histone Acetyltransferase/Deacetylase Activity in Ejaculated Sperm from Normozoospermic Men

Purpose

The aim of this work was to evaluate nuclear histone acetylation level and total histone acetyltransferase (HAT) and deacetylase (HDAC) activity in ejaculated sperm and their relevance to conventional sperm parameters.

Materials and Methods

Thirty-three normozoospermic men were included in this study. Semen samples were processed by swim-up and then immunostained by six acetylation antibodies (H3K9ac, H3K14ac, H4K5ac, H4K8ac, H4K12ac, and H4K16ac). Our preliminary study verified the expression of HAT/HDAC1 in mature human sperm. From vitrified-warmed sperm samples, total HAT/HDAC activity was measured by commercially available kits. Nuclear DNA integrity was also measured by TUNEL assay.

Results

The levels of six acetylation marks were not related with conventional sperm parameters including sperm DNA fragmentation index (DFI) as well as HAT/HDAC activity. However, sperm DFI was positively correlated with HAT activity (r=0.038 after adjustment, p<0.02). HAT activity showed a negative relationship with HDAC activity (r=-0.51, p<0.01). Strict morphology was negatively correlated with acetylation enzyme index (=HAT activity/HDAC activity) (r=-0.53, p<0.01).

Conclusion

Our works demonstrated a significant relationship of acetylation-associated enzyme activity and strict morphology or sperm DFI.