Impact of a new distal attachment on colonoscopy performance in an academic screening center

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Long-Term Treatment of Eosinophilic Esophagitis With Budesonide Oral Suspension

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Slow low-dose oral immunotherapy: Threshold and immunological change

BackgroundWe examined the feasibility, efficacy and safety of slow low-dose oral immunotherapy (SLOIT) for egg, milk, wheat allergies, with accepted severity-stratified initial and maintenance doses.MethodsChildren with food allergies defined by low-dose oral food challenges (LD-OFCs) to hen's egg (cumulative protein dose up to 983 mg, n = 133), cow's milk (287 mg, n = 50), and wheat (226 mg, n = 45) were recruited. Participants were divided into two groups [SLOIT and control (complete avoidance]) based on their preferences. Participants who selected SLOIT were instructed to take the safe dose daily, with monthly increases, aiming to increase the dose by 10 times in one year. The primary outcome was the proportion of participants who passed the LD-OFCs following 1 year of therapy.ResultsThe participants in SLOIT group ingested their antigen 92.9% of the therapy's day on average. The proportion of participants who passed LD-OFCs was 35.9% (61/170) in the SLOIT group and 8.7% (4/46) in the control group (P < .001); no large differences were observed among allergens. Among the subjects who failed LD-OFCs, the median change in the total dose in the LD-OFC was 235% (interquartile range: 100%–512%) in the SLOIT group and 100% (42%–235%) in the control group (P < .001). Provoked allergic symptoms were observed in only 0.58% (280/48,486) per programmed intake and approximately 50% of the SLOIT group did not experience any obvious allergic symptoms throughout therapy.ConclusionsSLOIT showed significant feasibility, efficacy and safety, providing a promising option to manage patients with severe food allergies.     

经尿道给予前列腺素E1治疗阳萎的临床研究

为探索非注射性尿道给药替代海绵体内注射的可行性和安全度，对２４例阳萎患者采用随机分组、自身前后对照、交叉给药的方法，观察经尿道途径给予前列腺素Ｅ１（ＰＧＥ１）６００μｇ与海绵体内注射ＰＧＥ１１５μｇ的血流动力学作用。结果表明，从血管扩张、血流量增加及临床阴茎勃起程度等方面比较，两种给药方式的差异无统计学意义。提示经尿道给予ＰＧＥ１治疗阳萎疗效确实，安全可靠，其６００μｇ剂量足以产生经海绵体内注射ＰＧＥ１１５μｇ的临床疗效，可在临床推广试用。     

Cellular and functional biomarkers of clinical transplant tolerance

Development of tolerance protocols requires assays or biomarkers that distinguish tolerant recipients from non-tolerant ones to be established. In addition, a thorough understanding of the plausible mechanisms associated with clinical transplant tolerance is necessary to take the field forward. Unlike the majority of molecular signature analyses utilized by others, the emphasis of this article is on the cellular and functional biomarkers of induced transplant tolerance. Immunity to an organ transplant is very complex, comprised of two broad categories – innate and acquired or adaptive immune responses. Innate immunity can be avoided by eliminating or preventing ischemic injuries to the donor organ and tolerance at the level of adaptive immunity can be induced by infusions of a number of cellular products. Since adaptive immune response consists of inflammatory hypersensitivity, cellular (cytotoxic and helper) and humoral aspects, all these need to be measured, and the recipients who demonstrate donor-specific unresponsiveness in all can be considered tolerant or candidates for immunosuppression minimization and/or withdrawal. The mechanisms by which these agents bring about transplant tolerance include regulation, anergy, exhaustion, senescence and deletion of the recipient immune cells. Another proven mechanism of tolerance is full or mixed donor chimerism. However, it should be cautioned that non-deletional tolerance can be reversed.     

What is new in Chicago Classification version 4.0?

Since publication of Chicago Classification version 3.0 in 2015, the clinical and research applications of high‐resolution manometry (HRM) have expanded. In order to update the Chicago Classification, an International HRM Working Group consisting of 52 diverse experts worked for two years and utilized formally validated methodologies. Compared with the prior iteration, there are four key modifications in Chicago Classification version 4.0 (CCv4.0). First, further manometric and non‐manometric evaluation is required to arrive at a conclusive, actionable diagnosis of esophagogastric junction (EGJ) outflow obstruction (EGJOO). Second, EGJOO, distal esophageal spasm, and hypercontractile esophagus are three manometric patterns that must be accompanied by obstructive esophageal symptoms of dysphagia and/or non‐cardiac chest pain to be considered clinically relevant. Third, the standardized manometric protocol should ideally include supine and upright positions as well as additional manometric maneuvers such as the multiple rapid swallows and rapid drink challenge. Solid test swallows, postprandial testing, and pharmacologic provocation can also be considered for particular conditions. Finally, the definition of ineffective esophageal motility is more stringent and now encompasses fragmented peristalsis. Hence, CCv4.0 no longer distinguishes between major versus minor motility disorders but simply separates disorders of EGJ outflow from disorders of peristalsis.     

Hyperglycemia Control of the Nil Per Os Patient in the Intensive Care Unit: Introduction of a Simple Subcutaneous Insulin Algorithm

Background

Diabetes patients in the intensive care unit (ICU) and either nil per os, on enteral feedings, or on total parenteral nutrition are often treated with sliding-scale insulin (despite lack of evidence showing benefit) or intravenous insulin (IVI) infusion, a nursing intensive procedure requiring hourly glucose measurements, and insulin rate adjustments. We introduced a subcutaneous insulin algorithm (SQIA) that would equal the glucose goals for IVI but have the simplicity of q4 hour adjustable sliding-scale insulin.

Methods

As part of a quality improvement project, we developed a simple SQIA that titrates insulin to the requirements of the individual patient. Glucoses were monitored q4 h and SQ rapid-acting insulin administered based on both the previous insulin dose and current glucose level. Fourteen consecutive hyperglycemic patients admitted to ICU-A were placed on the SQIA. Glucose and insulin data were also obtained on 18 patients in an identical ICU-B who were treated with the usual IVI protocol, which is q1–2 h.

Results

Duration on the SQIA was 4.5 ± 0.6 days (range 0.8–7) and on IVI 1.9 ± 0.6 days (range 0.25–9). Due to difference in length on protocols, only data for the first 3 days could be statistically compared. During this time, the mean ± standard error of glucoses for the SQ and IV groups were 157.3 ± 3.8 and 157.0 ± 2.2 (not significant). No differences were seen in hypoglycemia rates.

Conclusions

A simple SQIA allows insulin doses to be adjusted to the individual patient’s needs and meet current ICU goals for glycemic control. Its adoption may reduce the workload of nurses.     

Comparison of Von Willebrand factor (VWF) activity VWF:Ac with VWF ristocetin cofactor activity VWF:RCo

Introduction

Ristocetin cofactor activity of Von Willebrand factor (VWF:RCo) and the ratio VWF:RCo to its antigen VWF:Ag are used as routine screening to estimate VWF function and to detect types of Von Willebrand disease (VWD) caused by loss of high molecular weight multimers. However, the VWF:RCo test is prone to analytic imprecisions due to various reasons. We compared an assay for VWF activity (VWF:Ac) with VWF:RCo putting emphasis on the ratios to VWF:Ag.

Materials and Methods

We evaluated 942 samples from 432 patients and evaluated three groups in detail: normal patients (normal multimers, VWF:Ag and VWF:RCo > 0.5 U/ml, VWD type 1 excluded; n = 258), VWD type 1 (n = 76) and acquired Von Willebrand syndrome (AVWS, n = 326). In addition, 30 healthy subjects were analysed.

Results

VWF:Ac and VWF:RCo correlated well (Pearson´s r = 0.96, p < 0.01), so did their ratios to VWF:Ag (Pearson´s r = 0.82, p < 0.01). We calculated the normal range of VWF:Ac/VWF:Ag for healthy subjects as 0.8-1.16. In comparison, the reference range (mean ± 2std) derived from normal patient samples was 0.73-1.14. The corresponding ranges for VWF:RCo/VWF:Ag came to 0.74-1.23 (healthy) and 0.62-1.25 (normal patients). The ratios showed similar results regarding VWD type 1. The sensitivity for AVWS was higher with VWF:Ac/VWF:Ag than with VWF:RCo/VWF:Ag (97.5% versus 84.7%).

Conclusions

The data suggest that the results obtained with the VWF:Ac assay are comparable to that of the VWF:RCo assay. An AVWS was more reliably detected by VWF:Ac/VWF:Ag. We assume that the VWF:Ac assay could replace VWF:RCo for routine screening for AVWS, especially when prompt evaluation is required.