Chronic mesenteric ischemia: diagnosis and management

Chronic mesenteric ischemia (CMI) is the most common vascular disorder involving the intestines, however it is unusual in clinical practice. The redundancy of the visceral circulation with multiple interconnections between the superior mesenteric artery (SMA) and the inferior mesenteric artery (IMA) is the most likely explanation for the infrequent occurrence of CMI in clinical practice. Atherosclerosis is by the far the most common etiology of CMI. The increased utilization of diagnostic abdominal cross-sectional imaging has increased the recognition of atherosclerotic mesenteric stenoses. CMI is a clinical diagnosis, based upon symptoms and consistent anatomic findings. The classic setting for CMI is a female patient presenting with post-prandial abdominal discomfort that results in significant weight loss. Endovascular therapy with stenting has become the most common method chosen for revascularization having replaced open surgery with its associated morbidity and mortality.     

Cost-effectiveness of vaccination of the elderly against herpes zoster in The Netherlands

Background

Each year a substantial number of Dutch elderly suffers from herpes zoster (HZ), caused by the reactivation of the varicella zoster virus (VZV). A potential complication of HZ is postherpetic neuralgia (PHN) which results in a prolonged loss of quality of life. A large randomized clinical trial, labelled the Shingles Prevention study (SPS), demonstrated that a live attenuated VZV vaccine can reduce the incidence of HZ and PHN.

Objective

We aimed to estimate the incremental cost-effectiveness ratio (ICER) of vaccination of the elderly against HZ versus no such vaccination in The Netherlands.

Methods

A cohort model was developed to compare the costs and effects in a vaccinated and a non-vaccinated age- and gender-stratified cohort of immune-competent elderly. Vaccination age was varied from 60 to 75 years. Data from published literature such as the SPS were used for transition probabilities. The study was performed from the societal as well as the health care payer's perspective and results were expressed in euros per quality-adjusted life year (QALY) gained.

Results

In the base case, we estimated that vaccination of a cohort of 100,000 60-year-olds would prevent 4136 cases of HZ, 305 cases of PHN resulting in a QALY-gain of 209. From the societal perspective, a total of €1.9 million was saved and the ICER was €35,555 per QALY gained when a vaccine price of €87 was used. Vaccination of women resulted in a lower ICER than vaccination of men (€33,258 vs. €40,984 per QALY gained). The vaccination age with the most favourable ICER was 70 years (€29,664 per QALY gained). Parameters with a major impact on the ICER were the vaccine price and HZ incidence rates. In addition, the model was sensitive to utility of mild pain, vaccine efficacy at the moment of uptake and the duration of protection induced by the vaccine.

Conclusion

Vaccination against HZ might be cost-effective for ages ranging from 60 to 75 when a threshold of €50,000 per QALY gained would be used, at €20,000 per QALY this might not be the case. Additional information on the duration of vaccine-protection is needed to further optimize cost-effectiveness estimations.     

Endothelial cell presentation of antigen to human T cells

Activation of human T cells requires presentation of antigen by Ia (HLA-DR in man) bearing cells of the mononuclear phagocytic series (macrophages, MØ), and more recently Langerbans cells, dendritic cells, and vascular endothelial cells. Since T cells must cross endothelial barriers to enter extavasulcar tissues during immune reactions, we investigated the role of endothelial cells in antigen presentation. Endothelial cells were cultured from human umbilical veins and identified by classic morphology and specific markers (factor VIII related antigen, and so on). Antigen-pulsed endothelial cells were used to present antigen to MØ-depleted human T cells; activation was assessed by ³H-thymidine uptake. The HLA-DR compatible endothelial cells were as effective as MØ-in reconstituting MØ-depleted T-cell responses. The endothelial cell reconstituted responses were antigen specific, HLA-DR restricted, and blocked by monoclonal antibodies to HLA-DR framework structures. Moreover, the T-cell responses were clonal with respect to HLA-DR. A monoclonal antibody completely eliminated MØ reconstitution of the MØ-depleted response without diminution of endothelial cell reconstitution of the same response. Fibroblasts and smooth muscle cells cultured from the same umbilical veins could not reconstitute the MØ-depleted T-cell response. These data indicate that endothelial cells play an important and distinctive role in lymphocyte triggering.     

Atopic allergy and delayed type hypersensitivity in Estonian children

BACKGROUND: A shift in the balance ofT helper (Th) cell subsets towards a polarized Th2 population is generally accepted to occur in atopic disease, however, both Th1 and Th2 disorders have increased over the past decades in Western communities. OBJECTIVE: The aim of our study was to investigate delayed type hypersensitivity (DTH) response in atopic and non-atopic children in a population with a low prevalence of allergic disorders. METHODS: Skin prick tests (SPT) were performed with fresh egg white and extracts of five inhalant allergens, i.e. cat, dog, house dust mite (Dermatophagoides pteronyssinus), birch and timothy, and DTH response was evaluated by Multitest CMI in 72 Estonian 4- to 6-year-old children. RESULTS: The frequency of response to diphtheria was significantly increased in SPT-positive children (55% vs. 26%, chi2 = 5.5; P = 0.038). The induration to diphtheria (2.4 +/- 0.5 vs. 0.9 +/- 0.2 mm; P = 0.004), and tetanus (3.5 +/- 0.6 vs. 2.1 +/- 0.3 mm; P = 0.025) was significantly greater in the SPT-positive children. The cumulative size of induration in the positive DTH tests was significantly greater in the SPT-positive children (9.0 +/- 1.2 vs. 5.2 +/- 0.6 mm, P = 0.01). CONCLUSION: In this group of children our findings do not support the hypothesis of an immune deviation with decreased Th1 and increased Th2 responses leading to atopic disease, but rather a process of immune modulation whereby both Th1 and Th2 responses are increased in atopic subjects.     

Chloromethylisothiazolone/methylisothiazolone (CMI/MI) use test with a shampoo on patch-test-positive subjects Results of a multicentre double-blind crossover trial

A randomized, multicentre, double-blind, 2–period crossover study with 2 shampoos was performed on subjects patch-test-positive to 100 ppm CMI/MI. One shampoo was preserved with 15 ppm a.i. CMI/MI, the other with 0.3% imidazolidinyl urea (IU). 27 subjects from 5 European dermatology clinics participated. 1 subject discontinued use after severe adverse reactions to the CMI/MI-preserved shampoo and did not evaluate the other shampoo. Another 2 subjects developed moderate symptoms with the CMI/MI-preserved shampoo and discontinued its use, but tolerated the lU-preserved shampoo for the full 2–week period. 2 subjects discontinued use after 1 or 2 washes after severe adverse reactions to the lU-preserved shampoo. 1 of these subjects tolerated the CMI/MI-preserved shampoo for 2 weeks without any untoward effects. However, the majority of subjects had negative findings on the scalp, face, neck, and hands for both shampoos. The physicians' global evaluation data indicated that shampoo with CMI/MI caused fewer skin problems than shampoo with IU (38% versus 27%, n.s.), with over 1/3 of the subjects (35%) having no skin problems with either preservative. The current study showed that most subjects previously sensitized to CMI/MI can successfully use shampoo preserved with CMI/MI. Since some subjects previously sensitized to CMI/MI, or possibly to IU, may develop clinical reactions, it would still be prudent for the clinician to advise alternative products to patients with sensitivity to a shampoo or cosmetic ingredient. Full ingredient labelling will ensure that this is possible. As the overall rate of adverse effects in sensitized individuals was low, studies of this nature should also be conducted for other allergens. This will be helpful in determining the relevance of patch test data.     

Post-treatment effects of exposure therapy and clomipramine in obsessive-compulsive disorder

We sought to determine whether adults with obsessive-compulsive disorder (OCD) who respond to intensive exposure and response (ritual) prevention (EX/RP) with or without clomipramine (CMI) fare better 12 weeks after treatment discontinuation than responders receiving CMI alone. After receiving 12 weeks of treatment (EX/RP, CMI, EX/RP+CMI, or pill placebo [PBO] in a randomized clinical trial conducted at three outpatient research centers), 46 adults with OCD who responded to treatment (18 EX/RP, 11 CMI, 15 EX/RP+CMI, 2 PBO) were followed after treatment discontinuation for 12 weeks. Patients were assessed every 4 weeks with the Yale-Brown Obsessive-Compulsive Scale, the National Institutes of Health Global Obsessive-Compulsive Scale, and the Clinical Global Impressions scale by an evaluator who was blind to original treatment assignment. The primary hypothesis was that EX/RP and EX/RP+CMI responders would be less likely to relapse 12 weeks after treatment discontinuation than responders to CMI alone. Twelve weeks after treatment discontinuation, EX/RP and EX/RP+CMI responders, compared to CMI responders, had a significantly lower relapse rate (4/33 = 12% versus 5/11 = 45%) and a significantly longer time to relapse. The CMI relapse rate was lower than previously reported. Nonetheless, responders receiving intensive EX/RP with or without CMI fared significantly better 12 weeks after treatment discontinuation than responders receiving CMI alone.     

Nocardiosis in persons with human immunodeficiency virus infection, transplant recipients, and large, geographically defined populations

To quantify the risk of nocardiosis in various populations, I systematically reviewed articles published between 1966 and 2004. The incidence of nocardiosis in 3 large, geographically defined populations ranged from 0.35 to 0.4 cases per 10(5) persons year. In contrast, the incidence of nocardiosis among people with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) in 1 study was 53 nocardiosis cases per 10(5) persons x year, approximately 140 times greater than that in the geographically defined populations. The frequency of nocardiosis cases in 4 populations of HIV-infected people averaged 608 cases per 10(5) persons. The incidence of nocardiosis in bone marrow-transplant recipients at 1 hospital was 128 cases per 10(5) persons x year, an incidence approximately 340 times greater than that in the geographically defined populations and in the same range as in HIV-infected people. The frequency of nocardiosis in 21 series of cases in recipients of a variety of transplanted organs averaged 1122 cases per 10(5) persons. These estimated incidence rates are imprecise because they were not collected through prospective surveillance systems, but the estimates for the 3 groups were internally consistent and provide useful information for clinicians.     

In vitro induction of apoptosis vs. necrosis by widely used preservatives: 2-phenoxyethanol, a mixture of isothiazolinones, imidazolidinyl urea and 1,2-pentanediol

Preservatives are added to many final products, such as detergents, cosmetics, pharmaceuticals and vaccines. We conducted an in vitro investigation of the apoptosis- and necrosis-inducing potential of brief applications (10 min) of four common preservatives: ethylene glycol monophenyl ether, 2-phenoxyethanol (EGPE), imidazolidinyl urea (IMU), a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (CMI/MI), and 1,2-pentanediol, a "preservative-non-preservative" best known as pentylene glycol. Using HL60 cells, we monitored the kinetics of cell toxicity with the MTT test and analysed extranuclear end points of apoptosis, i.e. phosphatidylserine exposure and nuclear fragmentation. Preservative treatment resulted in a dose-dependent decrease of cell viability. The mode of cell death was dose-dependent: necrosis occurred at high concentrations while apoptosis, shown by DNA laddering, DNA sub-diploid peak and caspase-3 activation, occurred at lower concentrations 0-24hr after exposure to a single dose: CMI/MI induced apoptosis at low concentrations (0.001-0.01%) and necrosis at high concentrations (0.5-0.1%); IMU and EGPE required higher concentrations to induce apoptosis (IMU 0.01-0.1% and EGPE 0.01-0.5%) or necrosis (IMU 0.5-1% and EGPE only at 1%). PG induced apoptosis only at 5%. Externalization of PS, a hallmark of apoptosis, occurred early in HL60 treated with low concentrations of CMI/MI and EGPE and was concomitant with the subdiploid peak in HL60 treated with PG. However, it did not occur in HL60 treated with IMU. In conclusion, at appropriate concentrations, each of the four preservatives modulates the apoptotic machinery by a caspase-dependent mechanism. Thus, apoptosis could be a good parameter to evaluate the cytoxicity of these chemical compounds.     

基于DRG的分级诊疗实现路径研究

目的:通过DRG中的CMI值进行医疗机构诊治疾病难易程度分布状况的研究,为各级医疗机构确定合适的诊疗病种提供参考。方法:利用某三甲医院2017—2019年的病案首页数据,以北京版DRG分组器进行分组,通过聚类分析法确定CMI值各区间分类标准,用于疾病难易程度分析。结果:医院诊治病例集中在CMI值小于1.44的区间范围,2019年累计占84.89%;CMI值大于4.93的病例数量逐年增加。结论:用CMI值界定疾病难易程度,明确不同级别医疗机构的服务能力和水平,可以为落实分级诊疗提供参考。     

Nivolumab in routine practice for older patients with advanced or metastatic non-small cell lung cancer

Background

Nivolumab is approved worldwide as second-line treatment for metastatic non-small cell lung cancer (NSCLC). Despite the fact that most of these cancers are being diagnosed in the older patients, few of the patients were included in pivotal trials. We aimed to describe efficacy and safety in a “real-world” older population.