Micronutrients,their potential effect on patients with systemic sclerosis

Abstract

Over the past years, several evidences have supported an important role of specific micronutrients, including vitamin A, vitamin D and vitamin E in immune dysfunction, vascular involvement and fibrotic changes involved in systemic sclerosis (SSc) development. In PubMed, eight clinical trials about the therapy of micronutrients on SSc patients were searched out using medical subject headings terms (SSc: “scleroderma, localized”, “scleroderma, systemic”, “scleroderma, diffuse” and “scleroderma, limited”; vitamins “vitamin A”, “thiamin”, “riboflavin”, “niacin”, “pantothenic acid”, “vitamin B 6”, “biotin”, “folic acid”, “vitamin B 12”, “inositol”, “choline”, “ascorbic acid”, “vitamin D”, “vitamin E”, “tocopherols”, “vitamin K” and “vitamin P”; and minerals: “calcium”, “magnesium”, “potassium”, “sodium”, “phosphorus”, “sulfur”, “chlorine”, “iron”, “copper”, “iodine”, “zinc”, “selenium”, “manganese”, “molybdenum”, “cobalt”, “chromium”, “tin”, “vanadium”, “silicon”, “nickel” and “fluorine”). This brief review will summarize current understanding on that for the further prospect of future studies. Though the clinical trials for the treatment of SSc with micronutrients are still in their infancy, more researches are needed to substantiate the current results and accelerate the knowledge in this field.     

Clopidogrel “Resistance”: Where are We Now?

Antiplatelet therapy with aspirin and clopidogrel in PCI patients, though effective, is still associated with thrombotic complications. These are multifactorial in origin, but partially attributable to “clopidogrel resistance.” However, how best to identify and manage “clopidogrel resistance” remains unclear. Targeting therapeutic changes specifically at those individuals with poor response to clopidogrel is likely to be a solution. A “one size fits all” approach to clopidogrel dosing is probably flawed. This review will explore (1) the definition and mechanisms of clopidogrel resistance, (2) assessment of clopidogrel resistance by (i) platelet function testing and (ii) genetic testing, (3) the management of “clopidogrel resistance,” and (4) newer antiplatelet agents, and evolving stent technology. A pubmed literature review was performed using the keywords “clopidogrel”, “resistance”, “poor response”, “adverse events”, “platelet function tests”, and “genetic tests”. In looking at new agents, keywords “prasugrel”, “cangrelor”, “ticagrelor”“Elinogrel”, and “P2Y12 receptor antagonists” were used. Third, a search was performed looking at “stent design”, “IVUS”, “bioabsorbable stents”, and “stent apposition”. Whilst new P2Y12 receptor antagonists and improved stent technology may reduce thrombotic events in the future, there is still a need for clopidogrel. There is good evidence that poor response to clopidogrel is associated with adverse outcome. Platelet function tests probably provide more clinically useful data than genetic tests, but the question of how best to identify and manage variability in response to clopidogrel demands further research.     

The use of GLP‐1 receptor agonists in hospitalised patients: An untapped potential

In the outpatient setting, glucagon‐like peptide‐1 (GLP‐1) receptor agonists have proved to be highly efficacious drugs that provide glycaemic control with a low risk of hypoglycaemia. These characteristics make GLP‐1 receptor agonists attractive agents to treat dysglycaemia in perioperative or high‐dependency hospital settings, where glycaemic variability and hyperglycaemia are associated with poor prognosis. GLP‐1 also has a direct action on the myocardium and vasculature—which may be advantageous in the immediate aftermath of a vascular insult. This is a narrative review of the work in this area. The aim was to determine the populations of hospitalised patients being evaluated and the clinical and mechanistic end‐points tested, with the institution of GLP‐1 therapy in hospital. We searched the PubMed, Embase, and Google scholar databases, combining the term “glucagon‐like peptide 1” OR “GLP‐1” OR “incretin” OR “liraglutide” OR “exenatide” OR “lixisenatide” OR “dulaglutide” OR “albiglutide” AND “inpatient” OR “hospital” OR “perioperative” OR “postoperative” OR “surgery” OR “myocardial infarction” OR “stroke” OR “cerebrovascular disease” OR “transient ischaemic attack” OR “ICU” OR “critical care” OR “critical illness” OR “CCU” OR “coronary care unit.” Pilot studies were reported in the fields of acute stroke, cardiac resuscitation, coronary care, and perioperative care that showed advantages for GLP‐1 therapy, with normalisation of glucose, lower glucose variability, and lower risk of hypoglycaemia. Animal and human studies have reported improvements in myocardial performance when given acutely after vascular insult or surgery, but these have yet to be translated into randomised clinical trials.     

Screening,prophylaxis and counselling before the start of biological therapies: A practical approach focused on IBD patients

The standard of care in the management of immune-mediated inflammatory conditions relies on immunomodulators, glucocorticoids, and biologicals (including anti-tumour necrosis factor −α and other monoclonal antibodies). These agents have an overall favourable benefit/risk ratio; however, they modulate the immune response as part of their mechanisms of action, and therefore they may increase the risk of developing infections, particularly in older patients or in patients with concomitant corticosteroids. Some of these infections may be preventable by immunization, chemoprophylaxis or counselling. AIM: screening for and monitoring infections throughout these therapies is so mandatory to ensure patients’ safety. Still, standardized guidelines focused on these procedures have yet to be established. This review aims to fill such a gap. The authors searched for articles published in English from 2009 until 2017 using PUBMED, with the terms “immunomodulators”, “biological drugs”, “anti-TNF α”, “inflammatory bowel diseases”, “immunomediated inflammatory diseases”, “risk of infection”, “infection prevention”, “screening”, “immunization”, “tuberculosis”, “latent tuberculosis”, “listeriosis”, “endemic mycosis”, “Pneumocystis jiroveci pneumonia”, “granulomatous infection”, “varicella”, “herpes virus”, “hepatitis B”, “hepatitis A”, “hepatitis C” and identified the journal articles. Based on the literature and in their own experience the authors established recommendations and a practical guide for infections’ screening, monitoring and prevention before and during immunomodulatory and biological therapies.     

Life priorities in the HIV-positive Asians: a text-mining analysis in young vs. old generation

HIV/AIDS is one of the most urgent and challenging public health issues, especially since it is now considered a chronic disease. In this project, we used text mining techniques to extract meaningful words and word patterns from 45 transcribed in-depth interviews of people living with HIV/AIDS (PLWHA) conducted in Taipei, Beijing, Shanghai, and San Francisco from 2006 to 2013. Text mining analysis can predict whether an emerging field will become a long-lasting source of academic interest or whether it is simply a passing source of interest that will soon disappear. The data were analyzed by age group (45 and older vs. 44 and younger). The highest ranking fragments in the order of frequency were: “care”, “daughter”, “disease”, “family”, “HIV”, “hospital”, “husband”, “medicines”, “money”, “people”, “son”, “tell/disclosure”, “thought”, “want”, and “years”. Participants in the 44-year-old and younger group were focused mainly on disease disclosure, their families, and their financial condition. In older PLWHA, social supports were one of the main concerns. In this study, we learned that different age groups perceive the disease differently. Therefore, when designing intervention, researchers should consider to tailor an intervention to a specific population and to help PLWHA achieve a better quality of life. Promoting self-management can be an effective strategy for every encounter with HIV-positive individuals.     

Alcoholism Disease Concept and Loss of Control Revisited*

Recent criticism of the applicability of the disease concept, the medical model and “loss of control”, to alcoholism, all seem in part to be based on semantic “man-of-straw” arguments. If each of the terms “disease”, “medical”, “alcoholism”, “loss of control” is equated with organic physical changes only, such criticism might perhaps be justified—with the proviso that knowledge on alcoholism at present is still far from complete. These criticisms, however, lose much of their basis if the terms “disease”, “medical”, “alcoholism”, and “loss of control” are taken to include psychosomatic and psycho-social factors as well as physical ones. Medical men are concerned with psychological and social, as well as physical, conditions. If “loss of control” is viewed as a multi-factorial condition affected by psychological and social, as well as physico-chemical factors, the finding that under certain favourable psychological and social conditions some alcoholics can drink in moderation for shorter or longer periods, becomes easily understandable-this, however, by no means affects the basic applicability of the “loss of control” concept, the alcoholics' inability to drink safely in moderation for very long, and the advisability of adhering to the principle of total abstinence.     

Thirteen cases of pyruvate kinase deficiency found in Japan

Thirteen cases of pyruvate kinase (PK) deficiency, considered to be heterozygous for different PK mutants because of no consanguinities in their parents, were characterized by the International Committee for Standardization in Haematology (ICSH) recommended methods. These deficiency cases are named PK “Kagoshima,” PK “Kyoto,” PK “Takamatsu,” PK “Abeno,” PK “Kobe,” PK “Marugame,” PK “Hoenzaka,” PK “Osaka,” PK “Motomachi,” PK “Gifu,” PK “Hiroshima” PK “Matsumoto,” and PK “Tama.” The characteristics of mutant PK enzymes suggest that the cause of chronic hemolysis depends mainly on decreased affinity for phosphoenolpyruvate, thermolability, increased inhibition by adenosine triphosphate, and low activation by fructose-1, 6-diphosphate.     

Post-colectomy assessment of gastrointestinal function: a prospective study on colorectal cancer patients

Background

Anatomical changes after intestinal resection and the effects of adjuvant treatment for colorectal cancer may lead to gastrointestinal disturbances. The aim of our study was to assess gastrointestinal function using validated health-related quality of life (HRQoL) questionnaires that are able to reliably quantify patients’ symptoms.

Methods

Two hundred and eighty-nine colorectal cancer patients underwent HRQoL assessment preoperatively and at 3,6 and 12 months postoperatively. They were evaluated with the Gastrointestinal Quality of Life Index (GIQLI) [“global” and “symptoms” scales and questions 3 (“bloating”), 4 (“excessive gas”), 6 (“gurgling noises”), 7 (“frequent bowel movements (BMs)”), 30 (“urgent BMs”), 31 (“diarrhea”), 32 (“constipation”), 36 (“uncontrolled stools”)] and the European Organization for Research and Treatment of Cancer (EORTC) modules QLQ-C30 (symptom scales: “constipation” and “diarrhea”) and QLQ-CR29 (symptom scales: “defecation problems,” “incontinence,” and “bloating”).

Results

GIQLI “global” and “symptom” indices and the majority of single-item scores and the EORTC QLQ-C30 “constipation” and “diarrhea” subscales showed significant postoperative improvement (p < 0.05). Females and younger age (<70 years) patients appeared to have worse postoperative gastrointestinal function. Rectal cancer patients had more “urgent BMs,” “uncontrolled stools” and worse “global” and “symptom” scores at 3 months and more “diarrhea” at 3 and 6 months than colon cancer patients (p < 0.03). Right colectomy patients had less “excessive passage of gas,” “constipation,” and “uncontrolled stools” than left colectomy patients (3 months, p < 0.01). Anterior resection patients faced more gastrointestinal difficulties, especially in the first 6 months after surgery. Adverse effects related to stage and adjuvant treatment were predominant only at baseline (p < 0.05). GIQLI “diarrhea” and “constipation” scores were correlated with the respective EORTC QLQ-C30 domains (p = 0.0001).

Conclusions

Overall, gastrointestinal function is improved after colorectal cancer surgery. However, women and younger patients are at higher risk of postoperative gastrointestinal dysfunction.     

北京市基层医生医学知识获取途径及临床问题解决方式的现状研究

目的 :了解北京市基层一、二级医院医生获取新的医学知识的主要途径 ,及其在临床实践中解决问题的主要方式。分析影响基层医生将知识转化为临床能力的因素。方法 :北京市海淀区和朝阳区 4 2家基层医院 (包括二级医院 9家 ,一级医院 17家 ,乡卫生院 16家 )共计 6 32名内科系列的医生 ,采用问卷调查方式 ,进行继续医学教育和临床能力调查。结果 :1 基层医生获取医学知识的主要途径中“参加院外市级或区级继续教育培训”排在第一位 (4 4 % ) ,其次是阅读专业期刊书籍 (2 2 % )和上级医生指导 (15 % )。 2 .高级职称医生中通过阅读获取知识的比例明显高于初中级职称的医生。 3.当在临床实践中遇到问题时 ,高级职称医生最常用的解决途径为“查看有关疾病的诊疗指南”、“查看相关书籍、期刊” ,而中低职称医生解决的主要途径为“请教上级医生”、“查看有关疾病的诊疗指南”。 4 .基层医生认为影响诊疗水平提高的原因为“缺乏学习时间”(34% )和“缺乏专家的实际指导”(33% )。 5 .基层医生认为目前继续教育系统存在的问题包括 :与临床实际联系不足 ,且内容重复、陈旧 ,授课时间和地点不合理 ,授课形式枯燥。结论 :1.继续医学教育课程是基层医生获取临床知识的主要途径。 2 .该系统课程设置、教学方式、教学?     

Verifying Hellström-Lindberg score as predictive tool for response to erythropoietin therapy according to the “International Working Group” criteria, in anemic patients affected by myelodysplastic syndrome: a monocentric experience

The Hellström-Lindberg score (HLS) (1997) is designed to predict erythroid response to erythropoietin treatment in myelodysplastic patients. In order to test the validity of this scoring system, 58 patients affected by myelodysplastic syndrome, treated with a “standard dose” approach between 2001 and 2010, were analyzed. The response to erythropoietin treatment was evaluated in accordance with the “international working group” (IWG) criteria. Among the patients only two were scored “poor,” 12 “intermediate,” and 44 “good” (15 of whom were scored “3” and 29 “4”). Although the system was verified as a predictive tool for response to erythropoietin therapy, we noted that of patients scored as “good,” those with a numerical score of “4” responded more frequently than did those scored “3”, as evaluated under both the 2006- and 2000-IWG (“major response”) criteria. The modest response rate in patients scoring “3” did not show a difference in response rate in comparison to the “intermediate” group. The present data suggest that only patients scoring “4” on the scale may show an adequate response to the standard dose erythropoietin therapy, while frontline high-dose therapy should be offered to other patients. A further analysis considering endogenous erythropoietin as a possible determinant of response revealed the optimal cut-off value of 80 mIU/mL, instead of the value of 100 mIU/mL utilized by the HLS.     

对“One Health”行动计划的建议与译文的商榷

在科学技术高度发达的今天,许多经典传染病并未消失,反而新发传染病时有暴发,许多“文明相关疾病”患病率逐渐升高。人们逐步认识到,人类健康与动物和微生物,以及地球上多姿多彩的环境生态密切相关。为此国外有学者提出“One Health”的理念,试图从人类-动物-环境的交互作用出发,为战胜包括人兽共患病在内的诸多传染病找到一条有效的途径。本文就“One Health”的提出和内涵、“One Health”行动计划与我国“大健康”理念的衔接以及“One Health”的中文翻译等问题进行了讨论和分析,以期为“One Health”理念的实践提供参考。     

Exploring Lay Definitions of Asthma and Interpersonal Barriers to Care in a Predominantly Puerto Rican,Inner-City Community

Lay definitions of asthma were elicited through a single open-ended question from a population-based sample of mostly Puerto Rican, inner-city residents in Buffalo, New York. One hundred fifty-five household responses to the question, “What do you think asthma is?” were analyzed qualitatively using the editing approach. Five common codes emerged in order of significance: “symptoms,” “disease,” “triggers,” “threat,” and “coping.” Overall, expressions of illness reflected a largely symptomatic perception of asthma regardless of asthma status. Perceptions of “disease” increased with higher level of education. Patients’ definitions of illness should be considered to help reduce interpersonal barriers to asthma care.     

“Urinary Tract Infection”—Requiem for a Heavyweight

“Urinary tract infection” (“UTI”) is an ambiguous, expansive, overused diagnosis that can lead to marked, harmful antibiotic overtreatment. “Significant bacteriuria,” central to most definitions of “UTI,” has little significance in identifying individuals who will benefit from treatment. “Urinary symptoms” are similarly uninformative. Neither criterion is well defined. Bacteriuria and symptoms remit and recur spontaneously. Treatment is standard for acute uncomplicated cystitis and common for asymptomatic bacteriuria, but definite benefits are few. Treatment for “UTI” in older adults with delirium and bacteriuria is widespread but no evidence supports the practice, and expert opinion opposes it. Sensitive diagnostic tests now demonstrate that healthy urinary tracts host a ubiquitous, complex microbial community. Recognition of this microbiome, largely undetectable using standard agar‐based cultures, offers a new perspective on “UTI.” Everyone is bacteriuric. From this perspective, most people who are treated for a “UTI” would probably be better off without treatment. Elderly adults, little studied in this regard, face particular risk. Invasive bacterial diseases such as pyelonephritis and bacteremic bacteriuria are also “UTIs.” Mindful decisions about antibiotic use will require a far better understanding of how pathogenicity arises within microbial communities. It is likely that public education and meaningful informed‐consent discussions about antibiotic treatment of bacteriuria, emphasizing potential harms and uncertain benefits, would reduce overtreatment. Emphasizing the microbiome's significance and using the term “urinary tract dysbiosis” instead of “UTI” might also help and might encourage mindful study of the relationships among host, aging, microbiome, disease, and antibiotic treatment.     

Prevention of strongyloides hyperinfection syndrome: A rheumatological point of view

BackgroundStrongyloides stercoralis (S.stercoralis) is a parasite that infects humans and in conditions of immunodeficiency may disseminate, causing the potentially fatal strongyloides hyperinfection syndrome (SHS). The aim of this review was to investigate the literature evidence on the prophylaxis of SHS in immunosuppressed patients with rheumatological disorders.Material and methodsThe MEDLINE database (from 1966 to 2008) was searched using the following terms: “strongyloidiasis”, “disseminated strongyloidiasis”, “Strongyloides stercoralis”, “Strongyloides stercoralis dissemination”, “strongyloides hyperinfection syndrome”, “treatment”, “prophylaxis”, “prevention”, “immunocompromised”, “immunodepression”, “immunosuppressed”, “immunosuppression”, “corticosteroids”, “glucocorticoids”, “lupus erythematosus”, “rheumatoid arthritis”, “rheumatic diseases”. A search of the therapeutic studies using the same set of terms was carried out.ResultsNo study on the prophylaxis of SHS restricted to rheumatic immunosuppressed patients was identified. However, two articles have been published on the prophylaxis of strongyloidiasis in other immunosuppressed patients. Additionally, 13 studies dealing with different therapeutical options for strongyloidiasis were identified and presented.ConclusionsSince there is no evidence on the prophylaxis of SHS in immunosuppressed rheumatic patients, the suggested regimen for that prophylaxis may rely on the results obtained from therapeutical studies. Ivermectin has the best safety profile, lower cost and best efficacy and should be the drug of choice for the prophylaxis of SHS in such patients. Although a definitive prophylactic regimen has not been defined, the option for 200 µg/kg/day for 2 days, repeated within 2 weeks, seems to be a reasonable approach. Such regimen should be repeated every 6 months in case of persisting immunosuppression in permanent residents of endemic areas.     

Management of hip involvement in ankylosing spondylitis

Ankylosing spondylitis (AS) is an inflammatory rheumatologic disease characterized by inflammation and progressive structural damage of the affected joints. Hip involvement often results in severe deformities and significant impairment on function. Although, tremendous progress has been made in conservative management for AS, effective prevention strategies for hip involvement and long-term need for total hip arthroplasty (THA) remain indefinite. When hip involvement has progressed to intractable pain and disability, THA is still the most effective treatment strategy to relieve pain and restore function. However, certain AS-specific problems regarding “preoperative preparation,” “intraoperative difficulties,” “perioperative pharmacological management,” “postoperative physiotherapy,” “operation benefits,” and “operation complications” need more concern and further discussion.     

Variability of postural orthostatic tachycardia in patients with myalgic encephalomyelitis and orthostatic intolerance

Central nervous system dysfunction with myalgic encephalomyelitis (ME) has been suggested as the main cause of chronic fatigue syndrome. Fluctuation of the symptom severity and hierarchy is a characteristic feature in ME patients. The characteristics of the sympathetic activation may differ between the “good days” and “bad days” in them. Twenty-four ME patients with orthostatic intolerance underwent a conventional 10-min active standing test and echocardiography both on a “good day” and a “bad day”, defined according to the severity of their symptoms. The mean heart rate at rest was significantly higher on the “bad days” than on the “good days”. During the standing test on a “bad day”, 5 patients (21 %) failed to maintain an upright posture for 10 min, whereas on a “good day” all the 24 patients maintained it. Postural orthostatic tachycardia (POT) (increase in heart rate ≥30 beats/min) or severe POT (heart rate ≥120 beats/min) was observed on the “bad days” in 10 patients (43 %) who did not suffer from the severe tachycardia on the “good days”, suggesting the exaggerated sympathetic nervous activation. In contrast, POT did not occur or severe POT was attenuated on the “bad days” in 5 patients (21 %) who developed POT or severe POT on the “good days”, suggesting the impaired sympathetic activation. Echocardiography revealed significantly lower mean values of both the left ventricular end-diastolic diameter and stroke volume index on the “bad days” compared with the “good days”. In conclusion, in ME patients with orthostatic intolerance, the exaggerated activation of the sympathetic nervous system while standing appears to switch to the impaired sympathetic activation after the system is loaded with the additional accentuated stimuli associated with the preload reduction.     

Complete and incomplete revascularization at aortocoronary bypass surgery: experience with 392 consecutive patients

This report presents our experience with “complete” and “incomplete” revascularization in 392 consecutive patients undergoing aortocoronary artery bypass surgery. Patients were considered to have had “complete” revascularization only if all major coronary arteries with 70 per cent occlusion received at least one bypass graft. Patients were considered “incompletely” revascularized if any vessel with a 70 per cent or more occlusion did not receive at least one bypass graft. The “completely” revascularized cohort contained 186 patients and the “incompletely” revascularized cohort contained 206 patients. The survival of the “completely” and “incompletely” revascularized cohorts was compared postoperatively and at 6, 12, and 24 months using the Chi-square test. Relief of anginal pain rates were compared at 6, 12, and 24 months using the Chi-square test. Analyses were repeated after stratifying for number of vessels diseased. The subgroup with one vessel diseased was, by definition, “completely” revascularized. No significant difference in survival or relief of anginal pain was demonstrated in the total group or in subgroups with 2 and with 3 vessels diseased. The data indicate that “complete” revascularization is not closely coupled to two-year survival or relief of anginal pain.     

Chloride: The queen of electrolytes?

BackgroundChannelopathies, defined as diseases that are caused by mutations in genes encoding ion channels, are associated with a wide variety of symptoms and have been documented extensively over the past decade. In contrast, despite the important role of chloride in serum, textbooks in general do not allocate chapters exclusively on hypochloremia or hyperchloremia and information on chloride other than channelopathies is scattered in the literature.Study designTo systematically review the function of chloride in man, data for this review include searches of MEDLINE, PubMed, and references from relevant articles including the search terms “chloride,” “HCl,” “chloride channel” “acid-base,” “acidosis,” “alkalosis,” “anion gap” “strong anion gap” “Stewart,” “base excess” and “lactate.” In addition, internal medicine, critical care, nephrology and gastroenterology textbooks were evaluated on topics pertaining the assessment and management of acid-base disorders, including reference lists from journals or textbooks.ConclusionChloride is, after sodium, the most abundant electrolyte in serum, with a key role in the regulation of body fluids, electrolyte balance, the preservation of electrical neutrality, acid-base status and it is an essential component for the assessment of many pathological conditions. When assessing serum electrolytes, abnormal chloride levels alone usually signify a more serious underlying metabolic disorder, such as metabolic acidosis or alkalosis. Chloride is an important component of diagnostic tests in a wide array of clinical situations. In these cases, chloride can be tested in sweat, serum, urine and feces. Abnormalities in chloride channel expression and function in many organs can cause a range of disorders.     

Ancient Egyptian medicine and the concept of heart failure

BackgroundThe cardiac glosses of the Ebers papyrus comprise the concepts and notions of the Egyptian physicians about the heart and its diseases. We sought to analyze some of the cardiac glosses of the Ebers papyrus, focusing on those which may describe early concepts of the syndrome of heart failure.Methods and ResultsReview of Joachim's German translation and both Bryan's and Ghalioungui's English translations of the Ebers papyrus. One clinical scenario describes patients with “weakness of the heart” or “cardiac dysfunction:” “His heart is bored,” “The heart weakens,” “This means that the heart does not speak or that the vessels of the heart are dumb. Its information under your hands normally appears because of the air with which they are filled is missing….” Debility that has arisen in the heart.” The other clinical scenario supplies information about patients with heart failure and “fluid retention” or “congestion”: “His heart is flooded. This is the liquid of the mouth. His body parts are all together weak”…“His heart is over flooded….”ConclusionWhether or not Egyptian medicine and the contents of the papyri paved the way for future knowledge, the clinical scenarios included in the Ebers papyrus may represent one of the earliest documented observations of the syndrome of heart failure.