Lyme disease: the quest for magic bullets

Lyme disease represents a growing public health threat. Recent molecular and genetic studies have confirmed that Borrelia burgdorferi, the spirochetal agent of Lyme disease, is one of the most complex bacteria known to man. Affinity for multiple cell types and the presence of non-replicating forms of B. burgdorferi have contributed to persistent infection and failure of simple antibiotic regimens. The controversial clinical science of Lyme disease has impeded reliable diagnosis and effective treatment of this protean illness. Two major clinical hurdles are the absence of a therapeutic endpoint in treating Lyme disease and the presence of tick-borne coinfections that may complicate the course of the illness. New strategies for the diagnosis, treatment and prevention of Lyme disease are urgently needed.     

维生素C在脓毒症及脓毒性休克患者治疗中疗效的Meta分析

目的系统评价静脉输注维生素C对脓毒症及脓毒性休克患者的疗效。 方法计算机检索PubMed、EMBASE、The Cochrane Library、Web of Science、万方、CBM、CNKI电子数据库自建库至2018年8月以来关于维生素C治疗脓毒症及脓毒性休克患者的随机对照研究。由2位研究者按照纳入标准进行文献筛选、数据提取及质量评价后,采用RevMan 5.3软件进行Meta分析。 结果共纳入6个随机对照试验,涉及患者318例。Meta分析结果通过随机效应模型分析得出,试验组与对照组对脓毒症及脓毒性休克患者病死率的影响,差异无统计学意义[RR= 0.82,95%CI（0.48,1.38）,Z= 0.76,P= 0.45]。漏斗图显示各研究间存在发表偏倚。 结论静脉输注维生素C不能改善脓毒症及脓毒性休克患者的病死率。     

Recently published papers: Treating sepsis,measuring troponin and managing the obese

Sepsis and septic shock continue to contribute to our workload and stimulate our research activities although many fundamental questions remain. Studies reported on here focus on inotrope use and a novel way of predicting inotrope response. Continuing this theme more fundamental work is reported examining the mitochondrial respiratory chain and the effects of sepsis coupled with interesting work on lactic acidosis. Troponin raises its head again and we are still left quizzing over its value in the ICU. Finally we discuss a paper on the outcome of the obese patient on a general ICU. Like sepsis a continuing challenge.     

Current role of high dose vitamin C in sepsis management: A concise review

Sepsis and septic shock are common diagnoses for patients requiring intensive care unit admission and associated with high morbidity and mortality. In addition to aggressive fluid resuscitation and antibiotic therapy, several other drugs have been tried as adjuvant therapies to reduce the inflammatory response and improve outcomes. Vitamin C has been shown to have several biological actions, including anti-inflammatory and immunomodulatory effects, which may prove beneficial in sepsis management. Initial trials showed improved patient outcomes when high dose vitamin C was used in combination with thiamine and hydrocortisone. These results, along with relative safety of high-dose (supra-physiological) vitamin C, encouraged physicians across the globe to add vitamin C as an adjuvant therapy in the management of sepsis. However, subsequent large-scale randomised control trials could not replicate these results, leaving the world divided regarding the role of vitamin C in sepsis management. Here, we discuss the rationale, safety profile, and the current clinical evidence for the use of high-dose vitamin C in the management of sepsis and septic shock.     

Vitamin A stimulation of parathyroid hormone: interactions with calcium, hydrocortisone, and vitamin E in bovine parathyroid tissues and effects of vitamin A in man

The effect of vitamin A, a membrane surface-active agent, on parathyroid hormone secretion was studied in vitro, using bovine parathyroid tissue, and in vivo in man. Parathyroid tissues were incubated with vitamin A (retinol), retinoic acid, and calcium, and with hydrocortisone and vitamin E, agents that antagonize the membrane effects of vitamin A. The stimulation of parathyroid hormone release by vitamin A, 10(-6) to 10(-9) mol/1 in vitro, was dose and time dependent. Retinoic acid did not stimulate secretion. High calcium concentration, hydrocortisone, 10(-5) mol/1 and 10(-6) mol/1, and vitamin E, 10(-5) mol/1, antagonized vitamin A-induced parathyroid hormone secretion. Vitamin A increased the lysosomal cathepsin D activity of parathyroid tissues. In human studies, eleven healthy men received two intramuscular injections of vitamin A palmitate, 25 000 units each, within 24 h. In every subject, serum parathyroid hormone increased after vitamin A administration. Our studies indicate that: (1) vitamin A stimulates parathyroid hormone secretion in vitro, possibly through modification of the cell or secretion granule membrane, or through stimulation of lysosomal proteolytic activity, and (2) vitamin A increases serum parathyroid hormone in vivo, and this effect may be important in clinical states of vitamin A excess.     

Adjunctive therapy with vitamin c and thiamine in patients treated with steroids for refractory septic shock: A propensity matched before-after,case-control study

PurposeTriple therapy with steroids, vitamin C and thiamine has been recently proposed as a safe and beneficial in patients with sepsis. In 2017, we added the use of intravenous vitamin C and thiamine in septic shock patients receiving low dose hydrocortisone because poorly responsive to vasopressors. Aim of this study is to verify whether triple therapy rather than steroids alone can improve outcome in patients with refractory shock.Materials and methodsIn this before-after retrospective analysis, we compared septic shock patients admitted to our intensive care unit (ICU) who received triple therapy from June 2017 to November 2019 to septic shock patients who received only hydrocortisone from January 2015 to June 2017. Patients of the two study periods were matched 1:1 using a propensity score model.ResultsA final cohort of 56 patients treated with triple therapy were matched to 56 patients treated only with steroids. Triple therapy reduced the length of mechanical ventilation (p = 0,01) and showed a trend in lowering the 30-day and hospital mortality compared to therapy with only hydrocortisone.ConclusionsAlthough with significant limitations, our experience indicated that triple therapy seems to provide an improvement of clinical outcomes in patients with refractory septic shock.     

脓毒症/严重脓毒症患儿维生素D水平与预后

目的 了解儿童重症监护病房(pediatric intensive care unit,PICU)脓毒症/严重脓毒症患儿维生素D缺乏程度;分析患者入院时维生素D水平与预后之间的关系.方法 本研究为多中心、前瞻性、观察性研究.以2013年3月1日至2014年3月30日期间入住3家儿童医院PICU符合危重症标准的脓毒症/严重脓毒症患儿作为研究对象.入组患者入院24h内留取静脉血2 mL,采用酶联免疫法检测血清25 (OH)维生素D水平.根据维生素D水平,将患者分为维生素D充足、轻度维生素D缺乏和重度维生素D缺乏三组.分析入院时维生素D水平与PICU住院时间、总住院时间、出院病死率、28d病死率和经济费用之间的关系.结果 共纳入病例194例.其中男117例(60.3％),女77例(39.7％).脓毒症/严重脓毒症患分别为96例和98例.出院病死率和28 d病死率分别为6.7％和24.2％.入院时中位维生素D水平9.79 ng/mL (5.32,18.46) ng/mL,维生素D缺乏率77.8％ (151/194),其中重度维生素D缺乏率达50.5％ (98/194).入院时存在重度维生素D缺乏的患者出院病死率显著增加(P=0.011).维生素D水平与PICU住院时间、总住院时间和经济花费间没有进行相关分析.结论 PICU脓毒症/严重脓毒症儿童中维生素D缺乏率高达77.8％;重度维生素D缺乏患者,出院病死率更高.     

Novel biomarker for predicting sepsis mortality: vitamin D receptor

ObjectiveThere are currently no studies on the role of vitamin D receptor (VDR) levels as a cause of or risk factor for sepsis. We aimed to establish the association between VDR levels and 28-day mortality in critically ill patients with sepsis.MethodsThis prospective cross-sectional observational study included 148 patients diagnosed with sepsis who were treated in the intensive care unit. We measured VDR levels, laboratory characteristics, and health scores and related them to survival.ResultsThe 148 patients included 96 survivors and 52 non-survivors, with VDR levels of 1.92 and 1.36 ng/mL, respectively. Baseline VDR was a significant predictor of 28-day mortality, with an area under the curve of 0.778. A low VDR level was significantly associated with lower overall survival in patients with sepsis according to Kaplan–Meier curve analysis. VDR levels were also negatively correlated with lactate, C-reactive protein, acute physiological and clinical health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, and disease severity.ConclusionsVDR levels were associated with high 28-day mortality and negatively correlated with lactate, C-reactive protein, APACHE II and SOFA scores, and disease severity in patients with sepsis. VDR levels can predict poor outcomes in patients with sepsis.     

Preventing the common cold with a vitamin C supplement: a double-blind,placebo-controlled survey

One hundred sixty-eight volunteers were randomized to receive a placebo or a vitamin C supplement, two tablets daily, over a 60-day period between November and February. They used a five-point scale to assess their health and recorded any common cold infections and symptoms in a daily diary. Compared with the placebo group, the active-treatment group had significantly fewer colds (37 vs 50, P<.05), fewer days challenged virally (85 vs 178), and a significantly shorter duration of severe symptoms (1.8 vs 3.1 days, P<.03). Consequently, volunteers in the active group were less likely to get a cold and recovered faster if infected. Few side effects occurred with the active treatment, and volunteers reported greatly increased satisfaction with the study supplement compared with any previous form of vitamin C. This well-tolerated vitamin C supplement may prevent the common cold and shorten the duration of symptoms. Volunteers were generally impressed by the protection afforded them during the winter months and the general acceptability of the study medication.     

硒及维生素E和C对帕金森病患者血液抗氧化功能的调节

目的：探讨不同时期帕金森病患者与正常人体内氧化和抗氧化功能状态及硒、维生素E，C的抗氧化作用。 方法：收集2003—03／2005—03大连市友谊医院神经内科门诊与病房帕金森病患者、可能帕金森病患者、健康体检者，共计90例。①帕盒森病患者组30例，其中男18例。女12例；1年龄43—80岁，平均（66&;#177;8．4）岁，病程1-20年。②很可能帕金森病患者30例，男16例，女14例；年龄37&;#177;73岁，平均（56&;#177;6．3）岁。病程1—12年。③对照组30例，为随机选择的与患者年龄、性别相配的健康人。所有参与者均自愿参加本实验。④受检者苒次化验于服药前，清晨空腹时抽取静脉血2mL，采用亚铁嗪显色比色分析法测定血浆维生素C，E,邻苯三酚自氧化抑制法测定超氧化物歧化酶活性，硫代巴比妥酸反应产物比色分析法测定脂质过氧化水平，采用改良的Hafeman法测定谷胱甘肽过氧化物酶活性。2、3-三氨基萘荧光分光光度法测定硒含量。⑤首次检测后每位受试者服用维生素C，每天服用0．1g，维生素E，每天服用0．1g，古稀胶囊，3次／d，每次3粒，均服用3个月。3个月后，再次检测各组受检者血抗氧化指标。 结果：参加实验90例研究对象，均进入结果分析。④服药前，帕金森病组血浆硒、维生索E、C水平，超氧化物歧化酶、谷胱甘肽过氧化物酶活性明显低于对照组[（121．8&;#177;38.6），（145．6&;#177;51）μg／L；（21．2&;#177;9．5），（26．8&;#177;8.2）μmol／L；（45．2&;#177;13.0），（53．6&;#177;22.8）μmol／L；（281．7&;#177;185）．（398．4&;#177;181．7）μkat／L；（913．5&;#177;216．7），（1020.2&;#177;188．4）μkat／L]，脂质过氧化水平与对照组比较差异无显著性；可能帕金森病组谷胱甘肽过氧化物酶活性、硒水平低于对照组[（945．2&;#177;183．4）μkat／L。（130．4&;#177;42）μg／L]。其余指标比较差异无显著性。②服药后，帕金森病组超氧化物歧化酶、谷胱甘肽过氧化物酶活性、硒水平[（343．4&;#177;126．7）μkat／L，（953．5&;#177;133．4）μkat／L。（132．8&;#177;42）μg/L]高于服药前，维生素E、C、脂质过氧化水平无变化；可能帕金森病组硒、维生索E、C、超氧化物歧化酶、谷胱甘肽过氧化物酶活性水平[（140．2&;#177;39）μg／L，（28．9&;#177;6．7）μmol／L，（54．3&;#177;6．6）μmol／L，（410．1&;#177;6．0）μkat／L，（993．5&;#177;201．7）μkat／L]高于服药前，脂质过氧化水平无显著变化。 结论：帕金森病患者抗氧化的酶类及非酶类系统水平均低于正常，随病情进展而加重。早期干预治疗，有可能提高抗氧化水平。     

硒及维生素E和C对帕金森病患者血液抗氧化功能的调节

目的:探讨不同时期帕金森病患者与正常人体内氧化和抗氧化功能状态及硒、维生素E,C的抗氧化作用。方法:收集2003-03/2005-03大连市友谊医院神经内科门诊与病房帕金森病患者、可能帕金森病患者、健康体检者,共计90例。①帕金森病患者组30例,其中男18例,女12例;年龄43～80岁,平均(66±8.4)岁,病程1～20年。②很可能帕金森病患者30例,男16例,女14例;年龄37～73岁,平均(56±6.3)岁,病程1～12年。③对照组30例,为随机选择的与患者年龄、性别相配的健康人。所有参与者均自愿参加本实验。④受检者首次化验于服药前,清晨空腹时抽取静脉血2mL,采用亚铁嗪显色比色分析法测定血浆维生素C,E,邻苯三酚自氧化抑制法测定超氧化物歧化酶活性,硫代巴比妥酸反应产物比色分析法测定脂质过氧化水平,采用改良的Hafeman法测定谷胱甘肽过氧化物酶活性,2、3-三氨基萘荧光分光光度法测定硒含量。⑤首次检测后每位受试者服用维生素C,每天服用0.1g,维生素E,每天服用0.1g,古稀胶囊,3次/d,每次3粒,均服用3个月。3个月后,再次检测各组受检者血抗氧化指标。结果:参加实验90例研究对象,均进入结果分析。①服药前,帕金森病组血浆硒、维生素E、C水平,超氧化物歧化酶、谷胱甘肽过氧化物酶活性明显低于对照组[(121.8±38.6),(145.6±51)μg/L;(21.2±9.5),(26.8±8.2)μmol/L;(45.2±13.0),(53.6±22.8)μmol/L;(281.7±185),(398.4±181.7)μkat/L;(913.5±216.7),(1020.2±188.4)μkat/L],脂质过氧化水平与对照组比较差异无显著性;可能帕金森病组谷胱甘肽过氧化物酶活性、硒水平低于对照组[(945.2±183.4)μkat/L,(130.4±42)μg/L],其余指标比较差异无显著性。②服药后,帕金森病组超氧化物歧化酶、谷胱甘肽过氧化物酶活性、硒水平[(343.4±126.7)μkat/L,(953.5±133.4)μkat/L,(132.8±42)μg/L]高于服药前,维生素E、C、脂质过氧化水平无变化;可能帕金森病组硒、维生素E、C、超氧化物歧化酶、谷胱甘肽过氧化物酶活性水平[(140.2±39)μg/L,(28.9±6.7)μmol/L,(54.3±6.6)μmol/L,(410.1±6.0)μkat/L,(993.5±201.7)μkat/L]高于服药前,脂质过氧化水平无显著变化。结论:帕金森病患者抗氧化的酶类及非酶类系统水平均低于正常,随病情进展而加重。早期干预治疗,有可能提高抗氧化水平。     

Living with fair use and TEACH: a quest for compliance

With the expansion of Web-based courses in nursing education, faculty members are faced with a greater responsibility to be copyright compliant. This article reviews the changes in copyright law. The Conference on Fair Use (CONFU), the passage of the Digital Millennium and Copyright Act (DMCA), the passage of the Technology Education and Copyright Harmonization (TEACH) Act, and recent legal cases will be discussed. The strategies and resources the authors used to secure copyright permission while designing a Web-based continuing education course will also be described.