钛颗粒负荷对切应力作用下骨髓间质干细胞F-actin表达和DNA含量的影响

假体磨损碎屑颗粒是引起假体一骨界面无菌性炎症和骨溶解而致全关节置换术失败的主要原因之一。磨屑颗粒所诱发的骨溶解须有周围骨组织中成骨细胞分泌足够的骨基质以弥补丢失的骨量，而成骨细胞正常的数量和质量有赖于其来源骨髓祖细胞—骨髓问质干细胞的正常增殖分化能力的维持。为了探讨磨屑钛颗粒对大鼠骨髓间质干细胞(Rat MSCs，rMSCs)产生细胞毒性的可能细胞分子机制，选用健康3月龄SD雄性大鼠，采用Percoll等密度梯度离心法分离获取rMSCs，经体外传代纯化培养后，与不同直径、不同负荷浓度、不同负荷作用时间的钛颗粒悬液共孵育，再采用精准的流室系统对钛颗粒负荷的rMSCs施加一定的流体剪切应力(Fluid shear stress，FSS)后立刻固定细胞，经免疫荧光抗体染色，结合激光共聚焦显微镜技术和图像分析软件定性定量分析rMSCs F—actin表达和DNA含量的变化情况。同时设置相应的未经钛颗粒孵育的rMSCs细胞为对照组细胞。结果显示，切应力作用可上调rMSCs胞内F—actin的表达。亚微(Submieron)直径(0．9μm)的钛颗粒负荷对rMSCs F—actin表达和DNA含量的抑制作用最为显著，并伴有凋亡小体出现；直径为2．7μm的钛颗粒负荷产生的抑制作用略为减弱，而较大直径(6．9μm)的抑制效应最弱。相同条件下，钛颗粒负荷对F—actin的抑制效应有一定的时间和浓度依赖性：以0．1wt％浓度对F—actin表达和DNA含量的抑制效应最为明显，亦有凋亡小体的出现；随着浓度的降低，抑制作用亦减弱，以0．01wt％浓度最弱；随着作用时间的延长，F—actin表达和DNA含量逐渐降低，至实验中的32h达到最低值。提示：磨屑颗粒对rMSCs活力的抑制作用是假体无菌性松动的可能分子机制，对其具体细胞分子机制进行深入研究，必将有助于有效防治假体松动药物的研发应用以及人工关节材料的优化设计，从而为全关节置换术患者真正带来福音。     

Why did persons invited to train in cardiopulmonary resuscitation not do so?

All citizens (N = 22066) aged 16 to 65 of a medium-sized Belgiantown were personally invited to CPR training sessions held intheir neighbourhood. 1152 responded by attending a trainingsession. Those who did not so respond were surveyed (randomsample N=600) for reasons of their not coming. The sample fittedwell with census data for gender, age and suburb location butnot for job, because retired persons and women at home wereover represented. 123 persons did not want to answer the questions. 116 personssaid they were already trained in CPR, 276 said they would accepton a future occasion and 82 said they would not. Three personsdid not answer this question. There was no discrimination for job, gender and suburb locationbetween those who did and did not accept a future training opportunity,nor was the existence of a heart patient among relatives. Theolder the person, the less inclined was that person to participatein CPR training (age effect x² = 17.17, d.f. = 9, P<0.05).The 276 who accepted future training, chose their workplace(221) and/or their social meeting place (club etc.) as the placewhere this future training should be held. We suggest that CPR training is well accepted and that the trainingopportunities should be given at places of work and social gatherings.     

Endobronchiale Applikation von Adrenalin in der kardiopulmonalen Reanimation Pharmakokinetische und -dynamische Untersuchungen beim Hund

Zusammenfassung Das Ziel der vorliegenden Untersuchungen bestand darin, das pharmakokinetische Profil von Adrenalin bei endobronchialer (e.b.) und intravenöser (i.v.) Applikation zu erarbeiten und die gemessenen Adrenalin-Plasmaspiegel mit hämodynamischen Messungen zu korrelieren. Die e.b. Applikation von 100 g/kg Adrenalin erwies sich als ebenso effektiv, wie die i.v.-Gabe von 10 g/kg. Dabei war der Wirkungseintritt der e.b.-Gabe von Adrenalin nur geringfügig um einige Sekunden verzögert. Die Bioverfügbarkeit für e.b. verabreichtes Adrenalin lag zwischen 80 und 85%. Der therapeutische Effekt blieb nach e.b.-Applikation von 100 g/kg Adrenalin wesentlich länger erhalten (ca. 30 min) als nach i.v.-Gabe von 10 g/kg (ca. 3–5 min). Aus den Ergebnissen wird geschlossen, daß die tiefe endobronchiale Instillation von 2–3 mg Adrenalin (verdünnt in 5–10 ml Kochsalzlösung) als alternative Dosierungstechnik bei klinischen Reanimationen betrachtet werden kann.

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Pharmacokinetics and -dynamics of epinephrine administered endobronchially

Summary The present animal study was designed to investigate the pharmacokinetic behavior of epinephrine after endobronchial (e.b.) and intravenous (i.v.) administration and its correlation to pharmacodynamic measurements. We found the effectiveness of e.b.-epinephrine (100 g/kg BW) to be in the same magnitude as i.v.-epinephrine (100 g/kg BW) with only a slight delay in the pharmacodynamic onset of a few seconds. The bioavailability of e.b.-administration of epinephrine was in the range of 80–85%. The therapeutic effect of e.b.-epinephrine (100 pg/kg BW) lasted much longer (30 min) when compared to i.v.-epinephrine (10 g/kg BW) where the pharmacodynamic effect was terminated after 3 to 5 min. For the clinical situation of cardiopulmonary resuscitation a dose of 2–3 mg epinephrine in 5–10 ml of physiological saline instilled deeply into the bronchial system should be considered as alternative administration technique with fast onset and good effectiveness.

Herrn Prof. Dr. Dr. h.c. F. Stelzner zum 65. Geburtstag gewidmet     

极早产儿支气管肺发育不良影响因素的多中心临床研究

目的探讨极早产儿发生支气管肺发育不良(BPD)的影响因素。 方法选择2020年1月1日至12月31日,于青岛大学附属医院、青岛市市立医院、济宁市第一人民医院及枣庄市妇幼保健院出生并接受治疗的208例极早产儿为研究对象。根据是否发生BPD,将其分为BPD组(n＝153)和非BPD组(n＝55);再根据BPD严重程度分度,将BPD组极早产儿分为Ⅰ度BPD亚组(n＝31)、Ⅱ度BPD亚组(n＝17)及Ⅲ度BPD亚组(n＝7)。采用回顾性分析法,统计学比较BPD组与非BPD组,以及3个BPD亚组极早产儿出生与治疗情况、生后14 d内液体摄入量等。采用多因素非条件logistic回归分析,探讨极早产儿发生BPD及BPD极早产儿发生Ⅲ度BPD的影响因素。本研究经青岛大学附属医院医学伦理委员会批准(审批文号：QYFYWZLL26841),并且与所有患儿监护人签署临床研究知情同意书。 结果①BPD组极早产儿出生胎龄、体重、头围及身长,以及生后1、5、10 min Apgar评分,均小于、轻于、短于、低于非BPD组;而孕母产前激素使用率,极早产儿出生窒息率、肺表面活性剂(PS)使用率及早发型败血症(EOS)发生率,以及有创及无创机械通气时间,均高于、长于非BPD组,并且差异均有统计学意义(P<0.05)。②BPD组极早产儿生后第2、4、5、7、11、12天的总液体摄入量,以及生后第6、8~14天肠外液体静脉输注量,均多于非BPD组;生后第1~14天肠内液体摄入量,则均少于非BPD组,并且上述差异均有统计学意义(P<0.05)。③多因素非条件logistic回归分析：极早产儿生后1 min Apgar评分低(OR＝1.866,95%CI：1.063~3.274,P＝0.030),有创机械通气时间长(OR＝1.834,95%CI：1.158~2.905,P＝0.010),无创机械通气时间长(OR＝1.163,95%CI：1.067~1.267,P＝0.001),发生EOS(OR＝0.071,95%CI：0.011~0.465,P＝0.006)是极早产儿发生BPD的独立危险因素;生后第3、4、5天肠内液体摄入量多(OR＝0.671、0.708、0.746,95%CI：0.483~0.932、0.511~0.846、0.583~0.955,P＝0.017、0.004、0.020),是极早产儿发生BPD的独立保护因素。④3个BPD亚组极早产儿出生胎龄、孕母产前激素使用率、出生窒息率、EOS发生率及有创机械通气时间,生后第1、2、4、5、6天总液体摄入量及肠外液体静脉输注量,以及生后第1天肠内液体摄入量比较,差异均有统计学意义(均为P<0.05)。但是,这16项因素均不是BPD极早产儿发生Ⅲ度BPD的独立影响因素。 结论极早产儿发生BPD是多种因素共同作用的结果,减少出生窒息及EOS发生率,优化呼吸支持策略,增加生后第3~5天肠内液体摄入量,有望降低极早产儿BPD发生率。     

测定白血病脑脊液中SIL—2R，IL—6表达的临床意义

为了探讨急性淋巴细胞性白血病 (ALL)患者脑脊液中可溶性白介素 - 2受体 (SIL - 2R)、白介素 6(IL - 6)的表达及意义 ,采用双抗夹心ELISA法测定 3 0例ALL患者脑脊液 (CSF)中SIL - 2R ,IL - 6水平 ,并与 10名正常者进行对照 .结果 :ALL合并中枢神经系统白血病 (CNS -L)组较CNS -L已缓解及未合并CNS -L组二者水平显著升高 (P <0 0 1) ;CNS -L已缓解组二者水平接近对照组 (P >0 0 5 ) ;骨髓缓解及好转组二者水平低于治疗无效组 .结果表明 :监测二者水平变化有助于CNS -L早期诊断、估计预后、判断疗效 .     

Is the Parkland formula still the best method for determining the fluid resuscitation volume in adults for the first 24 hours after injury? — A retrospective analysis of burn patients in Germany

BackgroundR Rapid fluid resuscitation is a crucial therapy during the treatment of patients with extensive burns. In 1968, the Parkland Formula was introduced for the calculation of the estimated volume of the resuscitation fluid. Since then, different methods for the calculation of fluid resuscitation volume have been developed. We aimed to evaluate if the Parkland formula is still the most effective method for fluid resuscitation volume calculation in burn patients.MethodsIn the period between January 2015 and January 2019, data from 569 patients over 16 years old with burns of more than 20% total body surface area (TBSA) and at least 15% TBSA full thickness burns were entered in the German burn registry. The patients were divided into 5 groups (0, +1, ?1, +2, ?2) according to the volume of the resuscitation fluid they received. Group 0 patients received the amount of fluid calculated according to the Parkland formula (n = 83). The 4 other groups received reduced (-1, -2) or increased (+1, +2) fluid volumes in comparison to the value obtained by the Parkland formula.ResultsPatients in Group 0 presented a significantly lower mortality in the first week (4.5%) compared to groups –2 (16.7%) and group +2 (19.5%) (p = 0.021). Furthermore, the mean number of operations in group +2 (5.81) was higher than in group ?2 (3.81). Surviving patients from group +2 presented a longer hospital stay (68.1 days) compared to the other groups. Additionally, the logistic regression analysis showed a higher survival of patients in groups ?2 and ?1 (regression coefficients ?0.11 and ?0.086; Odds Ratio 0.896 and 0.918; 95% Confidence Interval (CI) 0,411–1.951 and 0.42–2.004).ConclusionIn this retrospective study, register based analysis a restrictive fluid regime was associated with a higher survival compared to the liberal Parkland guided fluid regime.     

Mathematical model of volume kinetics and renal function after burn injury and resuscitation

This paper presents a mathematical model of blood volume kinetics and renal function in response to burn injury and resuscitation, which is applicable to the development and non-clinical testing of burn resuscitation protocols and algorithms. Prior mathematical models of burn injury and resuscitation are not ideally suited to such applications due to their limited credibility in predicting blood volume and urinary output observed in wide-ranging burn patients as well as in incorporating contemporary knowledge of burn pathophysiology. Our mathematical model consists of an established multi-compartmental model of blood volume kinetics, a hybrid mechanistic-phenomenological model of renal function, and novel lumped-parameter models of burn-induced perturbations in volume kinetics and renal function equipped with contemporary knowledge on burn-related physiology and pathophysiology. Using the dataset collected from 16 sheep, we showed that our mathematical model can be characterized with physiologically plausible parameter values to accurately predict blood volume kinetic and renal function responses to burn injury and resuscitation on an individual basis against a wide range of pathophysiological variability. Pending validation in humans, our mathematical model may serve as an effective basis for in-depth understanding of complex burn-induced volume kinetic and renal function responses as well as development and non-clinical testing of burn resuscitation protocols and algorithms.     

Variation in acute fluid resuscitation among pediatric burn centers

BackgroundAccurate resuscitation of pediatric patients with large thermal injury is critical to achieving optimal outcomes. The goal of this project was to describe the degree of variability in resuscitation guidelines among pediatric burn centers and the impact on fluid estimates.MethodsFive pediatric burn centers in the Pediatric Injury Quality Improvement Collaborative (PIQIC) contributed data from patients with ≥15% total body surface area (TBSA) burns treated from 2014 to 2018. Each center's resuscitation guidelines and guidelines from the American Burn Association were used to calculate estimated 24-h fluid requirements and compare these values to the actual fluid received.ResultsDifferences in the TBSA burn at which fluid resuscitation was initiated, coefficients related to the Parkland formula, criteria to initiate dextrose containing fluids, and urine output goals were observed. Three of the five centers’ resuscitation guidelines produced statistically significant lower mean fluid estimates when compared with the actual mean fluid received for all patients across centers (4.53 versus 6.35 ml/kg/% TBSA, p < 0.001), (4.90 versus 6.35 ml/kg/TBSA, p = 0.002) and (3.38 versus 6.35 ml/kg/TBSA, p < 0.0001).ConclusionsThis variation in practice patterns led to statistically significant differences in fluid estimates. One center chose to modify its resuscitation guidelines at the conclusion of this study.     

Adoption of rescue colloid during burn resuscitation decreases fluid administered and restores end-organ perfusion

IntroductionTraditionally, lactated Ringer’s solution (LR) has been utilized for the resuscitation of thermally injured patients via the Parkland or Brooke formulas. Both of these formulas include colloid supplementation after 24 h of resuscitation. Recently, the addition of albumin within the initial resuscitation has been reported to decrease fluid creep and hourly fluids given. Our institution has previously advocated for a crystalloid-driven resuscitation. Given reports of improved outcomes with albumin, we pragmatically adjusted these practices and present our findings for doing so.MethodsOur burn registry, consisting of prospectively collected patient data, was queried for those at least 18 years of age who, between July 2017 and December 2018, sustained a thermal injury and completed a formal resuscitation (24 h). At the attending physician’s discretion, rescue colloid was administered using 25% albumin for those failing to respond to traditional resuscitation (patients with sustained urine output of <0.5 mL/kg over 2–3 h, or unstable vital signs and ongoing fluid administration). We compared the total volume of the crystalloid-only and rescue colloid resuscitation fluids given to patients. We also examined the in/out fluid balances during resuscitation. Statistical analysis was performed using Stata software.ResultsA total of 91 patients with thermal injuries were included: the median age was 40 (IQR 31–57), 73% were male, and 30 patients received rescue albumin. The percentage of total body surface area burned (%TBSA) was greater in those who received rescue albumin (40.3% vs. 34%; p = 0.047). Despite a higher %TBSA in the albumin group, the total LR given during resuscitation was not significantly different between groups (15,914.43 mL vs. 11,828.71 mL; p = 0.129) even when normalized for TBSA and weight (ml LR/kg/%TBSA: 4.31 vs. 3.66; p = 0.129. The average in/out fluid ratio for the rescue group was higher than for the crystalloid group (0.83 ± 0.05 vs. 0.59 ± 0.11; p = 0.06) and returned to normal after colloid administration.ConclusionRescue albumin administration decreases the amount of fluid administered per %TBSA during resuscitation, and also increases end organ function as evidenced by increased urinary output. These effects occurred in patients who sustained larger burns and failed to respond to traditional crystalloid resuscitation. Our findings led us to modify our current protocol and a related prospective study of clinical outcomes.