Effects of unilateral superimposed high-frequency jet ventilation on porcine hemodynamics and gas exchange during one-lung flooding

BACKGROUND Superimposed high-frequency jet ventilation(SHFJV)is suitable for respiratory motion reduction and essential for effective lung tumor ablation.Fluid filling of the target lung wing one-lung flooding(OLF)is necessary for therapeutic ultrasound applications.However,whether unilateral SHFJV allows adequate hemodynamics and gas exchange is unclear.AIM To compared SHFJV with pressure-controlled ventilation(PCV)during OLF by assessing hemodynamics and gas exchange in different animal positions.METHODS SHFJV or PCV was used alternatingly to ventilate the non-flooded lungs of the 12 anesthetized pigs during OLF.The animal positions were changed from left lateral position to supine position(SP)to right lateral position(RLP)every 30 min.In each position,ventilation was maintained for 15 min in both modalities.Hemodynamic variables and arterial blood gas levels were repeatedly measured.RESULTS Unilateral SHFJV led to lower carbon dioxide removal than PCV without abnormally elevated carbon dioxide levels.SHFJV slightly decreased oxygenation in SP and RLP compared with PCV;the lowest values of PaO_(2) and PaO_(2)/FiO_(2) ratio were found in SP[13.0;interquartile range(IQR):12.6-5.6 and 32.5(IQR:31.5-38.9)kPa].Conversely,during SHFJV,the shunt fraction was higher in all animal positions(highest in the RLP:0.30).CONCLUSION In porcine model,unilateral SHFJV may provide adequate ventilation in different animal positions during OLF.Lower oxygenation and CO_(2) removal rates compared to PCV did not lead to hypoxia or hypercapnia.SHFJV can be safely used for lung tumor ablation to minimize ventilation-induced lung motion.

German critical incident reporting system database of prehospital emergency medicine: Analysis of reported communication and medication errors between 2005–2015

BACKGROUND: Communication failure in prehospital emergency medicine can affect patient safety as it does in other areas of medicine as well. We analyzed the database of the critical incident reporting system for prehospital emergency medicine in Germany retrospectively regarding communication errors.METHODS: Experts of prehospital emergency medicine and risk management screened the database for verbal communication failure, non-verbal communication failure and missing communication at all.RESULTS: Between 2005 and 2015, 845 reports were analyzed, of which 247 reports were considered to be related to communication failure. An arbitrary classifi cation resulted in six different kinds: 1) no acknowledgement of a suggestion; 2) medication error; 3) miscommunication with dispatcher; 4) utterance heard/understood improperly; 5) missing information transfer between two persons; and 6) other communication failure.CONCLUSION: Communication defi cits can lead to critical incidents in prehospital emergency medicine and are a very important aspect in patient safety.

Pathogen detection in patients with perihilar cholangiocarcinoma:Implications for targeted perioperative antibiotic therapy

Background:Cholestasis should be relieved by biliary drainage prior to major liver resection.This condition is often associated with bacterial colonization of the otherwise sterile biliary system.Cholangitis reduces the regenerative capacity of the remaining liver.Therefore,targeted antibiotic therapy is a key feature in perioperative treatment in patients with perihilar cholangiocarcinoma(pCCC).Methods:Between December 1999 and December 2017,251 pCCC patients were treated in our center.In total,115 patients underwent a microbiological analysis.In addition to the characterization of the specific microorganisms and antibiotic resistance,we analyzed subgroups according to preoperative intervention.Results:Enterococci(87/254,34%)and Enterobacteria(65/254,26%)were the most frequently detected genera.In 43%(50/115)of patients,Enterococcus faecalis was found in the bile duct sample.Enterococcus faecium(29/115)and Escherichia coli(29/115)were detected in 25%of patients.In patients with percutaneous transhepatic biliary drainage(3/8,38%)or stents(24/79,30%),Enterococcus faecium was diagnosed most frequently(P<0.05).Enterococcus faecium and Klebsiella oxytoca were significantly more frequently noted in the time period after 2012(P<0.05).With regard to fungal colonization,the focus was on various Candida strains,but these strains generally lacked resistance.Conclusions:pCCC patients exhibit specific bacterial colonization features depending on the type of preoperative biliary intervention.Specifically,targeted antibiosis should be applied in this patient cohort to minimize the risk of biliary complications after major liver resection.In our cohort,the combination of meropenem and vancomycin represents an effective perioperative medical approach.

面瘫患者健侧面部动静态指标的三维测量分析

目的基于面部三维动态定量分析系统(3-Dimensional Analysis System for Facial Motion,3D-ASFM)对健康受试者及面瘫患者健侧面部测量,探讨面瘫后健侧面部静态和动态指标的变化。方法纳入23例单侧面瘫患者,匹配年龄相当的健康受试者作为对照。同时纳入74例不同年龄段的单侧面瘫患者。对所有受试者均进行面部主观评估(House-Brackmann分级和Sunnybrook评分)和面部三维动态测量。比较面瘫患者健侧面部动静态指标与正常人面部指标的差异。分析健侧指标是否受年龄、性别、面瘫程度及侧别等影响。结果面瘫患者健侧静态指标各数值均大于正常人。部分动态指标为面瘫组大于对照组,余指标未见明显统计学差异。与对照组相比,面瘫后男女间上下睑间距差异更明显,但动态指标无显著性差异。健侧除了鼻唇沟宽度与年龄有一定正相关性外,余指标未明显受年龄影响。不同面瘫侧别患者健侧指标无显著性差异。面瘫的程度与健侧指标无明显相关性。结论面瘫之后,患者健侧面部无论是静态还是运动均会发生改变,大部分改变与面瘫程度、年龄、性别、侧别等无关。

单侧面神经切除后面部运动特征定量分析

目的应用面部三维动态定量分析系统(3-Dimensional Analysis System for Facial Motion,3D-ASFM)对面神经部分切除术后的患者进行测量,探讨修复与未修复患者面部静态和动态指标的变化。方法14例面神经部分切除患者,分为神经修复组(9例)和未修复组(5例)。对所有患者进行半年以上跟踪随访,中位随访期13个月。所有患者术前及术后均进行面部运动主观评估(House-Brackmann分级和Sunnybrook评分)和面部三维动态测量。比较三种评估结果相关性。比较修复组与未修复组患者术前、术后各评估结果,对修复组患者各面部区域进行分析。结果3D-ASFM分析结果分别与House-Brackmann分级(H-BGS)、Sunnybrook评分(SFGS)进行秩相关分析,相关系数分别为-0.707(P<0.05)和0.798(P<0.05)。面瘫越严重,3D-ASFM与主观评价系统的相关性越差。术后H-BGS、SFGS总分均存在统计学差异(P<0.05),修复组好于未修复组,3D-ASFM总分在两组间无统计学差异(P>0.05),但鼻旁运动好于未修复者。修复组患者术前、术后H-BGS、SFGS、3D-ASFM总分均无统计学差异(P>0.05)。所有患者健侧动态指标中,上面部运动较术前减小,下面部运动较术前增加。结论面部三维动态定量分析结果与传统主观评价系统有较好的相关性。神经修复对面中部运动影响最大。面神经切除手术不仅造成同侧面部运动改变,也会影响对侧面部运动。

颞骨内段面神经前移的效果分析

目的分析颞骨内段面神经移位对于面神经功能的影响,总结颞骨内段面神经移位外科技术要点。方法回顾性分析我单位2015年5月至2018年1月行侧颅底手术中未受肿瘤侵犯或轻度侵犯的患者面神经前移的临床资料,选择术前House-Brackmann(H-B)面瘫分级系统I级,且影像学评估面神经未被肿瘤包绕或包绕小于180°的病例,评估其术后面部运动(H-B分级)情况。结果共14例患者,其中颞下窝进路TypeA 9例,TypeA+B 5例。病理类型包括副神经节瘤10例(71.43%),神经鞘瘤3例(21.43%),岩尖胆脂瘤1例(7.14%)。平均随访时间23.42月(12个月至44个月)。14例(100%)术后平均5.67月时恢复至H-B I-II级。结论在面神经未收肿瘤侵犯或轻度侵犯的情况下,移位面神经导致术后永久面瘫的几率很小。面神经移位过程中保持神经被膜完整、避免神经张力过大、轻柔止血等手术技术是保护面神经功能的保证。

Magnetic resonance imaging in children and adolescents with chronic inflammatory bowel disease

Inflammatory bowel diseases(IBD) represent challenges, both from a diagnostic, and therapeutic point of view. Deep-seated anatomic structures are difficult to assess by ultrasound technique alone. As radiation-free alternative cross-sectional imaging method, magnetic resonance imaging of the intestinal structures is costly and time-consuming. Examination of pediatric patients imply additional considerations: reduction of body motions in younger children and consideration of the most appropriate preparation, and examination technique. The demanding Sellink technique is the only means for appropriately distending the lesser intestine in order to detect small bowel strictures. Oral intake of contrast medium(CM) alone shows its limitations regarding distensibility. The need for intravenous contrast media application needs to be considered, too. Active inflammation of both intestinal wall, and mesentery can be demonstrated accurately. Nevertheless, viable alternatives to CM application is desirable, considering non-negligible adverse reactions. Recent data suggest diffusion weighted imaging might fill this diagnostic gap. Irrespective of sequence technique chosen, bowel movement remains a major obstacle. Antispasmolytics in their function as smooth muscle relaxants help in improving image quality, however, their use in children might be off-label. Optimal preparation for the examination and appropriate imaging technique allow for diagnosing typical patterns of changes in IBD, such as bowel wall thickening, ulcers, mural stratification, strictures, creeping fat, and comb sign, and lymphadenopathy. The article gives a detailed overview of current significance of magnetic resonance imaging pediatric patients suffering from IBD, considering indications, limitations, and safety aspects.

Individualized treatment of gastric cancer:Impact of molecular biology and pathohistological features

Gastric cancer is one of the most common malignancies worldwide.The overall prognosis remains poor over the last decades even though improvements in surgical outcomes have been achieved.A better understanding of the molecular biology of gastric cancer and detection of eligible molecular targets might be of central interest to further improve clinical outcome.With this intention,first steps have been made in the research of growth factor signaling.Regarding morphogens,cell cycle and nuclear factor-κB signaling,a remarkable count of target-specific agents have been developed,nevertheless the transfer into the field of clinical routine is still at the beginning.The potential utility of epigenetic targets and the further evaluation of micro RNA signaling seem to have potential for the development of novel treatment strategies in the future.

Current techniques for AB0-incompatible living donor liver transplantation

For a long time, it was considered medical malpractice to neglect the blood group system during transplantation. Because there are far more patients waiting for organs than organs available, a variety of attempts have been made to transplant AB0-incompatible(AB0i) grafts. Improvements in AB0 i graft survival rates have been achieved with immunosuppression regimens and plasma treatment procedures. Nevertheless, some grafts are rejected early after AB0 i living donor liver transplantation(LDLT) due to antibody mediated rejection or later biliary complications that affect the quality of life. Therefore, the AB0 i LDLT is an option only for emergency situations, and it requires careful planning. This review compares the treatment possibilities and their effect on the patients' graft outcome from 2010 to the present. We compared 11 transplant center regimens and their outcomes. The best improvement, next to plasma treatment procedures, has been reached with the prophylactic use of rituximab more than one week before AB0 i LDLT. Unfortunately, no standardized treatment protocols are available. Each center treats its patients with its own scheme. Nevertheless, the transplant results are homogeneous. Due to refined treatment strategies, AB0 i LDLT is a feasible option today and almost free of severe complications.

DNA plasticity and damage in amyotrophic lateral sclerosis

The pathophysiology of amyotrophic lateral sclerosis （ALS） is particularly challenging due to the heteroge- neity of its clinical presentation and the diversity of cellular, molecular and genetic peculiarities involved. Molecular insights unveiled several novel genetic factors to be inherent in both familial and sporadic dis- ease entities, whose characterizations in terms of phenotype prediction, pathophysiological impact and putative prognostic value are a topic of current researches. However, apart from genetically well-defined high-confidence and other susceptibility loci, the role of DNA damage and repair strategies of the genome as a whole, either elicited as a direct consequence of the underlying genetic mutation or seen as an autono- mous parameter, in the initiation and progression of ALS, and the different cues involved in either process are still incompletely understood. This mini review summarizes current knowledge on DNA alterations and counteracting DNA repair strategies in ALS pathology and discusses the putative role of unconventional DNA entities including transposable elements and extrachromosomal circular DNA in the disease process. Focus is set on SODl-related pathophysiology, with extension to FUS, TDP-43 and C90RF72 mutations. Advancing our knowledge in the field will contribute to an improved understanding of this relentless dis- ease, for which therapeutic options others than symptomatic approaches are almost unavailable.

Regulation of neuronal survival by DNA methyltransferases

The limited regenerative capacity of neuronal cells requires tight orchestration of cell death and survival regulation in the context of longevity, age-associated diseases as well as during the development of the nervous system. Subordinate to genetic networks epigenetic mechanisms like DNA methylation and histone modifications are involved in the regulation of neuronal development, function and aging. DNA methylation by DNA methyltransferases （DNMTs）, mostly correlated with gene silencing, is a dynamic and reversible process. In addition to their canonical actions performing cytosine methylation, DNMTs influence gene expression by interactions with histone modifying enzymes or complexes increasing the complexity of epigenetic transcriptional networks. DNMTs are expressed in neuronal progenitors, post-mi- totic as well as adult neurons. In this review, we discuss the role and mode of actions of DNMTs including downstream networks in the regulation of neuronal survival in the developing and aging nervous system and its relevance for associated disorders.

Intestinal Wnt in the transition from physiology to oncology

Adult stem cells are necessary for self-renewal tissues and regeneration after damage.Especially in the intestine,which self-renews every few days,they play a key role in tissue homeostasis.Therefore,complex regulatory mechanisms are needed to prevent hyperproliferation,which can lead in the worst case to carcinogenesis or under-activation of stem cells,which can result in dysfunctional epithelial.One main regulatory signaling pathway is the Wnt/β-catenin signaling pathway.It is a highly conserved pathway,withβ-catenin,a transcription factor,as target protein.Translocation ofβ-catenin from cytoplasm to nucleus activates the transcription of numerous genes involved in regulating stem cell pluripotency,proliferation,cell differentiation and regulation of cell death.This review presents a brief overview of the Wnt/β-catenin signaling pathway,the regulatory mechanism of this pathway and its role in intestinal homeostasis.Additionally,this review highlights the molecular mechanisms and the histomorphological features of Wnt hyperactivation.Furthermore,the central role of the Wnt signaling pathway in intestinal carcinogenesis as well as its clinical relevance in colorectal carcinoma are discussed.

LHX1–a multifunctional regulator in preoptic area-derived interneuron development

In the cerebral cortex,local inhibition is achieved by different types of gamma-aminobutyric(GABA)-expressing interneurons,representing essential key players of cortical information processing(Marin,2012).Their development has to be highly orchestrated to ensure proper numbers and subtype composition in the adult cortex and defects in interneuron development contribute to the pathophysiology of psychiatric diseases(Marin,2012).

Treatment options for spontaneous and postoperative sclerosing mesenteritis

Sclerosing mesenteritis is a rare pathology with only a few described cases in the literature. The etiology is unclear; however, several potential triggers, including abdominal surgery and abdominal trauma, have been discussed. The pathology includes a benign acute or chronic inflammatory process affecting the adipose tissue of the mesenterium. Despite it being a rare disease, sclerosing mesenteritis is an important differential diagnosis in patients after abdominal surgery or patients presenting spontaneously with signs of acute inflammation and abdominal pain. We present here three cases with sclerosing mesenteritis. In two cases, sclerosing mesenteritis occurred postoperatively after abdominal surgery. One patient was treated because of abdominal pain and specific radiological signs revealing spontaneous manifestation of sclerosing mesenteritis. So far there are no distinct treatment algorithms, so the patients were treated differently, including steroids, antibiotics and watchful waiting. In addition, we reviewed the current literature on treatment options for this rare disease.

Suicidal behavior-advances in clinical and neurobiological research and improvement of prevention strategies

Suicide is the 14^(th)leading cause of death worldwide.It is responsible for 1%-5%of all mortality.This article highlights the latest developments in universal,selective,and indicated prevention strategies.Concerning universal suicide prevention,current research has shown that strategies such as restricting access to lethal means(e.g.,control of analgesics and hot-spots for suicide by jumping)and school-based awareness programs are most efficacious.Regarding selective prevention,substantial progress can be expected in psychological screening methods for suicidal behavior.The measurement of implicit cognition proved to be more valid in predicting future suicide attempts than classic clinical assessment.Latest developments are smartphone-based interventions and realtime monitoring of suicidal behavior.Great effort has been made to establish valid neurobiological screening methods(e.g.,genetic and epigenetic risk factors for suicide,hypothalamic-pituitary-adrenal axis)without yielding a major breakthrough.Potentially,multiple biomarkers rather than a single one are necessary to identify individuals at risk.With regard to indicated prevention in form of psychopharmacological treatment,recent pharmacoepidemiological studies and meta-analyses have supported a protective role of antidepressants,lithium,and clozapine.However,the data concerning a specific anti-suicidal effect of these drugs are currently not consistent.Promising results exist for ketamine in reducing suicidal ideation,independently of its antidepressant effect.Concerning psychotherapy,recent findings suggest that psychotherapeutic interventions specifically designed to prevent suicide re-attempts are most efficacious.Specifically,cognitive behavioral therapy and psychodynamic therapy approaches proved to decrease the number of suicide re-attempts significantly.

Antibacterial Zinc Oxide Nanoparticle Coating of Polyester Fabrics

Polyester knitted fabrics have been equipped with antibacterial properties by coating with aqueous suspensions of zinc oxide (ZnO) with different particle diameters. It can be shown that the antibacterial efficacy against Staphylococcus aureus and Klebsiella pneumonia and the permanence of the coating after defined washing cycles depends on the composition of the ZnO dispersion. To improve the wettability of the textile, the combustion chemical vapor deposition (CCVD) is used to generate a hydrophilic nano layer of a hydroxyl terminated silicon network on the surface of the textiles. The comparison of CCVD-treated and untreated polyester samples does not show differences in the antibacterial activity. The influence of the coating in terms of amount and particle size of ZnO on the viability and proliferation of 3T3 mouse fibroblast cells is examined. A particle content of a maximum of 20 μg ZnO/cm2 is found to be cytocompatible for coating of textiles.

Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia

CDC42 controls intestinal epithelial(IEC)stem cell(IESC)division.How aberrant CDC42 initiates intestinal inflammation or neoplasia is unclear.We utilized models of inflam-matory bowel diseases(IBD),colorectal cancer,aging,and IESC injury to determine the loss of intestinal Cdc42 upon inflammation and neoplasia.Intestinal specimens were collected to determine the levels of CDC42 in IBD or colorectal cancer.Cdc42 floxed mice were crossed with Villin-Cre,Villin-CreERT2 and/or Lgr5-eGFP-IRES-CreERT2,or Bmi1-CreERT2 mice to generate Cdc42 deficient mice.Irradiation,colitis,aging,and intestinal organoid were used to evaluate CDC42 upon mucosal inflammation,IESC/progenitor regenerative capacity,and IEC repair.Our studies revealed that increased CDC42 in colorectal cancer correlated with lower survival;in contrast,lower levels of CDC42 were found in the inflamed IBD colon.Colonic Cdc42 depletion significantly reduced Lgr5+IEsCs,increased progenitors'hyperplasia,and induced mucosal inflammation,which led to crypt dysplasia.Colonic Cdc42 depletion markedly enhanced irra-diation-or chemical-induced colitis.Depletion or inhibition of Cdc42 reduced colonic Lgr5+IESC regeneration.In conclusion,depletion of Cdc42 reduces the IESC regeneration and IEC repair,leading to prolonged mucosal inflammation.Constitutive monogenic loss of Cdc42 in-duces mucosal inflammation,which could result in intestinal neoplasia in the context of aging.

Small extrachromosomal circular DNA in amyotrophic lateral sclerosis matter

Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity and ancestry(GBD 2016 Motor Neuron Disease Colla borators,2018).While~10% of diagnoses involve a family history(fALS),most cases are considered sporadic(sALS).However,population-based studies suggest that even cases without a common index mutation impart heritability(Ryan et al.,2019),indicating a crucial role of rare and as yet unknown genetic denominators.

Adipose tissue induces a better liver regeneration after living liver donation in normal weight donors

Background:Extrahepatic body fat could be a relevant factor affecting liver regeneration after partial hepatectomy.The aim of this study was to evaluate the potential role of body fatty tissue in liver regeneration capacity after liver resection in a cohort of living donors.Methods:We observed liver regeneration in 120 patients:70 living donors who underwent right hepatectomy and 50 recipients who got a right graft transplantation.Liver volumetry and body fat analysis were performed based on the computed tomography images with volumetry software.The gain of liver volume was calculated between three points in time considering the absolute and percentage values:before surgery and early(median 10 days,range 4-21 days)and late(median 27 weeks,range 18-40 weeks)after surgery.Pearson’s correlation was used to examine the potential correlation between adipose tissue and liver regeneration.Results:Pearson’s correlation showed a significant correlation between the subcutaneous fat mass index(sFMI)and early(r=0.173,P=0.030),as well late(r=0.395,P=0.0004)percental liver volume gain in the whole collective.Under stratification in donor’s and recipient’s collectives,the effect of extrahepatic adipose tissue appears in multiple regression only in the donor’s collective:early(β=0.219,T=2.137,P=0.036)and late(β=0.390,T=2.552,P=0.015)percental volume gain.Conclusions:Subcutaneous adipose tissue is a positive predictive factor to estimate the goodness of liver regeneration after partial hepatectomy in normosthenic donors.

Evaluation of Ultrasound-based Surveillance for Hepatocellular Carcinoma in Patients at Risk:Results From a German Multicenter Retrospective Cohort Study

Background and Aims:Hepatocellular carcinoma(HCC)surveillance in patients at risk is strongly recommended and usually performed by ultrasound(US)semiannually with or without alfa-fetoprotein(AFP)measurements.Quality pa-rameters except for surveillance intervals have not been strictly defined.We aimed to evaluate surveillance success and risk factors for surveillance failure.Methods:Patients with≥1 US prior to HCC diagnosis performed at four tertiary referral hospitals in Germany between 2008 and 2019 were retrospectively analyzed.Surveillance success was defined as HCC detection within Milan criteria.Results:Only 47%of 156 patients,median age 63(interquartile range:57-70)years,56%male,and 96%with cirrhosis,received recom-mended surveillance modality and interval.Surveillance fail-ure occurred in 29%and was significantly associated with lower median model for end-stage liver disease(MELD)score odds ratio(OR)1.154,95%confidence interval(CI):1.027-1.297,p=0.025)and HCC localization within right liver lobe(OR:6.083,95%CI:1.303-28.407,p=0.022),but not with AFP≥200μg/L.Patients with surveillance failure had sig-nificantly more intermediate/advanced tumor stages(93%vs.6%,p<0.001),fewer curative treatment options(15%vs.75%,p<0.001)and lower survival at 1 year(54%vs.75%,p=0.041),2 years(32%vs.57%,p=0.019)and 5 years(0%vs.16%,p=0.009).Alcoholic and non-alcoholic fatty liver disease(OR:6.1,95%CI:1.7-21.3,p=0.005)and ascites(OR:3.9,95%CI:1.2-12.6,p=0.021)were in-dependently associated with severe visual limitations on US.Conclusions:US-based HCC surveillance in patients at risk frequently fails and its failure is associated with unfavorable patient-related outcomes.Lower MELD score and HCC lo-calization within right liver lobe were significantly associated with surveillance failure.