Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory functions.In only approximately 5%of the cases,AD is familial,as often predis...Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory functions.In only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the cases.The amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.展开更多
Mineral and bone disorder(MBD)in chronic kidney disease(CKD)is tightly linked to cardiovascular disease(CVD).In this study,we aimed to compare the prognostic value of nine MBD biomarkers to determine those associated ...Mineral and bone disorder(MBD)in chronic kidney disease(CKD)is tightly linked to cardiovascular disease(CVD).In this study,we aimed to compare the prognostic value of nine MBD biomarkers to determine those associated best with adverse cardiovascular(CV)outcomes and mortality.In 5217 participants of the German CKD(GCKD)study enrolled with an estimated glomerular filtration rate(eG FR)between 30–60 mL·min-1 per 1.73 m2 or overt proteinuria,serum osteoprotegerin(OPG),C-terminal fibroblast growth factor-23(FGF23),intact parathyroid hormone(iP TH),bone alkaline phosphatase(BAP),cross-linked C-telopeptide of type 1 collagen(CTX1),procollagen 1intact N-terminal propeptide(P1NP),phosphate,calcium,and 25-OH vitamin D were measured at baseline.Participants with missing values among these parameters(n=971)were excluded,leaving a total of 4246 participants for analysis.During a median follow-up of6.5 years,387 non-CV deaths,173 CV deaths,645 nonfatal major adverse CV events(MACEs)and 368 hospitalizations for congestive heart failure(CHF)were observed.OPG and FGF23 were associated with all outcomes,with the highest hazard ratios(HRs)for OPG.In the final Cox regression model,adjusted for CV risk factors,including kidney function and all other investigated biomarkers,each standard deviation increase in OPG was associated with non-CV death(HR 1.76,95%CI:1.35–2.30),CV death(HR 2.18,95%CI:1.50–3.16),MACE(HR 1.38,95%CI:1.12–1.71)and hospitalization for CHF(HR 2.05,95%CI:1.56–2.69).Out of the nine biomarkers examined,stratification based on serum OPG best identified the CKD patients who were at the highest risk for any adverse CV outcome and mortality.展开更多
AIM:To assess the efficacy and safety of non-penetrating deep sclerectomy(NPDS)with uveoscleral implant plus subconjunctival and intrascleral collagen matrix overcoming the superficial scleral flap lips(modified deep ...AIM:To assess the efficacy and safety of non-penetrating deep sclerectomy(NPDS)with uveoscleral implant plus subconjunctival and intrascleral collagen matrix overcoming the superficial scleral flap lips(modified deep sclerectomy technique,DS)and minimal use of mitomycin C in glaucoma surgery.METHODS:A retrospective review of 47 consecutive glaucoma patients who underwent NPDS with DS between January 2017 and May 2018.Best-corrected visual acuity,intraocular pressure(IOP),post-operative need for glaucoma medications,visual field mean deviation(MD),re-interventions,needling revisions and laser goniopuncture were noted.Absolute success was defined as IOP≤18 mm Hg without topical medication.Relative success was defined as the same criteria but with the addition of any antihypertensive medication.IOP over 18 mm Hg on two consecutive followup visits was considered as a failure.RESULTS:Fifty-two eyes of 47 patients were evaluated.Mean preoperative IOP was 25.37±6.47 mm Hg,and decreased to 15.04±4.73 at 12mo and 12.21±4.1 at 24mo(all P<0.0001).Requirement for topical medications dropped from a mean of 3.06±0.25 per patient to 0.51±0.99 and 1.11±1.23 respectively after 12 and 24mo(all P<0.0001).No medications were required in 45.5%of patients after 24mo.Relative and absolute success rate at 24mo were 85.5%±5%and 48.5%±7.4%,respectively.CONCLUSION:DS is a safe and effective nonpenetrating glaucoma surgery variation.It aims to retain the patency of all pathways created for aqueous humor drainage:the intrascleral bleb,the supraciliary space and the open communication between intrascleral and subconjunctival compartments.展开更多
AIM： To evaluate prognostic indicators for the outcome of patients with perihilar extrahepatic cholangiocarcinoma in an unselected cohort. METHODS： We retrospectively analyzed 98 patients with perihilar cholangiocar...AIM： To evaluate prognostic indicators for the outcome of patients with perihilar extrahepatic cholangiocarcinoma in an unselected cohort. METHODS： We retrospectively analyzed 98 patients with perihilar cholangiocarcinoma. Twenty-three patients （23.5%） underwent tumor resection. Patients with non-resectable tumors underwent either transpapillary or percutaneous transhepatic biliary drainage. Additionally, 32 patients （32.7%） received photodynamic therapy （PDT） and 18 patients （18.4%） systemic chemotherapy. Predefined variables at the time of diagnosis and characteristics considering the mode of treatment were entered into a Cox＇s proportional hazards model. Included in the analysis were age, tumor stage following the modified Bismuth-Corlette classification, bilirubin, prothrombin time （PT）, C-reactive protein （CRP）, carbohydrate antigen 19-9 （CA19-9）, history of weight loss, surgical resection, chemotherapy and PDT. RESULTS： The Kaplan-Meier estimate of overall median survival was 10.5 （95%CI： 8.4-12.6） mo. In the univariate analysis, low Bismuth stage, low CRP and surgical resection correlated significantly with better survival. In the multivariate analysis, only CRP （P = 0.005） and surgical resection （P = 0.029） were found to be independently predictive of survival in the cohort. Receiver operating characteristic （ROC） analysis identified a CRP level of 11.75 mg/L as the value associated with the highest sensitivity and specificity predicting a survival 〉 5 too. Applying Kaplan-Meier analysis, patients with a CRP 〈 12 mg/L at the time of diagnosis had a significantly longer median survival than patients with higher values （16.2 vs 7.6 mo; P = 0.009）.CONCLUSION： This retrospective analysis identified CRP level at the time of diagnosis as a novel indicator for the prognosis of patients with perihilar cholangiocarcinoma. It should be evaluated in future prospective trials on this entity.展开更多
Constipation and fecal impaction are frequent and distressing complaints in pediatric gastroenterology. Especially in neurologically handicapped children, treatment of severe forms of slow-transit constipation (STC) c...Constipation and fecal impaction are frequent and distressing complaints in pediatric gastroenterology. Especially in neurologically handicapped children, treatment of severe forms of slow-transit constipation (STC) can be difficult. In the majority of cases, STC is of unknown etiology. However, in recent years, there is growing evidence that interstitial cells of Cajal (ICCs), which serve as electrical pacemakers and generate spontaneous electrical slow waves in the gastrointestinal tract, might play an important role in the pathophysiology of STC. It remains unclear whether morphological ICC alterations seen in affected patients are based on congenital developmental anomalies, or whether they are a consequence of long-term constipation with secondary damage of the gastrointestinal nervous system. To the best of our knowledge, we present the first case of a patient with histological alterations in ICC morphology who displayed multiple alterations of c-kit at the level of mRNA. The protein encoded by c-kit is the receptor tyrosine kinase Kit (CD117), which is crucial for development and function of ICCs. Therefore, these findings provide a new explanation for congenital alterations of ICC development that result in gastrointestinal motility disorders.展开更多
BACKGROUND Despite the emerging knowledge about colorectal anastomotic leakage(CAL)through the increasing number of clinical and experimental studies, there is no generally accepted definition of CAL. Because of the w...BACKGROUND Despite the emerging knowledge about colorectal anastomotic leakage(CAL)through the increasing number of clinical and experimental studies, there is no generally accepted definition of CAL. Because of the wide variety of definitions used in literature, comparison of study outcomes and quality of care is complicated.AIM To reach consensus on the definition of CAL using a modified Delphi method.METHODS The RAND/UCLA appropriateness method was used. The expert panel consisted of international colorectal surgeons and researchers who had published three or more articles about CAL. The consensus process consisted of two online distributed questionnaires and a third round with a recommendation. In the questionnaires participants were asked to rate the appropriateness of statements using a 1-9 Likert scale. Consensus was defined as a panel median between 1-3 or 7-9 without disagreement. In the final round a recommendation was formed regarding the definition of CAL and the expert panel was asked if they agreed or disagreed.RESULTSTwenty-three authors participated in the first round and twenty-one finished the second round. After two rounds consensus was reached on 37 items(80%) in nine different categories. The International Study Group of Rectal Cancer definition is the most frequently advised general definition by our panel. Consensus was reached regarding the clinical symptoms of CAL, which serum markers contributes to the suspicion of CAL, which radiological and perioperative findings should be considered as CAL, which grading system is appropriate and if there should be a range of postoperative days in the definition. Eventually, 19 experts completed all three rounds of which 16(84%) agreed with our final recommendations for the definition of CAL.CONCLUSION A consensus-based recommendation for the definition of CAL was formed using our modified Delphi method that can be widely incorporated in the field.展开更多
To investigate the impact of hepatic encephalopathy before orthotopic liver transplantation (OLT) and neurological complications after OLT on employment after OLT. METHODSOne hundred and fourteen patients with chronic...To investigate the impact of hepatic encephalopathy before orthotopic liver transplantation (OLT) and neurological complications after OLT on employment after OLT. METHODSOne hundred and fourteen patients with chronic liver disease aged 18-60 years underwent neurological examination to identify neurological complications, neuropsychological tests comprising the PSE-Syndrome-Test yielding the psychometric hepatic encephalopathy score, the critical flicker frequency and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), completed a questionnaire concerning their occupation and filled in the short form 36 (SF-36) to assess health-related quality of life before OLT and 12 mo after OLT, if possible. Sixty-eight (59.6%) patients were recruited before OLT, while on the waiting list for OLT at Hannover Medical School [age: 48.7 ± 10.2 years, 45 (66.2%) male], and 46 (40.4%) patients were included directly after OLT. RESULTSBefore OLT 43.0% of the patients were employed. The patients not employed before OLT were more often non-academics (employed: Academic/non-academic 16 (34.0%)/31 vs not employed 10 (17.6%)/52, P = 0.04), had more frequently a history of hepatic encephalopathy (HE) (yes/no; employed 15 (30.6%)/34 vs not employed 32 (49.2%)/33, P = 0.05) and achieved worse results in psychometric tests (RBANS sum score mean ± SD employed 472.1 ± 44.5 vs not employed 443.1 ± 56.7, P = 0.04) than those employed. Ten patients (18.2%), who were not employed before OLT, resumed work afterwards. The patients employed after OLT were younger [age median (range, min-max) employed 47 (42, 18-60) vs not employed 50 (31, 29-60), P = 0.01], achieved better results in the psychometric tests (RBANS sum score mean ± SD employed 490.7 ± 48.2 vs not employed 461.0 ± 54.5, P = 0.02) and had a higher health-related quality of life (SF 36 sum score mean ± SD employed 627.0 ± 138.1 vs not employed 433.7 ± 160.8; P < 0.001) compared to patients not employed after OLT. Employment before OLT (P < 0.001), age (P < 0.01) and SF-36 sum score 12 mo after OLT (P < 0.01) but not HE before OLT or neurological complications after OLT were independent predictors of the employment status after OLT. CONCLUSIONHE before and neurological complications after OLT have no impact on the employment status 12 mo after OLT. Instead younger age and employment before OLT predict employment one year after OLT.展开更多
BACKGROUND:Micro-RNAs(miRNAs) are small,non-coding RNA species considered to fine-tune basic cellular functions by modulating target gene translation and/or mRNA stability.A common G/C polymorphism(rs2910164) in the p...BACKGROUND:Micro-RNAs(miRNAs) are small,non-coding RNA species considered to fine-tune basic cellular functions by modulating target gene translation and/or mRNA stability.A common G/C polymorphism(rs2910164) in the precursor(pre-) miR-146a gene engaged in NF-κB signaling and apoptosis pathways has been reported to modulate the genetic risk of hepatocellular carcinoma by increased G-allelic production of mature miR-146a.We investigated rs2910164 in a large Europeanbased cholangiocarcinoma(CCA) cohort.METHODS:We recruited 182 CCA patients and 350 controls in three academic medical centers.Genotyping for rs2910164 was performed by PCR-based assays with 5’-nuclease and fluorescence detection.Genotype frequencies were tested for consistency with the Hardy-Weinberg equilibrium using an exact test;allelic and genotypic differences between the patients and controls were assessed by the Chi-square test and Armitage’s trend test.Exploratory subgroup analyses included gender,tumor localization(extra-versus intrahepatic CCA) and early-onset CCA.RESULTS:Genotype distributions were consistent with the Hardy-Weinberg equilibrium.No significant differences in either allele or genotype distributions were detected between the CCA and control groups or the respective subgroups investigated.However,there was a trend for a protective effect of the heterozygous single-nucleotide polymorphism state GC,as indicated by an underrepresentation in the CCA group in general(29% vs 35%;P=0.18) and,in particular,for extrahepatic tumor sites(26% vs 35%;OR=0.67;95% CI,0.43-1.02;P=0.065).CONCLUSIONS:Our data do not support a prominent contribution of the pre-miR-146a sequence variant in the genetic predisposition to CCA.However,current studies functionally characterizing rs2910164 have proposed that distinct repertoires of target genes are addressed by genotype-specific mature miR146a species.Given the detected trend towards a potentially protective role of GC heterozygosity,a subtle modulation of genetic CCA risk by the pre-miR-146a GC genotype may exist and should be evaluated further.展开更多
Hepatitis B represents a global health threat because its chronic course and sequelae contribute to a high morbidity and mortality. Hepatitis B virus(HBV) infection can be controlled by vaccines, antiviral treatment, ...Hepatitis B represents a global health threat because its chronic course and sequelae contribute to a high morbidity and mortality. Hepatitis B virus(HBV) infection can be controlled by vaccines, antiviral treatment, and by interrupting transmission. Rare vaccine escape mutants are serious because they eliminate vaccine protection. Here, we present a 74-year-old vaccinated patient with HBV reactivation 11 years after kidney transplantation. The patient was HBV-positive but HBs Ag-negative prior to vaccination 6 years before transplantation. The reactivated virus was HBV genotype F3 with vaccine escape mutations G145 R, P120 Q, and Q129 P. The patient was successfully treated with entecavir. The epidemiological reasons for this subgenotype, which is extremely rare in Western Europe, were unclear. This case illustrates that second-generation vaccines are not always effective in a specific group of patients.展开更多
As recognition of mast cell(MC) involvement in a range of chronic inflammatory disorders has increased, diagnosticians' suspicions of MC activation disease(MCAD) in their chronically mysteriously inflamed patients...As recognition of mast cell(MC) involvement in a range of chronic inflammatory disorders has increased, diagnosticians' suspicions of MC activation disease(MCAD) in their chronically mysteriously inflamed patients have similarly increased. It is now understood that the various forms of systemic mastocytosis- diseases of inappropriate activation and proliferation of MCs seemingly driven by a small set of rare, usually constitutively activating mutations in assorted MC regulatory elements-comprise merely the tip of the MCAD iceberg, whereas the far larger and far more clinically heterogeneous(and thus more difficult to recognize) bulk of the iceberg consists of assorted forms of MC activation syndrome(MCAS) which manifest little to no abnormal MC proliferation and may originate from a far more heterogeneous set of MC mutations. It is reasonable to suspect MCAD when symptoms and signs of MC activation are present and no other diagnosis better accounting for the full range of findings is present. Initial laboratory assessment should include not only routine blood counts and serum chemistries but also a serum total tryptase level, which helps direct further evaluation for mastocytosis vs MCAS. Appropriate tissue examinations are needed to diagnose mastocytosis, while elevated levels of relatively specific mast cell mediators are sought to support diagnosis of MCAS. Whether assessing for mastocytosis or MCAS, testing is fraught with potential pitfalls which can easily yield false negatives leading to erroneous rejection of diagnostic consideration of MCAD in spite of a clinical history highly consistent with MCAD. Efforts at accurate diagnosis of MCAD are worthwhile, as many patients then respond well to appropriately directed therapeutic efforts.展开更多
Primary central nervous system lymphomas (PCNSL) frequently reveal genomic instability. We analysed different functional genetic variants affecting the folate and homocysteine metabolism important for DNA integrity in...Primary central nervous system lymphomas (PCNSL) frequently reveal genomic instability. We analysed different functional genetic variants affecting the folate and homocysteine metabolism important for DNA integrity in 31 PCNSL patients and 142 controls. We found significantly less carriers of the methionine synthase c. 2756A> G (D919G) missense polymorphism among the patients (0.16 vs 0.42; odds ratio 0.26, CI(95%): 0.09-0.74; P=0.005), suggesting a protective function of the G allele. These data stimulate further epidemiological and functional studies focusing on the role of homoeysteine and folate metabolism in lymphoma tumorigenesis.展开更多
Background:Cells of the retinal pigment epithelium(RPE)accumulate different kinds of granules(lipofuscin,melanolipofuscin,melanosomes)within their cell bodies,with lipofuscin and melanolipofuscin being autofluorescent...Background:Cells of the retinal pigment epithelium(RPE)accumulate different kinds of granules(lipofuscin,melanolipofuscin,melanosomes)within their cell bodies,with lipofuscin and melanolipofuscin being autofluorescent after blue light excitation.High amounts of lipofuscin granules within the RPE have been associated with the development of RPE cell death and age-related macular degeneration(AMD);however,this has not been confirmed in histology so far.Here,based on our previous dataset of RPE granule characteristics,we report the characteristics of RPE cells from human donor eyes that show either high or low numbers of intracellular granules or high or low autofluorescence(AF)intensities.Methods:RPE flatmounts of fifteen human donors were examined using high-resolution structured illumination microscopy(HR-SIM)and laser scanning microscopy(LSM).Autofluorescent granules were analyzed regarding AF phenotype and absolute number of granules.In addition,total AF intensity per cell and granule density(number of granules per cell area)were determined.For the final analysis,RPE cells with total granule number below 5th or above the 95th percentile,or a total AF intensity±1.5 standard deviations above or below the mean were included,and compared to the average RPE cell at the same location.Data are presented as mean±standard deviation.Results:Within 420 RPE cells examined,42 cells were further analyzed due to extremes regarding total granule numbers.In addition,20 RPE cells had AF 1.5 standard deviations below,28 RPE cells above the mean local AF intensity.Melanolipofuscin granules predominate in RPE cells with low granule content and low AF intensity.RPE cells with high granule content have nearly twice(1.8 times)as many granules as an average RPE cell.Conclusions:In normal eyes,outliers regarding autofluorescent granule load and AF intensity signals are rare among RPE cells,suggesting that granule deposition and subsequent AF follows intrinsic control mechanisms at a cellular level.The AF of a cell is related to the composition of intracellular granule types.Ongoing studies using AMD donor eyes will examine possible disease related changes in granule distribution and further put lipofuscin´s role in aging and AMD further into perspective.展开更多
The aim of this study was to investigate an association between the development of cholangiocarcinoma(CCA)and the ABO variant rs505922(known to increase pan-creatic cancer risk)in a large cohort of European individual...The aim of this study was to investigate an association between the development of cholangiocarcinoma(CCA)and the ABO variant rs505922(known to increase pan-creatic cancer risk)in a large cohort of European individuals with CCA.In total,180 individuals with CCA and 350 CCA-free controls were included.The ABO variant rs505922 was genotyped using a polymerase chain reaction-based assay.Association between this single nucleotide polymorphism(SNP)and CCA was tested in contingency tables.Neither allele distributions nor association tests and regression analysis provided evidence for an increased risk of CCA among carriers of the ABO variant(all P > 0.05).Nevertheless,we documented a deviation from Hardy-Weinberg equilibrium in the entire CCA cohort(P = 0.028)and for patients with intrahe-patic(P = 0.037)but not extrahepatic tumor localization(P > 0.05).The association tests did not provide evidence for a prominent role of the investigated SNP in the genetic risk of CCA.However,Hardy-Weinberg disequilibrium in the entire cohort and the intrahepatic CCA subgroup warrants future studies investigating a potential CCA risk modulation by individual blood groups.展开更多
BACKGROUND Leiomyosacromas in the Extremities are rare malignant smooth muscle tumors.Adjuvant radiation therapy, in combination with wide surgical excision allows the best chance of treatment. During the follow up pa...BACKGROUND Leiomyosacromas in the Extremities are rare malignant smooth muscle tumors.Adjuvant radiation therapy, in combination with wide surgical excision allows the best chance of treatment. During the follow up pathological fractures are common complications that can be accompanied by Implant failure and defect situations that are most challenging in their management.CASE SUMMARY We present a case of a 52-year-old female suffering from a pathological fracture of the humeral shaft 10 yr after resection of a Leiomyosarcoma and postoperative radiotherapy. She developed implant failure after retrograde nailing and another failure after revision to double plate fixation. In a two-stage revision, the implants were removed and the huge segmental defect created after debridement was bridged by a compound osteosynthesis with nancy nails and bone cement for formation of the induced membrane. Due to the previous radiotherapy treatment,20 cm of the humeral shaft were declared devascularized but were left in situ as a scaffold. In the second stage, a vascularized fibula graft was used in combination with a double plate fixation and autologous spongiosa grafts for final reconstruction.CONCLUSION This combinatory treatment approach led to a successful clinical outcome and can be considered in similar challenging cases.展开更多
AIM: To test the methodical and pre-analytical performance of a new multiplex cancer biomarker panel using magnetic beads. METHODS: The MILLIPLEX? MAP Human Circulating Cancer Biomarker Magnetic Bead Panel 1 comprises...AIM: To test the methodical and pre-analytical performance of a new multiplex cancer biomarker panel using magnetic beads. METHODS: The MILLIPLEX? MAP Human Circulating Cancer Biomarker Magnetic Bead Panel 1 comprises the tumor markers carcinoembryonic antigen, alpha-fetoprotein, total prostate-specific antigen, cancer antigen 15-3, cancer antigen 19-9, cancer antigen 125, cytokeratine 19-fragment, β-human chorionic gonadotropin, human epididymis protein 4, osteopontin, prolactin, the cell death and angiogenesis markers soluble Fas, soluble Fas-ligand, tumor necrosis factor related apoptosisinducing ligand, vascular endothelial growth factor andthe immunological markers interleukin-6(IL-6), IL-8, tumor necrosis factor-α, transforming growth factor α, fibroblast growth factor-2, macrophage migration inhibitory factor, leptin, hepatocyte growth factor, and stem cell factor. We determined intra- and inter-assay imprecision as well as dilution linearity using quality controls and serum pools. Furthermore, the stability of the 24 biomarkers examined in this panel was ascertained by testing the influence of different storage temperatures and time span before centrifugation.RESULTS: For all markers measured in the synthetic internal quality controls, the intra-assay imprecision ranged between 2.26% and 9.41%, while for 20 of 24 measured markers in the physiological serum pools, it ranged between 1.68% and 12.87%. The inter-assay imprecision ranged between 1.48%-17.12% for 23 biomarkers in synthetic, and between 4.59%-23.88% for 18 biomarkers in physiological quality controls. Here, single markers with very low concentration levels had increased imprecision rates. Dilution linearity was acceptable(70%-130% recovery) for 20 biomarkers. Regarding pre-analytical influencing factors, most markers were stable if blood centrifugation was delayed or if serum was stored for up to 24 h at 4 ℃ and 25 ℃ after centrifugation. Comparable results were obtained in serum and plasma for most markers. However, great changes were observed for single markers.CONCLUSION: MILLIPLEX? MAP Human Circulating Cancer Biomarker Magnetic Bead Panel 1 assay is a stable and precise method for detection of most biomarkers included in the kit. However, single markers have to be interpreted with care.展开更多
Renal cell carcinoma (RCC) is one of the most important urological tumors and is one of the most common cancer diseases worldwide. Unfortunately, the treatment options are very limited due to resistances. Non-invasive...Renal cell carcinoma (RCC) is one of the most important urological tumors and is one of the most common cancer diseases worldwide. Unfortunately, the treatment options are very limited due to resistances. Non-invasive physical plasma (NIPP) is currently becoming a promising and very well tolerated treatment option for cancer. NIPP represents a highly energized gas and induc</span><span style="font-family:Verdana;">es varying antioncogenic cell responses in tumor cells. And also in t</span><span style="font-family:Verdana;">he case of RCC, NIPP treatment has great potential to enhance and supplement existing anticancer treatment options. Outstanding characteristics of NIPP treatment are 1) a precise and local effect on the treated tissue and 2) an almost exclusive effect on treated tumor cells without side effects. This allows </span><span style="font-family:Verdana;">an enormously large therapeutic window and makes the combination o</span><span style="font-family:Verdana;">f NIPP treatment and classical therapy appear particularly promising. In addition to R</span><span style="font-family:Verdana;">CC, plasma oncology offers an extremely innovative physical treatme</span><span style="font-family:Verdana;">nt method for future oncology in general.</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">This brief review article summarizes the current knowledge on the potential use of NIPP in RCC therapy.展开更多
<strong>Objective:</strong><span><span style="font-family:Verdana;"> Misoprostol vaginal insert (MVI) is proven to induce labor by a </span><span style="font-family:Verd...<strong>Objective:</strong><span><span style="font-family:Verdana;"> Misoprostol vaginal insert (MVI) is proven to induce labor by a </span><span style="font-family:Verdana;">continuously release of PGE1. Previous reports showed that MVI reduced</span><span style="font-family:Verdana;"> induction to delivery time as well as active labor time but it also increased uterine tachysystole. Here we attempted to clarify whether MVI is safe and </span><span style="font-family:Verdana;">efficient for women with pregnancies >40 weeks in a single institute.</span> <b><span style="font-family:Verdana;">Methods: </span></b><span style="font-family:Verdana;">This study was performed in Lutheran Hospital Bergisch Gladbach, Germany 2014-2019. A total of 304 women between 40 + 0 to 42 + 0 weeks underwent labor induction with MVI. Outcomes were</span></span><span style="font-family:Verdana;">:</span><span><span style="font-family:Verdana;"> 1) maternal: time from insertion </span><span style="font-family:Verdana;">to delivery, interventions, mode of delivery, and uterine tachysystole, 2)</span><span style="font-family:Verdana;"> neo</span></span><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;">natal: cord blood pH, APGAR scores, and admission to a neonatal clinic. This </span><span style="font-family:Verdana;">study ended unexpectedly due to the withdrawal of MVI (Misodel<span style="white-space:nowrap;"><sup>TM</sup></span>) in</span><span style="font-family:Verdana;"> September 2019. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">75.7% (n = 230) of women gave birth within 24 hours after MVI placement. 72.2% (n = 140) nulliparous women and 81.8% (n = 90) </span><span style="font-family:Verdana;">parous women delivered within 24 hours. In two cases emergency CS was</span><span style="font-family:Verdana;"> required. 67.8% (n = 206) of women delivered vaginal. 2.3% (n = 7) of cord pH levels were below 7.10. 3.3% (n = 10) of newborns were transmitted to a neonatal clinic. </span><b><span style="font-family:Verdana;">Conclusion: </span></b><span style="font-family:Verdana;">MVI is an efficient method to induce labor for </span><span style="font-family:Verdana;">pregnant women beyond 40 + 0 weeks. However, considering various</span><span style="font-family:Verdana;"> compli</span><span style="font-family:Verdana;">cations observed (uterine tachysystole and fetal distress leading to a high</span><span style="font-family:Verdana;"> number of CS), we cannot universally advocate the use of MVI.</span></span>展开更多
基金funded by the Deutsche Forschungsgemeinschaft(DFG),the BONFOR program of the Medical Faculty of the University of Bonn,and the Alexander-von-Humboldt Foundation.
文摘Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory functions.In only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the cases.The amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.
基金supported by grants from the Federal Ministry of Education and Research(Bundesministerium für Bildung und ForschungBMBF+7 种基金www.bmbf.deFKZ 01ER 0804,01ER 0818,01ER 0819,01ER 0820,and 01ER 0821)the Foundation for Preventive Medicine of the KfH(Kuratorium für Heimdialyze und Nierentransplantation e.V.-Stiftung Praventivmedizin),and corporate sponsorsfurther supported by the German Research Foundation(SFB/TRR219 project C1—Project-ID 322900939)supported by the clinician scientist program of the German Society of Internal Medicine(DGIM)the Else Kr?ner-FreseniusStiftung Excellence Fellowship(2022_EKES.03)supported by a clinician scientist position funded by the German Research Council(DFG)within the clinical research unit 344(CRU344)supported by BMBF within the framework of the e:Med research and funding concept(grant 01ZX1912B)。
文摘Mineral and bone disorder(MBD)in chronic kidney disease(CKD)is tightly linked to cardiovascular disease(CVD).In this study,we aimed to compare the prognostic value of nine MBD biomarkers to determine those associated best with adverse cardiovascular(CV)outcomes and mortality.In 5217 participants of the German CKD(GCKD)study enrolled with an estimated glomerular filtration rate(eG FR)between 30–60 mL·min-1 per 1.73 m2 or overt proteinuria,serum osteoprotegerin(OPG),C-terminal fibroblast growth factor-23(FGF23),intact parathyroid hormone(iP TH),bone alkaline phosphatase(BAP),cross-linked C-telopeptide of type 1 collagen(CTX1),procollagen 1intact N-terminal propeptide(P1NP),phosphate,calcium,and 25-OH vitamin D were measured at baseline.Participants with missing values among these parameters(n=971)were excluded,leaving a total of 4246 participants for analysis.During a median follow-up of6.5 years,387 non-CV deaths,173 CV deaths,645 nonfatal major adverse CV events(MACEs)and 368 hospitalizations for congestive heart failure(CHF)were observed.OPG and FGF23 were associated with all outcomes,with the highest hazard ratios(HRs)for OPG.In the final Cox regression model,adjusted for CV risk factors,including kidney function and all other investigated biomarkers,each standard deviation increase in OPG was associated with non-CV death(HR 1.76,95%CI:1.35–2.30),CV death(HR 2.18,95%CI:1.50–3.16),MACE(HR 1.38,95%CI:1.12–1.71)and hospitalization for CHF(HR 2.05,95%CI:1.56–2.69).Out of the nine biomarkers examined,stratification based on serum OPG best identified the CKD patients who were at the highest risk for any adverse CV outcome and mortality.
文摘AIM:To assess the efficacy and safety of non-penetrating deep sclerectomy(NPDS)with uveoscleral implant plus subconjunctival and intrascleral collagen matrix overcoming the superficial scleral flap lips(modified deep sclerectomy technique,DS)and minimal use of mitomycin C in glaucoma surgery.METHODS:A retrospective review of 47 consecutive glaucoma patients who underwent NPDS with DS between January 2017 and May 2018.Best-corrected visual acuity,intraocular pressure(IOP),post-operative need for glaucoma medications,visual field mean deviation(MD),re-interventions,needling revisions and laser goniopuncture were noted.Absolute success was defined as IOP≤18 mm Hg without topical medication.Relative success was defined as the same criteria but with the addition of any antihypertensive medication.IOP over 18 mm Hg on two consecutive followup visits was considered as a failure.RESULTS:Fifty-two eyes of 47 patients were evaluated.Mean preoperative IOP was 25.37±6.47 mm Hg,and decreased to 15.04±4.73 at 12mo and 12.21±4.1 at 24mo(all P<0.0001).Requirement for topical medications dropped from a mean of 3.06±0.25 per patient to 0.51±0.99 and 1.11±1.23 respectively after 12 and 24mo(all P<0.0001).No medications were required in 45.5%of patients after 24mo.Relative and absolute success rate at 24mo were 85.5%±5%and 48.5%±7.4%,respectively.CONCLUSION:DS is a safe and effective nonpenetrating glaucoma surgery variation.It aims to retain the patency of all pathways created for aqueous humor drainage:the intrascleral bleb,the supraciliary space and the open communication between intrascleral and subconjunctival compartments.
文摘AIM： To evaluate prognostic indicators for the outcome of patients with perihilar extrahepatic cholangiocarcinoma in an unselected cohort. METHODS： We retrospectively analyzed 98 patients with perihilar cholangiocarcinoma. Twenty-three patients （23.5%） underwent tumor resection. Patients with non-resectable tumors underwent either transpapillary or percutaneous transhepatic biliary drainage. Additionally, 32 patients （32.7%） received photodynamic therapy （PDT） and 18 patients （18.4%） systemic chemotherapy. Predefined variables at the time of diagnosis and characteristics considering the mode of treatment were entered into a Cox＇s proportional hazards model. Included in the analysis were age, tumor stage following the modified Bismuth-Corlette classification, bilirubin, prothrombin time （PT）, C-reactive protein （CRP）, carbohydrate antigen 19-9 （CA19-9）, history of weight loss, surgical resection, chemotherapy and PDT. RESULTS： The Kaplan-Meier estimate of overall median survival was 10.5 （95%CI： 8.4-12.6） mo. In the univariate analysis, low Bismuth stage, low CRP and surgical resection correlated significantly with better survival. In the multivariate analysis, only CRP （P = 0.005） and surgical resection （P = 0.029） were found to be independently predictive of survival in the cohort. Receiver operating characteristic （ROC） analysis identified a CRP level of 11.75 mg/L as the value associated with the highest sensitivity and specificity predicting a survival 〉 5 too. Applying Kaplan-Meier analysis, patients with a CRP 〈 12 mg/L at the time of diagnosis had a significantly longer median survival than patients with higher values （16.2 vs 7.6 mo; P = 0.009）.CONCLUSION： This retrospective analysis identified CRP level at the time of diagnosis as a novel indicator for the prognosis of patients with perihilar cholangiocarcinoma. It should be evaluated in future prospective trials on this entity.
文摘Constipation and fecal impaction are frequent and distressing complaints in pediatric gastroenterology. Especially in neurologically handicapped children, treatment of severe forms of slow-transit constipation (STC) can be difficult. In the majority of cases, STC is of unknown etiology. However, in recent years, there is growing evidence that interstitial cells of Cajal (ICCs), which serve as electrical pacemakers and generate spontaneous electrical slow waves in the gastrointestinal tract, might play an important role in the pathophysiology of STC. It remains unclear whether morphological ICC alterations seen in affected patients are based on congenital developmental anomalies, or whether they are a consequence of long-term constipation with secondary damage of the gastrointestinal nervous system. To the best of our knowledge, we present the first case of a patient with histological alterations in ICC morphology who displayed multiple alterations of c-kit at the level of mRNA. The protein encoded by c-kit is the receptor tyrosine kinase Kit (CD117), which is crucial for development and function of ICCs. Therefore, these findings provide a new explanation for congenital alterations of ICC development that result in gastrointestinal motility disorders.
基金Supported by the Dutch Research Council(NWO)research programme Vidi project,No.91719343。
文摘BACKGROUND Despite the emerging knowledge about colorectal anastomotic leakage(CAL)through the increasing number of clinical and experimental studies, there is no generally accepted definition of CAL. Because of the wide variety of definitions used in literature, comparison of study outcomes and quality of care is complicated.AIM To reach consensus on the definition of CAL using a modified Delphi method.METHODS The RAND/UCLA appropriateness method was used. The expert panel consisted of international colorectal surgeons and researchers who had published three or more articles about CAL. The consensus process consisted of two online distributed questionnaires and a third round with a recommendation. In the questionnaires participants were asked to rate the appropriateness of statements using a 1-9 Likert scale. Consensus was defined as a panel median between 1-3 or 7-9 without disagreement. In the final round a recommendation was formed regarding the definition of CAL and the expert panel was asked if they agreed or disagreed.RESULTSTwenty-three authors participated in the first round and twenty-one finished the second round. After two rounds consensus was reached on 37 items(80%) in nine different categories. The International Study Group of Rectal Cancer definition is the most frequently advised general definition by our panel. Consensus was reached regarding the clinical symptoms of CAL, which serum markers contributes to the suspicion of CAL, which radiological and perioperative findings should be considered as CAL, which grading system is appropriate and if there should be a range of postoperative days in the definition. Eventually, 19 experts completed all three rounds of which 16(84%) agreed with our final recommendations for the definition of CAL.CONCLUSION A consensus-based recommendation for the definition of CAL was formed using our modified Delphi method that can be widely incorporated in the field.
基金Supported by The German Federal Ministry of Education and Research,No.01EO0802
文摘To investigate the impact of hepatic encephalopathy before orthotopic liver transplantation (OLT) and neurological complications after OLT on employment after OLT. METHODSOne hundred and fourteen patients with chronic liver disease aged 18-60 years underwent neurological examination to identify neurological complications, neuropsychological tests comprising the PSE-Syndrome-Test yielding the psychometric hepatic encephalopathy score, the critical flicker frequency and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), completed a questionnaire concerning their occupation and filled in the short form 36 (SF-36) to assess health-related quality of life before OLT and 12 mo after OLT, if possible. Sixty-eight (59.6%) patients were recruited before OLT, while on the waiting list for OLT at Hannover Medical School [age: 48.7 ± 10.2 years, 45 (66.2%) male], and 46 (40.4%) patients were included directly after OLT. RESULTSBefore OLT 43.0% of the patients were employed. The patients not employed before OLT were more often non-academics (employed: Academic/non-academic 16 (34.0%)/31 vs not employed 10 (17.6%)/52, P = 0.04), had more frequently a history of hepatic encephalopathy (HE) (yes/no; employed 15 (30.6%)/34 vs not employed 32 (49.2%)/33, P = 0.05) and achieved worse results in psychometric tests (RBANS sum score mean ± SD employed 472.1 ± 44.5 vs not employed 443.1 ± 56.7, P = 0.04) than those employed. Ten patients (18.2%), who were not employed before OLT, resumed work afterwards. The patients employed after OLT were younger [age median (range, min-max) employed 47 (42, 18-60) vs not employed 50 (31, 29-60), P = 0.01], achieved better results in the psychometric tests (RBANS sum score mean ± SD employed 490.7 ± 48.2 vs not employed 461.0 ± 54.5, P = 0.02) and had a higher health-related quality of life (SF 36 sum score mean ± SD employed 627.0 ± 138.1 vs not employed 433.7 ± 160.8; P < 0.001) compared to patients not employed after OLT. Employment before OLT (P < 0.001), age (P < 0.01) and SF-36 sum score 12 mo after OLT (P < 0.01) but not HE before OLT or neurological complications after OLT were independent predictors of the employment status after OLT. CONCLUSIONHE before and neurological complications after OLT have no impact on the employment status 12 mo after OLT. Instead younger age and employment before OLT predict employment one year after OLT.
基金supported by a grant from the HOMFOR(T201000688 to ZV)
文摘BACKGROUND:Micro-RNAs(miRNAs) are small,non-coding RNA species considered to fine-tune basic cellular functions by modulating target gene translation and/or mRNA stability.A common G/C polymorphism(rs2910164) in the precursor(pre-) miR-146a gene engaged in NF-κB signaling and apoptosis pathways has been reported to modulate the genetic risk of hepatocellular carcinoma by increased G-allelic production of mature miR-146a.We investigated rs2910164 in a large Europeanbased cholangiocarcinoma(CCA) cohort.METHODS:We recruited 182 CCA patients and 350 controls in three academic medical centers.Genotyping for rs2910164 was performed by PCR-based assays with 5’-nuclease and fluorescence detection.Genotype frequencies were tested for consistency with the Hardy-Weinberg equilibrium using an exact test;allelic and genotypic differences between the patients and controls were assessed by the Chi-square test and Armitage’s trend test.Exploratory subgroup analyses included gender,tumor localization(extra-versus intrahepatic CCA) and early-onset CCA.RESULTS:Genotype distributions were consistent with the Hardy-Weinberg equilibrium.No significant differences in either allele or genotype distributions were detected between the CCA and control groups or the respective subgroups investigated.However,there was a trend for a protective effect of the heterozygous single-nucleotide polymorphism state GC,as indicated by an underrepresentation in the CCA group in general(29% vs 35%;P=0.18) and,in particular,for extrahepatic tumor sites(26% vs 35%;OR=0.67;95% CI,0.43-1.02;P=0.065).CONCLUSIONS:Our data do not support a prominent contribution of the pre-miR-146a sequence variant in the genetic predisposition to CCA.However,current studies functionally characterizing rs2910164 have proposed that distinct repertoires of target genes are addressed by genotype-specific mature miR146a species.Given the detected trend towards a potentially protective role of GC heterozygosity,a subtle modulation of genetic CCA risk by the pre-miR-146a GC genotype may exist and should be evaluated further.
文摘Hepatitis B represents a global health threat because its chronic course and sequelae contribute to a high morbidity and mortality. Hepatitis B virus(HBV) infection can be controlled by vaccines, antiviral treatment, and by interrupting transmission. Rare vaccine escape mutants are serious because they eliminate vaccine protection. Here, we present a 74-year-old vaccinated patient with HBV reactivation 11 years after kidney transplantation. The patient was HBV-positive but HBs Ag-negative prior to vaccination 6 years before transplantation. The reactivated virus was HBV genotype F3 with vaccine escape mutations G145 R, P120 Q, and Q129 P. The patient was successfully treated with entecavir. The epidemiological reasons for this subgenotype, which is extremely rare in Western Europe, were unclear. This case illustrates that second-generation vaccines are not always effective in a specific group of patients.
文摘As recognition of mast cell(MC) involvement in a range of chronic inflammatory disorders has increased, diagnosticians' suspicions of MC activation disease(MCAD) in their chronically mysteriously inflamed patients have similarly increased. It is now understood that the various forms of systemic mastocytosis- diseases of inappropriate activation and proliferation of MCs seemingly driven by a small set of rare, usually constitutively activating mutations in assorted MC regulatory elements-comprise merely the tip of the MCAD iceberg, whereas the far larger and far more clinically heterogeneous(and thus more difficult to recognize) bulk of the iceberg consists of assorted forms of MC activation syndrome(MCAS) which manifest little to no abnormal MC proliferation and may originate from a far more heterogeneous set of MC mutations. It is reasonable to suspect MCAD when symptoms and signs of MC activation are present and no other diagnosis better accounting for the full range of findings is present. Initial laboratory assessment should include not only routine blood counts and serum chemistries but also a serum total tryptase level, which helps direct further evaluation for mastocytosis vs MCAS. Appropriate tissue examinations are needed to diagnose mastocytosis, while elevated levels of relatively specific mast cell mediators are sought to support diagnosis of MCAS. Whether assessing for mastocytosis or MCAS, testing is fraught with potential pitfalls which can easily yield false negatives leading to erroneous rejection of diagnostic consideration of MCAD in spite of a clinical history highly consistent with MCAD. Efforts at accurate diagnosis of MCAD are worthwhile, as many patients then respond well to appropriately directed therapeutic efforts.
文摘Primary central nervous system lymphomas (PCNSL) frequently reveal genomic instability. We analysed different functional genetic variants affecting the folate and homocysteine metabolism important for DNA integrity in 31 PCNSL patients and 142 controls. We found significantly less carriers of the methionine synthase c. 2756A> G (D919G) missense polymorphism among the patients (0.16 vs 0.42; odds ratio 0.26, CI(95%): 0.09-0.74; P=0.005), suggesting a protective function of the G allele. These data stimulate further epidemiological and functional studies focusing on the role of homoeysteine and folate metabolism in lymphoma tumorigenesis.
文摘Background:Cells of the retinal pigment epithelium(RPE)accumulate different kinds of granules(lipofuscin,melanolipofuscin,melanosomes)within their cell bodies,with lipofuscin and melanolipofuscin being autofluorescent after blue light excitation.High amounts of lipofuscin granules within the RPE have been associated with the development of RPE cell death and age-related macular degeneration(AMD);however,this has not been confirmed in histology so far.Here,based on our previous dataset of RPE granule characteristics,we report the characteristics of RPE cells from human donor eyes that show either high or low numbers of intracellular granules or high or low autofluorescence(AF)intensities.Methods:RPE flatmounts of fifteen human donors were examined using high-resolution structured illumination microscopy(HR-SIM)and laser scanning microscopy(LSM).Autofluorescent granules were analyzed regarding AF phenotype and absolute number of granules.In addition,total AF intensity per cell and granule density(number of granules per cell area)were determined.For the final analysis,RPE cells with total granule number below 5th or above the 95th percentile,or a total AF intensity±1.5 standard deviations above or below the mean were included,and compared to the average RPE cell at the same location.Data are presented as mean±standard deviation.Results:Within 420 RPE cells examined,42 cells were further analyzed due to extremes regarding total granule numbers.In addition,20 RPE cells had AF 1.5 standard deviations below,28 RPE cells above the mean local AF intensity.Melanolipofuscin granules predominate in RPE cells with low granule content and low AF intensity.RPE cells with high granule content have nearly twice(1.8 times)as many granules as an average RPE cell.Conclusions:In normal eyes,outliers regarding autofluorescent granule load and AF intensity signals are rare among RPE cells,suggesting that granule deposition and subsequent AF follows intrinsic control mechanisms at a cellular level.The AF of a cell is related to the composition of intracellular granule types.Ongoing studies using AMD donor eyes will examine possible disease related changes in granule distribution and further put lipofuscin´s role in aging and AMD further into perspective.
文摘The aim of this study was to investigate an association between the development of cholangiocarcinoma(CCA)and the ABO variant rs505922(known to increase pan-creatic cancer risk)in a large cohort of European individuals with CCA.In total,180 individuals with CCA and 350 CCA-free controls were included.The ABO variant rs505922 was genotyped using a polymerase chain reaction-based assay.Association between this single nucleotide polymorphism(SNP)and CCA was tested in contingency tables.Neither allele distributions nor association tests and regression analysis provided evidence for an increased risk of CCA among carriers of the ABO variant(all P > 0.05).Nevertheless,we documented a deviation from Hardy-Weinberg equilibrium in the entire CCA cohort(P = 0.028)and for patients with intrahe-patic(P = 0.037)but not extrahepatic tumor localization(P > 0.05).The association tests did not provide evidence for a prominent role of the investigated SNP in the genetic risk of CCA.However,Hardy-Weinberg disequilibrium in the entire cohort and the intrahepatic CCA subgroup warrants future studies investigating a potential CCA risk modulation by individual blood groups.
文摘BACKGROUND Leiomyosacromas in the Extremities are rare malignant smooth muscle tumors.Adjuvant radiation therapy, in combination with wide surgical excision allows the best chance of treatment. During the follow up pathological fractures are common complications that can be accompanied by Implant failure and defect situations that are most challenging in their management.CASE SUMMARY We present a case of a 52-year-old female suffering from a pathological fracture of the humeral shaft 10 yr after resection of a Leiomyosarcoma and postoperative radiotherapy. She developed implant failure after retrograde nailing and another failure after revision to double plate fixation. In a two-stage revision, the implants were removed and the huge segmental defect created after debridement was bridged by a compound osteosynthesis with nancy nails and bone cement for formation of the induced membrane. Due to the previous radiotherapy treatment,20 cm of the humeral shaft were declared devascularized but were left in situ as a scaffold. In the second stage, a vascularized fibula graft was used in combination with a double plate fixation and autologous spongiosa grafts for final reconstruction.CONCLUSION This combinatory treatment approach led to a successful clinical outcome and can be considered in similar challenging cases.
文摘AIM: To test the methodical and pre-analytical performance of a new multiplex cancer biomarker panel using magnetic beads. METHODS: The MILLIPLEX? MAP Human Circulating Cancer Biomarker Magnetic Bead Panel 1 comprises the tumor markers carcinoembryonic antigen, alpha-fetoprotein, total prostate-specific antigen, cancer antigen 15-3, cancer antigen 19-9, cancer antigen 125, cytokeratine 19-fragment, β-human chorionic gonadotropin, human epididymis protein 4, osteopontin, prolactin, the cell death and angiogenesis markers soluble Fas, soluble Fas-ligand, tumor necrosis factor related apoptosisinducing ligand, vascular endothelial growth factor andthe immunological markers interleukin-6(IL-6), IL-8, tumor necrosis factor-α, transforming growth factor α, fibroblast growth factor-2, macrophage migration inhibitory factor, leptin, hepatocyte growth factor, and stem cell factor. We determined intra- and inter-assay imprecision as well as dilution linearity using quality controls and serum pools. Furthermore, the stability of the 24 biomarkers examined in this panel was ascertained by testing the influence of different storage temperatures and time span before centrifugation.RESULTS: For all markers measured in the synthetic internal quality controls, the intra-assay imprecision ranged between 2.26% and 9.41%, while for 20 of 24 measured markers in the physiological serum pools, it ranged between 1.68% and 12.87%. The inter-assay imprecision ranged between 1.48%-17.12% for 23 biomarkers in synthetic, and between 4.59%-23.88% for 18 biomarkers in physiological quality controls. Here, single markers with very low concentration levels had increased imprecision rates. Dilution linearity was acceptable(70%-130% recovery) for 20 biomarkers. Regarding pre-analytical influencing factors, most markers were stable if blood centrifugation was delayed or if serum was stored for up to 24 h at 4 ℃ and 25 ℃ after centrifugation. Comparable results were obtained in serum and plasma for most markers. However, great changes were observed for single markers.CONCLUSION: MILLIPLEX? MAP Human Circulating Cancer Biomarker Magnetic Bead Panel 1 assay is a stable and precise method for detection of most biomarkers included in the kit. However, single markers have to be interpreted with care.
文摘Renal cell carcinoma (RCC) is one of the most important urological tumors and is one of the most common cancer diseases worldwide. Unfortunately, the treatment options are very limited due to resistances. Non-invasive physical plasma (NIPP) is currently becoming a promising and very well tolerated treatment option for cancer. NIPP represents a highly energized gas and induc</span><span style="font-family:Verdana;">es varying antioncogenic cell responses in tumor cells. And also in t</span><span style="font-family:Verdana;">he case of RCC, NIPP treatment has great potential to enhance and supplement existing anticancer treatment options. Outstanding characteristics of NIPP treatment are 1) a precise and local effect on the treated tissue and 2) an almost exclusive effect on treated tumor cells without side effects. This allows </span><span style="font-family:Verdana;">an enormously large therapeutic window and makes the combination o</span><span style="font-family:Verdana;">f NIPP treatment and classical therapy appear particularly promising. In addition to R</span><span style="font-family:Verdana;">CC, plasma oncology offers an extremely innovative physical treatme</span><span style="font-family:Verdana;">nt method for future oncology in general.</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">This brief review article summarizes the current knowledge on the potential use of NIPP in RCC therapy.
文摘<strong>Objective:</strong><span><span style="font-family:Verdana;"> Misoprostol vaginal insert (MVI) is proven to induce labor by a </span><span style="font-family:Verdana;">continuously release of PGE1. Previous reports showed that MVI reduced</span><span style="font-family:Verdana;"> induction to delivery time as well as active labor time but it also increased uterine tachysystole. Here we attempted to clarify whether MVI is safe and </span><span style="font-family:Verdana;">efficient for women with pregnancies >40 weeks in a single institute.</span> <b><span style="font-family:Verdana;">Methods: </span></b><span style="font-family:Verdana;">This study was performed in Lutheran Hospital Bergisch Gladbach, Germany 2014-2019. A total of 304 women between 40 + 0 to 42 + 0 weeks underwent labor induction with MVI. Outcomes were</span></span><span style="font-family:Verdana;">:</span><span><span style="font-family:Verdana;"> 1) maternal: time from insertion </span><span style="font-family:Verdana;">to delivery, interventions, mode of delivery, and uterine tachysystole, 2)</span><span style="font-family:Verdana;"> neo</span></span><span style="font-family:Verdana;">-</span><span><span style="font-family:Verdana;">natal: cord blood pH, APGAR scores, and admission to a neonatal clinic. This </span><span style="font-family:Verdana;">study ended unexpectedly due to the withdrawal of MVI (Misodel<span style="white-space:nowrap;"><sup>TM</sup></span>) in</span><span style="font-family:Verdana;"> September 2019. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">75.7% (n = 230) of women gave birth within 24 hours after MVI placement. 72.2% (n = 140) nulliparous women and 81.8% (n = 90) </span><span style="font-family:Verdana;">parous women delivered within 24 hours. In two cases emergency CS was</span><span style="font-family:Verdana;"> required. 67.8% (n = 206) of women delivered vaginal. 2.3% (n = 7) of cord pH levels were below 7.10. 3.3% (n = 10) of newborns were transmitted to a neonatal clinic. </span><b><span style="font-family:Verdana;">Conclusion: </span></b><span style="font-family:Verdana;">MVI is an efficient method to induce labor for </span><span style="font-family:Verdana;">pregnant women beyond 40 + 0 weeks. However, considering various</span><span style="font-family:Verdana;"> compli</span><span style="font-family:Verdana;">cations observed (uterine tachysystole and fetal distress leading to a high</span><span style="font-family:Verdana;"> number of CS), we cannot universally advocate the use of MVI.</span></span>
