Health-related quality of life and its influencing factors in patients with primary cutaneous B-cell lymphomas: A multicentric study in 100 patients.

BACKGROUND: Primary cutaneous B-cell lymphomas (CBCL) are a group of rare malignant skin diseases that represent approximately 20%-30% of all primary cutaneous lymphomas (PCL). Previous studies revealed impaired health-related quality of life (HRQoL) in patients diagnosed with primary cutaneous T-cell lymphoma (CTCL). Currently, only small-sized studies investigated HRQoL in CBCL patients and lacked detailed analysis of respective subtypes. OBJECTIVES: This study aims to investigate HRQoL in CBCL patients to identify independent factors of HRQoL impairment in CBCL patients. METHODS: One hundred CBCL patients were recruited from eight German PCL centres in this multicentric, cross-sectional study from 2021 to 2022. The patients completed the dermatologic HRQoL questionnaire Skindex-29 and an investigator-designed 'CBCL-Questionnaire' with additional questions on HRQoL and clinical characteristics. RESULTS: The Skindex-29 revealed that HRQoL in CBCL patients is impaired on a mild to moderate level. The multiple regression analysis identified parameters like worries about dying, feeling prejudiced/discriminated and impairment of daily activities to be independently associated with impairment of HRQoL. Highest scores for HRQoL impairment were found in patients with primary cutaneous follicle centre lymphoma while on rituximab treatment and in patients with primary cutaneous marginal zone lymphoma while on watchful waiting. CONCLUSIONS: HRQoL is impaired in CBCL patients, even though, in the face of indolent disease course and favourable prognosis in the majority of cases. Of note, our investigator-designed tool identified worries about dying, feeling prejudiced/discriminated, and the type of treatment to have a negative impact on patients' HRQoL. Our study highlights the importance of a thorough patient-doctor communication to capture overall disease burden because generic HRQoL tools might lack of disease-specific items.

Value of routine intraoperative frozen sections of proximal bile duct margins in perihilar cholangiocarcinoma, a retrospective multicenter and matched case-control study.

BACKGROUND: Currently, the potential benefits of additional resection after positive proximal intraoperative frozen sections (IFS) in perihilar cholangiocarcinoma (pCCA) on residual disease and oncological outcome remain uncertain. Therefore, the aim of this study is to investigate the number of R0 resections after additional resection of a positive proximal IFS and the influence of additional resections on overall survival (OS) in patients with pCCA. MATERIALS AND METHODS: A retrospective, multicenter, matched case-control study was performed, including patients undergoing resection for pCCA between 2000 and 2019 at three tertiary centers. Primary outcome was the number of achieved 'additional' R0 resections. Secondary outcomes were OS, recurrence, severe morbidity and mortality. RESULTS: Forty-four out of 328 patients undergoing resection for pCCA had a positive proximal IFS. An additional resection was performed in 35 out of 44 (79.5%) patients, which was negative in 24 (68.6%) patients. Nevertheless, seven out of these 24 patients were eventually classified as R1 resection due to other positive resection margins. Therefore, 17 (48.6%) patients could be classified as "true" R0 resection after additional resection. Ninety-day mortality after R1 resections was high (25%) and strongly influenced OS. After correction for 90-day mortality, median OS after negative additional resection was 33 months (95%CI:29.5-36.5) compared to 30 months (95%CI:24.4-35.6) after initial R1 (P = 0.875) and 46 months (95%CI:32.7-59.3) after initial R0 (P = 0.348). CONCLUSION: There were only 17 patients (out of a total of 328 patients) that potentially benefitted from routine IFS. Additional resection for a positive IFS leading to R0 resection was not associated with improved long-term survival.

[Out-of-hospital airway management with a laryngeal tube or endotracheal intubation for out-of-hospital cardiac arrest : Influence on in-hospital mortality]. / Präklinisches Atemwegsmanagement mit Larynxtubus oder Endotrachealtubus bei präklinischem Herz-Kreislauf-Stillstand : Einfluss auf die Krankenhausmortalität.

BACKGROUND: Endotracheal (ET) intubation has been the gold standard in out-of-hospital airway management for a long time. Recent guidelines suggest an alternative airway management with supraglottic airway devices like the laryngeal tube (LT) especially for less experienced rescue personnel. However, scientific evidence on the prognostic impact of the laryngeal tube in the setting of cardiopulmonary resuscitation is limited. METHODS: We aimed to compare mortality outcomes in out-of-hospital cardiac arrest (OHCA) patients after preclinically initiated airway management with either ET or LT in a propensity score matched, single-center retrospective analysis. RESULTS: A total of 208 patients with OHCA were resuscitated and intubated with either ET (n = 160; 77%) or LT (n = 48; 23%) in the urban area of Frankfurt am Main, Germany, and treated thereafter on the intensive care unit of the University Hospital Frankfurt from 2006-2014. In-hospital mortality was 84% versus 85% in the ET and LT group (p = 0.86). No difference regarding in-hospital mortality has been observed between the two airway management techniques in univariate as well as in multivariate mortality analysis (HR = 0.98, 95% confidence interval [CI] 0.69-1.39; p = 0.92; adjusted HR = 1.01, 95% CI 0.76-1.56; p = 0.62). To adjust for potential confounders, propensity score matching was additionally performed resulting in a cohort of 120 matched patients in a 3:1 ratio (ET:LT). Again, survival to hospital discharge was comparable between the two patient groups (propensity-adjusted HR = 0.99, 95% CI 0.65-1.51, p = 0.97). Further, preclinical airway management with LT or ET showed no difference in mortality within first 24 h (propensity-adjusted HR = 1.02; 95% CI 0.44-2.36; p = 0.96). CONCLUSION: Preclinical airway management with LT shows similar mortality outcomes in direct comparison to intubation with ET in OHCA patients. Further randomized studies are warranted.

Clinical, oncological, and functional outcomes of Da Vinci (Xi)-assisted versus conventional laparoscopic resection for rectal cancer: a prospective, controlled cohort study of 51 consecutive cases.

PURPOSE: Despite the increasing use of telemanipulators in colorectal surgery, an additional benefit in terms of improved perioperative results is not proven. The aim of the study was to compare clinical, oncological, and functional results of Da Vinci (Xi)-assisted versus conventional laparoscopic (low) anterior resection for rectal cancer. METHODS: Monocenter, prospective, controlled cohort study with a 12-month follow-up of bladder and sexual function using the validated questionnaires International Prostate Symptom Score, International Index of Erectile Function, and Female Sexual Function Index. RESULTS: Fifty-one patients were included (18, Da Vinci (Xi) assisted; 33, conventional laparoscopy). Conversion to an open approach was more common in the Da Vinci cohort (p = 0.012). In addition, surgery and resumption of a normal diet took longer in the robotic group (p = 0.005; p = 0.042). Surgical morbidity and oncological quality did not differ. There was no difference in most functional domains, except for worsened ability to orgasm (p = 0.047) and sexual satisfaction (p = 0.034) in women after conventional laparoscopy. Moreover, we found a higher rate of improved bladder function in the conventional laparoscopy group (p = 0.023) and less painful sexual intercourse among women in the robot-assisted group (p = 0.049). CONCLUSION: In contrast to the ROLARR trial, a higher conversion rate was found in the robotic cohort, which may in part be explained by a learning curve effect. Nevertheless, the Da Vinci-assisted approach showed favorable results regarding sexual function.

[Baroreceptor activation therapy for therapy-resistant hypertension: indications and patient selection : Recommendations of the BAT consensus group 2017]. / Barorezeptorakivierungstherapie bei therapierefraktärer Hypertonie: Indikation und Patientenselektion : Empfehlungen der BAT-Konsensusgruppe 2017.

Baroreceptor activation therapy (BAT) has been available for several years for treatment of therapy-refractory hypertension (trHTN). This procedure is currently being carried out in a limited number of centers in Germany, also with the aim of offering a high level of expertise through sufficient experience; however, a growing number of patients who are treated with BAT experience problems that treating physicians are confronted with in routine medical practice. In order to address these problems, a consensus conference was held with experts in the field of trHTN in November 2016, which summarizes the current evidence and experience as well as the problem areas in handling BAT patients.

Clinical and morphometric parameters of frailty for prediction of mortality following hepatopancreaticobiliary surgery in the elderly.

BACKGROUND: Although frailty is a known determinant of poor postoperative outcomes, it can be difficult to identify in patients before surgery. The authors sought to develop a preoperative frailty risk model to predict mortality among patients aged 65 years or more. METHODS: Clinical and morphometric data including total psoas area (TPA), total psoas volume (TPV) and psoas density (Hounsfield unit average calculation, HUAC) were collected for patients undergoing hepatopancreaticobiliary (HPB) surgery between 2012 and 2014. Multivariable Cox proportional hazards regression was used to identify preoperative risk factors associated with 1-year mortality. RESULTS: The median age of the 518 patients included in the study was 72 (i.q.r. 68-76) years; 55·6 per cent of patients were men, and half of the cohort had multiple co-morbidities (Charlson co-morbidity index (CCI) of 4 or more, 55·6 per cent). TPA cut-offs to define sarcopenia were 552·7 mm(2) /m(2) in women and 702·9 mm(2) /m(2) in men; cut-offs for TPV were 18·2 cm(3) /m(2) in women and 26·2 cm(3) /m(2) in men, whereas HUAC cut-offs were 31·1 HU in women and 33·3 HU in men. The overall 1-year mortality rate was 14·1 per cent. In multivariable analysis, risk factors associated with 1-year mortality included CCI of 4 or above (hazard ratio (HR) 2·91, 95 per cent c.i. 1·47 to 5·77; P = 0·002), malignant disease (HR 3·94, 1·17 to 13·30; P = 0·027) and sarcopenia by HUAC (HR 1·85, 1·10 to 3·10; P = 0·021). A weighted 25-point composite score was developed to stratify patients at risk of 1-year postoperative mortality. The 1-year mortality rate was noted to be 2·5 per cent among patients scoring 0-10 (low risk), 17·3 per cent among patients scoring 11-20 (intermediate risk) and 29·2 per cent among those scoring between 21 and 25 (high risk) (P < 0·001). CONCLUSION: Clinical and morphometric measures of frailty accurately predict the risk of 1-year mortality following HPB surgery in elderly patients, and can be used to risk-stratify patients appropriately.

Impact of S3 training courses "Sedation and Emergency Management in Endoscopy for Endoscopy Nurses and Assisting Personnel" on the process and structure quality in gastroenterological endoscopy in practices and clinics - results of a nationwide survey.

INTRODUCTION: After the S3 Guideline Sedation in Gastrointestinal Endoscopy was published, a training curriculum for a three-day course for endoscopy nurses was developed. The aim of this study was to investigate what effect the course participation had on the daily routine process and structure quality by implementing a German-wide survey in gastroenterology practices and clinics. METHODS: A questionnaire with a total of 44 individual questions on personnel, space, and equipment structure, sedation, peri- and post-interventional monitoring, as well as discharge and complication management in endoscopy departments was sent to a total of 2113 course participants (1056 Institutions). They had completed the seminar between December 2008/January 2009 and June 2010. RESULTS: The response rate was 21.2 % (224 /1056). Fifty-four percent were from clinic endoscopy departments, 46 % from practices. Overall, some form of structural change occurred in 86.8 % of the clinics and in 84.5 % of the practices. New staff was hired in 28.1 % of the clinics and 12.6 % of the practices. Rosters were changed in 11.6 % of the clinics and 7.8 % of the practices. Almost all issues improved after course participation. However, they did not reach statistic significance with the exception of the availability of peri-interventional ECG-monitoring in practices. The "performance of sedation in threesomes" increased in clinics by more than 20 % and in practices by more than 15 %. The use of the ASA-classification to assess risk increased significantly in clinics (before 24 %, after 50 %) as well as practices (before 40 %, after 60 %) by more than 20 % (p = 0.0007 and p = 0.0385, respectively). The documentation of the discharge status (e. g. using checklists) more than doubled in clinics (before 19 %, after 41.3 %) and practices (before 17.5 %, after 38.8 %) after course completion. CONCLUSION: The only nationwide endoscopy nurses' survey on structure and process quality in endoscopy so far, shows that since the publication of the S3 guideline in 2008 numerous processes and structures have improved with respect to patient safety.

The Ca2+/Mn2+ ion-pump PMR1 links elevation of cytosolic Ca(2+) levels to α-synuclein toxicity in Parkinson's disease models.

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons, which arises from a yet elusive concurrence between genetic and environmental factors. The protein α-synuclein (αSyn), the principle toxic effector in PD, has been shown to interfere with neuronal Ca(2+) fluxes, arguing for an involvement of deregulated Ca(2+) homeostasis in this neuronal demise. Here, we identify the Golgi-resident Ca(2+)/Mn(2+) ATPase PMR1 (plasma membrane-related Ca(2+)-ATPase 1) as a phylogenetically conserved mediator of αSyn-driven changes in Ca(2+) homeostasis and cytotoxicity. Expression of αSyn in yeast resulted in elevated cytosolic Ca(2+) levels and increased cell death, both of which could be inhibited by deletion of PMR1. Accordingly, absence of PMR1 prevented αSyn-induced loss of dopaminergic neurons in nematodes and flies. In addition, αSyn failed to compromise locomotion and survival of flies when PMR1 was absent. In conclusion, the αSyn-driven rise of cytosolic Ca(2+) levels is pivotal for its cytotoxicity and requires PMR1.

Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain.

BACKGROUND: Antipsychotic-induced weight gain (AIWG) is a serious side-effect of antipsychotic medication leading to metabolic syndrome and increased cardiovascular morbidity. Unfortunately, there are still no valid predictors to assess an individual's risk to gain weight. Previous studies have indicated an impact of genetic variation in the genes encoding leptin, LEP, and leptin receptor, LEPR, on AIWG, but results have not been conclusive. Thus, we investigated polymorphisms in both genes for an association with AIWG. METHODS: A total of 181 schizophrenic and schizoaffective patients treated with various antipsychotics were included. In a small subset of patients, leptin plasma levels were additionally obtained. Five polymorphisms in LEP and LEPR (LEP: rs7799039 (-2548G/A polymorphism), rs10954173, rs3828942; LEPR: rs1327120, rs1137101 (Q223R polymorphism) were genotyped using TaqMan assays. Statistical association with % weight change from baseline weight was performed using ANCOVA with baseline weight as covariate. RESULTS: ANCOVA showed a non-significant trend for genotype association of the rs7799039 marker (p=.068). No significant association of the other LEP and LEPR SNPs with AIWG was detected. However, we found a significant association between a haplotype of LEP rs7799039G-rs10954173G-rs3828942G (p=.035) and AIWG. The rs7799039 G-allele (p=.042) and G-allele of rs3828942 (p=.032) were associated with higher weight gain. CONCLUSION: Our study supports the hypothesis of an impact of LEP gene variation on AIWG. Limitations of our study include heterogeneous samples, short treatment duration and multiple comparisons. Our findings were compared to previous studies in detail in order to provide the readers with a more conclusive picture. However, further studies are warranted including more gene variants and interaction analyses with other genes of the leptin-melanocortin pathway.

The propeptide of yeast cathepsin D inhibits programmed necrosis.

The lysosomal endoprotease cathepsin D (CatD) is an essential player in general protein turnover and specific peptide processing. CatD-deficiency is associated with neurodegenerative diseases, whereas elevated CatD levels correlate with tumor malignancy and cancer cell survival. Here, we show that the CatD ortholog of the budding yeast Saccharomyces cerevisiae (Pep4p) harbors a dual cytoprotective function, composed of an anti-apoptotic part, conferred by its proteolytic capacity, and an anti-necrotic part, which resides in the protein's proteolytically inactive propeptide. Thus, deletion of PEP4 resulted in both apoptotic and necrotic cell death during chronological aging. Conversely, prolonged overexpression of Pep4p extended chronological lifespan specifically through the protein's anti-necrotic function. This function, which triggered histone hypoacetylation, was dependent on polyamine biosynthesis and was exerted via enhanced intracellular levels of putrescine, spermidine and its precursor S-adenosyl-methionine. Altogether, these data discriminate two pro-survival functions of yeast CatD and provide first insight into the physiological regulation of programmed necrosis in yeast.

Apoptosis in yeast: triggers, pathways, subroutines.

A cell's decision to die is controlled by a sophisticated network whose deregulation contributes to the pathogenesis of multiple diseases including neoplastic and neurodegenerative disorders. The finding, more than a decade ago, that baker's yeast (Saccharomyces cerevisiae) can undergo apoptosis uncovered the possibility to investigate this mode of programmed cell death (PCD) in a model organism that combines both technical advantages and a eukaryotic 'cell room.' Since then, numerous exogenous and endogenous triggers have been found to induce yeast apoptosis and multiple yeast orthologs of crucial metazoan apoptotic regulators have been identified and characterized at the molecular level. Such apoptosis-relevant orthologs include proteases such as the yeast caspase as well as several mitochondrial and nuclear proteins that contribute to the execution of apoptosis in a caspase-independent manner. Additionally, physiological scenarios such as aging and failed mating have been discovered to trigger apoptosis in yeast, providing a teleological interpretation of PCD affecting a unicellular organism. Due to its methodological and logistic simplicity, yeast constitutes an ideal model organism that is efficiently helping to decipher the cell death regulatory network of higher organisms, including the switches between apoptotic, autophagic, and necrotic pathways of cellular catabolism. Here, we provide an overview of the current knowledge about the apoptotic subroutine of yeast PCD and its regulation.

Yeast unfolds the road map toward alpha-synuclein-induced cell death.

The budding yeast Saccharomyces cerevisiae has contributed significantly to our current understanding of eukaryotic cell biology. It served as a tool and model for unraveling the molecular basis of a wide variety of cellular phenomena, which seem to be conserved in other organisms. During the last decade, yeast has also extensively been used to study the mechanisms underlying several human diseases, including age-associated neurodegenerative disorders, such as Parkinson's, Huntington's and Alzheimer's disease. In this review, we focus on a yeast model for synucleinopathies and summarize recent studies that not only provided new clues on how the misfolding of alpha-synuclein (alpha-syn) triggers toxicity and eventually cell death, but that also led to the identification of conserved suppressor proteins, which are effective in protecting cells, including neurons, from the alpha-syn-induced cytotoxicity.

BAC-derived diagnostic markers for sex determination in asparagus.

A HindIII BAC (bacterial artificial chromosome) library of asparagus ( Asparagus officinalis L.) was established from a single male plant homozygous for the male flowering gene ( MM). The library represents approximately 5.5 haploid genome equivalents with an average insert size of 82 kb. A subset of the library (2.6 haploid genome equivalents) was arranged into DNA pools. Using nine sex-linked amplified fragment length polymorphism (AFLP) and two sequence-tagged site (STS) markers, 13 different BAC clones were identified from this part of the library. The BACs were arranged into a first-generation physical map around the sex locus. Four PCR-derived markers were developed from the BAC ends, one of which could be scored in a co-dominant way. Using a mapping population of 802 plants we mapped the BAC-derived markers to the same position close to the M gene as the corresponding AFLP and STS markers. The markers are useful for further chromosome walking studies and as diagnostic markers for selecting male plants homozygous for the M gene.

AFLPs represent highly repetitive sequences in Asparagus officinalis L.

The chromosomal and genomic organization of 5 cloned AFLP fragments in asparagus (Asparagus officinalis L.) were investigated. Two of the 5 AFLP loci were sex-linked. The fragments, amplified with EcoRI/Mse I primers, ranged from 107 to 267 bp and were AT-rich. Southern hybridization gave interspersed, middle repetitive to high copy sequence signals. Fluorescence in-situ hybridization (FISH) exhibited hybridization signals on all chromosomes with dispersed distribution pattern and varying signal intensities. Repetitive signals in the form of clusters were observed on all chromosomes. In addition, the 5S rRNA gene was physically mapped on one pair of chromosomes and the 18S-5.8S-25S rRNA genes on three pairs. The results of the FISH and Southern analyses showed that the AFLP marker technology relies on repetitive sequences. Since repetitive DNA sequences represent a fraction of the plant genome undergoing rapid changes during the course of evolution, the question of whether such molecular markers originating from repetitive DNA sequences remain stable is discussed.

Inhibition of peripheral blood lymphocyte apoptosis by soluble fas ligand in patients with hepatocellular carcinoma.

We monitored apoptosis of peripheral blood lymphocytes (PBL) obtained from patients with various degrees of chronic viral hepatitis, including hepatocellular carcinoma (HCC), in vitro and quantitated the serum levels of soluble Fas ligand (FasL) by ELISA. There was no difference in mean percent PBL mortality. However, in HCC patients, the variance was significantly high (P<0.05), and, unexpectedly, a negative association was found between the PBL mortality and the serum soluble FasL levels (P=0.035). These results suggest the inhibitory effect of serum soluble FasL on apoptosis of PBL, which may explain the induction of immunological abnormalities with the development of HCC.

[Endangerment of medicine by totalitarian basic principles]. / Die Gefährdung der Medizin durch totalitäre Grundbegriffe.

There are two different concepts of health which can be formulated: the abstract concept and the concrete concept. In the case of the abstract concept of health, illness appears as an evil which must be eliminated. Illness is not considered an integral part of a healthy organism. In the case of the concrete concept of health, the possibility that illness can occur is a necessary condition of being an organism. The structural connections between these concepts and totalitarian, political thinking will be discussed.

[Homeopathy as an independent and alternative form of therapy]. / Die Homöopathie als eigenständige und alternative Therepieform.

The homeopathic therapy is an independent form of therapy. In contrast to standard medical practice homeopathy regards the reactions of the body as the criterium by which one can characterize the medicine and determine its choice. Thus, in this context, the rule of similarity acts a bridge between the medicine and the symptoms of the illness. Homeopathic medicine cures in as much as it depicts the disease of the sick body as an external object which is, at the same time, similar to the illness itself. That is the reason why homeopathic medicine can be understood as a representation of the illness.

Purification and characterisation of an extracellular serine proteinase from Aspergillus fumigatus and its detection in tissue.

A serine proteinase (Alp) from the culture supernate of a clinical isolate of Aspergillus fumigatus was purified to virtual homogeneity at a yield of 41%. The procedure involved affinity chromatography on agarose-epsilon-amino-caproyl-D-tryptophan methyl ester. Alp had an estimated mol. wt of 32 Kda and the pI was determined at pH 7.9. The enzyme was fully inhibited by phenylmethyl sulphonyl fluoride, chymostatin and alpha-1-proteinase inhibitor, and it was largely inhibited by alpha-1-anti-chymotrypsin. Partial inhibition was observed with tosyl-phenylalanine chloromethyl ketone, but tosyl-lysine chloromethyl ketone was ineffective. Thus, Alp may be identical with the major chymotryptic activity of A. fumigatus, which has already been described. The N-terminal sequence of 25 amino acids revealed an 88% homology of Alp with the subtilisin-related proteinase of A. oryzae. Alp acted on casein over a broad range from pH 5.5 to 11.5 and also acts to a lesser extent on haemoglobin and serum albumin. The enzyme degraded elastin and a synthetic elastase substrate; hence, it may be identical with the previously described elastinolytic activity of the fungus. At pH 7.3 and a concentration of 1 microgram/ml, Alp was not toxic for Vero cells, but it efficiently detached such cells from a plastic surface. Specific antibodies against Alp were detected by enzyme immunoassay in the sera of patients and Alp-antigen was demonstrated by immunofluorescence in mycotic human lung. In addition, a second proteinase (Exalp) with extremely alkaline activity, and an aspartic proteinase of A. fumigatus are described.

[Heterologous and homologous radioimmunoassays of human prolactin. 2. Reference values]. / Heterologe und homologe Radioimmunoassays für humanes Prolaktin. 2. Mitteilung: Referenzbereiche.

Based on both selection of suitable substances for setting up and critical considerations of the developed heterologous and homologous prolactin radioimmunoassays, the reference ranges of prolactin serum levels for healthy women and men were estimated and compared with those of some other PRL-RIA-kits.