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1.
Sci Rep ; 14(1): 7761, 2024 04 02.
Article in English | MEDLINE | ID: mdl-38565603

ABSTRACT

Prognostic factors for overall survival (OS), percutaneous endoscopic gastrostomy (PEG) dependency, and long-term speech rehabilitation via voice prosthesis (VP) after laryngectomy for laryngeal or hypopharyngeal cancer were investigated in a retrospective population-based study in Thuringia, Germany. A total of 617 patients (68.7% larynx; hypopharynx; 31.3%; 93.7% men; median age 62 years; 66.0% stage IV) from 2001 to 2020 were included. Kaplan-Meier and Cox multivariable regression analyses were performed. 23.7% of patients received a PEG. 74.7% received a VP. Median OS was 131 months. Independent factors for lower OS were stage IV (compared to stage II; hazard ratio [HR] = 3.455; confidence interval [CI] 1.395-8.556) and laryngectomy for a recurrent disease (HR = 1.550; CI 1.078-2.228). Median time to PEG removal was 7 months. Prior partial surgery before laryngectomy showed a tendency for independent association for later PEG removal (HR = 1.959; CI 0.921-4.167). Postoperative aspiration needing treatment was an independent risk factor (HR = 2.679; CI 1.001-7.167) for later definitive VP removal. Laryngectomy continuously plays an important role in a curative daily routine treatment setting of advanced laryngeal or hypopharyngeal cancer in Germany. Long-term dependency on nutrition via PEG is an important issue, whereas use of VP is a stable long-term measure for voice rehabilitation.


Subject(s)
Hypopharyngeal Neoplasms , Laryngeal Neoplasms , Larynx , Male , Humans , Middle Aged , Female , Laryngectomy , Retrospective Studies , Hypopharyngeal Neoplasms/surgery , Laryngeal Neoplasms/surgery , Larynx/surgery , Treatment Outcome
2.
Sci Rep ; 13(1): 17612, 2023 10 17.
Article in English | MEDLINE | ID: mdl-37848528

ABSTRACT

Evidence-based indication for tonsil surgery in patients with recurrent acute tonsillitis (RAT) is an ongoing matter of debate. Since introduction of the German tonsillitis guideline in 2015, the indication criteria for tonsil surgery have become much stricter. It is unclear, if this has changed the indication policy. A retrospective population-based study was performed including all 1398 patients with RAT admitted for tonsil surgery in all Thuringian hospitals in 2011, 2015, and 2019. Changes over the years concerning patients' characteristics, number of tonsillitis episodes in the last 12 months treated with antibiotics (T12), and decision for tonsillectomy or tonsillotomy were analyzed using univariable and multivariable statistics. The surgical rates decreased from 28.56/100,000 population in 2011 to 23.57 in 2015, and to 11.60 in 2019. The relative amount of patients with ≥ 6 T12 increased from 14.1% in 2011 over 13.3% in 2015 to 35.9% in 2019. Most patients received a tonsillectomy (98% of all surgeries). Decision for tonsillotomy was seldom (1.2%). Multinomial logistic regression analysis with the year 2011 as reference showed that compared to the year 2015, the age of the patients undergoing surgery increased in 2015 (Odds ratio [OR] = 1.024; 95% confidence interval [CI] = 1.014-1.034; p < 0.001), and also in 2019 (OR 1.030: CI 1.017-1.043; p < 0.001). Compared to 2011, the number T12 was not higher in 2015, but in 2019 (OR 1.273; CI 1.185-1.367; p < 0.001). Stricter rules led to lower tonsil surgery rates but to a higher proportion of patients with ≥ 6 T12 before surgery. Tonsillectomy remained the dominating technique.


Subject(s)
Peritonsillar Abscess , Respiration Disorders , Tonsillectomy , Tonsillitis , Humans , Palatine Tonsil/surgery , Retrospective Studies , Tonsillitis/surgery , Tonsillectomy/methods
3.
Virulence ; 13(1): 2042-2058, 2022 12.
Article in English | MEDLINE | ID: mdl-36411449

ABSTRACT

Legionella pneumophila (L.p.) is a bacterial pathogen which is a common causative agent of pneumonia. In humans, it infects alveolar macrophages and transfers hundreds of virulence factors that interfere with cellular signalling pathways and the transcriptomic landscape to sustain its own replication. By this interaction, it has acquired eukaryote-like protein motifs by gene transfer events that partake in the pathogenicity of Legionella. In a computational screening approach for eukaryotic motifs in the transcriptome of Legionella, we identified the L.p. strain Corby protein ABQ55614 as putative histone-deacetylase and named it "suppressing modifier of histones 1" (Smh1). During infection, Smh1 is translocated from the Legionella vacuole into the host cytosol. When expressed in human macrophage THP-1 cells, Smh1 was localized predominantly in the nucleus, leading to broad histone H3 and H4 deacetylation, blunted expression of a large number of genes (e.g. IL-1ß and IL-8), and fostered intracellular bacterial replication. L.p. with a Smh1 knockdown grew normally in media but showed a slight growth defect inside the host cell. Furthermore, Smh1 showed a very potent histone deacetylation activity in vitro, e.g. at H3K14, that could be inhibited by targeted mutation of the putative catalytic center inferred by analogy with eukaryotic HDAC8, and with the deacetylase inhibitor trichostatin A. In summary, Smh1 displays functional homology with class I/II type HDACs. We identified Smh1 as a new Legionella virulence factor with a eukaryote-like histone-deacetylase activity that moderates host gene expression and might pave the way for further histone modifications.IMPORTANCELegionella pneumophila (L.p.) is a prominent bacterial pathogen, which is a common causative agent of pneumonia. In order to survive inside the host cell, the human macrophage, it profoundly interacts with host cell processes to advance its own replication. In this study, we identify a bacterial factor, Smh1, with yet unknown function as a host histone deacetylase. The activity of this factor in the host cell leads to attenuated gene expression and increased intracellular bacterial replication.


Subject(s)
Eukaryota , Legionella pneumophila , Humans , Histones/genetics , Legionella pneumophila/genetics , Eukaryotic Cells , Research , Virulence Factors/genetics , Histone Deacetylases , Repressor Proteins
4.
Eur Arch Otorhinolaryngol ; 279(2): 663-675, 2022 Feb.
Article in English | MEDLINE | ID: mdl-33683448

ABSTRACT

INTRODUCTION: To compare inpatient treated patients with idiopathic (ISSNHL) and non-idiopathic sudden sensorineural hearing loss (NISSNHL) regarding frequency, hearing loss, treatment and outcome. METHODS: All 574 inpatient patients (51% male, median age: 60 years) with ISSNHL and NISSNHL, who were treated in federal state Thuringia in 2011 and 2012, were included retrospectively. Univariate and multivariate statistical analyses were performed. RESULTS: ISSNHL was diagnosed in 490 patients (85%), NISSNHL in 84 patients (15%). 49% of these cases had hearing loss due to acute otitis media, 37% through varicella-zoster infection or Lyme disease, 10% through Menière disease and 7% due to other reasons. Patients with ISSNHL and NISSNHL showed no difference between age, gender, side of hearing loss, presence of tinnitus or vertigo and their comorbidities. 45% of patients with ISSNHL and 62% with NISSNHL had an outpatient treatment prior to inpatient treatment (p < 0.001). The mean interval between onset of hearing loss to inpatient treatment was shorter in ISSNHL (7.7 days) than in NISSNHL (8.9 days; p = 0.02). The initial hearing loss of the three most affected frequencies in pure-tone average (3PTAmax) scaled 72.9 dBHL ± 31.3 dBHL in ISSNHL and 67.4 dBHL ± 30.5 dBHL in NISSNHL. In the case of acute otitis media, 3PTAmax (59.7 dBHL ± 24.6 dBHL) was lower than in the case of varicella-zoster infection or Lyme disease (80.11 dBHL ± 34.19 dBHL; p = 0.015). Mean absolute hearing gain (Δ3PTAmaxabs) was 8.1 dB ± 18.8 dB in patients with ISSNHL, and not different in NISSNHL patients with 10.2 dB ± 17.6 dB. A Δ3PTAmaxabs ≥ 10 dB was reached in 34.3% of the patients with ISSNHL and to a significantly higher rate of 48.8% in NISSNHL patients (p = 0.011). CONCLUSIONS: ISSNHL and NISSNHL show no relevant baseline differences. ISSNHL tends to have a higher initial hearing loss. NISSHNL shows a better outcome than ISSNHL.


Subject(s)
Hearing Loss, Sensorineural , Hearing Loss, Sudden , Audiometry, Pure-Tone , Female , Glucocorticoids , Hearing , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sensorineural/epidemiology , Hearing Loss, Sudden/diagnosis , Hearing Loss, Sudden/epidemiology , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
5.
PDA J Pharm Sci Technol ; 76(3): 216-235, 2022.
Article in English | MEDLINE | ID: mdl-34782444

ABSTRACT

All products labeled as sterile are required to be free of microbial contamination throughout their shelf life (obligatory critical quality attribute). Container closure integrity (CCI) needs to be addressed with a holistic life cycle strategy comprising adequate primary packaging components selection and the assessment of critical unit operations and critical process parameters (CPPs) according to quality by design (QbD) principles. The helium leak method is currently the most sensitive CCI test method and preferably used for the initial container closure system (CCS) qualification and characterization studies. Currently, two different measuring principles are used in the pharmaceutical industry, and no data is available in the public domain for typical method performance parameters such as accuracy, precision, intermediate-precision, and limit of quantification of the method. Furthermore, the performance of different types and sizes of artificial leaks as well as certified helium leak standards have not yet been characterized across different test laboratories. In this multicompany study, we shared 17 artificially prepared leak samples using the most common types of artificial leaks in relevant nominal size ranges that are commercially available or can be easily prepared in a laboratory. Each participating company generated results according to their in-house methods, applying their established test parameters as the aim of the study was not to create a standard for helium leak measurements, but to compare real-world performance between different laboratories. Consequently, this study is not an interlaboratory study using the same test method across laboratories.


Subject(s)
Drug Contamination , Helium , Drug Contamination/prevention & control , Drug Industry , Drug Packaging , Glass , Helium/analysis
6.
J Otolaryngol Head Neck Surg ; 50(1): 55, 2021 Sep 20.
Article in English | MEDLINE | ID: mdl-34544499

ABSTRACT

OBJECTIVES: Analysis of frequency and reasons for planned and unplanned 30-day readmission in hospitalized pediatric otorhinolaryngology patients using German Diagnosis Related Group (G-DRG) system data. METHODS: A retrospective population-based cohort study in Thuringia, Germany, was performed for the year 2015 with 2440 cases under 18 years (55.6% male) out of a total number of 15.271 inpatient cases. The majority of pediatric patients were from 2 to 5 years old (54.5%). The most frequent diagnoses were hyperplasia of adenoids or/and tonsils (26.6%). 36 cases (1.5%) experienced readmission within 30-days. RESULTS: 30-day readmission was planned in 9 cases (25% of all readmission) and was unplanned in 27 cases (75%). The median interval between index and readmission treatment was 8 days. Postoperative bleeding after adenoidectomy, tonsillotomy/tonsillectomy or tracheostomy (33.4%) and infectious complications after surgery like acute otitis media, abscess formation or fever (36.2%) were the most frequent reasons for 30-day readmission. Compared to adults treated in 2015 in Thuringia, the readmission rate was higher in adult patients (8.9%) than in this pediatric cohort. In contrast to children, readmissions in adults were mainly planned (65.1%) with a different spectrum of underlying diseases and reasons for readmission. CONCLUSION: The 30-day readmission rate seemed to be lower for pediatric otolaryngology patients compared to adult patients. Unplanned readmissions dominated in pediatric patients, whereas planned readmissions dominated in adults.


Subject(s)
Otolaryngology , Patient Readmission , Adolescent , Adult , Child , Child, Preschool , Cohort Studies , Female , Humans , Inpatients , Male , Postoperative Complications , Retrospective Studies , Risk Factors
7.
Virulence ; 12(1): 1003-1010, 2021 12.
Article in English | MEDLINE | ID: mdl-33843461

ABSTRACT

Moraxella catarrhalis is a bacterial pathogen that causes respiratory tract infections in humans. The increasing prevalence of antibiotic-resistant M. catarrhalis strains has created a demand for alternative treatment options. We therefore tested 23 insect antimicrobial peptides (AMPs) for their activity against M. catarrhalis in a human in vitro infection model with primary macrophages, and against commensal bacteria. Effects on bacterial growth were determined by colony counting and growth curve analysis. The inflammatory macrophage response was characterized by qPCR and multiplex ELISA. Eleven of the AMPs were active against M. catarrhalis. Defensin 1 from the red flour beetle Tribolium castaneum significantly inhibited bacterial growth and reduced the number of colony forming units. This AMP also showed antibacterial activity in the in vitro infection model, reducing cytokine expression and release by macrophages. Defensin 1 had no effect on the commensal bacteria Escherichia coli and Enterococcus faecalis. However, sarcotoxin 1 C from the green bottle fly Lucilia sericata was active against M. catarrhalis and E. coli, but not against E. faecalis. The ability of T. castaneum defensin 1 to inhibit M. catarrhalis but not selected commensal bacteria, and the absence of cytotoxic or inflammatory effects against human blood-derived macrophages, suggests this AMP may be suitable for development as a new therapeutic lead against antibiotic-resistant M. catarrhalis.


Subject(s)
Antimicrobial Peptides , Defensins , Moraxella , Tribolium , Animals , Humans , Anti-Bacterial Agents/pharmacology , Antimicrobial Peptides/toxicity , Defensins/toxicity , Escherichia coli , Moraxella/physiology , Moraxella catarrhalis
8.
J Neurochem ; 157(6): 2128-2144, 2021 06.
Article in English | MEDLINE | ID: mdl-33583024

ABSTRACT

Neuronal network dysfunction is a hallmark of Alzheimer's disease (AD). However, the underlying pathomechanisms remain unknown. We analyzed the hippocampal micronetwork in transgenic McGill-R-Thy1-APP rats (APPtg) at the beginning of extracellular amyloid beta (Aß) deposition. We established two-photon Ca2+ -imaging in vivo in the hippocampus of rats and found hyperactivity of CA1 neurons. Patch-clamp recordings in brain slices in vitro revealed increased neuronal input resistance and prolonged action potential width in CA1 pyramidal neurons. We did neither observe changes in synaptic inhibition, nor in excitation. Our data support the view that increased intrinsic excitability of CA1 neurons may precede inhibitory dysfunction at an early stage of Aß-deposition and disease progression.


Subject(s)
Alzheimer Disease/metabolism , Disease Models, Animal , Excitatory Postsynaptic Potentials/physiology , Hippocampus/metabolism , Alzheimer Disease/pathology , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Animals , Female , Hippocampus/pathology , Male , Organ Culture Techniques , Rats , Rats, Transgenic
9.
Eur J Pharm Biopharm ; 154: 18-32, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32599272

ABSTRACT

Sustained release lipid microparticles for a potential veterinary application were produced by the means of spray congealing using saturated triglycerides with respective surfactants. The spray congealing process was optimized using unloaded and loaded microparticles, revealing the highest impact of the spray flow on material loss. Yield could be optimized by increasing the spray flow as well as a reduction of the melt temperature from 90 to 75 °C. For the delivery system developed in this study, a release of around 15 days was targeted. The release profile was in first hand determined with the use of model substances (aspartame and tryptophan), before incorporating the decapeptide Gonadorelin [6-D-Phe]. Release could be controlled between 2 and 28 d, which was dependent on stability of microparticles upon incubation, type and concentration of emulsifier, as well as the used triglyceride. Differential scanning calorimetry and X-ray powder diffraction confirmed the crystallization behavior of C14 and C16-triglycerides in combination with various emulsifiers in different modification without impact on release.


Subject(s)
Chemistry, Pharmaceutical/methods , Drug Delivery Systems/methods , Drug Liberation , Gonadotropin-Releasing Hormone/chemical synthesis , Lipids/chemical synthesis , Microspheres , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/chemical synthesis , Delayed-Action Preparations/pharmacokinetics , Gonadotropin-Releasing Hormone/administration & dosage , Gonadotropin-Releasing Hormone/pharmacokinetics , Lipids/administration & dosage , Lipids/pharmacokinetics , Particle Size , Peptide Fragments/administration & dosage , Peptide Fragments/chemical synthesis , Peptide Fragments/pharmacokinetics , X-Ray Diffraction/methods
10.
mBio ; 11(2)2020 03 24.
Article in English | MEDLINE | ID: mdl-32209695

ABSTRACT

Legionella pneumophila is an important cause of pneumonia. It invades alveolar macrophages and manipulates the immune response by interfering with signaling pathways and gene transcription to support its own replication. MicroRNAs (miRNAs) are critical posttranscriptional regulators of gene expression and are involved in defense against bacterial infections. Several pathogens have been shown to exploit the host miRNA machinery to their advantage. We therefore hypothesize that macrophage miRNAs exert positive or negative control over Legionella intracellular replication. We found significant regulation of 85 miRNAs in human macrophages upon L. pneumophila infection. Chromatin immunoprecipitation and sequencing revealed concordant changes of histone acetylation at the putative promoters. Interestingly, a trio of miRNAs (miR-125b, miR-221, and miR-579) was found to significantly affect intracellular L. pneumophila replication in a cooperative manner. Using proteome-analysis, we pinpointed this effect to a concerted downregulation of galectin-8 (LGALS8), DExD/H-box helicase 58 (DDX58), tumor protein P53 (TP53), and then MX dynamin-like GTPase 1 (MX1) by the three miRNAs. In summary, our results demonstrate a new miRNA-controlled immune network restricting Legionella replication in human macrophages.IMPORTANCE Cases of Legionella pneumophila pneumonia occur worldwide, with potentially fatal outcome. When causing human disease, Legionella injects a plethora of virulence factors to reprogram macrophages to circumvent immune defense and create a replication niche. By analyzing Legionella-induced changes in miRNA expression and genomewide chromatin modifications in primary human macrophages, we identified a cell-autonomous immune network restricting Legionella growth. This network comprises three miRNAs governing expression of the cytosolic RNA receptor DDX58/RIG-I, the tumor suppressor TP53, the antibacterial effector LGALS8, and MX1, which has been described as an antiviral factor. Our findings for the first time link TP53, LGALS8, DDX58, and MX1 in one miRNA-regulated network and integrate them into a functional node in the defense against L. pneumophila.


Subject(s)
Galectins/genetics , Host-Pathogen Interactions , Legionella pneumophila/physiology , Macrophages/microbiology , MicroRNAs/genetics , Myxovirus Resistance Proteins/genetics , Galectins/metabolism , Gene Expression Regulation/immunology , Humans , Legionnaires' Disease/microbiology , Macrophages/immunology , MicroRNAs/immunology , Myxovirus Resistance Proteins/metabolism , Proteome , Signal Transduction , THP-1 Cells , Virulence Factors
11.
Eur Arch Otorhinolaryngol ; 277(6): 1659-1666, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32124006

ABSTRACT

PURPOSE: Epistaxis is the most common ENT emergency. The aim was to determine population-based data on severe epistaxis needing inpatient treatment. METHODS: Retrospective population-based cohort study in the federal state Thuringia in 2016 performed on all 840 inpatients treated for epistaxis in otolaryngology departments (60.1% male, median age: 73 years; 63.9% under anticoagulation). The association between patients' and treatment characteristics and longer inpatient stay (≥ 4 days) as well as readmission for recurrent epistaxis was analyzed using univariable and multivariable statistics. RESULTS: The overall incidence of epistaxis needing inpatient treatment was higher for men (42 per 100,000) than for women (28 per 100,000). The highest incidence was reached for men > 85 years (222 per 100,000). Most important independent predictors for longer inpatient stay were localization of the bleeding not in the anterior nose (OR = 2.045; CI = 1.534-2.726), recurrent bleeding during inpatient treatment (OR = 2.142; CI = 1.508-3.042), no electrocoagulation (OR = 2.810; CI = 2.047-3.858), and blood transfusion (OR = 2.731; CI = 1.324-5.635). Independent predictors for later readmission because of recurrent epistaxis were male gender (OR = 1.756; CI = 1.155-2.668), oral anticoagulant use (OR = 1.731; CI = 1.046-2.865), and hereditary hemorrhagic telangiectasia (OR = 13.216; CI 5.102-34.231). CONCLUSIONS: Inpatient treatment of epistaxis seems to be variable in daily routine needing standardization by clinical guidelines and strategies to shorten inpatient treatment and to reduce the risk of readmission.


Subject(s)
Epistaxis , Hospitalization , Aged , Cohort Studies , Epistaxis/epidemiology , Epistaxis/therapy , Female , Germany/epidemiology , Health Services Research , Humans , Male , Retrospective Studies
12.
J Pharm Sci ; 109(1): 211-215, 2020 01.
Article in English | MEDLINE | ID: mdl-31655034

ABSTRACT

Lyophilization of protein formulations is an essential tool for stabilization and is becoming increasingly important for pharmaceutical development. Reconstitution of the lyophilized cakes is crucial to obtain an applicable product. Nowadays, manual reconstitution by patients or medical staff is the common method defined in instructions for marketed lyophilized drug products. Even though this step is influencing the quality of the final solution, it can represent a challenge to develop a standardized manual protocol and the performance is highly dependent on human factors. This study summarizes the implementation and performance of controlled reconstitution studies for protein lyophilizates applying a mechanical reconstitution device. Using automated and standardized protocols, reconstitution time of a bispecific antibody lyophilizate could be reduced effectively from 25 to below 5 min compared to the predeveloped manual protocol. It was shown that the reconstitution protocol is influencing the stability of sensitive proteins. Monomer content as well as formation of subvisible particles differed considerably between the tested protocols emphasizing the relevance of standardized procedures.


Subject(s)
Antibodies, Monoclonal/metabolism , Chemistry, Pharmaceutical/standards , Drug Compounding/standards , Protein Aggregates/physiology , Antibodies, Monoclonal/chemistry , Chemistry, Pharmaceutical/methods , Drug Compounding/methods , Drug Stability , Excipients/chemistry , Excipients/metabolism , Excipients/standards , Freeze Drying/methods , Freeze Drying/standards , Humans , Protein Stability , Reference Standards
13.
PLoS One ; 14(10): e0224146, 2019.
Article in English | MEDLINE | ID: mdl-31622434

ABSTRACT

PURPOSE: Analyze associations between patients' characteristics and treatment factors with 30-day unplanned readmissions in hospitalized otolaryngology patients in the German Diagnosis Related Group (D-DRG) system. METHODS: A retrospective cohort study was performed on 15.271 otolaryngology admissions of 12.859 patients in 2015 in Thuringia, Germany. The medical records of the 1173 cases (7.6%) with readmission within 30-days were analyzed in detail. RESULTS: The 30-day readmission was planned in 747 cases (4.9%) and was unplanned in 422 cases (2.8%). The median interval between primary and next inpatient treatment was 11 days. The principal diagnosis was the same as during the primary index treatment in 72% of the cases. The most frequent reasons for readmission were: Need for non-surgical therapy (31.2%), need for further surgery (26.3%), post-surgical complaints (16.9%), and recurrence of primary complaints (10.7%). The multivariate analysis revealed that discharge due to patient's request against medical advice was a strong independent factor with high risk for unplanned readmission (Odds Ratio [OR] = 9.62]; confidence interval [CI] = 2.69-34.48). Surgery at index admission (OR = 3.33; CI = 1.86-5.96) was the second important independent risk factor for unplanned readmission. Unplanned readmission had more frequently a non-surgical treatment at readmission than a surgical treatment (OR = 3.92; CI = 2.24-6.84) and needed more frequently further diagnostics (OR = 2.34; CI = 1.34-4.11). The following index International Classification of Diseases (ICD) categories had the highest risk for unplanned readmission: Injury, poisoning and certain other consequences of external causes, ICD: S00-T98 (OR = 66.67; CI = 15.87-333.33), symptoms, signs, abnormal findings, ill-defined causes, not otherwise classified, ICD: R00-R99 (OR = 62.5; CI = 11.76-333.33), blood forming organ diseases, ICD: D50-D90 (OR = 21.276; CI = 3.508-125), and eye/ ear diseases, ICD: H00-H95 (OR = 12.66; CI = 4.29-37.03). CONCLUSIONS: The causes of unplanned 30-day readmission in German otolaryngology inpatients are multifactorial. Specific patient and treatment characteristics were identified to be targeted with health care interventions to decrease unplanned readmissions.


Subject(s)
Otorhinolaryngologic Diseases/pathology , Patient Readmission/statistics & numerical data , Adult , Databases, Factual , Female , Germany , Humans , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Patient Discharge , Retrospective Studies , Risk Factors
14.
Virulence ; 10(1): 902-909, 2019 12.
Article in English | MEDLINE | ID: mdl-31657264

ABSTRACT

Streptococcus pneumoniae (S. pneumoniae) is the most common bacterial cause of community-acquired pneumonia. Increasing rates of antibiotic-resistant S. pneumoniae strains impair therapy and necessitate alternative treatment options. In this study, we analysed insect-derived antimicrobial peptides (AMPs) for antibacterial effects on S. pneumoniae in a human in vitro infection model.AMP effects on bacterial growth were examined by colony forming unit (CFU)-assays, and growth curve measurements. Furthermore, cytotoxicity to primary human macrophages was detected by measuring lactate-dehydrogenase release to the supernatant. One AMP (Defensin 1) was tested in a model of primary human monocyte-derived macrophages infected with S. pneumoniae strain D39 and a multi-resistant clinical isolate. Inflammatory reactions were characterised by qPCR and multiplex-ELISA.In total, the antibacterial effects of 23 AMPs were characterized. Only Tribolium castaneum Defensin 1 showed significant antibacterial effects against S. pneumoniae strain D39 and a multi-resistant clinical isolate. During in vitro infection of primary human macrophages with S. pneumoniae D39, Defensin 1 displayed strong antibacterial effects, and consequently reduced bacteria-induced cytokine expression and release.In summary, Tribolium castaneum Defensin 1 showed profound antibacterial effectivity against Streptococcus pneumoniae D39 and a multi-resistant clinical isolate without unwanted cytotoxic or inflammatory side effects on human blood-derived macrophages.


Subject(s)
Anti-Bacterial Agents/pharmacology , Defensins/pharmacology , Macrophages/drug effects , Macrophages/microbiology , Streptococcus pneumoniae/drug effects , Tribolium/chemistry , Animals , Cells, Cultured , Drug Resistance, Multiple, Bacterial , Humans , Macrophages/immunology , Microbial Sensitivity Tests , Pneumococcal Infections/microbiology
15.
Dtsch Med Wochenschr ; 144(6): 398-410, 2019 03.
Article in German | MEDLINE | ID: mdl-30870871

ABSTRACT

In case of an acute leg swelling a deep leg vein thrombosis needs to be excluded. In order to do this, compression sonography and the D-dimer-test are applied in the framework of an established diagnostic algorithm. The ensuing therapy consists in anticoagulation and compression.In case of a chronic leg swelling anamnesis and a clinical check-up often lead to a differential diagnosis. Chronic venous insufficiency is a generic term for a disturbed venous backflow. It is caused by an obstruction or an antegrade or retrograde flow insufficiency. Most common diseases in this context are varicosis or a post-thrombotic syndrome. Sonography and special function tests provide a diagnosis. The basic therapy consists in regular exercise, normalization of weight and compression therapy. In case of a hemodynamically relevant varicose vein surgery or endovascular treatment is advisable. The post-thrombotic syndrome must be treated consistently with the basic therapy.A lymphedema may be hereditary or acquired. In a first step diseases like neoplasia need to be excluded. The initial therapy consists in manual lymph drainage in combination with special compression bandages. Flat knit stockings should be prescribed. Surgical treatment is reserved for special circumstances.A lipedema is clinically diagnosed. It is characterized by lipohypertrophia, pressure sensitivity of the tissue and susceptibility to hematomas. Treatment options include weight reduction, regular exercise, lymph drainage and compression therapy, in some cases liposuction.


Subject(s)
Edema , Leg , Lymphedema , Vascular Diseases , Diagnosis, Differential , Edema/diagnosis , Edema/etiology , Edema/pathology , Edema/physiopathology , Humans , Leg/diagnostic imaging , Leg/pathology , Leg/physiopathology , Lymphedema/complications , Lymphedema/diagnosis , Lymphedema/pathology , Lymphedema/physiopathology , Vascular Diseases/complications , Vascular Diseases/diagnosis , Vascular Diseases/pathology , Vascular Diseases/physiopathology
16.
Org Biomol Chem ; 17(7): 1979-1983, 2019 02 13.
Article in English | MEDLINE | ID: mdl-30377683

ABSTRACT

Functionalization of surfaces with responsive molecular entities is currently an important research field allowing the organization of molecular functions in space in a defined way and thus accessing emergent properties not observed in solution. Herein we report on the synthesis of a hemithioindigo molecular motor bearing thioether feet for surface attachment on its thioindigo fragment. We also give a full theoretical description of its ground state energy profile together with an experimental evaluation of the visible light driven unidirectional rotation in solution. Comparison with the corresponding unsubstituted original motor shows that after feet-attachment the hemithioindigo molecular motor is fully operative with a similar maximum attainable speed and degree of unidirectionality.

17.
J Am Chem Soc ; 140(15): 5311-5318, 2018 04 18.
Article in English | MEDLINE | ID: mdl-29578704

ABSTRACT

Hemithioindigo-based molecular motors are powered by nondamaging visible light and provide very fast directional rotations at ambient conditions. Their ground state energy profile has been probed in detail, but the crucial excited state processes are completely unknown so far. In addition, very fast processes in the ground state are also still elusive to date and thus knowledge of the whole operational mechanism remains to a large extent in the dark. In this work we elucidate the complete light-driven rotation mechanism by a combination of multiscale broadband transient absorption measurements covering a time scale from fs to ms in conjunction with a high level theoretical description of the excited state. In addition to a full description of the excited state dynamics in the various time regimes, we also provide the first experimental evidence for the elusive fourth intermediate ground state of the original HTI motor. The fate of this intermediate also is followed directly proving complete unidirectionality for both 180° rotation steps. At the same time, we uncover the hitherto unknown involvement of an unproductive triplet state pathway, which slightly diminishes the quantum yield of the E to Z photoisomerization. A rate model analysis shows that increasing the speed of motor rotation is most effectively done by increasing the photoisomerization quantum yields instead of barrier reduction for the thermal ratcheting steps. Our findings are of crucial importance for improved future designs of any light-driven molecular motor in general to yield better efficiencies and applicability.

18.
Eur Arch Otorhinolaryngol ; 275(3): 699-707, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29330597

ABSTRACT

PURPOSE: The aim was to determine inpatient treatment rates of idiopathic sudden sensorineural hearing loss (ISSNHL) with focus on diagnostics, treatment, and outcome. METHODS: A retrospective population-based study in the federal state Thuringia in 2011 and 2012 was performed on all 490 inpatients (51% females, median age: 60 years) treated for ISSNHL (Median duration: 7 days). The association between analyzed parameters and the probability of recovery was tested using univariable and multivariable statistics. RESULTS: The inpatient treatment rate for ISSNHL was 11.23 per 100,000. 172 patients (35%) had an outpatient treatment prior to inpatient treatment. For pure-tone audiometry of the three most affected frequencies (3PTAmax), the initial median hearing loss was 66.67 dB, the median absolute hearing gain ΔPTAabs was 10.0 dB, and the median relative hearing gain in relation with the contralateral side ΔPTArel contral was 30.86%. 51% of the patients reached a ΔPTAabs of ≥ 10 dB. About 2 of 5 patients recovered to a ΔPTArel contral ≥ 50% or reached ≤ 10 dB of contralateral ear. The multivariate analysis revealed that an ISSNHL on the left side [Hazard ratio (HR) = 1.6.88; confidence interval (CI) = 1.161-2.454], no down-sloping audiogram type (HR = 2.016; CI = 1.391-2.921), and no prior outpatient prednisolone treatment (HR = 2.374; CI = 1.505-3.745) were independent factors associated with better recovery (ΔPTAabs ≥ 10 dB). CONCLUSION: Inpatient treatment of ISSNHL is variable in daily practice. The population-based recovery rate was worse than reported in clinical trials. More standardization and clearer criteria for outpatient, inpatient, and salvage therapy are needed.


Subject(s)
Hearing Loss, Sensorineural/drug therapy , Hearing Loss, Sudden/drug therapy , Hospitalization , Ambulatory Care , Audiometry, Pure-Tone , Female , Glucocorticoids/therapeutic use , Guideline Adherence , Health Services Research , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sudden/diagnosis , Humans , Male , Middle Aged , Multivariate Analysis , Practice Guidelines as Topic , Prednisolone/therapeutic use , Retrospective Studies , Treatment Outcome
19.
Angew Chem Int Ed Engl ; 56(46): 14536-14539, 2017 11 13.
Article in English | MEDLINE | ID: mdl-28892243

ABSTRACT

Hemithioindigo molecular motors undergo very fast unidirectional rotation upon irradiation with visible light, which has prevented a complete analysis of their working mechanism. In this work, we have considerably slowed down their motion by using a new synthesis for sterically hindered motor derivatives. This method allowed the first observation of all four intermediate states populated during rotation. The exact order in which each isomeric state is formed under irradiation conditions was elucidated using low temperature 1 H NMR spectroscopy in conjunction with other analytical methods. At the same time, complete unidirectionality could also be directly shown. Access to slowly rotating hemithioindigo motors opens up a plethora of new applications for visible-light-induced unidirectional motions, especially in areas such as catalysis, smart materials, and supramolecular chemistry.

20.
Otol Neurotol ; 38(10): e460-e469, 2017 12.
Article in English | MEDLINE | ID: mdl-28938275

ABSTRACT

OBJECTIVE: To determine inpatient treatment rates of patients with dizziness with focus on diagnostics, treatment and outcome. STUDY DESIGN: Retrospective population-based study. SETTING: Inpatients in the federal state Thuringia in 2014. PATIENTS: All 1,262 inpatients (62% females, median age: 61 yr) treated for inpatient dizziness were included. MAIN OUTCOME MEASURES: The association between analyzed parameters and probability of improvement and recovery was tested using univariable and multivariable statistics. RESULTS: Final diagnosis at demission was peripheral vestibular disorder (PVD), central vestibular disorder (CVD), cardiovascular syndrome, somatoform syndrome, and unclassified disease in 75, 9, 3, 0.6, and 13%, respectively. The most frequent diseases were acute vestibular neuritis (28%) and benign paroxysmal positional vertigo (22%). The follow-up time was 38 ±â€Š98 days. 88.5% of patients showed at least an improvement of complaints and 31.4% a complete recovery. The probability for no improvement from inpatient dizziness was higher if the patient had a history of ear/vestibular disease (hazard ratio [HR] = 1.506; 95% confidence interval [CI] = 1.301-1.742), and was taking more than two drugs for comorbidity (HR = 1.163; CI = 1.032-1.310). Compared with final diagnosis of cardiovascular syndrome, patients with PVD (HR = 1.715; CI = 1.219-2.415) and CVD (HR = 1.587; CI = 1.076-2.341) had a worse outcome. CONCLUSIONS: Inpatient treatment of dizziness was highly variable in daily practice. The population-based recovery rate was worse than reported in clinical trials. We need better ways to implement clinical trial findings for inpatients with dizziness.


Subject(s)
Dizziness/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Benign Paroxysmal Positional Vertigo/epidemiology , Cardiovascular Diseases/complications , Cardiovascular Diseases/epidemiology , Child , Child, Preschool , Dizziness/diagnosis , Dizziness/epidemiology , Female , Germany/epidemiology , Guideline Adherence , Humans , Inpatients , Male , Middle Aged , Population , Retrospective Studies , Treatment Outcome , Vestibular Diseases/diagnosis , Vestibular Diseases/epidemiology , Vestibular Diseases/therapy , Vestibular Neuronitis/diagnosis , Vestibular Neuronitis/epidemiology , Vestibular Neuronitis/therapy , Young Adult
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