[Impact of functional mass lesions in professional female singers : Biomechanics of vocal fold oscillation in the register transition regions]. / Auswirkungen von Phonationsverdickungen bei professionellen Sängerinnen : Biomechanik der Stimmlippenschwingungen in den Registerübergangsregionen.

BACKGROUND: The influence of functional mass lesions on vocal fold oscillation patterns in vocally challenging tasks is not yet understood in detail. MATERIALS UND METHODS: Glissandi on the vowel [a:] from 220 to 440 Hz and 440 to 880 Hz were analyzed in three groups of four professional female singers: without a mass lesion or dysphony (group A), with a functional mass lesion (swellings without a great impact on oscillation patterns during stroboscopy; group B), and with organic dysphony (group C). High-speed digital imaging (HSDI; 20,000 fps), and acoustic and electroglottographic (EGG) signals were used for analysis. Based on the EGG sample entropy, time windows for analysis of register transition phenomena were constructed. The voice signals (glottal area waveform, GAW; acoustic and EGG signals) were perceptually rated in terms of the noticeability of registration events. RESULTS: The absolute sample entropy revealed maxima in fundamental frequency regions where register transitions typically occur. Groups A and B could be distinguished neither by perceptual rating nor based on sample entropy values. In comparison to the other two groups, the absolute sample entropy values of group C were greater in the lower glissando. However, the larger vocal fold oscillatory irregularities were observable for the upper glissando in this group. CONCLUSION: Functional mass lesions do not influence biomechanics adversely in vocally challenging tasks such as register transitions. The use of sample entropy as a criterion for detection of register transitions is promising, but needs further validation.

[Extrapulmonary sarcoidosis: gastrointestinal involvement -case report and review of literature]. / Extrapulmonale Sarkoidose: Befall des Gastrointestinaltraktes - Fallbericht und Literaturrecherche.

Sarcoidosis is a rare systemic disease characterized by noncaseating granulomas in affected organs. With > 90 % of all cases lung involvement is the most frequent site of manifestation of sarcoidosis, nevertheless multiple other organs can be affected. Extrapulmonary manifestations are lymph nodes, skin, nervous system, heart, eyes, bone marrow, spleen or gastrointestinal tract including liver and pancreas. Involvement of the gastrointestinal tract is rare, it can affect the whole intestine and is most frequently found in the stomach. Despite its infrequent manifestation, gastrointestinal sarcoidosis can have a significant clinical impact depending on the organ involved, so that early diagnosis is warranted. Medical treatment mainly consists of immunosuppressive therapy, most frequently with corticosteroids being the first treatment of choice. Dosage and duration of therapy is not well established yet. In the literature very limited data are available on this topic with randomized trials missing completely. The aim of this paper is to give a summary of the available data to this date.

[Current methods for modelling voice production]. / Aktuelle Methoden zur Modellierung des Stimmgebungsprozesses.

BACKGROUND: Many details of the phonatory process are not yet fully understood. Besides observational research, scientists have long since been trying to explain the physical fundamentals of voicing using simulations. This approach is commonly called modeling. However, the knowledge gained often failed to find its way to professionals working with the voice, such as singing teachers, voice therapists, and voice coaches, and sometimes also to otorhinolaryngologists and phoniatricians. The reason for this is that scientific publications on this topic mostly contain very detailed mathematical and physical descriptions, which are often hard to understand. OBJECTIVE: A simplified presentation and explanation of current methods for modeling the phonatory process, which have contributed greatly to uncovering and understanding the relationships involved in voicing during recent years. METHODS: The presented methods cover a wide spectrum, ranging from numerically rather simple to mathematically highly complex models. Experimental models are based on self-oscillating silicon or static vocal folds. Cadaver models have the advantage of being representative of the natural phonation process. RESULTS: An overview of different kinds of models is given to show the diversity of modeling approaches without going into mathematical or physical details. CONCLUSION: Numerical and experimental models for simulating the phonatory process enable causalities and correlations to be uncovered, which can be used in the future to adapt conservative and surgical voice therapies, or even to suggest entire new treatment strategies.

[3D visualization and analysis of vocal fold dynamics]. / 3D-Visualisierung und Analyse von Stimmlippenschwingungen.

BACKGROUND: Visual investigation methods of the larynx mainly allow for the two-dimensional presentation of the three-dimensional structures of the vocal fold dynamics. The vertical component of the vocal fold dynamics is often neglected, yielding a loss of information. The latest studies show that the vertical dynamic components are in the range of the medio-lateral dynamics and play a significant role within the phonation process. OBJECTIVES: This work presents a method for future 3D reconstruction and visualization of endoscopically recorded vocal fold dynamics. MATERIALS AND METHODS: The setup contains a high-speed camera (HSC) and a laser projection system (LPS). The LPS projects a regular grid on the vocal fold surfaces and in combination with the HSC allows a three-dimensional reconstruction of the vocal fold surface. Hence, quantitative information on displacements and velocities can be provided. The applicability of the method is presented for one ex-vivo human larynx, one ex-vivo porcine larynx and one synthetic silicone larynx. RESULTS: The setup introduced allows the reconstruction of the entire visible vocal fold surfaces for each oscillation status. This enables a detailed analysis of the three dimensional dynamics (i. e. displacements, velocities, accelerations) of the vocal folds. CONCLUSIONS: The next goal is the miniaturization of the LPS to allow clinical in-vivo analysis in humans. We anticipate new insight on dependencies between 3D dynamic behavior and the quality of the acoustic outcome for healthy and disordered phonation.

[Colon Polypectomy - And Then?]. / Polypektomie am Kolon - und dann?

Colorectal cancer (CRC) is the most frequent gastrointestinal tumour. Most CRC appear to arise from adenomas of the colon in a period of 10 or 15 years. The ultimately progression of benign adenomas to malignant CRC is known as the adenoma-carcinoma sequence. In addition, the description of the "serrated pathway" has shifted the focus of interest also towards to sessile serrated adenomas and traditional serrated adenomas in the development of CRC. It has been proven that the screening colonoscopy might prevent CRC by early detection of adenomatous polyps as precursors for colorectal cancer and polypectomy. Thus, disease-associated mortality of CRC could be reduced. Colonoscopy, the gold standard in CRC diagnosis, is recommended to men and women from the age of 55. On the one hand, there are requirements to the endoscopists. On the other hand there are also essential requirements to pathologists' findings. After polypectomy a risk stratification for aftercare based on endoscopic and histological findings is necessary. Endoscopic follow-up of high-risk patients (≥ 3 tubular adenomas, ≥ 1 adenoma ≥ 1 cm, tubulovillous or villous adenoma, ≥ 1 adenoma with high-grade intraepithelial neoplasia, ≥ 10 adenoma no matter what size or histological findings) should be done sooner (< 3 years). In contrast, colonoscopy in low-risk patients (1 or 2 [tubular] adenomas, size < 1 cm) should be performed later rather than sooner (> 5 years). Colonoscopic surveys under 12 months should be done only in exceptional and very serious situations. Pharmaceutical chemoprevention of adenomas or CRC are still part of clinical trails. More data are necessary.

[Epidemiology and risk factors of hepatocellular carcinoma]. / Epidemiologie und Risikofaktoren des hepatozellulären Karzinoms.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) has increased over the past decades as a result of alcoholic liver disease, the metabolic syndrome and the increasing incidence of viral hepatitis B and C. OBJECTIVES: An evaluation of the epidemiology of HCC, presentation and discussion of the risk factors for the development of HCC. MATERIAL AND METHODS: This study was based on a literature review, analysis of the statistics of the World Health Organization (WHO), discussion of current basic research and expert recommendations. RESULTS: The results show that HCC already represents the fifth most common malignancy in men and the ninth most common malignancy in women, and the incidence is still rising. The pronounced regional differences in prevalence and underlying risk factors are mainly, but not exclusively, due to the prevalence of chronic viral hepatitis B. CONCLUSION: Hepatocellular carcinoma is a major medical problem. Primary prevention measures and suitable screening algorithms are gaining more and more importance.

[Evaluation of 2 German Parental Questionnaires: a comparative analysis of the FRAKIS questionnaire for early speech development and the early lexical development inventory ELAN for 2-year-olds]. / Validität der Elternfragebögen FRAKIS und ELAN bei der Vorsorgeuntersuchung U7.

OBJECTIVE: The German parental questionnaires FRAKIS and ELAN are 2 screening instruments, usable in the German preventive paediatric examinations for 2-year-olds. This study investigates the difference between the questionnaires with regard to validity, reliability, time and cost-efficiency and usability in daily clinical practice. METHOD: The parents of 25 children filled in the questionnaires FRAKIS and ELAN. As a reference test, the German speech development test 2 (SETK-2, Grimm 2000) was applied. Vocabulary results were compared with SETK-2 subtest production I (word production). RESULTS: Both parental questionnaires correlated significantly with the SETK-2 subtest production I. ELAN and FRAKIS showed equal results in classifying patients as "critical-below average" or "uncritical-indifferent". CONCLUSION: The ELAN as well as FRAKIS are both appropriate screening tools for identifying language developmental delay in 2-year-olds.

[Validation of an automatic speech analysis in children with isolated cleft palate]. / Validierung einer automatischen Analyse der Sprechproben von Kindern mit isolierter Gaumenspalte.

BACKGROUND: Following surgical repair of cleft lip and palate, hearing and speech and language development are important issues for the continued care of affected childhood and adolescent patients. Therefore, PEAKS (Program for Evaluation and Analysis of all Kinds of Speech Disorders) was developed in order to rate speech intelligibility automatically and reduce the time required for diagnostics. PEAKS is based on a speech recognition system and was extended to incorporate a speaker model. This investigation validated PEAKS for isolated cleft palate. METHODS: From each of the 39 children with isolated cleft palate (3.1-14.5 years), 99 word productions were recorded digitally and analyzed-once "subjectively" by five experts and five nonexperts; once "objectively" using PEAKS. RESULTS: The automatic speech recognition system and the experts arrive at similar results with regard to speech intelligibility. The expert and nonexpert ratings differ significantly from each other. Within the group of nonexperts, a weak interrater reliability demonstrates the uncertainty associated with their ratings. CONCLUSION: PEAKS delivers reliable and representative results with regard to speech intelligibility among children and adolescents with isolated cleft palate. The automatic measurement of speech quality in children and adolescents with isolated cleft palate is possible.

[Diagnosis of and therapy for hepatocellular carcinoma]. / Diagnostik und Therapie des hepatozellulären Karzinoms.

The interdisciplinary guidelines at the S3 level on the diagnosis of and therapy for hepatocellular carcinoma (HCC) constitute an evidence- and consensus-based instrument that is aimed at improving the diagnosis of and therapy for HCC since these are very challenging tasks. The purpose of the guidelines is to offer the patient (with suspected or confirmed HCC) adequate, scientifically based and up-to-date procedures in diagnosis, therapy and rehabilitation. This holds not only for locally limited or focally advanced disease but also for the existence of recurrences or distant metastases. Besides making a contribution to an appropriate health-care service, the guidelines should also provide the foundation for an individually adapted, high-quality therapy. The explanatory background texts should also enable non-specialist but responsible colleagues to give sound advice to their patients concerning specialist procedures, side effects and results. In the medium and long-term this should reduce the morbidity and mortality of patients with HCC and improve their quality of life.

Investigation of prescribed movement in fluid-structure interaction simulation for the human phonation process.

In a partitioned approach for computational fluid-structure interaction (FSI) the coupling between fluid and structure causes substantial computational resources. Therefore, a convenient alternative is to reduce the problem to a pure flow simulation with preset movement and applying appropriate boundary conditions. This work investigates the impact of replacing the fully-coupled interface condition with a one-way coupling. To continue to capture structural movement and its effect onto the flow field, prescribed wall movements from separate simulations and/or measurements are used. As an appropriate test case, we apply the different coupling strategies to the human phonation process, which is a highly complex interaction of airflow through the larynx and structural vibration of the vocal folds (VF). We obtain vocal fold vibrations from a fully-coupled simulation and use them as input data for the simplified simulation, i.e. just solving the fluid flow. All computations are performed with our research code CFS++, which is based on the finite element (FE) method. The presented results show that a pure fluid simulation with prescribed structural movement can substitute the fully-coupled approach. However, caution must be used to ensure accurate boundary conditions on the interface, and we found that only a pressure driven flow correctly responds to the physical effects when using specified motion.

[Perceptual and automatic voice and speech analysis of chronic laryngitis and T1 vocal cord cancer]. / Perzeptive und maschinelle Stimm- und Sprechanalyse bei chronischer Laryngitis und T1-Stimmlippenkarzinom.

BACKGROUND: Patients with chronic laryngitis and T1 vocal cord cancer were compared using perceptual and text-based objective voice and speech analyses in order to determine which group is more affected in its ability to communicate and whether a distinction between the two pathologies is possible. PATIENTS AND METHODS: In all, 13 patients with histologically proven chronic laryngitis and 13 patients with T1 vocal cord cancer were compared perceptually by five speech therapists on the basis of seven criteria and objectively by a speech recognition system and prosodic analysis. RESULTS: Both, the data of the five speech therapists and the results of the automatic analysis revealed no significant differences between the two patient groups. CONCLUSION: A distinction between chronic laryngitis and T1 vocal cord carcinoma by mere voice and speech analysis is not possible, because the patient groups do not show significant differences in their voice quality.

Subclinical ascites defines an intermediate stage between compensated and decompensated cirrhosis.

BACKGROUND: Clinical detection of ascites is a sign of decompensation and correlates with shorter survival in patients with cirrhosis. However, the prognostic relevance of sole detection of ascites by ultrasound (subclinical ascites) is not investigated so far. The aim of the study was to investigate the prognostic relevance of subclinical ascites detected by ultrasound in comparison to absent or clinically detectable ascites in patients with cirrhosis. METHODS: Between 11/1995 and 11/2004 a total of 729 patients with cirrhosis underwent sonographic and hemodynamic (including measurement of HVPG) evaluation. The mean follow up time was 47 months (range: 0.13 - 131). Kaplan-Meier survival curves and multivariate analysis were used to investigate differences. RESULTS: 443 patients were included in the final investigation - 153 patients without ascites, 38 with subclinical ascites and 252 patients with clinical ascites. Kaplan Meier survival curves were significantly different between the three groups (p < 0.001). Interestingly, patients with subclinical ascites had similar values compared to patients with clinical ascites regarding parameters of portal hypertension (HVPG) and liver dysfunction (INR), while parameters of systemic and renal dysfunction (heart beat, creatinin, serum sodium) were similar to patients without ascites. MELD, Child-Pugh score and ascites were independent predictors of mortality in the entire group, while Child-Pugh score and HVPG were independent factors in the subclinical ascites group. CONCLUSION: Detection of subclinical ascites by ultrasound allows the identification of a group of cirrhotic patients with intermediary survival compared to patients without or with clinical ascites. This group of patients is characterized by severe portal hypertension but absence of systemic and renal dysfunction.

[Expert opinion on boceprevir- and telaprevir-based triple therapies of chronic hepatitis C]. / Expertenempfehlungen zur Triple-Therapie der HCV-Infektion mit Boceprevir und Telaprevir.

With the approval of boceprevir and telaprevir the standard treatment of chronic hepatitis C virus (HCV) genotype 1 infection will be the triple therapy of a HCV protease inhibitor together with pegylated interferon alfa and ribavirin. In clinical studies a significant increase of sustained virological response rates from 38 - 44 % to 63 - 75 % for treatment-naïve and from 17 - 21 % to 59 - 66 % in treatment-experienced patients in comparison to the dual combination therapy with pegylated interferon alfa and ribavirin alone has been demonstrated. In addition, a large number of treatment-naïve patients and relapsers benefit from shorten treatment durations to 24 - 28 weeks. However, important differences exist between the administration of boceprevir and telaprevir in terms of a pegylated interferon alfa/ribavirin lead-in phase, the duration of dosing of the protease inhibitor, the overall treatment duration, HCV RNA measurements for response guided treatment durations and stopping rules. Furthermore, triple therapies with boceprevir and telaprevir may be associated with selection of resistant viral variants, new adverse events and clinically relevant drug-drug interactions. The present review gives an overview on the results of underlying clinical studies together with a guideline for the practical management of boceprevir- and telaprevir-based triple therapies.

KRAS mutation in metastatic pancreatic ductal adenocarcinoma: results of a multicenter phase II study evaluating efficacy of cetuximab plus gemcitabine/oxaliplatin (GEMOXCET) in first-line therapy.

BACKGROUND: Genetic alterations within the epidermal growth factor receptor (EGFR) pathway, including KRAS mutations, have been demonstrated to be associated with response to EGFR inhibitors like cetuximab in colorectal cancers. Mutations in the KRAS gene have been found in 70-90% of pancreatic cancers. Unfortunately, the addition of cetuximab to chemotherapy did not increase response or survival in patients with advanced pancreatic cancer in phase II and phase III studies. The aim of this study was to evaluate the relationship between KRAS mutations and response or survival in patients with metastatic pancreatic cancer treated with cetuximab plus chemotherapy. METHODS: Within a multicenter phase II trial, 64 patients with metastatic pancreatic cancer were treated with cetuximab in combination with gemcitabine and oxaliplatin until disease progression. Analyses of the EGFR pathway, including KRAS mutations, could be performed in 25 patients. Analyses were carried out following microdissection of the tumor. RESULTS: Fourteen (56%) of the 25 patients examined harbored a point mutation in codon 12 of the KRAS gene. No differences between the groups were noted in median progression-free survival (104 days in KRAS wild-type patients vs. 118 days in patients with KRAS mutations). Overall survival was longer in wild-type patients compared to patients with KRAS mutations (263 vs. 162 days), but the difference did not reach statistical significance. A further analysis of our clinical phase II trial showed that the presence of a rash was significantly correlated with overall survival. CONCLUSIONS: KRAS mutation in codon 12 may be associated with reduced survival compared to KRAS wild type. The role of KRAS mutations for cetuximab therapy in pancreatic cancer warrants further investigation in larger trials to exclude an epiphenomenon. Furthermore, the development of a rash is indicative of clinical benefit.

Assessment of local vocal fold deformation characteristics in an in vitro static tensile test.

Voice quality is strongly dependent on vocal fold dynamics, which in turn are dependent on lung pressure and vocal fold biomechanics. Numerical and physical models are often used to investigate the interactions of these different subsystems. However, the utility of numerical and physical models is limited unless appropriately validated with data from physiological models. Hence a method that enables analysis of local vocal fold deformations along the entire surface is presented. In static tensile tests, forces are applied to distinctive working points being located in cover and muscle, respectively, so that specific layer properties can be investigated. The forces are directed vertically upward and are applied along or above the vocal fold edge. The resulting deformations are analyzed using multiple perspectives and three-dimensional reconstruction. Deformation characteristics of four human vocal folds were investigated. Preliminary results showed two phases of deformation: a range with a small slope for small deformations fading into a significant nonlinear deformation trend with a high slope. An increase of tissue stiffness from posterior to anterior was detected. This trend is more significant for muscle and in the mid-anterior half of the vocal fold.

[Pregnancy under immunosuppression]. / Schwangerschaft unter Immunsuppression.

The desire to have children and pregnancy itself are important topics in the treatment of patients under immunosuppression. In this review the risks of frequently prescribed immunosuppressants are discussed regarding the safety of mother and child during and after pregnancy. Knowledge of the specific risks of immunosuppressants in pregnancy is important to balance the therapy between the patients' desire to be treated most effectively and to deliver a healthy child after an uncomplicated pregnancy. Generally, an interdisciplinary approach is advisable in treating and counseling immunosuppressed patients with a desire to have children and during pregnancy.

Clinical characterization of respiratory large droplet production during common airway procedures using high-speed imaging.

During the COVID-19 pandemic, a significant number of healthcare workers have been infected with SARS-CoV-2. However, there remains little knowledge regarding large droplet dissemination during airway management procedures in real life settings. 12 different airway management procedures were investigated during routine clinical care. A high-speed video camera (1000 frames/second) was for imaging. Quantitative droplet characteristics as size, distance traveled, and velocity were computed. Droplets were detected in 8/12 procedures. The droplet trajectories could be divided into two distinctive patterns (type 1/2). Type 1 represented a ballistic trajectory with higher speed large droplets whereas type 2 represented a random trajectory of slower particles that persisted longer in air. The use of tracheal cannula filters reduced the amount of droplets. Respiratory droplet patterns generated during airway management procedures follow two distinctive trajectories based on the influence of aerodynamic forces. Speaking and coughing produce more droplets than non-invasive ventilation therapy confirming these behaviors as exposure risks. Even large droplets may exhibit patterns resembling the fluid dynamics smaller airborne aerosols that follow the airflow convectively and may place the healthcare provider at risk.

Role of clinical and CT findings in the identification of adult small-bowel intussusception requiring surgical intervention.

BACKGROUND: In adults, intussusception has been considered traditionally to have an underlying aetiology. The aim of this study was to determine CT and clinical features of small-bowel intussusceptions that required surgical intervention. METHODS: Adult patients were identified in whom small-bowel intussusceptions were noted on CT images. The appearance, number, type (enteroenteric versus enterocolic), length and maximum short-axis diameter of intussusceptions, and presence of bowel obstruction (short-axis diameter of proximal small bowel greater than 3 cm) were analysed. The outcome was defined as surgical (complicated) or self-limiting (uncomplicated). Associations between complicated and uncomplicated intussusceptions and patient characteristics were investigated. RESULTS: Among 75 patients (56 male) with a mean age of 45 years, 103 intussusceptions were identified, of which 98 (95 per cent) were enteroenteric and 5 (5 per cent) enterocolic. Only 12 of 103 intussusceptions (12 per cent) in 12 of 75 (16 per cent) patients required surgical therapy and were considered to be complicated, with half of these having a neoplastic lead point. Length (P < 0.001), diameter (P < 0.001) and type (P = 0.002) of intussusception as well as presence of vessels (P = 0.023) within an intussusception on a CT scan, clinical symptoms (P = 0.007) and signs of bowel obstruction (P < 0.001) were associated with a surgical outcome. CONCLUSION: Clinical symptoms, signs of bowel obstruction, type and length of intussusception, and a visible tumour within an intussusception on CT scan were critical signs of complicated intussusception, requiring surgical intervention.

Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo.

OBJECTIVE: The hepatic integration of human adipose tissue derived mesenchymal stem cells (hAT-MSCs) in vivo with or without prior differentiation to hepatocyte-like cells in vitro was investigated. METHODS AND RESULTS: Cells, isolated either from peritoneal or subcutaneous adipose tissue, expressed mesenchymal stem cell surface markers and featured multiple lineage differentiation. Under conditions favouring hepatocyte differentiation, hAT-MSCs gained hepatocytic functions in vitro including urea formation, glycogen synthesis, cytochrome P450 enzyme activity, and expression of hepatocyte-specific transcripts of carbamoylphosphate synthetase, albumin and cytochrome P450 type 3A4 (CYP3A4). Transgenic expression of green fluorescent protein emerged upon hepatocyte differentiation when driven by the hepatocyte-specific promoter of the cytosolic phosphoenolpyruvate carboxykinase gene but was constitutive from the ubiquitin gene promoter. Human AT-MSCs were transplanted into livers of immunodeficient Pfp/Rag2-/- mice with or without prior hepatocyte differentiation in vitro. Donor-derived human cells engrafted in the mouse host liver predominantly in the periportal region of the liver lobule. They expressed HepPar1 and albumin, typical features of differentiated human hepatocytes, in the otherwise negative mouse liver background. Engraftment was significantly more efficient using hAT-MSCs pre-differentiated to hepatocyte-like cells in vitro as compared with undifferentiated cells. CONCLUSIONS: Pre-differentiation of human MSCs from adipose tissue into hepatocyte-like cells in vitro facilitates long term functional hepatic integration in vivo.