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1.
Nanotechnology ; 33(24)2022 Mar 23.
Article in English | MEDLINE | ID: mdl-35245911

ABSTRACT

Near-infrared detection is widely used for nondestructive and non-contact inspections in various areas, including thermography, environmental and chemical analysis as well as food and medical diagnoses. Common room temperature bolometer-type infrared sensors are based on architectures in theµm range, limiting miniaturization for future highly integrated 'More than Moore' concepts. In this work, we present a first principle study on a highly scalable and CMOS compatible bolometer-type detector utilizing Ge nanowires as the thermal sensitive element. For this approach, we implemented the Ge nanowires on top of a low thermal conducting and highly absorptive membrane as a near infrared (IR) sensor element. We adopted a freestanding membrane coated with an impedance matched platinum absorber demonstrating wavelength independent absorptivity of 50% in the near to mid IR regime. The electrical characteristics of the device were measured depending on temperature and biasing conditions. A strong dependence of the resistance on the temperature was shown with a maximum temperature coefficient of resistance of -0.07 K-1atT = 100 K. Heat transport simulations using COMSOL were used to optimize the responsivity and temporal response, which are in good agreement with the experimental results. Further, lock-in measurements were used to benchmark the bolometer device at room temperature with respect to detectivity and noise equivalent power. Finally, we demonstrated that by operating the bolometer with a network of parallel nanowires, both detectivity and noise equivalent power can be effectively improved.

2.
Ann Oncol ; 31(4): 495-500, 2020 04.
Article in English | MEDLINE | ID: mdl-32085891

ABSTRACT

BACKGROUND: Systemic second- and third-line therapies for malignant pleural mesothelioma (MPM) result in a median progression-free survival (mPFS) of <2 months and median overall survival (mOS) of 6-9 months. Lurbinectedin binds to the DNA of the regulatory region while inhibiting tumour-associated macrophage transcription. In early trials, encouraging outcomes occurred in patients (pts) with MPM treated with lurbinectedin. We aimed to generate lurbinectedin efficacy and safety data among pts with progressive MPM. PATIENTS AND METHODS: Pts with progressing MPM treated with first-line platinum-pemetrexed chemotherapy with or without immunotherapy received lurbinectedin monotherapy. Treatment was given intravenously at 3.2 mg/m2 dose every 3 weeks until progression or unacceptable toxicity. Using Simon's two-stage design, the primary endpoint, progression-free survival (PFS) at 12 weeks (PFS12wks), was met if achieved by ≥21 pts (p0 ≤35% versus p1 ≥55%). RESULTS: Forty-two pts from nine centres across Switzerland and Italy were recruited. Histology was epithelioid in 33 cases, sarcomatoid in 5, and biphasic in 4. Overall 10/42 (23.8%) underwent prior immunotherapy and 14/42 (33.3%) had progressed ≤6 months after first-line chemotherapy. At data cut-off PFS12wks was met by 22/42 pts (52.4%; 90% confidence interval (CI): 38.7% to 63.5%; P = 0.015) with an mPFS of 4.1 months and mOS of 11.1 months. The best response was complete and partial remission observed in one patient each and stable disease in 20 pts. The duration of disease control was 6.6 months (95% CI: 5.2-7.4). No significant difference in PFS12wks, mPFS, and mOS was recorded in epithelioid versus non-epithelioid cases and pts with prior immunotherapy versus those without. Similar mPFS but shorter mOS were observed among pts who progressed within ≤6 months after first-line chemotherapy. Lurbinectedin-related grade 3-4 toxicity was seen in 21 pts, mostly being neutropenia (23.8%) and fatigue (16.7%). CONCLUSIONS: The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity regardless of histology, prior immunotherapy, or outcome on prior treatment. CLINICALTRIALS. GOV IDENTIFIER: NCT03213301.


Subject(s)
Mesothelioma, Malignant , Mesothelioma , Pleural Neoplasms , Carbolines , Heterocyclic Compounds, 4 or More Rings , Humans , Italy , Mesothelioma/drug therapy , Palliative Care , Pleural Neoplasms/drug therapy , Switzerland
3.
BMC Cancer ; 20(1): 610, 2020 Jun 30.
Article in English | MEDLINE | ID: mdl-32605648

ABSTRACT

BACKGROUND: Feasibility testing of a simultaneous sparing approach of hippocampus, hypothalamus and pituitary gland in patients undergoing whole-brain radiotherapy (WBRT) with and without a concomitant boost to metastatic sites. INTRODUCTION: Cognitive impairment and hormonal dysfunction are common side effects of cranial radiotherapy. A reduced dose application to the patho-physiologically involved functional brain areas, i.e. hippocampus, hypothalamus and pituitary gland, could reduce these common side effects. While hippocampal sparing is already a common practice to improve cognitive outcome, technical experience of additional combined sparing of the hypothalamus/pituitary gland (HT-P) is insufficient. METHODS: Twenty patients were included in the planning study. In 11 patients, a total dose of 36 Gy of WBRT (2 Gy per fraction) plus a simultaneous integrated boost (SIB) of 9 Gy (0.5 Gy per fraction, total dose: 45 Gy) to the brain metastases was applied. In 9 patients, prophylactic cranial irradiation (PCI) was simulated with a total dose of 30 Gy (2 Gy per fraction). In both patient cohorts, a sparing approach of the hippocampus and the HT-P area was simulated during WBRT. For all treatment plans, volumetric modulated arc therapy (VMAT) was used. Quality assurance included assessment of homogeneity, conformality and target coverage. RESULTS: The mean dose to the hippocampus and HT-P region was limited to less than 50% of the prescribed dose to the planning target volume (PTV) in all treatment plans. Dose homogeneity (HI) of the target volume was satisfying (median HI = 0.16 for WBRT+SIB and 0.1 for PCI) and target coverage (conformation number, CN) was not compromised (median CN = 0.82 for SIB and 0.86 for PCI). CONCLUSION: Simultaneous dose reduction to the hippocampus and the HT-P area did not compromise the PTV coverage in patients undergoing WBRT+SIB or PCI using VMAT. While the feasibility of the presented approach is promising, prospective neurologic, endocrine outcome and safety studies are required.


Subject(s)
Brain Neoplasms/radiotherapy , Cranial Irradiation/adverse effects , Organ Sparing Treatments/methods , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Intensity-Modulated/adverse effects , Adult , Brain Neoplasms/diagnosis , Brain Neoplasms/secondary , Cranial Irradiation/methods , Dose Fractionation, Radiation , Dose-Response Relationship, Radiation , Feasibility Studies , Female , Hippocampus/diagnostic imaging , Hippocampus/radiation effects , Humans , Hypothalamus/diagnostic imaging , Hypothalamus/radiation effects , Male , Organ Sparing Treatments/adverse effects , Organs at Risk/diagnostic imaging , Organs at Risk/radiation effects , Pituitary Gland/diagnostic imaging , Pituitary Gland/radiation effects , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/methods , Tomography, X-Ray Computed
4.
Nature ; 507(7490): 81-5, 2014 Mar 06.
Article in English | MEDLINE | ID: mdl-24598636

ABSTRACT

Low-loss transmission and sensitive recovery of weak radio-frequency and microwave signals is a ubiquitous challenge, crucial in radio astronomy, medical imaging, navigation, and classical and quantum communication. Efficient up-conversion of radio-frequency signals to an optical carrier would enable their transmission through optical fibres instead of through copper wires, drastically reducing losses, and would give access to the set of established quantum optical techniques that are routinely used in quantum-limited signal detection. Research in cavity optomechanics has shown that nanomechanical oscillators can couple strongly to either microwave or optical fields. Here we demonstrate a room-temperature optoelectromechanical transducer with both these functionalities, following a recent proposal using a high-quality nanomembrane. A voltage bias of less than 10 V is sufficient to induce strong coupling between the voltage fluctuations in a radio-frequency resonance circuit and the membrane's displacement, which is simultaneously coupled to light reflected off its surface. The radio-frequency signals are detected as an optical phase shift with quantum-limited sensitivity. The corresponding half-wave voltage is in the microvolt range, orders of magnitude less than that of standard optical modulators. The noise of the transducer--beyond the measured 800 pV Hz-1/2 Johnson noise of the resonant circuit--consists of the quantum noise of light and thermal fluctuations of the membrane, dominating the noise floor in potential applications in radio astronomy and nuclear magnetic imaging. Each of these contributions is inferred to be 60 pV Hz-1/2 when balanced by choosing an electromechanical cooperativity of ~150 with an optical power of 1 mW. The noise temperature of the membrane is divided by the cooperativity. For the highest observed cooperativity of 6,800, this leads to a projected noise temperature of 40 mK and a sensitivity limit of 5 pV Hz-1/2. Our approach to all-optical, ultralow-noise detection of classical electronic signals sets the stage for coherent up-conversion of low-frequency quantum signals to the optical domain.

5.
Internist (Berl) ; 61(8): 875-890, 2020 Aug.
Article in German | MEDLINE | ID: mdl-32676723

ABSTRACT

The term neuroendocrine neoplasms (NEN) encompasses a molecularly and biologically very heterogeneous group of tumors, which have in common their origin in neuroendocrine cells. The also very heterogeneous subgroup of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) is the best classified and investigated group. This article provides a systematic review of the current classification, diagnostics and treatment options of GEP-NEN. In order to achieve a better overview, it was consciously decided not to use an approach based on the primary localization. Instead, a thematic organization according to classification, clinical phenotype, diagnostics and treatment was chosen.


Subject(s)
Gastrointestinal Neoplasms , Intestinal Neoplasms/pathology , Intestinal Neoplasms/therapy , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/therapy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/therapy , Humans
6.
BMC Cancer ; 19(1): 1213, 2019 Dec 12.
Article in English | MEDLINE | ID: mdl-31830931

ABSTRACT

BACKGROUND: Cranial radiotherapy (cRT) can induce hormonal deficiencies as a consequence of significant doses to the hypothalamic-pituitary (HP) axis. In contrast to profound endocrinological follow-up data from survivors of childhood cancer treated with cRT, little knowledge exists for adult cancer patients. METHODS: A systematic search of the literature was conducted using the PubMed database and the Cochrane library offering the basis for our debate of the relevance of HP axis impairment after cRT in adult cancer patients. Against the background of potential relevance for patients receiving whole brain radiotherapy (WBRT), a particular focus was set on the temporal onset of hypopituitarism and the radiation dose to the HP axis. RESULTS: Twenty-eight original papers with a total of 1728 patients met the inclusion criteria. Radiation doses to the HP area ranged from 4 to 97 Gray (Gy). Hypopituitarism incidences ranged from 20 to 93% for adult patients with nasopharyngeal cancer or non-pituitary brain tumors. No study focused particularly on hypopituitarism after WBRT. The onset of hypopituitarism occurred as early as within the first year following cRT (range: 3 months to 25.6 years). However, since most studies started follow-up evaluation only several years after cRT, early onset of hypopituitarism might have gone unnoticed. CONCLUSION: Hypopituitarism occurs frequently after cRT in adult cancer patients. Despite the general conception that it develops only after several years, onset of endocrine sequelae can occur within the first year after cRT without a clear threshold. This finding is worth debating particularly in respect of treatment options for patients with brain metastases and favorable survival prognoses.


Subject(s)
Brain Neoplasms/radiotherapy , Cranial Irradiation/adverse effects , Hypopituitarism/etiology , Hypothalamus/radiation effects , Pituitary Gland/radiation effects , Radiation Injuries/etiology , Humans , Hypopituitarism/pathology , Hypothalamus/pathology , Pituitary Gland/pathology , Radiation Injuries/pathology , Randomized Controlled Trials as Topic
7.
Neuropediatrics ; 50(3): 197-201, 2019 06.
Article in English | MEDLINE | ID: mdl-30939602

ABSTRACT

Mitochondrial dynamics such as fission and fusion play a vital role in normal brain development and neuronal activity. DNM1L encodes a dynamin-related protein 1 (Drp1), which is a GTPase essential for proper mitochondrial fission. The clinical phenotype of DNM1L mutations depends on the degree of mitochondrial fission deficiency, ranging from severe encephalopathy and death shortly after birth to initially normal development and then sudden onset of refractory status epilepticus with very poor neurologic outcome. We describe a case of a previously healthy 3-year-old boy with a mild delay in speech development until the acute onset of a refractory status epilepticus with subsequent epileptic encephalopathy and very poor neurologic outcome. The de novo missense mutation in DNM1L (c.1207C > T, p.R403C), which we identified in this case, seems to determine a unique clinical course, strikingly similar to four previously described patients in literature with the identical de novo heterozygous missense mutation in DNM1L.


Subject(s)
Brain Diseases/genetics , Dynamins/genetics , Epilepsy, Generalized/genetics , Mutation/genetics , Status Epilepticus/genetics , Brain Diseases/complications , Brain Diseases/diagnostic imaging , Child, Preschool , Epilepsy, Generalized/complications , Epilepsy, Generalized/diagnostic imaging , Humans , Male , Status Epilepticus/complications , Status Epilepticus/diagnostic imaging
8.
Anaesthesist ; 68(12): 821-826, 2019 12.
Article in German | MEDLINE | ID: mdl-31740986

ABSTRACT

Extracorporeal membrane oxygenation (ECMO) is becoming more and more clinically important. The extracorporeal circuit for membrane oxygenation consists of a pump, a membrane oxygenator and large volume tubing. The ECMO device forms an additional compartment, which can absorb drugs with high lipophilia and protein binding. Thus, ECMO affects the volume of distribution and the clearance. As a consequence, the pharmacokinetic-pharmacodynamic (pk-pd) target parameters cannot be achieved. The selection of an appropriate substance and the mode of application, combined with therapeutic drug monitoring (TDM), can significantly improve the therapeutic outcome of critically ill patients.


Subject(s)
Anti-Infective Agents/pharmacokinetics , Extracorporeal Membrane Oxygenation/adverse effects , Extracorporeal Membrane Oxygenation/instrumentation , Critical Illness
9.
Internist (Berl) ; 60(2): 122-127, 2019 02.
Article in German | MEDLINE | ID: mdl-30645664

ABSTRACT

The circadian clock is a complex and highly specialized network of the human organism and is key for metabolic health. Circadian rhythms are modulated by behavioral patterns, physical activity, food intake as well as sleep loss and sleep disorders. Furthermore, an altered expression of clock genes (e. g. PERIOD1 and 2) can alter circadian rhythms. Chronodisruption, i. e. the alteration of circadian rhythms, is associated with a variety of mental and physical illnesses. Recent studies show a significant association between quantitative and qualitative sleep rhythm disturbances and an increasing prevalence of obesity. Furthermore, reduced sleep quality and duration lead to decreased glucose tolerance and insulin sensitivity, thus increasing the risk of developing type 2 diabetes. In addition to the core components of the metabolic syndrome, there are also changes in hormonal and neuronal signaling pathways impinging on human energy metabolism. This review provides an overview of the current literature highlighting the close link between circadian rhythms and human energy metabolism.


Subject(s)
Chronobiology Disorders/physiopathology , Circadian Rhythm/physiology , Energy Metabolism , Obesity/physiopathology , Sleep/physiology , Chronobiology Disorders/complications , Diabetes Mellitus, Type 2/physiopathology , Humans , Metabolic Syndrome/complications , Metabolic Syndrome/physiopathology , Obesity/complications , Sleep Deprivation/physiopathology
10.
Internist (Berl) ; 60(2): 115-121, 2019 02.
Article in German | MEDLINE | ID: mdl-30617700

ABSTRACT

The metabolic functions of different kinds of adipose tissue are of growing scientific and clinical interest. White adipose tissue is not only an energy store but as a highly active endocrine organ it also plays an essential role in the development of diabetes mellitus, dyslipidemia, arterial hypertension and cardiovascular diseases. Brown adipose tissue, on the other hand, can convert chemical energy into heat and could therefore have an opposing, protective effect. The activation of brown adipose tissue and the induction of the development of adipocytes with the characteristics of brown fat cells could make a significant contribution to the treatment of these civilization diseases. This article provides an overview of the current understanding of the physiology and pathophysiology of different adipose tissue types and the resulting therapeutic potential.


Subject(s)
Adipocytes, Brown/metabolism , Adipocytes, White/metabolism , Adipose Tissue, Brown/metabolism , Energy Metabolism/physiology , Obesity/metabolism , Thermogenesis/physiology , Adipocytes, Brown/physiology , Adipose Tissue , Adipose Tissue, Brown/physiology , Adipose Tissue, White/metabolism , Humans , Obesity/physiopathology , Weight Gain
11.
Internist (Berl) ; 59(11): 1157-1162, 2018 Nov.
Article in German | MEDLINE | ID: mdl-30229367

ABSTRACT

BACKGROUND: Childhood cancer survivors are at risk of cancer- and treatment-related chronic health conditions. Since these sequelae may occur years after the end of treatment, many patients are already adults and have completed pediatric oncological care. Thus, successful transition is essential in order to ensure long-term surveillance. OBJECTIVES: The present review outlines the most frequent late effects of childhood cancer treatment. Moreover, difficulties in transition of these patients are discussed and interdisciplinary models of care are presented. RESULTS: Late effects following childhood cancer treatment occur in over two thirds of patients 30 years after the end of the oncological treatment and can affect different organs. The most frequent sequelae are endocrine disturbances, cardiac conditions, and subsequent neoplasms. Many late effects are effectively manageable if detected early. This necessitates an interdisciplinary approach as well as life-long surveillance. CONCLUSIONS: Transition from pediatric to internal medicine care as well as a change in the focus of care, shifting from relapse centered follow-up to late-effects centered surveillance, constitute a special challenge for a successful transition of long-term childhood cancer survivors. Specialized late-effects survivorship clinics offering interdisciplinary care from pediatric oncologists, specialists of internal medicine, and further disciplines enable the early diagnosis and treatment of late-effects.


Subject(s)
Cancer Survivors , Chronic Disease/therapy , Continuity of Patient Care , Neoplasms/therapy , Transition to Adult Care , Adult , Child , Disease Progression , Humans , Medical Oncology , Neoplasms/complications
12.
Internist (Berl) ; 58(10): 1020-1028, 2017 Oct.
Article in German | MEDLINE | ID: mdl-28849301

ABSTRACT

The diabetic emergencies diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS) and hypoglycemia represent severe and potentially life-threatening complications of diabetes mellitus that require prompt diagnostics and treatment. Absolute or relative insulin insufficiency is characteristic of DKA und HHS along with severe dehydration. They differ by the prevalence of ketone bodies and the severity of acidosis; however, the treatment regimens are similar. In contrast, hypoglycemia is the limiting factor for achieving ambitious glucose targets. This article decribes the clinical presentation, diagnostics and emergency management of these metabolic derangements.


Subject(s)
Diabetes Complications/diagnosis , Diabetic Ketoacidosis/diagnosis , Emergencies , Hyperglycemic Hyperosmolar Nonketotic Coma/diagnosis , Hypoglycemia/diagnosis , Blood Glucose/metabolism , Combined Modality Therapy , Diabetes Complications/blood , Diabetes Complications/mortality , Diabetes Complications/therapy , Diabetic Ketoacidosis/blood , Diabetic Ketoacidosis/mortality , Diabetic Ketoacidosis/therapy , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Early Diagnosis , Early Medical Intervention , Fluid Therapy , Humans , Hyperglycemic Hyperosmolar Nonketotic Coma/blood , Hyperglycemic Hyperosmolar Nonketotic Coma/mortality , Hyperglycemic Hyperosmolar Nonketotic Coma/therapy , Hypoglycemia/blood , Hypoglycemia/mortality , Hypoglycemia/therapy , Insulin/blood , Retrospective Studies , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
13.
World J Urol ; 34(2): 181-7, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26055646

ABSTRACT

BACKGROUND: Intratumoural lymphocytic infiltration is strongly associated with the outcome of many human epithelial cancers. The current paper investigated whether subpopulations of tumour-infiltrating T lymphocytes are associated with certain clinicopathological parameters and the prognosis of patients with invasive bladder cancer (BCa). PATIENTS AND METHODS: The infiltration densities of the adaptive immune markers CD3 (the whole T cell population), FOXP3 (regulatory T cells; Tregs), CD8 (T effector cells) and CD45R0 (T effector memory cells) were analysed by immunohistochemistry and image analysis with tissue microarrays of tumour tissues from 149 patients with invasive BCa treated with radical cystectomy. The findings were correlated with certain clinicopathological parameters. RESULTS: Higher FOXP3/CD3 [OS: p = 0.016, HR 1.29, 95% confidence intervals (95% CIs 1.05-1.59)] and FOXP3/CD8 (OS: p = 0.013, HR 1.32, 95% CIs 1.06-1.65) ratios were significantly associated with briefer overall survival and time to cancer-specific death; the latter ratio represented an independent prognostic factor according to a multivariate analysis adjusted for pathological T and N stages (HR 1.32, 95% CIs 1.05-1.67, p = 0.018). The infiltration densities of individual markers (CD3, CD8, FOXP3 and CD45R0) were not significantly associated with clinicopathological parameters or survival; however, a trend towards a better outcome was observed for higher log-transformed CD8 (p = 0.070, HR 0.80, 95% CIs 0.63-1.02) and CD3 (p = 0.113, HR 0.84, 95% CIs 0.68-1.04) infiltration values. CONCLUSIONS: A high fraction of Tregs amongst CD3- and CD8-positive lymphocytes indicated a poor prognosis, thereby emphasising the important role that Tregs play in the suppression of the anti-tumour immune response. No single lymphocytic marker was significantly correlated with clinical outcomes, but high CD3 and CD8 infiltration showed trends towards better prognosis.


Subject(s)
Adaptive Immunity , CD8-Positive T-Lymphocytes/pathology , Carcinoma, Transitional Cell/immunology , Lymphocytes, Tumor-Infiltrating/pathology , Neoplasm Staging , T-Lymphocytes, Regulatory/pathology , Urinary Bladder Neoplasms/immunology , Adult , Aged , Aged, 80 and over , CD8-Positive T-Lymphocytes/immunology , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Female , Follow-Up Studies , Germany/epidemiology , Humans , Immunohistochemistry , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate/trends , T-Lymphocytes, Regulatory/immunology , Time Factors , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology
14.
Zentralbl Chir ; 141(1): 105-20, 2016 Feb.
Article in German | MEDLINE | ID: mdl-26902582

ABSTRACT

Pulmonary typical (TC) and atypical carcinoids (AC) are lung tumors with neuroendocrine differentiation. Pulmonary carcinoids account for < 2 % of all lung cancers and the incidence is around 0,5/100 000. Depending on localization and extension they present incidentally or symptomatically with cough, hemoptysis and postobstructive pneumonia. Less than 1 % are associated with endocrine activity. TC and AC are differentiated by defined histopathologic criteria (mitotic rate, necrosis). Patients with TC have excellent long-term survival after non-anatomical lung resection. AC are associated with higher recurrence rates and anatomical lung resection should be preferred. Radical mediastinal lymph node dissection should be performed for both TC and AC. Complete surgical resection is the most significant prognostic factor for localized carcinoids. Surgical metastasectomy should also be considered in case of resectable metastatic disease.


Subject(s)
Carcinoid Tumor/surgery , Lung Neoplasms/surgery , Biopsy , Bronchoscopy , Carcinoid Tumor/diagnosis , Carcinoid Tumor/mortality , Carcinoid Tumor/pathology , Diagnosis, Differential , Humans , Lung/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lymph Node Excision , Neoplasm Staging , Pneumonectomy , Prognosis , Survival Rate , Tomography, X-Ray Computed
15.
Internist (Berl) ; 57(10): 971-977, 2016 Oct.
Article in German | MEDLINE | ID: mdl-27631528

ABSTRACT

BACKGROUND: Cachexia is a multifactorial and complex syndrome characterized by progressive functional impairment and ongoing loss in quality of life, which lead to a deterioration of the prognosis for affected patients. The prevalence of cachexia can be very high and is up to 80 % in patients with malignant tumors. OBJECTIVE: The aim of the study was to assess the relevance of exercise and nutrition in the prevention and therapy of cachexia. METHODS: An evaluation of the current literature on exercise and nutritional therapy in patients with cachexia or with advanced stage diseases where a high prevalence of cachexia is probable, was carried out. RESULTS: There is a lack of scientific evidence for the benefits of exercise in cachexia. A major problem of relevant studies was that cachexia was frequently not defined according to valid criteria; however, data indicate a benefit of exercise training in patients with advanced diseases associated with a high prevalence of cachexia. A solely nutritional intervention and dietary counselling seem to be of minimal benefit. The administration of omega 3 fatty acids is controversially discussed. CONCLUSION: Although there is a lack of data on the effects of exercise and nutritional therapy in cachexia, there is evidence for the benefits. The present data indicate the necessity for the use of a multimodal treatment including exercise, nutritional and pharmacological therapy in cachexia. There is a great necessity for prospective studies.


Subject(s)
Cachexia/diet therapy , Cachexia/prevention & control , Electric Stimulation Therapy/methods , Exercise Therapy/methods , Nutrition Therapy/methods , Palliative Care/methods , Chronic Disease , Combined Modality Therapy/methods , Evidence-Based Medicine , Germany , Humans , Treatment Outcome
16.
Ann Oncol ; 26(11): 2221-47, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26216388

ABSTRACT

BACKGROUND: In the past years, there has been significant progress in anticancer drug development for patients with metastatic castration-resistant prostate cancer (CRPC). However, the current instruments to assess clinical treatment response have limitations and may not sufficiently reflect patient benefit. Our objective was to systematically identify tools to evaluate both patient benefit and clinical anticancer-treatment response as basis for an international consensus process and development of a specific pragmatic instrument for men with CRPC. METHODS: PubMed, Embase and CINAHL were searched to identify currently available tools to assess anticancer-treatment benefit, other than standard imaging procedures and prostate-specific antigen measurements, namely quality of life (QoL), detailed pain assessment, physical function and objective measures of other complex cancer-related syndromes in patients with CRPC. Additionally, all CRPC phase III trials published in the last 5 years were reviewed as well as studies using physical function tools in a general cancer population. The PRIMSA statement was followed for the systematic review process. RESULTS: The search generated 1096 hits, 185 full-text papers were screened and finally 73 publications were included. Additional 89 publications were included by hand-search. We identified a total of 98 tools used in CRPC trials and grouped these into three categories: 22 tools assessing QoL domains and subgroups, 47 tools for pain assessment and 29 tools for objective measures, mainly physical function and assessment of skeletal disease burden. CONCLUSION: A wide variety of assessment tools and also efforts to standardize and harmonize patient-reported outcomes and pain assessment were identified. However, the specific needs of the increasing CRPC population living longer with their incurable cancer are insufficiently captured and objective physical outcome measures are under-represented. In the age of new anticancer drug targets and principles, new methods to monitor patient relevant outcomes of antineoplastic therapy are of utmost importance.


Subject(s)
Antineoplastic Agents/therapeutic use , Diagnostic Imaging , Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant/diagnosis , Prostatic Neoplasms, Castration-Resistant/drug therapy , Animals , Clinical Trials as Topic/methods , Diagnostic Imaging/methods , Humans , Male , Prostate-Specific Antigen/blood , Prostatic Neoplasms, Castration-Resistant/blood , Treatment Outcome
17.
Pituitary ; 18(2): 279-82, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25129688

ABSTRACT

PURPOSE: To show a rare case of Cushing's disease and possible cause of failed transsphenoidal surgery. METHOD: We report on a 50-year-old woman suffering from ACTH-dependent Cushing's syndrome. Endocrinological work-up including low-dose/high-dose dexamethasone test (Liddle-test) and CRH test were clearly compatible with pituitary origin. Although an MRI showed no pituitary tumor, CRH-stimulated petrosal sinus sampling revealed a significant central-peripheral gradient in ACTH concentrations, rendering Cushing's disease very likely. The patient underwent transsphenoidal surgery with negative exploration of the pituitary gland. After intraoperative re-evaluation of the preoperative MRI, a "polyp" at the bottom of the sphenoid sinus was identified. The intraoperative microscopic aspect as well as instantaneous sections and cytology of a biopsy confirmed an adenoma, which was then removed. Histological analysis demonstrated an ACTH-producing pituitary adenoma adjacent to respiratory mucous membrane consisting of ciliated epithelium with submucous connective tissue. Postoperatively, ACTH concentrations were decreased and intermittent hydrocortisone substitution treatment was initiated. At the 3-month follow up, Cushing's stigmata were found to be alleviated and the hydrocortisone dosage could be reduced. CONCLUSION: Ectopic pituitary adenoma tissue causing Cushing's disease is extremely rare but a potential cause for surgical failure or re-evaluation.


Subject(s)
ACTH Syndrome, Ectopic/diagnosis , ACTH-Secreting Pituitary Adenoma/diagnosis , Adenoma/diagnosis , Choristoma/diagnosis , Paranasal Sinus Neoplasms/diagnosis , Pituitary ACTH Hypersecretion/diagnosis , Sphenoid Sinus , ACTH-Secreting Pituitary Adenoma/complications , ACTH-Secreting Pituitary Adenoma/surgery , Adenoma/complications , Adenoma/surgery , Biopsy , Choristoma/pathology , Choristoma/surgery , Female , Humans , Immunohistochemistry , Magnetic Resonance Imaging , Middle Aged , Paranasal Sinus Neoplasms/pathology , Paranasal Sinus Neoplasms/surgery , Petrosal Sinus Sampling , Pituitary ACTH Hypersecretion/etiology , Pituitary ACTH Hypersecretion/surgery , Predictive Value of Tests , Sphenoid Sinus/pathology , Sphenoid Sinus/surgery
18.
Pathologe ; 36(3): 254-60, 2015 May.
Article in German | MEDLINE | ID: mdl-25917773

ABSTRACT

All tumours with C cell differentiation are designated as medullary carcinomas (MTC). MTC occur sporadically (75-80%) or hereditary (20-25%), the latter being part of the multiple endocrine neoplasia type 2. Familial MTC, which is commonly preceded by "neoplastic" C cell hyperplasia, is caused by autosomal-dominant inherited germ line mutation of the RET-protooncogene; dependent on the codon affected by the mutation, patients show substantially different clinical courses. Due to its morphological heterogeneity, the immunohistochemical demonstration of calcitonin is mandatory for the diagnosis of MTC. For early diagnosis of MTC calcitonin screening has been introduced in Germany and Austria approx. 10 years ago in patients with thyroid nodules; however, an increased calcitonin serum level may also be caused by "non-MEN2-associated" C cell, which is not regarded as a precursor of sporadic MTC. Very rarely tumours may show a mixed C cell-follicular cell differentiation.


Subject(s)
Calcitonin/blood , Carcinoma, Medullary/pathology , Thyroid Neoplasms/pathology , Austria , Carcinoma, Medullary/genetics , Early Detection of Cancer , Early Diagnosis , Germ-Line Mutation/genetics , Germany , Humans , Immunohistochemistry , Multiple Endocrine Neoplasia Type 2a/genetics , Multiple Endocrine Neoplasia Type 2a/pathology , Proto-Oncogene Proteins c-ret/genetics , Thyroid Gland/pathology
19.
Zentralbl Chir ; 140 Suppl 1: S8-15, 2015 Oct.
Article in German | MEDLINE | ID: mdl-26351767

ABSTRACT

Acute infection of the mediastinum remains a condition with high morbidity and lethality rates. The manifestation and course of the illness vary widely depending on the cause of infection. Lack of knowledge or awareness of the illness and mostly unspecific clinical symptoms often delay diagnosis and thereby the start of adequate therapy. Computed tomography (CT) of the neck and thorax is the method of choice for diagnostics and control of therapeutic success. An early diagnosis with immediate surgical debridement and drainage of all infected tissue compartments, as well as strict sepsis therapy, are decisive for the prognosis.


Subject(s)
Mediastinitis/diagnosis , Mediastinitis/surgery , Thoracic Surgery, Video-Assisted , Acute Disease , Algorithms , Debridement , Diagnosis, Differential , Humans , Mediastinitis/etiology , Mediastinitis/mortality , Mediastinoscopy , Necrosis , Survival Rate , Thoracoscopy , Thoracotomy , Tomography, X-Ray Computed
20.
Phys Rev Lett ; 113(22): 227201, 2014 Nov 28.
Article in English | MEDLINE | ID: mdl-25494083

ABSTRACT

Silicon nitride (SiN) micro- and nanomechanical resonators have attracted a lot of attention in various research fields due to their exceptionally high quality factors (Qs). Despite their popularity, the origin of the limiting loss mechanisms in these structures has remained controversial. In this Letter we propose an analytical model combining acoustic radiation loss with intrinsic loss. The model accurately predicts the resulting mode-dependent Qs of low-stress silicon-rich and high-stress stoichiometric SiN membranes. The large acoustic mismatch of the low-stress membrane to the substrate seems to minimize radiation loss and Qs of higher modes (n∧m≥3) are limited by intrinsic losses. The study of these intrinsic losses in low-stress membranes reveals a linear dependence with the membrane thickness. This finding was confirmed by comparing the intrinsic dissipation of arbitrary (membranes, strings, and cantilevers) SiN resonators extracted from literature, suggesting surface loss as ubiquitous damping mechanism in thin SiN resonators with Q_{surf}=ßh and ß=6×10^{10}±4×10^{10} m^{-1}. Based on the intrinsic loss the maximal achievable Qs and Qf products for SiN membranes and strings are outlined.

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