Current Concepts In Treatment Research Articles

Rotational bed therapy after blunt chest trauma: A nationwide online-survey on current concepts of care in Germany

IntroductionBlunt chest injuries are amongst the most life threatening injuries in adult multiple trauma patients. Nevertheless, the treatment of these thoracic injuries has not been standardized yet. Previous publications have reported on the prevention and the treatment of respiratory complications by using continuous lateral rotational bed therapy (CLRT), but there is still a lack of information using this approach in the presence of pulmonary contusions. Therefore current literature indicates a variety of treatment protocols and its use is contended. MethodsWe submitted a 32-item online-questionnaire to 155 hospitals participating in the nationwide TraumaNetwork to assess current treatment concepts in multiple trauma patients suffering from blunt chest trauma including lung contusions with particular focus on the use of CLRT. Overall, 21 level I, 53 level II and 81 level III trauma centres were contacted. The questionnaire was created using “interview 123 5.5.b.de ND6”. ResultsThe overall response rate was 35.5% (55/155) and responses were received from 10 level I (47.6%), 17 level II (32.1%) and 24 level III (29.6%) trauma centres. Thirty-five of the responders (63.6%) declared to be able to perform lateral rotational bed therapy. For level I and II trauma centres more than 80% were able to apply kinetic positioning in contrast to only 50% of level III trauma centres. Although 42.9% of the participants reported on the existence of standardized treatment protocols, 57.1% failed to report a standardized operating procedure for CLRT. The annual mean number of patients per centre treated via CLRT was 15 (0–130). Treatment modalities such as PEEP and the duration of CLRT also showed great variability. Against this background three out of four centres declared an urgent need for further clinical research in the field. ConclusionsOur data reflect the wide range of different CLRT treatment strategies performed for blunt pulmonary trauma involving lung contusions in German trauma centres. We conclude that a high-quality randomized-controlled trial is warranted to critically assess the role of CLRT in multiple trauma patients with blunt chest trauma to provide a sound basis for future clinical guidelines.

어린이의 구강 검사를 위한 International Caries Detection and Assessment System II의 적용

최근 치아우식증이 예방가능한 질환이라는 사실이 부각되면서 치료에 대한 개념이 다소 변화하게 되었다. 즉, 단순한 수복 치료가 아닌 '예방적 우식 조절(preventive caries control)'을 통한 관리가 필요하다는 것이다. 이러한 치아우식증에 대한 철학의 변화는 구강 검사의 방법이나 기준의 변화를 수반하였는데, 이미 형성된 우식 와동을 관찰하는데 그치는 것이 아니라, 와동형성이 이루어지기 전의 초기 단계에 해당하는 우식 병소를 정확하게 탐지하는 것이 필요하게 된 것이다. 최근 개발된 International Caries Detection and Assessment System II (ICDAS II)은 시진을 기반으로 한 치아우식증의 분류 기준이다. 이 분류 기준은 치아우식증의 예방 및 조기 진단과 환자 중심의 우식 관리를 지향하는 최근 경향을 바탕으로 하고 있는데, 이는 어린이의 양호한 구강 건강을 조기에 확립하여 이를 평생 유지할 수 있도록 돕는 것을 목표로 하는 소아치과학의 관점과 잘 부합한다고 볼 수 있다. 이에 저자는 어린이의 구강 검사에 ICDAS II를 적용하기 위한 기초를 제공하기 위해 이 분류 기준을 소개하고자 한다. Current treatment concept of dental caries has been changed, because it has been proved that it is a preventable disease. The philosophy has been changed from purely restorative treatment to preventive caries control. Therefore the methods or criteria of oral examination has been changed. The clinician have to detect not only cavitation, but also the lesion of non-cavitation stage. International Caries Detection and Assessment System II (ICDAS II) was developed recently, which is a new criteria of classification of dental caries. This system was based on the current concept of prevention, early detection and patient-centered management of caries. Therefore this philosophy is in accord with the perspective of pediatric dentistry. The purpose of this article is to introduce this system for oral examination of children.

Aktuelle Konzepte in der Therapie der dorsalen Endgliedbasisfraktur

Articular fractures of the dorsal part of the distal phalanx may result in a painful dysfunction and a bothersome deformity of the distal interphalangeal joint. For this injury multiple treatment procedures exist. We performed a survey among German hand surgeons and a review of the literature in order to present current concepts of treatment and to verify the feasibility of a randomized trial. There is a tendency to prefer conservative treatment options. The indication for operative treatment depends on size and displacement of the articular fragment as well as on subluxation of the joint. Operative techniques vary widely and the comparability of their results is restricted. Complications more often occur after operative treatment. The type of injury and the individual demands of the patient are the most relevant factors for the choice of treatment. From the results of the survey and the review of the literature, a randomized trial of conservative and operative treatment has to be considered as a challenge.

A GC/MS-based metabolomic approach for diagnosing citrin deficiency

Citrin is the hepatic mitochondrial aspartate-glutamate carrier that is encoded by the gene SLC25A13. Citrin deficiency often leads to hyperammonemia, for which the current treatment concept is different from that for primary hyperammonemias. Metabolite level diagnosis, often referred to as chemical diagnosis, is not always successful in identifying citrin deficiency immediately or in a timely fashion. We previously made the chemical diagnosis of citrin deficiency in ten patients from nine families. In order to devise a more rapid and more accurate chemical diagnosis of this disorder than is currently available, we reinvestigated the gas chromatography/mass spectrometry-based urine metabolome in these patients. In patients aged 2 to 5 months, prominent biomarkers detected included one or more of the following metabolites: tyrosine, p-hydroxyphenyllactate, p-hydroxyphenylpyruvate, and N-acetyltyrosine, galactose, galactitol and galactonate, glucose, glucitol, and cystathionine. These biomarkers are less prominent in older patients, but are not increased in argininosuccinate synthetase deficiency or other hyperammonemias. α-Ketoglutaramate (KGM), a recently recognized urinary biomarker of primary hyperammonemias associated with defects of the urea cycle, was increased in most patients with citrin deficiency studied here in spite of normal urinary levels of glutamine (the immediate precursor of KGM), 5-oxoproline, glutamate, aspartate, and asparagine. Other important urinary biomarkers that should be measured for differential diagnosis of hyperammonemias, including orotate, uracil, and β-ureidopropionate, were not increased. The presence of citrulline and citrulline-derived metabolites was noted in all cases. The present study shows that noninvasive urine metabolomics, together with an analysis of selected metabolites or groups of metabolites, provides a more reliable and rapid chemical diagnosis of citrin deficiency than was previously available and more readily differentiates this disorder from other hyperammonemic syndromes.

Periprothetische Infektion

Periprosthetic infections represent the most feared complications in orthopedic surgery. Frequently, the substantial challenges result more from a delayed diagnosis and an inadequate therapy than from the infection itself. The guiding symptom is pain. The determination of C-reactive protein (CRP) and the blood sedimentation rate (BSR) is the basic screening test for infection while joint aspiration is commonly used to confirm the diagnosis. Infection treatment with implant preservation is only promising and justifiable in the early postoperative infection period. The current concept of infection treatment consists of a two-stage revision with 6-8 weeks implant-free interval and an accompanying antibiotic therapy. The one-stage revision is the patient-friendliest procedure but requires strict prerequisites which may not be given in a number of cases. The reported mean success rates range from 80-100% with the respective therapeutic procedures. However, there is no single evidenced-based therapeutic concept throughout the whole course of treatment but frequently a various number of individual modifications. Nevertheless, a clear strategy in treatment planning using objective criteria without subjective decisions and emotions is essential for the success of therapy. If the healing rate falls under 80% the applied concept must be reconsidered.

Beatmungsassoziierte Pneumonie bei Kindern

According to current data obtained in the German KISS study ventilator-associated pneumonia (VAP) represents a rare but potentially life-threatening complication of mechanical ventilation in pediatric intensive care patients (PICU). Patients with pre-existing severe illness or congenital syndromes or malformations face an increased risk. The present article discusses current concepts in diagnosis, prevention and treatment of VAP in PICU patients and points to bundle approaches to reduce the incidence of VAP.

Characterization of the response to primary blast injury

Lung injuries, predominantly arising from blast exposure, are a clinical problem in a significant minority of current military casualties. This special feature consists of a series of articles on lung injury. This first article examines the mechanism of the response to blast lung (primary blast injury to the lung). Subsequent articles examine the incidence of blast lung, clinical consequences and current concepts of treatment, computer (in silico) modelling of lung injury and finally chemical injuries to the lungs. Blast lung is caused by a shock wave generated by an explosion causing widespread damage in the lungs, leading to intrapulmonary haemorrhage. This, and the ensuing inflammatory response in the lung, leads to a compromise in pulmonary gas exchange and hypoxia that can worsen over several hours. There is also a characteristic cardio-respiratory effect mediated via an autonomic reflex causing apnoea (or rapid shallow breathing), bradycardia and hypotension (the latter possibly also due to the release of nitric oxide). An understanding of this response, and the way it modifies other reflexes, can help the development of new treatment strategies for this condition and for the way it influences the patient's response to concomitant injuries.

Proximal humeral fractures: current concepts in classification, treatment and outcomes

Proximal humeral fractures: current concepts in classification, treatment and outcomes

Current Treatment Concepts of CML

The elucidation of the triggering molecular mechanism of chronic myeloid leukemia gave rise to the development of imatinib, a tyrosine kinase inhibitor and a prototype of target-oriented drugs. Imatinib led to impressing response and survival rates and now represents the standard therapy of CML. However, a significant proportion of patients do not tolerate or fail to respond to imatinib treatment. Alternative therapies can be offered to those patients. The particular challenge of CML patient management is to recognize an impending imatinib failure by adequate surveillance and to know about therapeutic options to prevent progression of the disease to accelerated phase or blast crisis since these are more difficult to control. Targeted therapy with second-generation tyrosine kinase inhibitors should be used in synopsis with mutational analysis and the patients' history. In this review we present current knowledge of diagnosis, monitoring and therapy strategies of patients with CML.

Das Prostatakarzinom: eine Krankheit im Wandel

Prostate cancer remains by far the most common malignant disease in male patients. Despite this fact, research in prostate cancer was limited for many years. Radical prostatectomy or external beam radiation for local treatment and androgen deprivation for advanced and metastatic treatment were perceived to be the only options. Over recent years however, knowledge about the disease has rapidly risen in many fields including epidemiology, prophylaxis, screening and treatment of localised and advanced disease. At the same time, obviously many new questions have arisen. The treatment of prostate cancer is currently undergoing great changes. This article summarises current treatment concepts and treatment possibilities for the near future.

Current Treatment Concepts of Philadelphia-Negative MPN

Since William Dameshek has described the concept of "myeloproliferative disorders (MPD)" by identifying common clinical characteristics (i.e. hemorrhage, thrombosis and leukemic transformation) of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), the advent of molecular biology has provided substantial molecular insight into the pathobiology of myeloproliferative neoplasia (MPN). Recently, the description of the gain-of-function mutation of JAK2 (JAK2V617F) has been identified in classical Philadelphia (Ph)-negative MPN, thus providing a rational target for novel innovative treatment strategies. In addition, molecular characterization of atypical Ph-negative MPN (e.g. the KITD816V mutation in mastocytosis and PDGF-receptor rearrangements in hypereosinophilic syndromes/chronic eosinophilic leukemia) complement the molecular knowledge of this heterogeneous disease family. Currently, clinical studies testing various JAK2-inhibitors in PV, ET as well as in primary and secondary myelofibrosis (MF) are under way. Interestingly, first data indicate that despite marked clinical activity in terms of spleen size reduction and improvement of constitutional symptoms, these inhibitors might not sufficiently reduce disease burden. Thus, alternative and well established treatment strategies, such as inhibition of thrombocyte aggregation by low dose aspirin, cytotoxics (e.g. hydroxyurea), immuno- and stroma-modifying therapy with interferon, tyrosine kinase inhibitors and, in selected cases, allogeneic stem cell transplantation are still important treatment options for patients suffering from MPN, which will be discussed in detail in this review.

Breast Cancer and Pregnancy: Current Concepts in Diagnosis and Treatment

The treatment of breast cancer diagnosed during pregnancy presents a challenging situation for the patient, family, and caregivers. Case series have demonstrated the efficacy and safety of using anthracycline-based chemotherapy during the second and third trimesters. Additionally, patients should be seen, evaluated, and treated in a multidisciplinary setting with facilitated communication among the medical oncologist, surgical oncologist, obstetrician, radiation oncologist, pathologist, and radiologist. This review details the available data regarding the diagnosis and management of the pregnant breast cancer patient.

Anaesthetic considerations during hepatic trauma surgery

The acute care of trauma patients poses unique challenges for both the anaesthesiologist and the surgeon. Current treatment concepts focus on the prevention of tissue ischaemia, rapid control of haemorrhage, haemostasis and maintenance of tissue perfusion. Successful resuscitation must also address the lethal triad: metabolic acidosis, coagulopathy and hypothermia, which characterize acute, fatal haemorrhagic shock, followed by circulatory system failure. The key elements include appropriate monitoring and mechanical and pharmacological protection of the vital organs to support the patient and restore perfusion. The goals for early resuscitation (prior to definitive control of haemorrhage) are: control of the airway and ventilation, expeditious control of haemorrhage maintaining a systolic blood pressure above 80 mmHg, limited use of crystalloid fluid and maintenance of haematocrit 25%–30%. The early use of plasma achieves normal clotting studies, and the possible use of cryoprecipitate and/or factor VIIa, if the patient is already coagulopathic, platelet count > 50000, stabilized core temperature of > 35°C and gradual conversion to deep general anaesthesia-analgesia are necessary. After the definitive control of haemorrhage, complete resuscitation is achieved by titrated administration of fluids until the following parameters are met: normal or hyperdynamic vital signs, haematocrit > 20%, normal serum electrolytes, normal coagulation function, Platelet count > 50000, restoration of adequate microvascular perfusion:-pH=7.40 with normal base deficit, normalized serum lactate, normal mixed venous oxygenation, normal or high cardiac output and normal urine output. The early management of patients who have major trauma and the prompt collaboration between the surgeon, the anaesthesiologist, the radiologist, the haematologist and the ICU can contribute to a positive outcome.

Intestinal ischemia: current treatment concepts

Mesenteric ischemia is a condition well-known among physicians treating patients with abdominal symptoms. Even so, mortality rates have not decreased significantly over the last decades. The purpose of this article is to review current treatment concepts of acute and chronic mesenteric ischemia. Early diagnosis is one of the most important features that determine a patient's prognosis. Conventional angiography and multidetector computed tomography are therefore appropriate to quickly diagnose mesenteric ischemia, the latter being commonly more available. Once a patient presents with signs of peritonitis, instant laparotomy is indicated, and infarcted bowel segments need to be resected, followed by a second-look operation if necessary. If bowel necrosis is clinically not suspected, different approaches should be applied according to source and nature of mesenteric ischemia. Besides established surgical treatment concepts, more and more interventional procedures are developed and evaluated. However, superiority of these new techniques could only be shown for selected patient groups so far. In chronic mesenteric ischemia, interventional approaches seem to be an attractive alternative in patients who are in a condition too bad to undergo surgery. Patients with colonic ischemia are treated best in a conservative manner and by resolving the underlying cause, if identified. Patients with acute mesenteric ischemia are still at highest risk for a fatal course of disease. New diagnostic and therapeutic developments have not been tested in larger studies yet, neither has any of these methods led to an increased survival in studies published so far. Taken together, mesenteric ischemia requires high awareness, earliest possible diagnosis, and treatment by an experienced interdisciplinary team of gastroenterologists, radiologists, and surgeons.

Wnt/β-Catenin/LEF-1 Signaling in Chronic Lymphocytic Leukemia (CLL): A Target for Current and Potential Therapeutic Options

There is a growing body of evidence that Wnt signaling, which is already known to play a critical role in various types of cancer, also has a vital function in B cell neoplasias, particularly in chronic lymphocytic leukemia (CLL). It is known that Wnt proteins are overexpressed in primary CLL cells and several physiological inhibitors are partly inactivated in this disease. Furthermore, β-catenin is upregulated upon Wnt stimulation and cooperates with the transcription factor lymphoid enhancer binding factor-1 (LEF-1). LEF-1 is excessively overexpressed in CLL cells by more than 3,000-fold compared to normal B cells. Moreover, LEF-1 could be identified as an important regulator of pathophysiologically relevant genes in CLL, and several Wnt/β-catenin signaling components substantially influence CLL cell survival. In this review we summarize the current state of knowledge about Wnt/β-catenin/LEF-1 signaling in CLL. Following a short overview of current treatment concepts in CLL, we briefly describe Wnt signaling in human cancers. We then discuss recent progress in understanding regulation of the Wnt/β-catenin/LEF-1 signaling pathway in this disease. Based on the present scientific evidence we highlight which components of this important signaling pathway could serve as therapeutic targets in CLL. We then present previous results gained from experimental approaches to target different parts of the Wnt/β-catenin/LEF-1 cascade. Together with potentially promising approaches we also critically reflect on the kind of difficulties and problems that may arise using such strategies.

Current treatment concepts of Pancoast tumors

BACKGROUND: Non-small-cell lung cancers involving the superior sulcus, also termed Pancoast tumors, are a challenging subset of lung carcinomas due to their proximity to vital structures at the thoracic inlet. METHODS: This review focuses on clinical outcome data of different treatment regimens and surgical approaches to Pancoast tumors. RESULTS: Therapeutical standards have constantly evolved over time leading to significantly improved long-term survival rates. CONCLUSIONS: A multimodal regimen approach consisting of induction chemoradiation followed by surgical resection has become the standard treatment concept in localized disease.

Recent advances in liver stem cell therapy

Patients with liver cirrhosis often require liver transplantation, which remains the only effective treatment of the end-stage cirrhosis. Here we briefly summarize the current concepts in treatment of liver diseases based on the transplantation of intrahepatic liver cells, capable of repopulating the injured liver. These cells include hepatocytes, oval cells (bipotential intrahepatic progenitor cells), bone marrow hematopoietic and mesenchymal stem cells, and induced pluripotent stem (iPS) cells. Although liver transplantation remains the only conventional treatment, liver cell transplantation is an experimental procedure which has been successfully used in clinical trials in patients with acute liver failure, chronic liver disease with end-stage cirrhosis. Extraordinary progress has been made in the field of hepatic progenitors and iPS. Liver precursor cells (oval cells) are recognized as bipotential precursor cells in the damaged liver. They can rapidly proliferate, change their cellular composition, and differentiate into hepatocytes and cholangiocytes to compensate for the cellular loss and maintain liver homeostasis in animal models of liver injury. Similarly, iPS are somatic cells obtained from patients and differentiated into hepatocytes in vitro. Future studies of iPS are designed to develop of specific conditions to expand and in vitro differentiate somatic cells into functionally mature liver cells. The current review defines and discusses different populations of hepatic cells which can be potentially used for liver cell transplantation to advance the therapy of hepatic cirrhosis.

Ist die primäre Chirurgie bei fortgeschrittenen Kopf-Hals-Karzinomen noch aktuell?

Organ preservation protocols for advanced head and neck carcinoma have proven to be successful in controlled clinical trials. This has led to an increase in the use of primary chemoradiation for these tumors. However, the intensification of nonoperative treatment protocols has been associated with a dramatic increase in acute treatment-related toxicity and mortality. In this paper, the role of primary surgical care is reviewed. Recent publications in the field and current treatment concepts are discussed.

Novel and Current Treatment Concepts Using Pulmonary Drug Delivery

The novel technologies in pulmonary drug delivery propelled the development of new strategies for pharmacological intervention in human diseases. In particular, this review will focus on pulmonary parameters which influence the delivery of inhaled therapeutics and summarize novel applications and recent innovations. The central issues of pulmonary drug application are optimal effectiveness under conditions of greatest safety. They not only depend on the properties of the drug but also feature the application vehicle and drug formulation. The optimization of the whole system (drug, formulation and vehicle) is therefore a necessary prerequisite for reliable inhaling medicines. Depending on the desired locus of drug action, the inhaled medicine has to be adjusted to particle size, concentration and chemical composition to guarantee a local or systemic drug action. Local asthma therapy represents the established concept for inhalation therapy. Due to the disease status, deposition of drugs is therefore often seen in central rather than peripheral airways. Recent developments in ultrafine therapeutic particles should therefore provide enough drug deposition even in the deeper airways. Recent approvals and interesting new therapy concepts will be discussed. Beside a pulmonary drug action there is an accumulating number of applications also for systemic drug action after pulmonary drug delivery. These involve among others inhaled insulin, glucagon-like-peptide 1 or growth hormone. But also novel therapeutic systems for gene therapy and vaccination are currently under investigation. Successful feasibility of these novel concepts will be expected in the near future.

Pathogenesis, diagnosis and treatment of neuromyelitis optica: Changing concept of an old disease

The concept of neuromyelitis optica (NMO) has changed considerably during the past few years. The identification of autoantibodies in the sera generated against the water channel aquaporin 4 (AQP4) has increased the specificity of diagnosis and modified guidelines. A pathogenic role of anti-AQP4 antibodies has recently been indicated; they evoke the pathological and clinical hallmarks of the disease on transfer and cause necrosis of astrocytes expressing AQP4. The diagnosis of NMO is based on clinical, neuroimaging and serological criteria. Early therapy preventing relapses is mandatory, because neurological impairment accumulated during relapses is the main cause of permanent disability. In a number of cases defined as NMO spectrum diseases, the clinical manifestation is spatially limited. Such events of separate myelitis or relapsing/bilateral optic neuritis challenge diagnosis and might delay proper therapy. Here, current concepts of diagnosis and treatment of NMO and NMO spectrum diseases are summarized. Diagnostic and treatment decisions in different clinical situations are shown by discussion of cases. (Clin. Exp. Neuroimmunol. doi: 10.1111/j.1759-1961.2010.00011.x, 2010)