[Infectious diseases - a specialty of internal medicine]. / Infektiologie ­ ein Schwerpunkt der Inneren Medizin.

Infectious diseases have recently gained wide public interest. Emerging infections and rising rates of antibiotic resistance are determining this trend. Both challenges will need to be addressed in international and local collaborations between different specialties in medicine and basic science. Infectious diseases as a clinical specialty in this scenario is directly responsible for the care of patients with infectious diseases. Its involvement in the care of patients with complicated infections has proved to be highly effective. Antibiotic stewardship programmes are effective measures in slowing the development of antibiotic resistance and have been widely implemented. But antibiotic stewardship specialists should not be confused with or taken as an alternative to infectious disease experts. Infectious diseases requires appropriate and specific training. It mainly uses the instrumentarium of internal medicine. With the current challenges in modern medicine, infectious diseases in Germany should thus be upgraded from a subspecialty to a clinical specialty, ideally within Internal Medicine.

[Response to and further development of the Choosing wisely initiative]. / Resonanz und Weiterentwicklung der Initiative Klug entscheiden.

The Choosing wisely initiative of the German Society of Internal Medicine ("Deutschen Gesellschaft für Innere Medizin," DGIM) and its 12 core focus area specialist societies were brought into being in 2014. The German initiative differs from the American campaign in that it not only considers overuse of diagnostic and therapeutic healthcare services, but also addresses procedures which are frequently not performed although they would bring benefits for patients. Furthermore, the recommendations were approved by an interdisciplinary consensus commission under consideration of all key internal medicine aspects. Since 2014, the initiative has received widespread attention. The 115 recommendations approved by the consensus commission have meanwhile been published in 20 articles. An array of measures were subsequently adopted to further promote the Choosing wisely recommendations ("Klug-entscheiden-Empfehlungen," KEE). These include the systematic incorporation of KEE symposia into DGIM annual congresses and the congresses of the core focus area specialist societies, as well as consideration of the KEE during establishment of future guidelines. Particular attention was paid to the importance of initiating and promoting a research project aimed at familiarizing medical students with the principles and content of the Choosing wisely initiative. The decision for or against specific diagnostic and therapeutic procedures represents an essential medical competence, which should therefore be trained prior to qualification.

[Flight and migration : A challenge for medicine in Germany]. / Flucht und Migration : Eine Herausforderung für die Medizin in Deutschland.

In 2015 about 1.1 million refugees came to Germany. As a consequence public health authorities as well as physicians in hospitals and surgeries were faced with considerable challenges and problems. Between January and March 2016 the German Society of Internal Medicine (DGIM) and the Professional Organisation of German Internists (BDI) initiated a survey among their members in order to ascertain which diseases and problems physicians were confronted with. A total of 28,063 members of the DGIM and BDI participated in the survey of which 3626 members answered all questions. This equals a response rate of 11.31 %. Of the respondents, 1865 (51.9 %) stated holding employment positions and 987 (27.4 %) were self-employed. The predominant number of physicians were under the impression that the composition of diseases needing treatment did not change within the time period under survey (55.7 % of employed and 73.7 % of self-employed physicians). Typical disease patterns of internal medicine were mentioned here. Most significant problems when treating migrants and refugees were linguistic communication, cultural affiliation, and psychological traumatic experiences. Little or nothing is known about the modalities of reimbursement for the respective health care areas, especially by physicians in employed positions (84.6 %). In agreement with the vote of the 119th Deutscher Ärztetag, DGIM and BDI recommend the introduction of a nationwide health insurance card for migrants and refugees.

[Choosing wisely together with the patient]. / Gemeinsam mit dem Patienten klug entscheiden.

Within the framework of the Choosing wisely initiative of the German Society for Internal Medicine, all scientific societies associated with internal medicine were requested to highlight the unnecessary or underused medical tests or procedures out of the 60 defined examples, which are of immediate relevance within the doctor-patient interaction. Each of the 12 scientific internal medicine societies compiled and substantiated 2 recommendations. This resulted in a spectrum of important recommendations covering the entire field of internal medicine. In difficult situations these recommendations should contribute to developing and supporting the dialogue with patients on an evidence-based level.

[Choosing wisely in internal medicine]. / Klug entscheiden in der Inneren Medizin.

"Choosing wisely - DGIM" is an initiative of the German Society of Internal Medicine (DGIM) to strengthen the quality of diagnostics and indications for therapy. Aspects of inappropriate patient care are identified based on scientific evidence in collaboration with12 internal medicine and associated societies. Identified aspects are reviewed and endorsed by an interdisciplinary consensus committee. Addressed are those diagnostic and therapeutic measures which are rarely used despite scientific evidence of their usefulness and those which are frequently used although clear evidence exists that the measures are not useful or even harmful. The resulting positive or negative recommendations are intended to support physicians in the assessment of indications. The relevance of the "Choosing wisely - DGIM" initiative is confirmed by a survey involving 4200 members of DGIM.

English language version of the S3-consensus guidelines on chronic pancreatitis: Definition, aetiology, diagnostic examinations, medical, endoscopic and surgical management of chronic pancreatitis.

Chronic pancreatitis is a disease of the pancreas in which recurrent inflammatory episodes result in replacement of pancreatic parenchyma by fibrous connective tissue. This fibrotic reorganization of the pancreas leads to a progressive exocrine and endocrine pancreatic insufficiency. In addition, characteristic complications arise, such as pseudocysts, pancreatic duct obstructions, duodenal obstruction, vascular complications, obstruction of the bile ducts, malnutrition and pain syndrome. Pain presents as the main symptom of patients with chronic pancreatitis. Chronic pancreatitis is a risk factor for pancreatic carcinoma. Chronic pancreatitis significantly reduces the quality of life and the life expectancy of affected patients. These guidelines were researched and compiled by 74 representatives from 11 learned societies and their intention is to serve evidence-based professional training as well as continuing education. On this basis they shall improve the medical care of affected patients in both the inpatient and outpatient sector. Chronic pancreatitis requires an adequate diagnostic workup and systematic management, given its severity, frequency, chronicity, and negative impact on the quality of life and life expectancy.

Cationic liposomal paclitaxel plus gemcitabine or gemcitabine alone in patients with advanced pancreatic cancer: a randomized controlled phase II trial.

BACKGROUND: Paclitaxel embedded in cationic liposomes (EndoTAG™-1; ET) is an innovative agent targeting tumor endothelial cells. This randomized controlled phase II trial evaluated the safety and efficacy of ET in combination with gemcitabine (GEM) in advanced pancreatic cancer (PDAC). PATIENTS AND METHODS: Chemotherapy-naive patients with locally advanced or metastatic disease were randomly assigned to receive weekly GEM 1000 mg/m(2) or GEM plus twice-weekly ET 11, 22 or 44 mg/m(2) for 7 weeks. After a safety run-in of 100 patients, a second cohort continued treatment. End points included overall survival (OS), progression-free survival (PFS), tumor response and safety. RESULTS: Two hundred and twelve patients were randomly allocated to the study and 200 were treated (80% metastatic, 20% locally advanced). Adverse events were manageable and reversible. Transient thrombocytopenia and infusion reactions with chills and pyrexia mostly grade 1 or 2 occurred in the ET groups. Disease control rate after the first treatment cycle was 43% with GEM and 60%, 65% and 52% in the GEM + ET cohorts. Median PFS reached 2.7 compared with 4.1, 4.6 and 4.4 months, respectively. Median OS was 6.8 compared with 8.1, 8.7 and 9.3 months, respectively. CONCLUSIONS: Treatment of advanced PDAC with GEM + ET was generally well tolerated. GEM + ET showed beneficial survival and efficacy. A randomized phase III trial should confirm this positive trend.

An internet portal for the development of clinical practice guidelines.

BACKGROUND: The complexity and quality requirements for the development of clinical practice guidelines steadily increase. Internet technologies support this process by optimizing the development process. OBJECTIVE: The aim of this internet based solution was to facilitate the development of clinical practice guidelines. METHODS: An internet portal was developed allowing for a shared workplace to support clinical practice guideline authoring. It is based on a Content Management System and combines different tools for document handling and editing, communication as well as process and team steering. RESULTS: Until now, the internet portal has been successfully implicated in the development of six evidence- and consensus-based clinical practice guidelines. Additional German and European clinical practice guidelines are currently generated with support of the internet portal. The available tools allow for a flexible design of the scheduled workflow, depending on the requirements of the respective group. An additional strength of the platform is the advantage to transfer all data from a previous version of a guideline into the next 'life-cycle'. CONCLUSION: The application of the portal results in a considerable reduction of costs and development time of the resulting clinical practice guidelines.

Increased proteasome subunit protein expression and proteasome activity in colon cancer relate to an enhanced activation of nuclear factor E2-related factor 2 (Nrf2).

An elevated proteasome activity contributes to tumorigenesis, particularly by providing cancer cells with antiapoptotic protection and efficient clearance from irregular proteins. Still, the underlying mechanisms are poorly known. In this study, we report that in colon cancer patients, higher proteasome activity was detected in tumoral tissue compared with surrounding normal tissue, and also that increased levels of proteasomal subunit proteins, such as S5a/PSMD4 and alpha-5/PSMA5, could be detected. Colon tumors showed higher nuclear levels of nuclear factor E2-related factor 2 (Nrf2), a transcription factor supposed to be involved in the control of proteasomal subunit protein expression. The induction or overexpression of Nrf2 led to stronger S5a and alpha-5 expression in the human colon cancer cell lines, Colo320 and Lovo, as well as in NCM460 colonocytes along with higher proteasome activity. The small interfering RNA (siRNA)-mediated Nrf2 knockdown decreased S5a and alpha-5 expression and reduced proteasome activity. Additionally, Nrf2-dependent S5a and alpha-5 expression conferred protection from tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, an effect preceded by an increased nuclear factor (NF)-kappaB activation and higher expression of antiapoptotic NF-kappaB target genes. These findings point to an important role of Nrf2 in the gain of proteasome activity, thereby contributing to colorectal carcinogenesis. Nrf2 may therefore serve as a potential target in anticancer therapy.

Fatal pneumocystis jirovecii pneumonia in a case of ectopic Cushing's syndrome due to neuroendocrine carcinoma of the kidney.

Immunosuppression with subsequent opportunistic infections is a well-recognized complication of severe hypercortisolism. We report a case of fatal pneumocystis jirovecii pneumonia (formerly pneumocystis carinii pneumonia) in a case of ectopic Cushing's syndrome caused by a neuroendocrine carcinoma of the kidney. The 36-year old male patient had consulted a physician because of weight gain. Further endocrine diagnostic work-up revealed ACTH-dependent hypercortisolism of non-pituitary origin. Because of rapid clinical deterioration therapy with metyrapone was initiated. A neuroendocrine carcinoma of the right kidney with regional lymph node infiltration was identified and was suspected to be the source of the ACTH excess. Before any causal therapy could be initiated, the patient developed severe pneumocystis jirovecii pneumonia and died shortly thereafter from multiorgan failure one month after he first consulted a physician. Pneumocystosis has been reported in only a few cases of Cushing's syndrome. There seems to be a relationship between the degree of hypercortisolism and the susceptibility to opportunistic infections. Since ACTH concentrations may be excessively high in ectopic Cushing's syndrome and pneumocystosis may deteriorate as a consequence of decreasing circulating cortisol levels under adrenolytic therapy, prophylaxis against pneumocystis jirovecii infection should be considered.