[ECMO treatment in acute lung failure : Who profits?] / ECMO-Therapie beim akuten Lungenversagen : Wer profitiert?

In intensive care medicine, rapid technical developments that are often beneficial to patients are taking place. On the other hand, there are also voices that generally criticize an increasing "interventionalism". This area of tension includes other important questions regarding usefulness, quality, ethical compliance, scientific evidence, structural capacities and economy. The treatment of acute respiratory distress syndrome (ARDS) using extracorporeal membrane oxygenation (ECMO) is an example of these considerations. Although ECMO has rarely been prospectively evaluated according to scientific criteria, it is still used with an increasing tendency, not least since the documented register survival rates in ECMO patients with severe ARDS are 60%. However, the implementation of this therapy means an immense effort. The necessary centralization and certification for ECMO treatment is currently under intensive discussion. Closely related to this are considerations about which criteria represent good quality in patient care. In order to be able to guarantee high quality, a precise indication is the first step. And here indications and contraindications still need to be defined. It has not yet been sufficiently clarified which prognosis factors need to be taken into account. This article summarizes what is known about ECMO prognosis and indication criteria. In conclusion, parameters are identified that should be developed scientifically in the future.

Perceived Impact of Motherhood on Adherence to Therapy in Mothers with Cystic Fibrosis.

AIM: To explore the stress related to motherhood and its perceived impact on adherence to therapy in women with cystic fibrosis (CF). METHODS: Cross-sectional study with a purpose-designed questionnaire. SAMPLE: 46/73 eligible women were enrolled and 38 returned the questionnaire. Mean age of mothers was 33.8 y  ±â€Š7.1 y, mean age of firstborn child was 6.9 y  ±â€Š5.7 y. Nine women had more than one biological child. 18 mothers (47%) were currently employed, 12 of whom worked 19 to 30 hours per week and none full-time. RESULTS: There were mothers who reported a detrimental effect on adherence (time constraints 38%; intentional nonadherence 42%), and mothers who reported that adherence had actually improved (29%). Both of these effects were related to daily CF therapy at home. By contrast, i. v. antibiotic therapy was less impaired by role strains, mainly due to home i. v. therapy being an alternative and/or due to intensive social support (husband, parents). Participants clearly addressed the importance of adherence and the need for adequate self-management in narrative comments. CONCLUSION: Motherhood may improve adherence to CF therapy as well as it may affect it negatively. Health caregivers are well-advised to address a possible detrimental effect, proactively.

[Mothers with cystic fibrosis: psychosocial data about an almost unknown group]. / Mütter mit Mukoviszidose: Ergebnisse einer Befragung einer nahezu unbekannten Patientengruppe.

AIMS: To explore pregnancy and motherhood in cystic fibrosis patients from the women's perspective. METHODS: Data were assessed with a purpose designed questionnaire and the paper focuses on the following sections: "pregnancy and birth" (feedback of significant others, women's knowledge, concerns, and overall judgement), and the "first year as a mother" (overall judgement). SAMPLE: 38/73 mothers filled in the questionnaire; mean age was 33.8 y ±â€Š7.1 y and mean age of firstborn child was 6.9 y ±â€Š5.7 years. Nine women had more than one biological child. 18 mothers (47 %) were currently employed, 12 of whom with 19 to 30 hours per week and none full-time. Mean FEV1 in perc. Pred. was 66 ±â€Š19 %. RESULTS: Pregnancy in CF should be planned and prepared, and this was achieved in 28 women, while 10 pregnancies were unplanned. The feedback of significant others towards wish for child/pregnancy was more positive in those who planned. Mothers' own parents reacted least enthusiastic, irrespective of whether or not pregnancy had been planned. The feedback of CF-teams differed according to women's lung function. The women's knowledge about "pregnancy and CF" was rather poor. Their concerns predominantly referred to detrimental effects of CF medication to the unborn child. CONCLUSIONS: Motherhood is increasingly becoming an option for young women with CF. Therefore, CF-teams are well-advised to proactively engage them in a dialogue about wish for child and impact of CF on motherhood. Knowledge about pregnancy/motherhood and CF should be increased.

The wingless-related integration site-5a/secreted frizzled-related protein-5 system is dysregulated in human sepsis.

Sepsis and type 2 diabetes exhibit insulin resistance as a common phenotype. In type 2 diabetes we and others have recently provided evidence that alterations of the proinflammatory wingless-related integration site (wnt)-5a/anti-inflammatory secreted frizzled-related protein (sFRP)-5 system are involved in the pathogenesis of insulin resistance. The aim of the present study was to investigate whether this novel cytokine system is dysregulated in human sepsis, which may indicate a potential mechanism linking inflammation to metabolism. In this single-centre prospective observational study, critically ill adult septic patients were examined and proinflammatory wnt5a and wnt5a inhibitor sFRP5 were measured in serum samples by enzyme-linked immunosorbent assay (ELISA) at admission to the intensive care unit (ICU) and 5 days later. Sixty sepsis patients were included, and 30 healthy individuals served as controls. Wnt5a levels were found to be increased significantly in septic patients compared to healthy controls (2·21 ± 0·33 versus 0·32 ± 0·03 ng/ml, P < 0·0001). In contrast, sFRP5 was not altered significantly in septic patients (19·72 ± 3·06 versus 17·48 ± 6·38 ng/ml, P = 0·07). On admission to the ICU, wnt5a levels exhibited a significant positive correlation with the leucocyte count (rs = 0·3797, P = 0·004). Interestingly, in patients recovering from sepsis, wnt5a levels declined significantly within 5 days (2·17 ± 0·38-1·03 ± 0·28 ng/ml, P < 0·01). In contrast, if sepsis was worsening, wnt5a levels increased in the same time-period by trend (2·34 ± 0·59-3·25 ± 1·02 ng/ml, P > 0·05). sFRP5 levels did not change significantly throughout the study period. The wnt5a/sFRP5 system is altered in human sepsis and might therefore be of interest for future studies on molecular pathophysiology of this common human disease.

[Eosinophilia - inflammation, proliferation, reaction. Part 1: diagnostics]. / Die Eosinophilie - Inflammation, Proliferation, Reaktion.

Eosinophilia presents a challenge to differential diagnostics due to the multitude of possible causes. An initial difficulty is often to distinguish between threatening disease symptoms and relatively harmless secondary reactions. A highly dynamic clinical progression with severe impairment of the vital functions, like breathing, for example, can make swift action necessary. An example of this is known as acute eosinophile pneumonia, which can often only be controlled with the rapid use of high steroid doses. However, a peripheral blood eosinophilia must not lead to an automatic use of steroids before the most important core tests, as this can compromise further diagnostic measures. Furthermore, less dramatic courses require careful handling of an eosinophilia. Various pneumological, infectological, rheumatological or haematological / oncological disease patterns with a prolonged course can develop seriously if they are not recognised in time and treated in a targeted manner. There is no guideline for eosinophile clinical pictures in general. Already the recommendations for a structured diagnosis are scarce and are often concentrated on internist emphases.

Synergism of imatinib mesylate and everolimus in attenuation of bronchiolitis obliterans after rat LTX.

Bronchiolitis obliterans (BO) is a progressive and fatal disease after lung transplantation (LTX). Dysregulated growth factor-induced proliferation of myofibroblasts seems to be responsible for the development of BO. The aim was to confirm the efficacy of both inhibitors of receptor tyrosine kinases (RTKI) and of mammalian target of rapamycin (mTORI) after rat LTX. We used a rat model of left lung allo-transplantation (F344-to-WKY) to evaluate the effect of imatinib (RTKI; 20 mg/kg/day; postoperative day (POD) 0-100) alone or in combination with everolimus (mTORI; 2.5 mg/kg/day; POD 14-100). Non-treated animals were the reference. In non-treated rats, acute rejection (AR) peaked between POD 20 and 30 (19/19) and ended in chronic rejection (CR) on POD 60/100 (12/12). Imatinib alone did not prevent AR (6/6), but attenuated the degree of degenerated bronchioles on POD 30 (non-treated, 57%; imatinib, 4%), and increased the allografts free of CR on POD 60/100 (3/12). A combination of imatinib and everolimus significantly reduced AR, attenuated fibrotic degenerated bronchioles (5%) and vessels (non-treated, 24%; combination therapy, 11%) on POD 30, and reduced fibrotic degenerated vessels (non-treated, 97%; combination therapy, 43%) and bronchioles (non-treated, 88%; combination therapy, 34%) on POD 60/100. Fifty percent of the animals were completely free of BO and vasculopathy. In conclusion, co-application of RTKI and mTORI attenuated the development of BO and vasculopathy. Thus, imatinib might be an interesting therapeutic approach after LTX.

[Pulmonary emergencies in connective tissues disorders and vasculitides]. / Pneumologische Notfälle bei Kollagenosen und Vaskulitiden.

Pulmonary emergencies in rheumatic diseases are rare, potentially life-threatening conditions that occur either as a manifestation of the disease itself or as an adverse event of immunosuppressive treatment. Diffuse alveolar hemorrhage, tracheal stenosis, acute pneumonitis and drug-induced lung injury belong to this category. The management of these emergencies requires intensive cooperation between rheumatology and pulmonology. The latter contributes its experience in the care of related conditions, specific endoscopic techniques and local interventions as well as the indispensable and life-supporting forms of assisted ventilation. The present article summarizes the current knowledge on diagnostic and therapeutic procedures including the newly available B-cell directed treatments.

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.

Systematic expression profiling of innate immune genes defines a complex pattern of immunosenescence in peripheral and intestinal leukocytes.

Immunosenescence is characterized by a quantitative decline of adequate immune responses, which renders the elderly individual particularly susceptible to bacterial, viral and fungal pathogens. Whereas changes of the aging adaptive immune system (for example, reduced immunoglobulin secretion) have been extensively characterized, alterations of the innate immune system are still poorly understood. The aim of the present study was to systematically examine mRNA expression levels of innate immune genes and proinflammatory cytokines in peripheral and intestinal leukocytes of subjects of different ages. In both, whole blood samples and in colonic biopsies most of the Toll-like receptors (TLRs) and nucleotide-binding and oligomerization domain-like receptors (NLRs) transcript levels were significantly downregulated in elderly subjects (90-99 years). Older individuals, when compared to the younger, exhibited an increased expression and/or secretion of proinflammatory cytokines by peripheral and intestinal leukocytes as well as an increased level of nuclear factor-kappaB activation in colonic biopsies. The observed downregulation of TLRs and NLRs during the aging process may contribute to the lack of effective recognition of invading pathogens or the commensal flora. This effect results in aberrant secondary immune cell activation and could significantly contribute to morbidity and mortality at advanced age.

Symptoms and signs of an acute myocardial ischemia caused by chemotherapy with Paclitaxel (Taxol) in a patient with metastatic ovarian carcinoma.

INTRODUCTION: Paclitaxel (Taxol) is an anticancer agent used for the treatment of breast and ovarian cancer. The major side effects are bone marrow suppression, alopecia, polyneuropathy and cardiac toxicity like bradycardia, myocardial infarction, congestive heart failure and cardiac death. SETTING: Intensive care unit (ICU) of a university hospital. PATIENT: We report on a 58-years-old woman with a metastatic ovarian carcinoma who had chest pain, nausea and collapse during their first Taxol infusion. The infusion was stopped and the patient was submitted to the intensive care unit (ICU) to exclude an acute coronary syndrome. RESULTS: The electrocardiography (ECG) showed a third-degree heart block and ST elevation in II, III and avF. In the initial and in the control laboratory investigation values of cardiac enzymes (creatininkinase and Troponine T) remained normal. The control ECG after 30 minutes turned back to normal. After one day the patient was submitted back to a normal ward. CONCLUSION: Symptomatic bradyarrhythmia and clinical sign of an myocardial infarction are rare but important cardiac side effects in patients treated with Taxol. Those patients should be under intensive care unit until patients conditions improve and acute myocardial ischemia has been excluded.

[The lethal ingestion of cigarettes in adults: does it really exist?]. / Die tödliche Zigaretten-Ingestion bei Erwachsenen. Gibt es sie wirklich?

HISTORY AND ADMISSION FINDINGS: A 35-year old patient suffering from a borderline personality disorder was admitted to our clinic with ingestions of cigarettes seven times within 15 months. The patient showed symptoms of a nicotine intoxication with agitation, hypertension, tachycardia, dizziness and nausea after ingestion of 7 up to 20 cigarettes. DIAGNOSIS: Mild nicotine intoxication. TREATMENT AND COURSE: After therapy with gastric lavages, activated charcoals and saline cathartics forced acid diuresis were performed in all seven cases of intoxication. All courses were without complications and unit every time the patient could be transferred to the psychiatry within 24 hours after the hospitalization in our clinic. CONCLUSION: An ingestion of more than 6 cigarettes is considered a life-threatening intoxication for adult persons. In spite of the ingestion of 7 up to 20 cigarettes our patient never showed any symptoms of a severe or life-threatening nicotine intoxication. In the last decades no lethal nicotine intoxication after ingestion of cigarettes in adults was published in the literature.

Fast T1- and T2-weighted pulmonary MR-imaging in patients with bronchial carcinoma.

PURPOSE: A prospective study to evaluate the diagnostic potential and limitations of three fast MRI sequences in patients with bronchial carcinoma based on the comparison with spiral CT. MATERIAL AND METHODS: Three fast chest MRI sequences from 20 patients with central or peripheral bronchial carcinoma were evaluated by two observers for relation of tumour to adjacent structures, lymph node enlargement, additional pulmonary lesions and artefacts. The information from MR-imaging was compared with the results from spiral CT. MRI comprised a T1-3D-GRE breath-hold examination ("VIBE", TR/TE 4.5/1.9 ms, flip-angle 12 degrees , matrix 502 x 512, 2.5 mm coronal slices), a breath-hold, T2-HASTE sequence (TR/TE 2000/43 ms, matrix 192 x 256, 10 mm coronal slices) and a respiration-triggered T2-TSE sequence (TR/TE 3000-6000/120 ms, matrix 270 x 512, 6 mm transverse slices). The FOV was adapted individually (380-480 mm). RESULTS: The presence of the primary bronchial carcinoma and infiltration of thoracic structures by tumour tissue could be demonstrated by all sequences. VIBE sequence was more suitable for detecting small pulmonary nodules than the other MRI examinations, but compared to CT still 20% of these lesions were missed. Contrary to VIBE and T2-weighted TSE scans, HASTE sequence was limited in imaging mediastinal lymph nodes due to missing relevant findings in 2/20 patients. HASTE images significantly provided the lowest rate of artefacts in imaging lung parenchyma (P < 0.001 in peripheral parenchyma), but spatial resolution was limited in this sequence. Concerning the differentiation between tumour and adjacent atelectasis (n = 8), T2-weighted TSE imaging was superior to CT and VIBE in all cases and to HASTE sequence in 4/8 patients. CONCLUSION: The combination of VIBE and HASTE sequence allows for an adaequate imaging of thoracic processes in patients with bronchial carcinoma, limited only in visualizing small pulmonary nodules. To obtain more detail resolution and to differentiate tumour tissue from adjacent atelectasis, T2-TSE examination may be added in selected cases.

Matrix metalloproteinase-9 in bronchiolitis obliterans syndrome after lung transplantation.

Bronchiolitis obliterans syndrome (BOS) is a severe complication after lung transplantation (LTX). In a retrospective cohort study 12 stable healthy recipients (non-BOS) and eight patients with BOS were enrolled after LTX and matrix metalloproteinases (MMP)-9, TIMP-1 and cell characteristics in bronchoalveolar lavage (BAL) samples (n = 145) were analysed. BALs from patients with BOS were further divided according to whether they were obtained before (pre-BOS) or after manifestation of BOS (BOS group). The MMP-9/TIMP-1 ratio was significantly increased in the BOS group compared with non-BOS or pre-BOS; furthermore, the ratio was negatively correlated with forced expiratory volume in one second. In zymography, the active form of MMP-9 was detected predominantly in the BOS group. In addition, zymography showed the banding pattern of neutrophil-derived MMP-9, indicating that polymorphonuclear neutrophils (PMNs) were the main source of MMP-9. According to that, MMP-9 was significantly correlated with the number of PMN. In immunocytochemistry, MMP-9 was also associated predominantly with PMN. This is the first study to evaluate the expression of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 over time during manifestation of a fibroproliferative lung disease in patients. It demonstrates development of bronchiolitis obliterans syndrome after lung transplantation is associated with an imbalance of matrix metalloproteinases-9/tissue inhibitors of metalloproteinase-1 ratio.

Anti-GM-CSF antibodies in paediatric pulmonary alveolar proteinosis.

BACKGROUND: Auto-antibodies against granulocyte-macrophage colony stimulating factor (GM-CSF) may be central to the pathogenesis of adult sporadic pulmonary alveolar proteinosis (PAP). The role of anti-GM-CSF auto-antibodies in paediatric forms of PAP is as yet unclear. METHODS: Anti-GM-CSF auto-antibodies were determined with the help of an antigen capture assay using serum and/or bronchoalveolar lavage (BAL) fluid from 27 patients with PAP (nine adults, 15 children, three neonates) and from 185 children with different diseases as disease controls (various pulmonary conditions and patients with malignancies). RESULTS: Anti-GM-CSF auto-antibodies were detected in the serum of five of seven adult PAP patients. They were not found in the serum of any of the children or neonates with PAP nor in any of the disease control patients. Raised anti-GM-CSF titres were found in BAL fluid from three of four adult patients with PAP. Anti-GM-CSF auto-antibodies were detected in BAL fluid of only one of the 15 children (age at diagnosis 11 years, age at BAL 24 years) and in none of the neonates with PAP, nor in any of the disease control patients. CONCLUSIONS: The presence of anti-GM-CSF auto-antibodies seems to define an autoimmune disease underlying most of the adult sporadic type of PAP, but age at diagnosis may cause an overlap with children in some rare instances. In most of the children and all of the neonates the anti-GM-CSF titres were not significantly increased, indicating that alternative explanations are needed for the pathogenesis of the disease in these patients.

[Short bowel ileus due to a stenotic ileocecal tumor of tuberculous origin]. / Dünndarmileus bei stenosierendem Ileozökaltumor und abdomineller Tuberkulose.

Abdominal tuberculosis is a rare disease. Therapy usually consists in drug treatment while surgery is only performed in complicated cases. We report on a 75 year-old man who presented with clinical and radiologic signs of bowel obstruction. The patient complained of weight loss and B-symptoms. There was a history of drug treatment for tuberculosis of the neck and throat in the medical department four weeks prior to admission. Intraoperatively a coecum stenosis was found due to a large tumor that macroscopically appeared with a diffuse carcinomatosis of the peritoneum. A right hemicolectomy was performed. Histopathology findings revealed a granulomatous inflammation with epithelioid cells. Signs of peritoneal carcinomatosis were not seen. The patient recovered well after an additional tuberculostatic treatment and was discharged after 14 days. At present he is free of symptoms. Even after tuberculostatic treatment lymphatic tuberculosis might show signs of progression that can lead to an abdominal presentation.

Mechanical thrombectomy of major and massive pulmonary embolism with use of the Amplatz thrombectomy device.

RATIONALE AND OBJECTIVES: To evaluate the feasibility of mechanical thrombectomy with the Amplatz thrombectomy device (ATD) in restoring patency of acutely thrombosed pulmonary arteries resulting from pulmonary embolism for the improvement of patient outcome. METHODS: Mechanical thrombectomy with the ATD (8F) was performed in nine consecutive patients with angiographically documented thrombus in the left or right pulmonary artery resulting from deep vein thrombosis (n = 4) or unknown cause (n = 5). RESULTS: The Miller index decreased from 18 to 11. In all patients, the majority of the thrombus in the pulmonary artery was cleared after a mean activation time of the ATD of 367 seconds. Thrombectomy was performed with the ATD alone (n = 4) or with additional long-term fibrinolysis therapy (n = 5) with infusion of recombinant tissue-type plasminogen activator. Pulmonary arterial pressure decreased from a mean of 57 mm Hg before mechanical thrombectomy to 55 mm Hg directly after the procedure and to 39 mm Hg after termination of the recombinant tissue-type plasminogen activator infusion. CONCLUSIONS: Mechanical thrombectomy with the ATD in patients with minor and major pulmonary embolism is technically feasible and safe. It is a potential alternative to drug-mediated thrombolysis and surgery. However, the incremental benefit of the ATD over conventional treatments could be shown only in a randomized controlled study.

Topical amphotericin B application in severe bronchial aspergillosis after lung transplantation: report of experiences in 3 cases.

Ulcerative tracheobronchial aspergillosis after lung transplantation (ltx) may lead to bronchial-pulmonary artery fistula that results in fatal bleeding. We report our early experience with combined systemic, aerolized and topical application of amphotericin B in 3 cases of bronchial aspergillosis after ltx. Two patients are still alive, but 1 died of bleeding from a fistula between the left upper lobe bronchus and the pulmonary artery. Aspergillosis in the second patient resolved with minimal stenosis of the left main and the left upper lobe bronchus, and the third patient developed an anastomotic stenosis that was successfully dilated.