[Heparin-induced thrombocytopenia type II (HIT II) : A medical-economic view]. / Die heparininduzierte Thrombozytopenie (HIT II) : Eine medizinökonomische Betrachtung.

BACKGROUND: In the context of inpatient and increasingly ambulatory thrombosis prophylaxis, heparins have been recognised as standard therapy for decades. In addition to the therapeutic benefit, therapy with heparins also entails the risk of undesirable side effects, such as bleeding and thrombocytopenia. Heparin-induced thrombocytopenia (HIT II) is deemed a serious side effect. AIM: In the following work, HIT II is subjected to a medico-economic consideration (treatment, pharmaceuticals, subsequent costs due to possible complications) and, with regard to a possible HIT II prophylaxis, aspects of increasingly respected patient safety are also considered. METHODS: In the context of a literature search the active ingredients argatroban and danaparoid, which are approved for HIT II treatment, were evaluated. RESULTS: HIT II - especially in combination with thromboembolic complications - represents a medical-economic burden for the hospital. Although this is only an orientation guide, it shows that HIT II syndrome is not adequately cost-covered by the G­DRG system. An early thrombosis prophylaxis with argatroban/danaparoid for HIT II risk patients should therefore be taken into account for medical-related as well as patient safety-relevant aspects. According to experience, the pharmaceutical supply for these medically needed products (anticoagulants) should be ensured for reasons of patient safety. CONCLUSION: The risk of an immunological response to heparin therapy is known. Within the context of increased patient safety, thrombosis prophylaxis should be issued with a risk-adjusted prophylaxis.

[Psoriasis in special localizations]. / Psoriasis in besonderen Lokalisationen.

A large proportion of patients with plaque psoriasis suffer from psoriatic lesions of the scalp, nails, and intertrigines. These locations can also be soley or predominantly affected. Scalp psoriasis, nail psoriasis, and inverse psoriasis are often perceived as particularly stigmatizing. Involvement of these parts of the body is associated with an increased risk of psoriatic arthritis. Location-specific features must be considered when choosing treatment. Evidence for topical therapy of scalp psoriasis with steroids and combinations of steroids and vitamin D analogues is high. These agents are regarded as safe and effective treatments of first choice. Efficacy of TNF antagonists and apremilast is well documented for refractory scalp psoriasis. Nail psoriasis often responds insufficiently to topical therapy. Several effective systemic medications including methotrexate and TNF antagonists are available for treatment of severe forms. Controlled trials for treatment of inverse psoriasis are scarce. Topical steroids, vitamin D analogues, dithranol, and off-label calcineurin inhibitors are used in clinical practice. This review provides a survey on the clinical presentation and current evidence for treatment of psoriasis in challenging locations.

Identification of the novel differentiation marker MS4A8B and its murine homolog MS4A8A in colonic epithelial cells lost during neoplastic transformation in human colon.

The CD20-homolog Ms4a8a has recently been shown to be a marker for alternatively activated macrophages but its expression is not restricted to hematopoietic cells. Here, MS4A8A/MS4A8B expression was detected in differentiated intestinal epithelium in mouse and human, respectively. Interestingly, no MS4A8B expression was found in human colon carcinoma. Forced overexpression of MS4A8A in the murine colon carcinoma cell line CT26 led to a reduced proliferation and migration rate. In addition, MS4A8A-expressing CT26 cells displayed an increased resistance to hydrogen peroxide-induced apoptosis, which translated in an increased end weight of subcutaneous MS4A8A+ CT26 tumors. Gene profiling of MS4A8A+ CT26 cells revealed a significant regulation of 225 genes, most of them involved in cytoskeletal organization, apoptosis, proliferation, transcriptional regulation and metabolic processes. Thereby, the highest upregulated gene was the intestinal differentiation marker cytokeratin 20. In conclusion, we show that MS4A8A/MS4A8B is a novel differentiation marker of the intestinal epithelium that supports the maintenance of a physiological barrier function in the gut by modulating the transcriptome and by conferring an increased resistance to reactive oxygen species. The absence of MS4A8B in human colonic adenocarcinomas shown in this study might be a helpful tool to differentiate between healthy and neoplastic tissue.

Matching physicians' treatment recommendations to patients' treatment preferences is associated with improvement in treatment satisfaction.

BACKGROUND: Dissatisfaction with treatment is common among those with psoriasis. While incorporating patients' preferences into the process of treatment decision-making may improve satisfaction, this relationship has not been clearly established. OBJECTIVE: To assess the extent to which matching physicians' treatment recommendations to patients' treatment preferences is associated with improvement in treatment satisfaction in patients with moderate-to-severe psoriasis. METHODS: This prospective cohort study design examined change from baseline to 3-month follow-up in four subscales of an established measure of treatment satisfaction. Separate multivariate regression models investigated the association of change in these subscale scores with an index measuring the match between physicians' treatment recommendations and patients' treatment preferences at the initial study visit. RESULTS: A closer match between physicians' recommendations and patients' preferences was associated with greater improvement in treatment satisfaction over time in each of the four subscales: effectiveness (ß = 0.53, P < 0.001), side-effects (ß = 0.25, P = 0.009), convenience (ß = 0.78, P < 0.001) and global satisfaction (ß = 0.49, P < 0.001). Adjusted models explained as much as 76% of the variation in change in treatment satisfaction subscales over 3 months. CONCLUSIONS: Further efforts to incorporate patients' preferences in treatment decision-making appear justified given the strength of independent associations between preference matching and improved treatment satisfaction and the extent to which our models explained variation in this relationship. An approach based on preference matching shows promise for increasing satisfaction in the management of other chronic diseases.

Patient preferences for psoriasis treatments: impact of treatment experience.

BACKGROUND: Patient preferences for psoriasis treatments can impact treatment satisfaction and adherence and may therefore influence clinical outcome. OBJECTIVE: To assess the impact of treatment experience (satisfaction with current treatment, number of prior visits, disease duration, number of preceding therapies and currently prescribed treatment modalities) on treatment preferences. METHODS: A computer-based conjoint analysis experiment was conducted to analyse preferences of patients with moderate or severe psoriasis (n = 163) treated at a German University Medical Center for outcome (probability, magnitude and duration of benefit; probability, severity and reversibility of side effects) and process attributes (location, frequency, duration, delivery method, individual cost) of psoriasis treatments. Relative importance scores (RIS) were calculated for each attribute and compared using anova, post hoc test and multivariate regression analysis. RESULTS: Participants with longer disease duration attached significantly greater importance to duration of benefit (ß = 0.206, P = 0.018), whereas participants on oral therapy were more concerned about magnitude of benefit by trend (ß = 0.218, P = 0.058). Participants receiving injectables not only set higher value to probability of benefit (RIS = 32.80 vs. 21.89, P = 0.025) but also to treatment location (RIS = 44.74 vs. 23.03, P = 0.011), delivery method (RIS = 43.75 vs. 19.29, P = 0.019), treatment frequency (RIS = 31.24 vs. 16.89, P = 0.005) and duration (RIS = 32.54 vs. 16.57, P = 0.003) when compared with others. Treatment satisfaction was significantly higher in participants on infusions or injections compared with those on phototherapy and mere topical therapy. CONCLUSIONS: Treatment preferences may change over time course and with treatment experience. Participants on injectables attach great importance to efficiency and convenience of therapies, and are highly satisfied with their treatment.

[The simultaneous distally based sural flap. A therapeutic option for coverage of both heels]. / Der simultane distal gestielte Suralislappen. Therapieoption zur Defektdeckung beider Fersen.

Exposed bradytrophic tissue in regions with high mechanical loading is an indication for defect coverage with (myo-, adipo-) fasciocutaneous flaps. In this case, distally based sural flaps were used for bilateral coverage of defects in weight-bearing areas of feet after fourth-degree frostbite. Residual defects can be covered with a split skin mesh graft. The definitive prosthetic supply of the foot assumes a stabilized plantar soft tissue situation. Among its advantages in comparison to free microvascular flaps, the locally based fasciocutaneous flap can be harvested with less donor site morbidity after elevation and does not require secondary debulking. It has been shown that the reduced stability at the border zone between flap and mesh graft has an adverse effect.

[Asymptomatic nodule on an elderly lady's thumb tip]. / Asymptomatischer Nodus am Daumen einer älteren Frau.

A 71-year-old woman presented with an asymptomatic growing dermal tumor on her thumb. Clinical picture, ultrasound, laboratory investigations and histology were consistent with the diagnosis of gouty tophus. Pathogenesis, risk factors and therapy of tophaceous gout are discussed.

Theragnostics for tumor and plaque angiogenesis with perfluorocarbon nanoemulsions.

Molecular imaging agents are extending the potential of noninvasive medical diagnosis from basic gross anatomical descriptions to complicated phenotypic characterizations based upon the recognition of unique cell-surface biochemical signatures. Although originally the purview of nuclear medicine, "molecular imaging" is now studied in conjunction with all clinically relevant imaging modalities. Of the myriad of particles that have emerged as prospective candidates for clinical translation, perfluorocarbon nanoparticles offer great potential for combining targeted imaging with drug delivery, much like the "magic bullet" envisioned by Paul Ehrlich 100 years ago. Perfluorocarbon nanoparticles, once studied in Phase III clinical trials as blood substitutes, have found new life for molecular imaging and drug delivery. The particles have been adapted for use with all clinically relevant modalities and for targeted drug delivery. In particular, their intravascular constraint due to particle size provides a distinct advantage for angiogenesis imaging and antiangiogenesis therapy. As perfluorocarbon nanoparticles have recently entered Phase I clinical study, this review provides a timely focus on the development of this platform technology and its application for angiogenesis-related pathologies.

Sequential methotrexate and 5-fluorouracil (FU) vs. FU alone in metastatic colorectal cancer. Results of a randomized multicenter trial. The Association of Medical Oncology (AIO) of the German Cancer Society.

Methotrexate (MTX) modulates 5-fluorouracil (FU) in several in vitro and in vivo experimental systems. Results of phase II studies have suggested improved response rates for the sequential application of MTX and FU in colorectal cancer. In a prospective randomized multicenter study we compared sequential MTX (300 mg/m2) and FU (900 mg/m2) using a seven-hour time interval and leucovorin rescue with FU (450 mg/m2/d for five days) in patients with previously untreated metastatic colorectal cancer. Of 172 patients randomized 159 were eligible for survival analysis and 153 for toxicity and response evaluation. Complete or partial response has been seen in 25.3% of patients receiving sequential MTX and FU and in 17.6% of those receiving FU alone (p = 0.11). There have been two long-term survivors, apparently cured by MTX/FU. Overall toxicity was more pronounced with FU alone, but sequential MTX/FU caused four toxic deaths. Median survival and survival rates at one and two years were not significantly different. It is concluded that this schedule of sequential MTX and FU is no more effective than a dose-intensive treatment with FU alone in metastatic colorectal cancer.

[Primary combined radiotherapy of carcinoma of the uterine cervix. Comparison of 192Ir with radium]. / Primäre kombinierte Strahlentherapie des Carcinoma colli uteri. Vergleich von 192Ir mit Radium.

A retrospective study of primary irradiated carcinomas of the uterine cervix was made in order to compare the effect of radium with the effect of a 192Ir afterloading therapy with high dose rate which had been introduced 2 1/2 years before. A group of 31 patients treated with iridium was opposed to a historical control group of 24 patients treated with radium. Both groups were submitted to the same method of simultaneous percutaneous irradiation. All consecutively treated patients exposed to a percutaneous focal dose of greater than 45 Gy were evaluated. The iridium and radium doses applied as well as the values measured in intestine and bladder are presented. The iridium group had the same or a slightly less favorable prognosis (prognostic factors compared: stage, percutaneous dose, histology, age) than the radium group. The remission rates were identical for both therapy methods. Patients treated with iridium have a slightly better curve of recurrence-free interval and survival time, even taking into consideration the shorter observation period. Two out of the patients treated with iridium and four out of those treated with radium presented severe long-term side effects with formation of fistulas (average incidence 12,5 months and 12,7 months after the beginning of therapy, respectively).

Sequential methotrexate and 5-fluorouracil: improved response rate in metastatic colorectal cancer.

The efficacy of chemotherapy with sequential methotrexate (MTX) and 5-fluorouracil (5-FU) in metastatic colorectal cancer was studied in a multicenter phase II trial using a seven-hour time interval. Forty-two patients were evaluable for response and 16 achieved objective tumor regression (greater than 50%). Median survival of all patients was 12.5 months. The result of this study indicates that MTX and 5-FU are synergistic in human colorectal cancer if given sequentially with a seven-hour time interval. This is supported by a review of the literature that reveals a significantly higher response rate in patients treated with a four-hour or more MTX/5-FU interval as compared to a one-hour interval.

[Interstitial brachytherapy--initial experiences using 192iridium in short-term therapy]. / Interstitielle Brachytherapie--erste Erfahrungen mit 192Iridium in der Kurzzeittherapie.

After a review of the literature dealing with the previous development and the methods of interstitial brachytherapy the high-dose-rate therapy with Iridium-192 is outlined. The proceeding by means of a new afterloading system are depicted. The hitherto acquired indications are treated and discussed in detail. The advantages of this method are emphasized.

[Chemotherapy with cisplatin-bleomycin and subsequent radiotherapy in advanced head and neck tumors]. / Chemotherapie mit Cisplatin-Bleomycin und nachfolgende Strahlentherapie bei fortgeschrittenen Kopf-Hals-Tumoren.

42 patients with advanced stage III and IV squamous cell carcinoma of the head and neck were treated with initial cisplatin and bleomycin chemotherapy and subsequent radiotherapy. 39 were evaluable for results, and 3 for toxicity only. 8 patients suffered from stage III and 31 from stage IV tumors, of these 10 with distant metastases. 5 patients underwent later a rescue operation. 27 were previously untreated (= group A) including 2 cases with localized relapses beyond the margins of surgical and/or radiotherapeutic treatment fields. 12 patients had a recurrence within pretreated areas (= group B). The induction chemotherapy alone showed the following results: In group A 4 (15%) CR, 10 (37%) PR, 7 (26%) MR; in group B 3 (25%) PR, 2 (17%) MR. The subsequent radiotherapy mostly consisted of a 65 Gy tumor dose given in 61/2 weeks. The results after completion of the combined modality therapy were: In group A 44% CR, 28% PR; in group B 10% CR and 30% PR. No patient resistant to the initial chemotherapy responded to the radiotherapy. The median survival time of stage III patients was 20 months but only 7 months in stage IV patients. 4 of all live with NED now between 30+ and 41+ months; 1 patient is alive with relapse. All the others are dead after a survival time of max. 32 months, included the 5 with rescue operation. In general, hematologic and renal toxicities were not severe, but nausea and vomiting were the worst tolerated side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

[The problem of multiple cancers]. / Zum Problem der Mehrfachkarzinome.

This retrospective study reports on the occurrence of multiple carcinomas among the patients of our Department of Radiotherapy. Examination of 1290 patients during 1978 to 1980 showed in 76 cases (5.8%) simultaneously or successively secondary or tertiary tumours. These multiple tumours were most frequent in the mammary gland, in the female genital organs and in the respiratory system. Women had an incidence which was double of that displayed by men. Diagnosis and therapy of malignant tumours must always consider the possibility of multiplicity of carcinomas, either simultaneously or successively, appearing spontaneously or as a result of iatrogenic influences. This applies in particular to the multicentric and bilateral occurrence of the early types of cancer of the female breast.

[The problem of multiple breast cancers (author's transl)]. / Zum Problem der multiplen Brusttumoren.

This retrospective study is based on the appearance of bilateral breast cancers -- occurring simultaneously or succeedingly -- in patients our therapeutical radiation section. The examination of 368 patients in the years 1978-1981 gave result of 12 cases (3,2%) showing simultaneous bilateral breast cancer and of 14 cases (3,8%) showing succeeding contralateral breast cancer. Therefore multiple breast cancers are not to be regarded as a limited process but as manifestation in a cancerogenic effective range. This is of prime importance to the diagnosis and therapy of breast cancer.