Response durability after cessation of immune checkpoint inhibitors in patients with metastatic Merkel cell carcinoma: a retrospective multicenter DeCOG study.

BACKGROUND: Immune checkpoint inhibitors (ICI) have led to a prolongation of progression-free and overall survival in patients with metastatic Merkel cell carcinoma (MCC). However, immune-mediated adverse events due to ICI therapy are common and often lead to treatment discontinuation. The response duration after cessation of ICI treatment is unknown. Hence, this study aimed to investigate the time to relapse after discontinuation of ICI in MCC patients. METHODS: We analyzed 20 patients with metastatic MCC who have been retrospectively enrolled at eleven skin cancer centers in Germany. These patients have received ICI therapy and showed as best overall response (BOR) at least a stable disease (SD) upon ICI therapy. All patients have discontinued ICI therapy for other reasons than disease progression. Data on treatment duration, tumor response, treatment cessation, response durability, and tumor relapse were recorded. RESULTS: Overall, 12 of 20 patients (60%) with MCC relapsed after discontinuation of ICI. The median response durability was 10.0 months. Complete response (CR) as BOR to ICI-treatment was observed in six patients, partial response (PR) in eleven, and SD in three patients. Disease progression was less frequent in patients with CR (2/6 patients relapsed) as compared to patients with PR (7/11) and SD (3/3), albeit the effect of initial BOR on the response durability was below statistical significance. The median duration of ICI therapy was 10.0 months. Our results did not show a correlation between treatment duration and the risk of relapse after treatment withdrawal. Major reasons for discontinuation of ICI therapy were CR (20%), adverse events (35%), fatigue (20%), or patient decision (25%). Discontinuation of ICI due to adverse events resulted in progressive disease (PD) in 71% of patients regardless of the initial response. A re-induction of ICI was initiated in 8 patients upon tumor progression. We observed a renewed tumor response in 4 of these 8 patients. Notably, all 4 patients showed an initial BOR of at least PR. CONCLUSION: Our results from this contemporary cohort of patients with metastatic MCC indicate that MCC patients are at higher risk of relapse after discontinuation of ICI as compared to melanoma patients. Notably, the risk of disease progression after discontinuation of ICI treatment is lower in patients with initial CR (33%) as compared to patients with initial PR (66%) or SD (100%). Upon tumor progression, re-induction of ICI is a feasible option. Our data suggest that the BOR to initial ICI therapy might be a potential predictive clinical marker for a successful re-induction.

[Cold atmospheric pressure plasma for the treatment of acute and chronic wounds]. / Kaltes Atmosphärendruckplasma zur Behandlung akuter und chronischer Wunden.

BACKGROUND: Besides acute wounds (through trauma or surgical interventions), chronic wounds comprise a relatively large and heterogeneous group of diseases. These include leg ulcers with venous disease greatly prevailing arterial disease, diabetic foot syndrome, and pressure ulcers. Due to a considerable treatment resistance against such therapies, new and effective, additive treatment options especially for chronic wounds are needed. Wound treatment with cold atmospheric plasma (CAP) constitutes such an innovative option. OBJECTIVES: Current research regarding the efficacy of cold plasma for healing of acute and chronic wounds is summarized. MATERIALS AND METHODS: The literature on CAP applications in wound healing has been screened and reviewed. RESULTS: With CAP, several effects that promote wound healing can be simultaneously applied in one application. On the one hand, CAP exerts a strong and broad antimicrobial activity against biofilm. On the other hand, the plasma cocktail, which consists of reactive nitrogen and oxygen species, UV, and charged particles (electrical current), mediates tissue-stimulating, blood flow-promoting, and anti-inflammatory effects. Marked germ reduction on wounds and accelerated wound healing have already been convincingly demonstrated in controlled clinical studies. CONCLUSIONS: The comprehensive CAP study landscape with structured case report summaries and randomized case-control studies allows the conclusion that CAP is safe, effective, and easy to handle for wound treatment. The utilization of CAP in addition to standard wound treatments is starting to enter routine clinical practice.

Gelatin-poly(lactic-co-glycolic acid) scaffolds with oriented pore channel architecture - From in vitro to in vivo testing.

A gelatin-poly(lactic-co-glycolic acid), PLGA, composite scaffold, featuring a highly oriented pore channel structure, was developed as a template for articular cartilage regeneration. As a design principle the composite scaffold was optimized to contain only medical grade educts and accordingly no chemical cross linking agents or other toxicological relevant substances or methods were used. Scaffolds were synthesized using a freeze structuring method combined with an electrochemical process followed by freeze-drying. Finally, cross linking was performed using dehydrothermal treatment, which was simultaneously used for sterilization purposes. These composite scaffolds were analyzed in regard to structural and biomechanical properties, and to their degradation behavior. Furthermore, cell culture performance was tested using chondrocytes originated from joint articular cartilage tissue from 6 to 10 months old domestic pigs. Finally, the scaffolds were tested for tissue biocompatibility and their ability for tissue integration in a rat model. The scaffolds showed both excellent functional performance and high biocompatibility in vitro and in vivo. We expect that these gelatin-PLGA scaffolds can effectively support chondrogenesis in vivo demonstrating great potential for the use in cartilage defect treatment.

[Glucocorticoids and androgens for treatment of tiredness and weakness in palliative care patients : a systematic review]. / Glukokortikoide und androgene zur behandlung von müdigkeit und schwäche bei palliativpatienten : eine systematische übersichtsarbeit.

BACKGROUND: The therapy of tiredness, weakness and fatigue in palliative care patients is of growing interest. Glucocorticoids and androgens are habitually mentioned drugs for treatment. In this review evidence for glucocorticoids and androgens for these indications in palliative care patients are presented. MATERIALS AND METHODS: A systematic search of PubMed and Embase for studies on glucocorticoids and androgens for fatigue, asthenia, sedation, tiredness, weakness, exhaustion, cachexia, drowsiness and wasting in palliative care was carried out in August 2011. Furthermore, the Cochrane Library, references from the literature and leading textbooks were also searched. Study information was entered in a standardized extraction sheet. By a categorization of studies five endpoints were distinguished: fatigue, strength/weakness, tiredness, well being/quality of life and energy/activity/performance. RESULTS: A total of 11 controlled studies with glucocorticoids and 13 controlled studies with androgens were included. In addition four uncontrolled studies, two case series and two surveys with glucocorticoids as well as six uncontrolled studies and one case series with androgen treatment were analyzed. All controlled trials of glucocorticoids were performed in cancer patients and all but one controlled trial of androgens in patients with HIV/AIDS. Glucocorticoids improved quality of life but results for changes of fatigue and weakness were inconsistent. Tiredness and energy were not improved. Androgens had a positive effect on fatigue and quality of life and showed variable effects on weakness. Androgens did not improve energy. Side effects were frequently documented but only rarely resulted in discontinuation of therapy. CONCLUSION: With the existing evidence no general recommendation for glucocorticoid and androgen use in tiredness and weakness in palliative care patients can be given; however, glucocorticoids in cancer patients and androgens in HIV positive-patients can be used in an individual trial for improving patient quality of life. The use in patients suffering from other disease entities should be evaluated in randomized controlled trials with a similar setting. The English full text version of this article will be available in SpringerLink as of November 2012 (under "Supplemental").

[Modern coronary surgery, the SYNTAX trial and updated guidelines]. / Moderne Koronarchirurgie in Zusammenhang mit der SYNTAX-Studie und aktuellen Leitlinien.

Coronary artery bypass grafting (CABG), a modern and safe procedure, is considered the therapy of choice in the care of patients with multi-vessel disease. The 3-year results of the SYNTAX trial not only showed surgical advantages in terms of repeat revascularisation, but the results also demonstrated significant surgical benefit for myocardial infarction and survival rates. More differentiated analyses showed distinct disadvantages in percutaneous coronary intervention (PCI) associated with the greater complexity of coronary pathology. PCI tends to be a comparable therapeutic option only in certain cases of left main stem lesions or multi-vessel disease. The findings from the SYNTAX study herald a new era in the treatment of coronary heart disease in which, as recommended in the updated guidelines issued by the EACTS/ESC in 2010, the interventionalist and the surgeon, working closely together as a"heart team", provide a sound therapy plan for affected patients.

The MIDCAB approach in its various dimensions.

INTRODUCTION: Minimally invasive direct coronary artery bypass grafting (MIDCAB) offers arterial revascularization of the left anterior descending coronary artery especially in lesions unsuitable for percutaneous coronary interventions. By avoidance of sternotomy and cardiopulmonary bypass its invasivity is less than that of conventional bypass surgery. METHODS: A literature search of all published minimal invasive direct coronary artery bypass grafting studies was performed for the period from January 1995 through November 2011. Additionally, the authors reviewed their experience in more than one thousand patients treated by minimal invasive direct coronary artery bypass grafting within the last 14 years at their institution. RESULTS: Early mortally ranged from 1.2 to 1.3%. Midterm mortality ranged up to 3.2%. At 6-month follow up 3.6% grafts were occluded and 7.2% had a significant stenosis which resulted in target vessel revascularization in 3.3% of cases. The conversion rate to sternotomy or cardiopulmonary bypass ranged between 1.2 and 6.2%. CONCLUSIONS: In the past MIDCAB was predominantly used in patients with isolated lesions of the left anterior descending coronary artery. In combination with percutaneous interventions it provides an attractive option for full revascularization in multi vessel disease especially in older patients with significant comorbidities. Overall minimal invasive direct coronary artery bypass grafting is associated with few perioperative complications and with high graft patency rates in the mid-term and long-term course.

Percutaneous valve replacement: weird or wonderful?

Percutaneous treatment of valve diseases has proven to be an effective alternative to open surgery since the early 1980's. For most patients with rheumatic mitral stenosis, use of percutaneous catheter-based techniques as balloon valvuloplasty for the treatment of both congenital pulmonary stenosis as well as trans-septal commissurotomy has become a good therapeutic option. Furthermore in the mid 1990's in vitro studies demonstrated the feasibility of percutaneous catheter-based valve implantation first in pulmonary and subsequently in aortic position. Afterwards initial in vivo implantations were successfully undertaken. Limitations of this new branch of transcatheter-based techniques are: risk of embolization due to pre-dilatation; difficult deployment; migration of valved stent; paravalvular leakage and limited durability of the implanted valve. Hence, many advances and improvements are necessary prior to pronouncing a new real alternative and safe therapeutic option. Up to now the gold standard for the treatment of heart valve disease is still open surgical valve repair and replacement. Percutaneous valve replacement procedures offer substantial advantages both to patients and medical care providers. From a medical point of view, they may help reduce surgical risks, offer a less invasive procedure, lower complication rates and shorten rehabilitation times in future. From an economic standpoint, shorter hospital stays result in overall cost reduction.

[Host range testing of tumour-selective strains of Clostridium butyricum by Bacteriophage 5 (author's transl)]. / Wirtsbereichstestung von tumorselektiven Clostridium-butyricum-Stämmen mit dem Phagen 5.

Subcultures of Clostridium oncolyticum M55 and in a slightly modified manner of an oncolytic strain of Cl. butyricum H8 are differentiated by lysotypic reaction of the bacteriophage 5 from several tumour-selective non-oncolytic strains and subcultures of Cl. butyricum.

[Microbiological studies on mouth-ringing, cooling and turbine-spray waters]. / Mikrobiologische Untersuchungen von Mund-, Kühl- und Turbinenspraywässern.

Microbiological examinations of mouth-cleaning, cooling, and turbine spray waters from various types of dental units showed different degrees of water contamination. The detection of Pseudomonas aeruginosa, because of the classification of this organism as a "problem germ", indicates the necessity for a more critical analysis of water used in stomatology including the elimination of possible sources of contamination.