Nasal involvement in atrophic polychondritis. A case report]

Relapsing polychondritis is a rare and little known inflammatory disease. The case of a 29-year-old woman who presented with a one-year history of saddle nose is discussed in this article. After waiting for one year, rhinoplasty was decided, with a good result at the 18th month. We prefer to use a calvarial bone graft for this disease and to only operate under stable and minor conditions.     

Tetraspanin CD9 participates in dysmegakaryopoiesis and stromal interactions in primary myelofibrosis

Primary myelofibrosis is characterized by clonal myeloproliferation, dysmegakaryopoiesis, extramedullary hematopoiesis associated with myelofibrosis and altered stroma in the bone marrow and spleen. The expression of CD9, a tetraspanin known to participate in megakaryopoiesis, platelet formation, cell migration and interaction with stroma, is deregulated in patients with primary myelofibrosis and is correlated with stage of myelofibrosis. We investigated whether CD9 participates in the dysmegakaryopoiesis observed in patients and whether it is involved in the altered interplay between megakaryocytes and stromal cells. We found that CD9 expression was modulated during megakaryocyte differentiation in primary myelofibrosis and that cell surface CD9 engagement by antibody ligation improved the dysmegakaryopoiesis by restoring the balance of MAPK and PI3K signaling. When co-cultured on bone marrow mesenchymal stromal cells from patients, megakaryocytes from patients with primary myelofibrosis displayed modified behaviors in terms of adhesion, cell survival and proliferation as compared to megakaryocytes from healthy donors. These modifications were reversed after antibody ligation of cell surface CD9, suggesting the participation of CD9 in the abnormal interplay between primary myelofibrosis megakaryocytes and stroma. Furthermore, silencing of CD9 reduced CXCL12 and CXCR4 expression in primary myelofibrosis megakaryocytes as well as their CXCL12-dependent migration. Collectively, our results indicate that CD9 plays a role in the dysmegakaryopoiesis that occurs in primary myelofibrosis and affects interactions between megakaryocytes and bone marrow stromal cells. These results strengthen the “bad seed in bad soil” hypothesis that we have previously proposed, in which alterations of reciprocal interactions between hematopoietic and stromal cells participate in the pathogenesis of primary myelofibrosis.     

Assessment of M867, a selective caspase-3 inhibitor,in an orthotopic mouse model for non-small cell lung carcinoma

Radiation-induced lung injury (RILI) is a significant dose limiting complication of thoracic radiation for lung, breast, and esophageal cancer. Strategies for increasing the therapeutic index of radiation involve the use of radiosensitizing agents. We investigated the potential of M867 to sensitize non-small cell lung cancer (NSCLC) to radiation in vivo, while assessing its protective effects in normal lung parenchyma. H460-Luc2 cells were implanted into the mediastinum of athymic nude mice, which were separated into four treatment groups: control, M867, radiation therapy (RT) or combination. H460-Luc2 cell cultures were treated in parallel. Tumor growth was followed using bioluminescence imaging. Immunohistochemistry staining was used to detect phospho-Smad2/3 and cleaved caspase-3 expression. Western blot was done for the detection of cleaved caspase-3 and phospho-Smad2/3. TUNEL assays were used to measure apoptosis. M867+RT group had significantly increased tumor growth inhibition relative to either treatment alone (p=0.02). M867+RT was associated with increased levels of apoptosis (p<0.01), but combination treatment was associated with a decrease in caspase-dependent apoptosis relative to RT alone (p<0.01). We found that this increase in apoptosis in the M867+RT group was due to caspase-independent cell death. Based on early biomarker analyses of phospho-Smad 2/3 and cleaved caspase-3, M867+RT had a radio-protective effect on normal lung parenchyma. M867 may increase the therapeutic ratio of RT by enhancing the radiosensitivity of NSCLC while mitigating RILI. Further research is warranted to examine the late effects of lung injury and to study differences in the mechanism of action of M867 on lung cancer and normal tissue.     

Classification of perioperative histamine-related reactions

Objective:Histamine release may cause anaphylactoid reactions. However, during anaesthesia and surgery especially cardiovascular effects may not be regarded as histamine-related. Therefore, we adapted the classical concept of histamine release reactions to the perioperative situation and validated the new paradigm. Methods:Elevated plasma histamine (diagnostic gold standard) was correlated to potentially related intraoperative signs and symptoms. The validity, repeatability and sensitivity of the ‘gold standard’ was tested by ROC analysis in volunteers, who also received H1-/H2-histamine antagonists. Additionally, a dose-response relationship was determined in dogs using the histamine releaser compound 48/80. Results:The ‘gold standard’ had a sensitivity of 96% (90%–100%) and a specificity of 93% (85%–100%). The reproducibility was proven by repeated injections of histamine. Skin reactions, tachycardia and hypertension were identified as histamine-related diagnostic variables. A dose-response curve of plasma histamine release was created. Conclusions:The defined ‘gold standard’ is valid for the diagnosis of histamine-related reactions during anaesthesia and surgery. It may help to identify patients, who could benefit from pre-anaesthetic antihistamine prophylaxis.     

Testicular carcinoma presenting as cutaneous nasal metastasis: case report and review of the literature

Testicular choriocarcinoma is a highly malignant germ cell neoplasm, which metastasises to lungs, and brain. Spread to the skin, however, is rare, with only 11 cases reported to our knowledge. This is the second reported case of a skin metastasis of choriocarcinoma to the head and neck, and the third in which a cutaneous metastasis was the first finding at initial presentation. A review of published reports showed that it had been described as individual firm, reddish or violaceous subcutaneous nodules with typical histological features.     

Basic life support with four different compression/ventilation ratios in a pig model: The need for ventilation

Background

During cardiac arrest the paramount goal of basic life support (BLS) is the oxygenation of vital organs. Current recommendations are to combine chest compressions with ventilation in a fixed ratio of 30:2; however the optimum compression/ventilation ratio is still debatable. In our study we compared four different compression/ventilation ratios and documented their effects on the return of spontaneous circulation (ROSC), gas exchange, cerebral tissue oxygenation and haemodynamics in a pig model.

Methods

Study was performed on 32 pigs under general anaesthesia with endotracheal intubation. Arterial and central venous lines were inserted. For continuous cerebral tissue oxygenation a Licox^® PtiO₂ probe was implanted. After 3 min of cardiac arrest (ventricular fibrillation) animals were randomized to a compression/ventilation-ratio 30:2, 100:5, 100:2 or compressions-only. Subsequently 10 min BLS, Advanced Life Support (ALS) was performed (100%O₂, 3 defibrillations, 1 mg adrenaline i.v.). Data were analyzed with 2-factorial ANOVA.

Results

ROSC was achieved in 4/8 (30:2), 5/8 (100:5), 2/8 (100:2) and 0/8 (compr-only) pigs. During BLS, PaCO₂ increased to 55 mmHg (30:2), 68 mmHg (100:5; p = 0.0001), 66 mmHg (100:2; p = 0.002) and 72 mmHg (compr-only; p < 0.0001). PaO₂ decreased to 58 mmg (30:2), 40 mmHg (100:5; p = 0.15), 43 mmHg (100:2; p = 0.04) and 26 mmHg (compr-only; p < 0.0001). PtiO₂ baseline values were 12.7, 12.0, 11.1 and 10.0 mmHg and decreased to 8.1 mmHg (30:2), 4.1 mmHg (100:5; p = 0.08), 4.3 mmHg (100:2; p = 0.04), and 4.5 mmHg (compr-only; p = 0.69).

Conclusions

During BLS, a compression/ventilation-ratio of 100:5 seems to be equivalent to 30:2, while ratios of 100:2 or compressions-only detoriate peripheral arterial oxygenation and reduce the chance for ROSC.     

Perioperative prophylaxis with granulocyte colony-stimulating factor (G-CSF) in high-risk colorectal cancer patients for an improved recovery: A randomized, controlled trial

BACKGROUND: We aimed to improve the postoperative outcome of high-risk patients (American Society of Anesthesiologists class 3 and 4) recovering from colorectal cancer surgery by using recombinant human G-CSF (filgrastim) as perioperative prophylaxis. METHODS: In a double-blinded, placebo-controlled trial, 80 patients undergoing left-sided colorectal resection were randomized to filgrastim or placebo. Filgrastim (5 mug/kg) or placebo was administered in the afternoon on day -1, 0, and +1 relative to the operation. Primary endpoints were in a hierarchic order: quality of life (QoL) over time (determined at discharge, 2 and 6 months after operation with the European Organization for Research and Treatment of Cancer questionnaire) and the McPeek recovery score, which measures death and duration of stays in the intensive care unit and hospital. Predefined secondary endpoints were global QoL, subdomains of QoL, postoperative recovery, duration of stay, 6-month overall survival, complication rates, and cellular and immunologic parameters. RESULTS: There were no significant differences in both primary endpoints between the treatment groups. A significant improvement (P < .05) was obtained by filgrastim prophylaxis in the QoL subdomain family life /- social functioning,; thus, more patients recovered to their preoperative state (14 vs 4 with placebo) as determined by structured interviews. Duration of hospital stay (14 vs 12 days) and noninfectious complications were decreased from 8% to 3%. CONCLUSIONS: High-risk patients undergoing major operation for colorectal cancer profited from filgrastim prophylaxis with regard to duration of hospital stay, noninfectious complications, social QoL, and subjective recovery from operation. These endpoints, however, were secondary, and the primary endpoints (overall QoL and the McPeek index) did not show comparable benefits. A new confirmatory trial with the successful endpoints of this trial, as well as a cost analysis, will be needed to confirm the results before a general recommendation for the prophylactic use of G-CSF in high-risk cancer patients can be given.     

Independent risk factors for postoperative shivering

Postoperative shivering (PAS) is uncomfortable for patients and potentially risky. In this observational trial we sought to identify independent risk factors for PAS after general anesthesia. Potential risk factors for PAS were recorded in 1340 consecutive patients. Signs of shivering, peripheral and core temperature, and thermal comfort were recorded in the postanesthetic care unit. The data were split into an evaluation data set (n = 1000) and a validation data set (n = 340). The first was used to identify independent risk factors for PAS and to formulate a risk score using backward-elimination logistic regression analysis. The proposed model was subsequently tested for its discrimination and calibration properties using receiver operating characteristic (ROC)-curve analysis and linear correlation between the predicted and the actual incidences of PAS in the validation group. The incidence of PAS was 11.6%. There were three major risk factors: young age, endoprosthetic surgery, and core hypothermia, with age being the most important. The risk score derived from this analysis had a reasonable discriminating power, with an area under the ROC-curve of 0.69 (95% confidence interval, 0.60-0.78; P < 0.0001). Furthermore the equation of the calibration curve (y = 0.69x + 6; R2= 0.82; P < 0.05) indicated a good and statistically significant agreement between predicted and actual PAS incidence. Postoperative shivering can be predicted with acceptable accuracy using the four risk factors identified in the present study. The presented model may serve as a clinical tool to help clinicians to rationally administer prophylactic antishivering drugs.