Impact of post printing cleaning methods on geometry, transmission, roughness parameters, and flexural strength of 3D-printed zirconia.

OBJECTIVE: To analyze the impact of different post printing cleaning methods on geometry, transmission, roughness parameters, and flexural strength of additively manufactured zirconia. METHODS: Disc-shaped specimens (N = 100) were 3D-printed from 3 mol%-yttria-stabilized zirconia (material: LithaCon 3Y 210; printer: CeraFab 7500, Lithoz) and were cleaned with five different methods (n = 20): (A) 25 s of airbrushing with the dedicated cleaning solution (LithaSol 30®, Lithoz) and 1-week storage in a drying oven (40 °C); (B) 25 s airbrushing (LithaSol 30®) without drying oven; (C) 30 s ultrasonic bath (US) filled with Lithasol30®; (D) 300 s US filled with LithaSol 30®; (E) 30 s US filled with LithaSol 30® followed by 40 s of airbrushing (LithaSol 30®). After cleaning, the samples were sintered. Geometry, transmission, roughness (Ra, Rz), characteristic strengths (σ0), and Weibull moduli (m) were analyzed. Statistical analyses were performed using Kolmogorov-Smirnov-, t-, Kruskal-Wallis-, and Mann-Whitney-U-tests (α < 0.05). RESULTS: Short US (C) resulted in the thickest and widest samples. Highest transmission was found for US combined with airbrushing (E, p ≤ 0.004), followed by D and B (same range, p = 0.070). Roughness was lowest for US combined with airbrushing (E, p ≤ 0.039), followed by A and B (same range, p = 0.172). A (σ0 = 1030 MPa, m = 8.2), B (σ0 = 1165 MPa, m = 9.8), and E (σ0 = 1146 MPa, m = 8.3) were significantly stronger (p < 0.001) and substantially more reliable than C (σ0 = 480 MPa, m = 1.9) and D (σ0 = 486 MPa, m = 2.1). SIGNIFICANCE: For 3D-printed zirconia, cleaning strategy selection is important. Airbrushing (B) and short US combined with airbrushing (E) were most favorable regarding transmission, roughness, and strength. Ultrasonic cleaning alone was ineffective (short duration) or detrimental (long duration). Strategy E could be particularly promising for hollow or porous structures.

Salvage surgery for cervical radioiodine refractory 18F-FDG-PET positive recurrence of papillary thyroid cancer.

PURPOSE: Five percent of patients with differentiated thyroid cancer are diagnosed with radioiodine refractory relapse in the course of the disease. For isolated or oligometastatic cervical recurrence, resection or another local treatment is recommended. In this study, the impact of surgical treatment of cervical radioiodine refractory 18F-FDG-PET positive relapse of papillary thyroid cancer (PTC) was evaluated. METHODS: Patients receiving radioiodine therapy between 2005 and 2015 at the University Hospital of Cologne, Germany, for PTC were screened. The subgroup of patients undergoing surgery during the course of disease after recommendation by a multidisciplinary endocrine team for cervical radioiodine refractory 18F-FDG-PET positive recurrence was identified. Demographics, clinic-pathologic characteristics, oncologic treatment, and outcome were analyzed. RESULTS: Thirty (3%) of 969 patients with PTC treated with radioiodine therapy at our institution underwent surgery for radioiodine refractory 18F-FDG-PET positive cervical recurrence during the course of the disease. In eight (26.6%) patients, more than one operation was performed. Sixteen (53%) patients received external beam radiation therapy (EBRT) after surgery. Follow-up was on average, 79.2 ± 61.6 months after the last surgical treatment. Biochemical and radiological cure was seen in 12 (40%) patients. Remission was significantly more frequent in younger patients (P = 0.0001) with lymph node rather than soft tissue tumor recurrence (P = 0.004). CONCLUSIONS: Surgical treatment of radioiodine refractory 18F-FDG-PET positive cervical recurrence led to biochemical and radiological cure in about 40% of patients in this study. Further data are needed concerning risk stratification of potential subgroups benefitting of surgical approach and the possible role of EBRT after repetitive surgery.

Impact of TP53 mutation status on systemic treatment outcome in ALK-rearranged non-small-cell lung cancer.

Background: We analyzed whether co-occurring mutations influence the outcome of systemic therapy in ALK-rearranged non-small-cell lung cancer (NSCLC). Patients and methods: ALK-rearranged stage IIIB/IV NSCLC patients were analyzed with next-generation sequencing and fluorescence in situ hybridization analyses on a centralized diagnostic platform. Median progression-free survival (PFS) and overall survival (OS) were determined in the total cohort and in treatment-related sub-cohorts. Cox regression analyses were carried out to exclude confounders. Results: Among 216 patients with ALK-rearranged NSCLC, the frequency of pathogenic TP53 mutations was 23.8%, while other co-occurring mutations were rare events. In ALK/TP53 co-mutated patients, median PFS and OS were significantly lower compared with TP53 wildtype patients [PFS 3.9 months (95% CI: 2.4-5.6) versus 10.3 months (95% CI: 8.6-12.0), P < 0.001; OS 15.0 months (95% CI: 5.0-24.9) versus 50.0 months (95% CI: 22.9-77.1), P = 0.002]. This difference was confirmed in all treatment-related subgroups including chemotherapy only [PFS first-line chemotherapy 2.6 months (95% CI: 1.3-4.1) versus 6.2 months (95% CI: 1.8-10.5), P = 0.021; OS 2.0 months (95% CI: 0.0-4.6) versus 9.0 months (95% CI: 6.1-11.9), P = 0.035], crizotinib plus chemotherapy [PFS crizotinib 5.0 months (95% CI: 2.9-7.2) versus 14.0 months (95% CI: 8.0-20.1), P < 0.001; OS 17.0 months (95% CI: 6.7-27.3) versus not reached, P = 0.049] and crizotinib followed by next-generation ALK-inhibitor [PFS next-generation inhibitor 5.4 months (95% CI: 0.1-10.7) versus 9.9 months (95% CI: 6.4-13.5), P = 0.039; OS 7.0 months versus 50.0 months (95% CI: not reached), P = 0.001). Conclusions: In ALK-rearranged NSCLC co-occurring TP53 mutations predict an unfavorable outcome of systemic therapy. Our observations encourage future research to understand the underlying molecular mechanisms and to improve treatment outcome of the ALK/TP53 co-mutated subgroup.

[Lung cancer. Molecular pathology and personalized therapy]. / Lungenkarzinom. Molekulare Pathologie und personalisierte Therapie.

Recent advances in the treatment of non-small cell lung cancer (NSCLC) are based on the identification of so-called driver mutations, resulting in a more personalized treatment setting. Currently about 15% of NSCLC patients benefit from improved treatment protocols based on the genetic background of the tumor. In the last few years cancer immunotherapy has returned to the center of attention and comprises a variety of treatment approaches incorporating adaptive, as well as innate immunity. Current strategies involve the use of monoclonal antitumor antibodies, cancer vaccines, adoptive transfer of ex vivo activated T and NK cells as well as the blockade of so-called immune checkpoints (immune inhibitory pathways). Especially the combination of current treatments with immunotherapy seems promising to achieve highly potent antitumor effects. However, a profound understanding of the dynamic and complex interaction between lung cancer and the host immune system and especially its immune checkpoints is the foundation to identify potential biomarkers for a personalized cancer immunotherapy approach.

[Minimally invasive follicular thyroid carcinoma : Not always total thyroidectomy]. / Minimal-invasives follikuläres Schilddrüsenkarzinom : Eine Thyreoidektomie ist nicht obligat.

Current treatment guidelines for follicular thyroid carcinoma (FTC) recommend total thyroidectomy, lymphadenectomy and radioiodine ablation. Considering the low malignant potential of minimally invasive follicular thyroid carcinoma (MIFTC), a limited radical therapeutic procedure may be adequate. MIFTC is an intensely discussed group of tumors and a review of the literature reveals disagreement among experts concerning the criteria for a distinct definition. Therefore, in 2005 Rosai proposed a clinically more significant classification of FTC based on the extent of capsular and vascular invasion: MIFTC with capsular invasion only, with limited (< or =3) vascular invasion, encapsulated FTC with extensive (>3) vascular invasion and broadly invasive FTC with extensive invasive growth.For the diagnosis of MIFTC a complete investigation of the encapsulated follicular lesion should be performed by the pathologist and examination of at least 10 tissue blocks is mandatory. Due to the excellent prognosis hemithyroidectomy constitutes an adequate therapeutic approach in MIFTC with capsular invasion only and may also be considered for MIFTC with limited vascular invasion. There are no indications for systematic lymphadenectomy.

[Frozen shoulder. Diagnosis and therapy]. / Die eingesteifte Schulter. Diagnose und Therapie.

The condition of shoulder stiffness is often called adhesive capsulitis or frozen shoulder. It is regarded as a distinct clinical entity showing a benign and regular course. The major clinical feature is significant reduction in both active and passive range of motion (ROM) accompanied by stage-dependent pain, allowing for a clinical diagnosis. There are primary and secondary forms, the former having an unknown etiology and increased occurrence in patients with metabolic disorders and the latter being seen with prior injury or operation. Three stages, each lasting 4-6 months, mark the clinical course. The progression of the disease is self-limiting and may occasionally resolve in partial restitution. In the first stage ("freezing"), the shoulder continuously loses passive motion and causes worsening pain. Continuing stiffness and improvements in pain and inflammation are characteristic of the second stage ("frozen"). In the third stage ("thawing"), restriction of shoulder motion decreases, and ROM increases. Treatment should be adjusted to these stages. Recommendations include analgesics and joint injections in the first stage and physiotherapy in combination with manual therapy in the second and third stages. In cases of failure, passive exercise under interscalene block, manipulation under general anesthesia, or arthroscopic arthrolysis should be considered.

Polymorphisms in VEGF and IL-8 predict tumor recurrence in stage III colon cancer.

BACKGROUND: Identifying molecular markers for tumor recurrence is critical in successfully selecting patients with stage III colon cancer who are more likely to benefit from adjuvant chemotherapy. The present study analyzed a subset of 10 polymorphisms within eight genes involved in the tumor angiogenesis pathway and their impact on prognosis in stage III colon cancer patients treated with adjuvant chemotherapy. PATIENTS AND METHODS: Blood samples were obtained from 125 patients with locally advanced colon cancer at University of Southern California medical facilities. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism and 5'-end [gamma-(33)P] ATP-labeled PCR protocols. RESULTS: Polymorphisms in vascular endothelial growth factor (VEGF) (C+936T; P = 0.003, log-rank test) and interleukin-8 (IL-8) (T-251A; P = 0.04, log-rank test) were independently associated with risk of recurrence in stage III colon cancer patients. In combined analysis, grouping alleles into favorable versus nonfavorable alleles, high expression variants of VEGF C+936T and IL-8 T-251A were associated with a higher likelihood of developing tumor recurrence (P < 0.001). CONCLUSION: High expression variants of VEGF C+936T and IL-8 T-251A were associated with shorter time to tumor recurrence, indicating that the analysis of angiogenesis-related gene polymorphisms may help to identify patient subgroups at high risk for tumor recurrence.

[Effectiveness of radiofrequency ablation of lung tumours ]. / Radiofrequenzablation von Lungentumoren : Eine wirklich effektive Therapiemassnahme?

BACKGROUND: There has been great success in the treatment of primary and secondary tumours of the liver using radiofrequency ablation (RFA) therapy, resulting in this method being used for other solid tumours such as in the lung. However, concerning lung cancer only few data are available about the histomorphological effects of this method. The aim of this study was to analyse the effects of RFA therapy in tumours of the lung. PATIENTS AND METHODS: Eleven patients with non-small-cell lung cancer and one with a lung metastasis (primary tumour identified as urothelial carcinoma) underwent RFA therapy followed by resection of the affected lobe. One patient with a metastasis of the liver was included for comparison of treatment effects. Histomorphological analysis of the collected material was used to measure the amount of necrosis. RESULTS: None of the treated tumours of the lung showed complete necrosis after applying RFA therapy. In contrast, this method with the control metastasis of the liver resulted in complete thermal destruction. CONCLUSION: Our results indicate that RFA therapy is not adequate for successful induction of necrosis in tumours of the lung. Therefore the use of this method has to be considered extremely carefully as a palliative treatment option in tumours of the lung.

Extensive H(+) release by bone substitutes affects biocompatibility in vitro testing.

Bone substitutes are widespread in orthopedic and trauma surgery to restore critical bony defects and/or promote local bone healing. Cell culture systems have been used for many years to screen biomaterials for their toxicity and biocompatibility. This study applies a human bone marrow cell culture system to evaluate the toxic in vitro effects of soluble components of different bone substitutes, which are already in clinical use. Different specimens of tricalcium phosphates (TCP) (Vitoss, Cerasorb), nondecalcified bovine bone (Lubboc), demineralized human bone matrices (DBM) (Grafton Flex/Putty), and collagen I/III matrix (ACI-Maix) were tested in Dulbecco's modified Eagle's medium (DMEM) and MesenCult culture solution and compared with a biomaterial-free cell culture. Biocompatibility parameters were cell viability evaluated by phase-contrast microscopy and laser flow cytometry, morphology, and the local H(+) release by bone substitutes. There were significant differences (p < 0.05) between the tested biomaterials and culture solutions. Collagen I/III, non-demineralized bovine bone, and TCP materials showed advantages for cell survival over other tested biomaterials (average values of vital cells/mL MesenCult/DMEM: Collagen I/III: 1090/1083; Vitoss: 893/483; Cerasorb: 471/523; Lubboc: 815/410; Grafton Putty: 61/44; Grafton Flex: 149/57). Especially the DBM materials lead to a significant decrease of pH, which is considered to be a major factor for cell death. DMEM culture solution supports cell survival for those bone substitutes that induce an alkaline reaction, whereas MesenCult media promotes cell vitality in biomaterials, which leads to an acidification of culture solution.

Osteogenic progenitor cell potency after high-dose chemotherapy (COSS-96).

BACKGROUND: Since the first trial of chemotherapy in patients with osteosarcoma the survival rate has gradually improved. For more than two decades, most osteosarcoma patients from Germany, Austria and Switzerland have been treated according to the protocols of the Cooperative Osteosarcoma Study Group (COSS). The uniform treatment concept of a high-dose polychemotherapy pre- and postoperatively improved the survival rate of these patients significantly. One severe side-effect of COSS chemotherapy is multiple osteonecrosis. PATIENTS AND METHODS: In this study the osteogenic stem cell potency of three different tissue types was elucidated after COSS-96 chemotherapy (high-risk arm). Mononuclear cells were obtained from the periosteum, cartilage and bone marrow of a 17-year-old female with a chondroblastic osteosarcoma. The cells were cultivated for 4 weeks in standard medium and stimulated for osteogenic differentiation after the second passage with dexamethasone, glycerolphosphate and ascorbine acid. Two weeks later, the cell cultures were analysed with respect to cell morphology and immunochemical stainings. RESULTS: All cells cultures showed an osteoblastic regeneration potential measured by osteocalcin (OC), osteopontin (OP) and alkaline phosphatase (ALP) expression. Compared to other donor tissues and localizations, the fibula periosteum showed significantly higher osteoblast rates in vitro, whereas collagen II, CD34 and CD45 were not expressed in any culture. CONCLUSION: The results of this study demonstrate the survival of mesenchymal progenitor cells in bone marrow during COSS-96 polychemotherapy, which allows for an osteogenic regeneration in vitro and potentially in vivo.

Arrangement and structural conservation of the mitochondrial control region of two species of Plecoptera: utility of tandem repeat-containing regions in studies of population genetics and evolutionary history.

Low levels of primary sequence similarity across insect taxa have led to the suggestion of conserved structural elements in the insect mitochondrial control region. Our aim was to determine whether previously described motifs and secondary structures exist in stoneflies (Plecoptera). Several motifs and structural elements previously described in Orthoptera and Diptera were found, including a conserved 'hairpin' structure that may play a role in the initiation of mtDNA replication. The repeat region had the highest percentage similarity, lowest A-T content and highest transition to transversion ratio, suggesting a unique evolutionary pattern for the repeats. Finally, we discuss the usefulness of the control region in population genetic and evolutionary studies.

Gene flow, dispersal, and nested clade analysis among populations of the stonefly Peltoperla tarteri in the southern Appalachians.

We examined the genetic structure and phylogeography of populations of the stonefly Peltoperla tarteri in the Southern Appalachians to determine the extent and likely mechanism for dispersal of this stream insect. A 454-base-pair (bp) portion of the mitochondrial control region was sequenced from a minimum of 20 individuals from eight populations. Pairwise FST and exact tests showed high levels of differentiation among almost all populations except those on the same stream. amova analysis detected significant genetic differentiation between streams within drainages (phi(SD) = 0.14, P < 0.001), and there was a slight positive correlation between aquatic distance and genetic distance (r = 0.295, P = 0.03). According to nested clade analysis, the present day pattern of genetic variation in P. tarteri is the result of a historical range expansion coupled with restricted gene flow with isolation by distance. Together, these analyses suggest that adult dispersal is limited and that movement by larvae is the primary dispersal mechanism for P. tarteri.

[Surgical revision of the pilonidal sinus with single shot antibiosis]. / Die operative Sanierung des Sinus pilonidalis unter Single-shot-Antibiose.

For a therapy of the pilonidal sinus there are different surgical and non-surgical methods to be found in literature. In our surgical wing 140 male patients have been operated on this disease from September 1990 to July 1992. 16 cases out of these 140 were re-operations. Using a special surgical technique we applied the excision with a primary closure under single-shot antibiosis in 139 cases. By modifying this antibiosis prophylaxis we could reach a primary success healing rate of up to 96%. A retrospective study among our patients showed a recurrence rate of 5%.

Ozone-induced airway hyperresponsiveness and loss of neuronal M2 muscarinic receptor function.

The effect of acute ozone exposure on the function of efferent parasympathetic nerves, M3 muscarinic receptors on airway smooth muscle, and inhibitory M2 muscarinic receptors on the parasympathetic nerves was studied. Immediately after exposure to 2.0 ppm ozone for 4 h, guinea pigs became hyperresponsive to electrical stimulation of the vagus nerves. The normal airway response to intravenous cholinergic agonists at this time demonstrates normal M3 receptor function. M2 muscarinic receptors on the nerves, which normally inhibit release of acetylcholine, were dysfunctional after ozone exposure, as demonstrated by the failure of the muscarinic agonist pilocarpine to inhibit, and the failure of the M2 antagonist gallamine to potentiate, vagally mediated bronchoconstriction. Thus, loss of inhibitory M2 muscarinic receptor function after ozone exposure potentiates release of acetylcholine from the vagus nerves, increasing vagally mediated bronchoconstriction. By 14 days, postozone responses to vagal nerve stimulation were not different from those of air-exposed animals and the function of the neuronal M2 muscarinic receptor was normal, confirming that ozone-induced hyperresponsiveness is reversible.

Guinea pig lung inflammatory cell changes following acute ozone exposure.

The time course of inflammatory cell infiltration into guinea pig lungs following a single 4 h exposure to 2 ppm O3 was established by measuring the changing cell populations recovered by both bronchoalveolar lavage (BAL) and collagenase tissue digestion. Analysis of BAL-recovered albumin was used as an indicator of permeability damage and demonstrated an increase immediately following ozone exposure, reaching a maximum within 24 h, but returning to air-control levels by 7 days post-ozone exposure. A twofold enhancement in macrophages was observed in the lavage-recovered cell population after 2 days, returning to air-control numbers by 7 days. Collagenase digest-recovered monocytes and macrophages, identified by nonspecific esterase staining, were found to be elevated between 2 and 14 days following O3 exposure. Immediately following O3 exposure, a 4.5-fold increase in collagenase digest-recovered neutrophils was observed, with a subsequent decline to air-exposed lung levels during the next 12 h. In contrast, BAL-recovered neutrophils were observed to be increased immediately following O3 exposure at a level that was sustained for up to 3 days. The tissue accumulation of neutrophils was not associated with their subsequent appearance in the lavageable spaces. Although significant increases in collagenase digest-recovered eosinophils could not be detected, lavage-recovered eosinophil numbers were transiently increased by threefold after 3 days. By employing both BAL and collagenase digestion to evaluate this model of reversible lung injury, this study demonstrated that the use of BAL-recovered cell measurements alone does not adequately reflect the early inflammatory cell changes taking place within oxidant-exposed lungs.

Inflammatory cell influx into ozone-exposed guinea pig lung interstitial and airways spaces.

As a model of non-immunological lung inflammation, guinea pigs were exposed to 2.0 ppm ozone for 4 hours. Polymorphonuclear leukocytes (PMNs) rapidly accumulated in lung interstitium but declined from 147 +/- 34 million cells to control values (33 +/- 6 million cells) within the first 24 hours. Bronchoalveolar lavage (BAL) recovered PMNs were maximal by 3-6 hours (4 +/- 1 million cells) and remained elevated for 3 days. Macrophage numbers were doubled in lavageable spaces but those in interstitium increased by only a third at 2 days post-exposure. By 7 days post-exposure BAL macrophages had declined to control values of 12 +/- 2 million cells while those in interstitium remained elevated through 14 days. These data demonstrate that BAL does not necessarily reflect cellular changes in lung interstitium.

Hypercholesterolemia: prevention, detection and management.

High serum cholesterol, leading to atherosclerosis, heart attack and stroke, is a major health problem in the United States and other Western countries. Hypercholesterolemia is amenable to dietary and other lifestyle changes that are brought about through education and supportive counseling. Dietary modification includes weight control, lowered intake of fats and cholesterol, and increased ingestion of water-soluble fiber. This article explores cholesterol metabolism and the mechanisms of factors lowering serum cholesterol in the body. The actions of chylomicrons, very low density lipoproteins, low density lipoproteins and high density lipoproteins are reviewed. Detection and evaluation of serum total and low density lipoproteins, and pharmacological therapy for hypercholesterolemia are discussed. Specific techniques for the health care provider to use in educating and counseling clients are emphasized.