Oral Health Status of Healthcare Workers in Ilembula/Tanzania during the COVID-19 Condition.

The challenge of reduced dental treatment and education infrastructure in the Tanzanian highlands affects the oral health situation of both the general population and local healthcare workers. The aim of this study was to investigate the oral health status of healthcare workers at Ilembula Lutheran Hospital (ILH), Tanzania, during the COVID-19 pandemic. In total, 134 healthcare workers (62 women, 72 men; mean age 36.48 ± 9.56 years, range 19-59 years; median age 35.00 years) participated in this cross-sectional study, conducted from 12 February to 27 February. A dental examiner trained in oral health screening performed the oral health data collection. Data collection was performed by probability sampling using the Ilembula Data Collection Form-Oral Health (IDCF-Oral Health) questionnaire distributed in paper form. Ethical approval was obtained from the National Institute for Medical Research/Tanzania. The decayed, missing, and filled teeth (DMF/T) index proposed by the World Health Organization (WHO) was used with the associated caries measurement method and the simplified oral hygiene index (OHI-S). Details regarding edentulism, nutritional habits, and socio-economic factors were collected. Statistical analysis was performed using linear regression (α = 0.05). The average DMF-T index was 3.33 ± 0.82, with age, gender, meal frequency, and soft drink consumption significantly influencing the index. No evidence of dental plaque was detected in 43.3% of the participants. Of the participants, 32.8% required prosthetic treatment (Kennedy Class III), while 16.4% needed it for acute malocclusions. Oral hygiene products were used in 97% of cases. A total of 35.8% of the participants had an OHI-S score of up to 1.0, with (p < 0.001) age and (p < 0.001) sex having a significant influence on the index. The current oral health situation of healthcare workers at ILH shows a moderate need for restorative and prosthetic treatment in rural Tanzania. Despite the COVID-19 pandemic, there was no change in the need for dental treatment, which may be explained by the generally restricted access to dental healthcare in the investigated region. The development of an interdisciplinary oral health prophylaxis system could help to reduce the need for future treatments.

Apical bulkheads accumulate as adaptive response to impaired bile flow in liver disease.

Hepatocytes form bile canaliculi that dynamically respond to the signalling activity of bile acids and bile flow. Little is known about their responses to intraluminal pressure. During embryonic development, hepatocytes assemble apical bulkheads that increase the canalicular resistance to intraluminal pressure. Here, we investigate whether they also protect bile canaliculi against elevated pressure upon impaired bile flow in adult liver. Apical bulkheads accumulate upon bile flow obstruction in mouse models and patients with primary sclerosing cholangitis (PSC). Their loss under these conditions leads to abnormally dilated canaliculi, resembling liver cell rosettes described in other hepatic diseases. 3D reconstruction reveals that these structures are sections of cysts and tubes formed by hepatocytes. Mathematical modelling establishes that they positively correlate with canalicular pressure and occur in early PSC stages. Using primary hepatocytes and 3D organoids, we demonstrate that excessive canalicular pressure causes the loss of apical bulkheads and formation of rosettes. Our results suggest that apical bulkheads are a protective mechanism of hepatocytes against impaired bile flow, highlighting the role of canalicular pressure in liver diseases.

A critical spotlight on the paradigms of FFPE-DNA sequencing.

In the late 19th century, formalin fixation with paraffin-embedding (FFPE) of tissues was developed as a fixation and conservation method and is still used to this day in routine clinical and pathological practice. The implementation of state-of-the-art nucleic acid sequencing technologies has sparked much interest for using historical FFPE samples stored in biobanks as they hold promise in extracting new information from these valuable samples. However, formalin fixation chemically modifies DNA, which potentially leads to incorrect sequences or misinterpretations in downstream processing and data analysis. Many publications have concentrated on one type of DNA damage, but few have addressed the complete spectrum of FFPE-DNA damage. Here, we review mitigation strategies in (I) pre-analytical sample quality control, (II) DNA repair treatments, (III) analytical sample preparation and (IV) bioinformatic analysis of FFPE-DNA. We then provide recommendations that are tested and illustrated with DNA from 13-year-old liver specimens, one FFPE preserved and one fresh frozen, applying target-enriched sequencing. Thus, we show how DNA damage can be compensated, even when using low quantities (50 ng) of fragmented FFPE-DNA (DNA integrity number 2.0) that cannot be amplified well (Q129 bp/Q41 bp = 5%). Finally, we provide a checklist called 'ERROR-FFPE-DNA' that summarises recommendations for the minimal information in publications required for assessing fitness-for-purpose and inter-study comparison when using FFPE samples.

Cumulative 10-year performance of endodontically treated teeth with prosthetic restorations of base metal alloy double crowns with friction pins-a retrospective study.

OBJECTIVES: This 120-month follow-up study aimed to investigate the complication rate of abutment teeth after endodontic pretreatment with base metal alloy double crowns with friction pins. MATERIALS AND METHODS: A total of 158 participants (n = 71, 44.9% women) aged 62.5 ± 12.7 years with 182 prostheses on 520 abutment teeth (n = 459, 88.3% vital) were retrospectively analyzed between 2006 and 2022. Of the endodontically treated abutment teeth, 6.9% (n = 36) were additionally treated with post and core reconstructions. Cumulative complication rates were calculated using the Kaplan-Meier estimator and log-rank test. In addition, Cox regression analysis was performed. RESULTS: The cumulative complication rate at 120 months for the entire set of abutment teeth was 39.6% (confidence interval [CI]: 33.0-46.2). Endodontically treated abutment teeth (33.8%; CI: 19.6-48.0) were found to have a significantly higher cumulative fracture rate than vital teeth (19.9%; CI: 13.9-25.9, p < 0.001). Endodontically treated teeth restored with post and core reconstructions (30.4%; CI: 13.2-47.6) showed a nonsignificant lower cumulative fracture rate than that of teeth with root fillings only (41.6%; CI: 16.4-66.8, p = 0.463). CONCLUSIONS: Higher 120-month cumulative fracture rates were observed in endodontically treated teeth. Comparable performance was observed in teeth with post and core reconstructions compared to teeth with root fillings only. CLINICAL RELEVANCE: If endodontically treated teeth are used as abutments for double crowns, the risk of complications from these teeth should be considered when planning treatment and communicating with the patient.

Ten-year clinical performance of non-precious metal double crowns with friction pins in severely reduced dentitions-a retrospective study.

OBJECTIVES: This follow-up study aimed at collecting long-term data for removable partial dentures (RPDs) retained by double crowns with spark-eroded friction pins (DCP) and comparing them in the presence of severely reduced dentition (SRD) and non-SRD (NSRD, i.e. residual dentition with more than three abutment teeth) after a 10-year wearing period. MATERIALS AND METHODS: A total of 158 participants (n = 71, 44.9% women) aged 62.5 ± 12.7 years with 182 prostheses on 520 abutment teeth were followed up between 2006 and 2022. The SRD group included 144 RPDs supported by 314 abutment teeth. The data collection was performed retrospectively. 10-year survival rates of RPDs and abutment teeth were determined using the Kaplan-Meier method and compared using the log-rank test for SRD and NSRD, among others. Cox regression analyses were conducted to isolate risk factors for the survival of both RPDs and abutment teeth. RESULTS: The 10-year cumulative survival rate of all abutment teeth was 65.6% with significantly lower values in the SRD group (53.5%) (p < 0.001). The survival rate for all RPDs was 65.5%. The SRD group showed lower survival rates (57.9%) (p = 0.004). The number and location of the abutment teeth had a significant influence on the survival rates of the RPDs and the abutment teeth. Age, sex, jaw, relining, and vitality had a significant influence on the abutment teeth survival rates. CONCLUSIONS: RPDs showed an acceptable clinical survival rate after 10 years. The number, location, and vitality of abutment teeth were factors that influenced the survival of both RPDs and abutment teeth. CLINICAL RELEVANCE: Consideration of the influencing factors found can help improve the prognostic assessment of double crown-retained dentures in the context of prosthetic therapy planning.

An Extremely Rare Cause of an Obstructive Jaundice in Adults: Limited Langerhans Cell Histiocytosis of the Extrahepatic Bile Duct.

Langerhans cell histiocytosis (LCH) is a rare group of idiopathic disorders (previously termed "histiocytosis X") which is characterized by the presence of cells with characteristics similar to bone marrow-derived Langerhans cells which infiltrate various tissues and organs. Like Langerhans cells located in the skin, they express histiocytic markers such as S100, CD1a, and CD68 and contain Birbeck granules, which are rod-shaped intracytoplasmic organelles best demonstrated in electron microscopy. LCH primarily affects the skeleton, but lung, skin, liver, and lymph node involvement may occur alike. Hepatic involvement is well recognized in children, with sclerosing cholangitis occurring in 10-15% of those with multisystemic involvement, whereas LCH confined to the liver appears to be very unusual in adults. Up to date, only one case of a solitary LCH affliction of the extrahepatic bile duct lacking liver involvement in adulthood has been reported on in the literature. We here report on a 60-year-old male patient with classical indolent progressive obstructive jaundice. The diagnostic workup revealed a tumorous lesion in the middle third of the common hepatic bile duct, initially being highly suspicious of an extrahepatic cholangiocarcinoma. CT scans further suspected an infiltration of the right portal vein, implicating a potentially extensive tumor growth, but a preoperative histological confirmation was not feasible. The serum tumor marker CA19-9 was 48 U/mL. The patient then underwent an explorative laparotomy with a pylorus preserving pancreaticoduodenectomy, as all frozen section tissue specimens revealed no tumor infiltration. The final result of the histopathological examination revealed an isolated LCH in the extrahepatic bile duct with a consecutive secondary sclerosing cholangitis. To complete the tumor staging, a thorax CT scan was performed and a generalized histiocytosis was ruled out, hence confirming the localized character of the disease. To the best of our knowledge and after a comprehensive literature review, we report on the second case globally, which describes a primary LCH limited to the extrahepatic bile duct in adulthood. A generalized sclerosing cholangitis in the liver was ruled out by radiological imaging. Preoperative histological affirmation of such findings is very confined due to the complexity and hence can only be diagnosed in the postoperative specimen. However, patients with nondisseminated sole findings, usually report a good prognostic outcome after surgical resection despite the paucity of corresponding data.

Oral health status of nursing staff in Ilembula, Wanging'ombe District, Njombe region, Tanzania: a cross-sectional study.

BACKGROUND: Owing to the reduced dental treatment infrastructure in the Tanzanian highlands, maintaining good oral health is a challenge for not only the general population but also individual professional groups. In this study, the caries prevalence and, subsequently, the prosthetic treatment needs of the nurses of the Ilembula Lutheran Hospital (ILH) and Ilembula Institute of Health and Allied Sciences (IIHAS), Tanzania, were investigated. MATERIALS AND METHODS: One hundred and sixty-eight ILH and IIHAS nurses and nursing students (87 women, 81 men; age 23.1 ± 6.1 years, range 18-58 years) participated in this cross-sectional study conducted in February 2020. The participants were examined at the dental office of ILH. The Decayed, Missing, and Filled Teeth (DMF/T) Index, Simplified Oral Hygiene Index, and details regarding edentulism, nutrition habits, and socioeconomic factors were collected. Linear regression and binary logistic regression were used for statistical analysis. RESULTS: The mean DMF/T-Index was 6.30 ± 4.52. In 7.14% of the investigated nurses, no dental plaque was detected. An enhanced prosthodontic treatment (Kennedy Class III) demand was identified in 31.50% of the participants, and 4.80% of the participants required treatment for acute malocclusion. Oral hygiene products were used by 99.4% of the patients. CONCLUSIONS: The current oral health situation of the study participants showed a moderate restorative and prosthetic treatment demand in the rural area of Tanzania. The development of an interdisciplinary oral health prophylaxis system could be a means to remedy this situation.

In Vitro Analysis of the Mechanical Properties of Hypoallergenic Denture Base Resins.

The development of hypoallergenic denture resins is key to the treatment of patients with allergies to polymethyl methacrylate (PMMA). In this study, the in vitro mechanical properties of hypoallergenic and PMMA denture base resins were compared. Ninety-six test specimens of hypoallergenic denture base resins (Polyan Plus®, Sinomer, TMS Acetal Dental, Erkocryl) and 72 test specimens of PMMA-based denture base resins (Paladon 65, PalaXpress, SR-Ivocap) were fabricated. The flexural strength, elastic modulus, compressive strength, macro- and microhardness, average roughness, water absorption, and water solubility of the resins were measured. None of the hypoallergenic denture resins matched all the mechanical properties of the PMMA resins. Polyan Plus® and TMS Acetal Dental were closest to matching the mechanical properties of the PMMA resins, and TMS Acetal Dental had some superior properties. Consequently, Polyan Plus® and TMS Acetal Dental hypoallergenic resins are recommended for further investigation as potential alternatives to PMMA resins for the fabrication of removable dentures.

Microbiota-dependent activation of the myeloid calcineurin-NFAT pathway inhibits B7H3- and B7H4-dependent anti-tumor immunity in colorectal cancer.

Bacterial sensing by intestinal tumor cells contributes to tumor growth through cell-intrinsic activation of the calcineurin-NFAT axis, but the role of this pathway in other intestinal cells remains unclear. Here, we found that myeloid-specific deletion of calcineurin in mice activated protective CD8+ T cell responses and inhibited colorectal cancer (CRC) growth. Microbial sensing by myeloid cells promoted calcineurin- and NFAT-dependent interleukin 6 (IL-6) release, expression of the co-inhibitory molecules B7H3 and B7H4 by tumor cells, and inhibition of CD8+ T cell-dependent anti-tumor immunity. Accordingly, targeting members of this pathway activated protective CD8+ T cell responses and inhibited primary and metastatic CRC growth. B7H3 and B7H4 were expressed by the majority of human primary CRCs and metastases, which was associated with low numbers of tumor-infiltrating CD8+ T cells and poor survival. Therefore, a microbiota-, calcineurin-, and B7H3/B7H4-dependent pathway controls anti-tumor immunity, revealing additional targets for immune checkpoint inhibition in microsatellite-stable CRC.

Impact of the Veneering Technique and Framework Material on the Failure Loads of All-Ceramic Computer-Aided Design/Computer-Aided Manufacturing Fixed Partial Dentures.

OBJECTIVES: Zirconia (Y-TZP) ceramics are considered as posterior fixed partial denture (FPD) materials; however, their applications are limited due to chipping. The use of monolithic lithium disilicate (LiDi) glass ceramics in posterior FPDs can be advantageous. This in vitro study aims to compare the loads until failure of posterior Y-TZP-FPDs and LiDi-FPDs before and after aging.

Temperature profile and residual heat of monopolar laparoscopic and endoscopic dissection instruments.

BACKGROUND: Endoscopic and laparoscopic electrosurgical devices (ED) are of great importance in modern medicine but can cause adverse events such as tissue injuries and burns from residual heat. While laparoscopic tools are well investigated, detailed insights about the temperature profile of endoscopic knives are lacking. Our aim is to investigate the temperature and the residual heat of laparoscopic and endoscopic monopolar instruments to increase the safety in handling ED. METHODS: An infrared camera was used to measure the temperature of laparoscopic and endoscopic instruments during energy application and to determine the cooling time to below 50 °C at a porcine stomach. Different power levels and cutting intervals were studied to investigate their impact on the temperature profile. RESULTS: During activation, the laparoscopic hook exceeded 120 °C regularly for an up to 10 mm shaft length. With regards to endoknives, only the Dual Tip Knife showed a shaft temperature of above 50 °C. The residual heat of the laparoscopic hook remained above 50 °C for at least 15 s after activation. Endoknives cooled to below 50 °C in 4 s. A higher power level and longer cutting duration significantly increased the shaft temperature and prolonged the cooling time (p < 0.001). CONCLUSION: Residual heat and maximum temperature during energy application depend strongly on the chosen effect and cutting duration. To avoid potential injuries, the user should not touch any tissue with the laparoscopic hook for at least 15 s and with the endoknives for at least 4 s after energy application. As the shaft also heats up to over 120 °C, the user should be careful to avoid tissue contact during activation with the shaft. These results should be strongly considered for safety reasons when handling monopolar ED.

[The Importance of Anatomy in the Training of the Vascular Surgeon]. / Der Stellenwert der Anatomie in der Weiterbildung des Gefäßchirurgen.

Vascular surgery has developed very dynamically in recent years, especially with the introduction of endovascular techniques. However, this has also changed surgeons' requirements. Classical surgical procedures have been almost completely displaced by endovascular techniques; new hybrid interventions have emerged while complex operations are concentrated in few centres. Therefore, developing expertise in open aortic surgery is increasingly challenging in vascular surgical training programs.Cadaver models provide an opportunity for exposure and repetitive training of individual surgical steps without endangering patients.As part of the training of highly complex vascular surgery operations, we carried out and evaluated the thoracoabdominal aortic replacement with 13 participants in 6 ethanol-preserved corpses.A simulation of surgical procedures on human cadaveric models cannot fully replace real experiences, but allows surgeons in training to practice and achieve dexterity in performing procedures in a safe and reproducible way.

Intraoperative Assessment of Gastric Sleeve Oxygenation Using Hyperspectral Imaging in Esophageal Resection: A Feasibility Study.

INTRODUCTION: Sufficient tissue oxygenation is essential for anastomotic healing in visceral surgery. Hyperspectral imaging (HSI) is a noncontact, noninvasive technique for clinical assessment of tissue oxygenation in real time. METHODS: In this case series, HSI was used in 4 patients who were admitted for either esophageal cancer or cardiac carcinoma (AEG type I or II). Thoraco-abdominal surgical esophageal resection was performed after staging and neoadjuvant therapy. Intraoperative oxygenation of superficial (StO2) and underlying tissue (NIR perfusion index) of the gastric sleeve were studied intrathoracic by means of the TIVITA® Tissue HSI camera. This was performed prior to esophagogastric anastomosis. The postoperative course, especially in view of surgical complications, was recorded. RESULTS: Assessment of StO2 and NIR perfusion index was performed in 4 regions of interest per gastric sleeve, aboral and oral of the clinically determined resection line. It allowed the fast quantification of gastric oxygenation prior gastroesophageal anastomosis. Median StO2 aboral of the determined resection line was 69%, while median StO2 in the oral part of the gastric sleeve was found at 53%. In contrast, the median NIR perfusion index was similar aboral (80) and oral (82) of the resection line. In none of the 4 studied patients, an anastomotic failure appeared. DISCUSSION/CONCLUSION: This report suggests that HSI is a feasible technique for intraoperative assessment of tissue oxygenation before gastroesophageal anastomosis and might reduce the incidence of anastomotic failure in the gastrointestinal tract.

Longitudinal Analysis of Circulating Tumor Cells in Colorectal Cancer Patients by a Cytological and Molecular Approach: Feasibility and Clinical Application.

INTRODUCTION: Liquid biopsies allowing for individualized risk stratification of cancer patients have become of high significance in individualized cancer diagnostics and treatment. The detection of circulating tumor cells (CTC) has proven to be highly relevant in risk prediction, e.g., in colorectal cancer (CRC) patients. In this study, we investigate the clinical relevance of longitudinal CTC detection over a course of follow-up after surgical resection of the tumor and correlate these findings with clinico-pathological characteristics. METHODS: In total, 49 patients with histologically proven colorectal carcinoma were recruited for this prospective study. Blood samples were analyzed for CTC presence by two methods: first by marker-dependent immunofluorescence staining combined with automated microscopy with the NYONE® cell imager and additionally, indirectly, by semi-quantitative Cytokeratin-20 (CK20) RT-qPCR. CTC quantification data were compared and correlated with the clinico-pathological parameters. RESULTS: Detection of CTC over a post-operative time course was feasible with both applied methods. In patients who were pre-operatively negative for CTCs with the NYONE® method or below the cut-off for relative CK20 mRNA expression after analysis by PCR, a statistically significant rise in the immediate post-operative CTC detection could be demonstrated. Further, in the cohort analyzed by PCR, we detected a lower CTC load in patients who were adjuvantly treated with chemotherapy compared to patients in the follow-up subgroup. This finding was contrary to the same patient subset analyzed with the NYONE® for CTC detection. CONCLUSION: Our study investigates the occurrence of CTC in CRC patients after surgical resection of the primary tumor and during postoperative follow-up. The resection of the tumor has an impact on the CTC quantity and the longitudinal CTC analysis supports the significance of CTC as a prognostic biomarker. Future investigations with an even more extended follow-up period and larger patient cohorts will have to validate our results and may help to define an optimal longitudinal sampling scheme for liquid biopsies in the post-operative monitoring of cancer patients to enable tailored therapy concepts for precision medicine.

Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease.

OBJECTIVE: Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date. DESIGN: We conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry. RESULTS: We demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix. CONCLUSION: HEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.

Loss of hepatic Mboat7 leads to liver fibrosis.

OBJECTIVE: The rs641738C>T variant located near the membrane-bound O-acyltransferase domain containing 7 (MBOAT7) locus is associated with fibrosis in liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease, hepatitis B and C. We aim to understand the mechanism by which the rs641738C>T variant contributes to pathogenesis of NAFLD. DESIGN: Mice with hepatocyte-specific deletion of MBOAT7 (Mboat7Δhep) were generated and livers were characterised by histology, flow cytometry, qPCR, RNA sequencing and lipidomics. We analysed the association of rs641738C>T genotype with liver inflammation and fibrosis in 846 NAFLD patients and obtained genotype-specific liver lipidomes from 280 human biopsies. RESULTS: Allelic imbalance analysis of heterozygous human liver samples pointed to lower expression of the MBOAT7 transcript on the rs641738C>T haplotype. Mboat7Δhep mice showed spontaneous steatosis characterised by increased hepatic cholesterol ester content after 10 weeks. After 6 weeks on a high fat, methionine-low, choline-deficient diet, mice developed increased hepatic fibrosis as measured by picrosirius staining (p<0.05), hydroxyproline content (p<0.05) and transcriptomics, while the inflammatory cell populations and inflammatory mediators were minimally affected. In a human biopsied NAFLD cohort, MBOAT7 rs641738C>T was associated with fibrosis (p=0.004) independent of the presence of histological inflammation. Liver lipidomes of Mboat7Δhep mice and human rs641738TT carriers with fibrosis showed increased total lysophosphatidylinositol levels. The altered lysophosphatidylinositol and phosphatidylinositol subspecies in MBOAT7Δhep livers and human rs641738TT carriers were similar. CONCLUSION: Mboat7 deficiency in mice and human points to an inflammation-independent pathway of liver fibrosis that may be mediated by lipid signalling and a potentially targetable treatment option in NAFLD.

The Digital Abutment Check: An Improvement of the Fully Digital Workflow.

By using modern digitalization techniques, an existing denture can be digitized and aid the provision of a new implant-supported denture according to a fully digital workflow. This includes fully navigated implant surgery and results in an immediately provided prosthetic restoration. However, even with the current digital workflow, it is challenging to achieve a definitive prosthetic restoration in a single treatment session. In order to achieve a definitive denture in as few treatment sessions as possible, we have implemented the digital abutment test. This test modified the existing data set and determined the final restoration. In the present case, the preexisting maxillary removable complete denture was converted into a fixed immediate restoration using the fully digital workflow. The workflow is divided into two treatment phases, each with three treatment sessions, where part of the second phase involves an innovative digital abutment check. The illustrated case shows an effective use of current digital possibilities. Special attention was also paid to a minimally invasive course of therapy.

Isolation and Enumeration of CTC in Colorectal Cancer Patients: Introduction of a Novel Cell Imaging Approach and Comparison to Cellular and Molecular Detection Techniques.

Circulating tumour cells (CTC) were proven to be prognostically relevant in cancer treatment, e.g., in colorectal cancer (CRC). This study validates a molecular detection technique through using a novel cell imaging approach for CTC detection and enumeration, in comparison to a size-based cellular and correlated the data to clinico-pathological characteristics. Overall, 57 CRC patients were recruited for this prospective study. Blood samples were analysed for CTCs by three methods: (1) Epithelial marker immunofluorescence staining combined with automated microscopy using the NYONE® cell imager; (2) isolation by size using membrane filtration with the ScreenCell® Cyto IS device and immunofluorescence staining; (3) detection by semi-quantitative Cytokeratin-20 RT-qPCR. Enumeration data were compared and correlated with clinic-pathological parameters. CTC were detected by either approach; however, with varying positivity rates: NYONE® 36.4%, ScreenCell® 100%, and PCR 80.5%. All methods revealed a positive correlation of CTC presence and higher tumour burden, which was most striking using the ScreenCell® device. Generally, no intercorrelation of CTC presence emerged amongst the applied techniques. Overall, enumeration of CTC after isolation by size demonstrated to be the most reliable strategy for the detection of CTC in CRC patients. Ongoing studies will have to unravel the prognostic value of this finding, and validate this approach in a larger cohort.

Stage IV Colorectal Cancer Patients with High Risk Mutation Profiles Survived 16 Months Longer with Individualized Therapies.

Personalized treatment vs. standard of care is much debated, especially in clinical practice. Here we investigated whether overall survival differences in metastatic colorectal cancer patients are explained by tumor mutation profiles or by treatment differences in real clinical practice. Our retrospective study of metastatic colorectal cancer patients of confirmed European ancestry comprised 54 Americans and 54 gender-matched Germans. The Americans received standard of care, and on treatment failure, 35 patients received individualized treatments. The German patients received standard of care only. Tumor mutations, tumor mutation burden and microsatellite status were identified by using the FoundationOne assay or the IDT Pan-Cancer assay. High-risk patients were identified according to the mutational classification by Schell and colleagues. Results: Kaplan-Meier estimates show the high-risk patients to survive 16 months longer under individualized treatments than those under only standard of care, in the median (p < 0.001). Tumor mutation profiles stratify patients by risk groups but not by country. Conclusions: High-risk patients appear to survive significantly longer (p < 0.001) if they receive individualized treatments after the exhaustion of standard of care treatments. Secondly, the tumor mutation landscape in Americans and Germans is congruent and thus warrants the transatlantic exchange of successful treatment protocols and the harmonization of guidelines.

Clinical performance of non-precious metal double crowns with friction pins in severely reduced dentitions.

OBJECTIVES: Several in vitro studies have investigated the retention of double crowns with friction pins (DCP); however, clinical data on their long-term success have not been reported. We sought to evaluate the 5-year survival rate of DCPs in patients with severely reduced dentition (SRD) and not severely reduced dentition (NSRD). MATERIALS AND METHODS: A total of 158 patients were treated with 182 dentures on 520 abutment teeth between 2006 and 2016. The SRD group included 144 dentures that had been inserted on 314 abutment teeth. We evaluated the influence of age, sex, jaw, number, tooth vitality, and abutment teeth localization (according to Steffel's classification) on the 60-month survival rates of dentures and abutment teeth using the Kaplan-Meier estimator, logrank test, and Cox regression. RESULTS: The cumulative 60-month survival rate was 84.3% (CI 77.1-91.5%) for all dentures; however, the survival rate in the SRD group (80.3%; CI 71.5-89.1%) was significantly lower than in the NSRD group (100%; p = 0.04). Dentures classified in Steffel's class A had the lowest survival rate (51.5%; CI 30.9-72.1%). Number, location, and vitality of the abutment teeth had a significant impact on survival rate. CONCLUSIONS: DCP dentures showed comparable clinical long-term success to double crown systems that have been previously reported in the literature. The number, localization, and vitality of abutment teeth had the greatest influence on the survival rates of denture and abutment teeth. CLINICAL RELEVANCE: DCP dentures have an acceptable 5-year survival rate. Clinical treatment planning must take into account key factors associated with the prognosis of the abutment teeth.