Search

The aim of this study was to analyse the radiological and clinical outcomes of condylar reconstruction by fibula free flap (FFF), comparing conventional freehand and CAD/CAM techniques. Fifteen patients (nine CAD/CAM, six freehand) who underwent condylar reconstruction with a FFF were reviewed retrospectively regarding pre- and postoperative computed tomography/cone beam computed tomography scans and clinical function. After surgery, all patients were free of temporomandibular joint pain. Mean postoperative mouth opening was 30.80 mm, with no significant difference between the freehand and CAD/CAM groups. In all patients, laterotrusion was decreased to the contralateral side (P = 0.002), with no difference between freehand and CAD/CAM, while the axis of mouth opening deviated to the side of surgery (P 0.001). All patients showed significant radiological deviation of the fibular neocondyle in the laterocaudal direction (lateral: P = 0.015; caudal: P = 0.001), independent of the technique. In conclusion, reconstruction of the mandibular condyle by FFF provided favourable functional results in terms of mouth opening, reduction of pain, and mandibular excursions. Radiological deviation of the neocondyle and deviation of laterotrusion and mouth opening did not impair clinical function. CAD/CAM planning facilitated surgery, decreased the surgery time, and improved the fit of the neocondyle in the fossa.

Zwangsbedingte Entnahmen gab es in der Forstwirtschaft schon früher. Die Klimaprognosen sowie die in letzter Zeit viel zu häufig auftretenden «Jahrhundertsommer» zeigen jedoch klar, dass ein rascher Waldumbau dringend nötig ist. Die Bayerischen Staatsforsten (BaySF) arbeiten deshalb gezielt und beschleunigt an der Bewältigung der Auswirkungen des Klimawandels. Das Ziel ist ein vielfältig gemischter, strukturierter Wald mit einem hohen Anteil an klimaangepassten Baumarten. Ein zentraler Baustein der Risikovorsorge in der Baumartenmischung ist das 4-Baum-Konzept: Nach Möglichkeit werden mindestens vier (Wirtschafts-)Baumarten in angemessenen Anteilen (mind. 5 %) erhalten oder eingebracht, wovon mindestens drei Baumarten klimatolerant sein müssen. Auch die Vorausverjüngung in Altholzbeständen ist wichtig zur Risikovorsorge. Für die Wahl der geeigneten Baumarten im Klimawandel haben die BaySF gemeinsam mit Forstverwaltung und Wissenschaft eine Vielzahl von Baumarten in vier verschiedene Kategorien eingeteilt. Alternative Baumarten und alternative Herkünfte heimischer Baumarten werden in kleinflächigen Praxisanbauversuchen getestet. Die genetische Herkunft der Baumarten muss zweifelsfrei gesichert sein. Zudem ist die Jagd ein wichtiger Erfolgsfaktor beim Waldumbau.

Zusammenfassung Hintergrund Umfangreiche Daten aus prospektiven klinischen Studien liefern einen hohen Evidenzgrad für den Einsatz von CDK4/6-Hemmern in Kombination mit einer endokrinen Therapie (CDK4/6i + ET) als Standard bei der First-Line-Behandlung von metastatischem HER2-negativen hormonrezeptorpositiven (HER2−/HR+) Brustkrebs. Reale Daten von Patientinnengruppen, die damit in der Praxis behandelt wurden, liefern Erkenntnisse über Veränderungen von Patientenmerkmalen und Prognosen im Laufe der Zeit. Methoden Die Daten wurden dem prospektiven praxisbezogenen PRAEGNANT-Register (NCT02 338 167) entnommen. Die eingeschlossenen Patientinnen hatten fortgeschrittenen primären und metastasierten HER2−/HR+ Brustkrebs. Die gewählten Therapien, das progressionsfreie Überleben und das Gesamtüberleben der jeweiligen Therapie sowie die Zeitspanne, während der die Behandlung erfolgte, werden dargelegt. Ergebnisse Nachdem CDK4/6-Hemmer erstmals im November 2016 eingesetzt wurden, stieg die Häufigkeit ihres Einsatzes schnell an. In den letzten Jahren (2018–2022) wurden ca. 70–80 % aller Patientinnengruppen mit CDK4/6-Hemmern behandelt; eine endokrine Monotherapie wurde rund 10 % und eine Chemotherapie ungefähr 15 % aller Patientinnen verabreicht. Die schlechteste Prognose hatten Patientinnen, die eine Chemotherapie erhielten. Seit Kurzem erhalten hauptsächlich Patientinnen mit guter Prognose eine endokrine Monotherapie; Patientinnen, die eine Chemotherapie erhalten, haben eine ungünstigere Prognose. Das progressionsfreie Überleben und das Gesamtüberleben von mit CDK4/6i + ET behandelten Patientinnen blieb über einen längeren Zeitraum ähnlich, obwohl sich die Patientenmerkmale änderten. Schlussfolgerung Die Behandlung mit CDK4/6i + ET entwickelte sich rasch zum First-Line-Therapiestandard für Patienten mit fortgeschrittenem Mammakarzinom. Seit der Einführung von CDK4/6i + ET wird die endokrine Monotherapie nur bei Patientinnen mit einer sehr günstigen Prognose eingesetzt, während Chemotherapie meist nur an Patientinnen verabreicht wird, die eine eher ungünstige Prognose haben. Veränderungen der Patientenmerkmale scheinen die Prognose von mit CDK4/6i + ET behandelten Patientinnen nicht zu beeinflussen.

Aims Transoesophageal echocardiography (TOE) has increasingly been described as a possible complementary and point-of-care approach for patients with cardiac arrest (CA). It provides information about potentially reversible causes and prognosis and allows monitoring of resuscitation efforts without affecting ongoing chest compressions. The aim of this study was to assess the feasibility of TOE performed by emergency physicians (EPs) during CA in an emergency department (ED). Methods and results This prospective study was performed at the Department of Emergency Medicine at the Medical University of Vienna from February 2020 to February 2021. All patients of ≥18 years old presenting with ongoing resuscitation efforts were screened. After exclusion of potential contraindications, a TOE examination was performed and documented by EPs according to a standardized four-view imaging protocol. The primary endpoint represents feasibility defined as successful probe insertion and acquisition of interpretable images. Of 99 patients with ongoing non-traumatic CA treated in the ED, a total of 62 patients were considered to be examined by TOE. The examination was feasible in 57 patients (92%) [females, 14 (25%), mean age 53 ± 13, and witnessed collapse 48 (84%)]. Within these, the examiners observed 51 major findings in 32 different patients (66%). In 21 patients (37%), these findings led to a direct change of therapy. In 18 patients (32%), the examiner found ventricular contractions without detectable pulse. No TOE-related complications were found. Conclusion Our findings suggest that EPs may be able to acquire and interpret TOE images in the majority of patients during CA using a standardized four-view imaging protocol.

We present a historical study of Quantum Technology 2.0 using more than 66,000 papers from 1980 to 2020 that had been assigned to four subfields. We applied the method reference publication year spectroscopy to respective publication sets of the subfields in order to identify their historical roots and seminal papers. We found 126 of them in total, 43 in quantum metrology and sensing, 46 in quantum communication and cryptography, 42 in quantum computing, and 33 in quantum information science–with a significant overlap between subfields–which are all discussed in their relevance for the respective subfield. We compared the subfields regarding their interrelationship and distinctiveness in terms of their most influential papers and were able to deduce a common core set of five seminal publications in all four subfields.

Background Comprehensive data from prospective clinical trials have led to a high level of evidence establishing CDK4/6 inhibitors in combination with endocrine treatment (CDK4/6i + ET) as a standard for the treatment of HER2-negative, hormone receptor-positive (HER2− HR+) breast cancer patients in the first-line advanced therapy setting. Data on patient populations that have been treated in the real-world setting may provide an insight into changes of patient characteristics and prognosis over time. Methods The data were extracted from the prospective real-world registry PRAEGNANT (NCT02338167). Patients had to have HER2− HR+ advanced breast cancer in the first-line metastatic setting. The chosen therapies were described as well as progression-free survival (PFS) and overall survival (OS) in relation to the given therapies and time periods during which they were indicated. Results CDK4/6 inhibitors have been rapidly implemented since their introduction in November 2016. In recent years (2018 – 2022), about 70 – 80% of the patient population have been treated with CDK4/6 inhibitors, while endocrine monotherapy was given to about 10% and chemotherapy to about 15% of all patients. The prognosis was worst in patients treated with chemotherapy. Recently, mainly patients with a good prognosis are being treated with endocrine monotherapy, and patients who are treated with chemotherapy have an unfavorable prognosis. The PFS and OS of patients treated with CDK4/6i + ET have remained similar over time despite changes in patient characteristics. Conclusion A treatment with CDK4/6i + ET has rapidly become the therapy standard for patients in the first-line advanced breast cancer setting. After the implementation of CDK4/6i + ET, endocrine monotherapy is only given to patients with a very favorable prognosis, while chemotherapy is provided to patients with a rather unfavorable prognosis. These changes in patient characteristics did not seem to influence the prognosis of patients treated with CDK4/6i + ET.

(1) Background: The radial forearm flap (RFF) has evolved as the flap of choice for intraoral mucosal reconstructions, providing thin and pliable skin with a safe blood supply. Perforator flaps such as the anterolateral thigh (ALT) flap are increasingly being discussed for the same applications. (2) Methods: Patient history, treatment details, and outcome of 12 patents with moderate to extended defects of the lip and/or nose area that were reconstructed by a folded radial forearm flap were retrospectively evaluated for oncologic and functional outcomes. (3) Results: The mean oncologic and functional follow-up were 21.1 (min. 3.8; max. 83.3) and 31.2 (min. 6; max. 96) months, respectively. All flaps survived without revision. In eight cases, major lip defects were reconstructed by an RFF; in six patients, the palmaris longus tendon was included for lip suspension. The functional results in terms of eating, drinking, and mouth opening were good in five cases, while three patients were graded as fair due to moderate drooling. In seven cases, the major parts of the nose were reconstructed with two good and five fair (nostril constriction in three cases) functional results. (4) Conclusions: The folded RFF remains a unique free flap option for complex three-dimensional lip and nose reconstructions in terms of flexibility, versatility, and robustness.

The aim of this study was to investigate the clinical, histopathologic, and immunologic differences of oral squamous cell carcinoma of never-smokers/never-drinkers and smokers/drinkers. Immunohistochemical staining for CD4, CD8, FoxP3, CD1a, and p16 was performed in 131 oral squamous cell carcinomas from smokers/drinkers and never-smokers/never-drinkers. Associations of smoking/drinking status with clinicopathologic data, immunohistochemical antibody expression, and survival were examined. Oral squamous cell carcinoma in never-smokers/never-drinkers was associated with the female gender (p < 0.001). Never-smokers/never-drinkers were older at diagnosis than smokers/drinkers (p < 0.001). Never-smokers/never-drinkers had more tumors in the maxilla, mandible, and tongue (p < 0.001). Pre-existing oral potentially malignant disorders appeared to be more common in never-smokers/never-drinkers (p < 0.001). Perineural invasion was more common in smokers/drinkers (p = 0.039). Never-smoking/never-drinking was associated with better overall survival (p = 0.004) and disease-specific survival (p = 0.029). High CD4+ T cell infiltration was associated with never-smoking/never-drinking (p = 0.008). Never-smokers/never-drinkers also showed increased CD8+ T cell infiltration (p = 0.001) and increased FoxP3+ Treg infiltration (p = 0.023). Furthermore, the total group of tumor-infiltrating lymphocytes was associated with never smoking/never drinking (p = 0.005). To conclude oral squamous cell carcinoma of the never-smokers/never-drinkers appears to be a distinct type of tumor, as it appears to have unique clinical and pathologic features and a more immunogenic microenvironment.

The aim of this study was to examine the prevalence of synchronous upper aerodigestive tract (UAT) tumors within oral squamous cell carcinoma (OSCC) patients, and to specify distinct risk groups who benefit from panendoscopy. Definite clinical and pathohistological characteristics, as well as overall and recurrence-free survival (OAS and RFS, respectively) of OSCC patients with and without synchronous second UAT tumors, carcinomas in situ, or higher-grade dysplasia/metaplasia, were evaluated based on a retrospective population-based cohort study, including alignment with cancer registry data. Out of 727 included OSCC patients, 465 cases (64.0%) received panendoscopy. Among these, 18 UAT tumors were detected, all of which were linked to patients with a positive history of nicotine abuse. Every synchronous UAT tumor was revealed by panendoscopy, which, analyzed as an independent staging procedure, was accompanied by a low complication rate (1.7%). When illuminating the impact of a second UAT tumor in OSCC patients, survival analysis revealed reduced 5-year OAS (63.9% vs 43.5%, p = 0.010) and RFS (57.1% vs 32.4%, p = 0.016) for patients with a second oncology diagnosis of the UAT. Within the limitations of the study, it seems that panendoscopy should be performed in the majority of patients suffering from OSCC, because most of them have a history of smoking and drinking, which correlates with an increased risk of developing synchronous UAT tumors.

Background: More than two thirds of patients with advanced breast cancer (ABC) have estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) tumors. In most countries, current standard-of-care first-line treatments include an aromatase inhibitor or fulvestrant, a selective ER degrader, combined with cyclin-dependent kinase 4/6 inhibitors. Concurrent use of luteinizing hormone-releasing hormone agonists is recommended for men and premenopausal women with ABC. Nevertheless, almost all ABCs eventually become resistant to endocrine therapy and the disease is incurable in these cases. New therapies are needed to combat endocrine therapy resistance, maintain patient health-related quality-of-life, and delay the need for chemotherapy. AZD9833 (camizestrant) is a highly potent, next-generation selective ER degrader and pure ER antagonist that has demonstrated anticancer properties across a range of preclinical models, including those with ER-activating mutations (Scott et al, AACR 2020). A Phase I dose-escalation and expansion study (SERENA-1) has demonstrated that AZD9833 is well tolerated and has a promising antitumor activity when administered alone or in combination with the cyclin-dependent kinase 4/6 inhibitor palbociclib (Baird et al, SABCS 2020). SERENA-4 (NCT04711252) is a randomized, multicenter, double-blind, Phase III trial to evaluate the safety and efficacy of AZD9833 in combination with palbociclib for patients with ER+/HER2− ABC who have not received systemic treatment in the advanced disease setting. Methods: SERENA-4 will enroll 1342 patients with de novo or recurrent ER+/HER2− ABC who have not previously received systemic treatment for their locoregionally recurrent or metastatic disease. Patients with recurrent disease must have received adjuvant aromatase inhibitor or tamoxifen therapy for at least 24 months without relapse. Patients will be randomized 1:1 to receive oral treatment with either (a) AZD9833 75 mg once daily, palbociclib 125 mg once daily for 21 days followed by 7 days off treatment and a placebo for anastrozole 1 mg once daily or (b) anastrozole 1 mg once daily, palbociclib (same as active arm) and a placebo for AZD9833 75 mg once daily. Men and premenopausal women will also receive a luteinizing hormone-releasing hormone agonist. The primary endpoint is progression-free survival (PFS; up to 5 years). Secondary endpoints include overall survival (up to 8 years), second PFS, time to chemotherapy, objective response rate, and changes in health-related quality-of-life measures. Enrollment began in January 2021. As of 02 July 2021, the number of open sites is 57 across 15 countries. Acknowledgments: We thank Julia Mawer, PhD, of Oxford PharmaGenesis, Oxford, UK, for providing medical writing support funded by AstraZeneca Funding: The SERENA-4 trial is funded and overseen by AstraZeneca. © 2021 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2021 ASCO Annual Meeting. All rights reserved. Citation Format: Fabrice André, Seock-Ah Im, Patrick Neven, Richard D Baird, Johannes Ettl, Matthew P Goetz, Erika Hamilton, Hiroji Iwata, Zefei Jiang, Anil Abraham Joy, Vincent Haddad, Andrew Walding, Manuel Selvi Miralles, Cynthia Huang Bartlett, Antonio Llombart-Cussac. SERENA-4: A Phase III comparison of AZD9833 (camizestrant) plus palbociclib, versus anastrozole plus palbociclib, for patients with ER-positive/HER2-negative advanced breast cancer who have not previously received systemic treatment for advanced disease [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-11-06.

Background: Loss-of-function mutations in genes encoding components of the homologous recombination DNA damage response (DDR) machinery, notably BRCA1/2, are associated with tumor sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPi). In EMBRACA, the PARPi TALA improved progression-free survival (PFS) (HR [95% CI] 0.54 [0.41-0.71], P Citation Format: Hope S. Rugo, Joanne L. Blum, A. Douglas Laird, Sara A. Hurvitz, Johannes Ettl, Lida A. Mina, Kyung-Hun Lee, Anthony Gonçalves, Rinat Yerushalmi, Young-Hyuck Im, Miguel Martin, Louis Fehrenbacher, Henri H. Roché, Ying Chen, Silvana Lanzalone, Jijumon Chelliserry, Wolfgang Eiermann, Jennifer K. Litton. Identification of PD-L1+ status as a candidate predictive biomarker of response to talazoparib (TALA) in the phase 3 EMBRACA study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-08.

This supplementary appendix contains a listing of all the investigators involved in the ABRAZO study. It also includes information regarding key eligibility criteria for the study. Finally, a figure showing progression-free survival and overall survival by cohort is given.

Supplementary Data from Determinants of Response to Talazoparib in Patients with HER2-Negative, Germline BRCA1/2-Mutated Breast Cancer

Purpose:To assess talazoparib activity in germline BRCA1/2 mutation carriers with advanced breast cancer.Patients and Methods:ABRAZO (NCT02034916) was a two-cohort, two-stage, phase II study of talazoparib (1 mg/day) in germline BRCA mutation carriers with a response to prior platinum with no progression on or within 8 weeks of the last platinum dose (cohort 1) or ≥3 platinum-free cytotoxic regimens (cohort 2) for advanced breast cancer. Primary endpoint was confirmed objective response rate (ORR) by independent radiological assessment.Results:We enrolled 84 patients (cohort 1, n = 49; cohort 2, n = 35) from May 2014 to February 2016. Median age was 50 (range, 31–75) years. Triple-negative breast cancer (TNBC) incidence was 59% (cohort 1) and 17% (cohort 2). Median number of prior cytotoxic regimens for advanced breast cancer was two and four, respectively. Confirmed ORR was 21% [95% confidence interval (CI), 10–35; cohort 1] and 37% [95% CI, 22–55; cohort 2]. Median duration of response was 5.8 and 3.8 months, respectively. Confirmed ORR was 23% (BRCA1), 33% (BRCA2), 26% (TNBC), and 29% (hormone receptor–positive). The most common all-grade adverse events (AE) included anemia (52%), fatigue (45%), and nausea (42%). Talazoparib-related AEs led to drug discontinuation in 3 (4%) patients. In an exploratory analysis, longer platinum-free interval was associated with higher response rate in cohort 1 (0% ORR with interval 6 months).Conclusions:Talazoparib exhibited promising antitumor activity in patients with advanced breast cancer and germline BRCA mutation.

Purpose:PARP inhibitors (PARPi) have demonstrated efficacy in tumors with germline breast cancer susceptibility genes (gBRCA) 1 and 2 mutations, but further factors influencing response to PARPi are poorly understood.Experimental Design:Breast cancer tumor tissue from patients with gBRCA1/2 mutations from the phase III EMBRACA trial of the PARPi talazoparib versus chemotherapy was sequenced using FoundationOne CDx.Results:In the evaluable intent-to-treat population, 96.1% (296/308) had ≥1 tumor BRCA (tBRCA) mutation and there was strong concordance (95.3%) between tBRCA and gBRCA mutational status. Genetic/genomic characteristics including BRCA loss of heterozygosity (LOH; identified in 82.6% of evaluable patients), DNA damage response (DDR) gene mutational burden, and tumor homologous recombination deficiency [assessed by genomic LOH (gLOH)] demonstrated no association with talazoparib efficacy.Conclusions:Overall, BRCA LOH status, DDR gene mutational burden, and gLOH were not associated with talazoparib efficacy; however, these conclusions are qualified by population heterogeneity and low patient numbers in some subgroups. Further investigation in larger patient populations is warranted.

Supplementary Figure from Determinants of Response to Talazoparib in Patients with HER2-Negative, Germline BRCA1/2-Mutated Breast Cancer

Simple Summary In brief, this is the first prospective study using a multicentric approach to investigate the effectiveness of adjuvant radiotherapy in patients with early squamous cell carcinoma of the oral cavity (T1/2) and the oropharynx (T1) with one single ipsilateral cervical lymph node metastasis (pN1) in terms of overall survival, time to progression, and quality of life. After the inclusion of 209 patients into this prospective multicentric comprehensive cohort study (2009–2021) and analyzing the follow-up data, we can conclude that adjuvant radiotherapy in patients with early squamous cell carcinoma of the oral cavity and oropharynx does not seem to influence overall survival, but it positively affects the time to progression. However, irradiated patients report a significantly decreased quality of life up to three years after therapy compared to the observation group. Abstract (1) Background: Evaluation of impact of adjuvant radiation therapy (RT) in patients with oral squamous cell carcinoma of the oral cavity/oropharynx (OSCC) of up to 4 cm (pT1/pT2) and solitary ipsilateral lymph node metastasis (pN1). A non-irradiated group with clinical follow-up was chosen for control, and survival and quality of life (QL) were compared; (2) Methods: This prospective multicentric comprehensive cohort study included patients with resected OSCC (pT1/pT2, pN1, and cM0) who were allocated into adjuvant radiation therapy (RT) or observation. The primary endpoint was overall survival. Secondary endpoints were progression-free survival and QL after surgery; (3) Results: Out of 27 centers, 209 patients were enrolled with a median follow-up of 3.4 years. An amount of 137 patients were in the observation arm, and 72 received adjuvant irradiation. Overall survival did not differ between groups (hazard ratio (HR) 0.98 [0.55–1.73], p = 0.94). There were fewer neck metastases (HR 0.34 [0.15–0.77]; p = 0.01), as well as fewer local recurrences (HR 0.41 [0.19–0.89]; p = 0.02) under adjuvant RT. For QL, irradiated patients showed higher values for the symptom scale pain after 0.5, two, and three years (all p < 0.05). After six months and three years, irradiated patients reported higher symptom burdens (impaired swallowing, speech, as well as teeth-related problems (all p < 0.05)). Patients in the RT group had significantly more problems with mouth opening after six months, one, and two years (p < 0.05); (4) Conclusions: Adjuvant RT in patients with early SCC of the oral cavity and oropharynx does not seem to influence overall survival, but it positively affects progression-free survival. However, irradiated patients report a significantly decreased QL up to three years after therapy compared to the observation group.

Orbital floor fractures represent a common fracture type of the midface and are standardly diagnosed clinically as well as radiologically using linear measurement methods. The aim of this study was to evaluate the accuracy of diagnostic measurements of isolated orbital floor fractures based on two-dimensional (2D) and three-dimensional (3D) measurement techniques. A cohort of 177 patients was retrospectively and multi-centrically evaluated after surgical treatment of an orbital floor fracture between 2010 and 2020. In addition to 2D and 3D measurements of the fracture area, further fracture-related parameters were investigated. Calculated fracture areas using the 2D measurement technique revealed an average area of 287.59 mm2, whereas the 3D measurement showed fracture areas with a significantly larger average value of 374.16 mm2 (p < 0.001). On average, the 3D measurements were 1.53-fold larger compared to the 2D measurements. This was observed in 145 patients, whereas only 32 patients showed smaller values in the 3D-based approach. However, the process duration of the 3D measurement took approximately twice as long as the 2D-based procedure. Nonetheless, 3D-based measurement of orbital floor defects provides a more accurate estimation of the fracture area than the 2D-based procedure and can be helpful in determining the indication and planning the surgical procedure.

Background: Evaluating the tumor microenvironment and its influence on clinical management and therapy response is becoming increasingly important. However, only a few studies deal with the spatial distribution of immune cells within the tumor. This study aimed to describe the topology of immune cells in the microenvironment of oral squamous cell carcinoma (OSCC) sectioned by tumor invasion front and tumor center and to test their prognostic relevance regarding patient survival. Methods: A total of 55 OSCC patient specimens were collected retrospectively. The cancer tissue was immunohistochemically stained using an automated tissue stainer Ventana Benchmark Ultra (Roche) and analyzed using discrete expression marker profiles on immune cells. We investigated CD4+ lymphocytes, CD8+ lymphocytes, CD68+ macrophages, CD163+ macrophages, and M1 macrophages regarding their spatial distribution. Results: The statistical analysis revealed that the quantity and distribution of CD4+ (p = 0.007), CD8+ (p < 0.001), CD68+ (p < 0.001), CD163+ cells (p = 0.004), and M1 (p < 0.001) macrophages were significantly higher at the invasion front compared to the tumor center in all observed cases. However, high and low immune cell counts in the tumor center and invasion front were not associated with overall survival. Conclusion: Our results show two distinct immune microenvironments of the tumor center compared to the invasion front. Future studies are needed to explore how these results can be leveraged to improve patient therapy and outcome.

Head and neck squamous cell carcinomas (HNSCCs) evade immune responses through multiple resistance mechanisms. Extracellular vesicles (EVs) released by the tumor and interacting with immune cells induce immune dysfunction and contribute to tumor progression. This study evaluates the clinical relevance and impact on anti-tumor immune responses of gene signatures expressed in HNSCC and associated with EV production/release. Expression levels of two recently described gene sets were determined in The Cancer Genome Atlas Head and Neck Cancer cohort (n = 522) and validated in the GSE65858 dataset (n = 250) as well as a recently published single-cell RNA sequencing dataset (n = 18). Clustering into HPV(+) and HPV(−) patients was performed in all cohorts for further analysis. Potential associations between gene expression levels, immune cell infiltration, and patient overall survival were analyzed using GEPIA2, TISIDB, TIMER, and the UCSC Xena browser. Compared to normal control tissues, vesiculation-related genes were upregulated in HNSCC cells. Elevated gene expression levels positively correlated (P < 0.01) with increased abundance of CD4(+) T cells, macrophages, neutrophils, and dendritic cells infiltrating tumor tissues but were negatively associated (P < 0.01) with the presence of B cells and CD8(+) T cells in the tumor. Expression levels of immunosuppressive factors NT5E and TGFB1 correlated with the vesiculation-related genes and might explain the alterations of the anti-tumor immune response. Enhanced expression levels of vesiculation-related genes in tumor tissues associates with the immunosuppressive tumor milieu and the reduced infiltration of B cells and CD8(+) T cells into the tumor.

Elective tracheotomy (ET) secures the airway and prevents adverse airway-related events as unplanned secondary tracheotomy (UT), prolonged ventilation (PPV) or nosocomial infection. The primary objective of this study was to identify factors predisposing for airway complications after reconstructive lower ja surgery. We reviewed records of patients undergoing mandibulectomy and microvascular bone reconstruction (N = 123). Epidemiological factors, modus of tracheotomy regarding ET and UT, postoperative ventilation time and occurrence of hospital-acquired pneumonia HAP were recorded. Predictors for PPV and HAP, ET and UT were identified. A total of 82 (66.7%) patients underwent tracheotomy of which 12 (14.6%) were performed as UT. A total of 52 (42.3%) patients presented PPV, while 19 (15.4%) developed HAP. Increased operation time (OR 1.004, p = 0.005) and a difficult airway (OR 2.869, p = 0.02) were predictors, while ET reduced incidence of PPV (OR 0.054, p = 0.006). A difficult airway (OR 4.711, p = 0.03) and postoperative delirium (OR 6.761, p = 0.01) increased UT performance. HAP increased with anesthesia induction time (OR 1.268, p = 0.001) and length in ICU (OR 1.039, p = 0.009) while decreasing in ET group (HR 0.32, p = 0.02). OR for ET increased with mounting CCI (OR 1.462, p = 0.002) and preoperative radiotherapy (OR 2.8, p = 0.018). ET should be strongly considered in patients with increased CCI, preoperative radiotherapy and prolonged operation time. ET shortened postoperative ventilation time and reduced HAP.

Bone marrow-derived mesenchymal stromal cells (BMSCs) respond to a variety of tumor cell-derived signals, such as inflammatory cytokines and growth factors. As a result, the inflammatory tumor microenvironment may lead to the recruitment of BMSCs. Whether BMSCs in the tumor environment are more likely to promote tumor growth or tumor suppression is still controversial. In our experiments, direct 3D co-culture of BMSCs with tumor cells from the head and neck region (HNSCC) results in strong expression and secretion of MMP-9. The observed MMP-9 secretion mainly originates from BMSCs, leading to increased invasiveness. In addition to our in vitro data, we show in vivo data based on the chorioallantoic membrane (CAM) model. Our results demonstrate that MMP-9 induces hemorrhage and increased perfusion in BMSC/HNSCC co-culture. While we had previously outlined that MMP-9 expression and secretion originate from BMSCs, our data showed a strong downregulation of MMP-9 promoter activity in HNSCC cells upon direct contact with BMSCs using the luciferase activity assay. Interestingly, the 2D and 3D models of direct co-culture suggest different drivers for the downregulation of MMP-9 promoter activity. Whereas the 3D model depicts a BMSC-dependent downregulation, the 2D model shows cell density-dependent downregulation. In summary, our data suggest that the direct interaction of HNSCC cells and BMSCs promotes tumor progression by significantly facilitating angiogenesis via MMP-9 expression. On the other hand, data from 3D and 2D co-culture models indicate opposing regulation of the MMP-9 promoter in tumor cells once stromal cells are involved.

TRPCs (transient receptor potential classical or cation channels) play a crucial role in tumor biology, especially in the Ca2+ homeostasis in cancer cells. TRPC4 is a pH-sensitive member of this family of proteins. As solid tumors exhibit an inversed pH-gradient with lowered extracellular and increased intracellular pH, both contributing to tumor progression, TRPC4 might be a signaling molecule in the altered tumor microenvironment. This is the first study to investigate the expression profiles of TRPC4 in common skin cancers such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma (MM) and nevus cell nevi (NCN). We found that all SCCs, NCNs, and MMs show positive TRPC4-expression, while BCCs do only in about half of the analyzed samples. These data render TRPC4 an immunohistochemical marker to distinguish SCC and BCC, and this also gives rise to future studies investigating the role of TRPC4 in tumor progression, and especially metastasis as BCCs very rarely spread and are mostly negative for TRPC4.

Late-onset infection of an inserted temporomandibular joint prosthesis is a difficult complication to treat. Most treatment protocols for late prosthetic infections include device replacement. A 40-year-old female patient with an infected and exposed temporomandibular joint prosthesis presented 3 years after implant placement. The patient was treated with prosthesis revision including fistula coverage with a temporalis muscle flap and prolonged antibiotic therapy for 10 weeks. Since completion of treatment, the patient has been infection-free.

Background Adenoid cystic carcinoma (ACC) is a rare type of cancer commonly occurring in salivary glands. It is characterized by slow but infiltrative growth, nerve infiltration and overall poor prognosis, with late recurrence and distant metastasis. The treatment of ACC is still limited to surgery and/or (adjuvant) radiotherapy. Till now no promising systemic therapy option exists. However, various studies deliver promising results after treatment with anti-angiogenetic agents, such as anti-EGFR-antibody Cetuximab or Tyrosinkinase inhibitor Lenvatinib. Methods By using of immunohistological methods we analyzed and compared the macrophage and lymphocyte populations, vascularization, and PD-L1-status in 12 ACC of the salivary glands. Results All cases showed a significant elevation of macrophages with M2 polarization and a higher vascularization in ACC compared to normal salivary gland tissue. The CD4/CD8 quotient was heterogenous. ACC does not show relevant PD-L1 expression. Conclusions The predominant M2 polarization of macrophages in ACC could be responsible for elevated vascularization, as already been proved in other cancer types, that M2 macrophages promote angiogenesis.

Simple Summary Here, we examined the presence and clinical relevance of A20 in oral squamous cell carcinoma (OSCC). Using a tissue microarray (TMA), immunohistochemical A20 expression as well as tumor-infiltrating lymphocytes (TIL) were analyzed. Hereby, A20 expression was significantly increased in TILs and patients with elevated A20 expression in stromal CD3+ cells showed ameliorated survival in uni- as well as multivariable analyses. Abstract A20, known as a potent inhibitor of NF-κB signaling, has been characterized in numerous clinical as well as preclinical studies. Recently, especially in various malignant diseases, the prognostic and therapeutic relevance of A20 was investigated. In oral squamous cell carcinoma (OSCC) however, the characterization of A20 is uncharted territory. We analyzed a tissue microarray (TMA) of 229 surgically-treated OSCC patients (2003–2013). Immunohistochemical (IHC) stainings were performed for A20 and CD3; additionally, standard haematoxylin-eosin staining was applied. IHC findings were correlated with a comprehensive dataset, comprising clinical and pathohistological information. A20 expression was analyzed in tumor cells as well as in tumor infiltrating lymphocytes (TILs) and correlated with the overall survival (OS) and recurrence-free survival (RFS) using uni- and multivariable Cox regression. The median follow-up time was 10.9 years and the A20 expression was significantly decreased in CD3+ TILs compared to mucosa-infiltrating lymphocytes (MILs). In the Kaplan–Meier analyses, higher A20 expression in TILs was correlated with better OS (p = 0.017) and RFS (p = 0.020). In the multivariable survival analysis, A20 overexpression correlated with improved OS (HR: 0.582; 95% CI 0.388–0.873, p = 0.009) and RFS (HR 0.605; 95% CI 0.411–0.889, p = 0.011). Our results indicate a novel prognostic role for A20 in OSCC. Due to its elevated expression in TILs, further research is highly desirable, which therefore could offer new therapeutic opportunities for patients suffering from OSCC.

Journal Netzwerk Frauen- und Geschlechterforschung NRW, vol. 2022, no. 51, p. 58

Die vorliegende bibliometrische Analyse hat neben dem Fachgebiet „Biotechnologie“ die angrenzenden Fachgebiete „Synthetische Biologie“ und „Bioinformatik“ zum Gegenstand. „Synthetische Biologie“ und „Bioinformatik“ überlappen teilweise mit der „Biotechnologie“. Ausgangspunkt für die bibliometrische Analyse sind Publikationen, die in PubMed (National Center for Biotechnology Information) den MeSH-Terms „biotechnology“, „computational biology“ und „synthetic biology“ zugeordnet sind. Betrachtet wurden Publikationen im Zeitraum 2010 bis 2021. Für die Analyse des Citation Impact (Anzahl der Publikationen, die zu den 10% der meist-zitierten in ihrem Fachgebiet und Publikationsjahr gehören) wurde der Publikationszeitraum auf 2010 bis 2019 beschränkt. Das Zitierfenster bezieht sich auf den Zeitraum seit derPublikation bis Ende 2021.

Already a single clothing item (e.g., a Hijab) signals various social characteristics simultaneously – for example, gender (e.g., woman), religion (e.g., Muslim), or values (e.g., modesty). Nevertheless, research on the communication of social identities has paid little attention to the role of attire. Compared to other signals (e.g., voices, faces, body movements), clothing is under greater volitional control, yet less changeable, once put on our bodies. The garments we wear function as humans’ chosen skin in everyday life. Clothing offers a valuable research subject for the study of impression management, especially concerning perceptually ambiguous groups, such as sexual orientation (SO). In this research, we examined systematic differences in dress styles between individuals of varying gender (women vs. men) and SO (lesbian/gay vs. straight) to investigate whether SO is accurately communicated via appearance-related aspects, especially clothing. Therefore, we produced full-body photographs of N = 94 lesbian/gay and straight women and men in everyday dress and additionally measured psychological characteristics potentially moderating whether people express their gender-related social identities through attire (e.g., gender conformity). Images were standardized (e.g., size matching) and subjected to quantitative visual content analysis. For this, we manually coded 63 physical appearance-related attributes (e.g., posture; clothing fit) according to a pre-established codebook.

Transforming growth factor β (TGFβ) is a major component of tumor-derived small extracellular vesicles (TEX) in cancer patients. Mechanisms utilized by TGFβ+ TEX to promote tumor growth and pro-tumor activities in the tumor microenvironment (TME) are largely unknown. TEX produced by head and neck squamous cell carcinoma (HNSCC) cell lines carried TGFβ and angiogenesis-promoting proteins. TGFβ+ TEX stimulated macrophage chemotaxis without a notable M1/M2 phenotype shift and reprogrammed primary human macrophages to a pro-angiogenic phenotype characterized by the upregulation of pro-angiogenic factors and functions. In a murine basement membrane extract plug model, TGFβ+ TEX promoted macrophage infiltration and vascularization (p < 0.001), which was blocked by using the TGFβ ligand trap mRER (p < 0.001). TGFβ+ TEX injected into mice undergoing the 4-nitroquinoline-1-oxide (4-NQO)-driven oral carcinogenesis promoted tumor angiogenesis (p < 0.05), infiltration of M2-like macrophages in the TME (p < 0.05) and ultimately tumor progression (p < 0.05). Inhibition of TGFβ signaling in TEX with mRER ameliorated these pro-tumor activities. Silencing of TGFβ emerges as a critical step in suppressing pro-angiogenic functions of TEX in HNSCC.

BackgroundFace-to-face medical education was restricted during the COVID-19 pandemic, leading to alternative teaching methods. Moodle® (Modular Object-Oriented Dynamic Learning Environment) – an online course format – has not yet been sufficiently evaluated for its feasibility and effectiveness in teaching cardiopulmonary resuscitation.MethodsMedical students in the eighth semester took part in a Moodle® course teaching basic life support, the ABCDE-approach, airway management, and advanced life support. The content was presented using digital background information and interactive videos. A multiple-choice test was conducted at the beginning and at the end of the course. Subjective ratings were included as well.ResultsOut of 594 students, who were enrolled in the online course, 531 could be included in this study. The median percentage of correctly answered multiple-choice test questions increased after completing the course [78.9%, interquartile range (IQR) 69.3–86.8 vs. 97.4%, IQR 92.1–100, p < 0.001]. There was no gender difference in the median percentage of correctly answered questions before (female: 79.8%, IQR 70.2–86.8, male: 78.1%, IQR 68.4–86.8, p = 0.412) or after (female: 97.4%, IQR 92.1–100, male: 96.5%, IQR 92.6–100, p = 0.233) the course. On a 5-point Likert scale, 78.7% of students self-reported ≥4 when asked for a subjective increase in knowledge. Noteworthy, on a 10-point Likert scale, male students self-reported their higher confidence in performing CPR [female 6 (5–7), male 7 (6–8), p < 0.001].ConclusionThe Moodle® course led to a significant increase in theoretical knowledge. It proved to be a feasible substitute for face-to-face courses – both objectively and subjectively.

Transforming growth factor β (TGFβ) is a major component of tumor-derived small extracellular vesicles (TEX) in cancer patients. Mechanisms utilized by TGFβ

Background Impressive survival rates have been achieved for public out-of-hospital cardiac arrest (OHCA) in selected areas (airports and similar places), but residential areas as a location for public OHCA remain unexplored. This study aimed to investigate incidence, survival, and bystander intervention when public OHCA occurs in residential areas. Methods Residential and non-residential areas were defined using Urban Atlas, an open-source database that categorizes urban area surface in the European Union based on land cover use. Residential and non-residential areas were defined based on prespecified Urban Atlas classification. Nature and agricultural areas were excluded. All public OHCAs from 2016–2020 registered with the Danish Cardiac Arrest Registry were included and divided into residential and non-residential areas, excluding OHCAs in nursing homes and medical facilities. The variables have been compared between residential and non-residential areas using the Kruskal Wallis test for non-parametric continuous data and Fischer's exact test for categorical data. A logistic regression model adjusting for age and sex was used to compare bystander cardiopulmonary resuscitation (CPR), bystander defibrillation, and 30-day survival between residential and non-residential areas. A sub-analysis included bystander witnessed OHCAs only. Results A total of 1,939 public OHCAs were included, evenly distributed between residential (969 [0.17 OHCA/km2/year]) and non-residential areas (970 [0.21 OHCA/km2/year]). OHCAs in residential areas differed from those in non-residential areas by having a lower proportion of bystander CPR (84.7% [95% CI: 82.3–86.9%] vs. 88.9% [95% CI: 86.7–90.8%], p-value = 0.007), bystander defibrillation (17.2% [95% CI: 14.9–19.8%] vs. 29.5% [95% CI: 26.6–32.4%], p-value Conclusion Half of all OHCAs in public occur in residential areas. They are less likely to receive bystander interventions and have a lower likelihood of 30-day survival compared to public OHCAs in non-residential areas. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Tryg Foundation

Die malignen Speicheldrusentumoren sind eine extrem heterogene Gruppe seltener Tumoren mit groser klinischer, pathologischer und molekularbiologischer Variabilitat. Die chirurgische Resektion stellt in den meisten Fallen die Therapie der Wahl dar. Bei lokal fortgeschrittenen oder aggressiven malignen Tumoren ist haufig eine adjuvante Radiotherapie indiziert, die das Risiko fur ein Lokalrezidiv reduziert. Kontrovers diskutiert wird das Ausmas der Parotidektomie bei Karzinomen der Glandula parotis, insbesondere die Behandlung des N. facialis. Einigkeit herrscht weitestgehend daruber, diesen Nerv, wann immer moglich, zu erhalten, sofern nicht eine praoperative Parese oder eine offensichtliche intraoperative Tumorinfiltration einem Nervenerhalt entgegenstehen. Resezierte Anteile des N. facialis sollten moglichst sofort rekonstruiert werden. Die Chirurgie der von den kleinen Speicheldrusen ausgehenden Karzinome entspricht weitgehend dem Vorgehen bei Kopf-Hals-Plattenepithelkarzinomen. Bei adenoidzystischen Karzinomen ist aufgrund des perineuralen Wachstums und des haufigen Bezugs zur Schadelbasis eine R0-Resektion oft nicht zu erreichen, was die besondere Bedeutung der adjuvanten Radiotherapie bei dieser Entitat unterstreicht. Die Indikation der elektiven „neck dissection“ im cN0-Fall wird ebenfalls uneinheitlich gestellt. Wahrend einige Autoren die generelle Lymphknotenausraumung bei allen Karzinomen fordern, lautet der uberwiegende Konsens, eine elektive „neck dissection“ bei fortgeschrittener Tumorgrose, High-grade-Karzinomen und erhohtem Sicherheitsbedurfnis durchzufuhren. Die zunehmende Erkenntnis genomischer Alterationen und tumorspezifischer Signalwege eroffnet neue vielversprechende Moglichkeiten zielgerichteter molekularer Therapien im fortgeschrittenen Tumorstadium.

The second quantum technological revolution started around 1980 with the control of single quantum particles and their interaction on an individual basis. These experimental achievements enabled physicists, engineers, and computer scientists to utilize long-known quantum features—especially superposition and entanglement of single quantum states—for a whole range of practical applications. We use a publication set of 54,598 papers from Web of Science, published between 1980 and 2018, to investigate the time development of four main subfields of quantum technology in terms of numbers and shares of publications, as well as the occurrence of topics and their relation to the 25 top contributing countries. Three successive time periods are distinguished in the analyses by their short doubling times in relation to the whole Web of Science. The periods can be characterized by the publication of pioneering works, the exploration of research topics, and the maturing of quantum technology, respectively. Compared to the USA, China’s contribution to the worldwide publication output is overproportionate, but not in the segment of highly cited papers.

The aim of this study was to analyze and compare the accuracy and quality of six 3D printing systems available on the market. Data acquisition was performed with 12 scans of human mandibles using an industrial 3D scanner and saved in STL format. These STL files were printed using six different printing systems. Previously defined distances were measured with a sliding caliper on the 72 printed mandibles. The printed models were then scanned once again. Measurements of volumes and surfaces for the STL files and the printed models were compared. Accuracy and quality were evaluated using industrial software. An analysis of the punctual aberration between the template and the printed model, based on a heat map, was also carried out. Secondary factors, such as costs, production times and expendable materials, were also examined. All printing systems performed well in terms of accuracy and quality for clinical usage. The Formiga P110 and the Form 2 showed the best results for volume, with average aberrations of 0.13 ± 0.23 cm3 and 0.12 ± 0.17 cm3, respectively. Similar results were achieved for the heat map aberration, with values of 0.008 ± 0.11 mm (Formiga P110) and 0.004 ± 0.16 mm (Form 2). Both printers showed no significant difference from the optimal neutral line (Formiga P110, p = 0.15; Form 2, p = 0.60). The cheapest models were produced by the Ultimaker 2+, with an average of 5€ per model, making such desktop printers affordable for rapid prototyping. Meanwhile, advanced printing systems with sterilizable and biocompatible printing materials, such as the Formiga P110 and the Form 2, fulfill the high expectations for maxillofacial surgery.

Purpose Assessment of HER2 overexpression using immunohistochemistry (IHC) and/or in situ hybridisation (ISH) for the detection of HER2 amplifications is standard to identify patients for established HER2-directed treatments. Patients with lower HER2 expression levels have recently also become candidates for novel therapies targeting HER2. This study aimed to assess tumour and patient characteristics and prognosis in patients with advanced breast cancer (aBC), relative to low HER2 expression levels. Methods PRAEGNANT is a prospective aBC registry (NCT02338167), focusing on molecular biomarkers. Patients in all therapy lines receiving any kind of treatment are eligible. This analysis includes patients with conventionally HER2-negative aBC. Clinical outcome was compared in the groups with no (IHC score 0) or with low HER2 expression (IHC 1+, or IHC 2+/ISH negative). Results Low HER2 expression levels in triple-negative aBC patients did not influence progression-free survival. Overall survival appeared poorer in patients with IHC 2+ compared with patients with no HER2 expression in the unadjusted analysis (hazard ratio 2.24, 95% confidence interval 0.1.12–4.47). However, this effect was not maintained in the adjusted analysis. In HER2-negative, hormone receptor–positive patients, low HER2 expression appeared to have no effect on prognosis, neither progression-free survival nor overall survival. Conclusions We could not demonstrate that HER2 expression at a low level and assessed in clinical routine can differentiate patients into prognostic groups. However, the prevalence of patients with a low expression makes this population interesting for clinical trials with potentially active treatments using HER2 as a target.