Antiresorptive agents enhance ossification of free flap reconstructions of the mandible: a radiological retrospective cohort study.

Background: The aim of this study was to investigate the effect of antiresorptive agents on the ossification of reconstructed mandibles by free bone grafts for the first time. Methods: A total of 38 reconstructions of the jaw were retrospectively evaluated for ossification between bone segments by two raters based on postoperative panoramic radiographs. The study group (n = 13) had segmental resection of the mandible and free bone flap reconstruction due to medication-related osteonecrosis of the jaw (MRONJ). The control group (noMRONJ, n = 25) comprised segmental mandibular resections and free bone flap reconstructions due to tumors, chronic osteomyelitis, or trauma without any radiation. Ossification time and influencing factors were evaluated. Results: Both duration of surgery (346 ± 90 min. vs. 498 ± 124 min.; p < 0.001) and hospitalization (8.7 ± 2.8 days vs. 13.4 ± 5.3 days, p = 0.006) were shorter in the MRONJ group compared to the noMRONJ group. Ossification after mandibular reconstruction was significantly faster in the MRONJ study group [224 days, interquartile range (IQR) 175-287] compared to the control group (288 days, IQR 194-445; p < 0.001). Moreover, good initial contact between the segments resulted in faster ossification (p < 0.001) in the MRONJ group. Ossification rate between original and grafted bone or between grafted bone segments only did not differ in both the study and control groups (MRONJ, p = 0.705 vs. control, p = 0.292). The type of antiresorptive agent did not show any significance for ossification. The rate of wound healing disturbances did also not differ between the study and control groups (p = 0.69). Conclusion: Advanced MRONJ (stage 3) can be resected and reconstructed safely with free microvascular bone flaps. Antiresorptive agents enhance the ossification of the bone segments. Optimal initial contact of the bone segments accelerates bone healing. Surgery and hospitalization are markedly shortened in this vulnerable group of MRONJ patients compared to oncologic patients.

Patient's Perception of Outcome after Extracapsular Fractures of the Mandibular Condyle Differs from Objective Evaluation-Experience of a Third-Level Hospital.

Background: The aim of this study is to assess patients' subjective perception of treatment outcome after extracapsular fractures of the mandibular condyle. Methods: A questionnaire survey regarding facial nerve palsy (FNP), malocclusion, pain, reduction in maximum mouth opening (MMO) and further discomfort after 3, 6, and 12 months was carried out. Patients aged 18 or more presenting with an extracapsular condylar fracture between 2006 and 2020 were identified by purposive sampling Questionnaires were received from 115 patients. Fractures were classified on the basis of the pre-treatment imaging, the way of treatment was obtained from patients' medical records. Data were analyzed using Pearsons' chi-square-test, descriptive statistics and Student's t-test. Results: 93.0% of the fractures were treated by open reduction and internal fixation (ORIF). MMO reduction was the most common post-treatment complication (55.6%). ORIF was associated with less pain after 3 months (p = 0.048) and lower VAS scores compared to conservative treatment (p = 0.039). Comminuted fractures were more frequently associated with post-treatment malocclusion (p = 0.048), FNP (p = 0.016) and MMO reduction (p = 0.001). Bilateral fractures were significantly accompanied by malocclusion (p = 0.029), MMO reduction (p = 0.038) and pain occurrence (p < 0.001). Conclusions: Patients report less pain after ORIF. Comminuted and bilateral fractures seem to be major risk factors for complications. Subjective perception of complications after extracapsular condylar fractures differs from objectively assessed data.

Correction: Schuderer et al. Risk Factors for Flap Loss: Analysis of Donor and Recipient Vessel Morphology in Patients Undergoing Microvascular Head and Neck Reconstructions. J. Clin. Med. 2023, 12, 5206.

In the original publication by Schuderer et al., there was a mistake in Table 1 as published [...].

Treatment of late-onset temporomandibular joint prosthesis infection by prosthesis revision: a case report.

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.

Animal Bite Injuries to the Face: A Retrospective Evaluation of 111 Cases.

The treatment of bite wounds to the face is discussed controversially in relation to surgery and antibiotics. The aim of this study is a retrospective evaluation of 111 cases of animal bite injuries to the face that presented to our unit of oral and maxillofacial surgery over a 13-year period. Children under 10 years of age were predominantly involved. A total of 94.5% of the assessed injuries were caused by dogs. Wound infections occurred in 8.1%. Lackmann type II was the most common type of injury (36.9%). The perioral area was affected most frequently (40.5%). Primary wound closure was carried out in 74.8% of the cases. In 91.9% of the cases, antibiotic prophylaxis was prescribed. The most often administered type of antibiotic was amoxicillin with clavulanic acid (62.1%). Patients without antibiotics showed an increased infection rate without significance. Wound infections occurred significantly more frequently in wounds to the cheeks (p = 0.003) and when local flap reconstruction was necessary (p = 0.048). Compared to the other surgical treatment options, primary closure showed the lowest infection rates (4.8%, p = 0.029). We recommend antibiotic prophylaxis using amoxicillin with clavulanic acid and wound drains for wounds of Lackmann class II or higher. Primary closure seems to be the treatment of choice whenever possible.

Performance of T-Track® SARS-CoV-2, an Innovative Dual Marker RT-qPCR-Based Whole-Blood Assay for the Detection of SARS-CoV-2-Reactive T Cells.

T-cell immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a central role in the control of the virus. In this study, we evaluated the performance of T-Track® SARS-CoV-2, a novel CE-marked quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay, which relies on the combined evaluation of IFNG and CXCL10 mRNA levels in response to the S1 and NP SARS-CoV-2 antigens, in 335 participants with or without a history of SARS-CoV-2 infection and vaccination, respectively. Of the 62 convalescent donors, 100% responded to S1 and 88.7% to NP antigens. In comparison, of the 68 naïve donors, 4.4% were reactive to S1 and 19.1% to NP. Convalescent donors <50 and ≥50 years of age demonstrated a 100% S1 reactivity and an 89.1% and 87.5% NP reactivity, respectively. T-cell responses by T-Track® SARS-CoV-2 and IgG serology by recomLine SARS-CoV-2 IgG according to the time from the last immunisation (by vaccination or viral infection) were comparable. Both assays showed a persistent cellular and humoral response for at least 36 weeks post immunisation in vaccinated and convalescent donors. Our results demonstrate the very good performance of the T-Track® SARS-CoV-2 molecular assay and suggest that it might be suitable to monitor the SARS-CoV-2-specific T-cell response in COVID-19 vaccinations trials and cross-reactivity studies.

Novel Three-Dimensional and Non-Invasive Diagnostic Approach for Distinction between Odontogenic Keratocysts and Ameloblastomas.

Aim of this study was to demonstrate the diagnostic ability to differentiate odontogenic keratocysts (OKCs) from ameloblastomas (AMs) based on computed tomography (CT) or cone beam computed tomography (CBCT) scans. Preoperative CT and CBCT scans from 2004 to 2019 of OKCs and AMs were analyzed in 51 participants. Lesions were three-dimensionally (3D) assessed and Hounsfield units (HU) as well as gray scale values (GSV) were quantified. Calculated HU spectra were compared within the same imaging modalities using unpaired t-tests and correlated with participants characteristics by calculating Pearsons correlation coefficients. Within the CT scans, AMs had highly significantly higher HU values compared to OKCs (43.52 HU and 19.79 HU, respectively; p < 0.0001). Analogous, within the CBCT scans, AMs had significantly higher GSV compared to OKCs (-413.76 HU and -564.76 HU, respectively; p = 0.0376). These findings were independent from participants' gender and age, anatomical site, and lesion size, indicating that the HU- and GSV-based difference reflects an individual configuration of the lesion. HU and GSV spectra calculated from CT and CBCT scans can be used to discriminate between OKCs and AMs. This diagnostic approach represents a faster and non-invasive option for preoperative diagnosis of such entities and has potential to facilitate therapeutic decision making.

Thin PDS Foils Represent an Equally Favorable Restorative Material for Orbital Floor Fractures Compared to Titanium Meshes.

Orbital floor fractures (OFFs) are common injuries of the midface and may result in long-term complications. The aim of this study was to compare two restoration materials, PDS foils and titanium meshes, with regards to (1) clinical outcome and (2) reduction in orbital volume. The monocentric discovery cohort was analyzed retrospectively and included 476 patients with OFFs treated between 2010 and 2020. A subcohort of 104 patients (study cohort) with isolated OFFs and available high-resolution imaging material was used for volume measurements. Postoperative complications were not significantly different between patients treated with different restoration materials. Prevalence of revision surgery was significantly higher in patients treated with thick PDS foils (25 mm). OFFs treated with PDS foils and titanium meshes showed a significant reduction in orbital volume (p = 0.0422 and p = 0.0056, respectively), however, this volume decrease was significantly less pronounced in patients treated with PDS foils alone (p = 0.0134). Restoration using PDS foil in an isolated OFF reduces the orbital volume to a lesser extent than titanium mesh. Class III patients according to the classification of Jaquiéry with a missing bony ledge medial to the infraorbital fissure particularly benefit from restoration with PDS foils due to a lower reduction in the orbital volume. Regarding short- and long-term postoperative complications, a PDS foil thickness of 0.15 mm appears equivalent to titanium mesh in the treatment of OFFs.

Risk Factors for Flap Loss: Analysis of Donor and Recipient Vessel Morphology in Patients Undergoing Microvascular Head and Neck Reconstructions.

In microvascular head and neck reconstruction, various factors such as diabetes, alcohol consumption, and preoperative radiation hold a risk for flap loss. The primary objective of this study was to examine the vessel morphology of both recipient and donor vessels and to identify predictors for changes in the diameters of H.E.-stained specimens associated with flap loss in a prospective setting. Artery and vein samples (N = 191) were collected from patients (N = 100), with sampling from the recipient vessels in the neck area and the donor vessels prior to anastomosis. External vessel diameter transverse (ED), inner vessel diameter transverse (ID), thickness vessel intima (TI), thickness vessel media (TM), thickness vessel wall (TVW), and intima-media ratio (IMR) for the recipient (R) and transplant site (T) in arteries (A) and veins (V) were evaluated using H.E. staining. Flap loss (3%) was associated with increased ARED (p = 0.004) and ARID (p = 0.004). Preoperative radiotherapy led to a significant reduction in the outer diameter of the recipient vein in the neck (p = 0.018). Alcohol consumption (p = 0.05), previous thrombosis (p = 0.007), and diabetes (p = 0.002) were associated with an increase in the total thickness of venous recipient veins in the neck. Diabetes was also found to be associated with dilation of the venous media in the neck vessels (p = 0.007). The presence of cardiovascular disease (CVD) was associated with reduced intimal thickness (p = 0.016) and increased total venous vessel wall thickness (p = 0.017) at the transplant site. Revision surgeries were linked to increased internal and external diameters of the graft artery (p = 0.04 and p = 0.003, respectively), while patients with flap loss showed significantly increased artery diameters (p = 0.004). At the transplant site, alcohol influenced the enlargement of arm artery diameters (p = 0.03) and the intima-media ratio in the radial forearm flap (p = 0.013). In the anterolateral thigh, CVD significantly increased the intimal thickness and the intima-media ratio of the graft artery (p = 0.01 and p = 0.02, respectively). Patients with myocardial infarction displayed increased thickness in the A. thyroidea and artery media (p = 0.003). Facial arteries exhibited larger total vessel diameters in patients with CVD (p = 0.03), while facial arteries in patients with previous thrombosis had larger diameters and thicker media (p = 0.01). The presence of diabetes was associated with a reduced intima-media ratio (p < 0.001). Although the presence of diabetes, irradiation, and cardiovascular disease causes changes in vessel thickness in connecting vessels, these alterations did not adversely affect the overall success of the flap.

Head and neck oncology management in the time of COVID-19: results of a head and neck cancer center.

PURPOSE: Given the concerns about the effects of the COVID-19 pandemic on cancer care, we analyzed the treatment quality of the head and neck cancer center Regensburg before and throughout 2 years of the pandemic. We included data of 3 years to reflect the extended pandemic period as new developments continued to influence its course. METHODS: This retrospective review included all patients diagnosed with head and neck cancer in 2019, 2020, and 2021 who had not started treatment elsewhere prior to being referred to the head and neck cancer center. We compared tumor characteristics and times to therapy of patients diagnosed before COVID-19 in 2019 (n = 253), during COVID-19 in 2020 (n = 206), and in a phase of partial normalization in a persistent pandemic situation in 2021 (n = 247). RESULTS: Our data revealed no decrease in diagnoses or drift in stages toward more advanced stages. There was an increased percentage of diagnoses confirmed at the head and neck cancer center from 2019 (57.3%) to 2020 (68.0%) and to 2021 (65.6%) compared to confirmation at other institutions (2019, 42.7%; 2020, 32.0%; 2021, 34.4%; P = 0.041). Surgery and radiotherapy were performed with the same frequency. The median days between diagnosis and surgery were decreased in 2020 (19.5 days; P = 0.049) and 2021 (20.0 days; P = 0.026) in comparison to 2019 (23 days). The days to radiotherapy were not affected. CONCLUSION: The data indicate a consistent oncological performance for head and neck cancer patients in all waves of the pandemic and thereafter without a decrease in diagnoses or shift in stages.

Treatment of extracapsular fractures of the mandibular condylar process: A retrospective evaluation of 377 cases.

BACKGROUND/AIM: Mandibular condylar fractures represent 25%-35% of all mandibular fractures. Despite profound research, there is still a controverse debate about treating these fractures conservatively or by open reduction and internal fixation (ORIF). The aim of this study is to analyse the outcome after open and closed treatment of extracapsular mandibular condyle fractures regarding general characteristics, post-treatment malocclusion, facial nerve palsy (FNP), maximum mouth opening (MMO) and parotid complications. METHODS: A retrospective cohort of 377 fractures (350 open, 27 closed treatment) was reviewed by reference to clinical and radiological pre- and postoperative documentation. Follow-up period was 12 months. Pearsons' chi-square-test, correlations, Kruskal-Wallis test and t-test were carried out for statistical analysis. RESULTS: The dominant type of fracture was type II in Spiessl and Schroll classification (50.1%). In the open treated fractures, the most common approach was retromandibular transparotid (91.7%). Post-treatment malocclusion occurred in 18.0% and was significantly increased in bilateral fractures (p = .039), in luxation fractures (p = .016) and in patients with full dentition (p = .004). After open reduction and internal fixation (ORIF), temporary FNP was documented in 7.1% whereas a permanent paresis occurred in 1.7%. FNP was significantly associated with high fractures (p = .001), comminution (p = .028) and increased duration of surgery (p = .040). Parotid complications were significantly associated with revision surgery (p = .009). Post-treatment reduction of MMO mainly occurred in female patients (p < .001) as well as in patients with bilateral fractures (p < .001), high fractures (p = .030) and concomitant mandibular (p = .001) and midfacial fractures (p = .009). CONCLUSION: Malocclusion seems to be the most frequent long-term complication after open reduction and osteosynthesis of extracapsular mandibular condyle fractures. We suggest ORIF by a transparotid approach to be an appropriate treatment with a low complication rate regarding especially FNP for extracapsular fractures of the mandibular condyle.

The Folded Radial Forearm Flap in Lip and Nose Reconstruction-Still a Unique Choice.

(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.

Direct Anthropometry Overestimates Cranial Asymmetry-3D Digital Photography Proves to Be a Reliable Alternative.

This study compared manual and digital measurements of plagiocephaly and brachycephaly in infants and evaluated whether three-dimensional (3D) digital photography measurements can be used as a superior alternative in everyday clinical practice. A total of 111 infants (103 with plagiocephalus and 8 with brachycephalus) were included in this study. Head circumference, length and width, bilateral diagonal head length, and bilateral distance from the glabella to the tragus were assessed by manual assessment (tape measure and anthropometric head calipers) and 3D photographs. Subsequently, the cranial index (CI) and cranial vault asymmetry index (CVAI) were calculated. Measured cranial parameters and CVAI were significantly more precise using 3D digital photography. Manually acquired cranial vault symmetry parameters were at least 5 mm lower than digital measurements. Differences in CI between the two measuring methods did not reach significance, whereas the calculated CVAI showed a 0.74-fold decrease using 3D digital photography and was highly significant (p < 0.001). Using the manual method, CVAI calculations overestimated asymmetry, and cranial vault symmetry parameters were measured too low, contributing to a misrepresentation of the actual anatomical situation. Considering consequential errors in therapy choices, we suggest implementing 3D photography as the primary tool for diagnosing deformational plagiocephaly and positional head deformations.

Two-Dimensional Post-Traumatic Measurements of Orbital Floor Blowout Fractures Underestimate Defect Sizes Compared to Three-Dimensional Approaches.

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.

Performance of T-Track® TB, a Novel Dual Marker RT-qPCR-Based Whole-Blood Test for Improved Detection of Active Tuberculosis.

Tuberculosis (TB) is one of the leading causes of death by an infectious disease. It remains a major health burden worldwide, in part due to misdiagnosis. Therefore, improved diagnostic tests allowing the faster and more reliable diagnosis of patients with active TB are urgently needed. This prospective study examined the performance of the new molecular whole-blood test T-Track® TB, which relies on the combined evaluation of IFNG and CXCL10 mRNA levels, and compared it to that of the QuantiFERON®-TB Gold Plus (QFT-Plus) enzyme-linked immunosorbent assay (ELISA). Diagnostic accuracy and agreement analyses were conducted on the whole blood of 181 active TB patients and 163 non-TB controls. T-Track® TB presented sensitivity of 94.9% and specificity of 93.8% for the detection of active TB vs. non-TB controls. In comparison, the QFT-Plus ELISA showed sensitivity of 84.3%. The sensitivity of T-Track® TB was significantly higher (p < 0.001) than that of QFT-Plus. The overall agreement of T-Track® TB with QFT-Plus to diagnose active TB was 87.9%. Out of 21 samples with discordant results, 19 were correctly classified by T-Track® TB while misclassified by QFT-Plus (T-Track® TB-positive/QFT-Plus-negative), and two samples were misclassified by T-Track® TB while correctly classified by QFT-Plus (T-Track® TB-negative/QFT-Plus-positive). Our results demonstrate the excellent performance of the T-Track® TB molecular assay and its suitability to accurately detect TB infection and discriminate active TB patients from non-infected controls.

Elective Tracheotomy in Patients Receiving Mandibular Reconstructions: Reduced Postoperative Ventilation Time and Lower Incidence of Hospital-Acquired Pneumonia.

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.

TGFß carrying exosomes in plasma: potential biomarkers of cancer progression in patients with head and neck squamous cell carcinoma.

OBJECTIVES: Contributions of TGFß to cancer progression are well documented. However, plasma TGFß levels often do not correlate with clinicopathological data. We examine the role of TGFß carried in exosomes isolated from murine and human plasma as a contributor to disease progression in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: The 4-nitroquinoline-1-oxide (4-NQO) mouse model was used to study changes in TGFß expression levels during oral carcinogenesis. In human HNSCC, TGFß and Smad3 protein expression levels and TGFB1 gene expression were determined. Soluble TGFß levels were evaluated by ELISA and TGFß bioassays. Exosomes were isolated from plasma using size exclusion chromatography, and TGFß content was quantified using bioassays and bioprinted microarrays. RESULTS: During 4-NQO carcinogenesis, TGFß levels in tumour tissues and in serum increased as the tumour progressed. The TGFß content of circulating exosomes also increased. In HNSCC patients, TGFß, Smad3 and TGFB1 were overexpressed in tumour tissues and correlated with increased soluble TGFß levels. Neither TGFß expression in tumours nor levels of soluble TGFß correlated with clinicopathological data or survival. Only exosome-associated TGFß reflected tumour progression and correlated with tumour size. CONCLUSIONS: Circulating TGFß+ exosomes in the plasma of patients with HNSCC emerge as potential non-invasive biomarkers of disease progression in HNSCC.

Tumor gene signatures that correlate with release of extracellular vesicles shape the immune landscape in head and neck squamous cell carcinoma.

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.

Prehabilitation of dysphagia in the therapy of head and neck cancer- a systematic review of the literature and evidence evaluation.

Background: Prehabilitation is becoming increasingly important in oncology because of the significant survival benefits that the reduction of malnutrition provide. Specifically, tumor- and therapy-related dysphagia leads to malnutrition in more than half of head and neck tumor patients. Studies describe the positive effects of an early onset of swallow-specific prehabilitation on the protection of the swallowing function. This paper intents to evaluate the existing evidence on the efficacy of preventive forms of swallowing therapy. Methods: A systematic literature search was performed in February 2022 in the Cochrane Library, MEDLINE via PubMed, and ClinicalTrials.gov databases for randomized controlled trials investigating preventive swallowing therapy in head and neck tumor patients. This Procedure complies with the PRISMA statement. The RCTs were evaluated by using the PEDro Scale and the Cochrane Risk of Bias tool RoB2. Results: Five randomized-controlled trials with 423 participants were identified. Four Studies showed moderate to high quality in the PEDro analysis, one showed less. The risk of bias was high in all studies because there was no possibility for blinding and there were high dropout rates. Heterogeneity in interventions, measurement instruments, measurement time points, and outcomes limits a general statement about which swallowing exercises are suitable for the prevention of dysphagia in head and neck tumor patients. Evidence is provided for short-term effects (≤24 months) on functional aspects of swallowing and quality of life. Overall, a decreasing adherence over time was observed in the intervention groups. Discussion: Initial studies describe swallowing-specific prehabilitation programs in head and neck tumor patients as effective, at least in the short term, whereas long-term effects need to be further investigated. At the current time the evidence base for clear recommendations does not appear to be sufficiently high and studies share a high risk of bias. Further well-designed research, especially considering the conditions in the national health care system, is needed. Other: There was no funding and no registration.

TGFß+ small extracellular vesicles from head and neck squamous cell carcinoma cells reprogram macrophages towards a pro-angiogenic phenotype.

Transforming growth factor ß (TGFß) is a major component of tumor-derived small extracellular vesicles (TEX) in cancer patients. Mechanisms utilized by TGFß+ 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 TGFß and angiogenesis-promoting proteins. TGFß+ 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, TGFß+ TEX promoted macrophage infiltration and vascularization (p < 0.001), which was blocked by using the TGFß ligand trap mRER (p < 0.001). TGFß+ 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 TGFß signaling in TEX with mRER ameliorated these pro-tumor activities. Silencing of TGFß emerges as a critical step in suppressing pro-angiogenic functions of TEX in HNSCC.