The macroscopic and microscopic anatomy of the oral cavity is complex and unique in the human body. Soft-tissue structures are in close interaction with mineralized bone, but also dentine, cementum ...and enamel of our teeth. These are exposed to intense mechanical and chemical stress as well as to dense microbiologic colonization. Teeth are susceptible to damage, most commonly to caries, where microorganisms from the oral cavity degrade the mineralized tissues of enamel and dentine and invade the soft connective tissue at the core, the dental pulp. However, the pulp is well-equipped to sense and fend off bacteria and their products and mounts various and intricate defense mechanisms. The front rank is formed by a layer of odontoblasts, which line the pulp chamber towards the dentine. These highly specialized cells not only form mineralized tissue but exert important functions as barrier cells. They recognize pathogens early in the process, secrete antibacterial compounds and neutralize bacterial toxins, initiate the immune response and alert other key players of the host defense. As bacteria get closer to the pulp, additional cell types of the pulp, including fibroblasts, stem and immune cells, but also vascular and neuronal networks, contribute with a variety of distinct defense mechanisms, and inflammatory response mechanisms are critical for tissue homeostasis. Still, without therapeutic intervention, a deep carious lesion may lead to tissue necrosis, which allows bacteria to populate the root canal system and invade the periradicular bone via the apical foramen at the root tip. The periodontal tissues and alveolar bone react to the insult with an inflammatory response, most commonly by the formation of an apical granuloma. Healing can occur after pathogen removal, which is achieved by disinfection and obturation of the pulp space by root canal treatment. This review highlights the various mechanisms of pathogen recognition and defense of dental pulp cells and periradicular tissues, explains the different cell types involved in the immune response and discusses the mechanisms of healing and repair, pointing out the close links between inflammation and regeneration as well as between inflammation and potential malignant transformation.
The continued development of transition-metal-mediated C–C bond activation/cleavage methods would provide even more opportunities to implement novel synthetic strategies. We have explored the ...Rh(I)-catalyzed C–C activation of cyclobutanols resident in hydroxylated derivatives of pinene, which proceed in a complementary manner to the C–C bond cleavage that we have observed with many traditional electrophilic reagents. Mechanistic and computational studies have provided insight into the role of C–H bond activation in the stereochemical outcome of the Rh-catalyzed C–C bond activation process. Using this new approach, functionalized cyclohexenones that form the cores of natural products, including the spiroindicumides and phomactin A, have been accessed.
Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy can improve the outcome of patients with advanced metastatic castration-resistant prostate cancer, but patients do not respond ...uniformly. We hypothesized that using the salivary glands as a reference organ can enable selective patient stratification. We aimed to establish a PSMA PET tumor-to-salivary gland ratio (PSG score) to predict outcomes after
LuPSMA.
In total, 237 men with metastatic castration-resistant prostate cancer treated with
LuPSMA were included. A quantitative PSG (qPSG) score (SUV
ratio of whole-body tumor to parotid glands) was semiautomatically calculated on baseline
GaPSMA-11 PET images. Patients were divided into 3 groups: high (qPSG > 1.5), intermediate (qPSG = 0.5-1.5), and low (qPSG < 0.5) scores. Ten readers interpreted the 3-dimensional maximum-intensity-projection baseline
GaPSMA-11 PET images and classified patients into 3 groups based on visual PSG (vPSG) score: high (most of the lesions showed higher uptake than the parotid glands) intermediate (neither low nor high), and low (most of the lesions showed lower uptake than the parotid glands). Outcome data included a more than 50% prostate-specific antigen decline, prostate-specific antigen (PSA) progression-free survival, and overall survival (OS).
Of the 237 patients, the numbers in the high, intermediate, and low groups were 56 (23.6%), 163 (68.8%), and 18 (7.6%), respectively, for qPSG score and 106 (44.7%), 96 (40.5%), and 35 (14.8%), respectively, for vPSG score. The interreader reproducibility of the vPSG score was substantial (Fleiss weighted κ, 0.68). The more than 50% prostate-specific antigen decline was better in patients with a higher PSG score (high vs. intermediate vs. low, 69.6% vs. 38.7% vs. 16.7%, respectively, for qPSG
< 0.001 and 63.2% vs 33.3% vs 16.1%, respectively, for vPSG
< 0.001). The median PSA progression-free survival of the high, intermediate, and low groups by qPSG score was 7.2, 4.0, and 1.9 mo (
< 0.001), respectively, by qPSG score and 6.7, 3.8, and 1.9 mo (
< 0.001), respectively, by vPSG score. The median OS of the high, intermediate, and low groups was 15.0, 11.2, and 13.9 mo (
= 0.017), respectively, by qPSG score and 14.3, 9.6, and 12.9 mo (
= 0.018), respectively, by vPSG score.
The PSG score was prognostic for PSA response and OS after
LuPSMA. The visual PSG score assessed on 3-dimensional maximum-intensity-projection PET images yielded substantial reproducibility and comparable prognostic value to the quantitative score.
An approach to construct enantiopure complex natural product-like frameworks, including the first reported synthesis of a C17 oxygenated taxoid scaffold, is presented. A palladium-catalyzed C–C ...activation/cross-coupling is utilized to access these structures in a short sequence from (+)-carvone; the scope of this reaction is explored.
Osteosarcomas are the most common primary bone tumor while occurrence in the craniofacial skeleton is relatively rare. There are clinical differences of osteosarcomas regarding their location. In ...this regard craniofacial osteosarcomas (COS) have special characteristics. Extracranial osteosarcomas (EOS) occur mainly in the long bones of the extremities (tibia, humerus and femur). These tumors metastasize hematogenically at a very early stage. In comparison, COS are mainly localized in the mandible and maxilla, occur later in life and show significantly less and later metastasis and respond differently to adjuvant therapy. In the literature, clinical characteristics of COS and EOS are rarely compared directly. The aim of this systematic review is to answer the question whether COS and EOS exhibit fundamentally different clinical behavior and how they differ in terms of survival rates and response to different therapies.
A systemic review was performed. Pubmed, Cochrane and Google Scholar were used as search engines. The literature research was done by using clearly defined terms and their links. 124 full texts were selected and evaluated for this review. The inclusion criteria were determined using the PICO model.
COS have significantly better survival rates, especially if they are located in the jawbone. Surgical R0 resection is crucial for therapeutic success. The study situation regarding the benefit of neoadjuvant chemotherapy in COS is very inhomogeneous. There is also no evidence for the benefit of adjuvant radio- or chemotherapy in COS. The large heterogeneity of the studies in terms of therapeutic concept, initial situation of the patients and outcome considered, as well as the small number of patients with craniofacial osteosarcoma were limiting factors.
The results of this study show the clear therapeutic and prognostic differences between COS and EOS and underline the necessity to consider both types of osteosarcoma as independent tumor entities in future studies. Furthermore, the study highlights the importance of surgical R0 resection for the prognosis of COS patients. There is no evidence for therapeutic benefit of adjuvant/neoadjuvant radio-/chemotherapy in R0 resected COS cases.
Historically, molecular imaging of somatostatin receptor (SSTR) expression in patients with neuroendocrine tumors (NET) was performed using SSTR scintigraphy (SRS). Sustained advances in medical ...imaging have led to its gradual replacement with SSTR positron-emission tomography (SSTR-PET). The higher sensitivity in comparison to SRS on the one hand and conventional cross-sectional imaging, on the other hand, enables more accurate staging and allows for image quantification. In addition, in recent years, a growing body of evidence has assessed the prognostic implications of SSTR-PET-derived prognostic biomarkers for NET patients, with the aim of risk stratification, outcome prognostication, and prediction of response to peptide receptor radionuclide therapy. In this narrative review, we give an overview of studies examining the prognostic value of advanced SSTR-PET-derived (semi-)quantitative metrics like tumor volume, uptake, and composite metrics. Complementing this analysis, a discussion of the current trends, clinical implications, and future directions is provided.
The anatomically complex and often spatially restricted conditions of anastomosis in the head and neck region cannot be adequately reproduced by training exercises on current ex vivo or small animal ...models. With the development of a Realistic Anatomical Condition Experience (RACE) model, complex spatial-anatomical surgical areas and the associated intraoperative complexities could be transferred into a realistic training situation in head and neck surgery. The RACE model is based on a stereolithography file generated by intraoperative use of a three-dimensional surface scanner after neck dissection and before microvascular anastomosis. Modelling of the acquired STL file using three-dimensional processing software led to the model's final design. As a result, we have successfully created an economical, sustainable and realistic model for microsurgical education and provide a step-by-step workflow that can be used in surgical and general medical education to replicate and establish comparable models. We provide an open source stereolithography file of the head-and-neck RACE model for printing for educational purposes. Once implemented in other fields of surgery and general medicine, RACE models could mark a shift in medical education as a whole, away from traditional teaching principles and towards the use of realistic and individualised simulators.
We aimed to systematically determine the impact of tumor burden on 68Ga-prostate-specific membrane antigen-11 (68Ga-PSMA) PET biodistribution by the use of quantitative measurements. Methods: This ...international multicenter, retrospective analysis included 406 men with prostate cancer who underwent 68Ga-PSMA PET/CT. Of these, 356 had positive findings and were stratified by quintiles into a very low (quintile 1, ≤25 cm3), low (quintile 2, 25–189 cm3), moderate (quintile 3, 189–532 cm3), high (quintile 4, 532–1,355 cm3), or very high (quintile 5, ≥1,355 cm3) total PSMA-positive tumor volume (PSMA-VOL). PSMA-VOL was obtained by semiautomatic segmentation of total tumor lesions using qPSMA software. Fifty prostate cancer patients with no PSMA-positive lesions (negative scan) served as a control group. Normal organs, which included salivary glands, liver, spleen, and kidneys, were semiautomatically segmented using 68Ga-PSMA PET images, and SUVmean was obtained. Correlations between the SUVmean of normal organs and PSMA-VOL as continuous and categoric variables by quintiles were evaluated. Results: The median PSMA-VOL was 302 cm3 (interquartile range IQR, 47–1,076 cm3). The median SUVmean of salivary glands, kidneys, liver, and spleen was 10.0 (IQR, 7.7–11.8), 26.0 (IQR, 20.0–33.4), 3.7 (IQR, 3.0–4.7), and 5.3 (IQR, 4.0–7.2), respectively. PSMA-VOL showed a moderate negative correlation with the SUVmean of the salivary glands (r = −0.44, P < 0.001), kidneys (r = −0.34, P < 0.001), and liver (r = −0.30, P < 0.001) and a weak negative correlation with the spleen SUVmean (r = −0.16, P = 0.002). Patients with a very high PSMA-VOL (quintile 5, ≥1,355 cm3) had a significantly lower PSMA uptake in the salivary glands, kidneys, liver, and spleen than did the control group, with an average difference of −38.1%, −40.0%, −43.2%, and −34.9%, respectively (P < 0.001). Conclusion: Tumor sequestration affects 68Ga-PSMA biodistribution in normal organs. Patients with a very high tumor load showed a significantly lower uptake of 68Ga-PSMA in normal organs, confirming a tumor sink effect. As similar effects might occur with PSMA-targeted radioligand therapy, these patients might benefit from increased therapeutic activity without exceeding the radiation dose limit for organs at risk.
We aimed to validate the metric accuracy of a 3-dimensional (3D) facial scanner (FS) and an intraoral scanner (IOS) in capturing the nasolabial region in ex vivo unilateral cleft lip and palate ...(UCLP) models. The nasolabial region of 10 UCLP models was scanned using a 3D FS as well as an IOS and a previously validated stationary 3D scanner as a reference. Intraoral scan was performed directly on the UCLP models. In order to apply the FS on the models, they were embedded in a 3D printed sample face. Both test groups were aligned to the reference by applying a section-based best-fit algorithm. Subsequent analysis of the metric deviation from the reference was performed with a 3D analysis tool. Mean distance and integrated distance served as main parameters for surface and volume comparison. Point comparison served as an additional parameter. Statistical analysis was carried out using t-test for unconnected samples. Considering mean distance and integrated distance as main parameters for 3D evaluation of the scanner's accuracy, FS and IOS differ significantly in their metric precision in scanning the cleft model compared to the reference. The IOS proved to be significantly more accurate than the FS compared to the previously described stationary 3D scanner as reference and validated baseline. Further validation of the tested IOS and FS for 3D assessment of the nasolabial region is presented by adding the previously validated ATOS III Triple Scan blue light scanner as a reference. The IOS shows, compared to a validated baseline scan, significantly higher metric precision in experimental cleft model scanning. The collected data provides a basis for clinical application of the IOS for 3D assessment of the nasolabial region.
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