Digital analysis of the human maxilla to enable semistandardized template tool reconstructions with free fibula transplants.

OBJECTIVES: This study analyzed the human maxilla to support the development of mean-value-based cutting guide systems for maxillary reconstruction, bridging the gap between freehand techniques and virtual surgical planning (VSP). MATERIALS AND METHODS: This retrospective cohort study used routine CT scans. DICOM data enabled 3D modelling and the maxilla was divided into four regions: paranasal (R1), facial maxillary sinus wall (R2), zygomatic bone (R3) and alveolar process (R4). Surface comparisons were made with a reference skull. Statistical analyses assessed anatomical variations, focusing on mean distance (Dmean), area of valid distance (AVD), integrated distance (ID) and integrated absolute distance (IAD). The study addressed hemimaxillectomy defects for two-segmental reconstructions using seven defined bilateral points to determine segmental distances and angles. RESULTS: Data from 50 patients showed R2 as the most homogeneous and R4 as the most heterogeneous region. Significant age and gender differences were found in R3 and R4, with younger patients and females having more outliers. Cluster analysis indicated that males had R1 and R3 positioned anterior to the reference skull. The mean angle for segmental reconstruction was 131.24° ± 1.29°, with anterior segment length of 30.71 ± 0.57 mm and posterior length of 28.15 ± 0.86 mm. CONCLUSIONS: Anatomical analysis supported the development of semistandardized segmental resection approaches. Although gender and anatomical differences were noted, they did not significantly impact the feasibility of mean-value-based cutting-guide systems. CLINICAL RELEVANCE: This study provides essential anatomical data for creating cost-effective and efficient reconstruction options for maxillary defects, potentially improving surgical outcomes and expanding reconstructive possibilities beyond current techniques.

Early morbidity and mortality after one-stage bilateral shoulder arthroplasty.

PURPOSE: One-stage bilateral shoulder arthroplasty has the advantage of requiring a single hospital stay and a single anaesthesia. The topic has been little reported, unlike one stage bilateral hip and knee arthroplasty, which have demonstrated their interest. The aim of the present study was to determine peri- and early post-operative morbidity and mortality after this procedure. The study hypothesis was that peri- and early post-operative morbidity and mortality in one stage bilateral shoulder arthroplasty is low in selected patients and that satisfaction is high. METHODS: A single-centre retrospective study assessed peri- and early post-operative morbidity and mortality in one stage bilateral shoulder arthroplasty. Twenty-one patients, aged < 80 years, with ASA score ≤ 3, were consecutively operated on between 1999 and 2020. Indications comprised primary osteoarthritis, aseptic osteonecrosis, inflammatory arthritis, massive rotator cuff tear, and dislocation fracture, involving both shoulders. RESULTS: There were no early deaths. The complication rate was 10% (4/21 cases). No prosthesis dislocation or sepsis was reported. Mean blood loss was 145 ± 40 cc, mean surgery time 164 ± 63 min, and mean hospital stay five ± four days. Only one patient required postoperative transfusion. Functional results at six months showed significantly improved range of motion and good patient satisfaction. CONCLUSIONS: One-stage bilateral shoulder arthroplasty was feasible in selected patients. Mortality was zero, and morbidity was low. Surgery time was reasonable and required no repositioning. Postoperative home help is indispensable for patient satisfaction during rehabilitation.

An ex vivo model for education and training of unilateral cleft lip surgery.

BACKGROUND: Unilateral cleft lip surgery is a complex procedure, and the outcome depends highly on the surgeon's experience. Digital simulations and low-fidelity models seem inadequate for effective surgical education and training. There are only few realistic models for haptic simulation of cleft surgery, which are all based on synthetic materials that are costly and complex to produce. Hence, they are not fully available to train and educate surgical trainees. This study aims to develop an inexpensive, widely available, high-fidelity, ex vivo model of a unilateral cleft lip using a porcine snout disc. METHODS: A foil template was manufactured combining anatomical landmarks of the porcine snout disc and the anatomical situation of a child with a unilateral cleft. This template was used to create an ex vivo model of a unilateral cleft lip from the snout disc. Millard II technique was applied on the model to proof its suitability. The individual steps of the surgical cleft closure were photo-documented and three-dimensional scans of the model were analysed digitally. Sixteen surgical trainees were instructed to create a unilateral cleft model and perform a unilateral lip plasty. Their self-assessment was evaluated by means of a questionnaire. RESULTS: The porcine snout disc proved highly suitable to serve as a simulation model for unilateral cleft lip surgery. Millard II technique was successfully performed as we were able to perform all steps of unilateral cleft surgery, including muscle suturing. The developed foil-template is reusable on any porcine snout disc. The creation of the ex vivo model is simple and inexpensive. Self-assessment of the participants showed a strong increase in comprehension and an eagerness to use the model for surgical training. CONCLUSIONS: A porcine snout disc ex vivo model of unilateral cleft lips was developed successfully. It shows many advantages, including a haptic close to human tissue, multiple layers, low cost, and wide and rapid availability. It is therefore very suitable for teaching and training beginners in cleft surgery and subsequently improving surgical skills and knowledge. Further research is needed to finally assess the ex vivo model's value in different stages of the curriculum of surgical residency.

An ex vivo model for education and training of bilateral cleft lip surgery.

BACKGROUND: Bilateral cleft lip surgery is very challenging and requires a high level of skill, knowledge and experience. Existing high-fidelity simulation models that can be used by novice cleft surgeons to gain experience and expand their knowledge are rare and expensive. In this study, we developed a bilateral cleft lip model using porcine snout discs, which are available anywhere and inexpensive. METHODS: Anatomic reference points of a patient with a bilateral cleft lip were superimposed with landmarks of the porcine snout disc on a foil template. The template was used to construct an ex vivo bilateral cleft lip model. Surgery was performed on the model according to Millard and the surgical steps were photodocumented analogous to two clinical cases of bilateral cleft lip surgery. The suitability of the model was further tested by twelve participants and evaluated using self-assessment questionnaires. RESULTS: The bilateral cleft lip ex vivo model made of a porcine snout disc proved to be a suitable model with very low cost and ease of fabrication, as the template is reusable on any snout disc. The Millard procedure was successfully performed and the surgical steps of the lip plasty were simulated close to the clinical situation. Regarding the nasal reconstruction, the model lacks three-dimensionality. As a training model, it enhanced the participants comprehension of cleft surgery as well as their surgical skills. All participants rated the model as valuable for teaching and training. CONCLUSIONS: The porcine snout discs can be used as a useful ex vivo model for bilateral cleft lip surgery with limitations in the construction of the nose, which cannot be realistically performed with the model due to anatomical differences with humans. Benefits include a realistic tissue feel, the simulation of a multi-layered lip construction, a wide and rapid availability and low cost. This allows the model to be used by novice surgeons also in low-income countries. It is therefore useful as a training model for gaining experience, but also as a model for refining, testing and evaluating surgical techniques for bilateral lip plasty.

Validation of the shoulder range of motion software for measurement of shoulder ranges of motion in consultation: coupling a red/green/blue-depth video camera to artificial intelligence.

PURPOSE: Clinical evaluation of the shoulder range of motion (RoM) may vary significantly depending on the surgeon. We aim to validate an automatic shoulder RoM measurement system associating image acquisition by an RGB-D (red/green/blue-depth) video camera to an artificial intelligence (AI) algorithm. METHODS: Thirty healthy volunteers were included. A 3D RGB-D sensor that simultaneously generated a colour image and a depth map was used. Then, an open-access convolutional neural network algorithm that was programmed for shoulder recognition provided a 3D motion measure. Each volunteer adopted a randomized position successively. For each position, two observers made a visual (EyeREF) and goniometric measurement (GonioREF), blind to the automated software which was implemented by an orthopaedic surgeon. We evaluated the inter-tester intra-class correlation (ICC) between observers and the concordance correlation coefficient (CCC) between the three methods. RESULTS: For manual evaluations EyeREF and GonioREF, ICC remained constantly excellent for the widest motions in the vertical plane (i.e., abduction and flexion). It was very good for ER1 and IR2 and fairly good for adduction, extension, and ER2. Differences between the measurements' means of EyeREF and shoulder RoM was significant for all motions. Compared to GonioREF, shoulder RoM provided similar results for abduction, adduction, and flexion and EyeREF provided similar results for adduction, ER1, and ER2. The three methods showed an overall good to excellent CCC. The mean bias between the three methods remained under 10° and clinically acceptable. CONCLUSION: RGB-D/AI combination is reliable in measuring shoulder RoM in consultation, compared to classic goniometry and visual observation.

Lateral acromioplasty cannot sufficiently reduce the critical shoulder angle if preoperatively measured over 40°.

PURPOSE: To investigate whether arthroscopic lateral acromion resection can sufficiently reduce the critical shoulder angle (CSA) without damaging deltoid muscle insertion. METHODS: Ninety patients who underwent arthroscopic rotator cuff (RC) repair were retrospectively analysed. According to the preoperative CSA, patients were categorized as Group I (CSA < 35°) and Group II (CSA ≥ 35°). Additional arthroscopic lateral acromion resection was performed in Group II. The CSA was measured 1 week postoperatively, while RC integrity and the deltoid attachment were assessed at 3, 6 and 12 months via ultrasound. Deltoid function was evaluated using the Akimbo test, in which patients place their hands on the iliac crest with abduction in the coronal plane and internal rotation of the shoulder joint while simultaneously flexing the elbow joint and pronating the forearm. RESULTS: Large and massive RC tears were more prevalent in Group II (p = 0.017). In both groups, the CSA reduction was statistically significant (Group I = 1°: range 0°-3°, Group II = 3.7°: range 1°-8°; p < 0.001). When the preoperative CSA was > 40°, the respective postoperative CSA remained > 35° in 83.3% of cases (p < 0.001). Final shoulder strength was correlated with the amount of CSA reduction (rho = 0.41, p = 0.002). The postoperative CSA was higher, but not significantly different (n.s.), in patients with re-torn (36°, range 32°-40°) than with healed RC (33°, range 26°-38°). No clinical detachment or hypotrophy of the deltoid was observed with the Akimbo test and ultrasound evaluation. CONCLUSIONS: Arthroscopic lateral acromion resection is a safe procedure without affecting deltoid muscle origin or function, and it is effective in significantly reducing the CSA. However, the CSA cannot always be reduced to < 35°, especially in patients with preoperative CSA values > 40°. LEVEL OF EVIDENCE: III.

The interplay of stress and work-related musculoskeletal disorders in dental practitioners.

OBJECTIVES: Prevalence of work-related musculoskeletal disorders (WRMSDs) among general dental practitioners and orthodontists is approximated to range between 64% and 93%. Etiology of WRMSDs in the mentally and physically demanding occupation remains unclear, for which reason the aim of the study was to clarify the interplay of physical, psychological, and mental factors on WRMSDs. METHOD AND MATERIALS: Of 94 orthodontists and 187 general dental practitioners (mean age = 35 years) questioned using an online survey, 84% reported persisting tension or pain in the back, neck, or shoulders. While 71% of females were employed (29% self-employed), only 39% of male participants were employed. Cluster analysis was used to characterize dental practitioners according to their movement profile and the moderating effect of stress on certain WRMSDs. RESULTS: Three movement profiles of general dental practitioners and orthodontists were significantly predictive of WRMSD. The minority could be characterized as healthy (n = 45), whereas twice as many reported nearly twice as much pain (n = 90). Stress proved to be a strong, significant moderator of WRMSDs in relation to sex, employment status, and body mass index. CONCLUSION: The prevalence of WRMSDs found was alarming. Given the feminization of dentistry, and that being female, stressed, and an employee (rather than self-employed) is a significant predictor of WRMSDs, this represents a danger to the German health system.

The glenoid track concept is insufficient to predict Bankart failures: a computed tomography scan study.

Background: The glenoid track concept identifies patients with "off-track" (engaging) Hill-Sachs lesions (HSLs) as poor candidates for arthroscopic Bankart repair (ABR) due to the high risk of shoulder instability recurrence. Purpose: To retrospectively calculate the glenoid track index, using preoperative computed tomography (CT) scans, in a cohort of patients with failed ABR. We hypothesized that all patients with a failed ABR would have engaging ("off-track") HSLs on preoperative CT scan. Type of Study: CT scan study. Methods: Preoperative CT scan of 45 patients, seen in our facility for failed ABR, was used to retrospectively calculate the glenoid track index. The risk of recurrence was also calculated for each patient using Instability Severity Index Score (ISI-Score) and Glenoid Track Instability Management Score (GTIMS). There were 37 failed isolated ABRs and 8 associated HS remplissage. The mean t age at surgery was 24 years (range, 15-52) and instability recurred at a mean of 29 months postoperative (range, 3-167). Results: Preoperative CT scan imaging identified "off-track" bony lesions in 85% of patients (38/45) and "on-track" lesions in 15% (7/45). No significant differences were noted between the 2 groups (off-track vs. on-track) regarding patient age, hyperlaxity, sports participation, size of HS lesion, or ISI-Score. The mean glenoid bone loss was 15.7% (range, 4-36%) with mean HS width was greater than 20 mm in 66% of CT scans. The preoperative ISI-Score was predictive of failures (>3 points in all patients) with no difference between on-track and off-track patients (6.3 ± 1.7 vs. 6.6 ± 1.7, P = .453). By contrast, the GTIMS did not predict failures as there was a significant difference between GTIMS for on-track and off-track patients (2.1 ± 1.3 vs. 6.6 ± 1.7). Conclusions: The glenoid track concept alone is insufficient to predict Bankart failures: in the present series of failed ABR, 15% of shoulders had "on-track" (non-engaging) lesions on preoperative CT scan. In patients, with "on-track" bony lesions, the ISI-Score is a useful predictive tool to detect patients at risk of failure, while the GTIMS is not.

Development of a porcine training model for microvascular fasciocutaneous free flap reconstruction.

BACKGROUND: In reconstructive surgery, improvements are needed in the effective teaching of free flap surgery. There is a need for easily accessible and widely available training without high financial costs or ethical concerns while still providing a realistic experience. Our aim was to develop an appropriate training model for microvascular flaps. METHODS: We identified pig head halves as most appropriate regarding availability, cost, and realism. These accrue largely by the food industry, so no animals need to be sacrificed, making it more ethical from an animal welfare perspective. We evaluated the suitability as flap donor site and analyzed the vascular anatomy of 51 specimens. RESULTS: Anatomical evaluation revealed a reliable and constant vascular anatomy, allowing the design of a flap model that can effectively illustrate the entire process of microvascular flap surgery. The process was divided into 6 key steps. The flap can be harvested after marking the vascular pedicle 5.3 cm from the lateral corner of the mouth. Skin island design and subsequent tissue dissection follow until a fasciocutaneous flap is raised, similar to a radial flap. Upon completion of flap harvesting, it can be freely transferred for defect reconstruction. Microvascular anastomosis can be performed on recipient vessels in the cervical region, and the difficulty can be individually adjusted. CONCLUSIONS: The developed training model is a reasonable compromise in terms of surgical realism, availability, didactic value, and cost/time effectiveness. We believe it is a powerful and effective tool with high potential for improving surgical education and training.

Developing an optimised method for accurate wear testing of dental materials using the 'Rub&Roll' device.

Dental materials are challenged by wear processes in the oral environment and should be evaluated in laboratory tests prior to clinical use. Many laboratory wear-testing devices are high-cost investments and not available for cross-centre comparisons. The 'Rub&Roll' wear machine enables controlled application of force, chemical and mechanical loading, but the initial design was not able to test against rigid antagonist materials. The current study aimed to probe the sensitivity of a new 'Rub&Roll' set-up by evaluating the effect of force and test solution parameters (deionized water; water + abrasive medium; acid + abrasive medium) on the wear behaviour of direct and indirect dental resin-based composites (RBCs) compared with human molars against 3D-printed rod antagonists. Molars exhibited greater height loss than RBCs in all test groups, with the largest differences recorded with acidic solutions. Direct RBCs showed significantly greater wear than indirect RBCs in the groups containing abrasive media. The acidic + abrasive medium did not result in increased wear of RBC materials. The developed method using the 'Rub&Roll' wear machine in the current investigation has provided a sensitive wear test method to allow initial screening of resin-based composite materials compared with extracted human molars under the influence of different mechanical and erosive challenges.

Glomus tumor of the scapular neck with axillary nerve compression at the shoulder. A case report.

Background: Glomus tumors, also known as benign acral tumors are extremely rare. Previous glomus tumors from other regions of the body have been linked to neurological compression symptoms, however axillary compression at the scapular neck has never been described. Case presentation: Here, we report a case of axillary nerve compression in a 47-year-old man, secondary to a glomus tumor of the neck of the right scapula, initially misdiagnosed with biceps tenodesis performed and no pain improvement. The magnetic resonance imaging demonstrated a well-contoured, 12 mm tumefaction at the inferior pole of the scapular neck T2-hyperintense and T1-isointense and interpreted as a neuroma. An axillary approach allowed the dissection of the axillary nerve, and the tumor was completely removed. The pathological anatomical analysis resulted in a nodular red lesion measuring 14 × 10 mm, delimited and encapsulated with a definitive diagnostic of glomus tumor. The neurologic symptoms and pain disappeared 3 weeks after surgery and the patient reported satisfaction with the surgical procedure. After 3 months, the results remain stable with a complete resolution of the symptoms. Conclusions: In cases of unexplained and atypical pain in the axillary area, and to avoid potential misdiagnoses and inappropriate treatments, an in-depth exploration for a compressive tumor should be performed as a differential diagnosis.

Recipient bed perfusion as a predictor for postoperative complications in irradiated patients with microvascular free tissue transfer of the head and neck area: a clinical analysis of 191 microvascular free flaps.

PURPOSE: Despite microvascular free tissue transfer being the mainstay of care in the reconstruction of larger maxillofacial defects, a significant number of patients experience postoperative complications due to impaired blood supply of the flap. In this context, the early influence of recipient bed perfusion remains unclear, but there is evidence that it is associated with free flap viability immediately after surgery. METHODS: We analyzed flap and recipient bed perfusion within the first 2 weeks after surgery by using the oxygen-to-see device. One hundred ninety-one patients who underwent free flap surgery in our department were included. RESULTS: Flow parameters were higher and postoperative complications were less frequent in radial forearm free flaps compared to any other type of flap. Flow parameters of the recipient bed were higher than transferred tissue at all times, implicating flap autonomization is not completed within 2 weeks. Previous radiotherapy significantly decreased flow parameters of the recipient bed but not of the flaps. Furthermore, irradiated patients with postoperative complications were found to have reduced flow parameters of their recipient bed compared to non-irradiated patients with postoperative complications. CONCLUSION: We conclude that monitoring of recipient bed perfusion is useful for detecting flap compromise of irradiated patients in the early postoperative period.

3D assessment of the nasolabial region in cleft models comparing an intraoral and a facial scanner to a validated baseline.

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.

A novel approach to microsurgical teaching in head and neck surgery leveraging modern 3D technologies.

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.

Determination of factors associated with early readmission of patients with mental illness in two cities in Colombia during 2018.

INTRODUCTION: Early rehospitalisation in mental health units (SMHUs) is when a patient needs to be readmitted in the first 30 days after receiving discharge, and is mainly due to recurrent decompensation of their mental illness. This phenomenon is related to a worse prognosis and has an impact on the family, social and work environment. Absenteeism from work and additional hospital time are expenses for the health and employment system which have made rehospitalisation a phenomenon of special interest. The present study was carried out with the objective of exploring the factors associated with the readmission of patients with psychiatric illnesses treated in two MHUs during 2018, as well as those modifiable factors that act as protection for this condition. METHODS: Observational, descriptive study with analytical component of cases and controls in two MHUs in different cities of Colombia. Information was obtained by collecting data from the medical records of patients who were admitted between 1 January 2018 and 31 December 2018. The data were collected between 20 February and 27 May 2019. The sample was composed of all the patients who met the criteria for early readmission in both institutions. The study group consisted of 113 patients: (28 cases and 85 controls), matched by by the variables: age, sex, place of hospitalisation and diagnosis. RESULTS: In the two hospital MHUs the diagnoses found were: depression (15.5%), bipolar affective disorder (33.1%) and schizophrenia (37.3%). In Bogotá, the most prevalent was depression (31.1%) and, in Tunja, it was schizophrenia (44.8%). For both institutions, the factor most associated with readmission was alcohol consumption, but other variables of treatment, family nucleus, and individual intervention were also associated with a greater probability of early readmission. CONCLUSIONS: It was possible to demonstrate that the use of atypical and/or depot antipsychotics, hospitalisations longer than 15 days, and prescriptions of less than three drugs at discharge, reduce the number of early readmissions to MHUs.

Early MDO with a Virtually Planned Distractor in a Neonate with Pierre Robin Sequence.

Pierre Robin sequence (PRS) is characterized by mandibular micrognathia, glossoptosis, and airway obstruction. We report a case of a female infant with PRS in combination with deletion of chromosome 4q and cardiac insufficiency due to an atrioventricular septum defect. The child was transferred to our center from a peripheral hospital with respiratory insufficiency. Initially, respiration was ensured using a continuous positive airway pressure (CPAP) device because a Tuebingen plate was not tolerated. After a pediatric cardiac surgery intervention, CPAP ventilation proved to be insufficient, and the young patient had to be resuscitated and endotracheal intubation was required for recurrent severe respiratory failure. To avoid tracheostomy, an interdisciplinary decision was made to perform an early mandibular distraction. In the fifth week of life, two patient-specific internal distractors were implanted after prior virtual surgery planning. This approach allows for shorter surgical time through preoperative vector planning and fabrication of a patient-specific distractor, in combination with reduced morbidity through maximum protection of adjacent structures such as the tooth follicles and inferior alveolar nerves. An advancement of the mandible by 15 mm could be achieved within 2 weeks. Thereafter, the small patient could be extubated successfully, and there was no further episode of major respiratory insufficiency. We demonstrate that mandibular early distraction with a patient-specific distractor is a successful method to treat severe respiratory insufficiency in PRS, and it can prevent the necessity for tracheostomy with the resulting disadvantages. We provide details concerning our therapeutic algorithm, metric analyses, and a discussion of relevant literature.

Beyond PD-L1-Identification of Further Potential Therapeutic Targets in Oral Cancer.

BACKGROUND: The involvement of immune cell infiltration and immune regulation in the progression of oral squamous cell carcinoma (OSCC) is shown. Anti-PD-1 therapy is approved for the treatment of advanced OSCC cases, but not all patients respond to immune checkpoint inhibitors. Hence, further targets for therapeutic approaches are needed. The number of identified cellular receptors with immune checkpoint function is constantly increasing. This study aimed to perform a comparative analysis of a large number of immune checkpoints in OSCC in order to identify possible targets for therapeutic application. MATERIALS AND METHODS: A NanoString mRNA analysis was performed to assess the expression levels of 21 immune regulatory checkpoint molecules in OSCC tissue (n = 98) and healthy oral mucosa (NOM; n = 41). The expression rates were compared between the two groups, and their association with prognostic parameters was determined. Additionally, relevant correlations between the expression levels of different checkpoints were examined. RESULTS: In OSCC tissue, significantly increased expression of CD115, CD163, CD68, CD86, CD96, GITRL, CD28 and PD-L1 was detected. Additionally, a marginally significant increase in CD8 expression was observed. BTLA and PD-1 levels were substantially increased, but the differential expression was not statistically significant. The expression of CD137L was significantly downregulated in OSCC compared to NOM. Correlations between immune checkpoint expression levels were demonstrated, and some occurred specifically in OSCC tissue. CONCLUSIONS: The upregulation of inhibitory receptors and ligands and the downregulation of activators could contribute to reduced effector T-cell function and could induce local immunosuppression in OSCC. Increased expression of activating actors of the immune system could be explained by the increased infiltration of myeloid cells and T-cells in OSCC tissue. The analysis contributes to the understanding of immune escape in OSCC and reveals potential targets for oral cancer immunotherapy.

Case report: Patient specific combination of surgery and immunotherapy in advanced squamous cell carcinoma of the head and neck - a case series and review of literature.

Background: Prognosis of patients with recurrent or metastatic head and neck cancer is generally poor. Adjuvant immunotherapy (IT) featuring immune checkpoint inhibition (ICI) is standard of care in advanced stage head and neck squamous cell carcinoma (HNSCC) and cutaneous squamous cell carcinoma (CSCC). ICI response rates in CSCC are described as higher than in HNSCC. IT is constantly shifting into earlier disease stages which confronts the surgeon with immunotherapeutically pre-treated patients. It is therefore becoming increasingly difficult to assess which patients with symptomatic tumor disease and a lack of curative surgical option might benefit from salvage surgery. Case presentations: The following 6 cases describe therapeutic decision-making regarding ICI and (salvage) surgery in patients with advanced stage HNSCC or CSCC. Cases A and B focus on neoadjuvant ICI followed by salvage surgery. In Cases C and D salvage surgery was performed after short-term stabilization with partial response to ICI. The last two cases (Cases E and F) address the surgical approach after failure of ICI. All cases are discussed in the context of the current study landscape and with focus on individual decision-making. For better understanding, a timetable of the clinical course is given for each case. Conclusions: ICI is rapidly expanding its frontiers into the neoadjuvant setting, frequently confronting the surgeon with heavily pretreated patients. Salvage surgery is a viable therapeutic concept despite the rise of systemic treatment options. Decision-making on surgical intervention in case of a salvage surgery remains an individual choice. For neoadjuvant ICI monitoring regarding pathological tumor response or tumor necrosis rate, we suggest correlation between the initial biopsy and the definite tumor resectate in order to increase its significance as a surrogate marker. Scheduling of neoadjuvant ICI should be further investigated, as recent studies indicate better outcomes with shorter time frames.

Determination of Factors Associated with Early Readmission of Patients with Mental Illness in Two Cities in Colombia During 2018. / Determinación de los factores asociados con el reingreso temprano de pacientes con enfermedad mental en dos ciudades de Colombia durante 2018.

INTRODUCTION: Early rehospitalisation in mental health units (SMHUs) is when a patient needs to be readmitted in the first 30 days after receiving discharge, and is mainly due to recurrent decompensation of their mental illness. This phenomenon is related to a worse prognosis and has an impact on the family, social and work environment. Absenteeism from work and additional hospital time are expenses for the health and employment system which have made rehospitalisation a phenomenon of special interest. The present study was carried out with the objective of exploring the factors associated with the readmission of patients with psychiatric illnesses treated in two MHUs during 2018, as well as those modifiable factors that act as protection for this condition. METHODS: Observational, descriptive study with analytical component of cases and controls in two MHUs in different cities of Colombia. Information was obtained by collecting data from the medical records of patients who were admitted between 1 January 2018 and 31 December 2018. The data were collected between 20 February and 27 May 2019. The sample was composed of all the patients who met the criteria for early readmission in both institutions. The study group consisted of 113 patients: (28 cases and 85 controls), matched by by the variables: age, sex, place of hospitalisation and diagnosis RESULTS: In the two hospital MHUs the diagnoses found were: depression (15.5%), bipolar affective disorder (33.1%) and schizophrenia (37.3%). In Bogotá, the most prevalent was depression (31.1%) and, in Tunja, it was schizophrenia (44.8%). For both institutions, the factor most associated with readmission was alcohol consumption, but other variables of treatment, family nucleus, and individual intervention were also associated with a greater probability of early readmission. CONCLUSIONS: It was possible to demonstrate that the use of atypical and/or depot antipsychotics, hospitalisations longer than 15 days, and prescriptions of less than three drugs at discharge, reduce the number of early readmissions to MHUs.

Neoadjuvant Immunotherapy of Oral Squamous Cell Carcinoma: Case Report and Assessment of Histological Response.

BACKGROUND: The treatment of oral cancer remains challenging due to its infiltrative nature and a high tendency for tumour relapse leading to an overall poor prognosis. In the case of early recurrence, the patient's prognosis deteriorates dramatically, with survival rate dropping to below 30%. Minimal improvements in survival trends in recurrent and advanced stage tumours have been reported in recent decades. Neoadjuvant immunotherapy may represent a new therapeutic approach changing the standard of care in advanced oral cancer therapy. CASE PRESENTATION: We describe the case of a woman in her late 30's who presented in mid-2019 with oral squamous cell carcinoma (OSCC) localized to the floor of the mouth. After initial R0 resection, selective neck dissection, and adjuvant brachytherapy, an early recurrence of OSCC located between the hyoid bone and the mandible was diagnosed at the end of 2019. An off-label treatment regimen was performed with neoadjuvant use of Pembrolizumab 19 days prior to salvage surgery. Radiological and histological assessment of T-cell and programmed cell death protein 1 ligand 1 (PD-L1) expression was performed before and after checkpoint inhibitor application. Neoadjuvant immunotherapy resulted in increased T-cell infiltration and PD-L1 expression, as well as a significant tumour necrosis rate. One cycle of Pembrolizumab led to significant regressive tumour changes with increases in immune infiltration, sclerosis, and necrosis of 75% of the tumour mass with only 25% vital tumour cells remaining. By June 2020, the patient remained without recurrence. CONCLUSIONS: The case presented outlines the potential effects of neoadjuvant immunotherapy in recurrent or advanced OSCC prior to definitive surgical tumour treatment. The benefit of additional adjuvant treatment after histologic response will be discussed. The case is also analysed considering ongoing clinical trials of neoadjuvant immunotherapy for head and neck malignancies.