Reproducibility of c-Met Immunohistochemical Scoring (Clone SP44) for Non-Small Cell Lung Cancer Using Conventional Light Microscopy and Whole Slide Imaging.

Emerging therapies for non-small cell lung cancer targeting c-Met overexpression have recently demonstrated promising results. However, the evaluation of c-Met expression can be challenging. We aimed to study the inter and intraobserver reproducibility of c-Met expression evaluation. One hundred ten cases with non-small cell lung cancer (40 biopsies and 70 surgical specimens) were retrospectively selected in a single laboratory (LPCE) and evaluated for c-Met expression. Six pathologists (4 seniors and 2 juniors) evaluated the H-score and made a 3-tier classification of c-Met expression for all cases, using conventional light microscopy (CLM) and whole slide imaging (WSI). The interobserver reproducibility with CLM gave global Cohen Kappa coefficients (ƙ) ranging from 0.581 (95% CI: 0.364-0.771) to 0.763 (95% CI: 0.58-0.92) using the c-Met 3-tier classification and H-score, respectively. ƙ was higher for senior pathologists and biopsy samples. The interobserver reproducibility with WSI gave a global ƙ ranging from 0.543 (95% CI: 0.33-0.724) to 0.905 (95% CI: 0.618-1) using the c-Met H-score and 2-tier classification (≥25% 3+), respectively. ƙ for intraobserver reproducibility between CLM and WSI ranged from 0.713 to 0.898 for the c-Met H-score and from 0.600 to 0.779 for the c-Met 3-tier classification. We demonstrated a moderate to excellent interobserver agreement for c-Met expression with a substantial to excellent intraobserver agreement between CLM and WSI, thereby supporting the development of digital pathology. However, some factors (scoring method, type of tissue samples, and expertise level) affect reproducibility. Our findings highlight the importance of establishing a consensus definition and providing further training, particularly for inexperienced pathologists, for c-Met immunohistochemistry assessment in clinical practice.

Long-Term Pharmacokinetic Follow-Up of Abiraterone Acetate in Patients with Metastatic Castration-Resistant Prostate Cancer.

This ABIGENE pharmacokinetic (PK) study sought mainly to characterize the unchanged drug PK during long-term abiraterone acetate (AA) administration in advanced prostate cancer patients (81 patients). It was observed that individual AA concentrations remained constant over treatment time, with no noticeable changes during repeated long-term drug administration for up to 120 days. There was no correlation between AA concentrations and survival outcomes. However, a significant association between higher AA concentrations and better clinical benefit was observed (p = 0.041). The safety data did not correlate with the AA PK data. A significant positive correlation (r = 0.40, p < 0.001) was observed between mean AA concentration and patient age: the older the patient, the higher the AA concentration. Patient age was found to impact steady-state AA concentration: the older the patient, the higher the mean AA concentration. Altogether, these data may help to guide future research and clinical trials in order to maximize the benefits of AA metastatic castration-resistant prostate cancer patients.

StatiCAL: an interactive tool for statistical analysis of biomedical data and scientific valorization.

BACKGROUND: In the realm of biomedical research, the growing volume, diversity and quantity of data has escalated the demand for statistical analysis as it is indispensable for synthesizing, interpreting, and publishing data. Hence the need for accessible analysis tools drastically increased. StatiCAL emerges as a user-friendly solution, enabling researchers to conduct basic analyses without necessitating extensive programming expertise. RESULTS: StatiCAL includes divers functionalities: data management, visualization on variables and statistical analysis. Data management functionalities allow the user to freely add or remove variables, to select sub-population and to visualise selected data to better perform the analysis. With this tool, users can freely perform statistical analysis such as descriptive, graphical, univariate, and multivariate analysis. All of this can be performed without the need to learn R coding as the software is a graphical user interface where all the action can be performed by clicking a button. CONCLUSIONS: StatiCAL represents a valuable contribution to the field of biomedical research. By being open-access and by providing an intuitive interface with robust features, StatiCAL allow researchers to gain autonomy in conducting their projects.

Impact of virtual surgical planning and three-dimensional modeling on time to surgery in mandibular reconstruction by free fibula flap.

PURPOSE: Mandible reconstruction using a free fibula flap (FFF) is preferably performed with virtual surgical planning (VSP) to potentially improve functional and aesthetic outcomes. However, VSP is time-consuming. This study aims to assess the impact of VSP on time to surgery (TS). MATERIALS AND METHODS: All patients who underwent FFF for oral cavity cancer between 2007 and 2020 were included. Time to surgery (from the date of the first consultation to the surgery date) was compared between patients without VSP and with VSP. In our department, VSP and 3D modeling were performed by an external engineering laboratory. RESULTS: One hundred sixty-five patients were included retrospectively. VSP was utilized for 90 patients (55%). The mean time to surgery was 31 ± 16 days for patients undergoing conventional surgery without VSP and 44 ± 19 days for patients with VSP (p < 0.001). No clinical or tumoral characteristic were associated with a TS extended, except for the utilization of VSP (p < 0.001). By constituting groups of 25 consecutive patients, there is no difference in TS between the groups. CONCLUSION: The use of VSP significantly increased the time to surgery in our study, unrelated to clinical differences or year of surgery. This delay may have an impact on oncologic outcomes, so it should be considered in the care organization for each patient. Implementing new procedures to reduce this difference is warranted.

Artificial Intelligence and Anticancer Drug Development-Keep a Cool Head.

Artificial intelligence (AI) is progressively spreading through the world of health, particularly in the field of oncology. AI offers new, exciting perspectives in drug development as toxicity and efficacy can be predicted from computer-designed active molecular structures. AI-based in silico clinical trials are still at their inception in oncology but their wider use is eagerly awaited as they should markedly reduce durations and costs. Health authorities cannot neglect this new paradigm in drug development and should take the requisite measures to include AI as a new pillar in conducting clinical research in oncology.

Time-to-detection in culture of Mycobacterium tuberculosis: performance for assessing index cases contact-positivity.

OBJECTIVES: Time-to-detection (TTD) in culture on liquid media is inversely correlated to bacillary load and should be a contributing factor for assessing tuberculosis transmission. We wanted to assess if TTD was a better alternative than smear status to estimate transmission risk. METHODS: From October 2015 to June 2022, we retrospectively studied a cohort of index cases (IC) with pulmonary tuberculosis (tuberculosis disease [TD]) from which samples were culture-positive before treatment. We studied the correlation between TTD and contact-positivity (CP) of IC contacts: CP was defined as CP = 1 (CP group) in case of TD or latent tuberculosis infection (LTI) in at least one screened contact of an IC, and CP = 0 otherwise (contact-negativity [CN] group). Univariate and multivariable analyses (logistic regression) were done. RESULTS: Of the 185 IC, 122 were included, generating 846 contact cases of which 705 were assessed. A transmission event (LTI or TD) was identified in 193 contact cases (transmission rate: 27%). At day 9, 66% and 35% of the IC had their sample positive in culture for CP and CN groups, respectively. Age and TTD ≤9 days were independent criteria of CP (odds ratio 0.97, confidence interval [0.95-0.98], P = 0.002 and odds ratio 3.52, confidence interval [1.59-7.83], P = 0.001, respectively). CONCLUSION: TTD was a more discriminating parameter than smear status to evaluate the transmission risk of an IC with pulmonary tuberculosis. Therefore, TTD should be considered in the contact-screening strategy around an IC.

Comparative Performance of Four Staging Classifications to Select «High-Risk¼ Head and Neck Cutaneous Squamous Cell Carcinomas.

BACKGROUND: Many classifications exist to select patients with "high-risk" head and neck cutaneous squamous cell carcinoma (HNCSCC). OBJECTIVE: To compare the performance of the Brigham and Women's Hospital (BWH) classification with the performance of the American Joint Committee on Cancer 8th Edition (AJCC8), the Union for International Cancer Control 8th Edition (UICC8), and the National Comprehensive Cancer Network (NCCN) classifications. METHODS: In this single-center retrospective study, HNCSCC resected in a tertiary care center were classified as "low-risk" or "high-risk" tumors according to the four classifications. Rates of local recurrence (LR), lymph node recurrence (NR), and disease-specific death (DSD) were collected. The performance of each classification was then calculated in terms of homogeneity, monotonicity, and discrimination and compared. RESULTS: Two hundred and seventeen HNCSCC from 160 patients, with a mean age of 80 years, were included. For predicting the risk of any poor outcome and risk of NR, the BWH classification had the best specificity and positive predictive value. However, its concordance index was not significantly higher than that of the AJCC8 and UICC8 classifications. The NCCN classification was the least discriminant. CONCLUSIONS AND RELEVANCE: This study suggests that the BWH classification is the most appropriate for predicting the risk of poor outcomes in patients with HNCSCC when compared with the NCCN, UICC8, and AJCC8 classifications.

Enteral Nutrition during Radiotherapy for Oropharyngeal Cancers: Prevalence and Prognostic Factors Based on HPV Status (A GETTEC Study).

Nutritional support during radiotherapy is crucial to tolerating and completing oropharyngeal squamous cell carcinoma (OPSCC) treatment. The impact of HPV status on nutritional support is debated. The objective was to evaluate the rate of Reactive Feeding Tube (RFT) use and determine its prognostic factors during definitive radiotherapy for OPSCC. All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. The impact of tumor p16 status on the risk of RFT was assessed through multivariate analyses. Among the 543 patients, 103 patients required an RFT (19.0%). The use of RFT differed between centers (5% to 32.4%). In multivariate analysis, only tongue base involvement and concurrent chemotherapy were significantly associated with RFT (OR = 2.18 and 3.7, respectively). Tongue base involvement and concomitant chemotherapy were prognostic factors for RFT. HPV status was not a prognostic factor for enteral nutrition during radiotherapy for OPSCC.

Validation of RUBY for Breast Cancer Knowledge Extraction From a Large French Electronic Medical Record System.

PURPOSE: RUBY is a tool for extracting clinical data on breast cancer from French medical records on the basis of named entity recognition models combined with keyword extraction and postprocessing rules. Although initial results showed a high precision of the system in extracting clinical information from surgery, pathology, and biopsy reports (≥92.7%) and good precision in extracting data from consultation reports (81.8%), its validation is needed before its use in routine practice. METHODS: In this work, we analyzed RUBY's performance compared with the manual entry and we evaluated the generalizability of the approach on different sets of reports collected on a span of 40 years. RESULTS: RUBY performed similarly or better than the manual entry for 15 of 27 variables. It showed similar performances when structuring newer reports but failed to extract entities for which changes in terminology appeared. Finally, our tool could automatically structure 15,990 reports in 77 minutes. CONCLUSION: RUBY can automate the data entry process of a set of variables and reduce its burden, but a continuous evaluation of the format and structure of the reports and a subsequent update of the system is necessary to ensure its robustness.

Breakthrough infections due to SARS-CoV-2 Delta variant: relation to humoral and cellular vaccine responses.

Introduction: COVID-19 vaccines are expected to provide effective protection. However, emerging strains can cause breakthrough infection in vaccinated individuals. The immune response of vaccinated individuals who have experienced breakthrough infection is still poorly understood. Methods: Here, we studied the humoral and cellular immune responses of fully vaccinated individuals who subsequently experienced breakthrough infection due to the Delta variant of SARS-CoV-2 and correlated them with the severity of the disease. Results: In this study, an effective humoral response alone was not sufficient to induce effective immune protection against severe breakthrough infection, which also required effective cell-mediated immunity to SARS-CoV-2. Patients who did not require oxygen had significantly higher specific (p=0.021) and nonspecific (p=0.004) cellular responses to SARS-CoV-2 at the onset of infection than those who progressed to a severe form. Discussion: Knowing both humoral and cellular immune response could allow to adapt preventive strategy, by better selecting patients who would benefit from additional vaccine boosters. Trial registration numbers: https://clinicaltrials.gov, identifier NCT04355351; https://clinicaltrials.gov, identifier NCT04429594.

Docetaxel-Cisplatin-Fluorouracil Induction Chemotherapy for Larynx Preservation in Patients with Locally Advanced Hypopharyngeal Cancer: Predictive Factors of Oncologic and Functional Outcomes.

BACKGROUND: The aims of this study were to evaluate the clinical outcomes and their predictive factors in locally advanced hypopharyngeal cancer (HC) patients included in a docetaxel-cisplatin-fluorouracil induction chemotherapy (ICT)-based larynx preservation (LP) program. METHODS: Between 2005 and 2021, 82 patients with a locally advanced resectable HC who received ICT in an LP program were included in this retrospective study. The predictors of oncologic and swallowing outcomes were determined in univariate and multivariate analyses. RESULTS: The three- and five-year overall survival (OS) rates were 67 and 54%, respectively. The T4 tumor stage was the only predictive factor of poor response to ICT (p = 0.03). In multivariate analysis, a T stage = 4 (p = 0.02), an ICT cycle number < 3 (p = 0.003) and the absence of a response to ICT (p = 0.03) were significantly associated with worse OS. A low body mass index before therapy (p = 0.003) and enteral nutrition during therapy (p = 0.005) were significantly associated with severity of dysphagia 6 months after treatment. CONCLUSIONS: The T stage, number of ICT cycles performed and response to ICT are the main predictors of oncologic outcomes. Patients with T4 HC are poor candidates for LP and should be referred to immediate radical surgery.

Application of machine learning methods to guide patient management by predicting the risk of malignancy of Bethesda III-V thyroid nodules.

OBJECTIVE: Indeterminate thyroid nodules (ITN) are common and often lead to (sometimes unnecessary) diagnostic surgery. We aimed to evaluate the performance of two machine learning methods (ML), based on routinely available features to predict the risk of malignancy (RM) of ITN. DESIGN: Multi-centric diagnostic retrospective cohort study conducted between 2010 and 2020. METHODS: Adult patients who underwent surgery for at least one Bethesda III-V thyroid nodule (TN) with fully available medical records were included. Of the 7917 records reviewed, eligibility criteria were met in 1288 patients with 1335 TN. Patients were divided into training (940 TN) and validation cohort (395 TN). The diagnostic performance of a multivariate logistic regression model (LR) and its nomogram, and a random forest model (RF) in predicting the nature and RM of a TN were evaluated. All available clinical, biological, ultrasound, and cytological data of the patients were collected and used to construct the two algorithms. RESULTS: There were 253 (19%), 693 (52%), and 389 (29%) TN classified as Bethesda III, IV, and V, respectively, with an overall RM of 35%. Both cohorts were well-balanced for baseline characteristics. Both models were validated on the validation cohort, with performances in terms of specificity, sensitivity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve of 90%, 57.3%, 73.4%, 81.4%, 84% (CI95%: 78.5%-89.5%) for the LR model, and 87.6%, 54.7%, 68.1%, 80%, 82.6% (CI95%: 77.4%-87.9%) for the RF model, respectively. CONCLUSIONS: Our ML models performed well in predicting the nature of Bethesda III-V TN. In addition, our freely available online nomogram helped to refine the RM, identifying low-risk TN that may benefit from surveillance in up to a third of ITN, and thus may reduce the number of unnecessary surgeries.

Salvage vs. Primary Total Laryngectomy in Patients with Locally Advanced Laryngeal or Hypopharyngeal Carcinoma: Oncologic Outcomes and Their Predictive Factors.

BACKGROUND: The aims of this study were to compare the survival outcomes of salvage vs. primary total laryngectomy (TL) in patients with locally advanced laryngeal or hypopharyngeal carcinoma and to determine their predictive factors. METHODS: Overall (OS), cause-specific (CSS) and recurrence-free survival (RFS) of primary vs. salvage TL were compared in univariate and multivariate analysis taking into account other potential predictive factors (tumor site, tumor stage, comorbidity level etc.). RESULTS: A total of 234 patients were included in this study. Five-year OS was 53% and 25% for the primary and salvage TL groups, respectively. Multivariate analysis confirmed the independent negative impact of salvage TL on OS (p = 0.0008), CSS (p < 0.0001) and RFS (p < 0.0001). Hypopharyngeal tumor site, ASA score ≥ 3, N-stage ≥ 2a and positive surgical margins were the main other predictors of oncologic outcomes. CONCLUSIONS: Salvage TL is associated with significantly worse survival rates than primary TL highlighting the need for careful selection of patients who are candidates for larynx preservation. The predictive factors of survival outcomes identified here should be considered in the therapeutic decision-making, especially in the setting of salvage TL, given the poor prognosis of these patients.

Differences in sensitivity to new therapies between primary and metastatic breast cancer: A need to stratify the tumor response?

OBJECTIVE: We compared therapeutic response of Varlitinib + Capecitabine (VC) versus Lapatinib + Capecitabine (LC) in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer after trastuzumab therapy by assessing changes in target lesion (TL) diameter and volume per location. METHODS: We retrospectively analyzed the CT data of the ASLAN001-003 study (NCT02338245). We analyzed TL size and number at each location focusing on therapeutic response from baseline to Week 12. We used TL diameter and volume to conduct an inter-arm comparison of the response according to: RECIST 1.1; stratified per TL location and considering TLs independently. Multiple pairwise intra-arm comparisons of therapeutic responses were performed. Considering TL independently, weighted models were designed by adding weighted mean TL responses grouped by location. RESULTS: We evaluated 42 patients (88 TL) and 35 patients (74 TL), respectively, at baseline and Week 12. We found reductions in breast TL burden in the VC arm compared to the LC arm (p = 0.002 (diameter), p < 0.001 (volume)). Responses and TL sizes at baseline were not correlated. Explained variabilities of volume change per TL location, patient and patient:TL interaction were 36%, 10% and 4% (VC), and 13%, 1% and 23%, (LC). A test of inter-arm difference of responses yielded p = 0.07 (diameter), and p < 0.001 (volume). CONCLUSIONS: The therapeutic responses differed across tumors' locations; the magnitude of the differences of responses across the tumors' locations were drug-dependent. Stratified analysis of the response by tumor location improved drug comparisons and is a powerful tool to understand TL heterogeneity.

Accuracy of mandibular anterior subapical osteotomy by virtual planning in orthognathic surgery using patient-specific implants.

INTRODUCTION: Mandibular anterior subapical osteotomy (MASO) is a complementary procedure during orthognathic surgery to correct proclination or extrusion of the anterior incisors when orthodontic movements fail. The increasing use of patient-specific implants (PSI, titanium plates) in orthognathic surgery has extended to this procedure. Digital orthognathic surgery planning involves manufacturing cutting/drilling guides and specific implants to provide better accuracy and allow complex movement with reduced surgical times compared to conventional planning. This study aimed to assess the accuracy of computer-aided surgery with patient-specific implants in mobilising the MASO segment according to planning. METHODS: Eleven consecutive patients with mean age 26.82 years (15-41, SD = 10.65) were treated with MASO in addition to other conventional orthognathic procedures incorporating digital planning and patient-specific implants. A three-dimensional "stl" format file of the mandibular dental arch was obtained using an intraoral scanner at the end of the surgical procedure. The accuracy of the MASO segment displacement imposed by PSI was assessed by comparing preoperative 3D-planned mandibular dental arch with the immediate postoperative 3D-measured arch, using surface superimposition and 7 standard dental landmarks. Deviations between the preoperative and postoperative landmarks were calculated and compared to determine whether MASO segment repositioning is sufficiently accurate to be safely used to reposition the incisor/canine axis. RESULTS: Quantitative analysis revealed an absolute linear difference of 0.66 mm (SD = 0.51) between preoperative 3D digital dental arch impression and postoperative planned 3D dental arch. Overall, the median absolute discrepancies in the x-axis (right-left direction), y-axis (antero-posterior direction), and z-axis (supero-inferior direction) were respectively 0.56 mm (SD = 0.42), 0.77 mm (SD = 0.45) and 0.65 mm (SD = 0.61). CONCLUSION: A high degree of accuracy between the virtual plan and the immediate postoperative result was observed. According to our results, PSI can be used safely with accuracy in MASO as an adjunct to other conventional orthognathic procedures.

Validation and Improvement of a Convolutional Neural Network to Predict the Involved Pathology in a Head and Neck Surgery Cohort.

The selection of patients for the constitution of a cohort is a major issue for clinical research (prospective studies and retrospective studies in real life). Our objective was to validate in real life conditions the use of a Deep Learning process based on a neural network, for the classification of patients according to the pathology involved in a head and neck surgery department. 24,434 Electronic Health Records (EHR) from the first visit between 2000 and 2020 were extracted. More than 6000 EHR were manually classified in ten groups of interest according to the reason for consultation with a clinical relevance. A convolutional neural network (TensorFlow, previously reported by Hsu et al.) was then used to predict the group of patients based on their pathology, using two levels of classification based on clinically relevant criteria. On the first and second level of classification, macro-average performances were: 0.95, 0.83, 0.85, 0.97, 0.84 and 0.93, 0.76, 0.83, 0.96, 0.79 for accuracy, recall, precision, specificity and F1-score versus accuracy, recall and precision of 0.580, 580 and 0.582 for Hsu et al., respectively. We validated this model to predict the pathology involved and to constitute clinically relevant cohorts in a tertiary hospital. This model did not require a preprocessing stage, was used in French and showed equivalent or better performances than other already published techniques.

Accuracy of Segmented Le Fort I Osteotomy with Virtual Planning in Orthognathic Surgery Using Patient-Specific Implants: A Case Series.

Background: When maxillary transversal expansion is needed, two protocols of treatment can be used: a maxillary orthodontic expansion followed by a classical bimaxillary osteotomy or a bimaxillary osteotomy with maxillary segmentation. The aim of this study was to assess the accuracy of segmented Le Fort I osteotomy using computer-aided orthognathic surgery and patient-specific titanium plates in patients who underwent a bimaxillary osteotomy for occlusal trouble with maxillary transversal insufficiencies. Methods: A virtual simulation of a Le Fort I osteotomy with maxillary segmentation, a sagittal split ramus osteotomy, and genioplasty (if needed) was conducted on a preoperative three-dimensional (3D) model of each patient's skull using ProPlan CMF 3.0 software (Materialise, Leuven, Belgium). Computer-assisted osteotomy saw-and-drill guides and patient-specific implants (PSIs, titanium plates) were produced and used during the surgery. We chose to focus on the maxillary repositioning accuracy by comparing the preoperative virtual surgical planning and the postoperative 3D outcome skulls using surface superimpositions and 13 standard dental and bone landmarks. Errors between these preoperative and postoperative landmarks were calculated and compared to discover if segmental maxillary repositioning using PSIs was accurate enough to be safely used to treat transversal insufficiencies. Results: A total of 22 consecutive patients­15 females and 7 males, with a mean age of 27.4 years­who underwent bimaxillary computer-assisted orthognathic surgery with maxillary segmentation were enrolled in the study. All patients presented with occlusion trouble, 13 with Class III malocclusions (59%) and 9 (41%) with Class II malocclusions. A quantitative analysis revealed that, overall, the mean absolute discrepancies for the x-axis (transversal dimension), y-axis (anterior−posterior dimensions), and z-axis (vertical dimension) were 0.59 mm, 0.74 mm, and 0.56 mm, respectively. The total error rate of maxillary repositioning was 0.62 mm between the postoperative cone-beam computed tomography (CBCT) and the preoperatively planned 3D skull. According to the literature, precision in maxilla repositioning is defined by an error rate (clinically relevant) at each landmark of <2 mm and a total error of <2 mm for each patient. Conclusions: A high degree of accuracy between the virtual plan and the postoperative result was observed.

RUBY: Natural Language Processing of French Electronic Medical Records for Breast Cancer Research.

PURPOSE: Electronic medical records are a valuable source of information about patients' clinical status but are often free-text documents that require laborious manual review to be exploited. Techniques from computer science have been investigated, but the literature has marginally focused on non-English language texts. We developed RUBY, a tool designed in collaboration with IBM-France to automatically structure clinical information from French medical records of patients with breast cancer. MATERIALS AND METHODS: RUBY, which exploits state-of-the-art Named Entity Recognition models combined with keyword extraction and postprocessing rules, was applied on clinical texts. We investigated the precision of RUBY in extracting the target information. RESULTS: RUBY has an average precision of 92.8% for the Surgery report, 92.7% for the Pathology report, 98.1% for the Biopsy report, and 81.8% for the Consultation report. CONCLUSION: These results show that the automatic approach has the potential to effectively extract clinical knowledge from an extensive set of electronic medical records, reducing the manual effort required and saving a significant amount of time. A deeper semantic analysis and further understanding of the context in the text, as well as training on a larger and more recent set of reports, including those containing highly variable entities and the use of ontologies, could further improve the results.

Impact of a new combined preoperative cleft assessment on dental implant success in patients with cleft and palate: a retrospective study.

BACKGROUND: Bone height assessment alone is frequently used to guide rehabilitation choice, without consideration for soft tissues or adjacent teeth. This study aimed to evaluate the impact of different preoperative cleft assessments on implant success and patient satisfaction. METHODS: The study involved a retrospective assessment of records from 40 patients with cleft lip and palate (CLP). The alveolar cleft score (ACS; clinical criteria), interdental alveolar bone height (IABH) score (radiological criteria), patient compliance score (dental hygiene, medical visit observance, and smoking), and a novel combined score (IABH-ACS-Compliance) were assessed from patient records. Patients who required prosthetic tooth rehabilitation in the cleft dental arch space were included. Twenty-six patients (Group 1) were treated with dental implants, and 14 patients (Group 2) selected another prosthetic option (fixed prosthodontics, removal prosthesis), orthodontic space closure, or no rehabilitation. The main outcomes measured were relative implant success (no implant loss involving marginal bone loss ≤ 1.9 mm) for patients treated with dental implant therapy (Group 1) and patient satisfaction for all patients (Groups 1 and 2). RESULTS: Forty dental implants were placed in the patients in Group 1. Four implants in four patients (Group 1 relative failure, RF) were lost (implant survival rate of 90%) after 36 (± 12.4) months of follow-up. Twenty-two patients who received implants belonged to the relative implant success group (Group 1 RS). The average "IABH-ACS-Compliance" scores were significantly different (p < 0.05): 16.90 ± 2.35 and 12.75 ± 0.43 for the Group 1 RS and RF groups, respectively. CONCLUSIONS: Preoperative cleft parameters have an impact on relative implant success and patient satisfaction. The new cleft assessment combined-score ("IABH-ACS-Compliance") allows an accurate selection of cleft cases eligible for dental implants, thereby improving postoperative outcomes.

Humoral and cellular responses after a third dose of SARS-CoV-2 BNT162b2 vaccine in patients with lymphoid malignancies.

Patients with hematological malignancies have impaired immune response after two doses of BNT162b2 (Pfizer/BioNTech) vaccine against SARS-CoV-2. Here, in this observational study (registration number HDH F20210324145532), we measure SARS-CoV-2 anti-Spike antibodies, neutralizing antibodies and T-cell responses after immune stimulation with a third dose (D3) of the same vaccine in patients with chronic lymphocytic leukemia (n = 13), B cell non-Hodgkin lymphoma (n = 14), and multiple myeloma (n = 16)). No unexpected novel side effects are reported. Among 25 patients with positive anti-S titers before D3, 23 (92%) patients increase their anti-S and neutralizing antibody titer after D3. All 18 (42%) initially seronegative patients remain negative. D3 increases the median IFN-γ secretion in the whole cohort and induces IFN-γ secretion in a fraction of seronegative patients. Our data thus support the use of a third vaccine dose amongst patients with lymphoid malignancies, even though some of them will still have vaccine failure.