Development and Assessment of an Artificial Intelligence-Based Tool for Ptosis Measurement in Adult Myasthenia Gravis Patients Using Selfie Video Clips Recorded on Smartphones.

Introduction: Myasthenia gravis (MG) is a rare autoimmune disease characterized by muscle weakness and fatigue. Ptosis (eyelid drooping) occurs due to fatigue of the muscles for eyelid elevation and is one symptom widely used by patients and healthcare providers to track progression of the disease. Margin reflex distance 1 (MRD1) is an accepted clinical measure of ptosis and is typically assessed using a hand-held ruler. In this work, we develop an AI model that enables automated measurement of MRD1 in self-recorded video clips collected using patient smartphones. Methods: A 3-month prospective observational study collected a dataset of video clips from patients with MG. Study participants were asked to perform an eyelid fatigability exercise to elicit ptosis while filming "selfie" videos on their smartphones. These images were collected in nonclinical settings, with no in-person training. The dataset was annotated by non-clinicians for (1) eye landmarks to establish ground truth MRD1 and (2) the quality of the video frames. The ground truth MRD1 (in millimeters, mm) was calculated from eye landmark annotations in the video frames using a standard conversion factor, the horizontal visible iris diameter of the human eye. To develop the model, we trained a neural network for eye landmark detection consisting of a ResNet50 backbone plus two dense layers of 78 dimensions on publicly available datasets. Only the ResNet50 backbone was used, discarding the last two layers. The embeddings from the ResNet50 were used as features for a support vector regressor (SVR) using a linear kernel, for regression to MRD1, in mm. The SVR was trained on data collected remotely from MG patients in the prospective study, split into training and development folds. The model's performance for MRD1 estimation was evaluated on a separate test fold from the study dataset. Results: On the full test fold (N = 664 images), the correlation between the ground truth and predicted MRD1 values was strong (r = 0.732). The mean absolute error was 0.822 mm; the mean of differences was -0.256 mm; and 95% limits of agreement (LOA) were -0.214-1.768 mm. Model performance showed no improvement when test data were gated to exclude "poor" quality images. Conclusions: On data generated under highly challenging real-world conditions from a variety of different smartphone devices, the model predicts MRD1 with a strong correlation (r = 0.732) between ground truth and predicted MRD1.

A decentralized, prospective, observational study to collect real-world data from patients with myasthenia gravis using smartphones.

Introduction: We conducted a 3-month, prospective study in a population of patients with Myasthenia Gravis (MG), utilizing a fully decentralized approach for recruitment and monitoring (ClinicalTrials.gov Identifier: NCT04590716). The study objectives were to assess the feasibility of collecting real-world data through a smartphone-based research platform, in order to characterize symptom involvement during MG exacerbations. Methods: Primary data collection included daily electronically recorded patient-reported outcomes (ePROs) on the presence of MG symptoms, the level of symptom severity (using the MG-Activities of Daily Living assessment, MG-ADL), and exacerbation status. Participants were also given the option to contribute data on their physical activity levels from their own wearable devices. Results: The study enrolled and onboarded 113 participants across 37 US states, and 73% (N= 82) completed the study. The mean age of participants was 53.6 years, 60% were female. Participants were representative of a moderate to severe MG phenotype, with frequent exacerbations, high symptom burden and multiple comorbidities. 55% of participants (N=45) reported MG exacerbations during the study, with an average of 6.3 exacerbation days per participant. Median average MG-ADL scores for participants during self-reported exacerbation and non-exacerbation periods were 7 (interquartile range 4-9, range 1-19) and 0.3 (interquartile range 0-0.8, range 0-9), respectively. Analyses examining relationships between patient-reported and patient-generated health data streams and exacerbation status demonstrated concordance between self-reported MG-ADL scores and exacerbation status, and identified features that may be used to understand and predict the onset of MG symptom exacerbations, including: 1.) dynamic changes in day-to-day symptom reporting and severity 2.) daily step counts as a measure of physical activity and 3.) clinical characteristics of the patient, including the amount of time since their initial diagnosis and their active medications related to MG treatment. Finally, application of unsupervised machine learning methods identified unique clusters of exacerbation subtypes, each with their own specific representation of symptoms and symptom severity. Conclusion: While these symptom signatures require further study and validation, our results suggest that digital phenotyping, characterized by increased multidimensionality and frequency of the data collection, holds promise for furthering our understanding of clinically significant exacerbations and reimagining the approach to treating MG as a heterogeneous condition.

Racial disparities in inpatient palliative care consultation among frail older patients undergoing high-risk elective surgical procedures in the United States: a cross-sectional study of the national inpatient sample.

Surgical interventions are common among seriously ill older patients, with nearly one-third of older Americans facing surgery in their last year of life. Despite the potential benefits of palliative care among older surgical patients undergoing high-risk surgical procedures, palliative care in this population is underutilized and little is known about potential disparities by race/ethnicity and how frailty my affect such disparities. The aim of this study was to examine disparities in palliative care consultations by race/ethnicity and assess whether patients' frailty moderated this association. Drawing on a retrospective cross-sectional study of inpatient surgical episodes using the National Inpatient Sample of the Healthcare Cost and Utilization Project from 2005 to 2019, we found that frail Black patients received palliative care consultations least often, with the largest between-group adjusted difference represented by Black-Asian/Pacific Islander frail patients of 1.6 percentage points, controlling for sociodemographic, comorbidities, hospital characteristics, procedure type, and year. No racial/ethnic difference in the receipt of palliative care consultations was observed among nonfrail patients. These findings suggest that, in order to improve racial/ethnic disparities in frail older patients undergoing high-risk surgical procedures, palliative care consultations should be included as the standard of care in clinical care guidelines.

A retrospective cohort study on peri-implant complications in implants up to 10 years of functional loading in periodontally compromised patients.

BACKGROUND: Prevalence of peri-implantitis is directly proportional to the time of functional loading. The aim of this retrospective study was to assess the survival and success rates as well as the incidence of peri-implantitis among patients with a history of periodontitis and among implants with 1 to 10 years of functional loading. METHODS: We evaluated clinical records of periodontally compromised patients treated between January 1998 and July 2002, with implants enrolled in a supportive periodontal and peri-implant treatment follow-up program. The following assessment indexes during follow-up were recorded: suppuration on probing, modified bleeding on probing, probing depth, implant mobility, bone changes, and criteria of success of Albrektsson. RESULTS: Clinical data of 475 patients with 1,991 implants were analyzed for a period of 10 years of functional loading. The survival and success rates were 91.8% and 75.4%, respectively, and the cumulative incidence of peri-implantitis among patients was 24.4%. The survival rate was 96.1%, and the success rate was 83.7% among implants. The incidence of peri-implantitis exhibited a peak rate after the seventh year (2.1%). The prevalence of peri-implantitis increased from 3.2% to 9.7% between 5 and 10 years of follow-up, and the peri-implantitis rate among implants was 12.9% after 10 years of functional loading. CONCLUSION: Peri-implantitis begins to appear more frequently after the fifth year of functional loading, especially between the seventh and eighth years of function.

A computer vision system for deep learning-based detection of patient mobilization activities in the ICU.

Early and frequent patient mobilization substantially mitigates risk for post-intensive care syndrome and long-term functional impairment. We developed and tested computer vision algorithms to detect patient mobilization activities occurring in an adult ICU. Mobility activities were defined as moving the patient into and out of bed, and moving the patient into and out of a chair. A data set of privacy-safe-depth-video images was collected in the Intermountain LDS Hospital ICU, comprising 563 instances of mobility activities and 98,801 total frames of video data from seven wall-mounted depth sensors. In all, 67% of the mobility activity instances were used to train algorithms to detect mobility activity occurrence and duration, and the number of healthcare personnel involved in each activity. The remaining 33% of the mobility instances were used for algorithm evaluation. The algorithm for detecting mobility activities attained a mean specificity of 89.2% and sensitivity of 87.2% over the four activities; the algorithm for quantifying the number of personnel involved attained a mean accuracy of 68.8%.

Therapeutic efficacy of chlorhexidine-based mouthwashes and its adverse events: Performance-related evaluation of mouthwashes added with Anti-Discoloration System and cetylpyridinium chloride.

OBJECTIVES: To compare 3 mouthwashes: 0.20% chlorhexidine (CHX) with Anti-Discoloration System (ADS), 0.20% CHX and 0.12% CHX with 0.05% cetylpyridinium chloride (CPC), in terms of reduction of plaque and gingival bleeding and side effects. METHODS: Mild gingivitis patients were randomly divided into three Groups: they underwent professional oral hygiene and received instructions: oral rinse with 10 mL for 1', twice a day, 30' after tooth brushing, for 14 days. Primary outcomes were plaque and gingival bleeding, assessed with Plaque Control Record and Gingival Bleeding Index. Feedback questionnaire and spectrophotometer evaluated secondary outcomes: adverse events. Timing of the study was T0 (baseline), T1 (professional oral hygiene) and T2 (14th day after mouthwash use). RESULTS: Sixty-six patients were recruited, two patients dropped out, and 64 patients completed the study. PCR T1-T2 mean variation was 30.67 (SD = 15.22; 95% CI 23.55 to 37.80; P = 0.000), 19.93 (SD = 11.03; 95% CI 14.90 to 24.95; P = 0.000) and 16.24 (SD = 15.35; 95% CI 9.60 to 22.88; P = 0.000) respectively in Groups 0.2% CHX + ADS, 0.2% CHX and 0.12% CHX + CPC. GBI mean variation (T0-T2) was -9.82 (SD = 9.27; 95% CI -5.48 to 14.16; P = 0.000), -19.31 (SD = 11.33; 95% CI -14.15 to -24.47; P = 0.000) and -21.13 (SD = 12.56; 95% CI -15.70 to -26.56; P = 0.000) respectively in Groups 0.2% CHX + ADS, 0.2% CHX and 0.12% CHX + CPC. Statistical significance was found in lower efficacy of 0.2% CHX + ADS Group. Patients tolerated 0.12% CHX + CPC mouthwash better in bleeding perception (95.5%; P = 0.046), burning sensation (13.6%; P = 0.006), and mouthwash taste (100%; P = 0.000). Results on staining were no statistically significant (P = 0.106). CONCLUSIONS: Addition of CPC allows reduction of CHX percentage in mouthwash formulation while keeping equal efficacy and less side effects. ADS addition decreases CHX efficacy in reducing plaque and bleeding, while resulting more tolerated than CHX.

Ergonomic risk and preventive measures of musculoskeletal disorders in the dentistry environment: an umbrella review.

INTRODUCTION: Dental practitioners are exposed to different occupational hazards during the course of their professional activity, such as physical, chemical, biological, ergonomic factors. The ergonomic hazards, caused by strained posture and prolonged repetitive movements, can induce musculoskeletal disorders. It occurs in 54-93% of dental professionals and involve the spine, shoulder and hand-wrist tract. Through a systematic review of international literature, we analyzed specific ergonomic risk factors and preventive measures of musculoskeletal disorders in professional dental activity. METHODS: This systematic review is coherent with the PRISMA statement. The scientific research on the major online databases was based on the following keywords: dentist, prevention, ergonomic, dentistry, musculoskeletal, neck pain, posture, ergonomics, work and occupational. The studies included in this review focus on disorders related to ergonomics and on the most effective preventive measures to be adopted. No restrictions were applied for language or publication type. We excluded reports not related to ergonomic prevention in dentistry, reports of minor academic significance, editorial articles, individual contributions, and studies published in scientific conferences. RESULTS: Online research indicated 4188 references: PubMed (2919), Scopus (1257) e Cochrane Library (12). We excluded 3012 of these, because they were unrelated to ergonomics theme and 187 due to duplication. From the remaining 989 studies, 960 papers did not meet inclusion criteria and they were excluded. Therefore, we analyzed 29 articles, including 16 narrative reviews and 13 original article. The main risk factor for the development of musculoskeletal disorders found in our analysis is static posture adopted during work, highlighted in 87.5% of reviews and 84% of original articles. With regard to preventive measures, 75% of the reviews highlighted the importance of stretching after each working session and at the end of the working day, while 61.5% of the original articles emphasized the use of modern and ergonomic instruments. DISCUSSION: This review showed that static postures are strongly responsible in the etiology of musculoskeletal disorders. The awkward postures more frequently identified among dental professionals are: extreme forward-head and neck flexion; trunk inclination and rotation towards one side; lifting one or both shoulders; increased curvature of the thoracic vertebral column; incorrect positioning of the lower limbs with thigh-leg angle of less than 90°. It is really important to use of a modern workstation with appropriate ergonomic supports. Among the preventive ergonomic measures, literature has widely recognized the role of physical activity and of a neutral and balanced posture. The present review has some limits: a large part of the selected studies did not have a high methodological quality score and an inadequate statistical analysis.

The RASSF1A tumor suppressor regulates XPA-mediated DNA repair.

RASSF1A may be the most frequently inactivated tumor suppressor identified in human cancer so far. It is a proapoptotic Ras effector and plays an important role in the apoptotic DNA damage response (DDR). We now show that in addition to DDR regulation, RASSF1A also plays a key role in the DNA repair process itself. We show that RASSF1A forms a DNA damage-regulated complex with the key DNA repair protein xeroderma pigmentosum A (XPA). XPA requires RASSF1A to exert full repair activity, and RASSF1A-deficient cells exhibit an impaired ability to repair DNA. Moreover, a cancer-associated RASSF1A single-nucleotide polymorphism (SNP) variant exhibits differential XPA binding and inhibits DNA repair. The interaction of XPA with other components of the repair complex, such as replication protein A (RPA), is controlled in part by a dynamic acetylation/deacetylation cycle. We found that RASSF1A and its SNP variant differentially regulate XPA protein acetylation, and the SNP variant hyperstabilizes the XPA-RPA70 complex. Thus, we identify two novel functions for RASSF1A in the control of DNA repair and protein acetylation. As RASSF1A modulates both apoptotic DDR and DNA repair, it may play an important and unanticipated role in coordinating the balance between repair and death after DNA damage.

Evaluation of obstructive sleep apnea in pediatric patients with facio-craniostenosis: a brief communication.

PURPOSE: This study aimed to evaluate our experience in treating cranio-maxillo-mandibular malformations with hypoplasia of the upper and middle third of the face. We wished to determine a new diagnostic path involving a new clinical questionnaire for obstructive sleep apnea (OSA) evaluation, which we have developed by merging existing tests, literature findings, and our clinical experience to obtain a high level of information with minimal cost. This questionnaire is an improvement of the other anamnestic tests in the literature. METHODS: The study was carried out on 17 pediatric patients affected by syndromic craniofacial malformations and treated with surgical advancement of the middle third of the face, associated with or without upper third advancement, through osteodistraction. We used the obstructive airway child test (OACT) for clinical evaluation. The OACT is an OSA assessment test based on questions proposed to the patient's relatives. All patients underwent polysomnography for instrumental assessment of OSA. These patients were also required to have a computed tomography scan for surgical planning. At the start of the treatment, 11 patients had severe OSA, 4 patients had moderate OSA, and 2 patients had slight OSA. RESULTS: At the end of the treatment, 6 patients had slight OSA and 11 patients had no OSA; these data were confirmed with OACT and polysomnography. CONCLUSIONS: Based on our results, we suggest the following flowchart: OACT for OSA clinical evaluation; CT scan for evaluation of the volume of the rhinoropharyngeal air column, anatomical obstruction detection, and surgical planning; and polysomnography for diagnostic confirmation.

Clinical evaluation of obstructive sleep apnea in children.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is often found in children affected by congenital or acquired craniomaxillomandibular malformations. This disease carries different levels of risk, ranging from attention problems at school to growth problems and serious disorders, such as cor pulmonale or sudden infant death. The examination that is most commonly used to evaluate the severity of OSAS is polysomnography, and the therapeutic course is often determined by the disease state. Considering the discrepancy between clinical history and polysomnographic findings, we felt the need to identify an instrument for evaluating OSA to be used as a support for polysomnography. MATERIALS AND METHODS: This study was carried out on pediatric patients affected by congenital or acquired craniomaxillofacial malformations. We selected 34 pediatric patients, including 15 boys and 19 girls, aged between 1 and 16 years, with a mean age of 7.3 years. The study consisted of individuation of common clinical history data obtained from each patient and associating those data with the level of OSA severity identified by polysomnography. We were able to isolate certain symptoms and signs that can be predictive of OSA from research in the literature and our clinical experience with pediatric patients. In the clinic, we have found that the clinical history, given by the parents, often differs significantly from the instrumental findings obtained with polysomnography. From the previously expressed considerations and comparison of clinical history data and questionnaires, we have extracted the most significant questions for our questionnaire, which are present in the literature but formulated for adults. RESULTS AND CONCLUSIONS: The obstructive airway child test was found to be a very efficient method to evaluate and diagnose OSA. In all patients, it consistently revealed the pathology and never underestimated OSA severity. The examination focuses on clinical signs and symptoms because, in our opinion, clinical history, reported by the parents, can be more accurate than any instrumental examination.

Hilotherm efficacy in controlling postoperative facial edema in patients treated for maxillomandibular malformations.

BACKGROUND: A cooling system based on polyurethane preshaped masks for postoperative cryotherapy, named Hilotherm, has been recently introduced. The purpose of this study was to evaluate the effectiveness of this equipment in controlling postoperative edema and compare the results with those obtained with a group treated with conventional cryotherapy and a group not treated with cryotherapy. METHODS: Ninety patients were included in this randomized controlled trial. The 90 patients were divided into 3 groups. Group A was treated with Hilotherm. Group B was treated with conventional cryotherapy. Group C was not treated with cryotherapy. Using a tape measure, we measured for both sides of the face the distances in centimeters between point 0 and external canthus ([alpha]), most lateral point on the ala of the nose ([beta]), commissura labialis ([gamma]), and Pos ([delta]). We performed a Kruskal-Wallis test comparing the average variation of edema on the right and left sides of the face for each facial segment of patients of the 3 groups from time 0 to time 24 hours. RESULTS: No cryotherapy is the worst treatment for every segment studied. In anatomic regions defined [beta], [gamma], and [delta], Hilotherm was more effective in containing edema than the ice pack 24 hours after the first measurement. Opposite results were seen on district [alpha], the site not completely enclosed in the mask. CONCLUSIONS: The substantial difference between different treatments probably consisted in the greater reliability of the Hilotherm system, which is characterized by easy handling, constant temperature control, comfort, and practicality of the masks.

Cleavage of PGRP-LC receptor in the Drosophila IMD pathway in response to live bacterial infection in S2 cells.

Drosophila responds to Gram-negative bacterial infection by activating the immune deficiency (IMD) pathway, leading to production of antimicrobial peptides (AMPs). As a receptor for the IMD pathway, peptidoglycan-recognition protein (PGRP), PGRP-LC is known to recognize and bind monomeric peptidoglycan (DAP-type PGN) through its PGRP ectodomain and in turn activate the IMD pathway. The questions remain how PGRP-LC is activated in response to pathogen infection to initiate the IMD signal transduction in Drosophila. Here we present evidence to show that proteases such as elastase and Mmp2 can also activate the IMD pathway but not the TOLL pathway. The elastase-dependent IMD activation requires the receptor PGRP-LC. Importantly, we find that live Salmonella/E. coli infection modulates PGRP-LC expression/receptor integrity and activates the IMD pathway while dead Salmonella/E. coli or protease-deficient E. coli do neither. Our results suggest an interesting possibility that Gram-negative pathogen infection may be partially monitored through the structural integrity of the receptor PGRP-LC via an infection-induced enzyme-based cleavage-mediated activation mechanism.

Loss of NKX3.1 favors vascular endothelial growth factor-C expression in prostate cancer.

Decreased levels of the prostate-specific homeobox protein NKX3.1 are correlated with hormone-refractory and metastatic prostate cancer. Thus, it is compelling to define the NKX3.1-regulated genes that may be important for the progression of the advanced stage of the disease. In this study, we showed that vascular endothelial growth factor-C (VEGF-C) is one such target gene of NKX3.1. NKX3.1 inhibited VEGF-C expression in prostate cancer, and the loss of NKX3.1 led to increased VEGF-C expression. Histone deacetylase 1 acted as a corepressor of VEGF-C expression along with NKX3.1. Activated RalA acted in synergy with the loss of NKX3.1 for VEGF-C transcription. Patients with deletions at chromosome 8p21.1-p21.2 as a sole deletion developed lymph node metastasis. Interestingly, the higher expression of VEGF-C in prostate cancer is also correlated with lymph node metastasis. Therefore, regulation of VEGF-C expression by NKX3.1 provides a possible mechanism by which the loss of NKX3.1 protein level leads to lymphangiogenesis in the late stages of advanced prostate cancer.

Upregulation of VEGF-C by androgen depletion: the involvement of IGF-IR-FOXO pathway.

Androgen ablation therapy is eventually followed by a more metastatic and androgen-refractory stage of prostate cancer. The detailed molecular mechanism of this gradual transition is not clearly understood. Recent reports correlate the high abundance of vascular endothelial growth factor-C (VEGF-C) to the lymph node metastasis seen in human prostate cancer (Tsurusaki et al., 1999). In this study, we report that androgen ablation in LNCaP cells augment the transcriptional upregulation of VEGF-C and the downregulation of the IGF-IR pathway, due to androgen withdrawal, is a potential mechanism for this observed VEGF-C transcription. Forkhead transcription factor FOXO-1, activated by SIRT-1, was identified as the downstream molecule within this pathway. Furthermore, the VEGF-C-induced increase of Bag-IL expression in LNCaP cells suggests that VEGF-C plays a role in the androgen-independent reactivation of the androgen receptor, resulting in androgen-refractory prostate cancer growth.