Efficacy of intrathecal mesenchymal stem cell-neural progenitor therapy in progressive MS: results from a phase II, randomized, placebo-controlled clinical trial.

BACKGROUND: Mesenchymal stem cell-neural progenitors (MSC-NPs) are a bone marrow mesenchymal stem cell (MSC)-derived ex vivo manipulated cell product with therapeutic potential in multiple sclerosis (MS). The objective of this study was to determine efficacy of intrathecal (IT) MSC-NP treatment in patients with progressive MS. METHODS: The study is a phase II randomized, double-blind, placebo-controlled clinical trial with a compassionate crossover design conducted at a single site. Subjects were stratified according to baseline Expanded Disability Status Scale (EDSS) (3.0-6.5) and disease subtype (secondary or primary progressive MS) and randomized into either treatment or placebo group to receive six IT injections of autologous MSC-NPs or saline every two months. The primary outcome was EDSS Plus, defined by improvement in EDSS, timed 25-foot walk (T25FW) or nine-hole peg test. Secondary outcomes included the individual components of EDSS Plus, the six-minute walk test (6MWT), urodynamics testing, and brain atrophy measurement. RESULTS: Subjects were randomized into MSC-NP (n = 27) or saline (n = 27) groups. There was no difference in EDSS Plus improvement between the MSC-NP (33%) and saline (37%) groups. Exploratory subgroup analysis demonstrated that in subjects who require assistance for ambulation (EDSS 6.0-6.5) there was a significantly higher percentage of improvement in T25FW and 6MWT in the MSC-NP group (3.7% ± 23.1% and - 9.2% ± 18.2%) compared to the saline group (-54.4% ± 70.5% and - 32.1% ± 30.0%), (p = 0.030 and p = 0.036, respectively). IT-MSC-NP treatment was also associated with improved bladder function and reduced rate of grey matter atrophy on brain MRI. Biomarker analysis demonstrated increased MMP9 and decreased CCL2 levels in the cerebrospinal fluid following treatment. CONCLUSION: Results from exploratory outcomes suggest that IT-MSC-NP treatment may be associated with a therapeutic response in a subgroup of MS patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03355365, registered November 14, 2017, https://clinicaltrials.gov/study/NCT03355365?term=NCT03355365&rank=1 .

Reduced Fascicle Area Demonstrated in Ilioinguinal Nerves Resected from Primary Inguinal Herniorrhaphy Patients as Evidence of Compression Neuropathy.

Methods: 30 male patients with primary inguinal hernias undergoing primary inguinal herniorrhaphy were prospectively recruited for ilioinguinal nerve resection and evaluation. Three samples of the resected ilioinguinal nerve (proximal, canal, and distal) were evaluated using Masson's trichrome stain to measure fascicle and total nerve cross-sectional area and detect changes in collagen. Results: The fascicle cross-sectional area in the canal segment was significantly decreased compared to the proximal control with a large effect size observed (p = 0.016, η2 = 0.16). There was no significant difference in the nerve cross-sectional area between locations, but there was a moderate to large effect size observed between locations (p = 0.165, η2 = 0.105). There was no significant difference in collagen content nor effect size observed between locations (p = 0.99, η2 = 1.503 × 10-4). Interpretation. The decrease in the fascicle cross-sectional area within the inguinal canal further suggests that there is chronic pressure applied by hernia tissue consistent with axon degeneration. Collagen content is uniformly distributed along the length of the nerve. Further studies with larger samples are needed to confirm the observed effect of nerve location on the total nerve cross-sectional area and axon loss.

Distance to endoscopy services amplifies racial inequities in colorectal cancer mortality in Washington state.

BACKGROUND: This study evaluates relationships among race, access to endoscopy services, and colorectal cancer (CRC) mortality in Washington state (WA). METHODS: We overlayed the locations of ambulatory endoscopy services with place of residence at time of death, using Department of Health data (2011-2018). We compared CRC mortality data within and outside a 10 â€‹km buffer from services. We used linear regression to assess the impact of distance and race on age at death while adjusting for gender and education level. RESULTS: Age at death: median 72.9y vs. 68.2y for white vs. non-white (p â€‹< â€‹0.001). The adjusted model showed that non-whites residing outside the buffer died 6.9y younger on average (p â€‹< â€‹0.001). Non-whites residing inside the buffer died 5.2y younger on average (p â€‹< â€‹0.001), and whites residing outside the buffer died 1.6y younger (p â€‹< â€‹0.001). We used heatmaps to geolocate death density. CONCLUSIONS: Results suggest that geographic access to endoscopy services disproportionately impacts non-whites in Washington. These data help identify communities which may benefit from improved access to alternative colorectal cancer screening methods.

Optimization of a standardized letter of recommendation for faculty who wish to support candidates applying to surgical training programs.

Letters of recommendation (LORs) play an important role in applicant selection for graduate medical education programs. LORs may be of increasing importance in the evaluation of applicants given the recent change of the USMLE Step 1 to pass/fail scoring and the relative lack of other objective measures by which to differentiate and stratify applicants. Narrative letters of recommendation (NLORs), although widely used, have certain limitations, namely variability in interpretation, introduction of gender/race bias, and performance inflation. Standardized letters of recommendation (SLOR) have been proposed as a potential corrective to these limitations. We conducted a series of semi-structured interviews and focus groups to gather perspectives from letter writers and readers to inform methods for improving information elicited by SLORs from which we collected and analyzed data using the constant comparative method and a process of iterative coding. We applied our findings to the development of a novel SLOR for use in surgical residency program applications and were subsequently invited to help revise existing SLORs for a surgical post-graduate training program.

Surgical journal clubs: Navigating the post-pandemic landscape.

Pandemic-related distancing regulations gave medical educators at our college an opportunity to reimagine and expand our evidenced-based medicine curriculum to an asynchronous, virtual format. We share the experience of course directors, faculty, and students with our new surgical journal club format. Our goal was to support learners' critical appraisal skills of the surgical literature through active learning modalities such as visual abstract generation and audio-synopsis creation. We included surgeons whose practice locations and schedules may preclude participation. The curriculum was applied to our pre-existing community-based journal clubs. The asynchronous, virtual format allowed us to expand these journal clubs to include rural surgeons.

Population Pharmacokinetic Model of N-Acetylcysteine During Periods of Recurrent Hypoglycemia in Healthy Volunteers.

Recurrent hypoglycemia leads to impaired awareness of hypoglycemia where the blood glucose threshold that elicits the counterregulatory response is lowered. Hypoglycemia-induced oxidative stress is hypothesized to contribute to impaired awareness of hypoglycemia development and hypoglycemia-associated autonomic failure. Our group conducted a randomized, double-blinded, placebo-controlled, crossover study in healthy individuals undergoing experimentally induced recurrent hypoglycemia to evaluate the impact of intravenous N-acetylcysteine (NAC) during experimental hypoglycemia to preserve the counterregulatory response to subsequent hypoglycemia. The work presented herein aimed to characterize the NAC pharmacokinetics and its effects on oxidative stress. Whole blood and plasma samples were collected at specified time points during separate NAC and placebo infusions from 10 healthy volunteers. Samples were analyzed for NAC, cysteine, and glutathione (GSH) concentrations. A 2-compartment population NAC pharmacokinetic model was developed. Estimates for central compartment clearance and volume of distribution were 19.8 L/h, and 12.2 L, respectively, for a 70-kg person. Peripheral compartment clearance and volume of distribution estimates were 34.9 L/h and 13.1 L, respectively, for a 70-kg person. The PK parameters estimated here were different from those reported in the literature, suggesting a higher NAC clearance during hypoglycemic episodes. NAC leads to a significant increase in circulating cysteine concentration in a NAC concentration-dependent manner, suggesting rapid biotransformation. A transient decrease in plasma GSH was observed, supporting the hypothesis that NAC can act as a reducing agent displacing glutathione from the disulfide bond allowing for increased clearance and/or distribution of GSH.

Role of Physiotherapy in HPV Proven Cases of Oral Submucous Fibrosis.

Background: To assess the role of physiotherapy in human papillomavirus (HPV) proven cases of oral submucous fibrosis (OSMF). Materials and Methods: Overall, 100 patients got recruited. Only histopathologic confirmed cases of OSMF were enrolled. Purified DNA of tissue blocks was quantified by spectrophotometry. Prevalence of HPV was evaluated. The participants got randomized into 2 cohorts: HPV positive cases and HPV negative cases. Physiotherapy was done and outcome was done and outcome was assessed and compared. Assessment of results was done by SPSS software followed by statistical evaluation. Results: HPV was seen in 80% of the patients. Mean mouth opening pretreatment and postphysiotherapy among patients with HPV positive status was 26.31 mm and 30.12 mm, respectively. Mean mouth opening pretreatment and postphysiotherapy among patients with HPV negative status was 25.11 mm and 29.74 mm, respectively. Nonsignificant results were obtained while comparing the outcome of physiotherapy among HPV positive and negative groups. Conclusion: Outcome of physiotherapy among OSMF patients is independent of HPV status.

Humoral and cellular responses to repeated COVID-19 exposure in multiple sclerosis patients receiving B-cell depleting therapies: a single-center, one-year, prospective study.

Multiple sclerosis patients treated with anti-CD20 therapy (aCD20-MS) are considered especially vulnerable to complications from SARS-CoV-2 infection due to severe B-cell depletion with limited viral antigen-specific immunoglobulin production. Therefore, multiple vaccine doses as part of the primary vaccination series and booster updates have been recommended for this group of immunocompromised individuals. Even though much less studied than antibody-mediated humoral responses, T-cell responses play an important role against CoV-2 infection and are induced efficiently in vaccinated aCD20-MS patients. For individuals with such decoupled adaptive immunity, an understanding of the contribution of T-cell mediated immunity is essential to better assess protection against CoV-2 infection. Here, we present results from a prospective, single-center study for the assessment of humoral and cellular immune responses induced in aCD20-MS patients (203 donors/350 samples) compared to a healthy control group (43/146) after initial exposure to CoV-2 spike antigen and subsequent re-challenges. Low rates of seroconversion and RBD-hACE2 blocking activity were observed in aCD20-MS patients, even after multiple exposures (responders after 1st exposure = 17.5%; 2nd exposure = 29.3%). Regarding cellular immunity, an increase in the number of spike-specific monofunctional IFNγ+-, IL-2+-, and polyfunctional IFNγ+/IL-2+-secreting T-cells after 2nd exposure was found most noticeably in healthy controls. Nevertheless, a persistently higher T-cell response was detected in aCD20-MS patients compared to control individuals before and after re-exposure (mean fold increase in spike-specific IFNγ+-, IL-2+-, and IFNγ+/IL-2+-T cells before re-exposure = 3.9X, 3.6X, 3.5X/P< 0.001; after = 3.2X, 1.4X, 2.2X/P = 0.002, P = 0.05, P = 0.004). Moreover, cellular responses against sublineage BA.2 of the currently circulating omicron variant were maintained, to a similar degree, in both groups (15-30% T-cell response drop compared to ancestral). Overall, these results highlight the potential for a severely impaired humoral response in aCD20-MS patients even after multiple exposures, while still generating a strong T-cell response. Evaluating both humoral and cellular responses in vaccinated or infected MS patients on B-cell depletion therapy is essential to better assess individual correlations of immune protection and has implications for the design of future vaccines and healthcare strategies.

Do the research priorities identified in SAGES Delphi studies resonate with rural general surgeons: a Washington state perspective.

BACKGROUND: Rural surgeons operate in an environment significantly different from that of their colleagues, and as such they face unique challenges. We hypothesized the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) research agenda (as identified in the results of the 2014 Delphi study) will differ in its priorities from those identified by rural surgeons. We aimed to pilot a study in Washington state that could be replicated in other areas of the USA and the world. METHODS: We identified general surgeons working at rural critical access hospitals in the state of Washington. We then conducted virtual, semi-structured interviews and followed up with surveys and site visits. The survey included the 2014 SAGES Delphi-ranked research priorities. We asked rural surgeons to rank their top 5 of these 40 priorities and to detail any additional which were not on the list. RESULTS: We contacted 79 surgeons with a 30% response rate. We conducted 25 semi-structured interviews and received 18 completed follow-up surveys. These interviews were followed by site visits at 4 of the 23 sites. Of the original Delphi research priorities, those most cited by rural surgeons were #8 ("What is the best method for incorporating new techniques and technology for surgeons of variable levels of experience or training?") and #1 ("How do we best train, assess, and maintain proficiency of surgeons and surgical trainees in flexible endoscopy, laparoscopy, and open surgery?"). Four surgeons included the last SAGES priority (#40 "Is quality of life improved after ventral hernia repair?") among their top 5. CONCLUSION: This study suggests that although rural surgeons' research priorities align with the published SAGES Delphi survey, these surgeons rank the priorities differently. This may be because the predominant study population of the Delphi is SAGES membership who work in urban and academic centers. Plans for future SAGES Delphi survey could capture these unique priorities by intentional involvement of rural and community surgeons.

Oral examination of fourth-year medical students on surgery rotations allows faculty to assess Core Entrustable Professional Activities for entering Residency (CEPAR): Proof-of-concept and analysis of student submissions.

BACKGROUND: As a community-based medical school which recruited faculty preceptors new to teaching, we sought to create objective assessments for fourth-year surgery experiences via administration of an oral exam. Students provided three authentic cases, which faculty used as a springboard to ascertain student proficiency in five entrustable professional activities: 1-oral presentation, 2-recognition of urgency/instability, 3-calling consults, 4-transitions of care, 5-informed consent. We present proof-of-concept and analysis of student case submissions. METHODS: Twenty-seven student submissions (79 cases in total) were evaluated for case complexity, level-appropriateness, and an estimation of the ability to conduct a quality exam based on the information provided (subjective measures). Objective metrics included word count, instruction adherence, inclusion of figures/captions. A resident-in-training rated cases via the same metrics. In-examination data was separately culled. RESULTS: The average word count was 281.70 (SD 140.23; range 40-743). Figures were included in 26.1% of cases. Faculty raters scored 29.0% as low-complexity, 37.7% medium-complexity, and 33.3% high-complexity. Raters felt 62.3% of cases provided enough information to conduct a quality exam. The majority of cases submitted (65.2%) were level-appropriate or higher. The resident rater scored cases more favorably than surgeons (Cohen's kappa of -0.5), suggesting low inter-rater agreement between those of differing experience levels. CONCLUSION: Student's case submissions lessened faculty burden and provided assessors with adequate information to deliver a quality exam to assess proficiency in clinical skills essential for residency. Cases demonstrated sufficient complexity and level-appropriateness. The request to correlate case rating with exam performance is under review by our institution's assessment office. Near-peer tutoring by resident alumni is a program under development.

Homeschooling Surgery Students: Washington State University's Longitudinal Integrated Clerkship Transitioned to a Hybrid-Virtual Platform Triggered by the COVID-19 Pandemic.

When COVID-19 curtailed elective surgeries, our college transitioned to a virtual platform. "Benched" surgeons statewide engaged students online. Third-year students who had completed 2/3 of a longitudinal integrated clerkship (LIC) studied online modules on topics germane to surgery for 1 week. Core entrustable professional activities (EPAs) for entering residency were the backbone of lessons/assignments/assessments. Surgeons coached students around EPAs. Fifty-eight students in consistent small groups, spent 2 hours/day for 4 days with the same pair of surgeon coaches. Off-line, students created a unique hypothetical case/day, practiced and peer-reviewed EPAs. Online, coaches posed scenarios to drill EPAs. Pre/during/post assessments demonstrated progressive proficiency. High level of engagement resulted in 100% attendance and ease of recruitment/retention of faculty. Although variability in students' clinical settings was high, a virtual week had aided in leveling the learning environment. Prior experience with 2/3 of their total surgery exposure in the LIC allowed for a smooth transition to virtual.

Relationship Between Hypoglycemia Awareness Status on Clarke/Gold Methods and Counterregulatory Response to Hypoglycemia.

Context: Impaired awareness of hypoglycemia (IAH) is characterized by the diminished ability to perceive symptoms of hypoglycemia. Gold and Clark questionnaires are commonly used to identify patients with IAH. The relationship between IAH status on questionnaires and a person's symptom and epinephrine responses to hypoglycemia are not well understood. Objective: We aimed to examine the relationship between hypoglycemia awareness status on Clarke and Gold questionnaires with both hormonal and symptomatic responses to experimental hypoglycemia. Methods: In this university medical center study, we examined data from 78 subjects with type 1 diabetes (T1D) who completed both questionnaires and underwent a hyperinsulinemic hypoglycemic clamp (target glucose 50 mg/dL). Results: Clarke and Gold scores were highly correlated with one another (r = 0.82) and each had a moderate negative relationship with epinephrine (Clarke: r = -0.51, Gold: r = -0.50) and total symptom response (Clarke: r = -0.59, Gold: r = -0.57). However, 32% of the subjects were classified inconsistently by Clark vs Gold. A clustering analysis was done to examine how disagreement between the 2 questionnaires on IAH classification relates to epinephrine and symptoms responses during hypoglycemia. Subjects who had partial loss of symptoms or of epinephrine response were more likely to be classified inconsistently. Conclusion: Our results show that IAH classification may be discordant between Clark and Gold questionnaires and that hypoglycemia awareness status on Clarke and Gold questionnaires poorly predicts hormonal and symptomatic responses to hypoglycemia in subjects with T1D and moderate blunting of symptoms or epinephrine.

Heterogeneity in Epinephrine Response to Experimental Hypoglycemia in Type 1 Diabetes and Controls.

Context: The epinephrine response (Epi) to a first episode of hypoglycemia (HG) has been proposed to be predictive of Epi in subsequent HG and to provide insight into the risk for developing HG-associated autonomic failure (HAAF) in healthy controls (HCs). Objective: To determine if Epi and symptom response (SR) to the first episode of HG predicts who will develop HAAF after exposure to recurrent HG in volunteers with type 1 diabetes (T1D) and in HCs. Design: Review of data collected between 2013 and 2019. Setting: Academic clinical research unit. Patients or Participants: Volunteers with T1D and HCs. Interventions: Subjects participated in a preinduction protocol where they were exposed to three 2-hour episodes of clamped HG over 2 days. Data collected during clamp 1 were compared with data collected during clamp 3. Main outcome measure: Difference in Epi and SR. Results: Using the standard definition of HAAF in which HG-induced Epi during clamp 3 is at least 20% lower than during clamp 1, 21/28 HCs and 13/19 volunteers with T1D developed HAAF. Epi during clamp 1 was significantly higher in those subjects who developed HAAF than in those who did not in both groups (P = 0.02). If HAAF is defined as achieving a 20% reduction in HG-induced SR measured during clamp 3 compared with clamp 1, 10/27 HCs and 10/19 volunteers with T1D developed SR-based HAAF. Conclusion: There was heterogeneity in the response to the preinduction protocol. Epi during clamp 1 was higher than in clamp 3 in HCs and in those with T1D who developed HAAF.

Different FreeSurfer versions might generate different statistical outcomes in case-control comparison studies.

PURPOSE: Neuroimaging pipelines have long been known to generate mildly differing results depending on various factors, including software version. While considered generally acceptable and within the margin of reasonable error, little is known about their effect in common research scenarios such as inter-group comparisons between healthy controls and various pathological conditions. The aim of the presented study was to explore the differences in the inferences and statistical significances in a model situation comparing volumetric parameters between healthy controls and type 1 diabetes patients using various FreeSurfer versions. METHODS: T1- and T2-weighted structural scans of healthy controls and type 1 diabetes patients were processed with FreeSurfer 5.3, FreeSurfer 5.3 HCP, FreeSurfer 6.0 and FreeSurfer 7.1, followed by inter-group statistical comparison using outputs of individual FreeSurfer versions. RESULTS: Worryingly, FreeSurfer 5.3 detected both cortical and subcortical volume differences out of the preselected regions of interest, but newer versions such as FreeSurfer 5.3 HCP and FreeSurfer 6.0 reported only subcortical differences of lower magnitude and FreeSurfer 7.1 failed to find any statistically significant inter-group differences. CONCLUSION: Since group averages of individual FreeSurfer versions closely matched, in keeping with previous literature, the main origin of this disparity seemed to lie in substantially higher within-group variability in the model pathological condition. Ergo, until validation in common research scenarios as case-control comparison studies is included into the development process of new software suites, confirmatory analyses utilising a similar software based on analogous, but not fully equivalent principles, might be considered as supplement to careful quality control.

Randomized control trial of unconditional versus conditional incentives to increase study enrollment rates in participants at increased risk of lung cancer.

INTRODUCTION: Understanding how incentives and their timing influence study enrollment rates is important to efficient study design and increasing the generalizability of findings. This 2-arm, parallel randomized trial evaluated how conditional vs. unconditional mailed incentives of a $20 gift card affected study enrollment in a sample of participants screened for lung cancer screening. METHODS: Eligible participants included Black and White adults who underwent lung cancer screening with low-dose CT and had negative screening results at two North Carolina imaging facilities in 2018. We used a stratified randomization scheme, by sex and race, to assign incentive type (conditional vs. unconditional). We used the Tailored Design Method with six points of mailed contact to engage participants. We compared study enrollment rates using chi-square tests and logistic regression analyses. RESULTS: After adjusting for sex, race, age, smoking status, participant residence, and screening site, participants who received unconditional incentives were 74% more likely to enroll than those who received conditional incentives (adjusted OR = 1.74 (95% CI: 1.01, 3.00). CONCLUSIONS: Type of incentive can play a role in increasing study enrollment, especially mailed surveys that target individuals who currently or previously smoked. Unconditional incentives may be worth the initial cost to engage study participants.

Monitoring the Neurotransmitter Response to Glycemic Changes Using an Advanced Magnetic Resonance Spectroscopy Protocol at 7T.

The primary excitatory and inhibitory neurotransmitters glutamate (Glu) and gamma-aminobutyric acid (GABA) are thought to be involved in the response of the brain to changes in glycemia. Therefore, their reliable measurement is critical for understanding the dynamics of these responses. The concentrations of Glu and GABA, as well as glucose (Glc) in brain tissue, can be measured in vivo using proton (1H) magnetic resonance spectroscopy (MRS). Advanced MRS methodology at ultrahigh field allows reliable monitoring of these metabolites under changing metabolic states. However, the long acquisition times needed for these experiments while maintaining blood Glc levels at predetermined targets present many challenges. We present an advanced MRS acquisition protocol that combines commercial 7T hardware (Siemens Scanner and Nova Medical head coil), BaTiO3 dielectric padding, optical motion tracking, and dynamic frequency and B0 shim updates to ensure the acquisition of reproducibly high-quality data. Data were acquired with a semi-LASER sequence [repetition time/echo time (TR/TE) = 5,000/26 ms] from volumes of interest (VOIs) in the prefrontal cortex (PFC) and hypothalamus (HTL). Five healthy volunteers were scanned to evaluate the effect of the BaTiO3 pads on B 1 + distribution. Use of BaTiO3 padding resulted in a 60% gain in signal-to-noise ratio in the PFC VOI over the acquisition without the pad. The protocol was tested in six patients with type 1 diabetes during a clamp study where euglycemic (~100 mg/dL) and hypoglycemic (~50 mg/dL) blood Glc levels were maintained in the scanner. The new protocol allowed retention of all HTL data compared with our prior experience of having to exclude approximately half of the HTL data in similar clamp experiments in the 7T scanner due to subject motion. The advanced MRS protocol showed excellent data quality (reliable quantification of 11-12 metabolites) and stability (p > 0.05 for both signal-to-noise ratio and water linewidths) between euglycemia and hypoglycemia. Decreased brain Glc levels under hypoglycemia were reliably detected in both VOIs. In addition, mean Glu level trended lower at hypoglycemia than euglycemia for both VOIs, consistent with prior observations in the occipital cortex. This protocol will allow robust mechanistic investigations of the primary neurotransmitters, Glu and GABA, under changing glycemic conditions.

Analysis of Clinical, Radiographic, and Treatment Profile of 10 Cases of Neurogenic Tumors and Tumor-Like Lesions of the Oral and Maxillofacial Region: An Observational Study.

BACKGROUND: Soft tissues of the head and neck areas are a very frequent site of occurrence of certain benign tumors of the peripheral nerve sheath, especially the neurofibromas. Hence, the present study was conducted for assessing clinical, radiographic, and treatment profile of 10 cases of neurogenic tumors and tumor-like lesions of the oral and maxillofacial region. MATERIALS AND METHODS: Data records of a total of 10 patients who were diagnosed with tumors of neurogenic origin were enrolled in the present study. Data files were analyzed over a time period of 2 years, and complete clinical and radiographic details were evaluated. All the patients in which incomplete information was present in the record files were excluded from the present study. The assessment of the histopathologic reports was done, and final diagnosis was recorded separately in the master chart. RESULTS: Neurofibroma was the diagnosis in two cases. In another set of two cases, final diagnosis of traumatic neuroma was achieved. A single case Schwannoma of mandible depicting multilocular radiolucency was present. Granular cell tumor was present in three cases. It was present clinically in the form of swelling, ulcerative nodule, and nodular growth in the three respective cases. Surgical excision was carried out in all the cases, and follow-up records did not depict any case of recurrence of complication posttreatment. CONCLUSION: Neurogenic tumors of oral and maxillafacial region are a rare phenomenon and mainly present in the form of benign neoplasm. However, careful recognition and diagnosis of these lesions are necessary to rule any possible malignant changes.

Prevalence of Shoulder Arthroplasty in the United States and the Increasing Burden of Revision Shoulder Arthroplasty.

Existing data on the epidemiology of shoulder arthroplasty are limited to future projections of incidence. However, the prevalence of shoulder arthroplasty (the number of individuals with a shoulder arthroplasty alive at a certain time and its implications for the burden of revision procedures) remains undetermined for the United States. Hence, the purpose of this study was to estimate the prevalence of shoulder arthroplasty in the United States. METHODS: The National Inpatient Sample (NIS) was queried to count all patients who underwent total shoulder arthroplasty (TSA), including both anatomic and reverse TSA, and hemiarthroplasty between 1988 and 2017. The counting method was used to calculate the current prevalence of TSA and hemiarthroplasty using age and sex-specific population and mortality data from the U.S. Census Bureau. RESULTS: In 2017, an estimated 823,361 patients (95% confidence interval [CI], 809,267 to 837,129 patients) were living in the United States with a shoulder replacement. This represents a prevalence of 0.258%, increasing markedly from 1995 (0.031%) and 2005 (0.083%). Female patients had a higher prevalence at 0.294% than male patients at 0.221%. Over 2% of people who were ≥80 years of age in the United States were living with a shoulder replacement. Furthermore, approximately 60% of patients living with a shoulder replacement had undergone the operation between 2013 and 2017. The incidence of revision shoulder arthroplasty is increasing on an annual basis, with 10,290 revision procedures performed in 2017, costing the U.S. health-care system $205 million. CONCLUSIONS: The prevalence of shoulder arthroplasty in the United States has markedly increased over time. This trend will likely continue given increasing life expectancies and exponentially increasing shoulder arthroplasty incidence rates. Most patients do not have long-term follow-up, and revision shoulder arthroplasty rates are increasing, a trend that is projected to continue. The data from our study highlight the enormous public health impact of shoulder replacement and shed light on a potentially increasing revision burden.

Glenohumeral osteoarthritis with intact rotator cuff treated with reverse shoulder arthroplasty: a systematic review.

BACKGROUND: Although reverse shoulder arthroplasty (RSA) has shown satisfactory outcomes in rotator cuff-deficient shoulders, its performance in shoulders with an intact rotator cuff has not been fully elucidated. Shoulder osteoarthritis can present with alterations in glenoid morphology, which have contributed to inconsistent outcomes in anatomic shoulder replacement. The glenoid component is responsible for a predominance of these arthroplasty complications. Given these glenoid-related difficulties, RSA may provide a more favorable option. We aimed to summarize the current literature on rotator cuff intact osteoarthritis treated with primary RSA and to determine whether morphologic changes in the glenoid led to inferior outcomes. METHODS: A literature search was performed using an inclusion criterion of primary RSA for osteoarthritis with an intact rotator cuff. The Modified Coleman Methodology Score was calculated to analyze reporting quality. Following appropriate exclusions, of the 1002 studies identified by the databases, 13 were selected. RESULTS: Postoperative improvement in weighted means for Constant scores reached statistical significance (P = .02). The mean rate of major complications was 3.8%. A subset of 8 studies was created that detailed the following descriptions of altered glenoid morphology: "static posterior instability," "severe posterior subluxation," "posterior glenoid wear >20°," "significant posterior glenoid bone loss," "biconcave glenoid," "B2 glenoid," and "B/C glenoid." Within this subset, the mean complication rate was 4.7%, with 4 of the 7 studies having a rate ≤ 3%, and improvements in the Constant score (P = .002) and external rotation (P = .02) reached statistical significance. DISCUSSION: RSA as treatment for osteoarthritis with an intact rotator cuff provides optimal outcomes with low complication rates across a short term of follow up. Preoperative considerations for using reverse arthroplasty in the treatment of osteoarthritis with an intact rotator cuff include glenoid retroversion, posterior humeral subluxation, and glenoid bone loss. The attributes of reverse arthroplasty that contribute to favorable outcomes in arthritic shoulders include its semiconstrained design and robust glenoid fixation. Soft-tissue imbalances as a consequence of pathologic glenoid morphology and chronic humeral subluxation can be mitigated with the RSA semiconstrained design. Glenoid bone loss can be effectively managed with RSA's robust glenoid fixation, with and without the use of bone graft. The capability to lateralize the joint center of rotation may be valuable when faced with a medialized glenoid wear pattern. The current findings suggest that reverse arthroplasty can achieve highly favorable outcomes for glenohumeral osteoarthritis with an intact rotator cuff.