DLX6 and MSX1 from saliva samples as potential predictors of mandibular size: A cross-sectional study.

INTRODUCTION: Morphologic features of the mandible are influenced by the genes of each individual. Mandible size is important to orthodontists because the mandible is the mechanism by which the lower face influences facial esthetics and dental function. To date, no biological marker has been identified that indicates eventual mandible size. This study aimed to correlate the expression of DLX5, DLX6, EDN1, HAND2, PRRX1, and MSX1 to mandible size. METHODS: Fifty-nine orthodontic patients aged >6 years who had available cephalometric radiographs were studied. Patients were classified on the basis of condylion-to-gnathion measurements. Messenger RNA was isolated from saliva and subjected to real-time quantitative polymerase chain reaction. RESULTS: Threshold cycle values for subjects with small mandibles (>1 standard deviation [SD] from the mean) had the least expression of DLX6 and MSX1. Threshold cycle values for subjects with large mandibles (>1 SD) had less expression of DLX6 and MSX1 than subjects within 1 SD but more than those with small mandibles. CONCLUSIONS: DLX6 and MSX1 are related to mandible development and size. This finding could be used to improve treatment planning for medical and dental professionals seeking to understand the impact of genetics on bone growth.

Cheek Donor Site for Full-Thickness Skin Graft Repair of the Nasal Ala: Outcomes of a Retrospective Cohort Study.

BACKGROUND: Full-thickness skin grafts (FTSGs) are useful repairs for reconstructing nasal alar defects. Traditional donor sites include the preauricular, postauricular, and supraclavicular skin. OBJECTIVE: To evaluate esthetic outcomes and complications of nasal alar defects repaired with FTSGs from the medial cheek. MATERIALS AND METHODS: A retrospective chart review of Mohs surgery patients who had FTSG repair of the nasal ala between January 2015 and August 2020 was performed. Demographic, surgery, and follow-up visit data were reviewed. Cosmesis was rated by a facial plastic surgeon, a Mohs surgeon, and a plastic surgeon using baseline, defect, and follow-up visit photographs. RESULTS: Sixty-nine patients with FTSG repairs of nasal alar defects were identified. 51 of 69 patients (73.9%) had the cheek donor site, and 18 of 69 patients (26.1%) had a noncheek donor site. The mean (SD) rater visual analog score for both cohorts was good with no significant difference (cheek: 65.9 [13.8]; noncheek: 66.1 [15.3]; p = .96). A notable difference in the complication rate by donor site was observed (cheek: 6.9%, noncheek: 16.7%; p = .13), although it did not reach significance. CONCLUSION: The cheek is a reliable FTSG donor site for nasal alar defects after Mohs micrographic surgery, with a trend toward fewer complications.

Umbilical Cord Milking in Extremely Preterm Infants: A Randomized Controlled Trial Comparing Cord Milking with Immediate Cord Clamping.

OBJECTIVE: This study aimed to assess potential benefits of umbilical cord milking (UCM) when compared with immediate cord clamping (ICC) in extremely preterm infants. STUDY DESIGN: This is a single-center, randomized controlled trial of infants 240/7 to 276/7 weeks' gestation who received UCM versus ICC. In the experimental group, 18 cm of the umbilical cord was milked three times. The primary aim was to assess the initial hemoglobin and to assess the number of blood transfusions received in the first 28 days after birth. Secondary outcomes were also assessed, including intraventricular hemorrhage (IVH). A priori, neurodevelopmental follow-up was planned at 15 to 18 months corrected gestational age (CGA). RESULTS: Baseline characteristics for 56 enrolled infants were similar in both groups with a mean gestational age of 26.1 ± 1.2 weeks and a mean birth weight of 815 ± 204 g. There were no differences in the mean initial hemoglobin in the UCM group when compared with the ICC group, 13.7 ± 2.0 and 13.8 ± 2.6 g/dL, respectively (p = 0.95), with no differences in median number of blood transfusions after birth between the ICC group and the UCM group, 2 (interquartile range [IQR]: 1-4) versus 2.5 (IQR: 1-5) (p = 0.40). There was also no difference in the rate of severe IVH. At 15 to 18 months CGA, there were no differences in death or disability in the ICC group compared with the UCM group (26 vs. 22%; p = 1.0) and no differences in neurodevelopmental outcomes. CONCLUSION: In a randomized trial of ICC versus UCM in extremely preterm infants, no differences were seen in initial hemoglobin or number of blood transfusions. KEY POINTS: · Umbilical cord milking may be an alternative to delayed cord clamping, but its safety and efficacy are not established in extremely premature infants.. · There are minimal available published data on the longer term neurodevelopmental outcomes in extremely premature infants who receive umbilical cord milking compared with immediate clamping.. · We did not find a significant difference in the primary outcomes of initial hemoglobin and blood transfusions between the groups, nor did we find a difference in severe IVH with umbilical cord milking..

Appropriate use criteria for ancillary diagnostic testing in dermatopathology: New recommendations for 11 tests and 220 clinical scenarios from the American Society of Dermatopathology Appropriate Use Criteria Committee.

BACKGROUND: Appropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests. METHODS: RAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2. RESULTS: For 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid-Schiff, Gömöri methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated "usually appropriate" or "rarely appropriate" and 45 of 148 (30%), "appropriateness uncertain." LIMITATIONS: The study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded. CONCLUSIONS: AUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery.

Sun Protection Outreach Teaching by Students (SPOTS)-Evaluating the Efficacy of Skin Cancer Prevention Education for Adolescents.

BACKGROUND: The Sun Protection Outreach Teaching by Students (SPOTS) program addresses an unmet need by training medical students to teach adolescents about skin cancer prevention and early detection. OBJECTIVE: To measure (1) changes in adolescents' knowledge, attitudes, and behaviors regarding sun protection and (2) the impact on medical students' confidence in skin cancer preventive counseling. METHODS: Pre-SPOTS and 1-month post-SPOTS program surveys were completed by adolescent participants and medical student instructors. RESULTS: Amongst adolescent students, analysis of 1,142 pre-program surveys and 618 post-program surveys revealed statistically significant improvements in knowledge, attitudes, and behaviors. Among the favorable results, 26%, 41%, and 20% improvements over baseline were observed in SPF knowledge, preference for natural untanned skin, and intent to wear sunscreen, respectively (p < .001). One-third of adolescents reported having tried to increase sunscreen use. Amongst medical students, analysis of 78 pre-teaching and 74 post-teaching surveys revealed an increase in feeling "very confident" in counseling patients, from 23% pre-teaching to 82% post-teaching (p < .001). CONCLUSION: SPOTS demonstrated a dual benefit to adolescents and medical students. The program is available for dermatologists to implement in their communities.

Whole Blood Thiamine in Organ Donors After the Neurologic Determination of Death.

INTRODUCTION: Metabolic resuscitation of organ donors and the attenuation of oxidative stress incurred by organs following brain death and transplantation have the potential to improve organ yield and allograft function. Thiamine (vitamin B1) is a vital coenzyme in both energy metabolism and the production of antioxidants that has not been studied in the donor population. RESEARCH AIM: To determine the frequency of subclinical thiamine deficiency in brain-dead organ donors and its correlation with demographics, length of hospitalization, donor management, lactic acidosis, and the requirement for vasoactive support. DESIGN: Prospective cohort study of brain-dead donors managed at a single organ procurement organization's organ recovery facility. RESULTS: A total 64 donors were enrolled; 24 donors had thiamine levels drawn upon arrival and 40 donors had levels drawn at the time of organ procurement. Whole blood thiamine levels were inversely correlated with the time from death (P = .007) and 20% (8/40) of donors had levels below the normal range at the time of organ procurement. Demographic features of the donor were not associated with thiamine levels although longer hospital stays prior to death were associated with lower levels (P < .05). The presence and resolution of lactic acidosis was not associated with whole blood thiamine level. Higher thiamine levels were associated with earlier discontinuation of vasoactive support (P = .04). DISCUSSION: Whole blood thiamine deficiency was not uncommon at the time of organ procurement. Thiamine may be associated with the requirement for hemodynamic support.

Economic and Humanistic Burden Associated with Depression and Anxiety Among Adults with Non-Communicable Chronic Diseases (NCCDs) in the United States.

INTRODUCTION: Patients with both major depressive disorder (MDD) and generalized anxiety disorder (GAD) in addition to one or multiple comorbid non-communicable chronic diseases (NCCDs) face unique challenges. However, few studies have characterized how the burden of co-occurring MDD and GAD differs from that of only MDD or only GAD among patients with NCCDs. METHODS: In this study, we used Medical Expenditures Panel Survey data from 2010-2017 to understand how the economic and humanistic burden of co-occurring MDD and GAD differs from that of MDD or GAD alone among patients with NCCDs. We used generalized linear models to investigate this relationship and controlled for patient sociodemographics and clinical characteristics. RESULTS: Co-occurring MDD and GAD was associated with increases in mean annual per patient inpatient visits, office visits, emergency department visits, annual drug costs, and total medical costs. Among patients with 3+ NCCDs, MDD or GAD only was associated with lower odds ratios (ORs) of limitations in activities of daily living (ADLs; 0.532 and 0.508, respectively) and social (0.503, 0.526) and physical limitations (0.613, 0.613) compared to co-occurring MDD and GAD. Compared to patients with co-occurring MDD and GAD, having MDD only or GAD only was associated with significantly lower odds of cognitive limitations (0.659 and 0.461, respectively) in patients with 1-2 NCCDs and patients with 3+ NCCDs (0.511, 0.416). DISCUSSION: Comorbid MDD and GAD was associated with higher economic burden, lower quality of life, and greater limitations in daily living compared to MDD or GAD alone. Health-related economic and humanistic burden increased with number of NCCDs.

Economic and humanistic burden associated with noncommunicable diseases among adults with depression and anxiety in the United States.

Aims: This study estimated the economic and humanistic burden associated with chronic non-communicable diseases (NCCDs) among adults with comorbid major depressive and/or any anxiety disorders (MDD and/or AAD).Materials and methods: A retrospective analysis was conducted using the Medical Expenditure Panel Survey data (2010-2015). The analytic cohort included adults (≥18 years) with MDD only (C1), AAD only (C2), or both (C3). The presence of either of 6 NCCDs (cardiovascular diseases [CVD], pulmonary disorders [PD], pain, high cholesterol, diabetes, and obesity) were assessed. Study outcomes included healthcare costs, activity limitations, and quality of life. Multivariate regressions were conducted in each of the 3 cohorts to evaluate the association between the presence of NCCDs and outcomes.Results: The analytic sample included 9,160,465 patients: C1 (4,391,738), C2 (3,648,436), C3 (1,120,292). Pain (59%) was the most common condition, followed by CVD (55%), high cholesterol (50%), obesity (42%), PD (17%), and diabetes (14%). Mean annual healthcare costs were the greatest for C3 ($14,317), followed by C1 ($10,490) and C2 ($7,906). For C1, CVD was associated with the highest increment in annual costs ($3,966) followed by pain ($3,617). For C2, diabetes was associated with the highest incremental annual costs ($4,281) followed by PD ($2,997). For C3, cost trends were similar to those seen in C2. NCCDs resulted in a significant decrease in physical quality of life across all cohorts. Pain was associated with a significantly higher likelihood of self-reported physical, social, cognitive, and activity limitations compared to those without pain.Conclusions: 60% of patients with MDD and/or AAD had at least one additional NCCD, which significantly increased the economic and humanistic burden. These findings are important for payers and clinicians in making treatment decisions. These results underscore the need for development of multi-pronged interventions which aim to improve quality of life and reduce activity limitations among patients with mental health disorders and NCCDs.

Real-World Impact of Retrievable Stents for Acute Ischemic Stroke on Disability Utilizing the National Inpatient Sample.

PURPOSE: We assess the impact of retrievable stent (RS) compared to first-generation devices on in-hospital mortality and disability in patients with acute ischemic stroke (AIS). METHODS: Using the National Inpatient Sample, data were obtained for patients with a primary diagnosis of AIS who underwent mechanical thrombectomy (MT) and were admitted to US hospitals between 2010 and 2014. Two time periods were compared: 2010-2012 (pre-RS Food and Drug Administration [FDA] approval) and 2013-2014 (post-RS FDA approval). Disability level was used to classify outcomes as minimal disability, moderate to severe disability, or in-hospital mortality. Weighted, multivariable logistic regression was used to assess the association between MT device type and disability. RESULTS: A total of 2,443,713 weighted patients admitted with AIS were identified; 148,923 (4.9%) of these received intravenous tissue plasminogen activator; and 23,719 (0.8%) underwent MT. In multivariable logistic regression analysis, the odds of in-hospital mortality decreased (OR 0.69, 95% CI 0.59-0.82) in the post-RS time-period compared with pre-RS time. The odds of moderate-to-severe disability decreased (OR 0.88, 95% CI 0.73-1.06) compared with minimal disability. In-hospital mortality rates decreased successively over the 4 years in the MT-treated patients (p < 0.001). CONCLUSIONS: The FDA approval of RS technology after 2012 was associated with decreased in-hospital mortality when compared with the 3-year interval prior. These findings provide an indication that the RCT data on the efficacy of RS technology are translating into improved real-world outcomes.

Three-dimensional modeling and comparison of nasal flap designs.

Few studies exist that compare local flap repair designs either mathematically or clinically. Previous mathematical studies use a two-dimensional modeling approach, which is not suited to complex structures like the nose. To quantitatively analyze and compare flap designs for nasal repair using three-dimensional, photographic models. via a three-dimensional imaging system (Vectra M3, Canfield Scientific, Parsippany, NJ, USA), images were captured of actual post-Mohs nasal defects on 12 consecutive patients. Transposition, rotation, and advancement flap designs were designed and assessed based on tissue efficiency (Et = SAwound/(SAwound + SAtrimmed) × 100), suture efficiency (Es = SAwound/Lengthsutured × 100), total area undermined, combined 1° and 2° flap motion efficiency (Efm = SAwound/(SAundermined - (SAwound + SAtrimmed)) × 100), incision efficiency (Ei = SAwound/lengthincision × 100), and undermining efficiency (Eu = SAwound/SAundermined × 100). Rotation flap designs are the most tissue efficient (p < 0.001). Transposition designs are the least suture efficient (p = 0.012) and require less undermining than the corresponding rotation flaps (although not statistically significant). Advancement flaps have the highest flap motion efficiency (p = 0.027). Incision and undermining efficiency is equivalent between all three designs (p = 0.308 and p = 0.158, respectively). While statistically significant differences exist between the flaps studied, the clinical significance is unknown. Consequently, the choice in repair design should be made based on its ability to attain a functionally and aesthetically successful reconstruction.

Oral immunotherapy tolerizes mice to enzyme replacement therapy for Morquio A syndrome.

Immune response to therapeutic enzymes poses a detriment to patient safety and treatment outcome. Enzyme replacement therapy (ERT) is a standard therapeutic option for some types of mucopolysaccharidoses, including Morquio A syndrome caused by N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency. Current protocols tolerize patients using cytotoxic immunosuppressives, which can cause adverse effects. Here we show development of tolerance in Morquio A mice via oral delivery of peptide or GALNS for 10 days prior to ERT. Our results show that using an immunodominant peptide (I10) or the complete GALNS enzyme to orally induce tolerance to GALNS prior to ERT resulted in several improvements to ERT in mice: (a) decreased splenocyte proliferation after in vitro GALNS stimulation, (b) modulation of the cytokine secretion profile, (c) decrease in GALNS-specific IgG or IgE in plasma, (d) decreased GAG storage in liver, and (e) fewer circulating immune complexes in plasma. This model could be extrapolated to other lysosomal storage disorders in which immune response hinders ERT.

Efficacy, rate of tumor response, and safety of a short course (12-24 weeks) of oral vismodegib in various histologic subtypes (infiltrative, nodular, and superficial) of high-risk or locally advanced basal cell carcinoma, in an open-label, prospective case series clinical trial.

BACKGROUND: Vismodegib demonstrated 60% response rates in the ERIVANCE trial. Basal cell carcinoma has various histopathologies. Their effect on response is unclear. OBJECTIVE: The purpose of this study was to determine whether basal cell carcinoma histopathology affected vismodegib response. METHODS: This phase 2b, single-center, prospective case series study compared the efficacy of vismodegib in infiltrative, nodular, and superficial basal cell carcinomas treated for 12 or 24 weeks in 27 patients. Patients had 1 target lesion and up to 3 nontarget lesions. RESULTS: Twenty-seven patients were enrolled, with 65 tumors (27 target lesions/38 nontarget lesions). At 24 weeks, most basal cell carcinomas achieved histologic clearance, with positive biopsy results in 10.5% of target lesions, 30.4% of nontarget lesions, and 21.4% overall. No statistical differences were observed between histopathologic subtypes. One hundred percent of patients experienced an adverse event, 94% grade 1 or 2. The most common adverse events were dysgeusia/loss of taste (86%), muscle spasms (82%), and alopecia (71%). Clinically progressive disease during treatment was low (1.5%). Two patients had recurrence within 1 year of treatment. LIMITATIONS: Limitations included sample size of basal cell carcinoma histopathologic subtypes, sampling punch biopsies, and short follow-up. CONCLUSIONS: Basal cell histopathologic subtype did not significantly affect response to vismodegib. Each subtype was observed to completely respond at 12 weeks of therapy, 24 weeks, or both.

Dermatopathologist assessment of "pathologist-to-dermatologist" communication for dermatopathology services.

BACKGROUND: While patients are the ultimate beneficiaries of pathology services, pathologist to clinician communication is an essential component of excellent patient care. OBJECTIVE: To survey dermatologists on how well pathologists communicate with them and to assess which aspects of pathologists' communication skills are deemed most significant to dermatologists, stratified by practice type. METHODS: A survey-based instrument was developed and sent to dermatologists through various email listservs. Of the approximately 400 potential Association of Professors of Dermatology respondents, 64 returned the survey questionnaire (response rate 16%). Of the 79 state and regional dermatologic societies, seven agreed to distribute the survey on their listservs (response rate 9%). RESULTS: Surveyed dermatologists believe that the pathologists with whom they work are meeting expectations in the areas of diagnostic accuracy, communicating pertinent information in a timely fashion, integrating written pathology reports into the electronic medical record, and making a clinically meaningful histopathologic interpretation. Discussion of cost of ancillary testing is an area of improvement. University affiliated dermatologists are more likely to use electronic medical records as their predominant mode of communication compared to community dermatologists with and without academic affiliations. Community dermatologists are more likely to use faxed written pathology reports as their predominant mode of communication. CONCLUSION: Physician-to-physician communication is a key component of effective patient care. When it comes to dermatopathology services, dermatologists appear overall satisfied with the indicators examined, however, potential opportunities for improvement exist.