Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease.

To understand the dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune, and clinical markers of microbiomes from four body sites in 86 participants over 6 years. We found that microbiome stability and individuality are body-site specific and heavily influenced by the host. The stool and oral microbiome are more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment. We identify individual-specific and commonly shared bacterial taxa, with individualized taxa showing greater stability. Interestingly, microbiome dynamics correlate across body sites, suggesting systemic dynamics influenced by host-microbial-environment interactions. Notably, insulin-resistant individuals show altered microbial stability and associations among microbiome, molecular markers, and clinical features, suggesting their disrupted interaction in metabolic disease. Our study offers comprehensive views of multi-site microbial dynamics and their relationship with host health and disease.

Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease.

To understand dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune and clinical markers of microbiomes from four body sites in 86 participants over six years. We found that microbiome stability and individuality are body-site-specific and heavily influenced by the host. The stool and oral microbiome were more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment. Also, we identified individual-specific and commonly shared bacterial taxa, with individualized taxa showing greater stability. Interestingly, microbiome dynamics correlated across body sites, suggesting systemic coordination influenced by host-microbial-environment interactions. Notably, insulin-resistant individuals showed altered microbial stability and associations between microbiome, molecular markers, and clinical features, suggesting their disrupted interaction in metabolic disease. Our study offers comprehensive views of multi-site microbial dynamics and their relationship with host health and disease. Study Highlights: The stability of the human microbiome varies among individuals and body sites.Highly individualized microbial genera are more stable over time.At each of the four body sites, systematic interactions between the environment, the host and bacteria can be detected.Individuals with insulin resistance have lower microbiome stability, a more diversified skin microbiome, and significantly altered host-microbiome interactions.

Real-world clinical, psychosocial and economic burden of atopic dermatitis: Results from a multicountry study.

BACKGROUND: Atopic dermatitis (AD), a relapsing, inflammatory skin disease, is associated with pruritus that can negatively affect patients' quality of life. Understanding the burden of AD is critical for informing and tailoring treatment and disease management to improve patient outcomes. This study characterized global treatment patterns and the clinical, psychosocial and economic burden of moderate-to-severe AD. METHODS: MEASURE-AD was a cross-sectional 28-country study in patients with physician-confirmed moderate-to-severe AD who were either receiving or eligible for systemic therapy for AD. Patients ≥12 years were enrolled between December 2019 and December 2020 while attending routine office or clinic visit. Primary outcomes included Worst Pruritus Numeric Rating Scale (WP-NRS; range: 0-10) and Dermatology Life Quality Index (DLQI; range: 0-30) and Children's DLQI (CDLQI; range: 0-30). Secondary outcomes included physician- and patient-reported clinical, psychosocial and economic burden. RESULTS: Of the 1591 patients enrolled, 1558 (1434 adults and 124 adolescents) fulfilled all patient selection criteria and were included in this analysis. Almost all patients (98.4%) in the total population were using AD medications and more than half (56%) were receiving systemic medication (15% systemic monotherapy). The most used systemic therapies were dupilumab (56.3%), systemic glucocorticoids (18.1%) and methotrexate (16.2%). Mean WP-NRS was 5.3 in the total population, and most patients (≥55%) reported moderate-to-severe pruritus (WP-NRS ≥4). Mean DLQI was 10.8 and mean CDLQI was 9.6. Secondary endpoints demonstrated substantial clinical, psychosocial, and economic burden of disease. Subgroup analysis demonstrated that patients receiving systemic therapy had lower disease burden than those not taking systemic medications. CONCLUSIONS: While systemic therapy lowers overall disease burden, patients with moderate-to-severe AD continue to have substantial multidimensional disease burden and uncontrolled disease. Overall, there is a need for effective disease management, including effective treatments that improve patients' psychosocial outcomes and reduce the economic burden of AD.

Patient Perspectives on Selecting an Academic Aesthetic Surgeon: A Qualitative Analysis.

BACKGROUND: Growth of the aesthetic surgery marketplace has increased patient choice in provider selection. This study aimed to characterize how patients choose an aesthetic surgeon, identify knowledge gaps in this decision-making process, and understand why patients select academic aesthetic surgeons. METHODS: A qualitative interview study of aesthetic surgery patients from an academic center was conducted. Purposive sampling maximized representation regarding surgeon, surgery type, and patient demographics. An interview guide was developed in collaboration with content and methodology experts, then refined through pilot testing. Emergent themes were identified using a codebook constructed by grounded theory. RESULTS: Thematic saturation was achieved with 24 patients. When selecting a surgeon, participants valued bedside manner (24 of 24) and past patients' satisfaction (18 of 24). Most participants (16 of 24) ascribed low importance to board certification. Reasons given for choosing an academic practice included the institution's reputation (13 of 24) and the availability of medical records and other specialties if complications arise (8 of 24). Participants demonstrated knowledge gaps regarding medical training and licensure. No participant (0 of 24) was aware that any licensed physician can offer aesthetic surgery, and nearly all participants (23 of 24) expressed discomfort with this. CONCLUSIONS: Patients prioritize subjective elements when selecting an aesthetic surgeon, relying less on objective and meaningful qualifications like board certification and training background. Academic aesthetic practice is valued because of reputation and ability to function as a medical home. Given the lack of public understanding regarding physician training, initiatives promoting transparency are needed to ensure that patients can make safe, informed decisions.

Deconstructing the Excellent Plastic Surgeon: A Survey of Key Attributes.

Background: Most plastic surgeons practice in nonacademic settings, leaving a small subset of academic plastic surgeons with the responsibility of selecting the future generation of plastic surgeons without representation from a majority of our field. This raises questions as to whether the academic attributes valued during residency selection are valid predictive markers of who will become an excellent plastic surgeon. A survey was conducted of both academic and nonacademic plastic surgeons, as well as trainees, to determine what traits are considered most essential to being an excellent plastic surgeon. Methods: An electronic survey was distributed before the American Council of Academic Plastic Surgeons 10th Annual Winter Meeting. Demographics and information regarding the respondents' training and academic status were collected. Respondents were asked to select five traits that they considered most important to be an excellent plastic surgeon from a list of 20 preselected traits. Chi-square and Fisher exact tests were used to perform subgroup analyses. Results: A total of 187 responses were received from meeting attendees, representing an 89.0% response rate. Overall, the five values endorsed as most important for a plastic surgeon were being technically sound (53%), collaborative (48%), ethical (44%), compassionate (37%), and emotionally intelligent (33%). However, the emphasis placed on these different attributes differed significantly amongst different demographic groups. Conclusion: It is important that we use methods such as holistic review when evaluating plastic surgery applicants to ensure our selection process is congruent with the traits we value.

A SWOT Analysis of Hot Topics in Plastic Surgery Resident Education: Consensus From the ACAPS 10th Annual Winter Meeting.

Background: With the aim of facilitating a critical self-reflection on how to align plastic surgery education with making excellent plastic surgeons, a rotating small-group session followed by live interactive audience polling was used to perform a SWOT (strengths, weaknesses, opportunities, and threats) analysis at the 10th Annual American Council of Academic Plastic Surgeons Winter Meeting. Methods: The final day of the conference included a 3-hour session of rotating small groups followed by live interactive audience polls discussing the following six relevant educational topics: the Plastic Surgery Common Application and resident selection, aesthetic surgery education, leadership development and business education, embedded fellowships and focused training, mentorship, and faculty retention. Results: A total of 60 individuals participated in the activity. A SWOT analysis was successfully performed for each educational topic, and a minimum of four opportunities were identified per topic to help guide future endeavors. Examples of opportunities include releasing recommendations for the implementation of holistic review; developing formal guidelines for aesthetic surgery education in residency via collaboration between ACAPS, American Society of Plastic Surgeons, and The Aesthetic Society; creating extended focused elective rotations; integrating business education into formal curricula for all training levels; enforcing transparency regarding position expectations and offerings including salary, call schedule, and current challenges; and more. Conclusion: The results of this study will help guide future initiatives by the ACAPS to improve resident education and academic retention.

Policy stringency and the spread of COVID-19: The moderating role of culture and its implications on first responses.

There has been a noticeable variance between countries in the growth rate of COVID-19 since the start of the pandemic. Researchers attempted to understand this variance from two primary perspectives: the policies implemented to curb the spread of the virus [1] and the cross-country cultural differences [2]. However, little research to date has looked at the joint effects of policy responses and national culture. We argue that the effectiveness of restrictive policies depends on cultural values. Specifically, when policies are non-mandatary, cultural values influence people's voluntary adherence to these policies, and hence, the spread of COVID-19. We analyzed the growth data in daily new cases across 78 countries, focusing on the joint impact of containment policies and cultural values. We found that although policy responses (i.e., containment policies) significantly predicted the spread rate of COVID-19 over time, their effects were moderated by cultural variables as well. Implications for policymaking are discussed.

The Utility of the Plastic Surgery Standardized Letter of Recommendation Form in Predicting Residency Match Outcomes.

BACKGROUND: Letters of recommendation play an important role in resident selection. While plastic surgery's Standardized Letter of Recommendation (SLOR) form most commonly serves as an adjunct to narrative letters, the SLOR provides objective data in the review process and could eventually replace narrative letters. The utility of the SLOR in predicting Match outcomes has not been studied. METHODS: Applicant data from 225 first-time residency applicants in 2020-21 were collected. Logistic regression modeling was used to predict Match outcomes. This model was validated using 100 randomly selected applicants from 2019-20. RESULTS: Rank placement (SLOR Question 6) was the most important factor when predicting Match outcomes (p<0.0001). All other SLOR questions were not predictive and subject to notable score inflation. No SLOR score differences were noted based on race; female applicants were rated higher in two of ten domains (p<0.05). CONCLUSIONS: One question on the plastic surgery SLOR was highly predictive of an applicant matching. However, the remaining SLOR questions had little utility and were subject to gross score inflation. Further work should be done to optimize the utility of the SLOR in differentiating applicants. This has important implications in ensuring the selection of professional, competent residents according to the aims of the Accreditation Council of Graduate Medical Education.

Overlapping Surgeries From the Patient's Perspective.

INTRODUCTION: Overlapping surgery (OS) occurs when a single surgeon is concurrently caring for patients in multiple operating rooms (OR) but is present for all critical portions of each surgery. Although this is common practice, most studies have found public disapproval of OS. This study aims to better understand attitudes toward OS of patients who gave informed consent for OS. METHODS: Participant interviews covered topics including trust, OR personnel roles, and attitudes toward OS. Four representative transcripts were distributed among researchers for independent code identification. These were aggregated into a codebook, applied by two coders. Iterative and emergent thematic analyses were done. RESULTS: Twelve participants were interviewed to reach thematic saturation. Three themes shaped how participants felt about OS: trust in their surgeon, worries about OS, and understanding of OR personnel roles. Factors contributing to trust included personal research and the surgeon's experience. Frequently cited concerns were unpredictability of complications during operations and the surgeon's divided attention. Two participants inaccurately understood personnel roles, believing the surgeon did most or all the hands-on work while trainees were observers. Most participants felt a high or neutral level of comfort toward OS and indicated trust as the reason. CONCLUSIONS: In contrast to prior research, this study found that most participants had a neutral or positive view of OS. This suggests that a trusting relationship with their surgeon and informed consent are important factors in increasing comfort for OS. Participants who misunderstood OR roles felt less comfortable toward OS. This highlights an opportunity for patient education on trainee roles.

Compartment Syndrome in the Foot and Leg.

Chronic exertional compartment syndrome is a common cause of exercise-related leg pain that can be debilitating to many athletes. Diagnosis of this syndrome is based on patient history and clinical examination in correlation with intracompartmental pressure measurement or other advanced diagnostic tests. Treatments include initial nonsurgical management, such as modification of causative activity and gait retraining with physical therapy. If symptoms persist, surgical fasciotomy may be warranted via an open or minimally invasive approach. In this article, we review the anatomy, pathophysiology, history and physical examination, diagnostic modalities, treatment, and complications of chronic exertional compartment syndrome in the athlete.

Prediction of cognitive impairment using higher order item response theory and machine learning models.

Timely detection of cognitive impairment (CI) is critical for the wellbeing of elderly individuals. The MyCog assessment employs two validated iPad-based measures from the NIH Toolbox® for Assessment of Neurological and Behavioral Function (NIH Toolbox). These measures assess pivotal cognitive domains: Picture Sequence Memory (PSM) for episodic memory and Dimensional Change Card Sort Test (DCCS) for cognitive flexibility. The study involved 86 patients and explored diverse machine learning models to enhance CI prediction. This encompassed traditional classifiers and neural-network-based methods. After 100 bootstrap replications, the Random Forest model stood out, delivering compelling results: precision at 0.803, recall at 0.758, accuracy at 0.902, F1 at 0.742, and specificity at 0.951. Notably, the model incorporated a composite score derived from a 2-parameter higher order item response theory (HOIRT) model that integrated DCCS and PSM assessments. The study's pivotal finding underscores the inadequacy of relying solely on a fixed composite score cutoff point. Instead, it advocates for machine learning models that incorporate HOIRT-derived scores and encompass relevant features such as age. Such an approach promises more effective predictive models for CI, thus advancing early detection and intervention among the elderly.

Management of the Charcot Foot and Ankle: Nonreconstructive Surgery.

Diabetic neuroarthropathy is a complication of diabetes mellitus that results in instability of the foot, structural deformity, and soft-tissue breakdown. Commonly, midfoot collapse of the medial, lateral, or both longitudinal arches may result in increased plantar pressures and subsequent midfoot ulceration. Many of these wounds can be successfully managed with local wound care and off-loading; however, surgical intervention becomes necessary in cases of osteomyelitis or when the wound fails to heal despite conservative efforts. In cases where surgical reconstruction may not be indicated, nonreconstructive surgical efforts have shown effectiveness in resolving wounds and allowing patients to return to ambulatory lifestyles. This article serves as an update to current treatment recommendations for the nonreconstructive surgical management of Charcot neuroarthropathy.

Board Certification in Cosmetic Surgery: An Examination of Online Advertising Practices.

BACKGROUND: Aesthetic surgery patients commonly use online resources to select a surgeon. The American Board of Plastic Surgery is the American Board of Medical Specialties member board that certifies plastic surgeons. The American Board of Cosmetic Surgery (ABCS) provides aesthetic surgery credentials through a non-American Board of Medical Specialties-recognized process. This study examines use of the phrases "plastic surgery" and "plastic surgeon" by ABCS-certified surgeons when advertising online. METHODS: Diplomates of the ABCS were identified from the ABCS Web site. Professional Web sites, Facebook business pages, and Instagram profiles were located by online search. Use of the descriptor "plastic" and ABCS board certification on practice Web sites, Facebook business page categorization, and plastic surgery-related hashtag use on Instagram were recorded. RESULTS: A total of 298 non-American Board of Plastic Surgery-certified ABCS diplomates were included. One hundred eighty-nine (69.5%) categorized their Facebook business page as "plastic surgeon." Within Instagram posts, 123 (57.2%) used #plasticsurgeon, and 172 (80.0%) used #plasticsurgery. On professional Web sites, 90 (30.4%) identified themselves as a "plastic surgeon," 123 (41.6%) characterized their practice as "plastic surgery," and 196 (68.5%) used their ABCS credential to identify as a "board-certified" cosmetic surgeon. CONCLUSIONS: Diplomates of the ABCS frequently use "plastic surgeon" and "plastic surgery" in online advertisements despite a lack of accredited plastic surgery training or board certification. Furthermore, most ABCS diplomates use their ABCS credentials to market themselves as "board-certified" cosmetic surgeons, potentially violating American Medical Association-supported truth in advertising laws in some states and increasing public confusion regarding different board certifications.

A macaque clonal hematopoiesis model demonstrates expansion of TET2-disrupted clones and utility for testing interventions.

Individuals with age-related clonal hematopoiesis (CH) are at greater risk for hematologic malignancies and cardiovascular diseases. However, predictive preclinical animal models to recapitulate the spectrum of human CH are lacking. Through error-corrected sequencing of 56 human CH/myeloid malignancy genes, we identified natural CH driver mutations in aged rhesus macaques matching genes somatically mutated in human CH, with DNMT3A mutations being the most frequent. A CH model in young adult macaques was generated via autologous transplantation of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated gene-edited hematopoietic stem and progenitor cells (HSPCs), targeting the top human CH genes with loss-of-function (LOF) mutations. Long-term follow-up revealed reproducible and significant expansion of multiple HSPC clones with heterozygous TET2 LOF mutations, compared with minimal expansion of clones bearing other mutations. Although the blood counts of these CH macaques were normal, their bone marrows were hypercellular and myeloid-predominant. TET2-disrupted myeloid colony-forming units isolated from these animals showed a distinct hyperinflammatory gene expression profile compared with wild type. In addition, mature macrophages purified from the CH macaques showed elevated NLRP3 inflammasome activity and increased interleukin-1ß (IL-1ß) and IL-6 production. The model was used to test the impact of IL-6 blockage by tocilizumab, documenting a slowing of TET2-mutated expansion, suggesting that interruption of the IL-6 axis may remove the selective advantage of mutant HSPCs. These findings provide a model for examining the pathophysiology of CH and give insights into potential therapeutic interventions.

Clinical Evaluation of BD Veritor SARS-CoV-2 and Flu A+B Assay for Point-Of-Care System.

Differential diagnosis of COVID-19 and/or influenza (flu) at point of care is critical for efficient patient management and treatment of both these diseases. The study presented here characterizes the BD Veritor System for Rapid Detection of SARS-CoV-2 and Flu A+B ("Veritor SARS-CoV-2/Flu") triplex assay. The performance for SARS-CoV-2 detection was determined using 298 specimens from patients reporting COVID-19 symptoms within 7 days from symptom onset (DSO) in comparison with the Lyra SARS-CoV-2 RT-PCR (reverse transcriptase PCR) assay ("Lyra SARS-CoV-2") as the reference. The performance for flu A and flu B detection was determined using 75 influenza-positive and 40 influenza-negative retrospective specimens in comparison with the previously FDA-cleared BD Veritor System for Rapid Detection of Flu A+B assay ("Veritor Flu") as the reference. The Veritor SARS-CoV-2/Flu assay met the FDA EUA acceptance criteria (86.7%; 95% confidence interval [95% CI]: 75.8 to 93.1) for SARS-CoV-2 testing compared to Lyra SARS-CoV-2. The Veritor SARS-CoV-2/Flu assay also demonstrated 100% agreement with the Veritor Flu for Flu A+B assay. For flu A detection, the lower bound of the 95% CI was 91.2%; for flu B detection, the lower bound was 90.0%. The dual detection capability of Veritor SARS-CoV-2/Flu for the etiologic agents causing COVID-19 and flu will allow efficient differentiation between the two illnesses, inform disease management, and facilitate optimal treatment. IMPORTANCE COVID-19 and flu are two respiratory illnesses which share similar clinical symptoms. The BD Veritor SARS-CoV-2/Flu assay has high sensitivity and specificity for detecting the SARS-CoV-2 and influenza A/B, the two etiologic agents causing COVID-19 and flu, respectively. This dual detection capability is critical when overlap occurs between the COVID-19 pandemic and the flu season. This triplex assay will allow efficient differentiation between the two respiratory illnesses and support a point-of-care physician diagnosis to facilitate the proper treatment and disease management for patients exhibiting overlapping symptoms.

Safety of Tibial Half Pins With Circular External Fixation for Foot and Ankle Reconstruction in Patients With Peripheral Neuropathy.

The primary aim of the study was to evaluate the rate of tibial fracture with half pin placement in conjunction with tensioned wires in Ilizarov static external fixator in patients with peripheral neuropathy. Concentric visualization through a rancho cube and careful identification of anterior, posterior, medial, and lateral borders of the tibia, the "perfect circle" technique was used to ensure avoidance of cortical breach. Bivariate analysis was performed comparing the rates of tibia fractures in those who did and did not employ the "perfect circle" technique for placement of tibial half pins; evaluating for demographics, rationale for external fixation use, and postoperative amputation and complication rates. Tibial stress fractures, and early removal of pin/wires from external fixator secondary to breakage both occurred at statistically significant higher rates in patients in which the "perfect circle" technique was not employed (p < .001 and p = .03 respectively). The overall rate of tibia stress fractures was 2.08% (2/96), 0% (0/85) when "perfect circle" technique was used, compared to 18.18% (2/11) when it was not used. This study demonstrates a substantially low rate of tibia stress fractures with half pin use, in contrast to prior literature and should provide foot and ankle surgeons confidence, particularly when appropriate placement is observed in this high-risk population.

The association between social ties and changes in depressive symptoms among veterans enrolled in a collaborative depression care management program.

A greater understanding of factors that are associated with successful outcomes among patients receiving collaborative depression care services is needed. This study sought to examine the unique associations between 3 indices of social ties and changes in depressive symptoms among veterans receiving collaborative depression care management. Data on sociodemographics, behavioral health indices, perceived general health, perceived social support, frequency of negative social exchanges, and degree of social contact were extracted from the electronic health records of 868 veterans meeting criteria for at least moderate depressive symptom severity and enrolled in a Primary Care-Mental Health Integration (PCMHI) program. Veterans were on average 51.3 (SD = 15.9) years old and primarily male. Higher depressive symptoms at baseline were significantly correlated with less perceived social support, less frequent contact with family and friends, and greater frequency of negative social exchanges. Adjusted regression analyses revealed that only social contact was significantly related to changes in depressive symptoms over the course of care management, once controlling for covariates. The results highlight the value of taking multiple indices of social ties into account when providing depression care management services. Routinely assessing patients' level of social contact can potentially help tailor and inform intervention efforts aimed at reducing depressive symptoms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Prediction and validation of hematopoietic stem and progenitor cell off-target editing in transplanted rhesus macaques.

The programmable nuclease technology CRISPR-Cas9 has revolutionized gene editing in the last decade. Due to the risk of off-target editing, accurate and sensitive methods for off-target characterization are crucial prior to applying CRISPR-Cas9 therapeutically. Here, we utilized a rhesus macaque model to compare the predictive values of CIRCLE-seq, an in vitro off-target prediction method, with in silico prediction (ISP) based solely on genomic sequence comparisons. We use AmpliSeq HD error-corrected sequencing to validate off-target sites predicted by CIRCLE-seq and ISP for a CD33 guide RNA (gRNA) with thousands of off-target sites predicted by ISP and CIRCLE-seq. We found poor correlation between the sites predicted by the two methods. When almost 500 sites predicted by each method were analyzed by error-corrected sequencing of hematopoietic cells following transplantation, 19 off-target sites revealed insertion or deletion mutations. Of these sites, 8 were predicted by both methods, 8 by CIRCLE-seq only, and 3 by ISP only. The levels of cells with these off-target edits exhibited no expansion or abnormal behavior in vivo in animals followed for up to 2 years. In addition, we utilized an unbiased method termed CAST-seq to search for translocations between the on-target site and off-target sites present in animals following transplantation, detecting one specific translocation that persisted in blood cells for at least 1 year following transplantation. In conclusion, neither CIRCLE-seq or ISP predicted all sites, and a combination of careful gRNA design, followed by screening for predicted off-target sites in target cells by multiple methods, may be required for optimizing safety of clinical development.