Search

We aimed to establish a relationship between the amount of Montgomery tubercles (MTs) per nipple-areolar complex (NAC) given patient characteristics such as age, BMI, menopausal status, race/ethnicity, and NAC size to better inform current 3D NAC tattooing practices.Preoperative photographs of patients pursuing breast reconstruction after mastectomy in 2010 through 2018 were reviewed. The number of MTs on each native NAC was quantified. The impact of patient factors on the quantity of MTs was evaluated via Pearson correlation and bivariate analyses.Two hundred and eleven patients (399 breasts) were reviewed. On average, patients had 5.0 ± 5.2 MTs (range, 0-25 MTs). Number of MTs did not correlate with patient age, BMI, or NAC size. Premenopausal females were more likely than postmenopausal females to have a greater number of MTs per breast (p-value = 0.0183).Postmastectomy patients desiring a more "youthful" NAC may consider additional MTs when pursuing 3D NAC tattooing.

The effect of postoperative sensation on quality-of-life (QoL) following nipple-sparing mastectomy (NSM) with implant-based reconstruction is not well described. We evaluated the impact of breast and nipple sensation on patient QoL by using BREAST-Q.Patients undergoing NSM with implant reconstruction from 2008 to 2020 were mailed a survey to characterize their postoperative breast and nipple sensation. BREAST-Q metrics were compared between totally numb patients and those with sensation.A total of 349 patients were included. Overall, 131 (38%) responded; response rates regarding breast and nipple sensation were 36% (N = 124/349) and 34% (N = 117/349). Median time from surgery to survey completion was 6 years. The majority had bilateral procedures (101, 77%), including direct-to-implant (99, 76%) and tissue expander (32, 24%) reconstruction. Regarding breast sensation, the majority of patients reported their reconstructed breasts as totally numb (47, 38%) or much less sensation than before surgery (59, 48%). Regarding nipple sensation, the majority of patients reported their nipples were totally numb (67, 57%) or had much less sensation than before surgery (37, 32%). Total numbness of reconstructed breasts resulted in a significantly lower chest physical well-being (mean score: 73.5 vs. 81.2, respectively, P = 0.048). Total numbness of postoperative nipple(s) resulted in significantly lower chest physical (mean score: 74.8 vs. 85.2, respectively, P = 0.007), psychosocial (mean score 77.4 vs. 84.4, respectively, P = 0.041), and sexual well-being (mean score: 55.7 vs. 68.3, respectively, P = 0.002).Long-term breast and nipple sensation are significantly diminished after NSM with implant reconstruction. Patients with preserved sensation experience better physical, psychosocial, and sexual well-being.

Platelets are subcellular anucleate components of blood primarily responsible for initiating and maintaining hemostasis. After injury to a blood vessel, platelets can be activated via several pathways, resulting in changed shape, adherence to the injury site, aggregation to form a plug, degranulation to initiate activation in other nearby platelets, and acceleration of thrombin formation to convert fibrinogen to fibrin before contracting to strengthen the clot. Platelet function assays use agonists to induce and measure one or more of these processes to identify alterations in platelet function that increase the likelihood of bleeding or thrombotic events. In severe trauma, these assays have revealed that platelet dysfunction is strongly associated with poor clinical outcomes. However, to date, the mechanism(s) causing clinically significant platelet dysfunction remain poorly understood. We review the pros, cons, and evidence for use of many of the popular assays in trauma, discuss limitations of their use in this patient population, and present approaches that can be taken to develop improved functional assays capable of elucidating mechanisms of trauma-induced platelet dysfunction. Platelet dysfunction in trauma has been associated with need for transfusions and mortality; however, most of the current platelet function assays were not designed for evaluating trauma patients, and there are limited data regarding their use in this population. New or improved functional assays will help define the mechanisms by which platelet dysfunction occurs, as well as help optimize future treatment.

Spontaneous tumor shrinkage during wait-and-scan management of sporadic vestibular schwannoma is generally considered an uncommon phenomenon. However, most data informing this understanding stem from single-slice linear tumor measurements taken in the axial imaging plane. The objective of the current work was to characterize the regression capacity of sporadic vestibular schwannomas using volumetric tumor measurements.Retrospective cohort study using slice-by-slice, three-dimensional volumetric tumor measurements.Three tertiary referral centers.Patients with sporadic vestibular schwannoma.Wait-and-scan.Regression-free survival rates with regression defined as a decrease of at least 20% of the tumor volume.Among 952 patients undergoing a total of 3,505 magnetic resonance imaging studies during observation, 123 experienced volumetric tumor regression after diagnosis at a median of 1.2 years (interquartile range, 0.6-2.9 yr). Volumetric regression-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after diagnosis were 94% (92-95%; 662), 86% (83-89%; 275), and 78% (73-82%; 132), respectively. Among 405 patients who demonstrated an initial period of tumor growth but continued wait-and-scan management, 48 experienced volumetric regression at a median of 1.2 years (interquartile range, 0.8-2.6 yr) after initial growth. Volumetric regression-free survival rates at 1, 3, and 5 years after initial growth were 94% (92-97%; 260), 84% (79-89%; 99), and 75% (67-83%; 43), respectively. Ultimately, only 82 of the 952 patients studied showed exclusively volumetric tumor regression (i.e., without any periods of tumor growth) by the time of last follow-up.Spontaneous volumetric tumor shrinkage during wait-and-scan management occurs more frequently than suggested by previous studies using linear tumor measurements and can even occur after previous episodes of documented tumor growth. These data further highlight the dynamic nature of vestibular schwannoma growth. To this end, the application of natural history data to patient management requires a nuanced approach that parallels the complex tumor behavior of vestibular schwannoma.

This study aimed to assess the durability of audiological outcomes after radiation and surgery in the management of vestibular schwannoma.Retrospective review.Tertiary academic center.Adults with sporadic vestibular schwannoma and serviceable hearing at the time of intervention.Gamma Knife, middle cranial fossa, or retrosigmoid approaches.Pure-tone audiometry and speech discrimination scores.Postintervention serviceable hearing (class A/B) was preserved in 70.4% (n = 130; mean follow-up, 3.31 yr; range, 0-15.25 yr). Of the 49 patients treated with radiation, 19 (39.6%) had serviceable hearing at last follow-up, compared with 38 (46.9% of 81) who underwent retrosigmoid (n = 36 [44.4%]) and middle cranial fossa (n = 45 [55.6%]) approaches (odds ratio [OR], 1.40; 95% confidence interval [CI], 0.67-2.82; p = 0.47). A matched analysis by age, tumor volume, and preintervention hearing (n = 38) also found no difference in hearing preservation (HP) likelihood between surgery and radiation (OR, 2.33; 95% CI, 0.24-35.91; p = 0.59). After initial HP, 4 (9.5%) surgical versus 10 (37.0%) radiated patients subsequently lost residual serviceable (A/B) hearing (OR, 0.18; 95% CI, 0.06-0.69; p = 0.01) at a mean 3.74 ± 3.58 and 4.73 ± 3.83 years after surgery and radiation, respectively. Overall, 5- and 10-year HP rates (A/B) after initially successful HP surgery were 84.4 and 63.0%, respectively. However, survival estimates declined to 48.9% at 5 years and 32.7% at 10 years when patients with immediate postoperative serviceable hearing loss were also included, which were comparable to radiation-HP rates at 5 and 10 years of 28.0 and 14.2%, respectively ( p = 0.75).After vestibular schwannoma intervention, overall HP was similar between radiated and surgical cohorts. However, when successful, surgical approaches offered more durable hearing outcomes at long-term follow-up.

To assess endoscopic and microscopic ossiculoplasty audiometric outcomes.Retrospective review.Tertiary academic center.Adult patients who underwent ossiculoplasty with either partial ossicular replacement prosthesis (PORP) or total ossicular replacement prosthesis (TORP) from 2010 to 2019 with at least 1 year of audiometric follow-up were included.Endoscopic or microscopic ossiculoplasty.Postoperative air-bone gap (ABG) after at least 1 year.A total of 198 patients, 53.5% female, and a median age of 47.5 years, met inclusion criteria. 64.1% of patients were reconstructed with a PORP, and 31.8% were reconstructed using an endoscopic approach. The median audiometric follow-up was 27 months. The median postoperative ABG was 16.9 dB overall, 15.6 dB for PORP reconstruction, and 19.4 dB for TORP reconstruction (PORP versus TORP, p = 0.002). For TORP reconstructions, the median ABG for both endoscopic and microscopic TORP was 19.4 dB ( p = 0.92). For PORP reconstructions, the median ABG for endoscopic PORP was 12.3 dB compared with 16.3 dB for microscopic PORP ( p = 0.02). Using multivariate linear regression to predict postoperative PORP ABG, and controlling for age, prior ossiculoplasty, middle ear mucosal disease (granulation, fibrosis, polyposis), middle ear atelectasis, myringitis, contralateral middle ear disease, and use of byte prostheses, endoscopic PORP reconstruction was associated with improvement in ABG over the microscopic approach by 4.4 dB ( p = 0.04).For PORP ossiculoplasty procedures, endoscopic ossiculoplasty is associated with improved postoperative ABG compared with microscopic ossiculoplasty.

Behavioral problems, such as noncompliance and aggression, are a common referral reason to mental health services for young children. Behavioral parent training (BPT) is the leading intervention for addressing behavioral problems and leads to benefits in a variety of parental factors (e.g., parenting efficacy and parenting stress). While the COVID-19 pandemic dramatically shifted service delivery toward telehealth services, limited work has evaluated the effectiveness of BPT when delivered in a brief, group format through telehealth. The current retrospective chart review study evaluated the engagement to and preliminary effectiveness of a brief version of BPT delivered through telehealth to 64 families of 3- to 7-year-olds referred for behavioral problems. Families attended an average of 4.55 of 6 sessions and most families had two caregivers who engaged in the intervention. Significant reductions in caregivers’ report of children’s behavioral problems and improvements in parenting self-efficacy resulted. Future research and clinical implications are discussed.

Minimally invasive inguinal lymphadenectomy (MILND) is safe and feasible, but limited data exist regarding oncologic outcomes.This study performed a multi-institutional retrospective cohort analysis of consecutive MILND performed for melanoma between January 2009 and June 2016. The open ILND (OILND) comparative cohort comprised patients enrolled in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II) between December 2004 and March 2014.The pre-defined primary end point was the same-basin regional nodal recurrence, calculated using properties of binomial distribution. Time to events was calculated using the Kaplan-Meier method. The secondary end points were overall survival, progression-free survival, melanoma-specific survival (MSS), and distant metastasis-free survival (DMFS).For all the patients undergoing MILND, the same-basin regional recurrence rate was 4.4 % (10/228; 95 % confidence interval [CI], 2.1-7.9 %): 8.2 % (4/49) for clinical nodal disease and 3.4 % (6/179) for patients with a positive sentinel lymph node (SLN) as the indication. For the 288 patients enrolled in MSLT-II who underwent OILND for a positive SLN, 17 (5.9 %) had regional node recurrence as their first event. After controlling for ulceration, positive LN count and positive non-SLNs at the time of lymphadenectomy, no difference in OS, PFS, MSS or DMFS was observed for patients with a positive SLN who underwent MILND versus OILND.This large multi-institutional experience supports the oncologic safety of MILND for melanoma. The outcomes in this large multi-institutional experience of MILND compared favorably with those for an OILND population during similar periods, supporting the oncologic safety of MILND for melanoma.

Consolidation of physician practices is well-documented in recent years, yet minimal data exist regarding consolidation in general surgery. This study evaluates current trends in general surgery practice consolidation.Data were obtained through the CMS Physician Compare database. Surgeons and practices were categorized by size, and trends were analyzed using the Cochran-Armitage test. Data were stratified by US region.From 2012 to 2020, practicing general surgeons increased from 20,044 to 20,637 (+3%). Unique general surgery practices declined from 8178 to 6489 (-21%). The percentage of surgeons in practices of 1 or 2 declined from 19% to 12%, while surgeons in groups of 500 or more grew from 20% to 31%. Tests for trends towards consolidation at both the individual surgeon and unique practice levels were significant (p .001). The Midwest region demonstrated the highest degree of consolidation.Consistent with trends in medicine overall, general surgery is experiencing substantial practice consolidation.

Introduction: The transition from a normal fundus to one with early drusen (≥20 small hard drusen) to age-related macular degeneration (AMD) in the form of drusen ≥63 μm in diameter is of interest, because small hard drusen may be precursors of large drusen. Study of AMD precursor lesions may provide valuable insight into factors that initiate AMD. Here, the progression of drusen was studied over an interval of 20 years in a population-based twin cohort. Methods: Single-center, 20-year follow-up of 138 twins include biometry, fundus optical coherence tomography, and fundus photography. Macular characteristics were hierarchically classified as (per eye) (1) Results: Median participant age was 59 (range 41–66) years. Of 25 (18%) cases of incident macular drusen, 7 had ≥20 small hard drusen, and 18 had drusen ≥63 μm at follow-up, whereas no participant had developed both traits simultaneously. Smoking was associated with incident ≥20 small hard drusen (p = 0.04) and incident drusen ≥63 μm (p = 0.003). Having ≥20 small hard drusen at baseline was associated with incident drusen ≥63 μm at follow-up (p = 0.02). Development of drusen ≥63 μm was attributable to 49% genetic effects and 51% environmental effects. Conclusion: The risk of progressing from 0 to 19 small hard macular drusen per eye to having ≥20 small hard drusen or drusen ≥63 μm at follow-up was associated with smoking and genetic predisposition. Having ≥20 small hard drusen in the absence of drusen ≥63 μm at baseline was associated with incident drusen ≥63 μm when examined 20 years later. The study confirms that small hard macular drusen is a forewarning of AMD and that progression to AMD may be hindered by avoidance of smoking.

Contemporary research on human sociality is heavily influenced by the social identity approach, positioning social categorization as the primary mechanism governing social life. Building on the distinction between agency and identity in the individual self (“I” vs. “Me”), we emphasize the analogous importance of distinguishing collective agency from collective identity (“We” vs. “Us”). While collective identity is anchored in the unique characteristics of group members, collective agency involves the adoption of a shared subjectivity that is directed toward some object of our attention, desire, emotion, belief, or action. These distinct components of the collective self are differentiated in terms of their mental representations, neurocognitive underpinnings, conditions of emergence, mechanisms of social convergence, and functional consequences. Overall, we show that collective agency provides a useful complement to the social categorization approach, with unique implications for multiple domains of human social life, including collective action, responsibility, dignity, violence, dominance, ritual, and morality.

Cytotoxic CD8+ T cells (CTL) are a crucial component of the immune system notable for their ability to eliminate rapidly proliferating malignant cells. However, the T-cell intrinsic factors required for human CTLs to accomplish highly efficient antitumor cytotoxicity are not well defined. By evaluating human CD8+ T cells from responders versus nonresponders to treatment with immune checkpoint inhibitors, we sought to identify key factors associated with effective CTL function. Single-cell RNA-sequencing analysis of peripheral CD8+ T cells from patients treated with anti–PD-1 therapy showed that cells from nonresponders exhibited decreased expression of the cytolytic granule-associated molecule natural killer cell granule protein-7 (NKG7). Functional assays revealed that reduced NKG7 expression altered cytolytic granule number, trafficking, and calcium release, resulting in decreased CD8+ T-cell–mediated killing of tumor cells. Transfection of T cells with NKG7 mRNA was sufficient to improve the tumor-cell killing ability of human T cells isolated from nonresponders and increase their response to anti–PD-1 or anti–PD-L1 therapy in vitro. NKG7 mRNA therapy also improved the antitumor activity of murine tumor antigen–specific CD8+ T cells in an in vivo model of adoptive cell therapy. Finally, we showed that the transcription factor ETS1 played a role in regulating NKG7 expression. Together, our results identify NKG7 as a necessary component for the cytotoxic function of CD8+ T cells and establish NKG7 as a T-cell–intrinsic therapeutic target for enhancing cancer immunotherapy. See related article by Li et al., p. 154.

Introduction Cochlear implantation (CI) is an underutilized treatment for hearing loss in the United States for reasons which remain unclear. This study explores self-identified barriers to CI employing a survey of adults who qualified for CI. Methods A single-institutional review of CI candidates between December 2010 and December 2018 was performed to identify patients who did not pursue surgery. A 21-question survey was developed, aimed at rating patients' concerns regarding CI, including surgical risks, adaptation, costs, time commitment, loss of residual hearing, and lack of benefit, among others. Current hearing aid usage and familiarity with other CI users were also analyzed. The survey was administered to patients who did not pursue CI and a control group who eventually did pursue CI, via email or telephone. Results There were 199 patients who initially did not pursue CI. Fifty-two survey responses were received, comprised of 27 patients who did not pursue CI and 25 patients who did. A belief that CI would not significantly improve the ability to communicate was the most common reported barrier, followed by the postoperative recovery process, risks of surgery, and risks of losing music appreciation. Anesthetic risk and cost were the least important reasons not to pursue CI. Half of patients reported concerns regarding the period of adjustment with the CI. Conclusion The decision not to pursue CI despite eligibility is multifactorial and includes concern for minimal hearing benefit and perioperative risks. These factors should be taken into consideration when counseling patients on CI surgery.

This article systematically reviews the evidence base for couple and family interventions for depressive and bipolar disorders published from 2010 to 2019. Included in the review were intervention studies on depression for couples (n = 6), depression for families (n = 13), and bipolar for families (n = 5); zero studies on couple interventions for bipolar were located. Well-established interventions include cognitive and/or behavioral couple and family interventions for depression and psychoeducational family interventions for bipolar. Attachment-based couple and family interventions for depression are probably efficacious. Finally, family psychoeducation for depression is possibly efficacious, and integrative couple interventions and family play-based interventions for depression are experimental. Couple and family interventions also improved relationship dynamics, which is noteworthy since poor relationships are associated with non-remission, relapse, and recurrence of depressive and bipolar symptoms. Future research is needed on couple interventions for bipolar disorders and interventions for minoritized populations.

Objective Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are two debilitating, moderately comorbid illnesses in which chronic musculoskeletal pain symptoms are prevalent. These individuals can experience post-exertional malaise (PEM), a phenomenon in which symptom severity is worsened for 24 hours or longer after physical stress, but the pain-related component of PEM is not well characterized. Design Systematic review and meta-analysis. Methods Case–control studies involving adults with ME/CFS or FM and measuring pain symptoms before and after exposure to a standardized aerobic exercise test were included. Hedges’ d effect sizes were aggregated with random-effects models, and potential moderators were explored with meta-regression analysis. Results were adjusted for nesting effects with three-level modeling. Results Forty-five effects were extracted from 15 studies involving 306 patients and 292 healthy controls. After adjusting for nesting effects, we observed a small to moderate effect indicating higher post-exercise pain in patients than in controls (Hedges’ d = 0.42; 95% confidence interval [CI]: 0.16–0.67). The mean effect was significantly moderated by pain measurement time point (b = –0.19, z = –2.57, P = 0.01), such that studies measuring pain 8–72 hours after exercise showed larger effects (d = 0.71, 95% CI = 0.28–1.14) than did those measuring pain 0–2 hours after exercise (d = 0.32, 95% CI = 0.10–0.53). Conclusions People with ME/CFS and FM experience small to moderate increases in pain severity after exercise, which confirms pain as a component of PEM and emphasizes its debilitating impact in ME/CFS and FM. Future directions include determining mechanisms of pain-related PEM and developing exercise prescriptions that minimize symptom exacerbation in these illnesses.

BACKGROUND AND PURPOSE This study aims todetermine the sensitivity of superficial white matter (SWM) integrity as a metric to distinguish early multiple sclerosis (MS) patients from healthy controls (HC). METHODS Fractional anisotropy and mean diffusivity (MD) values from SWM bundles across the cortex and major deep white matter (DWM) tracts were extracted from 29 early MS patients and 31 age- and sex-matched HC. Thickness of 68 cortical regions and resting-state functional-connectivity (RSFC) among them were calculated. The distribution of structural and functional metrics between groups were compared using Wilcoxon rank-sum test. Utilizing a machine learning method (adaptive boosting), 6 models were built based on: 1-SWM, 2-DWM, 3-SWM and DWM, 4-cortical thickness, or 5-RSFC measures. In model 6, all features from previous models were incorporated. The models were trained with nested 5-folds cross-validation. Area under the receiver operating characteristic curve (AUCroc ) values were calculated to evaluate classification performance of each model. Permutation tests were used to compare the AUCroc values. RESULTS Patients had higher MD in SWM bundles including insula, inferior frontal, orbitofrontal, superior and medial temporal, and pre- and post-central cortices (p < .05). No group differences were found for any other MRI metric. The model incorporating SWM and DWM features provided the best classification (AUCroc = 0.75). The SWM model provided higher AUCroc (0.74), compared to DWM (0.63), cortical thickness (0.67), RSFC (0.63), and all-features (0.68) models (p < .001 for all). CONCLUSION Our results reveal a non-random pattern of SWM abnormalities at early stages of MS even before pronounced structural and functional alterations emerge.

The purpose of this article is to outline the current state of evaluating children with unilateral hearing loss, with significant focus on cochlear implantation, in terms of reviewing the key points of the history, including the duration of deafness, outlining the recommended audiometric testing battery, and discussing issues related to imaging of the auditory system and related anatomy. In addition, a comprehensive and up-to-date summary of outcomes in terms of speech perception, sound localization, and quality of life for both the child with unilateral hearing loss as well as their parent(s) is reported.

To compare closure rates and hearing outcomes of microscopic and endoscopic tympanoplasty in pediatric patients.Retrospective chart review.Tertiary university medical center.Pediatric patients who underwent tympanoplasty surgery by a fellowship-trained neurotologist between 2010 and 2019 with a minimum of 2 months of follow-up, a tympanic membrane perforation, and no preoperative cholesteatoma.Transcanal endoscopic tympanoplasty or microscopic tympanoplasty (MT) surgery.The primary outcome is postoperative closure of the tympanic membrane perforation, assessed using otomicroscopy at the last follow-up appointment. Secondary outcomes include operative time and changes in the air-bone gap (ABG) and pure-tone average (PTA).Two hundred eleven tympanoplasty operations were analyzed: 121 in the transcanal endoscopic ear surgery (TEES) group and 90 in the MT group. Tympanic membrane closure rates were no different between the two groups (TEES, 82.6%; MT, 88.9%; p = 0.24), and no significant association was found on multivariable analysis (TEES: odds ratio, 0.8; p = 0.61). Both groups showed improvements in the 4-month PTA and ABG and the 12-month PTA, but the 12-month ABG only improved in the TEES group ( p0.01). The TEES group had a shorter average operative time (109.8 versus 123.5 min; p = 0.03) and less need for a postauricular incision (2.5% versus 93.3%; p0.01).In pediatric tympanoplasty, TEES gives similar membrane closure and hearing outcomes as the microscopic technique, with less operative time and less need for a postauricular incision.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent of the COVID-19 pandemic, remains a global medical problem. Angiotensin-converting enzyme 2 (

Baboons inform on human gut microbiota Commensal bacteria are found throughout an organism, but it is not known whether associations between gut bacteria and their host are heritable. Grieneisen et al. examined changes in the microbiomes of 585 wild baboons from fecal samples collected over 14 years (see the Perspective by Cortes-Ortiz and Amato). Almost all microbiome traits tested demonstrated some level of statistically significant heritability. Most heritability values were low but varied over time correlating with the age of the host. Baboons live in an environment similar to that postulated for early humans and have a microbiome similar to that of humans. Thus, this heritability of the microbiome may reflect similar genetic determinants in humans, for which similar datasets are not available. Science , aba5483, this issue p. 181 ; see also abj5287, p. 159

Public health and social measures (PHSM) have been central to the COVID‐19 response. Consequently, there has been much pressure on decision‐makers to make evidence‐informed decisions and on researchers to synthesize the evidence regarding these measures. This article describes our experiences, responses and lessons learnt regarding key challenges when planning and conducting rapid reviews of PHSM during the COVID‐19 pandemic. Stakeholder consultations and scoping reviews to obtain an overview of the evidence inform the scope of reviews that are policy‐relevant and feasible. Multiple complementary reviews serve to examine the benefits and harms of PHSM across different populations and contexts. Conceiving reviews of effectiveness as adaptable living reviews helps to respond to evolving evidence needs and an expanding evidence base. An appropriately skilled review team and good planning, coordination and communication ensures smooth and rigorous processes and efficient use of resources. Scientific rigor, the practical implications of PHSM‐related complexity and likely time savings should be carefully weighed in deciding on methodological shortcuts. Making the best possible use of modeling studies represents a particular challenge, and methods should be carefully chosen, piloted and implemented. Our experience raises questions regarding the nature of rapid reviews and regarding how different types of evidence should be considered in making decisions about PHSM during a global pandemic. We highlight the need for readily available protocols for conducting studies on the effectiveness, unintended consequences and implementation of PHSM in a timely manner, as well as the need for rapid review standards tailored to “rapid” versus “emergency” mode reviewing.

Objective Activation of brown adipose tissue is a promising strategy to treat and prevent obesity and obesity-related disorders. Activation of uncoupling protein 1 (UCP1) leads to uncoupled respiration and dissipation of stored energy as heat. Induction of UCP1-rich adipocytes in white adipose tissue, a process known as ‘browning’, serves as an alternative strategy to increase whole body uncoupling capacity. Here, we aim to assess the association between parathyroid hormone (PTH) receptor expression and UCP1 expression in human adipose tissues and to study PTH effects on human white and brown adipocyte lipolysis and UCP1 expression. Design A descriptive study of human neck adipose tissue biopsies substantiated by an interventional study on human neck-derived adipose tissue cell models. Methods Thermogenic markers and PTH receptor gene expression are assessed in human neck adipose tissue biopsies and are related to individual health records. PTH-initiated lipolysis and thermogenic gene induction are assessed in cultured human white and brown adipocyte cell models. PTH receptor involvement is investigated by PTH receptor silencing. Results PTH receptor gene expression correlates with UCP1 gene expression in the deep-neck adipose tissue in humans. In cell models, PTH receptor stimulation increases lipolysis and stimulates gene transcription of multiple thermogenic markers. Silencing of the PTH receptor attenuates the effects of PTH indicating a direct PTH effect via this receptor. Conclusion PTH 1 receptor stimulation by PTH may play a role in human adipose tissue metabolism by affecting lipolysis and thermogenic capacity.

Background Capsular contracture causes pain, poor cosmesis, and reoperations. This study analyzes its incidence and risk factors in a more modern treatment era. Methods Patients undergoing mastectomy with implant reconstruction from 2010 to 18 were reviewed. Univariate and multivariate analysis evaluated rates and risk factors for capsular contracture. Results Among 451 patients, the majority underwent nipple-sparing mastectomy (262, 58.1%) with one-stage reconstruction (283, 62.7%) utilizing subpectoral implants (353, 77.4%) and acellular dermal matrix (354, 78.5%). Overall capsular contracture incidence was 9.8%; the rate after post-mastectomy radiation therapy (PMRT) was 18.7%, and 7.5% for patients without PMRT. Significant factors included neoadjuvant chemotherapy (P = 0.006), hematoma (P = 0.047), and PMRT (P = 0.001). Multivariate analysis showed that PMRT increased risk of capsular contracture (OR = 3.12, 95% CI 1.55–6.26, P = 0.001), and adjuvant chemotherapy was protective (OR = 0.289, 95% CI 0.114–0.731, P = 0.01). Conclusions Incidence of capsular contracture is lower than previously reported. Advancing therapeutic techniques may reduce the risk of this complication.

Objectives: To describe trends in cochlear implantation (CI) disparities in Texas using an all-payer database from 2010 to 2017. Methods: Texas Outpatient Surgical and Radiological Procedure Data, a public use data file, was accessed to analyze outpatient CI cases for Texas. Variables analyzed include patient age, sex, race/ethnicity, and insurance status. Population data from the American Community Survey generated CI utilization rates by patient demographic characteristics. Results: There were 6158 CI cases identified during the study period. The number of CI per year nearly doubled from 497 in 2010 to 961 in 2017. The majority of CI recipients were white (59.5%), male (51.9%), and privately insured (47.9%). All sub-populations statewide had more CI in 2017 compared to 2010, with the overall CI per 100 000 population increasing from 1.98 to 3.50 per 100 000 population. Patients over 75 demonstrated the greatest increase in the CI rate per 100 000 population, increasing from 4.60 in 2010 to 14.30 in 2017. Regarding race/ethnicity, all sub-populations noted an increase in the CI per 100 000 population, with white patients demonstrating the highest rate in 2017, at 4.36 CI per 100 000 population. Asian patients had a 502% increase in the CI rate (from 0.42 to 2.53), compared with 87.9%, 84.4%, and 69.2% increases for white, Black, and Hispanic populations, respectively. Conclusions: CI became more widespread between 2010 and 2017, benefiting certain populations more than others. Black and Hispanic populations had lower CI per 100 000 population than their white peers, while patients >65 years of age accounted for the greatest increase in CI.

Study conducted to determine frequency and timing of unplanned breast implant removal after mastectomy, reconstruction, and postmastectomy radiation (PMRT). From 2010-2017, 52 patients underwent mastectomy, reconstruction, and PMRT. With median follow-up of 3.1 years, 23 patients (44%) experienced implant removal. Implant removal occurred in 9 (17%) patients before starting PMRT and 14 (27%) patients after starting PMRT. Implant removal rates were similar for hypofractionated PMRT compared with standard fractionation and for proton compared with photon PMRT. Implant removal is common for women undergoing mastectomy and reconstruction followed by PMRT. The risk is clinically significant even before starting radiation.

Study Objective To analyze outcomes and postoperative complications in patients undergoing robot-assisted rectus abdominis flap harvest for pelvic floor reconstruction. Design Case series. Setting Academic setting. Patients Pelvic reconstruction surgery patients. Interventions The rectus abdominis muscle flap can be used as a flap for pelvic reconstruction, providing a large volume of soft tissue that can be used in the treatment of many comorbid conditions, including genital fistulas, postradiation pelvic exenteration, and abdominoperineal resection defects. Intraperitoneal harvest of the rectus muscle using a robotic approach allows avoidance of laparotomy and subsequent disruption of the anterior rectus sheath, thus preserving the integrity of the abdominal wall. Measurements and Main Results A retrospective analysis of patient demographic and clinical characteristics was performed for all patients who underwent robot-assisted rectus abdominis flap harvest for pelvic floor reconstruction at our institution from October 1, 2016, to October 31, 2018. The postoperative complications analyzed included bowel obstructions, surgical site infections, emergency room visits, and need for readmission. Six patients (4 women and 2 men), with a mean age of 69.2 years (range = 57–79 years) and median follow-up time of 9.2 months (range = 5–12 months), were included. Muscle flap harvest was performed on the right side in 4 patients and on the left in 2 patients. The indications for reconstructive surgery included vesicovaginal fistula, complex pelvic organ prolapse, anterior and posterior exenteration, partial and total vaginectomy, partial vulvectomy, and abdominoperineal resection. Two patients received neoadjuvant chemoradiation. One of the 6 cases was converted to laparotomy; however, this was not owing to the rectus harvest. Three patients experienced no complications after reconstruction; 1 patient reported occasional abdominal pain; 1 patient had intermittent bowel obstruction; and 1 patient developed a pelvic abscess, requiring readmission. All 6 patients achieved satisfactory healing of the pelvic wound after robot-assisted rectus abdominis flap inset. Conclusion Robot-assisted rectus abdominis flap harvest for pelvic floor reconstruction is a reliable means of defect closure, despite the presence of substantial comorbidities and risk factors in this patient cohort. Patient selection and counseling are crucial to optimize surgical outcomes in this complex population.

Ramifications of postoperative complications on long-term survival after mastectomy are uncertain.Overall complications (Clavien-Dindo Grades I-IIIB) and wound complications were analyzed using the Kaplan-Meier method for impact on 5-year overall (OS) and disease-free survival (DFS).A total of 378 patients underwent mastectomy alone (157, 41%) or mastectomy with reconstruction (221, 59%) for Stage I-III disease with a median follow-up of 5 years. Postoperative complications occurred in 186 patients (49%), requiring non-surgical (I/II = 83, 22%) or surgical (IIIa/IIIb = 103, 27%) management. Wound complications occurred in 140 patients (37%). Reconstruction was associated with a higher rate of complication (P 0.001). Postoperative complications after mastectomy (with or without reconstruction) did not significantly affect OS or DFS. Wound complications also showed no significant effect on OS or DFS following mastectomy alone, or mastectomy with reconstruction.Postoperative complications after mastectomy, with or without reconstruction, bear no significant impact on 5-year survival.

Rates of maternal mortality are increasing in the United States with significant rural-urban disparities. Pre-pregnancy hypertension is a well-established risk factor for adverse maternal and offspring outcomes.The purpose of this study was to describe trends in maternal pre-pregnancy hypertension among women in rural and urban areas in 2007 to 2018 in order to inform community-engaged prevention and policy strategies.We performed a nationwide, serial cross-sectional study using maternal data from all live births in women age 15 to 44 years between 2007 and 2018 (CDC Natality Database). Rates of pre-pregnancy hypertension were calculated per 1,000 live births overall and by urbanization status. Subgroup analysis in standard 5-year age categories was performed. We quantified average annual percentage change using Joinpoint Regression and rate ratios (95% confidence intervals [CIs]) to compare yearly rates between rural and urban areas.Among 47,949,381 live births to women between 2007 and 2018, rates of pre-pregnancy hypertension per 1,000 live births increased among both rural (13.7 to 23.7) and urban women (10.5 to 20.0). Two significant inflection points were identified in 2010 and 2016, with highest annual percentage changes between 2016 and 2018 in rural and urban areas. Although absolute rates were lower in younger compared with older women in both rural and urban areas, all age groups experienced similar increases. The rate ratios of pre-pregnancy hypertension in rural compared with urban women ranged from 1.18 (95% CI: 1.04 to 1.35) for ages 15 to 19 years to 1.51 (95% CI: 1.39 to 1.64) for ages 40 to 44 years in 2018.Maternal burden of pre-pregnancy hypertension has nearly doubled in the past decade and the rural-urban gap has persisted.

Background H3K27M-mutant diffuse midline glioma (DMG) is a lethal brain tumor that usually occurs in children. Despite advances in our understanding of its underlying biology, efficacious therapies are severely lacking. Methods We screened a library of drugs either FDA-approved or in clinical trial using a library of patient-derived H3K27M-mutant DMG cell lines with cell viability as the outcome. Results were validated for clinical relevance and mechanistic importance using patient specimens from biopsy and autopsy, patient-derived cell lines, inhibition by gene knockdown and small molecule inhibitors, and patient-derived xenografts. Results Kinase inhibitors were highly toxic to H3K27M-mutant DMG cells. Within this class, STAT3 inhibitors demonstrated robust cytotoxic activity in vitro. Mechanistic analyses revealed one form of activated STAT3, phospho-tyrosine- 705 STAT3 (pSTAT3), was selectively upregulated in H3K27M-mutant cell lines and clinical specimens. STAT3 inhibition by CRISPR/Cas9 knockout, shRNA or small molecule inhibition reduced cell viability in vitro, and partially restored expression of the polycomb repressive mark H3K27me3, which is classically lost in H3K27M-mutant DMG. Putative STAT3-regulated genes were enriched in an H3K27M-knockout DMG cell line, indicating relative gain of STAT3 signaling in K27M-mutant cells. Treatment of patient-derived intracranial xenografts with WP1066, a STAT3 pathway inhibitor currently in clinical use for pediatric brain tumors, resulted in stasis of tumor growth, and increased overall survival. Finally, pSTAT3(Y705) was detected in circulating plasma extracellular vesicles of patients with H3K27M-mutant DMG. Conclusions STAT3 is a biologically relevant therapeutic target in H3K27M-mutant DMG. STAT3 inhibition should be considered in future clinical trials.

Clinical guidelines recommend titration of angiotensin converting enzyme inhibitors (ACEi) and beta-blockers among patients with heart failure with reduced ejection fraction (HFrEF) to maximally tolerated doses. Patient characteristics associated with dose titration and clinical outcomes subsequent to dose titration remain poorly characterized.Among 1999 ambulatory patients with chronic HFrEF in the HF-ACTION trial, use and dosing of ACEi and evidence-based beta-blockers were examined at baseline and 6-month follow-up. Multivariable logistic regression models were used to assess factors associated with dose escalation (medication initation or dosing increase) or dose de-escalation (medication discontinuation or dosing decrease). Cox proportional hazard regression models were used to examine associations between dose trajectory group (stable target, stable sub-target, dose escalation, and dose de-escalation) and subsequent mortality and hospitalization outcomes.For both ACEi and beta-blockers, hospitalization for heart failure in the 6 months prior to enrollment (odds ratio [OR] 2.32 [95% confidence interval 1.58-3.42]) for ACEi; 1.42 [1.05-1.9] for beta-blockers) and higher systolic blood pressure (OR 1.01 [1.00-1.03] per 1 mmHg increase for ACEi; 1.01 [1.00-1.02] for beta-blockers) were associated with dose escalation. Hospitalization 6 months prior to enrollment for any cause (including HF or non-HF causes) was associated with dose de-escalation (OR 1.60 [1.14-2.25] for ACEi; 1.67 [1.20-2.33] for beta-blockers). After adjustment for patient characteristics, compared with stable target dosing, dose de-escalation of either medication was associated with greater all-cause mortality (adjusted hazard ratio [aHR] 1.64 [1.11-2.42] for ACEi; 1.62 [1.04-2.53] for beta-blockers). Compared with stable target dosing, both dose de-escalation (aHR 1.98 [1.36-2.87]) and stable sub-target dosing (aHR 1.49 [1.18-1.87]) of beta-blockers were associated with greater cardiovascular mortality or hospitalization for heart failure.Among outpatients with chronic HFrEF, patient characteristics including recent hospitalization status and blood pressure were associated with odds of subsequent escalation and de-escalation of ACEi and beta-blocker therapy. Compared with patients receiving guildeline-recommended target doses, dose de-escalation of either medication and sub-target dosing of beta-blockers were associated with greater morbidity and mortality over long-term follow-up.

Objective This study describes a quality improvement (QI) process to reduce bias and increase inclusion and equity in the recruitment of health service psychology interns in an American Psychological Association-accredited psychology internship program at a national children’s hospital. Methods This QI project utilized two Plan-Do-Study-Act (PDSA) cycles targeting the application review and the interview processes primarily using supervisor engagement and feedback to inform these processes. The goal of the PDSA cycles was to increase diversity in psychology doctoral interns offered interviews and ultimately recruited to the internship program. Results The application rating form was revised to place a greater emphasis on factors related to diversity, such as increasing the number of points applicants could earn for being bilingual. Regarding the interview process, structured interview questions were created, and a new, unified rubric was used to score interviewees. The changes in demographics of applicants selected for interviews and feedback from applicants who interviewed are reported. Conclusions The QI process resulted in tangible changes to improve equitable and inclusive internship recruitment. Lessons learned throughout this process included the need for continual auditing of practices through an equity lens, engaging supervisors at all stages of the process, and implementing incremental actions.

As biomolecular approaches for hearing restoration in profound sensorineural hearing loss evolve, they will be applied in conjunction with or instead of cochlear implants. An understanding of the current state-of-the-art of this technology, including its advantages, disadvantages, and its potential for delivering and interacting with biomolecular hearing restoration approaches, is helpful for designing modern hearing-restoration strategies. Cochlear implants (CI) have evolved over the last four decades to restore hearing more effectively, in more people, with diverse indications. This evolution has been driven by advances in technology, surgery, and healthcare delivery. Here, we offer a practical treatise on the state of cochlear implantation directed towards developing the next generation of inner ear therapeutics. We aim to capture and distill conversations ongoing in CI research, development, and clinical management. In this review, we discuss successes and physiological constraints of hearing with an implant, common surgical approaches and electrode arrays, new indications and outcome measures for implantation, and barriers to CI utilization. Additionally, we compare cochlear implantation with biomolecular and pharmacological approaches, consider strategies to combine these approaches, and identify unmet medical needs with cochlear implants. The strengths and weaknesses of modern implantation highlighted here can mark opportunities for continued progress or improvement in the design and delivery of the next generation of inner ear therapeutics.

Microbial resistance to currently available antibiotics poses a great threat in the global fight against infections. An important step in determining bacterial antibiotic resistance can be selective DNA sequence capture and fluorescence labeling. In this paper, we demonstrate the fabrication of simple, robust, inexpensive microfluidic devices for DNA capture and fluorescence detection of a model antibiotic resistance gene sequence. We laser micromachined polymethyl methacrylate microchannels and enclosed them using pressure-sensitive adhesive tapes. We then formed porous polymer monoliths with DNA capture probes in these microchannels and used them for sequence-specific capture, fluorescent labeling, and laser-induced fluorescence detection of picomolar (pM) concentrations of synthetic and plasmid antibiotic resistance gene targets. The relative fluorescence for the elution peaks increased with loaded target DNA concentration. We observed higher fluorescence signal and percent recovery for synthetic target DNA compared to plasmid DNA at the same loaded target concentration. A non-target gene was used for control experiments and produced 3% capture relative to the same concentration of target. The full analysis process including device fabrication was completed in less than 90 min with a limit of detection of 30 pM. The simplicity of device fabrication and good DNA capture selectivity demonstrated herein have potential for application with processes for bacterial plasmid DNA extraction and single-particle counting to facilitate determination of antibiotic susceptibility. Graphical abstract.