The Use of Hyaluronidase in Aesthetic Practice: A Comparative Study of Practitioner Usage in Elective and Emergency Situations.

BACKGROUND: Hyaluronic acids (HAs) continue to be the fillers of choice worldwide and their popularity is growing. Adverse events (AEs) are able to be resolved through the use of hyaluronidase (HYAL). However, routine HYAL use has been at issue due to perceived safety issues. OBJECTIVES: There are currently no guidelines on the use of HYAL in aesthetic practice, leading to variability in storage, preparation, skin testing, and beliefs concerning AEs. This manuscript interrogated the use of this agent in daily practice. METHODS: A 39-question survey concerning HYAL practice was completed by 264 healthcare practitioners: 244 from interrogated databases and 20 from the consensus panel. Answers from those in the database were compared to those of the consensus panel. RESULTS: Compared to the database group, the consensus group was more confident in the preparation of HYAL, kept reconstituted HYAL for longer, and was less likely to skin test for HYAL sensitivity and more likely to treat with HYAL in an emergency, even in those with a wasp or bee sting anaphylactic history. Ninety-two percent of all respondents had never observed an acute reaction to HYAL. Just over 1% of respondents had ever observed anaphylaxis. Five percent of practitioners reported longer-term adverse effects, including 3 respondents who reported loss of deep tissues. Consent before injecting HA for the possible requirement of HYAL was always obtained by 74% of practitioners. CONCLUSIONS: Hyaluronidase would appear to be an essential agent for anyone injecting hyaluronic acid filler. However, there is an absence of evidence-based recommendations with respect to the concentration, dosing, and treatment intervals of HYAL, and these should ideally be available.

Disparities in Pharmacologic Restraint for Children Hospitalized in Mental Health Crisis.

BACKGROUND AND OBJECTIVES: Children hospitalized with a mental health crisis often receive pharmacologic restraint for management of acute agitation. We examined associations between pharmacologic restraint use and race and ethnicity among children admitted for mental health conditions to acute care nonpsychiatric children's hospitals. METHODS: We performed a retrospective cohort study of children (aged 5-≤18 years) admitted for a primary mental health condition from 2018 to 2022 at 41 US children's hospitals. Pharmacologic restraint use was defined as parenteral administration of medications for acute agitation. The association of race and ethnicity and pharmacologic restraint was assessed using generalized linear multivariable mixed models adjusted for clinical and demographic factors. Stratified analyses were performed based on significant interaction analyses between covariates and race and ethnicity. RESULTS: The cohort included 61 503 hospitalizations. Compared with non-Hispanic Black children, children of non-Hispanic White (adjusted odds ratio [aOR], 0.81; 95% confidence interval [CI], 0.72-0.92), Asian (aOR, 0.82; 95% CI, 0.68-0.99), or other race and ethnicity (aOR, 0.68; 95% CI, 0.57-0.82) were less likely to receive pharmacologic restraint. There was no significant difference with Hispanic children. When stratified by sex, racial/ethnic differences were magnified in males (aORs, 0.49-0.68), except for Hispanic males, and not found in females (aORs, 0.83-0.93). Sensitivity analysis revealed amplified disparities for all racial/ethnic groups, including Hispanic youth (aOR, 0.65; 95% CI, 0.47-0.91). CONCLUSIONS: Non-Hispanic Black children were significantly more likely to receive pharmacologic restraint. More research is needed to understand reasons for these disparities, which may be secondary to implicit bias and systemic and interpersonal racism.

Pneumonia vaccine response in individuals with Down syndrome at three specialty clinics.

Individuals with Down syndrome (DS) have been particularly impacted by respiratory conditions, such as pneumonia. However, the description of co-occurring recurrent infections, the response to pneumococcal immunization, and the association of these was previously unknown. We screened individuals with DS using an 11-item screener and prospectively collected pneumococcal titers and laboratory results. We found that the screener did not successfully predict which individuals with DS who would have inadequate pneumococcal titers. Thirty four of the 55 individuals with DS (62%) had abnormal pneumococcal titers demonstrating an inadequate response to routine immunization. In the absence of a valid screener, clinicians should consider screening all individuals with DS through the use of pneumococcal titers to 23 serotypes to assess vaccine response.

An exploratory study of plasma ceramides in comorbidities in Down syndrome.

Plasma ceramide levels (henceforth, "ceramides") are biomarkers of some diseases that are comorbidities of Down syndrome (DS). We sought to determine if comorbidities in DS were associated with ceramides, studying a convenience cohort of 35 study participants, all ≥12 months old. To identify comorbidities, we reviewed the problem lists in electronic health records that were concurrent with sample collection. We placed clinically related comorbidities into one of five categories of comorbidities, henceforth, categories: obesity/overweight; autoimmune disease; congenital heart disease; bacterial infection; and central nervous system (CNS) condition. We measured the eight ceramides most frequently associated with disease using liquid chromatography-tandem mass spectrometry. We calculated a ceramide composite outcome score (CCOS) for each participant by normalizing each ceramide level to the mean for that level in the study population and then summing the normalized levels, to be proxy variable for all eight ceramides in aggregate. We used multivariable linear regression models adjusted for age and sex to test associations of categories with ceramides and with CCOSs. Post hoc, we realized that co-occurring comorbidities might interfere with establishing associations between predictor categories and ceramides and that stratified analyses might eliminate their influence on associations. We posited that CCOSs could be used to screen for associations of categories with multiple ceramides, since most diseases have been associated with more than one ceramide. We chose to omit in the stratified analyses the two categories that were the most different from one another in their associations with their CCOSs, having the most divergent regression coefficients (the highest positive and lowest negative coefficients). We first omitted one of these two divergent categories in a stratified analysis and tested in the remaining participants (those without a comorbidity in the interfering category) for associations of the other four categories with their CCOSs and then did the same for the other divergent category. In each of these two screening stratified analyses, we found one category was significantly associated with its CCOS. In the two identified categories, we then tested for associations with each of the eight ceramides, using the appropriate stratified analysis. Next, we sought to determine if the associations of the two categories with ceramides we found by omitting participants in the interfering categories held in our small sample for participants in the omitted categories as well. For each of the two categories, we therefore omitted participants without the interfering category and determined associations between the predictor category and individual ceramides in the remaining participants (those with a comorbidity in the interfering category). In the a priori analyses, autoimmune disease was inversely associated with C16 and CNS condition was inversely associated with C23. Obesity/overweight and CNS condition were the two categories with the most divergent regression coefficients (0.037 vs. -0.048). In post hoc stratified analyses, after omitting participants with obesity/overweight, thereby leaving participants without obesity/overweight, bacterial infection was associated with its CCOS and then with C14, C20, and C22. However, in the companion stratified analyses, omitting participants without obesity/overweight, thereby leaving participants with obesity/overweight, bacterial infection was not associated with any of the eight ceramides. Similarly, in post hoc stratified analyses after omitting participants with a CNS condition, thereby leaving participants without a CNS condition, obesity/overweight was associated with its CCOS and then with C14, C23, and C24. In the companion analyses, omitting participants without a CNS condition, thereby leaving participants with a CNS condition, obesity/overweight was inversely associated with C24.1. In conclusion, CNS and autoimmune disease were inversely associated with one ceramide each in a priori analyses. In post hoc analyses, we serendipitously omitted categories that interfered with associations of other categories with ceramides in stratified analyses. We found that bacterial infection was associated with three ceramides in participants without obesity/overweight and that obesity/overweight was associated with three ceramides in participants without a CNS condition. We therefore identified obesity/overweight and CNS conditions as potential confounders or effect modifiers for these associations. This is the first report of ceramides in DS and in human bacterial infection. Further study of ceramides in comorbidities of DS is justified.

Making Sense of Late Tissue Nodules Associated With Hyaluronic Acid Injections.

BACKGROUND: The pathogenesis of delayed-onset tissue nodules (DTNs) due to hyaluronic acid (HA) injections is uncertain. OBJECTIVES: To formulate a rational theory for DTN development and their avoidance and treatment. METHODS: A multidisciplinary and multicountry DTN consensus panel was established, with 20 questions posed and consensus sought. Consensus was set at 75% agreement. RESULTS: Consensus was reached in 16 of 20 questions regarding the pathogenesis of DTNs, forming the basis for a classification and treatment guide. CONCLUSIONS: The group believes that filler, pathogens, and inflammation are all involved in DTNs and that DTNs most likely are infection initiated with a variable immune response. Injected filler may incorporate surface bacteria, either a commensal or a true pathogen, if the skin barrier is altered. The initially high molecular weight HA filler is degraded to low molecular weight HA (LMWHA) at the edge of the filler. Commensals positioned within the filler bolus may be well tolerated until the filler is degraded and the commensal becomes visible to the immune system. LMWHA is particularly inflammatory in the presence of any local bacteria. Commensals may still be tolerated unless the immune system is generally heightened by viremia or vaccination. Systemic pathogenic bacteremia may also interact with the filler peripheral LMWHA, activating Toll-like receptors that induce DTN formation. Given this scenario, attention to practitioner and patient hygiene and early systemic infection treatment deserve attention. Classification and treatment systems were devised by considering each of the 3 factors-filler, inflammation, and infection-separately.

Cardiometabolic profiles in children and adults with overweight and obesity and down syndrome.

Individuals with Down syndrome (DS) are at increased risk for being overweight/obese, but the associated cardiometabolic risk (CR) is not clear. Cross-sectional anthropometric and clinical laboratory data from a multi-site, international cohort of individuals with DS were analyzed to determine cardiometabolic risk by reporting observed distributions of cardiometabolic biomarkers in overweight/obese individuals with DS throughout the lifespan. Descriptive statistics and regression analyses by age categories determined the distributive percentiles for cardiometabolic biomarkers and tested for adiposity as a predictor of CR. Across seven DS clinics, data were collected on 240 patients between the ages of 3 and 63 years, with one quarter overweight and three quarters obese among children and nearly all adults being obese. In children and adults, most cardiometabolic biomarker profiles showed distributive values within normal ranges. Blood lipids were positively associated with body mass index (BMI) in children (high density lipid-cholesterol, p = 0.01; low density lipid-cholesterol, p = 0.02). Levels of hs-CRP were elevated in both children and adults, with BMI positively associated with hs-CRP in adults with DS (p = 0.04). Liver enzyme values were positively associated with BMI in children and adults. The data suggest that in contrast to the general population, in individuals with Down syndrome, being overweight and obese does not appear to confer a significantly increased risk for cardiometabolic disease by biomarker profile. Individuals with DS who are overweight/obese appear to have unique cardiometabolic profiles unrelated to adiposity, notable for increased hs-CRP and normal HA1c levels.

Pharmacologic restraint use for children experiencing mental health crises in pediatric hospitals.

BACKGROUND: Children in mental health crises are increasingly admitted to children's hospitals awaiting inpatient psychiatric placement. During hospitalization, patients may exhibit acute agitation prompting pharmacologic restraint use. OBJECTIVE: To determine hospital-level incidence and variation of pharmacologic restraint use among children admitted for mental health conditions in children's hospitals. DESIGN, SETTING, AND PARTICIPANTS: We examined data for children (5 to ≤18 years) admitted to children's hospitals with a primary mental health condition from 2018 to 2020 using the Pediatric Health Information System database. Hospital rates of parenteral pharmacologic restraint use per 1000 mental health bed days were determined and compared after adjusting for patient-level and demographic factors. Cluster analysis (k-means) was used to group hospitals based on overall restraint use (rate quartiles) and drug class. Hospital-level factors for pharmacologic restraint use were compared. RESULTS: Of 29,834 included encounters, 3747 (12.6%) had pharmacologic restraint use. Adjusted hospital rates ranged from 35 to 389 pharmacologic restraint use days per 1000 mental health bed days with a mean of 175 (standard deviation: 72). Cluster analysis revealed three hospitals were high utilizers of all drug classes. No significant differences in pharmacologic restraint use were found in the hospital-level analysis. CONCLUSIONS: Children's hospitals demonstrate wide variation in pharmacologic restraint rates for mental health hospitalizations, with a 10-fold difference in adjusted rates between highest and lowest utilizers, and high overall utilizers order medications across all drug classes.

Systematic Review and Meta-analysis of Blood Glucose Response to High-intensity Interval Exercise in Adults With Type 1 Diabetes.

OBJECTIVES: Exercise-induced hyperglycemia is recognized in type 1 diabetes (T1D) clinical guidelines, but its association with high-intensity intermittent exercise (HIIE) in acute studies is inconsistent. In this meta-analysis, we examined the available evidence of blood glucose responses to HIIE in adults with T1D. The secondary, aim was to examine predictors of blood glucose responses to HIIE. We hypothesized that there would be no consistent effect on blood glucose from HIIE, unless examined in the context of participant prandial status. METHODS: We conducted a literature search using key words related to T1D and HIIE. Studies were required to include at least 6 participants with T1D with a mean age >18 years, involve an HIIE intervention, and contain pre- and postexercise measures of blood glucose. Analyses of extracted data were performed using a general inverse variance statistical method with a random effects model and a weighted multiple regression. RESULTS: Nineteen interventions from 15 reports were included in the analysis. A mean overall blood glucose decrease of -1.3 mmol/L (95% confidence interval [CI], -2.3 to -0.2 mmol/L) was found during exercise, albeit with high heterogeneity (I2=84%). When performed after an overnight fast, exercise increased blood glucose by +1.7 mmol/L (95% CI, 0.4 to 3.0 mmol/L), whereas postprandial exercise decreased blood glucose by -2.1 mmol/L (95% CI, -2.8 to -1.4 mmol/L), with a statistically significant difference between groups (p<0.0001). No associations with fitness (p=0.4), sex (p=0.4), age (p=0.9), exercise duration (p=0.9), or interval duration (p=0.2) were found. CONCLUSION: The effect of HIIE on blood glucose is inconsistent, but partially explained by prandial status.

Unexplained regression in Down syndrome: Management of 51 patients in an international patient database.

Research to guide clinicians in the management of the devastating regression which can affect adolescents and young adults with Down syndrome is limited. A multi-site, international, longitudinal cohort of individuals with a clinical diagnosis of Unexplained Regression in Down syndrome (URDS) was collated through seven Down syndrome clinics. Tiered medical evaluation, a 28-item core symptom list, and interim management are described naturalistically. Improvement-defined by the percentage of baseline function on a Parent-reported Functional Score, overall improvement in symptoms on a Clinician-administered Functional Assessment, or report of management type being associated with improvement-was analyzed. Improvement rates using ECT, IVIG, and others were compared. Across seven clinics, 51 patients with URDS had regression at age 17.6 years, on average, and showed an average 14.1 out of 28 symptoms. Longitudinal improvement in function was achieved in many patients and the medical management, types of treatment, and their impact on function are described. Management with intravenous immunoglobulin (IVIG) was significantly associated with higher rate of improvement in symptoms at the next visit (p = 0.001). Our longitudinal data demonstrates that URDS is treatable, with various forms of clinical management and has a variable course. The data suggests that IVIG may be an effective treatment in some individuals. Our description of the management approaches used in this cohort lays the groundwork for future research, such as development of standardized objective outcome measure and creation of a clinical practice guideline for URDS.

The Importance of Patient Mindset: Cosmetic Injectable Patient Experience Exploratory Study-Part 1.

Background: To meet the needs of each individual cosmetic injectable patient, focus is moving toward a detailed, patient-centered, holistic consultation with pretreatment exploration of the patient's mindset. The Cosmetic Injectables Patient Experience Exploratory Study (CIPEES) was developed to explore patient motivation, mindset, engagement, and factors impacting the patient-practitioner relationship. Objectives: In order to best meet the needs of individual aesthetic patients, the authors examine the variability and importance of mindset factors in patients seeking cosmetic injectables. Methods: A study was conducted through an online survey. Participants were asked to respond to a series of statements concerning their thoughts and feelings around appearance, treatment goals, and motivating factors. Participants were asked to select one of the following: "describes me well," "somewhat describes me," or "does not describe me." Results: In total, 1269 participants completed the relevant survey question. Respondents were 95.6% female and 4.4% male, with ages ranging from 18 to > 65 years old (median 33 years old). Responses were also analyzed according to age group. Data analysis revealed a majority of respondents seeking natural results, with a 15%-20% minority considering a "done" look to be acceptable or even ideal. High numbers of respondents reported being critical of their own appearance and concerned about a specific feature to be "fixed." Conclusions: Exploring the nuances of patient mindset will assist practitioners in meeting the unique needs of each patient and may also help them to avoid treating patients whose requirements or expectations are outside their circle of competence.

Plasmodium falciparum GBP2 Is a Telomere-Associated Protein That Binds to G-Quadruplex DNA and RNA.

In the early-diverging protozoan parasite Plasmodium, few telomere-binding proteins have been identified and several are unique. Plasmodium telomeres, like those of most eukaryotes, contain guanine-rich repeats that can form G-quadruplex structures. In model systems, quadruplex-binding drugs can disrupt telomere maintenance and some quadruplex-binding drugs are potent anti-plasmodial agents. Therefore, telomere-interacting and quadruplex-interacting proteins may offer new targets for anti-malarial therapy. Here, we report that P. falciparum GBP2 is such a protein. It was identified via 'Proteomics of Isolated Chromatin fragments', applied here for the first time in Plasmodium. In vitro, PfGBP2 binds specifically to G-rich telomere repeats in quadruplex form and it can also bind to G-rich RNA. In vivo, PfGBP2 partially colocalises with the known telomeric protein HP1 but is also found in the cytoplasm, probably due to its affinity for RNA. Consistently, its interactome includes numerous RNA-associated proteins. PfGBP2 is evidently a multifunctional DNA/RNA-binding factor in Plasmodium.

Movement of the Syringe During Filler Aspiration: An Ultrasound Study.

BACKGROUND: Aspiration prior to hyaluronic acid filler injection is often taught as a safety maneuver to minimize the risk of intravascular injection; however, the validity of this technique in aesthetic practice is being increasingly challenged. One key assumption underpinning the validity of the aspiration test is that the needle tip does not move during the aspiration and subsequent injection of filler. OBJECTIVES: The aim of this study was to visualize and measure needle tip movement in real time during aspiration and injection of filler. Secondary objectives were to assess the impact of injector experience and double-handed versus single-handed aspiration technique in maintaining stability of the syringe. METHODS: Under real-time ultrasound visualization, 3 injectors with different levels of experience injected hyaluronic acid filler into pork belly tissue utilizing both double-handed and single-handed aspiration techniques. Needle tip movements were recorded and measured by means of ultrasound and video. RESULTS: The aspiration maneuver is in all cases associated with retrograde movement of the needle tip, ranging from 1.1 to 5.3 mm (mean, 2.9 mm), whereas injection leads to anterograde movement ranging from 0.6 to 4.1 mm (mean, 1.9 mm). Double-handed aspiration is associated with less needle tip movement than single-handed aspiration (P = 0.037). Greater experience is also associated less movement of the needle tip (P < 0.0001). CONCLUSIONS: In all cases, the aspiration and injecting maneuver is associated with micromovements of the needle tip, of a magnitude consistently significant relative to the typical size of facial vessels. Although needle tip movement is only a single factor limiting the usefulness of the aspiration test, the results of this study suggest that it is not advisable to rely only on aspiration as a method to prevent intravascular injection.

Effective Treatment of Chronic Mastectomy Pain with Intercostal Sensory Neurectomy.

SUMMARY: Chronic postmastectomy pain affects up to 40 percent of patients and leads to diminished quality of life and increased risk of opioid dependence. The cause of this pain is incompletely understood; however, one hypothesis is that direct injury to cutaneous intercostal nerves at the time of mastectomy and/or reconstruction leads to chronic pain. As a result, proximal neurectomy of the involved sensory nerve(s) has been suggested to be effective for these patients. The purpose of this study was to determine whether chronic pain in postmastectomy patients can be diagnosed reliably in an office setting and pain reduced by intercostal sensory neurectomy. The authors performed a retrospective review of seven patients with a history of breast surgery and chronic pain who underwent intercostal neurectomy combined with muscle or dermal wrapping of the proximal end of the resected nerve. All patients were diagnosed by history and physical examination, and suspected nerves were further identified with local anesthetic nerve blocks. An average of 3.14 neurectomies were performed per patient (range, one to six). There was a significant reduction in visual analogue scale pain scores following surgery, from 9 preoperatively to 1 postoperatively (p = 0.02). Eighty-six percent of patients were pain-free or "considerably improved" at their latest follow-up appointment (average, 6.14 months). It is concluded that intercostal sensory nerve injury at the time of mastectomy and/or reconstruction can lead to chronic mastectomy pain, which can be easily diagnosed and effectively treated with intercostal neurectomy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Association of Race/Ethnicity and Social Determinants with Rehospitalization for Mental Health Conditions at Acute Care Children's Hospitals.

OBJECTIVE: To evaluate associations of race/ethnicity and social determinants with 90-day rehospitalization for mental health conditions to acute care nonpsychiatric children's hospitals. STUDY DESIGN: We conducted a retrospective cohort analysis of mental health hospitalizations for children aged 5-18 years from 2016 to 2018 at 32 freestanding US children's hospitals using the Children's Hospital Association's Pediatric Health Information System database to assess the association of race/ethnicity and social determinants (insurance payer, neighborhood median household income, and rurality of patient home location) with 90-day rehospitalization. Risk factors for rehospitalization were modeled using mixed-effects multivariable logistic regression. RESULTS: Among 23 556 index hospitalizations, there were 1382 mental health rehospitalizations (5.9%) within 90 days. Non-Hispanic Black children were 26% more likely to be rehospitalized than non-Hispanic White children (aOR 1.26, 95% CI 1.08-1.48). Those with government insurance were 18% more likely to be rehospitalized than those with private insurance (aOR 1.18, 95% CI 1.04-1.34). In contrast, those living in a suburban location were 22% less likely to be rehospitalized than those living in an urban location (suburban: aOR 0.78, 95% CI 0.63-0.97). CONCLUSIONS: Non-Hispanic Black children and those with public insurance were at greatest risk for 90-day rehospitalization, and risk was lower in those residing in suburban locations. Future work should focus on upstream interventions that will best attenuate social disparities to promote equity in pediatric mental healthcare.

Aspiration Before Tissue Filler-An Exercise in Futility and Unsafe Practice.

BACKGROUND: Aesthetic physicians rely on certain anecdotal beliefs regarding the safe practice of filler injections. These include a presumed safety advantage of bolus injection after a negative aspiration. OBJECTIVES: The authors sought to review and summarize the published literature on inadvertent intravascular injection of hyaluronic acid and to investigate whether the technique of aspiration confers any safety to the practitioner and the patient. METHODS: Pertinent literature was analyzed and the current understanding of the safety of negative and positive aspiration outlined. RESULTS: The available studies demonstrate that aspiration cannot be relied on and should not be employed as a safety measure. It is safer to adopt injection techniques that avoid injecting an intravascular volume with embolic potential than utilize an unreliable test to permit a risky injection. CONCLUSIONS: To prevent intravascular injection, understanding "injection anatomy" and injection plane and techniques such as slow, low-pressure injection are important safety measures. Assurance of safety when delivering a bolus after negative aspiration does not appear to be borne out by the available literature. If there is any doubt about the sensitivity or reliability of a negative aspiration, there is no role for its utilization. Achieving a positive aspiration would just defer the risk to the next injection location where a negative aspiration would then be relied on.

Novel PAX6 variant in a family with ophthalmologic, pancreatic, and olfactory features.

Variants in the PAX6 gene have been associated with ophthalmologic, neurologic, and pancreatic differences. We report on a proband, mother, and affected brother who presented with congenital cataracts and glaucoma at a young age. Nonocular findings are also reported among these family members. After a congenital cataracts next-generation sequencing (NGS) gene panel was found to be nondiagnostic in 2016, a more expanded panel in 2020 revealed a novel variant: c.178T > A; p.Tyr60Asn in exon 6 of the PAX6 gene in the proband. The variant is also present in the affected mother and affected brother; it is absent in an unaffected brother. The clinical findings of these three relatives, in conjunction with their genetic testing and the associated PAX6 features reported in the literature, suggest that this novel familial variant may be an underlying etiology for these individuals' ophthalmologic, pancreatic, and olfactory symptoms.

Early warning sign of forest loss in protected areas.

As humanity is facing the double challenge of species extinctions and climate change, designating parts of forests as protected areas is a key conservation strategy.1-4 Protected areas, encompassing 14.9% of the Earth's land surface and 19% of global forests, can prevent forest loss but do not do so perfectly everywhere.5-12 The reasons why protection only works in some areas are difficult to generalize: older and newer parks, protected areas with higher and lower suitability for agriculture, and more and less strict protection can be more effective at preventing forest loss than their counterparts.6,8,9,12-16 Yet predicting future forest loss within protected areas is crucial to proactive conservation. Here, we identify an early warning sign of subsequent forest loss, based on forest loss patterns in strict protected areas and their surrounding landscape worldwide, from 2000 to 2018.17,18 We found that a low level in the absolute forest cover immediately outside of a protected area signals a high risk of future forest loss inside the protected area itself. When the amount of forest left outside drops to <20%, the protected area is likely to experience rates of forest loss matching those in the wider landscape, regardless of its protection status (e.g., 5% loss outside will be matched by 5% loss inside). This knowledge could be used to direct funding to protected areas threatened by imminent forest loss, helping to proactively bolster protection to prevent forest loss, especially in countries where detailed information is lacking.

Dermatosensory Peripheral Nerve Interfaces: Prevention of Pain Recurrence Following Sensory Neurectomy.

Chronic pain is a significant health care problem. Many patients' pain can be linked to a neuropathic origin, diagnosed with a thorough history and physical examination, and confirmed with a diagnostic nerve block. There are new procedures designed to address neuropathic pain from symptomatic neuromas by providing physiologic targets for regenerating axons following neurectomy. Dermal wrapping of the end of a sensory nerve following transection, a technique called dermatosensory peripheral nerve interface, may provide an optimal environment to prevent neuroma pain and reduce chronic neuropathic pain.

Association of Clinical Complications of Chemotherapy and Patient-Reported Outcomes After Immediate Breast Reconstruction.

Importance: Women undergoing immediate breast reconstruction often require chemotherapy. The effects of chemotherapy on reconstruction are not well described. Objective: To evaluate the association of neoadjuvant and adjuvant chemotherapy with complications and patient-reported outcomes (PROs) in immediate reconstruction. Design, Setting, and Participants: The Mastectomy Reconstruction Outcomes Consortium Study is a cohort study that prospectively assessed PROs and retrospectively evaluated complications in patients undergoing immediate implant-based or autologous reconstruction at 11 centers from January 1, 2012, to December 31, 2017. Women 18 years or older undergoing immediate reconstruction after mastectomy with 2 years of follow-up were included. Patients were excluded if they had prophylactic mastectomy; delayed reconstruction; mixed-timing reconstruction; mixed reconstruction; a latissimus dorsi, superior gluteal artery perforator, or inferior gluteal artery perforator flap; or both neoadjuvant and adjuvant chemotherapy. Data were analyzed from May 1 to June 30, 2018. Main Outcomes and Measures: Complications and PROs (satisfaction with breast and physical, psychosocial, and sexual well-being) using the BREAST-Q questionnaire, a validated, condition-specific PRO measure. Baseline patient characteristics were collected. Results: A total of 1881 women were included in the analysis (mean [SD] age, 49.9 [9.9] years). Of these, 1373 (73.0%) underwent implant-based procedures; 508 (27.0%), autologous reconstruction; 200 (10.6%), neoadjuvant chemotherapy; 668 (35.5%), adjuvant chemotherapy; and 1013 (53.9%), no chemotherapy. Patients without chemotherapy were significantly older (mean [SD] age, 51.6 [9.4] years; P < .001), and patients with chemotherapy were more likely to have received radiotherapy (108 of 200 [54.0%] for neoadjuvant chemotherapy and 321 of 668 [48.1%] for adjuvant chemotherapy; P < .001). Among the cohort undergoing implant-based reconstruction, the rates of any complication were significantly different, with higher rates seen for adjuvant (153 of 490 [31.2%]) and neoadjuvant (44 of 153 [28.8%]) chemotherapy compared with no chemotherapy (176 of 730 [24.1%]; P = .02). On multivariable analysis, these differences were not statistically significant. For autologous reconstruction, no significant differences in complications were observed. Controlling for clinical covariates, no significant differences were seen across chemotherapy groups for the BREAST-Q subscales except for sexual well-being in the implant cohort, in which adjuvant chemotherapy had significantly lower scores (ß, -4.97 [95% CI, -8.68 to -1.27]; P = .009). Conclusions and Relevance: In this cohort study, neither neoadjuvant nor adjuvant chemotherapy was associated with the likelihood of complications in patients undergoing implant-based or autologous reconstruction, and chemotherapy was not associated with patient satisfaction with reconstruction or psychosocial well-being. This information can help patients and clinicians make informed decisions about breast reconstruction in the setting of chemotherapy.