Service evaluation suggests variation in clinical care provision in adults with congenital adrenal hyperplasia in the UK and Ireland.

BACKGROUND: Congenital adrenal hyperplasia (CAH) encompasses a rare group of autosomal recessive disorders, characterised by enzymatic defects in steroidogenesis. Heterogeneity in management practices has been observed internationally. The International Congenital Adrenal Hyperplasia registry (I-CAH, https://sdmregistries.org/) was established to enable insights into CAH management and outcomes, yet its global adoption by endocrine centres remains unclear. DESIGN: We sought (1) to assess current practices amongst clinicians managing patients with CAH in the United Kingdom and Ireland, with a focus on choice of glucocorticoid, monitoring practices and screening for associated co-morbidities, and (2) to assess use of the I-CAH registry. MEASUREMENTS: We designed and distributed an anonymised online survey disseminated to members of the Society for Endocrinology and Irish Endocrine Society to capture management practices in the care of patients with CAH. RESULTS: Marked variability was found in CAH management, with differences between general endocrinology and subspecialist settings, particularly in glucocorticoid use, biochemical monitoring and comorbidity screening, with significant disparities in reproductive health monitoring, notably in testicular adrenal rest tumours (TARTs) screening (p = .002), sperm banking (p = .0004) and partner testing for CAH (p < .0001). Adoption of the I-CAH registry was universally low. CONCLUSIONS: Differences in current management of CAH continue to exist. It appears crucial to objectify if different approaches result in different long-term outcomes. New studies such as CaHASE2, incorporating standardised minimum datasets including replacement therapies and monitoring strategies as well as longitudinal data collection, are now needed to define best-practice and standardise care.

Survival outcomes and toxicity of adjuvant immunotherapy after definitive concurrent chemotherapy with proton beam radiation therapy for patients with inoperable locally advanced non-small cell lung carcinoma.

INTRODUCTION: Adjuvant immunotherapy (IO) following concurrent chemotherapy and photon radiation therapy confers an overall survival (OS) benefit for patients with inoperable locally advanced non-small cell lung carcinoma (LA-NSCLC); however, outcomes of adjuvant IO after concurrent chemotherapy with proton beam therapy (CPBT) are unknown. We investigated OS and toxicity after CPBT with adjuvant IO versus CPBT alone for inoperable LA-NSCLC. MATERIALS AND METHODS: We analyzed 354 patients with LA-NSCLC who were prospectively treated with CPBT with or without adjuvant IO from 2009 to 2021. Optimal variable ratio propensity score matching (PSM) matched CPBT with CPBT + IO patients. Survival was estimated with the Kaplan-Meier method and compared with log-rank tests. Multivariable Cox proportional hazards regression evaluated the effect of IO on disease outcomes. RESULTS: Median age was 70 years; 71 (20%) received CPBT + IO and 283 (80%) received CPBT only. After PSM, 71 CPBT patients were matched with 71 CPBT + IO patients. Three-year survival rates for CPBT + IO vs CPBT were: OS 67% vs 30% (P < 0.001) and PFS 59% vs 35% (P = 0.017). Three-year LRFS (P = 0.137) and DMFS (P = 0.086) did not differ. Receipt of adjuvant IO was a strong predictor of OS (HR 0.40, P = 0.001) and PFS (HR 0.56, P = 0.030), but not LRFS (HR 0.61, P = 0.121) or DMFS (HR 0.61, P = 0.136). There was an increased incidence of grade ≥3 esophagitis in the CPBT-only group (6% CPBT + IO vs 17% CPBT, P = 0.037). CONCLUSION: This study, one of the first to investigate CPBT followed by IO for inoperable LA-NSCLC, showed that IO conferred survival benefits with no increased rates of toxicity.

Iatrogenic adrenal insufficiency in adults.

Iatrogenic adrenal insufficiency (IAI) is the most common form of adrenal insufficiency in adult patients, although its overall exact prevalence remains unclear. IAI is associated with adverse clinical outcomes, including adrenal crisis, impaired quality of life and increased mortality; therefore, it is imperative that clinicians maintain a high index of suspicion in patients at risk of IAI to facilitate timely diagnosis and appropriate management. Herein, we review the major causes, clinical consequences, diagnosis and care of patients with IAI. The management of IAI, particularly glucocorticoid-induced (or tertiary) adrenal insufficiency, can be particularly challenging, and the provision of adequate glucocorticoid replacement must be balanced against minimizing the cardiometabolic effects of excess glucocorticoid exposure and optimizing recovery of the hypothalamic-pituitary-adrenal axis. We review current treatment strategies and their limitations and discuss developments in optimizing treatment of IAI. This comprehensive Review aims to aid clinicians in identifying who is at risk of IAI, how to approach screening of at-risk populations and how to treat patients with IAI, with a focus on emergency management and prevention of an adrenal crisis.

Fertility and pregnancy in adrenal insufficiency.

Despite the availability of adrenal hormone replacement therapy, patients with adrenal insufficiency can be affected by reduced fertility and parity. Patients with well-managed adrenal insufficiency are expected to have uneventful pregnancies and favourable outcomes, but an increased risk of maternal and neonatal complications has been reported in some cases. Many physiological changes occur to the hypothalamic-pituitary-adrenal (HPA) axis during pregnancy, often making a new diagnosis and management of adrenal insufficiency challenging. The management of adrenal insufficiency also needs to reflect the physiologic changes of pregnancy, often requiring increased doses of glucocorticoid as pregnancy progresses and in some circumstances mineralocorticoid replacement (in primary adrenal insufficiency patients only), especially in the third trimester. To date, there are no prospective data guiding management of adrenal insufficiency in pregnancy. In this review, we focus on the impact of adrenal insufficiency on fertility and parity based on the aetiology of adrenal insufficiency and provide a practical approach to the management of patients with adrenal insufficiency before and during pregnancy.

Complications, Treatment, and Outcomes of Self-Injecting Substances Into the Face: A Systematic Review.

BACKGROUND: The increased demand for minimally invasive facial cosmetic procedures in tandem with the ease of acquiring injectable cosmetics through direct-to-consumer retailers has led to a rise in self-injecting cosmetics among untrained individuals. OBJECTIVE: To analyze complications, treatments, and outcomes associated with self-injecting fillers into the face. METHODS: A systematic review of the literature from PubMed and Embase databases was performed from inception to September 10, 2022, to identify studies pertaining to self-injection of facial fillers. RESULTS: A total of 15 articles describing 38 complications among 18 patients were included in the data collection. The most commonly injected substance was hyaluronic acid (76.4%). The lips were the most common site of injection (33%). The most reported complication was edema (61%). Severe complications included acute vascular compromise (11%) and acute hearing loss (5%). The most common intervention was use of hyaluronidase and/or antibiotics (87.5%). Patients generally healed after treatment although residual localized hyperpigmentation was noted among 11% of patients. CONCLUSION: Injecting commercially available substances into the face is associated with potentially irreversible aesthetic, infectious, and vascular complications, especially in the hands of untrained consumers. Patients and providers should be aware of this dangerous trend.

Identification of novel NRF2-dependent genes as regulators of lead and arsenic toxicity in neural progenitor cells.

Lead (Pb) and arsenic (As) are prevalent metal contaminants in the environment. Exposures to these metals are associated with impaired neuronal functions and adverse effects on neurodevelopment in children. However, the molecular mechanisms by which Pb and As impair neuronal functions remain poorly understood. Here, we identified F2RL2, TRIM16L, and PANX2 as novel targets of Nuclear factor erythroid 2-related factor 2 (NRF2)-the master transcriptional factor for the oxidative stress response-that are commonly upregulated with both Pb and As in human neural progenitor cells (NPCs). Using a ChIP (Chromatin immunoprecipitation)-qPCR assay, we showed that NRF2 directly binds to the promoter region of F2RL2, TRIM16L, and PANX2 to regulate expression of these genes. We demonstrated that F2RL2, PANX2, and TRIM16L have differential effects on cell death, proliferation, and differentiation of NPCs in both the presence and absence of metal exposures, highlighting their roles in regulating NPC function. Furthermore, the analyses of the transcriptomic data on NPCs derived from autism spectrum disorder (ASD) patients revealed that dysregulation of F2RL2, TRIM16L, and PANX2 was associated with ASD genetic backgrounds and ASD risk genes. Our findings revealed that Pb and As induce a shared NRF2-dependent transcriptional response in NPCs and identified novel genes regulating NPC function. While further in vivo studies are warranted, this study provides a novel mechanism linking metal exposures to NPC function and identifies potential genes of interest in the context of neurodevelopment.

Clinical Utility of GnRH Analogues in Female Androgen Excess: Highlighting Diagnostic and Therapeutic Applications.

Female androgen excess typically presents with hirsutism, acne, and frontotemporal alopecia. Although the majority of cases are due to underlying polycystic ovary syndrome, non-polycystic ovary syndrome pathology can present a diagnostic and therapeutic challenge. We present 3 cases highlighting the utility of GnRH analogues in diagnosis and treatment of ovarian hyperandrogenism. In case 1, we highlight the role of GnRH analogue testing to localize severe postmenopausal androgen excess, allowing full resolution of symptoms following resection of a benign ovarian steroid-cell tumor. Our second case demonstrates the dual utility of GnRH analogues as both a diagnostic and therapeutic agent for hyperandrogenism in a premenopausal woman with severe insulin resistance. We observed suppression of serum testosterone coupled with significant improvement in hirsutism scores. The final case describes GnRH analogue suppression as a therapeutic option for a postmenopausal woman with ovarian hyperthecosis wishing to avoid surgical intervention, with successful symptom resolution. This case series delineates the applications of GnRH analogue suppression in a variety of clinical contexts, in particular their potential role in controlling symptoms in cases of refractory androgen excess and an alternative to surgery in cases of benign ovarian hyperandrogenism.

Concerns and expectations in women with polycystic ovary syndrome vary across age and ethnicity: findings from PCOS Pearls Study.

Objective: To understand and explore the perceptions and opinions of women with polycystic ovary syndrome (PCOS) and further delineate the variations across age and ethnicity. Design: Qualitative survey focussed on lived experiences of people with PCOS. Participants could share their views either as written text or as voice note audio recording(s) on WhatsApp. The data from the audio were transcribed verbatim. Responses were coded by two study members independently, using a thematic inductive method with NVivo 12. Two senior study members then reviewed these codes to identify common themes. Subjects: Women with PCOS aged 18-60 years. Results: 43 of 45 participants had a formal diagnosis of PCOS, the remaining two had suspected PCOS which was under investigation. Four participants opted to share their views as voice note recordings. Poor mental health was the most reported (83.3% of participants), followed by dermatological (81.0%) and menstrual issues (76.2%). Participants were generally dissatisfied with the care they received (88.1%). A lengthy diagnostic journey was reported in 35.7% of cases. 52.6% felt less feminine, particularly regarding weight gain and infertility. As part of the recommendations by participants, it was emphasised that others with the condition should educate themselves and be proactive in their management. 46.3% reported that being more enlightened regarding their condition improved their health outcomes and enabled them to advocate for their own care. Women in their 20s expressed distress due to poor mental health, needing a longer time to get the diagnosis, and having weight and eating concerns. While women with PCOS in their 30s discussed their menstrual irregularities and fertility issues, those in their 40s expressed their concerns about the societal expectations of women when diagnosed with PCOS. The concerns varied across ethnicities as well. Conclusion: PCOS has wide-ranging consequences for women living with the condition, with many dissatisfied with the clinical support they currently receive. The concerns and expectations vary across ages and ethnicities. Therefore, we propose involving women with PCOS to co-create clinical and educational resources informed by lived experiences to provide end-user-informed services.

Factors Influencing Graduates of American Academy of Facial Plastic and Reconstructive Surgery Fellowships Career Choice of Academic or Private Practice: A 20-Year Review.

Background: Absence of published literature on facial plastic and reconstructive surgery (FPRS) fellows' pursuit of academic careers hampers informed decision making for those interested in the specialty, fellowship program directors, and leaders in the American Academy of Facial Plastic and Reconstructive Surgery. Objective: To examine career choices among FPRS fellows from 2000 to 2019 and identify factors linked to academic or private practice employment after fellowship. Methods: Data from 796 fellows were analyzed, including gender, medical school, residency program, fellowship program, fellowship year, and degrees, to categorize them based on academic or nonacademic career placement. Logistic regression analyses were conducted to explore the association between demographic factors and academic career placement. Results: Forty-three percent (n = 345) obtained academic positions, with significant associations found between academic placement and additional advanced degrees, completion of fellowship training in the northeast, and residency training at an institution offering FPRS fellowship. Conclusion: Although fellows in FPRS predominantly pursue private practice, the decision to pursue academia is influenced by complex and multifactorial factors among graduates in the field.

Building Career Paths for Ph.D., Basic and Translational Scientists in Clinical Departments in the United States: An Official American Thoracic Society Workshop Report.

Rationale: To identify barriers and opportunities for Ph.D., basic and translational scientists to be fully integrated into clinical units. Objectives: In 2022, an ad hoc committee of the American Thoracic Society developed a project proposal and workshop to identify opportunities and barriers for scientists who do not practice medicine to develop successful careers and achieve tenure-track faculty positions in clinical departments and divisions within academic medical centers (AMCs) in the United States. Methods: This document focuses on results from a survey of adult and pediatric pulmonary, critical care, and sleep medicine division chiefs as well as a survey of workshop participants, including faculty in departmental and school leadership roles in both basic science and clinical units within U.S. AMCs. Results: We conclude that full integration of non-clinically practicing basic and translational scientists into the clinical units, in addition to their traditional placements in basic science units, best serves the tripartite mission of AMCs to provide care, perform research, and educate the next generation. Evidence suggests clinical units do employ Ph.D. scientists in large numbers, but these faculty are often hired into non-tenure track positions, which do not provide the salary support, start-up funds, research independence, or space often associated with hiring in basic science units within the same institution. These barriers to success of Ph.D. faculty in clinical units are largely financial. Conclusions: Our recommendation is for AMCs to consider and explore some of our proposed strategies to accomplish the goal of integrating basic and translational scientists into clinical units in a meaningful way.

Generalizability of Deep Learning Classification of Spinal Osteoporotic Compression Fractures on Radiographs Using an Adaptation of the Modified-2 Algorithm-Based Qualitative Criteria.

RATIONALE AND OBJECTIVES: Spinal osteoporotic compression fractures (OCFs) can be an early biomarker for osteoporosis but are often subtle, incidental, and underreported. To ensure early diagnosis and treatment of osteoporosis, we aimed to build a deep learning vertebral body classifier for OCFs as a critical component of our future automated opportunistic screening tool. MATERIALS AND METHODS: We retrospectively assembled a local dataset, including 1790 subjects and 15,050 vertebral bodies (thoracic and lumbar). Each vertebral body was annotated using an adaption of the modified-2 algorithm-based qualitative criteria. The Osteoporotic Fractures in Men (MrOS) Study dataset provided thoracic and lumbar spine radiographs of 5994 men from six clinical centers. Using both datasets, five deep learning algorithms were trained to classify each individual vertebral body of the spine radiographs. Classification performance was compared for these models using multiple metrics, including the area under the receiver operating characteristic curve (AUC-ROC), sensitivity, specificity, and positive predictive value (PPV). RESULTS: Our best model, built with ensemble averaging, achieved an AUC-ROC of 0.948 and 0.936 on the local dataset's test set and the MrOS dataset's test set, respectively. After setting the cutoff threshold to prioritize PPV, this model achieved a sensitivity of 54.5% and 47.8%, a specificity of 99.7% and 99.6%, and a PPV of 89.8% and 94.8%. CONCLUSION: Our model achieved an AUC-ROC>0.90 on both datasets. This testing shows some generalizability to real-world clinical datasets and a suitable performance for a future opportunistic osteoporosis screening tool.

Standardising the biochemical confirmation of adult male hypogonadism; a joint position statement by the Society for Endocrinology and Association of Clinical Biochemistry and Laboratory Medicine.

Background: Inter-assay variation between different immunoassays and different mass spectrometry methods hampers the biochemical confirmation of male hypogonadism. Furthermore, some laboratories utilis eassay manufacturer reference ranges that do not necessarily mirror assay performance characteristics, with the lower limit of normality ranging from 4.9 nmol/L to 11 nmol/L. The quality of the normative data underlying commercial immunoassay reference ranges is uncertain.Design: A working group reviewed published evidence and agreed upon standardised reporting guidance to augment total testosterone reports. Results: Evidence-based guidance on appropriate blood sampling, clinical action limits, and other major factors likely to affect the interpretation of results are provided. Conclusions: This article aims to improve the quality of the interpretation of testosterone results by non-specialist clinicians. It also discusses approaches for assay harmonisation which have been successful in some but not all healthcare systems.

Pulse oximetry values from 33,080 participants in the Apple Heart & Movement Study.

Wearable devices that include pulse oximetry (SpO2) sensing afford the opportunity to capture oxygen saturation measurements from large cohorts under naturalistic conditions. We report here a cross-sectional analysis of 72 million SpO2 values collected from 33,080 individual participants in the Apple Heart and Movement Study, stratified by age, sex, body mass index (BMI), home altitude, and other demographic variables. Measurements aggregated by hour of day into 24-h SpO2 profiles exhibit similar circadian patterns for all demographic groups, being approximately sinusoidal with nadir near midnight local time, zenith near noon local time, and mean 0.8% lower saturation during overnight hours. Using SpO2 measurements averaged for each subject into mean nocturnal and daytime SpO2 values, we employ multivariate ordinary least squares regression to quantify population-level trends according to demographic factors. For the full cohort, regression coefficients obtained from models fit to daytime SpO2 are in close quantitative agreement with the corresponding values from published reference models for awake arterial oxygen saturation measured under controlled laboratory conditions. Regression models stratified by sex reveal significantly different age- and BMI-dependent SpO2 trends for females compared with males, although constant terms and regression coefficients for altitude do not differ between sexes. Incorporating categorical variables encoding self-reported race/ethnicity into the full-cohort regression models identifies small but statistically significant differences in daytime SpO2 (largest coefficient corresponding to 0.13% lower SpO2, for Hispanic study participants compared to White participants), but no significant differences between groups for nocturnal SpO2. Additional stratified analysis comparing regression models fit independently to subjects in each race/ethnicity group is suggestive of small differences in age- and sex-dependent trends, but indicates no significant difference in constant terms between any race/ethnicity groups for either daytime or nocturnal SpO2. The large diverse study population and study design employing automated background SpO2 measurements spanning the full 24-h circadian cycle enables the establishment of healthy population reference trends outside of clinical settings.

Standardising the biochemical confirmation of adult male hypogonadism: A joint position statement by the Society for Endocrinology and Association of Clinical Biochemistry and Laboratory Medicine.

BACKGROUND: Inter-assay variation between different immunoassays and different mass spectrometry methods hampers the biochemical confirmation of male hypogonadism. Furthermore, some laboratories utilise assay manufacturer reference ranges that do not necessarily mirror assay performance characteristics, with the lower limit of normality ranging from 4.9 nmol/L to 11 nmol/L. The quality of the normative data underlying commercial immunoassay reference ranges is uncertain. DESIGN: A working group reviewed published evidence and agreed upon standardised reporting guidance to augment total testosterone reports. RESULTS: Evidence-based guidance on appropriate blood sampling, clinical action limits, and other major factors likely to affect the interpretation of results are provided. CONCLUSIONS: This article aims to improve the quality of the interpretation of testosterone results by non-specialist clinicians. It also discusses approaches for assay harmonisation which have been successful in some but not all healthcare systems.

A retrospective analysis of pain and opioid usage in head and neck free flap reconstruction.

Objectives: Investigate opioid usage and postoperative pain in patients undergoing head and neck free flap surgery. Methods: A retrospective review of 100 consecutive patients undergoing head and neck free flap reconstruction at two academic centers was performed. Data captured included demographics, postoperative inpatient pain, pain at postoperative visits, morphine equivalent doses (MEDs) administration, medication history, and comorbidities. Data were analyzed using regression models, χ 2 tests, and student's t-tests. Results: Seventy-three percent of patients were discharged with opioid medication, with over half (53.4%) continuing to take opioids at their second postoperative visit, and over one-third (34.2%) continuing to take them around 4-month postoperatively. One out of every five (20.3%) opioid-naïve patients chronically took opioids postoperatively. There was a poor association between inpatient postoperative pain scores and daily MEDs administered (R 2 = 0.13, 0.17, and 0.22 in postoperative Days 3, 5, and 7, respectively). Neither preoperative radiotherapy nor postoperative complications were associated with an increase in opioid usage. Conclusions: For patients undergoing head and neck free flap operations, opioid medications are commonly used for postoperative analgesia. This practice may increase the chance an opioid-naïve patient uses opioids chronically. We found a poor association between MEDs administered and patient-reported pain scores, which suggests that standardized protocols aimed at optimizing analgesia while reducing opioid administration may be warranted. Level of Evidence: 3 (Retrospective cohort study).

Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy.

BACKGROUND: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11ß-hydroxysteroid dehydrogenase (11ß-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo. STUDY DESIGN AND METHODS: Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls. RESULTS: Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11ß-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11ß-HSD2 activity. Hepatic 11ß-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11ß-HSD1 in subcutaneous adipose tissue. CONCLUSION: Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC.

PFAS soil concentrations surrounding a hazardous waste incinerator in East Liverpool, Ohio, an environmental justice community.

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic compounds widely used in industrial and consumer products. While PFAS provide product durability, these chemicals are ubiquitous, persistent, bioaccumulative, and toxic. These characteristics make the ultimate disposal of PFAS a challenge. One current disposal method is incineration; however, little research has been conducted on the safety and effectiveness of PFAS incineration. The characteristics of communities with hazardous waste incinerators that have received PFAS shipments indicate that more individuals with lower incomes and individuals with less education than the US average are at higher risk of exposure, which presents important environmental justice and health equity concerns of PFAS incineration. Situated in eastern Ohio, East Liverpool is an Appalachian community that is home to a large hazardous-waste incinerator, operated by Heritage WTI, that began accepting PFAS in 2019. Residents are concerned that the disposal lacks the research necessary to assure safety for the residents. Due to both community interest and data gaps regarding PFAS incineration, our research team conducted a pilot study to examine the distribution and concentration of PFAS in soil samples surrounding the incinerator. All 35 soil samples had measurable amounts of PFAS including perfluorobutanesulfonic acid (PFBS), perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and hexafluoropropylene oxide dimer acid (HFPO-DA)/GenX. PFOS was measured in the majority of soil samples (97%) with a range of 50-8,300 ng/kg. PFOA was measured in 94% of soil samples with a range of 51 ng/kg to 1300 ng/kg. HFPO-DA/GenX was measurable in 12 soil samples with concentrations of ranging from 150 ng/kg to 1500 ng/kg. Further research on PFAS disposal will advance knowledge and action related to regulatory requirements and exposure prevention, ultimately improving individual and community protections and health equity.

Mortality among older adults with osteoporotic vertebral fracture.

We evaluated whether older adults who received kyphoplasty had reduced risk of mortality compared to those who did not. In unmatched analyses, those receiving kyphoplasty were at reduced risk of death but after matching on age and medical complications, patients who received kyphoplasty were at increased risk of death. PURPOSE: In previous observational studies, kyphoplasty for treatment of osteoporotic vertebral fractures has been associated with decreased mortality compared to conservative management. The purpose of this research was to determine whether older adults who received kyphoplasty had reduced risk of mortality compared to matched patients who did not. METHODS: Retrospective cohort study of US Medicare enrollees with osteoporotic vertebral fractures between 2017-2019 comparing patients who underwent kyphoplasty to those who did not. We identified 2 control groups a priori: 1) non-augmented patients who met inclusion criteria (group 1); 2) propensity-matched patients on demographic and clinical variables (group 2). We then identified additional control groups using matching for medical complications (group 3) and age + comorbidities (group 4). We calculated hazard ratios (HRs) and 95% confidence intervals (95% CIs) associated with mortality. RESULTS: A total of 235,317 patients (mean (± standard deviation) age 81.1 ± 8.3 years; 85.8% female) were analyzed. In the primary analyses, those who received kyphoplasty were at reduced risk of death compared to those who did not: adjusted HR (95% CI) in group 1 = 0.84 (0.82, 0.87); and in group 2 = 0.88 (0.85, 0.91). However, in post hoc analyses, patients who received kyphoplasty were at increased risk of death: adjusted HR (95% CI) in group 3 = 1.32 (1.25, 1.41) and 1.81 (1.58, 2.09) in group 4. CONCLUSION: An apparent benefit of kyphoplasty on mortality among patients with vertebral fractures was not present after rigorous propensity matching, illustrating the importance of comparing similar individuals when evaluating observational data.

Understanding the Impact of Aging on Attractiveness Using a Machine Learning Model of Facial Age Progression.

Background: Advances in machine learning age progression technology offer the unique opportunity to better understand the public's perception on the aging face. Objective: To compare how observers perceive attractiveness and traditional gender traits in faces created with a machine learning model. Methods: Eight surveys were developed, each with 10 sets of photographs that were progressively aged with a machine learning model. Respondents rated attractiveness and masculinity or femininity of each photograph using a sliding scale (range: 0-100). Mean attractiveness scores were calculated and compared between men and women as well as between age groups. Results: A total of 315 respondents (51% men, 49% women) completed the survey. Accuracy of the facial age progression model was 85%. Females were considered significantly less attractive (-10.43, p < 0.01) and less feminine (-7.59, p < 0.01) per decade with the greatest drop over age 40 years. Male attractiveness and masculinity were relatively preserved until age 50 years where attractiveness scores were significantly lower (-5.45, p = 0.39). Conclusions: In this study, observers were found to perceive attractiveness at older ages differently between men and women.