A pilot study to identify factors associated with frailty within the World Trade Center general responder cohort.

BACKGROUND: Given the significant exposures experienced by the World Trade Center (WTC) general responders, there is increasing interest in understanding the effect of these exposures on aging in this population. We aim to identify factors that may be associated with frailty, a clinical syndrome characterized by a decrease in one's reserve that has been linked to poor health outcomes. METHODS: WTC general responders enrolled in the WTC Health Program aged 50 and older provided informed consent. Validated frailty assessments, the Frailty Phenotype (with the Johns Hopkins Frailty Assessment Calculator) along with the FRAIL scale, categorized nonfrail from prefrail/frail. Fall risk, functional status, and cognition were also assessed. WTC variables, including an identified WTC-certified condition, were utilized. The risk of frailty was estimated using log binomial regression analysis. A 95% confidence interval (CI) was used to estimate the prevalence ratio (PR). RESULTS: One hundred and six participants were included; 38 (35.8%) were classified as pre-frail or frail. More of the pre-frail/frail group were obese (57.9% vs. 25%; p = 0.004) and had a WTC-certified condition (78.9% vs. 58.8%; p = 0.036). Obesity (PR = 2.43, 95% CI = 1.31, 4.53), a WTC-certified condition (PR = 1.77, 95% CI = 1.09, 2.89), and risk of falling (PR = 1.97, 95% CI = 1.01, 3.84) were independently associated with frailty. CONCLUSIONS: Obesity and having a WTC-certified condition were found to be risk factors for frailty in our pilot study. Future work may focus on further identifying risk factors for frailty in the larger WTC general responder population.

A Randomized Trial of a Multifactorial Strategy to Prevent Serious Fall Injuries.

BACKGROUND: Injuries from falls are major contributors to complications and death in older adults. Despite evidence from efficacy trials that many falls can be prevented, rates of falls resulting in injury have not declined. METHODS: We conducted a pragmatic, cluster-randomized trial to evaluate the effectiveness of a multifactorial intervention that included risk assessment and individualized plans, administered by specially trained nurses, to prevent fall injuries. A total of 86 primary care practices across 10 health care systems were randomly assigned to the intervention or to enhanced usual care (the control) (43 practices each). The participants were community-dwelling adults, 70 years of age or older, who were at increased risk for fall injuries. The primary outcome, assessed in a time-to-event analysis, was the first serious fall injury, adjudicated with the use of participant report, electronic health records, and claims data. We hypothesized that the event rate would be lower by 20% in the intervention group than in the control group. RESULTS: The demographic and baseline characteristics of the participants were similar in the intervention group (2802 participants) and the control group (2649 participants); the mean age was 80 years, and 62.0% of the participants were women. The rate of a first adjudicated serious fall injury did not differ significantly between the groups, as assessed in a time-to-first-event analysis (events per 100 person-years of follow-up, 4.9 in the intervention group and 5.3 in the control group; hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P = 0.25). The rate of a first participant-reported fall injury was 25.6 events per 100 person-years of follow-up in the intervention group and 28.6 events per 100 person-years of follow-up in the control group (hazard ratio, 0.90; 95% CI, 0.83 to 0.99; P = 0.004). The rates of hospitalization or death were similar in the two groups. CONCLUSIONS: A multifactorial intervention, administered by nurses, did not result in a significantly lower rate of a first adjudicated serious fall injury than enhanced usual care. (Funded by the Patient-Centered Outcomes Research Institute and others; STRIDE ClinicalTrials.gov number, NCT02475850.).

Decision making in frail patients at risk of postoperative delirium: A case study and literature review.

Preoperative frailty is strongly associated with risks of postoperative delirium. However, gaps exist in targeted recommendations for clinical decision making related to surgical interventions in frail older patients. A case study is presented involving a frail 74-year-old referred to the palliative care team for assistance with clinical decision making and in weighing risks and benefits of a surgical intervention. A literature review on the quantification of postoperative delirium risk and how this information might inform medical decision making in frail surgical patients did not identify clear clinical guidelines. In the absence of practice guidelines, the Patient Priorities Care model is proposed as a framework to help providers working with patients and caregivers facing complex medical decisions to better align interventions with patient values.

TNF-α and sTNF-RII Are Associated with Pain Following Hip Fracture Surgery in Older Adults.

Objective: To explore whether plasma inflammatory mediators on postoperative day 3 (POD3) are associated with pain scores in older adults after hip fracture surgery. Design: Cross-sectional study. Setting: Mount Sinai Hospital, New York, New York. Subjects: Forty patients age 60 years or older who presented with acute hip fracture at Mount Sinai Hospital between November 2011 and April 2013. Methods: Plasma levels of six inflammatory mediators of the nuclear factor kappa B pathway were measured using blood collected on POD3. Self-reported pain scores (i.e., pain with resting, walking, and transferring) were assessed at baseline (prefracture) and on POD3. Linear regression models using log-transformed data were performed to determine associations between inflammatory mediators and postoperative pain. Results: Interleukin 18 (IL-18) was positively associated with POD3 resting pain score in the unadjusted model (ß = 0.66, P = 0.03). Tumor necrosis factor α (TNF-α) and soluble TNF receptor II (sTNF-RII) were positively associated with POD3 resting pain score in the adjusted model (ß = 0.99, P = 0.03, and ß = 0.86, P = 0.04, respectively). Moreover, TNF-α was positively associated with POD3 walking pain score in the adjusted model (ß = 1.59, P = 0.05). Pain with transferring was not associated with these inflammatory mediators. Conclusions: These findings suggest that TNF-α and its receptors may influence pain following hip fracture. Further study of the TNF-α pathway may inform future clinical applications that monitor and treat pain in the vulnerable elderly who are unable to accurately report pain.

Prevalence of Frailty and Prefrailty in People With Human Immunodeficiency Virus Aged 50 or Older: A Systematic Review and Meta-Analysis.

Background: With effective antiretroviral therapy, there is an emerging population of adults aged 50 years or older with human immunodeficiency virus (HIV). Frailty is an increasingly recognized clinical state of vulnerability associated with disability, hospitalization, and mortality. However, there is a paucity of large studies assessing its prevalence in people with HIV (PWH) aged 50 or older. Methods: PubMed was systematically searched for studies published between January 2000 and August 2020 reporting the prevalence of frailty in PWH aged 50 or older. The pooled prevalence of frailty and prefrailty was synthesized using a random-effects meta-analysis. Results: Of the 425 studies identified, 26 studies were included in the analysis, with a total of 6584 PWH aged 50 or older. The included studies were published between 2012 and 2020, and all studies used the Fried frailty phenotype to define frailty. The overall pooled prevalence of frailty and prefrailty was 10.9% (95% confidence interval [CI], 8.1%-14.2%) and 47.2% (95% CI, 40.1%-54.4%), respectively. A high degree of heterogeneity was observed (I2 = 93.2%). In the subgroup analysis, HIV-related variables and other demographic variables were examined, and heterogeneity disappeared only in the group of a longer duration since HIV diagnosis (I2 = 0%). Conclusions: The pooled prevalence of frailty and prefrailty defined by the Fried frailty phenotype was assessed in PWH aged 50 or older. Findings from this study quantified the proportion of this specific population with this common geriatric syndrome. Future studies identifying effective strategies for frailty screening and intervention are required for this vulnerable population.

RNA-sequencing Reveals a Gene Expression Signature in Skeletal Muscle of a Mouse Model of Age-associated Postoperative Functional Decline.

This study aimed to characterize the effects of laparotomy on postoperative physical function and skeletal muscle gene expression in male C57BL/6N mice at 3, 20, and 24 months of age to investigate late-life vulnerability and resiliency to acute surgical stress. Pre and postoperative physical functioning was assessed by forelimb grip strength on postoperative day (POD) 1 and 3 and motor coordination on POD 2 and 4. Laparotomy-induced an age-associated postoperative decline in forelimb grip strength that was the greatest in the oldest mice. While motor coordination declined with increasing age at baseline, it was unaffected by laparotomy. Baseline physical function as stratified by motor coordination performance (low functioning vs high functioning) in 24-month-old mice did not differentially affect postlaparotomy reduction in grip strength. RNA sequencing of soleus muscles showed that laparotomy-induced age-associated differential gene expression and canonical pathway activation with the greatest effects in the youngest mice. Examples of such age-associated, metabolically important pathways that were only activated in the youngest mice after laparotomy included oxidative phosphorylation and NRF2-mediated oxidative stress response. Analysis of lipid mediators in serum and gastrocnemius muscle showed alterations in profiles during aging and confirmed an association between such changes and functional status in gastrocnemius muscle. These findings demonstrate a mouse model of laparotomy which recapitulated some features of postoperative skeletal muscle decline in older adults, and identified age-associated, laparotomy-induced molecular signatures in skeletal muscles. Future research can build upon this model to study molecular mechanisms of late-life vulnerability and resiliency to acute surgical stress.

Numb is required for optimal contraction of skeletal muscle.

BACKGROUND: The role of Numb, a protein that is important for cell fate and development and that, in human muscle, is expressed at reduced levels with advanced age, was investigated; adult mice skeletal muscle and its localization and function within myofibres were determined. METHODS: Numb expression was evaluated by western blot. Numb localization was determined by confocal microscopy. The effects of conditional knock out (cKO) of Numb and the closely related gene Numb-like in skeletal muscle fibres were evaluated by in situ physiology, transmission and focused ion beam scanning electron microscopy, three-dimensional reconstruction of mitochondria, lipidomics, and bulk RNA sequencing. Additional studies using primary mouse myotubes investigated the effects of Numb knockdown on cell fusion, mitochondrial function, and calcium transients. RESULTS: Numb protein expression was reduced by ~70% (P < 0.01) at 24 as compared with 3 months of age in gastrocnemius and tibialis anterior muscle. Numb was localized within muscle fibres as bands traversing fibres at regularly spaced intervals in close proximity to dihydropyridine receptors. The cKO of Numb and Numb-like reduced specific tetanic force by 36% (P < 0.01), altered mitochondrial spatial relationships to sarcomeric structures, increased Z-line spacing by 30% (P < 0.0001), perturbed sarcoplasmic reticulum organization and reduced mitochondrial volume by over 80% (P < 0.01). Only six genes were differentially expressed in cKO mice: Itga4, Sema7a, Irgm2, Vezf1, Mib1, and Tmem132a. Several lipid mediators derived from polyunsaturated fatty acids through lipoxygenases were up-regulated in Numb cKO skeletal muscle: 12-HEPE was increased by ~250% (P < 0.05) and 17,18-EpETE by ~240% (P < 0.05). In mouse primary myotubes, Numb knockdown reduced cell fusion (~20%, P < 0.01) and delayed the caffeine-induced rise in cytosolic calcium concentrations by more than 100% (P < 0.01). CONCLUSIONS: These findings implicate Numb as a critical factor in skeletal muscle structure and function and suggest that Numb is critical for calcium release. We therefore speculate that Numb plays critical roles in excitation-contraction coupling, one of the putative targets of aged skeletal muscles. These findings provide new insights into the molecular underpinnings of the loss of muscle function observed with sarcopenia.

Effect of the STRIDE fall injury prevention intervention on falls, fall injuries, and health-related quality of life.

BACKGROUND: Falls are common in older adults and can lead to severe injuries. The Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial cluster-randomized 86 primary care practices across 10 health systems to a multifactorial intervention to prevent fall injuries, delivered by registered nurses trained as falls care managers, or enhanced usual care. STRIDE enrolled 5451 community-dwelling older adults age ≥70 at increased fall injury risk. METHODS: We assessed fall-related outcomes via telephone interviews of participants (or proxies) every 4 months. At baseline, 12 and 24 months, we assessed health-related quality of life (HRQOL) using the EQ-5D-5L and EQ-VAS. We used Poisson models to assess intervention effects on falls, fall-related fractures, fall injuries leading to hospital admission, and fall injuries leading to medical attention. We used hierarchical longitudinal linear models to assess HRQOL. RESULTS: For recurrent event models, intervention versus control incidence rate ratios were 0.97 (95% confidence interval [CI], 0.93-1.00; p = 0.048) for falls, 0.93 (95% CI, 0.80-1.08; p = 0.337) for self-reported fractures, 0.89 (95% CI, 0.73-1.07; p = 0.205) for adjudicated fractures, 0.91 (95% CI, 0.77-1.07; p = 0.263) for falls leading to hospital admission, and 0.97 (95% CI, 0.89-1.06; p = 0.477) for falls leading to medical attention. Similar effect sizes (non-significant) were obtained for dichotomous outcomes (e.g., participants with ≥1 events). The difference in least square mean change over time in EQ-5D-5L (intervention minus control) was 0.009 (95% CI, -0.002 to 0.019; p = 0.106) at 12 months and 0.005 (95% CI, -0.006 to 0.015; p = 0.384) at 24 months. CONCLUSIONS: Across a standard set of outcomes typically reported in fall prevention studies, we observed modest improvements, one of which was statistically significant. Future work should focus on patient-, practice-, and organization-level operational strategies to increase the real-world effectiveness of interventions, and improving the ability to detect small but potentially meaningful clinical effects. CLINICALTRIALS: gov identifier: NCT02475850.

The Science of Frailty: Sex Differences.

Frailty is an important clinical syndrome of age-related decline in physiologic reserve and increased vulnerability. In older adults, frailty leads to progressive multisystem decline and increased adverse clinical outcomes. The pathophysiology of frailty is hypothesized to be driven by dysregulation of neuroendocrine, inflammatory, and metabolic pathways. Sex-specific differences in the prevalence of frailty have been observed. Treatment interventions of geriatric care can be applied to the care of frail older women with these differences in mind. As additional evidence regarding sex-specific differences in frailty emerges, research efforts should encompass the development of screening tools and therapeutic interventions that optimize outcomes.

HIV and Aging: Overcoming Challenges in Existing HIV Guidelines to Provide Patient-Centered Care for Older People with HIV.

With advances in antiretroviral therapy and subsequent increase in life expectancy, People with HIV (PWH) now experience multiple geriatric syndromes in the setting of advanced aging and increased multimorbidity. HIV clinicians bear the responsibility of delivering geriatric care to this vulnerable population, despite limited geriatric medicine training and limited support from HIV service networks that were not traditionally designed to care for an aging population. Although HIV clinicians reported formal guidelines specific to older PWH to be among the most helpful interventions, current HIV guidelines present multiple issues in their applicability to the care of older PWH, including multifactorial nature of conditions in older adults, difficulty measuring patient-centered outcomes, lack of representation of older PWH in clinical trials, limited guidelines addressing geriatric syndromes, and the use of chronological age as criteria for inclusion despite advanced aging in PWH. Understanding that updated guidelines addressing above challenges may take many years to develop, we offer strategies on the application of current guidelines, including using baseline attributes, time to benefit, and the Geriatrics 5M model to aid in shared decision making and improve outcomes among older PWH.

Barriers to implementation of STRIDE, a national study to prevent fall-related injuries.

BACKGROUND/OBJECTIVES: Evaluations of complex models of care for older adults may benefit from simultaneous assessment of intervention implementation. The STRIDE (Strategies To Reduce Injuries and Develop confidence in Elders) pragmatic trial evaluated the effectiveness of a multifactorial intervention to reduce serious fall injuries in older adults. We conducted multi-level stakeholder interviews to identify barriers to STRIDE intervention implementation and understand efforts taken to mitigate these barriers. DESIGN: Qualitative interviews with key informants. SETTING: Ten clinical trial sites affiliated with practices that provided primary care for persons at increased risk for fall injuries. PARTICIPANTS: Specially trained registered nurses working as Falls Care Managers (FCMs) who delivered the intervention (n = 13 individual interviews), Research Staff who supervised trial implementation locally (n = 10 group interviews, 23 included individuals), and members of Central Project Management and the National Patient Stakeholder Council who oversaw national implementation (n = 2 group interviews, six included individuals). MEASUREMENTS: A semi-structured interview guide derived from the consolidated framework for implementation research (CFIR). RESULTS: We identified eight key barriers to STRIDE intervention implementation. FCMs navigated complex relationships with patients and families while working with Research Staff to implement the intervention in primary care practices with limited clinical space, variable provider buy-in, and significant primary care practice staff and provider turnover. The costs of the intervention to individual patients and medical practices amplified these barriers. Efforts to mitigate these barriers varied depending on the needs and opportunities of each primary care setting. CONCLUSION: The many barriers to implementation and the variability in how stakeholders addressed these locally may have affected the overall STRIDE intervention's effectiveness. Future pragmatic trials should incorporate simultaneous implementation aims to better understand how research interventions translate into clinical care that improves the lives of older adults.

Development and Validation of a Clinical Frailty Index for the World Trade Center General Responder Cohort.

Objectives: To develop and validate a clinical frailty index to characterize aging among responders to the 9/11 World Trade Center (WTC) attacks. Methods: This study was conducted on health monitoring data on a sample of 6197 responders. A clinical frailty index, WTC FI-Clinical, was developed according to the cumulative deficit model of frailty. The validity of the resulting index was assessed using all-cause mortality as an endpoint. Its association with various cohort characteristics was evaluated. Results: The sample's median age was 51 years. Thirty items were selected for inclusion in the index. It showed a strong correlation with age, as well as significant adjusted associations with mortality, 9/11 exposure severity, sex, race, pre-9/11 occupation, education, and smoking status. Discussion: The WTC FI-Clinical highlights effects of certain risk factors on aging within the 9/11 responder cohort. It will serve as a useful instrument for monitoring and tracking frailty within this cohort.

Effect of a Multifactorial Fall Injury Prevention Intervention on Patient Well-Being: The STRIDE Study.

BACKGROUND/OBJECTIVES: In the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) study, a multifactorial intervention was associated with a nonsignificant 8% reduction in time to first serious fall injury but a significant 10% reduction in time to first self-reported fall injury relative to enhanced usual care. The effect of the intervention on other outcomes important to patients has not yet been reported. We aimed to evaluate the effect of the intervention on patient well-being including concern about falling, anxiety, depression, physical function, and disability. DESIGN: Pragmatic cluster-randomized trial of 5,451 community-living persons at high risk for serious fall injuries. SETTING: A total of 86 primary care practices within 10 U.S. healthcare systems. PARTICIPANTS: A random subsample of 743 persons aged 75 and older. MEASUREMENTS: The well-being measures, assessed at baseline, 12 months, and 24 months, included a modified version of the Fall Efficacy Scale, Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and depression scales, and Late-Life Function and Disability Instrument. RESULTS: Participants in the intervention (n = 384) and control groups (n = 359) were comparable in age: mean (standard deviation) of 81.9 (4.7) versus 81.8 (5.0) years. Mean scores were similar between groups at 12 and 24 months for concern about falling, physical function, and disability, whereas the intervention group's mean scores on anxiety and depression were .7 points lower (i.e., better) at 12 months and .6 to .8 points lower at 24 months. For each of these outcomes, differences between the groups' adjusted least square mean changes from baseline to 12 and 24 months, respectively, were quantitatively small. The overall difference in means between groups over 2 years was statistically significant only for depression, favoring the intervention: -1.19 (99% confidence interval, -2.36 to -.02), with 3.5 points representing a minimally important difference. CONCLUSIONS: STRIDE's multifactorial intervention to reduce fall injuries was not associated with clinically meaningful improvements in patient well-being.

Chronic Post-Surgical Pain in the Frail Older Adult.

Older adults are the fastest growing segment of the population and surgical procedures in this group increase each year. Chronic post-surgical pain is an important consideration in the older adult as it affects recovery, physical functioning, and overall quality of life. It is increasingly recognized as a public health issue but there is a need to improve our understanding of the disease process as well as the appropriate treatment and prevention. Frailty, delirium, and cognition influence post-operative outcomes in older adults and have been implicated in the development of chronic post-surgical pain. Further research must be conducted to fully understand the role they play in the occurrence of chronic post-surgical pain in the older adult. Additionally, careful attention must be given to the physiologic, cognitive, and comorbidity differences between the older adult and the general population. This is critical for elucidating the proper chronic post-surgical pain treatment and prevention strategies to ensure that the older adult undergoing surgical intervention will have an appropriate and desirable post-operative outcome.

Preoperative Frailty Evaluation: A Promising Risk-stratification Tool in Older Adults Undergoing General Surgery.

PURPOSE: General surgical procedures are among the most commonly performed operations in the United States. Despite advances in surgical and anesthetic techniques and perioperative care, complications after general surgery in older adults remain a significant cause of increased morbidity, mortality, and health care costs. Frailty, a geriatric syndrome characterized by multisystem physiologic decline and increased vulnerability to stressors and adverse clinical outcomes, has emerged as a plausible predictor of adverse outcomes after surgery in older patients. Thus, the goal of this topical review is to evaluate the evidence on the association between preoperative frailty and clinical outcomes after general surgery and whether frailty evaluation may have a role in surgical risk-stratification in vulnerable older patients. METHODS: A PubMed database search was conducted between September and October 2018 to identify relevant studies evaluating the association between frailty and clinical outcomes after general surgery. Key words (frailty and surgery) and Medical Subject Heading term (general surgery) were used, and specific inclusion and exclusion criteria were applied. FINDINGS: The available evidence from meta-analyses and cohort studies suggest that preoperative frailty is significantly associated with adverse clinical outcomes after emergent or nonemergent general surgery in older patients. Although these studies are limited by a high degree of heterogeneity of frailty assessments, types of surgery, and primary outcomes, baseline frailty appears to increase risk of postoperative complications and morbidity, hospital length of stay, 30-day mortality, and long-term mortality after general surgical procedures in older adults. IMPLICATIONS: Evidence supports the further development of preoperative frailty evaluation as a risk-stratification tool in older adults undergoing general surgery. Research is urgently needed to quantify and differentiate the predictive ability of validated frailty instruments in the context of different general surgical procedures and medical acuity and in conjunction with existing surgical risk indices widely used in clinical practice. Practical applicability of frailty instrument as well as geriatrics-centered outcomes need to be incorporated in future studies in this line of research. Furthermore, clinical care pathways that integrate frailty assessment, geriatric medicine focused perioperative and postoperative management, and patient-centered interdisciplinary care models should be investigated as a comprehensive intervention approach in older adults undergoing general surgery. Finally, early implementation of palliative care should occur at the outset of hospital encounter in frail older patients who present with indications for emergent general surgery.

Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE): A Cluster-Randomized Pragmatic Trial of a Multifactorial Fall Injury Prevention Strategy: Design and Methods.

Background: Fall injuries are a major cause of morbidity and mortality among older adults. We describe the design of a pragmatic trial to compare the effectiveness of an evidence-based, patient-centered multifactorial fall injury prevention strategy to an enhanced usual care. Methods: Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) is a 40-month cluster-randomized, parallel-group, superiority, pragmatic trial being conducted at 86 primary care practices in 10 health care systems across United States. The 86 practices were randomized to intervention or control group using covariate-based constrained randomization, stratified by health care system. Participants are community-living persons, ≥70 years, at increased risk for serious fall injuries. The intervention is a comanagement model in which a nurse Falls Care Manager performs multifactorial risk assessments, develops individualized care plans, which include surveillance, follow-up evaluation, and intervention strategies. Control group receives enhanced usual care, with clinicians and patients receiving evidence-based information on falls prevention. Primary outcome is serious fall injuries, operationalized as those leading to medical attention (nonvertebral fractures, joint dislocation, head injury, lacerations, and other major sequelae). Secondary outcomes include all fall injuries, all falls, and well-being (concern for falling; anxiety and depressive symptoms; physical function and disability). Target sample size was 5,322 participants to provide 90% power to detect 20% reduction in primary outcome rate relative to control. Results: Trial enrolled 5,451 subjects in 20 months. Intervention and follow-up are ongoing. Conclusions: The findings of the STRIDE study will have important clinical and policy implications for the prevention of fall injuries in older adults.

Rapid growth of a fetal sacrococcygeal teratoma in an HIV-infected woman: a case report.

BACKGROUND: Sacrococcygeal teratoma, the most common congenital neoplasm of the newborn, associated with fetal hydrops and high morbidity and mortality related to the secondary effects of the tumor mass, is of unknown etiology. Prompt diagnosis and early treatment have proven to be effective. CASE: A 24-year-old woman, gravida 3, para 2, at 385/7 weeks' gestation, with a pregnancy complicated by HIV diagnosed during pregnancy, seizure disorder and tobacco use, presented with premature rupture of membranes. Ultrasound examination at 17 weeks' gestation showed normal fetal anatomy. Cesarean delivery was complicated by difficulty delivering a live infant with a large sacral mass. Successful surgical excision of a 650-g mass and stabilization of the infant occurred in the neonatal period. CONCLUSION: This is the first case report to describe a rapidly growing sacrococcygeal teratoma in a neonate from a pregnancy complicated by HIV. Ultrasound in the first and second trimesters identified no fetal abnormalities of the spine. Further research concerning sacrococcygeal teratoma and HIV in pregnancy is necessary for prompt and early diagnosis and treatment of antepartum and peripartum complications.

Impaired mitochondrial degradation by autophagy in the skeletal muscle of the aged female interleukin 10 null mouse.

Mitochondrial dysfunction, chronic inflammation and muscle aging are closely linked. Mitochondrial clearance is a process to dampen inflammation and is a critical pre-requisite to mitobiogenesis. The combined effect of aging and chronic inflammation on mitochondrial degradation by autophagy is understudied. In interleukin 10 null mouse (IL-10(tm/tm)), a rodent model of chronic inflammation, we studied the effects of aging and inflammation on mitochondrial clearance. We show that aging in IL-10(tm/tm) is associated with reduced skeletal muscle mitochondrial death signaling and altered formation of autophagosomes, compared to age-matched C57BL/6 controls. Moreover, skeletal muscles of old IL-10(tm/tm) mice have the highest levels of damaged mitochondria with disrupted mitochondrial ultrastructure and autophagosomes compared to all other groups. These observations highlight the interface between chronic inflammation and aging on altered mitochondrial biology in skeletal muscles.

Laparotomy in mice induces blood cell expression of inflammatory and stress genes.

Surgical trauma induces immune and stress responses although its effects on postsurgical inflammatory and stress gene expression remain poorly characterized. This study sought to improve current scientific knowledge by investigating the effects of laparotomy on mouse blood cell inflammatory and stress gene expression. Three-month-old male C57BL/6J mice were subjected to 2% isoflurane or 2% isoflurane with laparotomy and sacrificed 4 h postintervention. Blood was collected and blood cell expression of 158 genes central to inflammatory and stress responses was assayed using quantitative polymerase chain reaction arrays. Mice subjected to isoflurane with laparotomy, compared with mice receiving isoflurane alone, had >2-fold upregulation of genes in inflammation (Osm, IL1rn, IL1b, and Csf1), oxidative stress (Hmox1), heat shock (Hspa1b), growth arrest (Cdkn1a), and DNA repair (Ugt1a2). These genes demonstrated similar expression patterns by Pearson correlation and cluster analysis. Thus, laparotomy induces coordinated, postsurgical blood cell expression of unique inflammatory and stress genes whose roles in influencing surgical outcomes need further investigation.