The Impact of Intraoperative Vasopressor Use and Fluid Status on Flap Survival in Traumatic Lower Extremity Reconstruction.

INTRODUCTION: Historically, the use of intraoperative vasopressors during free flap lower extremity reconstruction has been proposed to adversely affect flap survival due to concerns about compromising flap perfusion. This study aims to analyze the impact of intraoperative vasopressor use and fluid administration on postoperative outcomes in patients undergoing traumatic lower extremity (LE) reconstruction. METHODS: Patients who underwent LE free flap reconstruction between 2015-2023 at a Level 1 Trauma Center were retrospectively reviewed. Statistical analysis was conducted to evaluate the association between vasopressor use and intraoperative fluids with partial/complete flap necrosis, as well as the differential effect of vasopressor use on flap outcomes based on varying fluid levels. RESULTS: 105 LE flaps were performed over an 8-year period. Vasopressors were administered intraoperatively to 19 (18.0%) cases. Overall flap survival and limb salvage rates were 97.1% and 93.3%, respectively. Intraoperative vasopressor use decreased the overall risk of postoperative flap necrosis (OR 0.00005, 95% CI [9.11x10-9-0.285], p=0.025), while a lower net fluid balance increased the risk of this outcome (OR 0.9985, 95% CI [0.9975-0.9996], p=0.007). Further interaction analysis revealed that vasopressor use increased the risk of flap necrosis in settings with a higher net fluid balance (OR 1.0032, 95% CI [1.0008-1.0056], p-interaction=0.010). CONCLUSION: This study demonstrated that intraoperative vasopressor use and adequate fluid status may be beneficial in improving flap outcomes in LE reconstruction. Vasopressor use with adequate fluid management can optimize hemodynamic stability when necessary during traumatic LE microvascular reconstruction without concern for increased risk of flap ischemia.

Does Side Matter? The Impact of Free Flap Harvest Laterality on Ambulatory Function in Lower Extremity Traumatic Reconstruction.

BACKGROUND: Free flaps are essential for limb salvage in patients with lower extremity (LE) trauma; however, significant donor-site morbidity could impact functional outcomes. This study compares postoperative ambulatory function between contralateral and ipsilateral free flap harvest in LE traumatic reconstruction. METHODS: A retrospective review was performed on patients who underwent LE reconstruction at a level 1 trauma center from 2009 to 2022. Flap characteristics, injury history, and ambulatory function were collected. Flap harvest laterality was determined in relation to the injured leg. The flaps were categorized as either fasciocutaneous or those that included a muscle component (muscle/myocutaneous). Chi-squared and Mann-Whitney tests were used for statistical analysis. RESULTS: Upon review, 173 LE free flaps were performed, of which 70 (65.4%) were harvested from the ipsilateral leg and 37 (34.6%) were from the contralateral leg. Among all LE free flaps, the limb salvage rate was 97.2%, and the flap survival rate was 94.4%. Full ambulation was achieved in 37 (52.9%) patients in the ipsilateral cohort and 18 (48.6%) in the contralateral cohort (p = 0.679). The average time to full ambulation did not vary between these cohorts (p = 0.071). However, upon subanalysis of the 61 muscle/myocutaneous flaps, the ipsilateral cohort had prolonged time to full ambulation (6.4 months, interquartile range [IQR]: 4.8-13.5) compared with the contralateral one (2.3 months, IQR: 2.3 [1.0-3.9]) p = 0.007. There was no significant difference in time to full ambulation between flap harvest laterality cohorts among the fasciocutaneous flaps (p = 0.733). CONCLUSION: Among free flaps harvested from the ipsilateral leg, fasciocutaneous flaps were associated with faster recovery to full ambulation relative to muscle/myocutaneous flaps. Since harvesting muscle or myocutaneous flaps from the ipsilateral leg may be associated with a slower recovery of ambulation, surgeons may consider harvesting from a donor site on the contralateral leg if reconstruction requires a muscle component.

Clinical guideline highlights for the hospitalist: Diagnosis and treatment of diabetes-related foot infections.

GUIDELINE TITLE: IWGDF/IDSA Guidelines on the Diagnosis and Treatment of Diabetes-related Foot Infections RELEASE DATE: October 2, 2023 PRIOR VERSION: March 16, 2020 DEVELOPER: IWGDF Editorial Board FUNDING SOURCE: International Working Group on the Diabetic Foot (IWGDF), Infectious Diseases Society of America (IDSA) TARGET POPULATION: Adults with suspected or confirmed diabetes-related foot infections.

Clinical, Biomarker, and Research Tests Among US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

Importance: Since 2015, US government and related personnel have reported dizziness, pain, visual problems, and cognitive dysfunction after experiencing intrusive sounds and head pressure. The US government has labeled these anomalous health incidents (AHIs). Objective: To assess whether participants with AHIs differ significantly from US government control participants with respect to clinical, research, and biomarker assessments. Design, Setting, and Participants: Exploratory study conducted between June 2018 and July 2022 at the National Institutes of Health Clinical Center, involving 86 US government staff and family members with AHIs from Cuba, Austria, China, and other locations as well as 30 US government control participants. Exposures: AHIs. Main Outcomes and Measures: Participants were assessed with extensive clinical, auditory, vestibular, balance, visual, neuropsychological, and blood biomarkers (glial fibrillary acidic protein and neurofilament light) testing. The patients were analyzed based on the risk characteristics of the AHI identifying concerning cases as well as geographic location. Results: Eighty-six participants with AHIs (42 women and 44 men; mean [SD] age, 42.1 [9.1] years) and 30 vocationally matched government control participants (11 women and 19 men; mean [SD] age, 43.8 [10.1] years) were included in the analyses. Participants with AHIs were evaluated a median of 76 days (IQR, 30-537) from the most recent incident. In general, there were no significant differences between participants with AHIs and control participants in most tests of auditory, vestibular, cognitive, or visual function as well as levels of the blood biomarkers. Participants with AHIs had significantly increased fatigue, depression, posttraumatic stress, imbalance, and neurobehavioral symptoms compared with the control participants. There were no differences in these findings based on the risk characteristics of the incident or geographic location of the AHIs. Twenty-four patients (28%) with AHI presented with functional neurological disorders. Conclusions and Relevance: In this exploratory study, there were no significant differences between individuals reporting AHIs and matched control participants with respect to most clinical, research, and biomarker measures, except for objective and self-reported measures of imbalance and symptoms of fatigue, posttraumatic stress, and depression. This study did not replicate the findings of previous studies, although differences in the populations included and the timing of assessments limit direct comparisons.

Neuroimaging Findings in US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

Importance: US government personnel stationed internationally have reported anomalous health incidents (AHIs), with some individuals experiencing persistent debilitating symptoms. Objective: To assess the potential presence of magnetic resonance imaging (MRI)-detectable brain lesions in participants with AHIs, with respect to a well-matched control group. Design, Setting, and Participants: This exploratory study was conducted at the National Institutes of Health (NIH) Clinical Center and the NIH MRI Research Facility between June 2018 and November 2022. Eighty-one participants with AHIs and 48 age- and sex-matched control participants, 29 of whom had similar employment as the AHI group, were assessed with clinical, volumetric, and functional MRI. A high-quality diffusion MRI scan and a second volumetric scan were also acquired during a different session. The structural MRI acquisition protocol was optimized to achieve high reproducibility. Forty-nine participants with AHIs had at least 1 additional imaging session approximately 6 to 12 months from the first visit. Exposure: AHIs. Main Outcomes and Measures: Group-level quantitative metrics obtained from multiple modalities: (1) volumetric measurement, voxel-wise and region of interest (ROI)-wise; (2) diffusion MRI-derived metrics, voxel-wise and ROI-wise; and (3) ROI-wise within-network resting-state functional connectivity using functional MRI. Exploratory data analyses used both standard, nonparametric tests and bayesian multilevel modeling. Results: Among the 81 participants with AHIs, the mean (SD) age was 42 (9) years and 49% were female; among the 48 control participants, the mean (SD) age was 43 (11) years and 42% were female. Imaging scans were performed as early as 14 days after experiencing AHIs with a median delay period of 80 (IQR, 36-544) days. After adjustment for multiple comparisons, no significant differences between participants with AHIs and control participants were found for any MRI modality. At an unadjusted threshold (P < .05), compared with control participants, participants with AHIs had lower intranetwork connectivity in the salience networks, a larger corpus callosum, and diffusion MRI differences in the corpus callosum, superior longitudinal fasciculus, cingulum, inferior cerebellar peduncle, and amygdala. The structural MRI measurements were highly reproducible (median coefficient of variation <1% across all global volumetric ROIs and <1.5% for all white matter ROIs for diffusion metrics). Even individuals with large differences from control participants exhibited stable longitudinal results (typically, <±1% across visits), suggesting the absence of evolving lesions. The relationships between the imaging and clinical variables were weak (median Spearman ρ = 0.10). The study did not replicate the results of a previously published investigation of AHIs. Conclusions and Relevance: In this exploratory neuroimaging study, there were no significant differences in imaging measures of brain structure or function between individuals reporting AHIs and matched control participants after adjustment for multiple comparisons.

Loss of daylength sensitivity by splice site mutation in Cannabis pseudo-response regulator.

Photoperiod insensitivity (auto-flowering) in drug-type Cannabis sativa circumvents the need for short day (SD) flowering requirements making outdoor cultivation in high latitudes possible. However, the benefits of photoperiod insensitivity are counterbalanced by low cannabinoid content and poor flower quality in auto-flowering genotypes. Despite recent studies in cannabis flowering, a mechanistic understanding of photoperiod insensitivity is still lacking. We used a combination of genome-wide association study and genetic fine-mapping to identify the genetic cause of auto-flowering in cannabis. We then used gene expression analyses and transient transformation assays to characterize flowering time control. Herein, we identify a splice site mutation within circadian clock gene PSEUDO-RESPONSE REGULATOR 37 (CsPRR37) in auto-flowering cannabis. We show that CsPRR37 represses FT expression and its circadian oscillations transition to a less repressive state during SD as compared to long days (LD). We identify several key circadian clock genes whose expression is altered in auto-flowering cannabis, particularly under non-inductive LD. Research into the pervasiveness of this mutation and others affecting flowering time will help elucidate cannabis domestication history and advance cannabis breeding toward a more sustainable outdoor cultivation system.

Reliability of an AI-Powered Application Across Different Mobile Devices for Assessment of Chronic Wounds.

Objective: Evaluate the inter- and intrarater reliability of a wound assessment tool in iPhone 12 and 13 mini modalities against a validated iPad mini/Structure Sensor configuration. Approach: We assessed a wound measurement application (eKare inSight®) for result consistency in patients presenting with wounds. Assessments were analyzed using a two-way analysis of variance. Intraclass correlation coefficient (ICC) was computed for intrarater (ICC1,1) and inter-rater (ICC2,1) analysis using a two-way random effects model. Paired t-test assessed the statistical difference between measurement methods. Results: Forty-two lesions were analyzed with surface areas ranging from 0.2 to 23 cm2 (average 4.33 ± 5.44 cm2). A high level of reliability was observed for repeat wound area measurements by the same examiner (ICC1,1 = 0.997) and between examiners with iPhone 13 mini (ICC2,1 = 0.998). There was no significant difference between iPhone 12 and iPad mini/Structure Sensor (p = 0.78) or between iPhone 13 mini and iPhone 12 (p = 0.22). Minimal difference existed between iPhone 13 mini and iPad mini/Structure Sensor (p = 0.049, Cohen's d = 0.01). Innovation: Increased pervasiveness of smartphones in clinical care, coupled with advances in smartphone imaging and machine learning, allows for a potential solution to the problem of fast and accurate wound measurements. The application investigated produces wound measurement results quickly and with demonstrated accuracy. It does not require a calibration sticker or reference marker and allows for automatic wound boundary delineation. Conclusion: The results of this study suggest that a digital planimetry mobile application may offer high levels of reliability across devices and users.

Network analysis of neuropsychiatric, cognitive, and functional complications of stroke: implications for novel treatment targets.

AIM: Recovery from stroke is adversely affected by neuropsychiatric complications, cognitive impairment, and functional disability. Better knowledge of their mutual relationships is required to inform effective interventions. Network theory enables the conceptualization of symptoms and impairments as dynamic and mutually interacting systems. We aimed to identify interactions of poststroke complications using network analysis in diverse stroke samples. METHODS: Data from 2185 patients were sourced from member studies of STROKOG (Stroke and Cognition Consortium), an international collaboration of stroke studies. Networks were generated for each cohort, whereby nodes represented neuropsychiatric symptoms, cognitive deficits, and disabilities on activities of daily living. Edges characterized associations between them. Centrality measures were used to identify hub items. RESULTS: Across cohorts, a single network of interrelated poststroke complications emerged. Networks exhibited dissociable depression, apathy, fatigue, cognitive impairment, and functional disability modules. Worry was the most central symptom across cohorts, irrespective of the depression scale used. Items relating to activities of daily living were also highly central nodes. Follow-up analysis in two studies revealed that individuals who worried had more densely connected networks than those free of worry (CASPER [Cognition and Affect after Stroke: Prospective Evaluation of Risks] study: S = 9.72, P = 0.038; SSS [Sydney Stroke Study]: S = 13.56, P = 0.069). CONCLUSION: Neuropsychiatric symptoms are highly interconnected with cognitive deficits and functional disabilities resulting from stroke. Given their central position and high level of connectedness, worry and activities of daily living have the potential to drive multimorbidity and mutual reinforcement between domains of poststroke complications. Targeting these factors early after stroke may have benefits that extend to other complications, leading to better stroke outcomes.

Predicting incident dementia in cerebral small vessel disease: comparison of machine learning and traditional statistical models.

Background: Cerebral small vessel disease (SVD) contributes to 45% of dementia cases worldwide, yet we lack a reliable model for predicting dementia in SVD. Past attempts largely relied on traditional statistical approaches. Here, we investigated whether machine learning (ML) methods improved prediction of incident dementia in SVD from baseline SVD-related features over traditional statistical methods. Methods: We included three cohorts with varying SVD severity (RUN DMC, n = 503; SCANS, n = 121; HARMONISATION, n = 265). Baseline demographics, vascular risk factors, cognitive scores, and magnetic resonance imaging (MRI) features of SVD were used for prediction. We conducted both survival analysis and classification analysis predicting 3-year dementia risk. For each analysis, several ML methods were evaluated against standard Cox or logistic regression. Finally, we compared the feature importance ranked by different models. Results: We included 789 participants without missing data in the survival analysis, amongst whom 108 (13.7%) developed dementia during a median follow-up of 5.4 years. Excluding those censored before three years, we included 750 participants in the classification analysis, amongst whom 48 (6.4%) developed dementia by year 3. Comparing statistical and ML models, only regularised Cox/logistic regression outperformed their statistical counterparts overall, but not significantly so in survival analysis. Baseline cognition was highly predictive, and global cognition was the most important feature. Conclusions: When using baseline SVD-related features to predict dementia in SVD, the ML survival or classification models we evaluated brought little improvement over traditional statistical approaches. The benefits of ML should be evaluated with caution, especially given limited sample size and features.

Short-term Trajectories of Poststroke Cognitive Function: A STROKOG Collaboration Study.

BACKGROUND AND OBJECTIVES: Past studies on poststroke cognitive function have focused on the average performance or change over time, but few have investigated patterns of cognitive trajectories after stroke. This project used latent class growth analysis (LCGA) to identify clusters of patients with similar patterns of cognition scores over the first-year poststroke and the extent to which long-term cognitive outcome is predicted by the clusters ("trajectory groups"). METHODS: Data were sought from the Stroke and Cognition consortium. LCGA was used to identify clusters of trajectories based on standardized global cognition scores at baseline (T1) and at the 1-year follow-up (T2). One-step individual participant data meta-analysis was used to examine risk factors for trajectory groups and association of trajectory groups with cognition at the long-term follow-up (T3). RESULTS: Nine hospital-based stroke cohorts with 1,149 patients (63% male; mean age 66.4 years [SD 11.0]) were included. The median time assessed at T1 was 3.6 months poststroke, 1.0 year at T2, and 3.2 years at T3. LCGA identified 3 trajectory groups, which were characterized by different mean levels of cognition scores at T1 (low-performance, -3.27 SD [0.94], 17%; medium-performance, -1.23 SD [0.68], 48%; and high-performance, 0.71 SD [0.77], 35%). There was significant improvement in cognition for the high-performance group (0.22 SD per year, 95% CI 0.07-0.36), but changes for the low-performance and medium-performance groups were not significant (-0.10 SD per year, 95% CI -0.33 to 0.13; 0.11 SD per year, 95% CI -0.08 to 0.24, respectively). Factors associated with the low- (vs high-) performance group include age (relative risk ratio [RRR] 1.18, 95% CI 1.14-1.23), years of education (RRR 0.61, 95% CI 0.56-0.67), diabetes (RRR 3.78, 95% CI 2.08-6.88), large artery vs small vessel strokes (RRR 2.77, 95% CI 1.32-5.83), and moderate/severe strokes (RRR 3.17, 95% CI 1.42-7.08). Trajectory groups were predictive of global cognition at T3, but its predictive power was comparable with scores at T1. DISCUSSION: The trajectory of cognitive function over the first-year poststroke is heterogenous. Baseline cognitive function ∼3.6 months poststroke is a good predictor of long-term cognitive outcome. Older age, lower levels of education, diabetes, large artery strokes, and greater stroke severity are risk factors for lower cognitive performance over the first year.

Headaches in Traumatic Brain Injury: Improvement Over Time, Associations With Quality of Life, and Impact of Migraine-Type Headaches.

OBJECTIVE: To describe headache characteristics over time in patients with traumatic brain injury (TBI). SETTING: Patients enrolled and followed at the National Institutes of Health Clinical Center between 2011 and 2020. PARTICIPANTS: There were 147 patients with TBI, with 74 mild TBI (mTBI), 49 moderate (modTBI), 24 severe (sTBI), and 20 individuals without brain injury (IWBIs). DESIGN: Regular surveys of headache characteristics in patients with TBI were conducted. Patients were enrolled as early as 30 days post-injury and followed up to 5 years, for 419 total visits and 80 patients with multiple return visits. MAIN MEASURES: Surveys of headache characteristics, including headache severity, were measured on a 0- to 10-point Likert scale and headache frequency quantified as headaches per month. Patients with migraine-type headaches ( n = 39) were identified by a clinician-administered tool. Functional outcomes were measured using the Glasgow Outcome Scale-Extended (GOS-E) and quality of life by the Satisfaction with Life Scale (SWLS) and the 36-item Short Form Survey (SF-36). RESULTS: At their initial visit, patients with TBI had more severe and frequent headaches than IWBIs (median 5 vs 2.5, P < .001; median 2 vs 0.2, P < .001), as did patients with mTBI compared with modTBI/sTBI (all P ≤ .01). Migraines were associated with lower SWLS and SF-36 scores. Migraines and young age were associated with higher headache severity and frequency across time points. Longitudinally, time post-injury correlated with improvement in headache severity and frequency without differences by injury severity. However, time post-injury did not correlate with improvement in headache characteristics in a patient subgroup with moderate/severe headaches. CONCLUSION: Our findings suggest that patients with mild, moderate, or severe TBI see improvement in headaches over time. However, patients should be counseled that improvement is modest and seen more in patients with milder headache symptoms. Patients with migraine headaches in particular are at risk for worse headache characteristics with greater impact on quality of life.

Cognition, function, and prevalent dementia in centenarians and near-centenarians: An individual participant data (IPD) meta-analysis of 18 studies.

INTRODUCTION: There are limited data on prevalence of dementia in centenarians and near-centenarians (C/NC), its determinants, and whether the risk of dementia continues to rise beyond 100. METHODS: Participant-level data were obtained from 18 community-based studies (N = 4427) in 11 countries that included individuals ≥95 years. A harmonization protocol was applied to cognitive and functional impairments, and a meta-analysis was performed. RESULTS: The mean age was 98.3 years (SD = 2.67); 79% were women. After adjusting for age, sex, and education, dementia prevalence was 53.2% in women and 45.5% in men, with risk continuing to increase with age. Education (OR 0.95;0.92-0.98) was protective, as was hypertension (odds ratio [OR] 0.51;0.35-0.74) in five studies. Dementia was not associated with diabetes, vision and hearing impairments, smoking, and body mass index (BMI). DISCUSSION: Among the exceptional old, dementia prevalence remains higher in the older participants. Education was protective against dementia, but other factors for dementia-free survival in C/NC remain to be understood.

A case of Citrobacter koseri renal abscess and review of the literature.

Citrobacter species are anaerobic gram-negative bacteria that are known to cause infections in immunocompromised hosts, particularly in hospital settings. Their opportunistic nature and tendency to develop antibiotic resistance make Citrobacter species challenging to treat. Renal or perinephric abscess formation as a result of Citrobacter infection is uncommon, having only previously been reported in four cases. We present a case of a 70-year-old man with diabetes and prostate cancer who was diagnosed with an 18 cm perinephric and a 10 cm perihepatic abscess caused by Citrobacter koseri. The patient required drains and re-positioning of the drains multiple times in addition to a prolonged course of antibiotics to achieve complete radiographic resolution. This case highlights the challenges in treating renal and perinephric abscess, as it required drain re-placements two additional times after the initial placement and an additional 4 weeks of antibiotics. Successful treatment for larger abscesses usually requires a two-arm approach, with antibiotics in combination with either percutaneous or surgical abscess drainage.

Texture Features of Magnetic Resonance Images Predict Poststroke Cognitive Impairment: Validation in a Multicenter Study.

BACKGROUND: Imaging features derived from T1-weighted (T1w) images texture analysis were shown to be potential markers of poststroke cognitive impairment, with better sensitivity than atrophy measurement. However, in magnetic resonance images, the signal distribution is subject to variations and can limit transferability of the method between centers. This study examined the reliability of texture features against imaging settings using data from different centers. METHODS: Data were collected from 327 patients within the Stroke and Cognition Consortium from centers in France, Germany, Australia, and the United Kingdom. T1w images were preprocessed to normalize the signal intensities and then texture features, including first- and second-order statistics, were measured in the hippocampus and the entorhinal cortex. Differences between the data led to the use of 2 methods of analysis. First, a machine learning modeling, using random forest, was used to build a poststroke cognitive impairment prediction model using one dataset and this was validated on another dataset as external unseen data. Second, the predictive ability of the texture features was examined in the 2 remaining datasets by ANCOVA with false discovery rate correction for multiple comparisons. RESULTS: The prediction model had a mean accuracy of 90% for individual classification of patients in the learning base while for the validation base it was ≈ 77%. ANCOVA showed significant differences, in all datasets, for the kurtosis and inverse difference moment texture features when measured in patients with cognitive impairment and those without. CONCLUSIONS: These results suggest that texture features obtained from routine clinical MR images are robust early predictors of poststroke cognitive impairment and can be combined with other demographic and clinical predictors to build an accurate prediction model.

MicroRNA-378 contributes to osteoarthritis by regulating chondrocyte autophagy and bone marrow mesenchymal stem cell chondrogenesis.

Osteoarthritis (OA) is the most common joint disease; thus, understanding the pathological mechanisms of OA initiation and progression is critical for OA treatment. MicroRNAs (miRNAs) have been shown to be involved in the progression of osteoarthritis, one candidate is microRNA-378 (miR-378), which is highly expressed in the synovium of OA patients during late-stage disease, but its function and the underlying mechanisms of how it contributes to disease progression remain poorly understood. In this study, miR-378 transgenic (TG) mice were used to study the role of miR-378 in OA development. miR-378 TG mice developed spontaneous OA and also exaggerated surgery-induced disease progression. Upon in vitro OA induction, miR-378 expression was upregulated and correlated with elevated inflammation and chondrocyte hypertrophy. Chondrocytes isolated from articular cartilage from miR-378 TG mice showed impaired chondrogenic differentiation. The bone marrow mesenchymal stem cells (BMSCs) collected from miR-378 TG mice also showed repressed chondrogenesis compared with the control group. The autophagy-related protein Atg2a, as well as chondrogenesis regulator Sox6, were identified as downstream targets of miR-378. Ectopic expression of Atg2a and Sox6 rescued miR-378-repressed chondrocyte autophagy and BMSC chondrogenesis, respectively. Anti-miR-378 lentivirus intra-articular injection in an established OA mouse model was shown to ameliorate OA progression, promote articular regeneration, and repress hypertrophy. Atg2a and Sox6 were again confirmed to be the target of miR-378 in vivo. In conclusion, miR-378 amplified OA development via repressing chondrocyte autophagy and by inhibiting BMSCs chondrogenesis, thus indicating miR-378 may be a potential therapeutic target for OA treatments.

Is hospitalization a risk factor for cognitive decline in older age adults?

OBJECTIVES: Many studies document cognitive decline following specific types of acute illness hospitalizations (AIH) such as surgery, critical care, or those complicated by delirium. However, cognitive decline may be a complication following all types of AIH. This systematic review will summarize longitudinal observational studies documenting cognitive changes following AIH in the majority admitted population and conduct meta-analysis (MA) to assess the quantitative effect of AIH on post-hospitalization cognitive decline (PHCD). METHODS: We followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Selection criteria were defined to identify studies of older age adults exposed to AIH with cognitive measures. 6566 titles were screened. 46 reports were reviewed qualitatively, of which seven contributed data to the MA. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: The qualitative review suggested increased cognitive decline following AIH, but several reports were particularly vulnerable to bias. Domain-specific outcomes following AIH included declines in memory and processing speed. Increasing age and the severity of illness were the most consistent risk factors for PHCD. PHCD was supported by MA of seven eligible studies with 41,453 participants (Cohen's d = -0.25, 95% CI [-0.02, -0.49] I2 35%). CONCLUSIONS: There is preliminary evidence that AIH exposure accelerates or triggers cognitive decline in the elderly patient. PHCD reported in specific contexts could be subsets of a larger phenomenon and caused by overlapping mechanisms. Future research must clarify the trajectory, clinical significance, and etiology of PHCD: a priority in the face of an aging population with increasing rates of both cognitive impairment and hospitalization.

Long-Term Cognitive Decline After Stroke: An Individual Participant Data Meta-Analysis.

BACKGROUND: Poststroke cognitive impairment is common, but the trajectory and magnitude of cognitive decline after stroke is unclear. We examined the course and determinants of cognitive change after stroke using individual participant data from the Stroke and Cognition Consortium. METHODS: Nine longitudinal hospital-based cohorts from 7 countries were included. Neuropsychological test scores and normative data were used to calculate standardized scores for global cognition and 5 cognitive domains. One-step individual participant data meta-analysis was used to examine the rate of change in cognitive function and risk factors for cognitive decline after stroke. Stroke-free controls were included to examine rate differences. Based on the literature and our own data that showed short-term improvement in cognitive function after stroke, key analyses were restricted to the period beginning 1-year poststroke to focus on its long-term effects. RESULTS: A total of 1488 patients (mean age, 66.3 years; SD, 11.1; 98% ischemic stroke) were followed for a median of 2.68 years (25th-75th percentile: 1.21-4.14 years). After an initial period of improvement through up to 1-year poststroke, decline was seen in global cognition and all domains except executive function after adjusting for age, sex, education, vascular risk factors, and stroke characteristics (-0.053 SD/year [95% CI, -0.073 to -0.033]; P<0.001 for global cognition). Recurrent stroke and older age were associated with faster decline. Decline was significantly faster in patients with stroke compared with controls (difference=-0.078 SD/year [95% CI, -0.11 to -0.045]; P<0.001 for global cognition in a subgroup analysis). CONCLUSIONS: Patients with stroke experience cognitive decline that is faster than that of stroke-free controls from 1 to 3 years after onset. An increased rate of decline is associated with older age and recurrent stroke.

DANCR Mediates the Rescuing Effects of Sesamin on Postmenopausal Osteoporosis Treatment via Orchestrating Osteogenesis and Osteoclastogenesis.

As one of the leading causes of bone fracture in postmenopausal women and in older men, osteoporosis worldwide is attracting more attention in recent decades. Osteoporosis is a common disease mainly resulting from an imbalance of bone formation and bone resorption. Pharmaceutically active compounds that both activate osteogenesis, while repressing osteoclastogenesis hold the potential of being therapeutic medications for osteoporosis treatment. In the present study, sesamin, a bioactive ingredient derived from the seed of Sesamum Indicum, was screened out from a bioactive compound library and shown to exhibit dual-regulating functions on these two processes. Sesamin was demonstrated to promote osteogenesis by upregulating Wnt/ß-catenin, while repressing osteoclastogenesis via downregulating NF-κB signaling . Furthermore, DANCR was found to be the key regulator in sesamin-mediated bone formation and resorption . In an ovariectomy (OVX)-induced osteoporotic mouse model, sesamin could rescue OVX-induced bone loss and impairment. The increased serum level of DANCR caused by OVX was also downregulated upon sesamin treatment. In conclusion, our results demonstrate that sesamin plays a dual-functional role in both osteogenesis activation and osteoclastogenesis de-activation in a DANCR-dependent manner, suggesting that it may be a possible medication candidate for osteoporotic patients with elevated DNACR expression levels.

Minimal clinically important difference in means in vulnerable populations: challenges and solutions.

INTRODUCTION AND MOTIVATION: Many health studies measure a continuous outcome and compare means between groups. Since means for biological data are often difficult to interpret clinically, it is common to dichotomise using a cut-point and present the 'percentage abnormal' alongside or in place of means. Examples include birthweight where 'abnormal' is defined as <2500 g (low birthweight), systolic blood pressure with abnormal defined as >140 mm Hg (high blood pressure) and lung function with varying definitions of the 'limit of normal'. In vulnerable populations with low means, for example, birthweight in a population of preterm babies, a given difference in means between two groups will represent a larger difference in the percentage with low birthweight than in a general population of babies where most will be full term. Thus, in general, the difference in percentage of patients with abnormal values for a given difference in means varies according to the reference population's mean value. This phenomenon leads to challenges in interpreting differences in means in vulnerable populations and in defining an outcome-specific minimal clinically important difference (MCID) in means since the proportion abnormal, which is useful in interpreting means, is not constant-it varies with the population mean. This has relevance for study power calculations and data analyses in vulnerable populations where a small observed difference in means may be difficult to interpret clinically and may be disregarded, even if associated with a relatively large difference in percentage abnormal which is clinically relevant. METHODS: To address these issues, we suggest both difference in means and difference in percentage (proportion) abnormal are considered when choosing the MCID, and that both means and percentages abnormal are reported when analysing the data. CONCLUSIONS: We describe a distributional approach to analyse proportions classified as abnormal that avoids the usual loss of precision and power associated with dichotomisation.