CCN2/CTGF expression does not correlate with fibrosis in myeloproliferative neoplasms, consistent with noncanonical TGF-ß signaling driving myelofibrosis.

The classical BCR::ABL1-negative myeloproliferative neoplasms (MPN) form a group of bone marrow (BM) diseases with the potential to progress to acute myeloid leukemia or develop marrow fibrosis and subsequent BM failure. The mechanism by which BM fibrosis develops and the factors that drive stromal activation and fibrosis are not well understood. Cellular Communication Network 2 (CCN2), also known as CTGF (Connective Tissue Growth Factor), is a profibrotic matricellular protein functioning as an important driver and biomarker of fibrosis in a wide range of diseases outside the marrow. CCN2 can promote fibrosis directly or by acting as a factor downstream of TGF-ß, the latter already known to contribute to myelofibrosis in MPN.To study the possible involvement of CCN2 in BM fibrosis in MPN, we assessed CCN2 protein expression by immunohistochemistry in 75 BM biopsies (55 × MPN and 20 × normal controls). We found variable expression of CCN2 in megakaryocytes with significant overexpression in a subgroup of 7 (13%) MPN cases; 4 of them (3 × essential thrombocytemia and 1 × prefibrotic primary myelofibrosis) showed no fibrosis (MF-0), 2 (1 × post-polycythemic myelofibrosis and 1 × primary myelofibrosis) showed moderate fibrosis (MF-2), and 1 (primary myelofibrosis) severe fibrosis (MF-3). Remarkably, CCN2 expression did not correlate with fibrosis or other disease parameters such as platelet count or thrombovascular events, neither in this subgroup nor in the whole study group. This suggests that in BM of MPN patients other, CCN2-independent pathways (such as noncanonical TGF-ß signaling) may be more important for the development of fibrosis.

Effects of postnatal corticosteroids on lung development in newborn animals. A systematic review.

BACKGROUND: Postnatal systemic corticosteroids reduce the risk of bronchopulmonary dysplasia but the effect depends on timing, dosing, and type of corticosteroids. Animal studies may provide valuable information on these variable effects. This systematic review summarizes the effects of postnatal systemic corticosteroids on lung development in newborn animals. METHODS: A systematic search was performed in PubMed and Embase in December 2022. The protocol was published on PROSPERO (CRD42021177701). RESULTS: Of the 202 eligible studies, 51 were included. Only newborn rodent studies met the inclusion criteria. Most studies used dexamethasone (98%). There was huge heterogeneity in study outcome measures and corticosteroid treatment regimens. Reporting of study quality indicators was mediocre and risk of bias was unclear due to poor reporting of study methodology. Meta-analysis showed that postnatal corticosteroids caused a decrease in body weight as well as persistent alveolar simplification. Subgroup analyses revealed that healthy animals were most affected. CONCLUSION: In newborn rodents, postnatal systemic corticosteroids have a persistent negative effect on body weight and lung development. There was huge heterogeneity in experimental models, mediocre study quality, unclear risk of bias, and very small subgroups for meta-analysis which limited firm conclusions. IMPACT: Postnatal corticosteroids reduce the risk of bronchopulmonary dysplasia but the effect depends on timing, dosing, and type of corticosteroids while the underlying mechanism of this variable effect is unknown. This is the first systematic review and meta-analysis of preclinical newborn animal studies reviewing the effect of postnatal systemic corticosteroids on lung development. In newborn rodent models, postnatal corticosteroids have a persistent negative effect on body weight and lung alveolarization, especially in healthy animals.

Primary cerebral immunoglobulin light chain amyloidoma in a patient with multiple sclerosis.

A man in his 60s, known with multiple sclerosis, presented with seizures and paresis of the left arm and leg. Brain imaging showed a white matter lesion, right parietal, which was progressive over the last 6 years and not typical for multiple sclerosis. Brain biopsy showed a B-cell infiltrate with IgA lambda monotypic plasma cell differentiation and amyloid deposits, typed as lambda immunoglobulin light chain (AL). Bone marrow biopsy and PET/CT ruled out a systemic lymphoma. Extended history taking, blood and urine testing (including cardiac biomarkers) identified no evidence of systemic amyloidosis-induced organ dysfunction.Primary cerebral AL amyloidoma is a very rare entity where optimal treatment is difficult to assess. The patient was treated with locally applied volumetric modulated arc radiotherapy, 24 Gy, divided in 12 fractions. Afterwards, the paresis of the left arm partially resolved, and the function of the left leg improved. Seizures did not occur anymore.

What's in a score: A longitudinal investigation of scores based on item response theory and classical test theory for the Amsterdam Instrumental Activities of Daily Living Questionnaire in cognitively normal and impaired older adults.

OBJECTIVE: We aimed to investigate whether item response theory (IRT)-based scoring allows for a more accurate, responsive, and less biased assessment of everyday functioning than traditional classical test theory (CTT)-based scoring, as measured with the Amsterdam Instrumental Activities of Daily Living Questionnaire. METHOD: In this longitudinal multicenter study including cognitively normal and impaired individuals, we examined IRT-based and CTT-based score distributions and differences between diagnostic groups using linear regressions, and investigated scale attenuation. We compared change over time between scoring methods using linear mixed models with random intercepts and slopes for time. RESULTS: Two thousand two hundred ninety-four participants were included (66.6 ± 7.7 years, 54% female): n = 2,032 (89%) with normal cognition, n = 93 (4%) with subjective cognitive decline, n = 79 (3%) with mild cognitive impairment, and n = 91 (4%) with dementia. At baseline, IRT-based and CTT-based scores were highly correlated (r = -0.92). IRT-based scores showed less scale attenuation than CTT-based scores. In a subsample of n = 1,145 (62%) who were followed for a mean of 1.3 (SD = 0.6) years, IRT-based scores declined significantly among cognitively normal individuals (unstandardized coefficient [B] = -0.15, 95% confidence interval, 95% CI [-0.28, -0.03], effect size = -0.02), whereas CTT-based scores did not (B = 0.20, 95% CI [-0.02, 0.41], effect size = 0.02). In the other diagnostic groups, effect sizes of change over time were similar. CONCLUSIONS: IRT-based scores were less affected by scale attenuation than CTT-based scores. With regard to responsiveness, IRT-based scores showed more signal than CTT-based scores in early disease stages, highlighting the IRT-based scores' superior suitability for use in preclinical populations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Early Detection of Amyloid-Related Changes in Memory among Cognitively Unimpaired Older Adults with Daily Digital Testing.

OBJECTIVE: This study was undertaken to determine whether assessing learning over days reveals Alzheimer disease (AD) biomarker-related declines in memory consolidation that are otherwise undetectable with single time point assessments. METHODS: Thirty-six (21.9%) cognitively unimpaired older adults (aged 60-91 years) were classified with elevated ß-amyloid (Aß+) and 128 (78%) were Aß- using positron emission tomography with 11C Pittsburgh compound B. Participants completed the multiday Boston Remote Assessment for Neurocognitive Health (BRANCH) for 12 min/day on personal devices (ie, smartphones, laptops), which captures the trajectory of daily learning of the same content on 3 repeated tests (Digit Signs, Groceries-Prices, Face-Name). Learning is computed as a composite of accuracy across all 3 measures. Participants also completed standard in-clinic cognitive tests as part of the Preclinical Alzheimer's Cognitive Composite (PACC-5), with 123 participants undergoing PACC-5 follow-up after 1.07 (standard deviation = 0.25) years. RESULTS: At the cross-section, there were no statistically significant differences in performance between Aß+/- participants on any standard in-clinic cognitive tests (eg, PACC-5) or on day 1 of multiday BRANCH. Aß+ participants exhibited diminished 7-day learning curves on multiday BRANCH after 4 days of testing relative to Aß- participants (Cohen d = 0.49, 95% confidence interval = 0.10-0.87). Diminished learning curves were associated with greater annual PACC-5 decline (r = 0.54, p < 0.001). INTERPRETATION: Very early Aß-related memory declines can be revealed by assessing learning over days, suggesting that failures in memory consolidation predate other conventional amnestic deficits in AD. Repeated digital memory assessments, increasingly feasible and uniquely able to assess memory consolidation over short time periods, have the potential to be transformative for detecting the earliest cognitive changes in preclinical AD. ANN NEUROL 2024;95:507-517.

Increased intraindividual variability in reaction time performance is associated with emerging cognitive decline in cognitively unimpaired adults.

OBJECTIVE: To investigate whether intraindividual variability (IIV) in reaction time (RT) over monthly administered cognitive tasks is increased in cognitively unimpaired older adults who are at risk for cognitive decline, and whether this is independent of mean RT performance. METHOD: N = 109 cognitively unimpaired individuals (age 77.4 ± 5.0, 61.5% female, Mini-Mental State Examination 29.1 ± 1.3) from the Harvard Aging Brain Study completed the self-administered Computerized Cognitive Composite (C3) monthly at home for up to 1 year (12.7 ± 3.2 C3 assessments). Baseline C3 assessment coincided with routine in-clinic visits, including amyloid and tau positron emission tomography imaging and standardized cognitive testing, with cognitive testing repeated annually (1.6 ± 1.2 years follow-up). The C3 includes two simple RT tasks and two complex RT tasks. IIV estimates were derived by computing intraindividual standard deviations on residual RT scores after regressing out age and session order effects. Cross-sectional associations of IIV with cognition (global cognition, memory, executive functions [EF], processing speed) and amyloid and tau burden were examined using linear regression analyses correcting for demographics and mean RT. The association between IIV and cognitive decline was assessed using linear mixed models correcting for demographic factors, mean RT, and amyloid burden. RESULTS: After adjusting for mean RT, increased IIV on complex RT tasks was independently associated with worse EF performance (ß = -0.10, 95% CI [-.16, -0.03], p = .004), greater inferior-temporal tau deposition (ß = 0.18, 95% CI [0.02, 0.34], p = .024), and faster cognitive decline in those with elevated amyloid (ß = -0.62, 95% CI [-1.18, -0.06], p = .033). CONCLUSIONS: Increased variability in monthly RT may reflect subtle EF deficits and provide unique information about short-term cognitive decline in preclinical Alzheimer's disease. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Recovery to normal vital functions and acid-base status after a severe trauma in Level I versus Level II Trauma Centres.

PURPOSE: In the Netherlands, approximately 70% of severely injured patients (ISS ≥ 16) are transported directly to a Level I trauma center. This study compared the time needed to return to normal vital parameters and normal acid-base status in severely injured patients and some in-hospital processes in Level I versus Level II trauma centers. METHODS: This retrospective cohort study included all adult severely injured patients or adult trauma patients admitted to the intensive care unit between 2015 and 2020 in a Dutch trauma region. The primary endpoint was time until normal vital parameters and acid-base status. Secondary endpoints were complication rate, hospital length of stay, emergency department length of stay, and time until a computed tomography (CT) scan. RESULTS: A total of 2345 patients were included. Patients admitted to a Level I trauma center had a significantly higher rate of normalization of vital parameters over time (HR 1.51). There was no significant difference in normalization rate of the acid-base status over time (HR 1.10). In Level I trauma centers, time spent at the emergency department and time until the CT scan was significantly shorter (respectively, ß - 38 min and ß - 77 min), and the complication rate was significantly lower (OR 0.35). CONCLUSION: Severely injured patients admitted to a Level I trauma center require less time to normalize their vital functions. Level I centers are better equipped, resulting in better in-hospital processes with shorter time at the emergency department and shorter time until a CT scan.

Socioeconomic effects of establishing a new stroke center in Central Switzerland.

BACKGROUND: Establishment of dedicated Stroke Centers has shown to be effective on the outcome of patients with acute ischemic stroke, as well as mechanical thrombectomy (MTE) in acute large vessel occlusion. The cost-effectiveness of this treatment has also been proven in several countries, but so far not in Switzerland. METHODS: We compare the pathways and economic impact of patients with acute large vessel occlusions causing acute ischemic stroke before the establishment of the stroke center and MTE in 2016 with the time afterwards in the years 2016-2020. Local data from the Swiss Stroke Registry and hospital accounting as well as economic data from a healthcare insurance company was used for evaluation in an economic model. Both payer and societal perspectives were considered, and probabilistic sensitivity analysis was undertaken to explore uncertainty. RESULTS: Establishment of a new Stroke Center in Central Switzerland increased the absolute number of thrombectomies from 0 in 2015 to 55 in 2016 to 83 in 2020, as well as the percentage of MTE in large vessel occlusions (LVO) from 50.9% in 2016 to 58.2% in 2020. Over a 15-year horizon, predicted average additional costs of CHF 7,978 were associated with the establishment of a new stroke center, as well as 0.60 quality-adjusted life-years (QALY) per patient and an additional survival of 0.59 years per patient. The calculated incremental cost-effectiveness ratio was therefore CHF 13,297 per QALY gained. When societal costs were included, the new stroke care model was predicted to dominate the old care model. Robustness of model results was confirmed via probabilistic sensitivity analysis. LIMITATIONS: The results rely on data from a single stroke center and, therefore, cannot be generalized. CONCLUSIONS: Establishment of a new Stroke Center can be cost-effective and provide better outcomes in terms of functional independence as well as quality-adjusted life-years.

Recent contributions to the field of subjective cognitive decline in aging: A literature review.

Subjective cognitive decline (SCD) is defined as self-experienced, persistent concerns of decline in cognitive capacity in the context of normal performance on objective cognitive measures. Although SCD was initially thought to represent the "worried well," these concerns can be linked to subtle brain changes prior to changes in objective cognitive performance and, therefore, in some individuals, SCD may represent the early stages of an underlying neurodegenerative disease process (e.g., Alzheimer's disease). The field of SCD research has expanded rapidly over the years, and this review aims to provide an update on new advances in, and contributions to, the field of SCD in key areas and themes identified by researchers in this field as particularly important and impactful. First, we highlight recent studies examining sociodemographic and genetic risk factors for SCD, including explorations of SCD across racial and ethnic minoritized groups, and examinations of sex and gender considerations. Next, we review new findings on relationships between SCD and in vivo markers of pathophysiology, utilizing neuroimaging and biofluid data, as well as associations between SCD and objective cognitive tests and neuropsychiatric measures. Finally, we summarize recent work on interventions for SCD and areas of future growth in the field of SCD.

[Atlas block and alar ligament lesion-Underestimated or overrated?] / Atlasblockade und Lig.-alare-Läsion ­ unterschätzt oder übertrieben?

BACKGROUND: Disorders of the upper cervical spine, most notably lesions of the alar ligament and atlas block, are associated with numerous symptoms, especially as reported in the lay press. Thus, physicians are often confronted with patients who see in them a monocausal origin of complex complaints and hope for a quick remedy. OBJECTIVE: This review article presents the currently available evidence-based literature on atlas block and alar ligament lesions in order to adequately appreciate their significance. MATERIAL AND METHODS: Summary and critical evaluation of an extensive review of the literature on the diagnostics, clinical presentation, and treatment of disorders of the upper cervical spine. RESULTS: The current literature shows that alar ligament lesions are caused only by extremely high-speed trauma and that the reliability of their detection on magnetic resonance imaging (MRI) is moderate at best. As several studies have failed to demonstrate a correlation between symptoms and abnormalities of the alar ligaments on MRI, surgical stabilization of the upper cervical joints is not indicated. The diversity of symptoms associated with atlas block may be explained by the convergence of afferent neurons originating in C1-C3 on several cranial nerve nuclei found in neuroanatomical studies, but this association has yet to be proven. First studies show that highly significant improvements in cervical pain and range of motion can be achieved by means of manual therapy of the upper cervical spine with lasting effects even after 6 months. CONCLUSION: The importance of alar ligament lesions has often been overrated in the past; however, a more nuanced multifactorial understanding of the disorder should be conveyed to the patient. An atlas block should be considered mainly as a possible cause of pain and restricted range of motion of the cervical spine and in this context manual therapy can be an effective treatment option.

Implementing 3D fluoroscopy in the management of tibial plateau fractures: Shorter hospitalization and decline in revision surgery, but increase in the duration of surgery and radiation exposure.

BACKGROUND: Intraoperative 3D fluoroscopy (3DRX) is increasingly used in fracture management instead of conventional fluoroscopy (RX), but its effect on the treatment and outcome of tibial plateau fractures (TFs) is not well known. This study aims to evaluate whether the use of 3DRX in the treatment of tibial plateau fractures reduces the number of revision surgeries. METHODS: This retrospective cohort study includes all patients who underwent surgical treatment for TF in a single center from 2014 to 2018. Patient-, fracture-, and treatment characteristics were compared between the 3DRX and RX subgroups. The primary endpoint was the number of patients requiring revision surgery. Secondary endpoints were surgery duration, hospital length of stay, radiation exposure, postoperative complications, and secondary total knee arthroplasty. RESULTS: Eighty-seven patients were included, of which 36 were treated with 3DRX. Three patients in the RX group required revision surgery, while no revision surgery was performed in the 3DRX group (p = 0.265). The use of 3DRX resulted in significantly more intraoperative adjustments (25% versus 6%; p = 0.024) and an increase in surgery duration (by average of 28 min, p = 0.001), without a significant increase in postoperative wound infections (12% versus 19%; p = 0.374) or fracture-related infections (2% versus 2.8%; p = 0.802). The 3DRX group had an average radiation exposure of 7,985 mGy versus 1,273 mGy in the RX group (p<0.001). The hospital length of stay was 1 day shorter in the 3DRX group (5 days versus 4 days; p = 0.058). CONCLUSIONS: Implementing 3DRX in treating TFs improves the assessment of fracture alignment and implant position perioperatively, resulting in more intraoperative corrections and no revision surgeries within 6 weeks postoperatively. However, using 3DRX significantly increases perioperative radiation exposure and surgery duration without a significant rise in postoperative infections and a shorter hospital length of stay.

Can Presepsin Be Valuable in Reducing Unnecessary Antibiotic Exposure after Birth?

BACKGROUND: Due to a lack of rapid, accurate diagnostic tools for early-onset neonatal sepsis (EOS) at the initial suspicion, infants are often unnecessarily given antibiotics directly after birth. We aimed to determine the diagnostic accuracy of presepsin for EOS before antibiotic initiation and to investigate whether presepsin can be used to guide clinicians' decisions on whether to start antibiotics. METHODS: In this multicenter prospective observational cohort study, all infants who started on antibiotics for EOS suspicion were consecutively included. Presepsin concentrations were determined in blood samples collected at the initial EOS suspicion (t = 0). In addition to this, samples were collected at 3, 6, 12 and 24 h after the initial EOS suspicion and from the umbilical cord directly after birth. The diagnostic accuracy of presepsin was calculated. RESULTS: A total of 333 infants were included, of whom 169 were born preterm. We included 65 term and 15 preterm EOS cases. At the initial EOS suspicion, the area under the curve (AUC) was 0.60 (95% confidence interval (CI) 0.50-0.70) in the term-born infants compared to 0.84 (95% CI 0.73-0.95) in the preterm infants. A cut-off value of 645 pg/mL resulted in a sensitivity of 100% and a specificity of 54% in the preterm infants. The presepsin concentrations in cord blood and at other time points did not differ significantly from the concentrations at the initial EOS suspicion. CONCLUSIONS: Presepsin is a biomarker with an acceptable diagnostic accuracy for EOS (culture-proven and clinical EOS) in preterm infants and might be of value in reducing antibiotic exposure after birth when appended to current EOS guidelines. However, the small number of EOS cases prevents us from drawing firm conclusions. Further research should be performed to evaluate whether appending a presepsin-guided step to current EOS guidelines leads to a safe decrease in antibiotic overtreatment and antibiotic-related morbidity.

Comparing Patient-Reported Outcomes Measurement Information System Computer Adaptive Testing With Existing Measures After Operative Interventions for Extremity Fractures.

INTRODUCTION: Patient-Reported Outcomes Measurement Information System (PROMIS) enables the use of computer adaptive testing (CAT). The aim of this prospective cohort study was to compare the most commonly used disease-specific instruments with PROMIS CAT questionnaires in patients with trauma. METHODS: All patients with trauma (ages 18-75) who underwent an operative intervention for an extremity fracture between June 1, 2018, and June 30, 2019, were included. The disease-specific instruments were the Quick Disabilities of the Arm, Shoulder, and Hand for upper extremity fractures and the Lower Extremity Functional Scale (LEFS) for lower extremity fractures. Pearson's correlation (r) between the disease-specific instruments and the PROMIS CAT questionnaires (PROMIS Physical Function, PROMIS Pain Interference, and PROMIS Ability to Participate in Social Roles and Activities) was calculated at week 2, week 6, month 3, and month 6. Construct validity and responsiveness were calculated. RESULTS: A total of 151 patients with an upper extremity fracture and 109 patients with a lower extremity fracture were included. At month 3 and month 6, the correlation was strong between the LEFS and PROMIS Physical Function (r = 0.88 and r = 0.90, respectively), and at month 3, the correlation was strong between the LEFS and PROMIS Social Roles and Activities (r = 0.72). At week 6, month 3, and month 6, there was a strong correlation between the Quick Disabilities of the Arm, Shoulder, and Hand and PROMIS Physical Function (r = 0.74, r = 0.70, and r = 0.76, respectively). CONCLUSIONS: The PROMIS CAT measures are acceptably related to existing non-CAT instruments and may be a useful tool during follow-up after operative interventions for extremity fractures.

The international consensus classification of mastocytosis and related entities.

Mastocytosis is a neoplasm characterized by a clonal proliferation of mast cells, which accumulate in one or multiple organs, associated with an extremely heterogeneous clinical presentation. The disease can be limited to the skin (cutaneous mastocytosis) that is mostly seen in childhood and usually behaves in a benign fashion. Adult patients most often present with systemic disease with or without skin lesions. This includes indolent forms such as indolent systemic mastocytosis and its subvariant bone marrow mastocytosis, and smoldering systemic mastocytosis as well as aggressive forms including aggressive systemic mastocytosis, systemic mastocytosis with an associated myeloid neoplasm (previously called systemic mastocytosis with an associated hematologic neoplasm), and mast cell leukemia. In addition, mast cell sarcoma is a rare aggressive form of mastocytosis that can present in the skin as well as at extracutaneous sites. This review article focuses on the updates in mastocytosis of the 2022 international consensus classification (ICC).

Hematologic malignancies following immune checkpoint inhibition for solid tumors.

Immune checkpoint inhibition (ICI) can induce durable responses in patients with advanced malignancies. Three cases of hematological neoplasia following ICI for solid tumors have been reported to date. We present five patients treated at our tertiary referral center between 2017 and 2021 who developed chronic myeloid leukemia (two patients), acute myeloid leukemia, myelodysplastic syndrome and chronic eosinophilic leukemia during or after anti-PD-1-based treatment. Molecular analyses were performed on pre-ICI samples to identify baseline variants in myeloid genes. We hypothesize that PD-1 blockade might accelerate progression to overt myeloid malignancies and discuss potential underlying mechanisms.

Why a clinical trial is as good as its outcome measure: A framework for the selection and use of cognitive outcome measures for clinical trials of Alzheimer's disease.

A crucial aspect of any clinical trial is using the right outcome measure to assess treatment efficacy. Compared to the rapidly evolved understanding and measurement of pathophysiology in preclinical and early symptomatic stages of Alzheimer's disease (AD), relatively less progress has been made in the evolution of clinical outcome assessments (COAs) for those stages. The current paper aims to provide a benchmark for the design and evaluation of COAs for use in early AD trials. We discuss lessons learned on capturing cognitive changes in predementia stages of AD, including challenges when validating novel COAs for those early stages and necessary evidence for their implementation in clinical trials. Moving forward, we propose a multi-step framework to advance the use of more effective COAs to assess clinically meaningful changes in early AD, which will hopefully contribute to the much-needed consensus around more appropriate outcome measures to assess clinical efficacy of putative treatments. HIGHLIGHTS: We discuss lessons learned on capturing cognitive changes in predementia stages of AD. We propose a framework for the design and evaluation of performance based cognitive tests for use in early AD trials. We provide recommendations to facilitate the implementation of more effective cognitive outcome measures in AD trials.

Determining the Minimal Important Change of Everyday Functioning in Dementia: Pursuing Clinical Meaningfulness.

BACKGROUND AND OBJECTIVES: Decline in everyday functioning is a key clinical change in Alzheimer disease and related disorders (ADRD). An important challenge remains the determination of what constitutes a clinically meaningful change in everyday functioning. We aimed to investigate this by establishing the minimal important change (MIC): the smallest amount of change that has a meaningful effect on patients' lives. We retrospectively investigated meaningful change in a memory clinic cohort. METHODS: In the first, qualitative part of the study, community-recruited informal caregivers of patients with ADRD and memory clinic clinicians completed a survey in which they judged various situations representing changes in everyday functioning. Their judgments of meaningful change were used to determine thresholds for MIC, both for decline and improvement, on the Amsterdam Instrumental Activities of Daily Living (IADL) Questionnaire. In the second, quantitative part, we applied these values in an independent longitudinal cohort study of unselected memory clinic patients. RESULTS: MIC thresholds were established at the average threshold of caregivers (N = 1,629; 62.4 ± 9.5 years; 77% female) and clinicians (N = 13): -2.2 points for clinically meaningful decline and +5.0 points for clinically meaningful improvement. Memory clinic patients (N = 230; 64.3 ± 7.7 years; 39% female; 60% dementia diagnosis) were followed for 1 year, 102 (45%) of whom showed a decline larger than the MIC, after a mean of 6.7 ± 3.5 months. Patients with a dementia diagnosis and more atrophy of the medial temporal lobe had larger odds (odds ratio [OR] = 3.4, 95% CI [1.5-7.8] and OR = 5.0, 95% CI [1.2-20.0], respectively) for passing the MIC threshold for decline than those with subjective cognitive complaints and no atrophy. DISCUSSION: We were able to operationalize clinically meaningful decline in IADL by determining the MIC. The usefulness of the MIC was supported by our findings from the clinical sample that nearly half of a sample of unselected memory clinic patients showed a meaningful decline in less than a year. Disease stage and medial temporal atrophy were predictors of functional decline greater than the MIC. Our findings provide guidance in interpreting changes in IADL and may help evaluate treatment effects and monitor disease progression.

Cross-national harmonization of cognitive measures across HRS HCAP (USA) and LASI-DAD (India).

BACKGROUND: As global populations age, cross-national comparisons of cognitive health and dementia risk are increasingly valuable. It remains unclear, however, whether country-level differences in cognitive function are attributable to population differences or bias due to incommensurate measurement. To demonstrate an effective method for cross-national comparison studies, we aimed to statistically harmonize measures of episodic memory and language function across two population-based cohorts of older adults in the United States (HRS HCAP) and India (LASI-DAD). METHODS: Data for 3,496 HRS HCAP (≥65 years) and 3,152 LASI-DAD (≥60 years) participants were statistically harmonized for episodic memory and language performance using confirmatory factor analysis (CFA) methods. Episodic memory and language factor variables were investigated for differential item functioning (DIF) and precision. RESULTS: CFA models estimating episodic memory and language domains based on a priori adjudication of comparable items fit the data well. DIF analyses revealed that four out of ten episodic memory items and five out of twelve language items measured the underlying construct comparably across samples. DIF-modified episodic memory and language factor scores showed comparable patterns of precision across the range of the latent trait for each sample. CONCLUSIONS: Harmonization of cognitive measures will facilitate future investigation of cross-national differences in cognitive performance and differential effects of risk factors, policies, and treatments, reducing study-level measurement and administrative influences. As international aging studies become more widely available, advanced statistical methods such as those described in this study will become increasingly central to making universal generalizations and drawing valid conclusions about cognitive aging of the global population.

Torque acting on biodegradable magnesium screws during intramedullary insertion into a metacarpal bone - a biomechanical study.

Recently, biodegradable implants made from magnesium (Mg) alloys have been developed to obviate the need for later implant removal. Mg-based cannulated compression screws (CCS) are ideal for intramedullary screw (IMS) fixation of metacarpal fractures. The present study aimed at investigating the torque acting on Mg-based CCS at failure and at intramedullary metacarpal insertion. The devices were CE certified Magnezix 2.7 and 3.2 mm CCSs (Syntellix®, Hannover, Germany). Torque at failure was measured in a synthetic bone model using a standardized polyurethane foam block. In a second assessment, insertional torque was measured in ten cadaveric metacarpal bones. Mean torque at failure for the 2.7 mm and 3.2 mm CCSs was 42.8 Ncm (±1.9 Ncm) and 63.0 Ncm (±2.2 Ncm), respectively. In the human cadaver model, the torque distribution curve at metacarpal insertion showed three peaks. The highest reached 53.6% of the lowest torque at failure measured in the synthetic bone model for the 3.2 CCS (31.4 vs. 58.6 Ncm). The mean difference between peak torque at metacarpal insertion and torque at failure was 38.3 Ncm (99% CI [33.6, 43.0 Ncm], p < 0.0001). In terms of torque load, Mg-based CCSs are suitable for IMS fixation of metacarpal fractures. Biodegradable implants may represent an important improvement of this treatment method; confirmation by in-vivo studies is needed.