Location of Measurement Matters: Unveiling Regional Dynamics and Sex Differences in Patellar Tendon Strain In Vivo.

Patellar tendinopathy is more prevalent in males versus female athletes and commonly presents in the medial region of the tendon. Separate measures of patellar tendon strain in the medial, central, and lateral regions of the tendon, however, have not been quantified. The purpose was to investigate the differences in tendon strain between the medial, lateral, and central regions of the patellar tendon in healthy men and women. Strain in the medial and lateral regions of the patellar tendon in healthy participants (10 males, 10 females) was evaluated using ultrasound during isometric quadriceps contractions at 20%, 40%, 60%, 80%, and 100% of maximum voluntary contraction (MVIC) in 60° and 90° of knee flexion. Central strain was also measured at 60% MVIC in 90° of knee flexion. Mixed models were used to determine strain between tendon regions and sex at 60% MVIC in 90° of knee flexion. Sequential modeling was used to fit region, sex, %MVIC, and angle to predict strain. The central region had less strain compared with both medial and lateral regions. The lateral region had higher strain compared with the medial region regardless of sex. Females had higher strain compared with males, regardless of region. Knee position did not influence tendon strain. Patellar tendon strain differs by region and sex. The varying prevalence between sex and in location of patellar tendinopathy may in part be explained by the unbalanced strains. Differential assessment of regional patellar tendon strain may be of importance for understanding injury risk and recovery with exercise.

Reliability of Continuous Shear Wave Elastography in the Pathological Patellar Tendon.

OBJECTIVES: Patellar tendon injuries occur via various mechanisms such as overuse, or due to surgical graft harvest for anterior cruciate ligament reconstruction (ACLR). Quantified patellar tendon stiffness after injury may help guide clinical care. Continuous shear wave elastography (cSWE) allows for the assessment of viscosity and shear modulus in tendons. The reliability of the measure, however, has not been established in the patellar tendon. The purpose of this study was to investigate the interrater reliability, intrarater reliability, and between-day stability of cSWE in both healthy and pathological patellar tendons. METHODS: Participants with patellar tendinopathy (n = 13), history of ACLR using bone-patellar tendon-bone autograft (n = 9), and with no history of patellar tendon injury (n = 13) were recruited. cSWE was performed 4 times by multiple raters over 2 days. Intraclass correlations (ICC) and minimum detectable change (MDC95% ) were calculated. RESULTS: Good to excellent between-day stability were found for viscosity (ICC = 0.905, MDC95%  = 8.3 Pa seconds) and shear modulus (ICC = 0.805, MDC95%  = 27.4 kPa). The interrater reliability measures, however, were not as reliable (ICC = 0.591 and 0.532). CONCLUSIONS: cSWE is a reliable assessment tool for quantifying patellar tendon viscoelastic properties over time. It is recommended, however, that a single rater performs the measure as the interrater reliability was less than ideal.

Time to treat the tendon rupture induced by surgery: early hypertrophy of the patellar tendon graft site predicts strong quadriceps after ACLR with bone-patellar tendon-bone autograft.

PURPOSE: Quadriceps dysfunction is ubiquitous after anterior cruciate ligament reconstruction, especially when using bone-patellar tendon-bone (BPTB) autografts. The role of patellar tendon hypertrophy after graft harvest on knee extensor strength is unknown. The purpose of this study was to determine the predictive ability of patellar tendon (PT) and quadriceps muscle (Quad) cross-sectional area (CSA) on knee extensor strength 1-2 months after ACLR using BPTB autografts. METHODS: This is a cross-sectional analysis of a cohort 1-2 months after ACLR using BPTB autograft. Peak knee extensor torque, and PT and Quad CSA measured using ultrasound imaging, were collected in 13 males and 14 females. Simple linear regressions compared quadriceps strength index (QI) against limb symmetry index (LSI) in PT and Quad CSA. Multiple linear regressions with sequential model comparisons predicting peak knee extensor torque were performed for each limb. The base model included demographics. Quad CSA was added in the first model, then PT CSA was added in the second model. RESULTS: Both PT (p < 0.001, R2 = 0.693) and Quadriceps CSA (p = 0.013, R2 = 0.223) LSI had a positive linear relationship with QI. In the involved limb, addition of PT CSA significantly improved the model (R2 = 0.781, ΔR2 = 0.211, p for ΔR2 < 0.001). In the uninvolved limb, the addition of Quad CSA improved the model, but the addition of PT CSA did not. CONCLUSION: PT LSI was more predictive of QI than Quad CSA LSI. Involved limb PT CSA mattered more in predicting peak knee extensor torque than did Quad CSA, but in the uninvolved limb, Quad CSA was the most important predictor of peak knee extensor torque. Graft site patellar tendon hypertrophy is key for strong quadriceps early after ACLR. Early targeted loading via exercise to promote healing of the graft site patellar tendon may bring patients a step closer to winning their battle against quadriceps dysfunction. LEVEL OF EVIDENCE: Level I.

Nutritional intervention after an early assessment by a flexible endoscopic evaluation of swallowing is associated with a shorter hospital stay for patients with acute cerebral infarction: A retrospective study.

BACKGROUND AND OBJECTIVES: It is important to evaluate the swallowing function of patients with acute cerebral infarction. The effects of nutritional intervention after an early assessment by a flexible endoscopic evaluation of swallowing (FEES) were evaluated. METHODS AND STUDY DESIGN: This retrospective study included 274 patients who were hospitalized for acute cerebral infarction and underwent a FEES between 2016 and 2018. The effects of early nutritional intervention after an assessment by a FEES within 48 h from admission were evaluated. The patients were divided into a shorter hospital stay group (<30 days) and a longer group (≥30 days). A multivariate analysis was performed to identify the predictive factors for a shorter hospital stay. RESULTS: The overall patient characteristics were as follows: 166 men; median age, 81 years old; and median body mass index (BMI), 21.1 kg/m2. No significant differences in the age, sex, or BMI were found between the shorter and longer hospital stay groups. A FEES within 48 h of admission (odds ratio [OR], 2.040; 95% confidence interval [CI], 1.120-3.700; p=0.019), FILS level ≥6 at admission (OR, 2.300; 95% CI, 1.190-4.440; p=0.013), and an administered energy dose of ≥18.5 kcal/kg on hospital day 3 (OR, 2.360; 95% CI, 1.180-4.690; p=0.015) were independently associated with a hospital stay <30 days. CONCLUSIONS: Patients with acute cerebral infarction are more likely to have a shorter hospital stay (<30 days) if they undergo a FEES early after admission and receive optimal nutritional intervention.

Who's Afraid of Electrical Stimulation? Let's Revisit the Application of NMES at the Knee.

BACKGROUND: Restoring quadriceps strength is essential for successful rehabilitation of knee injuries, but many athletes return to their previous activity with persisting muscle weakness. Strong evidence supports using neuromuscular electrical stimulation (NMES) to improve quadriceps strength; however, there is a lack of widespread clinical implementation. We believe there is a critical need to provide clinical approaches that promote using NMES to improve patients' quadriceps strength and ensuring clinicians provide high-value rehabilitation care. CLINICAL QUESTION: What is best practice when using NMES to facilitate strength after injury, what are barriers to its use, and how can they be addressed? KEY RESULTS: We discuss the low clinical implementation of NMES, perceived barriers to using NMES, and provide recommendations for setup and dosage parameters for effective use of NMES. CLINICAL APPLICATION: We aim for this commentary, with accompanying videos, to serve as a resource for clinicians who are using commercially available NMES units in clinical practice. J Orthop Sports Phys Ther 2024;54(2):1-6. Epub 31 October 2023. doi:10.2519/jospt.2023.12028.

Regional healing trajectory of the patellar tendon after bone-patellar tendon-bone autograft harvest for anterior cruciate ligament reconstruction.

Graft site morbidities after bone-patellar tendon-bone (BPTB) autograft harvest for anterior cruciate ligament reconstruction (ACLR) negatively impacts rehabilitation. The purpose of this study was to establish tendon structural properties 1-month after BPTB autograft harvest compared to the uninvolved patellar tendon, and subsequently to quantify the healing trajectory of the patellar tendon over the course of rehabilitation. Patellar tendon morphology (ultrasound) and mechanical properties (continuous shear wave elastography) from 3 regions of the tendon (medial, lateral, central) were measured in 34 participants at 1 month, 3-4 months, and 6-9 months after ACLR. Mixed models were used to compare tendon structure between limbs at 1 month, and quantify healing over 3 timepoints. The involved patellar tendon had increased cross-sectional area and thickness in all regions 1-month after ACLR. Thickness reduced uniformly over time. Possible tendon elongation was observed and remained stable over time. Tendon viscosity was uniform across the three regions in the involved limb while the medial region had higher viscosity in the uninvolved limb, and shear modulus was elevated in all three regions at 1 month. Viscosity and shear modulus in only the central region reduced over time. Statement of Clinical Significance: The entire patellar tendon, and not just the central third, is altered after graft harvest. Tendon structure starts to normalize over time, but alterations remain especially in the central third at the time athletes are returning to sport. Early rehabilitation consisting of tendon loading protocols may be necessary to optimize biologic healing at the graft site tendon.

Hop Distance Symmetry Moderately Reflects Knee Biomechanics Symmetry During Landing But Not For Controlled Propulsions.

Background: Landing with poor knee sagittal plane biomechanics has been identified as a risk factor for Anterior Cruciate Ligament (ACL) injury. However, it is unclear if the horizontal hop test battery reflects knee function and biomechanics. Hypothesis/Purpose: To investigate the correlation between clinical limb symmetry index (LSI) and landing and propulsion knee biomechanics during the hop test battery using markerless motion capture. Study Design: Cross-sectional biomechanics laboratory study. Methods: Forty-two participants with and without knee surgery (age 28.0 ± 8.0 years) performed the hop test battery which consisted of a single hop for distance, crossover hop, triple hop, and 6-m timed hop in the order listed. Eight high speed cameras were used to collect simultaneous 3D motion data and Theia 3D (Theia Markerless Inc.) was used to generate 3D body model files. Lower limb joint kinematics were calculated in Visual3D. Correlation (Spearman's ρ) was computed between clinical LSI and symmetry in peak and initial contact (IC) knee flexion angle during propulsion and landing phases of each movement. Results: In the single hop, clinical LSI showed positive correlation with kinematic LSI at peak landing (ρ= 0.39, p=0.011), but no correlation at peak propulsion (ρ= -0.03, p=0.851). In the crossover hop, non-significant correlations were found in both propulsion and landing. In the triple hop, positive correlation was found at peak propulsion (ρ= 0.38, p=0.027), peak landing (ρ= 0.48 - 0.66, p<0.001), and last landing IC (ρ= 0.45, p=0.009). In the timed hop, peak propulsion showed positive correlation (ρ= 0.51, p=0.003). Conclusions: Single hop and triple hop distance symmetry reflected landing biomechanical symmetry better than propulsion symmetry. Poor scores on the hop test battery reflect asymmetrical knee landing biomechanics, emphasizing the importance of continuing to use the hop test battery as part of clinical decision making. Level of Evidence: 3b.

Prolonged quadriceps latency during gait early after anterior cruciate ligament injury predicts radiographic knee osteoarthritis 6-years after anterior cruciate ligament reconstruction.

BACKGROUND: The purpose was to explore quadriceps electromechanical function (quadriceps latency) during gait after anterior cruciate ligament injury as a predictor for radiographic knee osteoarthritis 6-years after anterior cruciate ligament reconstruction. Change in latency after preoperative physical therapy was also examined. METHODS: Quadriceps latency (time between peak knee moment and quadriceps electromyography) was calculated before preoperative physical therapy (2.4 [0.5-7.5] months after anterior cruciate ligament injury) and after preoperative physical therapy in 24 athletes. Participants were dichotomized into osteoarthritis (Kellgren and Lawrence grade ≥ 2) and non-osteoarthritis groups at 6-years. Forward selection logistic regression was performed using z-score normalized quadriceps latency and demographics. A 2 × 2 repeated measure ANOVA was performed for quadriceps latency between groups before and after preoperative physical therapy. FINDINGS: Quadriceps latency before preoperative physical therapy was the only predictor of 6-year radiographic osteoarthritis (p = 0.014, odds ratio [95% confidence interval] = 5.859 [1.435-23.924]). Time by group interaction was observed for quadriceps latency (p = 0.039, η2p = 0.179). In the osteoarthritis group, latency may reduce after training (before preoperative physical therapy = 115.7 ± 20.6 ms, after preoperative physical therapy = 99.5 ± 24.0 ms, p = 0.082). INTERPRETATION: Prolonged latency after anterior cruciate ligament injury may predict post-traumatic knee osteoarthritis 6-years after anterior cruciate ligament reconstruction. Latency may shorten with preoperative physical therapy, yet athletes still moved on to develop osteoarthritis. Quadriceps function may need intervention immediately following anterior cruciate ligament injury for prevention of post-traumatic knee osteoarthritis.

Rationale and Design of the Study to Investigate the Metabolic Action of Imeglimin on Patients with Type 2 Diabetes Mellitus (SISIMAI).

INTRODUCTION: Imeglimin is a first-in-class, novel, oral glucose-lowering agent for the treatment of type 2 diabetes mellitus. The efficacy and safety of imeglimin as an antidiabetic agent have been investigated in clinical trials. However, its metabolic effects in humans have not yet been fully elucidated. METHODS: The Study to InveStIgate the Metabolic Action of Imeglimin on patients with type 2 diabetes mellitus (SISIMAI) is a single-arm intervention study. In this study, we have recruited 25 patients with type 2 diabetes to receive 2000 mg/day imeglimin for 20 weeks. We perform a 75-g oral glucose tolerance test (OGTT) with double-glucose tracers, a two-step hyperinsulinemic-euglycemic clamp with glucose tracer, ectopic fat measurement by proton magnetic resonance spectroscopy, visceral/subcutaneous fat area measurement by magnetic resonance imaging, muscle biopsy, and evaluation of fitness level by cycle ergometer before and after imeglimin administration. PLANNED OUTCOMES: The primary outcome is the change in area under the curve of glucose levels during the OGTT after 20 weeks of imeglimin treatment. We also calculate the endogenous glucose production, rate of oral glucose appearance, and rate of glucose disappearance from the data during the 75-g OGTT and compare them between pre- and post-treatment. Additionally, we will compare other parameters, such as the changes in tissue-specific insulin sensitivity, ectopic fat accumulation, visceral/subcutaneous fat area accumulation, and fitness level between each point. This is the first study to investigate the organ-specific metabolic action of imeglimin in patients with type 2 diabetes mellitus using the 75-g OGTT with the double tracer method. The results of this study are expected to provide useful information for drug selection based on the pathophysiology of individual patients with type 2 diabetes mellitus. TRIAL REGISTRATION: jRCTs031210600.

Sex-specific impact of GCKR rs1260326 polymorphism on metabolic traits in an older Japanese population: the Bunkyo Health Study.

Background: Metabolic syndrome involves health problems influenced by aging and genetics. The glucokinase regulatory protein (GCKR) rs1260326 polymorphism (Leu446) is associated with metabolic traits. This study explores the impact of the GCKR rs1260326 polymorphism on metabolic traits in older Japanese with focusing on sex-specific differences. Methods: This cross-sectional study from the Bunkyo Health Study in Tokyo, Japan, examined 883 participants aged 65-84 years. Participants were excluded with diabetes, or on drug treatment for diabetes or dyslipidemia. The GCKR P446L polymorphism was analyzed and compared their characteristics of physical activity, dietary intake, body composition, and metabolic parameters. Results: Study participants with GCKR rs1260326 genotypes (C/C 20.7%, C/T 47.6%, T/T 31.7%) had a median age of 72 years, and 60.4% were women. Men with the T/T genotype, as compared to the C/C genotype, had a lower body weight, body mass index (BMI), and skeletal mass index. This genotype also associated with lower fasting insulin, homeostasis model assessment of insulin resistance index (HOMA-IR), and higher Matsuda index, but not after adjustment for age, BMI, and physical activity. In contrast, women with the T/T genotype, compared to the C/C genotype, showed higher C-reactive protein, fibroblast growth factor 21, and Matsuda index. They also had lower fasting insulin, insulin area under the curve, and HOMA-IR; with these associations being independent of age, BMI, and physical activity. Conclusion: The GCKR rs1260326 genotype-affected metabolic traits differentially by sex in older Japanese. This highlights the need to consider sex differences in GCKR-related metabolic outcomes.

How a certain gene change affects health differently for older men and women in Japan: a study from Bunkyo This study looks into how a certain genetic change affects the health of older Japanese people, focusing on whether there are differences between men and women. It involves participants aged 65 to 84 from Tokyo who are not taking medication for diabetes or dyslipidemia. The findings indicate that this genetic variation impacts men and women differently. Men with a specific version of this genetic change tend to have lower body weight, body mass index (BMI), and less skeletal mass. They also show lower insulin levels and resistance, but these associations weaken when considering age, BMI, and physical activity. On the other hand, women with this genetic variation showed higher levels of markers indicating inflammation and metabolic health, alongside better insulin sensitivity. These relationships held even after adjusting for age, BMI, and activity levels. From this research, it's clear that the effects of this genetic change on health vary between older Japanese men and women. This suggests the importance of considering gender differences when studying how genes influence our health, underlining the need for personalized approaches in understanding and managing health issues.

Fat Accumulation and Elevated Free Fatty Acid Are Associated With Age-Related Glucose Intolerance: Bunkyo Health Study.

Context: Older adults have a high prevalence of new-onset diabetes, often attributed to age-related decreases in insulin sensitivity and secretion. It remains unclear whether both insulin sensitivity and secretion continue to deteriorate after age 65. Objective: To investigate the effects of aging on glucose metabolism after age 65 and to identify its determinants. Methods: This cross-sectional study involved 1438 Japanese older adults without diabetes. All participants underwent a 75-g oral glucose tolerance test (OGTT). Body composition and fat distribution were measured with dual-energy X-ray absorptiometry and magnetic resonance imaging. Participants were divided into 4 groups by age (65-69, 70-74, 75-79, and 80-84 years) to compare differences in metabolic parameters. Results: Mean age and body mass index were 73.0 ± 5.4 years and 22.7 ± 3.0 kg/m2. The prevalence of newly diagnosed diabetes increased with age. Fasting glucose, fasting insulin, the area under the curve (AUC)-insulin/AUC-glucose and insulinogenic index were comparable between groups. AUC-glucose and AUC-insulin during OGTT were significantly higher and Matsuda index and disposition index (Matsuda index · AUC-insulin/AUC-glucose) were significantly lower in the age 80-84 group than in the age 65-69 group. Age-related fat accumulation, particularly increased visceral fat area (VFA), and elevated free fatty acid (FFA) levels were observed. Multiple regression revealed strong correlations of both Matsuda index and disposition index with VFA and FFA. Conclusion: Glucose tolerance declined with age in Japanese older adults, possibly due to age-related insulin resistance and ß-cell deterioration associated with fat accumulation and elevated FFA levels.

Low Handgrip Strength (Possible Sarcopenia) With Insulin Resistance Is Associated With Type 2 Diabetes Mellitus.

Context: Older adults with sarcopenic obesity are at high risk for type 2 diabetes mellitus (T2DM). However, few East Asians have sarcopenic obesity. Since many East Asians have insulin resistance (IR) without obesity, it is possible that older East Asians with sarcopenia and IR might be at high risk for T2DM. However, this relationship has not been studied. Methods: This cross-sectional study included 1629 older adults aged 65 to 84 years registered in the Bunkyo Health Study. All underwent a 75-g oral glucose tolerance test and handgrip strength measurement. Participants were classified into 4 groups by possible sarcopenia (handgrip strength <28 kg in men and <18 kg in women) and IR status (triglyceride glucose [TyG] index ≥8.79 for men and ≥8.62 for women [third quartile]). Modified Poisson regression was used to estimate relative risk (RR) and 95% CIs for T2DM with adjustment for confounding factors. Results: The mean age was 73.1 ± 5.4 years. T2DM was diagnosed in 212 (13.0%) participants. After adjusting for age, sex, body mass index, use of lipid-lowering medications, hypertension, and cardiovascular disease, possible sarcopenia and IR were associated with T2DM, with their coexistence showing a notably stronger association (control: RR, 1.00 [Reference]; possible sarcopenia: RR, 1.55 [95% CI, 1.04-2.30]; IR: RR, 2.69 [95% CI, 1.99-3.65]; and IR possible sarcopenia: RR, 4.76 [95% CI, 3.34-6.79]). Conclusion: Possible sarcopenia based on low handgrip strength and IR based on the TyG index are independently associated with T2DM in older Japanese individuals. Their coexistence shows a particularly strong association with T2DM.

Corrigendum: Playing basketball and volleyball during adolescence is associated with higher bone mineral density in old age: the Bunkyo Health Study.

[This corrects the article DOI: 10.3389/fphys.2023.1227639.].

The Basas Spanish Squat: Superimposition of Electrical Stimulation to Optimize Patellar Tendon Strain: A Case Series.

Background: The Basas Spanish Squat with electrical stimulation (E-stim) has shown promising results as a potential key exercise in treatment of athletes with patellar tendinopathy. Gold standard exercise therapy for tendon injuries consists of tendon loading exercises, or exercises that appropriately applies high levels of mechanical strain to the tendon. The theoretical pathway in which the Basas Spanish Squat with E-stim improves tendinopathy has been speculated to be the additional strain applied through the patellar tendon during superimposition of E-stim. This theory, however, has yet to be confirmed. Purpose: The purpose of this case series was to compare patellar tendon strain, during the Basas Spanish Squat with, and without E-stim, and open kinetic chain knee extension. Methods: Four healthy participants performed the three exercises while a physical therapist collected simultaneous unilateral ultrasound images from the patellar tendon. Strain was calculated as the change in patellar tendon length during contraction divided by the resting length. Results: Amongst all participants, patellar tendon strain was smallest during the Basas Spanish Squat without E-stim, followed by the open kinetic chain knee extension at 60% maximum voluntary isometric contraction. The Basas Spanish Squat with E-stim yielded approximately double or more strain compared to the without E-stim condition and demonstrated higher level of strain compared to open kinetic chain knee extension in all participants. Conclusion: The findings reflect a clear trend of increased strain through the patellar tendon when E-stim was superimposed. The results support the theory that the Basas Spanish Squat with E-stim increases patellar tendon strain and could explain the reported clinical benefits in individuals with patellar tendinopathy. Level of Evidence: 4, Case series.

Challenging the assumption of uniformity in patellar tendon structure: Regional patellar tendon morphology and mechanical properties in vivo.

Patellar tendons are assumed to be uniform in morphology and mechanical properties despite a higher prevalence of tendinopathies observed in the medial region. The purpose of this study was to compare the thickness, length, viscosity, and shear modulus of the medial, central, and lateral regions of healthy patellar tendons of young males and females in vivo. B-mode ultrasound and continuous shear wave elastography were performed on 35 patellar tendons (17 females, 18 males) over three regions of interest. A linear mixed-effects model (α = 0.05) was used to determine differences between the three regions and sexes followed by pairwise comparisons for significant findings. The lateral region (mean [95% confidence interval] = 0.34 [0.31-0.37] cm) was thinner compared with the medial (0.41 [0.39-0.44] cm, p < 0.001), and central (0.41 [0.39-0.44] cm, p < 0.001) regions regardless of sex. Viscosity was lower in the lateral (19.8 [16.9-22.7] Pa-s) versus medial region (27.4 [24.7-30.2] Pa-s, p = 0.001). Length had a region-by-sex interaction (p = 0.003) characterized by a longer lateral (4.83 [4.54-5.13] cm) versus medial (4.42 [4.12-4.72] cm) region in males (p < 0.001), but not females (p = 0.992). Shear modulus was uniform between regions and sexes. The thinner, and less viscous lateral patellar tendon may reflect the lower load the tendon experiences explaining the differences in regional prevalence of developing tendon pathology. Statement of Clinical Significance: Healthy patellar tendons are not uniform in morphology or mechanical properties. Considering regional tendon properties may help guide targeted interventions for patellar tendon pathologies.

Clinical characteristics of adrenal insufficiency induced by pembrolizumab in non-small-cell lung cancer.

BACKGROUND AND AIM: Immune checkpoint inhibitors have significantly improved the clinical outcomes of many cancer types, but they induce a range of immune-related adverse events (irAEs). Although adrenal insufficiency (AI) is a rare irAE, it can lead to serious consequences. This study aimed to determine the clinical features of patients with advanced non-small-cell lung cancer (NSCLC) who developed AI following pembrolizumab treatment. METHODS: We retrospectively reviewed and analyzed the clinical data of all patients with NSCLC treated with pembrolizumab at Juntendo University Hospital from February 2017 to December 2020. The diagnosis of AI was established based on the Endocrine Emergency Guidance for the acute management of endocrine complications of checkpoint inhibitor therapy in the UK and the clinical practice guidelines of the Japan Endocrine Society. RESULT: AI was clinically suspected in 59 out of 186 patients treated with pembrolizumab, and 10 (5.4%) cases were confirmed. The symptoms included hyponatremia (n = 9), fatigue (n = 8), and loss of appetite (n = 6). All patients had low adrenocorticotropic hormone (ACTH) levels, and five patients were diagnosed with isolated ACTH deficiency. All patients completely recovered with corticosteroid replacement. The median time to onset of AI was 8.0 (range 3.8-15.2) months. The median progression-free survival in these patients was 22.4 (95% confidence interval 11.2-not reached) months. CONCLUSION: The incidence of AI among patients treated with pembrolizumab is more frequent than previously reported. In addition, secondary AI, especially isolated ACTH deficiency, is a major form of AI induced by pembrolizumab.

Playing basketball and volleyball during adolescence is associated with higher bone mineral density in old age: the Bunkyo Health Study.

Introduction: Exercise is beneficial for increasing areal bone mineral density (aBMD) in adolescence and maintaining it in old age. Moreover, high-impact sports are more effective than low-impact sports in increasing aBMD. This study aimed to determine the types of adolescent sports played in school-based sports clubs associated with aBMD in old age. Methods: In total, 1,596 older adults (681 men and 915 women, age: 65-84 years) living in an urban area of Japan were evaluated for the femoral neck and lumbar spine aBMD using dual-energy X-ray absorptiometry. The association between adolescent sports played in sports clubs and aBMD in old age was analyzed using multiple regression analysis, with femoral neck and lumbar spine aBMD as dependent variables, and sports type and participant characteristics such as age, body weight, and serum 25-hydroxyvitamin D [25(OH)D] level, as independent variables. Results: For the femoral neck, basketball was associated with aBMD in older men (ß = 0.079, p < 0.05) and women (ß = 0.08, p < 0.01), whereas current body weight and 25(OH)D level were associated with aBMD in both sexes. For the lumbar spine, volleyball (ß = 0.08, p < 0.01) and swimming (ß = 0.06, p < 0.05) was significantly associated with lumbar spine aBMD, whereas current body weight, 25(OH)D, and diabetes mellitus were associated with aBMD in older women. Conclusion: Both men and women who played basketball in adolescence had higher femoral neck aBMD in old age. Moreover, women who played volleyball in adolescence had higher lumbar spine aBMD in old age.

Effects of exercise habits in adolescence and older age on sarcopenia risk in older adults: the Bunkyo Health Study.

BACKGROUND: Sarcopenia, defined as an age-associated loss of skeletal muscle mass and function, is a major risk factor for requiring long-term care. Because physical activity in adolescence and older age enhances peak muscle function in youth and prevents muscle function decline in older age, older adults with exercise habits during both periods may be at a lower risk for sarcopenia. We investigated the relationship between exercise habits in adolescence and older age and sarcopenia and its components in community-dwelling older Japanese adults. METHODS: This study included 1607 community-dwelling individuals (aged 65-84, medians 73 years, 679 men and 928 women) with complete health examinations, including measurements of skeletal muscle index, handgrip strength and gait speed, who were enrolled in the Bunkyo Health Study. We divided the participants into four groups according to exercise habits in adolescence and older age: no exercise in either period (none-none; NN), exercise only in adolescence (active-none; AN), exercise only in older age (none-active; NA) and exercise in both periods (active-active; AA). Multivariate-adjusted logistic regression models were used to estimate the odds ratios (ORs) and associated 95% confidence intervals (CIs) in each group for the prevalence of sarcopenia, defined as low muscle mass and low muscle performance, as compared with the NN group. Low muscle performance was defined as low muscle strength and/or low gait speed. RESULTS: The total prevalence of sarcopenia was 6.6% (45/679) in men and 1.7% (16/928) in women, the total prevalence of low muscle mass was 14.3% (97/679) in men and 5.2% (48/928) in women, and the total prevalence of low muscle performance was 25.6% (174/679) in men and 19.6% (182/928) in women. In men, the ORs (95% CIs) for sarcopenia, low muscle mass and low muscle performance were significantly lower in the AA group (sarcopenia: 0.29 [0.09-0.95], P = 0.041; low muscle mass: 0.21 [0.09-0.52], P = 0.001; and low muscle performance: 0.52 [0.28-0.97], P = 0.038). In women, the OR (95% CI) for low muscle performance was significantly lower in the AA group than in the other groups (0.48 [0.27-0.84], P = 0.010), whereas none of the ORs for sarcopenia and low muscle mass were significant. CONCLUSIONS: Older men with exercise habits in both adolescence and older age were at a lower risk of sarcopenia, low muscle mass and low muscle performance, whereas older women with exercise habits at both time periods were at a lower risk of low muscle performance.

Bone-Patellar Tendon-Bone Autograft Harvest Prolongs Extensor Latency during Gait 2 yr after ACLR.

PURPOSE: Bone-patellar tendon-bone (BPTB) graft harvest for anterior cruciate ligament reconstruction alters patellar tendon properties, which inflict poor quadriceps neuromuscular function. BPTB autografts are associated with higher rates of posttraumatic osteoarthritis, which in turn is associated with pathological gait. The purpose of this study was to investigate the latency between the time of peak quadriceps activity and the peak knee flexion moment during gait, between those with BPTB grafts ( n = 23) and other graft types (hamstring autograft or allografts, n = 54), 5 ± 2 months and 2 yr (25 ± 3 months) after anterior cruciate ligament reconstruction. We hypothesized that longer latencies would be observed in the BPTB graft group in the involved limb. We expected latencies to shorten over time. METHODS: Knee moments and quadriceps EMG were collected during gait, and vastus medialis, vastus lateralis, rectus femoris (RF), and quadriceps latencies were calculated. Linear mixed-effects models were used to compare latencies between graft types and over the two time points. RESULTS: The main effects of graft type were observed for vastus medialis ( P = 0.005) and quadriceps ( P = 0.033) latencies with the BPTB graft group demonstrating longer latencies. No main effects of graft type were observed for vastus lateralis ( P = 0.051) and RF ( P = 0.080) latencies. Main effects of time were observed for RF latency ( P = 0.022). CONCLUSIONS: Our hypothesis that the BPTB graft group would demonstrate longer extensor latency was supported. Contrary to our second hypothesis, however, latency only improved in RF and regardless of graft type, indicating that neuromuscular deficits associated with BPTB grafts may persist 2 yr after surgery. Persistent deficits may be mediated by changes in the patellar tendon's mechanical properties. Graft-specific rehabilitation may be warranted to address the long-term neuromechanical deficits that are present after BPTB graft harvest.

Identifying Gait Pathology after ACL Reconstruction Using Temporal Characteristics of Kinetics and Electromyography.

PURPOSE: Asymmetrical gait mechanics after anterior cruciate ligament reconstruction (ACLR) are associated with the development of posttraumatic knee osteoarthritis. Current measures of gait mechanics have focused heavily on peak magnitudes of knee kinematics, kinetics, and joint contact forces but have seldom considered the rate of knee loading, cumulative knee load, or the timing of motor input surrounding peaks. The purpose of this study was to introduce and describe novel metrics of gait using temporal characteristics of kinetics and EMG to identify neuromuscular deficits of the quadriceps in patients after ACLR. METHODS: Gait mechanics were assessed 6 months (n = 145) and 24 months (n = 116) after ACLR. External knee flexion rate of moment development (RMD) and knee flexion moment impulse (KFMI) leading up to the time of peak knee flexion moment (pKFM), peak RMD between initial contact to pKFM, and cumulative KFMI were calculated. Extensor latencies from the quadriceps, vastus medialis, vastus lateralis, and rectus femoris (time of pKFM - time of peak EMG activity) during the weight acceptance phase of gait were also calculated. Paired-sample t-tests (α = 0.05) were performed between limbs at both time points. RESULTS: Slower RMD, smaller KFMI, and longer extensor latencies in the involved compared with uninvolved limb were observed across all measures at 6 months (P < 0.005). At 24 months, RMDpeak was slower, and KFMI50ms, KFMI100ms, and KFMItotal were lower in the involved limb (P < 0.003), but no other asymmetries were found. CONCLUSIONS: Slower RMD, smaller KFMI, and prolonged extensor latencies may characterize neuromuscular deficits underlying aberrant gait mechanics early after ACLR. RMD, KFMI, and extensor latencies during gait should be considered in the future to quantify asymmetrical movement patterns observed after ACLR and as markers of recovery.