The Association of Free Testosterone with Sarcopenic Obesity in Community-Dwelling Older Men: A Cross-Sectional Study.

Background and Objectives: Sarcopenic obesity, a clinical condition coexisting with obesity and sarcopenia, is associated with a high risk of functional impairment, reduced quality of life, and increased mortality. A decline in age-related free testosterone (FT) levels has been reported to be associated with decreased muscle mass and muscle strength and increased fat mass. However, the association between low FT levels and risk of sarcopenic obesity has not been well studied. This study aimed to investigate the direct association between low FT levels and sarcopenic obesity. Materials and Methods: This cross-sectional study used data of 982 community-dwelling men aged 70-84 years from the Korean Frailty and Aging Cohort Study. Sarcopenia was defined according to the criteria of the Asian Group for Sarcopenia (AWGS) 2019. Obesity was defined as a body fat mass ≥28.3%. Participants who met both sarcopenia and obesity criteria were defined as having sarcopenic obesity. Low FT levels were defined as FT levels <17.35 pmol/L according to the Endocrine Society Clinical Practice Guidelines. Results: The prevalence of sarcopenia, obesity, and sarcopenic obesity was significantly higher in the low-FT group than in the normal-FT group. Low FT levels were significantly associated with a higher risk of obesity (odds ratio [OR], 2.09, 95% confidence interval [CI], 1.11-3.92), sarcopenia (2.57, 95% CI 1.08-6.10), and sarcopenic obesity (3.66, 95% CI 1.58-8.47) compared with the healthy control group. The risk of low appendicular skeletal muscle mass index (ASMI) (1.78, 95% CI 1.04-3.02) and high fat mass (1.92, 95% CI 1.12-3.31) was significantly higher in the low-FT group than in the normal-FT group. Conclusions: This study showed that low FT levels were associated with a higher risk of sarcopenic obesity. Low FT levels were mainly related to body composition parameters such as low ASMI and high fat mass.

Therapeutic Efficacy of Ultrasound-Guided Selective Nerve Block on Chronic Cervical Radiculopathy.

Background and Objectives: Cervical radiculopathy (CR) manifests as pain and sensorimotor disturbances in the upper extremities, often resulting from nerve root compression due to intervertebral disc herniation, degenerative changes, or trauma. While conservative treatments are initially preferred, persistent or severe cases may require surgical intervention. Ultrasound-guided selective nerve root block (SNRB) has emerged as a promising intervention for alleviating symptoms and potentially obviating the need for surgery. This study evaluates the therapeutic efficacy of ultrasound-guided SNRB in managing chronic CR, aiming to determine its potential in symptom relief and delaying or avoiding surgical procedures. Materials and Methods: A retrospective analysis was conducted on 720 outpatients treated for CR between October 2019 and March 2022. After excluding patients with traumatic CR, previous surgeries, malignancies, progressive neurological symptoms requiring immediate surgery, or inadequate conservative treatment, 92 patients who had experienced cervical radicular pain for more than three months and had failed to improve after more than six weeks of conservative treatment with VAS scores ≥ 5 were included. The patients underwent single or multiple ultrasound-guided SNRB procedures, involving the injection of dexamethasone and lidocaine under real-time ultrasound guidance. Symptom severity was assessed at the baseline, and at 4, 8, and 12 weeks post-procedure using the Visual Analog Scale (VAS). The data collected included age, sex, presence of neck and/or radicular pain, physical examination findings, recurrence of symptoms, improvement in symptoms, and whether surgical intervention was ultimately required. Statistical analyses were performed to identify the factors associated with symptom improvement or recurrence. Results: Significant symptom improvement was observed in 69 (75.0%) participants post-SNRB, with 55 (79.7%) showing improvement at 4 weeks, 11 (15.9%) at 8 weeks, and 3 (4.4%) at 12 weeks. Symptom recurrence, defined by an increase in VAS score accompanied by a pain flare lasting at least 24 h after a pain-free interval of at least one month, was noted in 48 (52.2%) patients. The presence of combined neck and radicular pain was a significant predictor of recurrence (p = 0.008). No significant associations were found between symptom relief and factors such as age, gender, initial pain severity, or MRI findings. Conclusions: Ultrasound-guided SNRB effectively manages chronic CR, providing substantial symptom relief and potentially reducing the need for surgical intervention. This technique offers a promising conservative treatment option, especially given its real-time visualization advantages and minimal radiation exposure.

Central obesity is associated with lower prevalence of sarcopenia in older women, but not in men: a cross-sectional study.

BACKGROUND: Obesity is a chronic disease that causes various medical health problems, increases morbidity, and reduces the quality of life. Obesity (especially central obesity) in older adults is expected to act with the development of sarcopenia. However, the relationship between obesity, central obesity, and sarcopenia remains controversial. This study aimed to investigate the impact of obesity on sarcopenia. METHODS: In this cross-sectional study, we used data from the Korean Frailty and Aging Cohort Study; 1,827 community-dwelling older adults (883 men and 944 women) aged 70-84 years were recruited. The Asian Working Group for Sarcopenia (AWGS) criteria were used to evaluate sarcopenia. Subjects with a low appendicular skeletal muscle mass index (ASMI; men: < 7.0 kg/m2, women: < 5.4 kg/m2) and either low handgrip strength (HGS; men: < 28 kg, women: < 18 kg) or low Short Physical Performance Battery (SPPB; ≤ 9) were diagnosed with sarcopenia. Obesity was defined as a body mass index (BMI) of ≥ 25 kg/m2, while central obesity was defined as WC measurements of ≥ 90 cm in men and ≥ 85 cm in women. Logistic regression analyses were performed to evaluate the impact of obesity and central obesity on sarcopenia and the parameters of sacropenia. RESULTS: In both sexes, the obese group, defined based on the BMI, had a significantly low prevalence of low ASMI (odds ratio [OR] = 0.14, 95% confidence interval CI = 0.10-0.20 in men, OR = 0.17, 95% CI = 0.12-0.25 in women) and sarcopenia (OR = 0.28, 95% CI = 0.16-0.50 in men, OR = 0.17, 95% CI = 0.08-0.35 in women) in the multivariable logistic regression analysis. In women, the central obese group had a low prevalence of sarcopenia (OR = 0.46, 95% CI = 0.27-0.77) in the multivariable logistic regression analysis. Meanwhile, the obese group had a significantly higher prevalence of low SPPB in women (OR = 1.75, 95% CI = 1.18-2.59). CONCLUSIONS: Obesity may have a protective effect on low ASMI and sarcopenia, as defined by the AWGS criteria. Central obesity was associated with a low prevalence of sarcopenia in women only. However, obesity did not have a positive impact on functional parameters of sarcopenia including muscle strength and physical performance.

Physicochemical characterization of dapagliflozin and its solid-state behavior in stress stability test.

As an active pharmaceutical ingredient, dapagliflozin propanediol monohydrate (D-PD) has been used in the solvated form consisting of dapagliflozin compounded with (S)-propylene glycol and monohydrate at a 1:1:1 ratio. However, dapagliflozin propanediol loses the solvent's reduced lattice structure at slightly higher temperatures. Due to its sensitive solid-state stability, the temperature and humidity are strictly controlled during the production and storage of dapagliflozin. Thus, crystalline molecular complexes containing pharmaceutical salts, solvates, monohydrates, and cocrystals have recently been developed as alternative strategies. This study investigated the dapagliflozin free base (D-FB), D-PD, and dapagliflozin l-proline cocrystals (D-LP). Their solid-state behavior was also evaluated in stress stability studies. The compounds were analyzed using scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, dynamic vapor sorption (DVS), and powder rheology testing. In addition, Carr's index, the Hausner ratio, contact angle, and intrinsic dissolution rate were calculated. Dapagliflozin exhibited distinct physical properties depending upon the differences in solid form and also showed significant differences in solid-state behavior in the stress stability test. In conclusion, D-LP was superior to D-FB or D-PD in physicochemical and mechanical properties.

Potential Therapeutic Strategies and Substances for Facial Nerve Regeneration Based on Preclinical Studies.

Despite advances in microsurgical technology and an improved understanding of nerve regeneration, obtaining satisfactory results after facial nerve injury remains a difficult clinical problem. Among existing peripheral nerve regeneration studies, relatively few have focused on the facial nerve, particularly how experimental studies of the facial nerve using animal models play an essential role in understanding functional outcomes and how such studies can lead to improved axon regeneration after nerve injury. The purpose of this article is to review current perspectives on strategies for applying potential therapeutic methods for facial nerve regeneration. To this end, we searched Embase, PubMed, and the Cochrane library using keywords, and after applying exclusion criteria, obtained a total of 31 qualifying experimental studies. We then summarize the fundamental experimental studies on facial nerve regeneration, highlighting recent bioengineering studies employing various strategies for supporting facial nerve regeneration, including nerve conduits with stem cells, neurotrophic factors, and/or other therapeutics. Our summary of the methods and results of these previous reports reveal a common feature among studies, showing that various neurotrophic factors arising from injured nerves contribute to a microenvironment that plays an important role in functional recovery. In most cases, histological examinations showed that this microenvironmental influence increased axonal diameter as well as myelination thickness. Such an analysis of available research on facial nerve injury and regeneration represents the first step toward future therapeutic strategies.

Interleukin-6 Receptor Polymorphisms Contribute to the Neurological Status of Korean Patients with Ischemic Stroke.

To investigate the contribution of the interleukin-6 receptor (IL-6R) gene single nucleotide polymorphisms (SNPs) to the neurological status of Korean patients with ischemic stroke (IS), two SNPs of the IL-6R gene (rs4845617, 5 UTR; rs2228144, Ala31Ala) were selected. IS patients were classified into clinical phenotypes according to two well-defined scores: the National Institutes of Health Stroke Survey (NIHSS) and the Modified Barthel Index scores. There were 121 IS patients and 291 control subjects. The SNP rs4845617 significantly contributed to the neurological status of patients with IS (P = 0.011 in codominant model 2, P = 0.006 in recessive model, and P = 0.008 in log-additive model). Allele frequencies of rs4845617 and rs2228144 demonstrated no significant difference in IS patients and controls. The AG and GG haplotypes differed between the NIHSS 1 (NIHSS scores < 6) group and the NIHSS 2 (NIHSS scores ≥ 6) group in patients with IS (P = 0.014, P = 0.0024). These results suggest that rs4845617 of the IL-6R gene is associated with the neurologic status of Korean patients with IS.

Association between BH3 interacting domain death agonist (BID) gene polymorphism and ossification of the posterior longitudinal ligament in Korean population.

The purpose of this study was to investigate single nucleotide polymorphisms (SNPs) of the BH3 interacting domain death agonist (BID) gene as a risk factor in Korean patients with ossification of the posterior longitudinal ligament (OPLL). To investigate the genetic association, two coding SNPs (rs8190315, Ser10Gly; rs2072392, Asp60Asp) of BID were genotyped in 157 OPLL patients and 209 control subjects. SNPStats, SNPAnalyzer Pro, Helixtree, and Haploview 4.2 programs were used for association analysis. Multiple logistic regression models (codominant, dominant, and recessive) were calculated for the odds ratios (ORs), 95 % confidence intervals (CIs), and corresponding P values. For multiple testing, Bonferroni correction was performed. After Bonferroni correction, genotype analysis of both rs8190315 and rs2072392 showed association between the OPLL group and the control group in the codominant model (P = 0.042, OR 1.86, 95 % CI 1.10-3.15). A complete linkage disequilibrium block was estimated between the two SNPs. Both of the G allele of rs8190315 and C allele of rs2072392 were strongly associated with an increased risk in the development of OPLL (P = 0.0052, OR 2.66, 95 % CI 1.51-4.68). These results suggest that BID is associated with OPLL, and both the G allele of a missense SNP (rs8190315, Ser10Gly) and C allele of a synonymous SNP (rs2072392, Asp60Asp) are risk factors for the development of OPLL in Korean population.

Obesity, Physical Performance, Balance Confidence, and Falls in Community-Dwelling Older Adults: Results from the Korean Frailty and Aging Cohort Study.

Obesity affects physical functions in numerous ways. We aimed to evaluate the association between obesity and falls, physical performance, and balance confidence in community-dwelling older adults. Using first-year baseline data from the Korean Frailty and Aging Cohort Study, 979 older adults were included. General obesity was defined based on the body mass index and body fat percentage, whereas central obesity was classified based on the waist circumference and waist-to-height ratio. Data regarding fall history and balance confidence were acquired using self-questionnaires, and a timed up-and-go test was performed to measure balance-related physical performance. Overall, 17.3% of participants experienced falls in the previous year. Central obesity, as determined by waist circumference (odds ratio, 1.461; 95% confidence interval, 1.024-2.086; p-value, 0.037) and by waist-to-height ratio (odds ratio, 1.808; 95% confidence interval, 1.015-3.221; p-value, 0.044) was significantly associated with falls. Interestingly, general obesity, measured by body fat percentage, was protective against fall-related fractures (odds ratio, 0.211; 95% confidence interval, 0.072-0.615; p-value, 0.004). Participants with central obesity had poorer physical performances in the timed up-and-go test (odds ratio, 2.162; 95% confidence interval, 1.203-3.889; p-value, 0.010) and lower balance confidence according to the Activities-specific Balance Confidence scale (odds ratio, 1.681; 95% confidence interval, 1.153-2.341; p-value 0.007). In conclusion, assessment of central obesity, particularly waist circumference, should be considered as a screening strategy for falls, and older adults with a high waist circumference should receive advice on fall prevention.

The Impact of the Physical Activity Level on Sarcopenic Obesity in Community-Dwelling Older Adults.

Previous studies have reported that low levels of physical activity result in sarcopenic obesity (SO). However, the effects of specific intensities of physical activity on SO and the optimal amount of physical activity for lowering the prevalence of SO have not been well studied. This study aimed to identify the effects of physical activity levels and intensity on SO and the optimal amount of physical activity related to a lower prevalence of SO. This cross-sectional study used data from the nationwide Korean Frailty and Aging Cohort Study (KFACS), which included 2071 older adults (1030 men, 1041 women). SO was defined according to the criteria of the European Society for Clinical Nutrition Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO). Multivariate logistic regression analysis was performed to investigate the association between the physical activity level and SO. The high activity group had a significantly lower prevalence of SO than the non-high activity (low and moderate activity) group. On the other hand, moderate-intensity physical activity was associated with a lower prevalence of SO. A total physical activity energy expenditure of > 3032 kcal/week (433 kcal/day) for men and 2730 kcal/week (390 kcal/day) for women was associated with a reduced prevalence of SO. The high physical activity and total physical energy expenditure described above may be beneficial for reducing the prevalence of SO.

Nanostructural and nanomechanical responses of collagen fibrils in the collagenase-induced Achilles tendinitis rat model.

Achilles tendons are vulnerable to acute or chronic injuries that lead to inflammation. We investigated nanostructural and nanomechanical changes in collagen fibrils from rat Achilles tendons over a period of 9 weeks after injury using atomic force microscopy (AFM). To evaluate the nanostructural changes in Achilles tendons, we measured the diameter and D-banding of collagen fibrils by AFM. And the adhesion forces, which were related to cross-linking of collagen, were calculated from the retraction process of a force-distance curve. We successfully observed the time course of changes in collagen fibrils during healing using AFM. The diameters and D-banding in healed tendons were similar to those of uninjured tendons at 9 weeks after injury, but the adhesion forces remained different from those of uninjured tendons. Our AFM results depicted the minute changes in Achilles tendon surface by natural healing quite well, even drawbacks to naturally healed tendon. Understanding changes in collagen cross-linking and structure while healing will lead to better understanding of healing mechanisms and subsequent improvements in treatment. And AFM can be applied as powerful tool to evaluate structural and property changes in collagen fibrils before and after injury and/or treatment in Achilles tendon.

Acute cricopharyngeal achalasia after general anesthesia in myotonic dystrophy: A case report.

RATIONALE: Myotonic dystrophy type 1 (DM-1) is a progressive multisystem genetic disorder that causes myotonia and both distal limb and facial/neck muscle weakness by expanding the CTG repeats of the DMPK gene in chromosome 19q13.3. General anesthesia is indicated in DM-1 patients owing to their sensitivity to anesthetic drugs such as opioids, hypnotics, and neuromuscular blocking agents. PATIENT CONCERNS: A 48-year-old male patient underwent a laparoscopic cholecystectomy for gallstones under general anesthesia. He experienced sudden cardiac arrest and respiratory failure the day after surgery. After a thorough review of past medical history, we recognized that 15 years prior, he had been diagnosed with classic type DM-1, but the diagnosis was not self-reported before general anesthesia. Symptoms of severe dysphagia developed subsequently. In a videofluoroscopic swallowing study (VFSS), we observed abrupt aggravation of myotonic dysphagia after general anesthesia. VFSS revealed cricopharyngeal opening dysfunction, with a remaining large residue in the pyriform sinus, resulting in a severe cricopharyngeal achalasia pattern. DIAGNOSIS: Acute cricopharyngeal achalasia after general anesthesia. INTERVENTION AND OUTCOME: The patient underwent a dysphagia rehabilitation program that included cricopharyngeal opening exercises and functional electrical stimulation. However, no significant improvement was observed in the cricopharyngeal achalasia in a 3-month follow-up VFSS. LESSONS: Low body temperature and anesthetic medications such as opioids and hypnotic agents can induce myotonia in the cricopharyngeal muscle.

Neutrophil-to-Lymphocyte Ratio as a Predictor of Short-Term Functional Outcomes in Acute Ischemic Stroke Patients.

Background: Neutrophil-to-lymphocyte ratio (NLR), a systemic inflammatory biomarker, has been associated with poorer outcomes in acute ischemic stroke patients. The present study was designed to expand these findings by investigating the association between NLR and short-term functional outcomes in acute ischemic stroke patients. Methods: This retrospective study evaluated patients within 7 days after the onset of acute ischemic stroke. Stroke severity on admission was measured using the National Institutes of Health Stroke Scale (NIHSS). The functional outcomes were assessed using the Berg Balance Scale (BBS), Manual Function Test (MFT), the Korean version of the modified Barthel Index (K-MBI), and the Korean Mini-Mental State Examination (K-MMSE) within 2 weeks of stroke onset. The modified Rankin Scale (mRS) was evaluated at discharge. Results: This study included 201 patients, who were grouped into three NLR tertiles (<1.84, 1.84−2.71, and >2.71) on admission. A multivariate analysis showed that the top tertile group (NLR > 2.71) had significantly higher risks of unfavorable outcomes on the K-MBI (p = 0.010) and K-MMSE (p = 0.029) than the bottom tertile group (NLR < 1.84). Based on the optimal cut-off values from a receiver operating characteristic curve analysis, a higher NLR was significantly associated with higher NIHSS scores (p = 0.011) and unfavorable outcomes on the K-MBI (p = 0.002) and K-MMSE (p = 0.001). Conclusions: A higher NLR is associated with poorer short-term functional outcomes in acute ischemic stroke patients.

Impact of Vitamin B12 Insufficiency on the Incidence of Sarcopenia in Korean Community-Dwelling Older Adults: A Two-Year Longitudinal Study.

The longitudinal effect of B12 insufficiency on sarcopenia has not yet been investigated in older adults. We aimed to study the impact of B12 levels on alterations in muscle mass, function and strength over two years. Non-sarcopenic older adults (n = 926) aged 70-84 were included. Using the Korean Frailty and Aging Cohort Study, this two-year longitudinal study used data across South Korea. The tools used for assessing muscle criteria were based on the Asian Working Group for Sarcopenia guidelines. Participants were divided into the insufficiency (initial serum B12 concentration < 350 pg/mL) and sufficiency groups (≥350 pg/mL). Logistic regression analyses were performed to evaluate the effect of initial B12 concentration on sarcopenia parameters over a two-year period. In women, multivariate analysis showed that the B12 insufficiency group had a significantly higher incidence of low SPPB scores (odds ratio [OR] = 3.28, 95% confidence interval [CI] = 1.59-6.76) and sarcopenia (OR = 3.72, 95% CI = 1.10-12.62). However, the B12 insufficiency group did not have a greater incidence of sarcopenia or other parameters in men. Our findings suggest B12 insufficiency negatively impacts physical performance and increases the incidence of sarcopenia only in women.

Association Between Clinical Symptoms, Electrodiagnostic Findings, Clinical Outcome, and Prodromal Symptoms in Patients With Bell's Palsy.

OBJECTIVE: This study aimed to determine which prodromal symptoms frequently occur in patients with Bell's palsy and evaluate the association between these symptoms and clinical severity of paresis or the severity of facial nerve injury. MATERIALS AND METHODS: The study included 86 patients with Bell's palsy between August 2018 and April 2020. Severity levels of Bell's palsy and facial nerve damage were evaluated using the House-Brackmann (H-B) grading scale and electrodiagnostic study, respectively. Subsequently, a self-reported questionnaire on prodromal symptoms was administered. To assess the degree of recovery, the H-B grade was reported at 9 weeks and 6 months after the onset of paralysis. RESULTS: The most common prodromal symptoms were postauricular pain, sensory decline in the tongue, headache on the affected side, myalgia, facial sensory decline on the affected side, taste impairment, and dry eye. Taste impairment was significantly correlated with severe facial paralysis reported at 9 weeks after onset (P < .05) and was not related to the severity of paresis assessed at initial examination or 6 months after onset or on electrodiagnostic findings. CONCLUSIONS: The prodromal symptoms of Bell's palsy were not associated with the severity of facial nerve injury in an electrodiagnostic study. Taste impairment was related to clinical severity of paralysis at subacute stage, 9 weeks after onset, but it was not associated with long-term prognosis.

Effects of extracorporeal shockwave therapy on nanostructural and biomechanical responses in the collagenase-induced Achilles tendinitis animal model.

The aim of this study was to quantitatively investigate the effects of extracorporeal shockwave therapy (ESWT) on the nanostructure and adhesion force of collagen fibrils in a rat model of collagenase-induced Achilles tendinitis (CIAT) using histology and atomic force microscopy. A total of 45 rats were divided into experimental groups of three rats each: a control group, 27 CIAT rats with nine time points, and 15 ESWT rats with five time points. Progressive changes in nanostructure including the fibrillary diameter and D-periodicity, and biomechanical properties including the fibrillary adhesion forces in each healing phase were investigated over a 5-week period after collagenase injection. On postoperative day 3, CIAT rats showed granulomatous tissue associated with subacute inflammation, and a deterioration in nanostructure and mechanical properties compared to controls. On postoperative day 12, the ESWT group showed increased vascularity, fibroblastic activity, lymphocyte and plasma cell infiltration, dense histocytes, and disorganization of the fibers compared to the CIAT group. The ESWT group showed and improvement in nanostructure and mechanical properties compared to controls, while the CIAT group showed a deterioration in nanostructure and mechanical properties compared to controls. On postoperative day 26, the ESWT group showed 30% inflamed tissue and 70% fibrotic tissue, while the CIAT group showed chronic inflammation. By the end of the experiments, in both groups the changes had reversed and the tissues were similar in appearance to those in the control group. Following ESWT the deformed and irregular collagen network returned to a well-aligned normal collagen network nanostructure. These results suggest that ESWT may promote the healing response in Achilles tendinitis.

A pro-inflammatory diet increases the risk of sarcopenia components and inflammatory biomarkers in postmenopausal women.

Inflammation is a risk factor for muscle wasting. The dietary inflammatory index (DII) is a tool used to predict the inflammatory potential of an individual's diet. We hypothesized that consuming a potentially pro-inflammatory diet may be associated with a decreased sarcopenia component in postmenopausal women. Therefore, this study aimed to investigate the association between DII, sarcopenia components (muscle mass, muscle strength, physical performance), and inflammatory biomarkers in postmenopausal women. This cross-sectional study included 70 healthy postmenopausal women aged 50 to 80 years. The DII was calculated based on 3-day food records, and participants were divided into 3 groups according to their DII score. Skeletal muscle mass was measured using dual-energy X-ray absorptiometry. Muscle strength was assessed based on handgrip and leg muscle strength. Associations between DII and sarcopenia components and inflammatory biomarkers were determined using analysis of covariance and a general linear model after adjusting for potential confounders. The DII scores ranged from -6.08 to 5.82. Higher DII scores were significantly associated with decreased appendicular skeletal muscle (ASM) (ß = -0.520), height-adjusted ASM (ß = -0.116), weight-adjusted ASM (ß = -0.469), knee extensor strength (ß = -3.175), knee flexion strength (ß = -1.941), increased body fat percentage (ß = 1.238), and erythrocyte sedimentation rate (ß = 5.582) (all P < .05). The present study confirmed a lower DII score, indicating that an anti-inflammatory diet is associated with higher muscle mass and strength and lower levels of inflammatory biomarkers.

Effect of multimodal intervention care on cachexia in patients with advanced cancer compared to conventional management (MIRACLE): an open-label, parallel, randomized, phase 2 trial.

BACKGROUND: Cancer cachexia (CC) is a multifactorial process characterized by progressive weight loss, muscle mass, and fat tissue wasting, which adversely affects the quality of life and survival of patients with advanced stages of cancer. CC has a complex and multifactorial pathophysiology, and there is no established standard treatment. Therefore, it is often irreversible and a single treatment modality is unlikely to suppress its progression. We are conducting a randomized trial to investigate the efficacy and safety of a multimodal intervention compared to the best supportive care for patients who received palliative chemotherapy. METHODS: Patients with lung or gastrointestinal cancers undergoing palliative chemotherapy are eligible. Patients are randomized into a multimodal intervention care (MIC) arm versus a conventional palliative care (CPC) arm. MIC includes ibuprofen, omega-3-fatty acid, oral nutritional supplement, weekly physical, psychiatric assessment, nutritional counseling, and complementary and alternative medicine. CPC includes basic nutritional counseling and megestrol acetate as needed (i.e., anorexia ≥ grade 2). All interventions are performed for 12 weeks per subject. The co-primary outcomes are change (kg) in total lean body mass and handgrip strength (kg) from the baseline. A total of 112 patients will be assigned to the two arms (56 in each group). DISCUSSION: The purpose of this study is to evaluate the effect of MIC in preventing or alleviating CC in patients who underwent palliative chemotherapy. As there is no established single treatment for CC, it is expected that the results of this clinical trial will provide new insights to significantly improve the quality of life of patients with cancer. Considering the complex mechanisms of cachexia, the effect of MIC rather than a single specific drug is more promising. In this study, we did not overly restrict the type of cancer or chemotherapy. Therefore, we attempted to measure the effects of complex interventions while preserving clinical situations. Thus, it is expected that the results of this study can be applied effectively to real-world practice. TRIAL REGISTRATION: This clinical trial was registered in the Clinical Research Information Service (KCT0004967), Korean Clinical Trial Registry on April 27, 2020, and ClinicalTrial.gov (NCT04907864) on June 1, 2021.

Association between interleukin 15 receptor, alpha (IL15RA) polymorphism and Korean patients with ossification of the posterior longitudinal ligament.

OBJECTIVES: Recently, a number of evidences have been reported concerning the genetic factor involved in the development of ossification of the posterior longitudinal ligament (OPLL). The purpose of this study was to investigate single nucleotide polymorphisms (SNPs) of the interleukin 15 receptor, alpha (IL15RA) gene as a risk factor in Korean patients with OPLL. DESIGN: To investigate the genetic association, two coding SNPs (rs2296139, Thr73Thr; rs2228059, Asn182Thr) in IL15RA were genotyped in 166 OPLL patients and 230 control subjects. SNPStats, SNPAnalyzer, and Helixtree programs were used for association analysis. RESULTS: In the present study, we found the association between a missense SNP (rs2228059) and the risk of OPLL in codominant (p = 0.0028, OR = 1.58, 95% CI = 1.17-2.14), dominant (p = 0.0071, OR = 1.82, 95% CI = 1.17-2.82), and recessive models (p = 0.036, OR = 1.79, 95% CI = 1.04-3.09). The frequency of rs2228059 allele was significantly associated with the susceptibility of OPLL (p = 0.0043, OR = 1.52, 95% CI = 1.14-2.02). After Bonferroni correction, the missense SNP (rs2228059, Asn182Thr) still had significant correlations (p = 0.0056 in codominant model; p = 0.0142 in dominant model; p = 0.0086 in allele analysis). Haplotype variation in IL15RA was associated with OPLL (global haplotype test, p = 0.025). CONCLUSIONS: These results suggest that IL15RA polymorphism may be associated with the susceptibility of OPLL in Korean population.

Changes in collagen fibril pattern and adhesion force with collagenase-induced injury in rat Achilles tendon observed via AFM.

The Achilles tendon consists mainly of type I collagen fibers that contain collagen fibrils. When the Achilles tendon is injured, it is inflamed. The collagenase-induced model has been widely used to study tendinitis. The major advantages of atomic force microscopy (AFM) over conventional optical and electron microscopy for bio-imaging include its non-requirement of a special coating and vacuum, and its capability to perform imaging in all environments. AFM force-distance measurements have become a fundamental tool in the fields of surface chemistry, biochemistry and materials science. Therefore, the changes in the ultrastructure and adhesion force of the collagen fibrils on the Achilles tendons of rats with Achilles tendinitis were observed using AFM. The changes in the structure of the Achilles tendons were evaluated based on the diameter and D-banding of the collagen fibrils. Collagenase-induced Achilles tendinitis was induced with the injection of 30 microl crude collagenase into 7-week-old male Sprague-Dawley rats. The animals were each sacrificed on the first, second, third, fifth and seventh day after the collagenase injection. The normal and injured Achilles tendons were fixed in 4% buffered formalin and dehydrated with increasing concentrations of ethanol. AFM was performed using the non-contact mode at the resolution of 512 x 512 pixels, with a scan speed of 0.8 line/sec. The adhesion force was measured via the force-distance curve that resulted from the interactions between the AFM tip and the collagen fibril sample using the contact mode. The diameter of the collagen fibrils in the Achilles tendons significantly decreased (p < 0.05) after the collagenase injection, and the pattern of the D-banding of the collagen fibrils was similar to that of the diameter changes. The adhesion force decreased until the fifth day after the collagenase injection, but increased on the seventh day after the collagenase injection (p < 0.0001).

Atypical supernumerary phantom limb and phantom limb pain in two patients with pontine hemorrhage.

Phantom limbs are usually observed after amputation of extremities. In patients after a stroke, a similar but rarely occurring phenomenon consisting of the patient experiencing the presence of an additional limb has been described. This phenomenon, generally called supernumerary phantom limb (SPL), may be caused by lesions in the right or left cerebral hemisphere, but has been predominantly reported in patients who have had a right hemispheric stroke. We report two cases of atypical SPL and phantom limb pain (PLP) after pontine hemorrhage. The patients were treated conservatively and their symptoms lasted more than 1 month. This is the first report of SPLs after left pontine hemorrhage, and phantom perception and pain lasted longer than those in previously observed cases. Our results indicate that SPL may be more common than reported; therefore, thorough examinations are essential for the care of stroke patients.