Randomized, double-blind, four-arm pilot study on the effects of chicken essence and type II collagen hydrolysate on joint, bone, and muscle functions.

BACKGROUND: Knee osteoarthritis (OA) is a leading cause of disability among older adults. Medical and surgical treatments are costly and associated with side effects. A natural nutraceutical, collagen hydrolysate, has received considerable attention due to its relieving effects on OA-associated symptoms. This study investigated the effects of hydrolyzed collagen type II (HC-II) and essence of chicken (BRAND'S Essence of Chicken) with added HC-II (EC-HC-II) on joint, muscle, and bone functions among older adults with OA. METHODS: Patients (n = 160) with grade 1-3 knee OA according to the Kellgren-Lawrence classification system, joint pain for ≥ 3 months, and a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score of > 6 were randomly assigned with equal probability to consume EC-HC-II, HC-II, glucosamine HCl, or a placebo for 24 weeks in combination with resistance training. Outcome measurements were WOMAC score, visual analogue scale (VAS) pain score, grip strength, fat-free mass (FFM), and bone mass. RESULTS: All groups exhibited similar levels of improvement in WOMAC index scores after 24 weeks. HC-II significantly reduced VAS pain score by 0.9 ± 1.89 (p = 0.034) after 14 days. A repeated-measures analysis of variance showed that HC-II reduced pain levels more than the placebo did (mean ± standard error: - 1.3 ± 0.45, p = 0.021) after 14 days; the EC-HC-II group also had significantly higher FFM than the glucosamine HCl (p = 0.02) and placebo (p = 0.017) groups and significantly higher grip strength than the glucosamine HCl group (p = 0.002) at 24 weeks. CONCLUSION: HC-II reduces pain, and EC-HC-II may improve FFM and muscle strength. This suggests that EC-HC-II may be a novel holistic solution for mobility by improving joint, muscle, and bone health among older adults. Large-scale studies should be conducted to validate these findings. TRIAL REGISTRATION: This trial was retrospectively registered at ClinicalTrials.gov (NCT04483024).

Risk factors of recurrent secondary hyperparathyroidism after adequate primary surgical treatment.

Background: Secondary hyperparathyroidism (SHPT) is a common condition in patients with end-stage renal disease (ESRD) who are on dialysis. Parathyroidectomy is a treatment for patients when medical therapy has failed. Recurrence may occur and is indicated for further surgery in the era of improved quality of care for ESRD patients. Methods: We identified, 1060 patients undergoing parathyroidectomy from January, 2011 to June, 2020. After excluding patients without regular check-up at our institute, primary hyperparathyroidism, or malignancy, 504 patients were enrolled. Sixty-two patients (12.3%, 62/504) were then excluded due to persistent SHPT even after the first parathyroidectomy. We aimed to identify risk factors for recurrent SHPT after the first surgery. Results: During the study period, 20% of patients who underwent parathyroidectomy at our institute (in, 2019) was due to recurrence after a previous parathyroidectomy. There were 442 patients eligible for analysis of recurrence after excluding patients with the persistent disease (n = 62). While 44 patients (9.95%) had recurrence, 398 patients did not. Significant risk factors for recurrent SHPT within 5 years after the first parathyroidectomy, including dialysis start time to first operation time < 3 years (p = 0.046), postoperative PTH >106.5 pg/mL (p < 0.001), and postoperative phosphorus> 5.9 mg/dL (p = 0.016), were identified by multivariate analysis. Conclusions: The starting time of dialysis to first operation time < 3 years in the patients with dialysis, postoperative PTH> 106.5 pg/mL, and postoperative phosphorus> 5.9 mg/dL tended to have a higher risk for recurrent SHPT within 5 years after primary treatment.

Ketoanalogues Supplemental Low Protein Diet Safely Decreases Short-Term Risk of Dialysis among CKD Stage 4 Patients.

Background: Rigid dietary controls and pill burden make a very-low protein (0.3−0.4 g/kg body weight per day), vegetarian diet supplemented with ketoanalogues of amino acids (sVLPD) hard to follow in the long-term. This study aimed to evaluate whether a ketoanalogue supplemental low-protein diet (sLPD) (0.6 g/kg body weight per day) could also reduce the risks of dialysis among CKD stage 4 patients. Methods: Patients aged >20 years with a diagnosis of stage 4 CKD who subsequently received ketosteril treatment, which is the most commonly used ketoanalogue of essential amino acids, between 2003 and 2018 were identified from the Chang Gung Research Database (CGRD). Then, these individuals were divided into two groups according to the continuation of ketosteril for more than three months or not. The primary outcome was ESKD requiring maintenance dialysis. Results: With one-year follow-up, the continuation group (n = 303) exhibited a significantly lower incidence of new-onset end-stage kidney disease (ESKD) requiring maintenance dialysis (6.8% vs. 10.4%, hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.41−0.94) in comparison to the discontinuation group (n = 238). Conclusions: This study demonstrated that initiating sLPDs since CKD stage 4 may additionally reduce the short-term risks of commencing dialysis without increasing CV events, infections, or mortality.

Supplementation with Folic Acid and Cardiovascular Outcomes in End-Stage Kidney Disease: A Multi-Institution Cohort Study.

BACKGROUND: Folate is a water-soluble vitamin and is essential for maintaining cell functions. Dialysis removes folate, and folate deficiency is reported in patients with end-stage kidney disease (ESKD). However, there is no consensus as to the appropriate dosage of folate supplements and their advantages and disadvantages for patients with ESKD. METHODS: This study was based on the electronic medical records of the Chang Gung Research Database (CGRD) of the Chang Gung Medical Foundation. We included patients who were diagnosed with ESKD, initiated hemodialysis, and were given folic acid supplements at any point from 1 January 2001 to 31 December 2019. The patients were divided into weekly and daily folic acid supplementation groups. We reduced the effects of confounding through the inverse probability of treatment weighting based on the propensity score. RESULTS: We identified 2081 and 954 newly diagnosed patients with ESKD, who received daily and weekly folic acid supplements. The mean follow-up time was 5.8 years, and the event rates of arteriovenous access thrombosis were 17.0% and 23.6% in the daily and weekly folic acid supplementation groups (sub-distribution hazard ratio = 0.69, 95% confidence interval = 0.61 to 0.77), respectively. Neither group significantly differed in the occurrence of other clinical events, such as major cardiovascular cardiac events (e.g., myocardial infarction and ischemic stroke), all-cause mortality, cardiovascular death, infection death, malignancy, and adverse effects. CONCLUSION: a daily 5 mg folic acid supplementation might result in a lower event rate of arteriovenous access thrombosis in patients with ESKD than weekly folic acid supplementation. Further prospective studies are warranted to explore the preventive effect of folate on thrombosis.

Supplemented Low-Protein Diet May Delay the Need for Preemptive Kidney Transplantation: A Nationwide Population-Based Cohort Study.

BACKGROUND: Although several studies suggest the benefit of a low-protein diet supplemented with amino acids and keto acids (sLPD) in delaying the initiation of hemodialysis, evidence on whether these nutritional approaches could delay the timing of preemptive transplantation is lacking. METHODS: Retrospective nationwide cohort study, from Taiwan's National Health Insurance Research Database. Patients having undergone a first preemptive kidney transplantation between 2001 and 2017 were identified and divided into two groups according to the presence of sLPD treatment or not. The primary outcome was the time between the diagnosis of advanced CKD and transplantation. Secondary outcomes were post-transplantation adverse events. RESULTS: A total of 245 patients who received their first preemptive kidney transplantation were identified from the nationwide database; 63 of them had been on an sLPD prior to transplantation (sLPD group). The duration between the day of advanced CKD diagnosis and the day of transplantation was significantly longer in the sLPD group compared with the non-sLPD group (median duration: 345 vs. 220 days, p = 0.001). The risk of post-transplantation adverse events did not differ between the two groups. CONCLUSIONS: Within the limits of its observational, retrospective design, this is the first study to suggest that nutritional management with sLPDs can safely delay the timing of preemptive kidney transplantation.

Advanced Chronic Kidney Disease with Low and Very Low GFR: Can a Low-Protein Diet Supplemented with Ketoanalogues Delay Dialysis?

BACKGROUND: Previous studies have demonstrated that dietary therapy can delay the initiation of dialysis, but little research has investigated whether patients with very poor renal function would benefit from a dietary therapy. METHODS: This study was performed by using the Chang Gung Research Database (CGRD), which is based on the largest medical system in Taiwan. Patients with estimated glomerular filtration rates (eGFR) < 15 mL/min/1.73 m2 between 2001 and 2015 with more than 3 months of low-protein diet supplemented with ketoanalogues (sLPD) were extracted (Ketosteril group). We then assigned five patients without any sLPD to match one patient of the Ketosteril group (comparison group). Both groups were followed up for 1 year for the initiation of dialysis and rates of major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: The Ketosteril group (n = 547), compared with the comparison group (n = 2735), exhibited a lower incidence of new-onset dialysis (40.2% vs. 44.4%, subdistribution hazard ratio (SHR): 0.80, 95% confidence interval (CI): 0.70-0.91) and MACCEs (3.7% vs. 5.9%, HR: 0.61, 95% CI: 0.38-0.97). The beneficial effect of an sLPD did not differ in patients with a baseline eGFR < 5 mL/min/1.73 m2. CONCLUSION: Even among patients with extremely low eGFR, sLPD treatment can safely delay the need for dialysis.

Mitochondrial lipoylation integrates age-associated decline in brown fat thermogenesis.

Thermogenesis in brown adipose tissue (BAT) declines with age; however, what regulates this process remains poorly understood. Here, we identify mitochondria lipoylation as a previously unappreciated molecular hallmark of aged BAT in mice. Using mitochondrial proteomics, we show that mitochondrial lipoylation is disproportionally reduced in aged BAT through a post-transcriptional decrease in the iron-sulfur (Fe-S) cluster formation pathway. A defect in the Fe-S cluster formation by the fat-specific deletion of Bola3 significantly reduces mitochondrial lipoylation and fuel oxidation in BAT, leading to glucose intolerance and obesity. In turn, enhanced mitochondrial lipoylation by α-lipoic acid supplementation effectively restores BAT function in old mice, thereby preventing age-associated obesity and glucose intolerance. The effect of α-lipoic acids requires mitochondrial lipoylation via the Bola3 pathway and does not depend on the anti-oxidant activity of α-lipoic acid. These results open up the possibility to alleviate the age-associated decline in energy expenditure by enhancing the mitochondrial lipoylation pathway.

Incidence of second hip fractures and associated mortality in Taiwan: A nationwide population-based study of 95,484 patients during 2006-2010.

OBJECTIVES: The aim of the study is was to determine the incidence and mortality of second hip fracture using a nationwide database. PATIENTS AND METHODS: A nationwide epidemiological study was conducted using the Taiwan National Health Insurance Research Database from 2001 to 2011. Patients older than 50 years with hip fractures from 2006 to 2011 were included in the study. A total of 95,484 hip fractures were identified, with subsequent second hip fracture occurred in 4102 of them. RESULTS: The incidence rate ratio of second hip fracture showed a 7.13 fold of risk of further hip fracture in 3 months, 5.21 fold in one year, and remained more than 2 fold in the end of 6th year when compared with the general population. The 6-year cumulative incidence of a second hip fracture was higher in female (8.0%) than in male (6.2%). A significantly higher 1-year mortality rate was seen after a second hip fracture (18.8%) compared to the first hip fracture (14.1%) (p < 0.05). Men had higher 1- and 5-year mortality rates after second hip fractures (12.1% and 41.2%, respectively) than women (17.4% and 47.3%, respectively). CONCLUSIONS: Patients with hip fractures would have a 2-7 fold of risk of a second fracture within 6 years. Women were more prone to a second hip fracture than men but men had a higher mortality rate.

Treatment of melasma with mixed parameters of 1,064-nm Q-switched Nd:YAG laser toning and an enhanced effect of ultrasonic application of vitamin C: a split-face study.

Melasma is an acquired pigment disorder showing symmetrical hyperpigmentation of the face characterized by light to dark brown patches with indistinct borders on both cheeks. Melasma is prevalent in middle-aged women with harmless hormone imbalances. It is also known as the mask of pregnancy and is prevalent in most child-bearing women. It fluctuates month by month, and yet, there is no promising treatment. The Q-switched neodymium-doped yttrium aluminum garnet (QS-Nd:YAG) laser (1,064-nm wavelength) was introduced in Asia years ago for both skin toning and treatment of facial pigment. This low-fluence, 1,064-nm QS-Nd: YAG laser also reportedly improved melasma. Adjunctive treatments such as vitamin C iontophoresis or chemical peels were recommended in other reports. The technique using the 1,064-nm QS-Nd:YAG laser for toning and the enhancement of adjunctive treatments need further investigation and long-term follow-up before recommendations for the ideal protocol for melasma treatment can be made. The aim of this study is to evaluate the improvement of melasma using different parameters with the 1,064-nm QS-Nd:YAG laser with ultrasonic application of topical vitamin C. Eight patients, ranging in age from 32 to 45 years (mean 37 years), with long-term melasma were studied. Most of the melasma cases were dermal or mixed-type melasma. The patients had no cosmetic treatment (laser, intense pulsed light, or chemical peel) 1 year prior to the study. The entire face of each patient was treated with the 1,064-nm QS-Nd:YAG laser for four sessions at 1-month intervals. The laser treatment was divided into three parts with different parameters. First, each patient underwent whole face exposure for one pass with an 8-mm spot size at a power of 2.0 J/cm(2). Next, the spot size was shifted to 6 mm at a power of 3.5 J/cm(2) for one full-face pass, and then ended with a 4-mm spot size at 3.2 J/cm(2) for one full-face pass, with multiple passes for the main lesions. The end point was mild erythema and swelling, without petechiae. All patients applied ice packs for 5 min before the adjunctive treatment. We designed a split-face study with or without ultrasonic application of topical vitamin C. Only the right side of the face received ultrasonic melasma application of vitamin C for 15 min after ice packing. The left side of the face was covered with a moisturizing lotion. Objective evaluation was performed with visual analog score. All eight patients completed the 3-month follow-up after the four laser treatments. Statistics showed significant improvement with ultrasonic application of vitamin C compared to laser monotherapy. The improvement was more pronounced during second to fourth sessions. There was no rebound or post-inflammatory hyperpigmentation detected during the 3-month follow-up period. The combination of 1,064-nm QS-Nd:YAG laser treatment with ultrasonic application of topical vitamin C exerted more prompt response of melasma. We recommended this protocol including mixed parameters of 1,064-nm QS-Nd:YAG laser toning method combining with vitamin C ultrasonic application that can yield higher satisfaction for the difficult facial pigmentation problems such as melasma.

Selective delivery of cargo entities to tumor cells by nanoscale artificial oil bodies.

Artificial oil bodies (AOBs) are oil droplets that result from self-assembly of a mixture containing triacylglycerols, phospholipids, and membrane proteins of plant seeds. Owing to their small size, stability, hydrophobic core, biocompatibility, and biodegradability, AOBs were explored to examine their feasibility as a drug delivery carrier. This was approached by fusion sesame oleosin (Ole), the primary membrane protein of seed oil bodies, with a small domain consisting of the arginine-glycine-aspartic acid (RGD) motif. The resulting Ole-RGD fusion protein was overproduced in Escherichia coli and then isolated for reconstitution of AOBs. At the optimal condition, the size of stable AOBs was within the range of 100-400 nm. Furthermore, AOBs entrapped with a hydrophobic fluorescence dye were incubated with human tumor cells. As visualized by fluorescent microscopy and confocal microscopy, the RGD-tagged AOBs were able to selectively target cells expressing the αvß3 integrin. Moreover, these AOBs were effectively internalized and the fluorescence dye that they carried was subsequently released inside the cells. The percentage of cells internalized by AOBs could reach 80% as analyzed by flow cytometry. Taken together, it illustrates a great promise of this proposed approach for targeted delivery of cargo entities to tumor cells.

Liposome encapsulation reduces cantharidin toxicity.

Several reports have demonstrated that cantharidin is a strong anticancer compound in vitro; however, its in vivo usefulness is often limited due to its high systemic toxicity. In this study, we encapsulated cantharidin into pegylated liposomes and studied its activity against human breast cancer MCF-7 cells in vitro and its systemic toxicity in mice. Another two methods were also used to reduce the dosage of cantharidin, including labeling liposomal cantharidin with octreotide and exposing cells to hyperbaric oxygen. The cytotoxic activity of pegylated liposomal cantharidin was drastically reduced compared with free cantharidin in vitro. Octreotide-labeled pegylated liposomal cantharidin induced cell death by specifically targeting somatostatin receptors in MCF-7 cells. Cell death was augmented with a low dose of cantharidin under hyperbaric oxygen. Liposomal cantharidin had significantly less systemic toxicity than free cantharidin in vivo and also exhibited a high efficacy against antitumor growth in nude mice. These results suggest that the systemic toxicity of cantharidin can be mitigated by liposome encapsulation; however, that did not decrease its antitumor activity.