Development of a rat model of lymphedema and the implantation of a collagen-based medical device for therapeutic intervention.

Secondary lymphedema is a common condition among cancer survivors, and treatment strategies to prevent or treat lymphedema are in high demand. The development of novel strategies to diagnose or treat lymphedema would benefit from a robust experimental animal model of secondary lymphedema. The purpose of this methods paper is to describe and summarize our experience in developing and characterizing a rat hindlimb model of lymphedema. Here we describe a protocol to induce secondary lymphedema that takes advantage of micro computed tomography imaging for limb volume measurements and visualization of lymph drainage with near infrared imaging. To demonstrate the utility of this preclinical model for studying the therapeutic benefit of novel devices, we apply this animal model to test the efficacy of a biomaterials-based implantable medical device.

Curbing COVID-19 progression and mortality with traditional Chinese medicine among hospitalized patients with COVID-19: A propensity score-matched analysis.

BACKGROUND: Viral- and host-targeted traditional Chinese medicine (TCM) formulae NRICM101 and NRICM102 were administered to hospitalized patients with COVID-19 during the mid-2021 outbreak in Taiwan. We report the outcomes by measuring the risks of intubation or admission to intensive care unit (ICU) for patients requiring no oxygen support, and death for those requiring oxygen therapy. METHODS: This multicenter retrospective study retrieved data of 840 patients admitted to 9 hospitals between May 1 and July 26, 2021. After propensity score matching, 302 patients (151 received NRICM101 and 151 did not) and 246 patients (123 received NRICM102 and 123 did not) were included in the analysis to assess relative risks. RESULTS: During the 30-day observation period, no endpoint occurred in the patients receiving NRICM101 plus usual care while 14 (9.27%) in the group receiving only usual care were intubated or admitted to ICU. The numbers of deceased patients were 7 (5.69%) in the group receiving NRICM102 plus usual care and 27 (21.95%) in the usual care group. No patients receiving NRICM101 transitioned to a more severe status; NRICM102 users were 74.07% less likely to die than non-users (relative risk= 25.93%, 95% confidence interval 11.73%-57.29%). CONCLUSION: NRICM101 and NRICM102 were significantly associated with a lower risk of intubation/ICU admission or death among patients with mild-to-severe COVID-19. This study provides real-world evidence of adopting broad-spectrum oral therapeutics and shortening the gap between outbreak and effective response. It offers a new vision in our preparation for future pandemics.

Retrograde Manual Lymphatic Drainage following Vascularized Lymph Node Transfer to Distal Recipient Sites for Extremity Lymphedema: A Retrospective Study and Literature Review.

BACKGROUND: Vascularized lymph node transfer is an efficacious treatment for extremity lymphedema. This study investigated the outcome of retrograde manual lymphatic drainage for vascularized lymph node transfer to distal recipient sites. METHODS: Lymphedema patients who underwent either complete decongestive therapy or vascularized lymph node transfer between 2013 and 2018 were retrospectively included. Retrograde manual lymphatic drainage was started with intermittent manual compression and the assistance of a sphygmomanometer and proximal-to-distal massage of the limb 1 month postoperatively. Outcomes evaluations used the circumferential reduction rate and the Lymphedema-Specific Quality-of-Life Questionnaire. Outcomes of vascularized lymph node transfer to proximal versus distal recipient sites in the literature between 2006 and 2018 were also compared. RESULTS: One hundred thirty-eight unilateral extremity lymphedema patients, including 68 patients in the complete decongestive therapy group and 70 patients in the vascularized lymph node transfer group, were included. The mean circumferential reduction rate of 38.9 ± 2.5 percent in the vascularized lymph node transfer group was statistically greater than the 13.2 ± 10.1 percent rate in the complete decongestive therapy group (p = 0.01). At a mean follow-up of 36 months, the improvement of overall Lymphedema-Specific Quality-of-Life Questionnaire score from 3.8 ± 0.3 to 7.5 ± 1.8 in the vascularized lymph node transfer group was statistically greater than that in the complete decongestive therapy group (from 4.7 ± 0.9 to 5.0 ± 1.9; p < 0.01). In total, 536 lymphedema patients who underwent 548 vascularized lymph node transfers in 23 published articles were reviewed; the distal recipient-site group was found to have more efficacious results than the proximal recipient-site group. CONCLUSION: Vascularized lymph node transfer to a distal recipient site with standard retrograde manual lymphatic drainage significantly improved circumferential reduction rates and Lymphedema-Specific Quality-of-Life Questionnaire scores. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Complementary therapy of traditional Chinese medicine for blood sugar control in a patient with type 1 diabetes.

OBJECTIVE: Using a case study to discuss the effects of traditional Chinese medicine (TCM) treatments on Type 1 diabetes mellitus. CLINICAL FEATURES: A 4-year-old girl with sudden polyuria and nocturia (fasting plasma glucose level: 270mg/dL) was diagnosed with type 1 diabetes. Although multiple daily insulin injections were applied, her plasma glucose levels were still unstable. Therefore, she received a complementary TCM therapy by taking modified Liu-Wei-Di-Huang-Wan (3.0g/day; three times daily) for 3 months. After the treatments, her plasma glucose levels appeared to be more stable. HbA1c 6.5% and insulin injections were reduced to only once a day. CONCLUSIONS: The results suggest that complementary TCM therapy has the ability to assist some patients with type 1 diabetes mellitus in controlling their plasma glucose levels.

Quantity of lymph nodes correlates with improvement in lymphatic drainage in treatment of hind limb lymphedema with lymph node flap transfer in rats.

PURPOSE: This study was conducted to investigate the correlation between the number of vascularized lymph nodes (LN) transferred and resolution of hind limb lymphedema in a rat model. METHODS: Unilateral hind limb lymphedema was created in 18 male Sprague-Dawley rats following inguinal and popliteal LN resection and radiation. A para-aortic LN flap based on the celiac artery was subsequently transferred to the affected groin. The three study groups consisted of Group A (no LN transfer), Group B (transfer of a single vascularized LN), and Group C (transfer of three vascularized LNs). Volumetric analysis of bilateral hind limbs was performed using micro-CT imaging at 1, 2, and 3 months postoperatively. Lymphatic drainage was assessed with Tc(99) lymphoscintigraphy preoperatively and at 3 months postoperatively. RESULTS: A statistically significant volume reduction was seen in Groups B and C compared to Group A at all time points. Volume reduction of Group A vs.Group B at 1 month (8.6% ± 2.0% vs. 2.7% ± 2.6%, P < 0.05), 2 months (9.3% ± 2.2% vs. -4.3% ± 2.7%, P < 0.05), and 3 months (7.6% ± 3.3% vs. -8.9% ± 5.2%, P < 0.05). Volume reduction of Group A vs. Group C at 1 month (8.6% ± 2.0% vs. -6.6% ± 3.1%, P < 0.05), 2 months (9.3% ± 2.2% vs. -10.2% ± 4.6%, P < 0.05), and 3 months (7.6% ± 3.3% vs. -9.1% ± 3.1%, P < 0.05). Of note, comparison of Groups B and C demonstrated greater volume reduction in Group C at 1 (P < 0.02) and 2 (P = 0.07) months postoperatively. CONCLUSIONS: LN flap transfer is an effective procedure for the treatment of lymphedema. The number of vascularized LNs transferred correlates positively with the degree of volume reduction.

The effect of FGF-1 loaded alginate microbeads on neovascularization and adipogenesis in a vascular pedicle model of adipose tissue engineering.

Engineered vascularized adipose tissue could serve as an alternative to traditional tissue reconstruction procedures. Adipose formation occurs in a coordinated fashion with neovascularization. Previous studies have shown that extracellular matrix-based materials supplemented with factors that stimulate neovascularization promote adipogenesis in a number of animal models. The present study examines the ability of fibroblast growth factor (FGF-1) delivered from alginate microbeads to induce neovascularization and adipogenesis in type I collagen gels in a vascular pedicle model of adipose tissue engineering. FGF-1 loaded microbeads stimulated greater vascular network formation in an in vitro 3D co-culture model than a single bolus of FGF-1. In in vivo studies, FGF-1 loaded beads suspended in collagen and implanted in a chamber surrounding the exposed femoral pedicle of a rat resulted in a significant increase in vascular density at 1 and 6 weeks in comparison to bolus administration of FGF-1. Staining for smooth muscle actin showed that over 48% of vessels had associated mural cells. While an increase in neovascularization was achieved, there was less than 3% adipose under any condition. These results show that delivery of FGF-1 from alginate beads stimulated a more persistent neovascularization response than bolus FGF-1 both in vitro and in vivo. However, unlike previous studies, this increased neovascularization did not result in adipogenesis. Future studies need to provide a better understanding of the relationship between neovascularization and adipogenesis in order to design advanced tissue engineering therapies.

The efficacy of acupoint stimulation for the management of therapy-related adverse events in patients with breast cancer: a systematic review.

The aim of the present study was to scrutinize the evidence on the use of acupoint stimulation for managing therapy-related adverse events in breast cancer. A comprehensive search was conducted on eight English and Chinese databases to identify clinical trials designed to examine the efficacy of acupressure, acupuncture, or acupoint stimulation (APS) for the management of adverse events due to treatments of breast cancer. Methodological quality of the trials was assessed using a modified Jadad scale. Using pre-determined keywords, 843 possibly relevant titles were identified. Eventually 26 papers, 18 in English and eight in Chinese, satisfied the inclusion criteria and entered the quality assessment stage. The 26 articles were published between 1999 and 2008. They assessed the application of acupoint stimulation on six disparate conditions related to anticancer therapies including vasomotor syndrome, chemotherapy-induced nausea and vomiting, lymphedema, post-operation pain, aromatase inhibitors-related joint pain and leukopenia. Modalities of acupoint stimulation used included traditional acupuncture, acupressure, electroacupuncture, and the use of magnetic device on acupuncture points. Overall, 23 trials (88%) reported positive outcomes on at least one of the conditions examined. However, only nine trials (35%) were of high quality; they had a modified Jadad score of 3 or above. Three high quality trials revealed that acupoint stimulation on P6 (NeiGuang) was beneficial to chemotherapy-induced nausea and vomiting. For other adverse events, the quality of many of the trials identified was poor; no conclusive remarks can be made. Very few minor adverse events were observed, and only in five trials. APS, in particular acupressure on the P6 acupoint, appears beneficial in the management of chemotherapy-induced nausea and vomiting, especially in the acute phase. More well-designed trials using rigorous methodology are required to evaluate the effectiveness of acupoint stimulation interventions on managing other distress symptoms.

Effects of tibolone on the breast of postmenopausal women.

For decades, hormone therapy (HT) has been the mainstay for managing menopausal symptoms. However, the prolonged use of either single estrogen therapy (ET) or a combination therapy of estrogen and progestogen (EPT) might be associated with a slightly increased risk of breast cancer. Alternative therapies that are effective in the prevention and/or treatment of menopause, having associated morbidities but no unwanted effects, are of primary interest in clinical practice. Tibolone (Livial; NV Organon, Oss, The Netherlands) is structurally related to 19-nortestosterone derivatives and is a new postmenopausal regimen with a unique pharmacological profile, licensed for the relief of climacteric symptoms and the prevention of osteoporosis in postmenopausal women. Tibolone exhibits weak estrogenic, progestogenic, and androgenic activities, which in theory might influence the breast. The effect of tibolone on breast tissue, however, is obscure. The purpose of this study was to assess the effects of tibolone on breast safety, and the collected data include preclinical models, clinical observation, and epidemiologic study. Although in vitro studies showed conflicting results (with the majority being favorable effects) regarding the effects of tibolone on breast cells, in vivo studies showed favorable effects of tibolone on the breast in animal models. Similarly, an epidemiologic study indicated an increased risk of breast cancer when tibolone was used to manage climacteric symptoms of postmenopausal women, but accumulated data obtained from radiologic studies (mammography) showed a possible protective effect of tibolone on the breast. Taken together, we conclude that tibolone, if not superior to conventional HT, may be more acceptable to clinicians as a therapeutic drug option for use with symptomatic menopausal women. Only time will tell whether tibolone will be the preferred option.

A simple method to accurately position Port-A-Cath without the aid of intraoperative fluoroscopy or other localizing devices.

BACKGROUND: To evaluate the efficacy and acceptability of the Port-A-Cath (PAC) insertion method with (conventional group as II) and without (modified group as I) the aid of intraoperative fluoroscopy or other localizing devices. METHODS: A total of 158 women with various kinds of gynecological cancers warranting PAC insertion (n = 86 in group I and n = 72 in group II, respectively) were evaluated. Data for analyses included patient age, main disease, dislocation site, surgical time, complications, and catheter outcome. RESULTS: There was no statistical difference between the two groups in terms of age, main disease, complications, and the experiencing of patent catheters. However, appropriate positioning (100% in group I, and 82% in group II) in the superior vena cava (SVC) showed statistical differences between the two groups (P = 0.001). In addition, the surgical time in group I was statistically shorter than that in group II (P < 0.001). CONCLUSIONS: The modified method for inserting the PAC offered the following benefits: including avoiding X-ray exposure for both the operator and the patient, defining the appropriate position in the SVC, and less surgical time.