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Purpose: Patients undergoing axillary lymph node dissection (ALND) for breast cancer face a high risk of lymphedema, further increased by high body mass index (BMI) and insulin resistance. GLP-1 receptor agonists (GLP-1RAs) have the potential to reduce these risk factors, but their role in lymphedema has never been investigated. The purpose of this study was to determine if GLP-RAs can reduce the risk of lymphedema in patients undergoing ALND. Methods: All patients who underwent ALND at a tertiary cancer center between 2010 and 2023 were reviewed. Patients with less than 2 years of follow-up from the time of ALND were excluded. Race, BMI, radiation, chemotherapy history, pre-existing diagnosis of diabetes, lymphedema development after ALND, and the use of GLP-1RAs were analyzed. Multivariate logistic regression analysis was performed to assess if there was a significant reduction in the risk of developing lymphedema after ALND. A sub-group analysis of non-diabetic patients was also performed. Results: 3,830 patients who underwent ALND were included, 76 of which were treated with. GLP-1 RAs. The incidence of lymphedema in the GLP-1 RA cohort was 6.6% (5 patients). Compared to 28.5% (1,071 patients) in the non-GLP-1 RA cohort. On multivariate regression analysis, patients who were treated with GLP-1 RA were 86% less likely to develop lymphedema compared to the non-GLP-1 RA cohort (OR 0.14, 95% CI 0.04-0.32, p < 0.0001). A BMI of 25 kg/m 2 or greater was a statistically significant risk factor for developing lymphedema with an odds ratio of 1.34 (95% CI 1.16-1.56, p < 0.0001). Diabetes was associated with lymphedema development that closely approached statistical significance (OR 1.32, 95% CI 0.97-1.78, p = 0.06). A subgroup analysis solely on non-diabetic patients showed similar results. The odds of developing lymphedema were 84% lower for patients without diabetes treated with GLP1-RAs compared to those who did not receive GLP-1 RAs (OR 0.16, 95% CI 0.05-0.40, p < 0.0001). Conclusion: GLP1-RAs appear to significantly reduce the risk of lymphedema in patientsundergoing ALND. The mechanism of action may be multifactorial and not limited to weight reduction and insulin resistance. Future prospective analysis is warranted to clarify the role of GLP-1RAs in reducing lymphedema risk. [ABSTRACT FROM AUTHOR]

Introduction: Lymphedema is a major public health issue for many women undergoing breast cancer treatment. Although weight loss has been reported to be beneficial in the treatment of lymphedema, no studies to date have examined the use of GLP-1RAs for the treatment of secondary lymphedema. This case report describes a patient who experienced significant resolution of her breast cancer-related lymphedema after initiation of a GLP-1RA for weight loss. Main symptoms and/or important clinical findings: Nine months postoperatively the patient developed arm swelling and disability. While on adjuvant chemo and hormonal therapy, her weight increased dramatically and peaked 4 years later. Corresponding to her weight gain was significant worsening of her symptoms. The main diagnoses, therapeutic interventions, and outcomes: Due to adjuvant cancer-related weight gain and inability to lose weight with diet and exercise, she was referred for evaluation and diagnosed with lymphedema. The patient started treatment with a Glucagon-like peptide 1 receptor agonist and lost 24% of her body weight over the next 13 months. The improvement in her lymphedema mirrored her weight loss. Her limb volume difference dropped from 10.3% down to 3.4% and she no longer required a compression garment. Her imaging demonstrated return of lymphatic pumping and she experienced a significant improvement in quality of life, assessed by a validated lymphedema-specific patient reported outcome (PROM). She remains on hormonal therapy, no longer needs compression and is back to regular exercise without impairment. Conclusions: GLP-1 RAs provide a potential medical option for many patients struggling with weight gain and lymphedema. We have observed by all objective measures a significant reduction in lymphedema and the elimination of compression in the case presented as a direct result of GLP-1 RA. This may also reduce a patient's BMI to the point where they become a good candidate for lymphovenous bypass or vascularized lymph node transplant when indicated. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) receptor 3 (VEGFR3), a receptor tyrosine kinase encoded by the FLT4 gene, plays a significant role in the morphogenesis and maintenance of lymphatic vessels. Under both normal and pathologic conditions, VEGF-C and VEGF-D bind VEGFR3 on the surface of lymphatic endothelial cells (LECs) and induce lymphatic proliferation, migration, and survival by activating intracellular PI3K-Akt and MAPK-ERK signaling pathways. Impaired lymphatic function and VEGFR3 signaling has been linked with a myriad of commonly encountered clinical conditions. This review provides a brief overview of intracellular VEGFR3 signaling in LECs and explores examples of dysregulated VEGFR3 signaling in various disease states, including (1) lymphedema, (2) tumor growth and metastasis, (3) obesity and metabolic syndrome, (4) organ transplant rejection, and (5) autoimmune disorders. A more complete understanding of the molecular mechanisms underlying the lymphatic pathology of each disease will allow for the development of novel strategies to treat these chronic and often debilitating illnesses. [ABSTRACT FROM AUTHOR]

Lymphedema is a chronic condition that commonly occur from lymphatic injury following surgical resection of solid malignancies. While many studies have centered on the molecular and immune pathways that perpetuate lymphatic dysfunction, the role of the skin microbiome in lymphedema development remains unclear. In this study, skin swabs collected from normal and lymphedema forearms of 30 patients with unilateral upper extremity lymphedema were analyzed by 16S ribosomal RNA sequencing. Statistical models for microbiome data were utilized to correlate clinical variables with microbial profiles. Overall, 872 bacterial taxa were identified. There were no significant differences in microbial alpha diversity of the colonizing bacteria between normal and lymphedema skin samples (p = 0.25). Notably, for patients without a history of infection, a one-fold change in relative limb volume was significantly associated with a 0.58-unit increase in Bray-Curtis microbial distance between paired limbs (95%CI = 0.11,1.05, p = 0.02). Additionally, several genera, including Propionibacterium and Streptococcus, demonstrated high variability between paired samples. In summary, we demonstrate high compositional heterogeneity in the skin microbiome in upper extremity secondary lymphedema, supporting future studies into the role of host-microbe interactions on lymphedema pathophysiology. [ABSTRACT FROM AUTHOR]

Purpose: Secondary lymphedema is a common complication of cancer treatment for which no effective drug treatments yet exist. Level I clinical data suggests that doxycycline is effective for treating filariasis-induced lymphedema, in which it decreases tissue edema and skin abnormalities; however, this treatment has not been tested for cancer-related lymphedema. Over the past year, we used doxycycline in an off-label manner in patients with breast cancer-related secondary lymphedema. The purpose of this report was to retrospectively analyze the efficacy of this treatment. Methods: Patients who presented to our lymphedema clinic between January 2021 and January 2022 were evaluated, and barring allergies or contraindications to doxycycline treatment, were counseled on the off-label use of this treatment. Patients who wished to proceed were treated with doxycycline (200 mg given orally once daily) for 6 weeks. After IRB approval of this study, lymphedema outcomes were retrospectively reviewed. Results: Seventeen patients with a mean follow-up of 17.0 ± 13.2 weeks were identified in our retrospective review. Although doxycycline treatment had no significant effect on relative limb volume change or L-Dex scores, we found a significant improvement in patient-reported quality of life. Analysis of patient responses to the Lymphedema Life Impact Scale showed a significant improvement in the total impairment score due to improvements in the physical and psychological well-being subscales (p = 0.03, p = 0.03, p = 0.04, respectively). Conclusion: This small, retrospective study did not show significant improvements in limb volume or L-Dex scores in patients with breast cancer-related lymphedema treated with doxycycline. However, our patients reported improvements in quality-of-life measures using a validated lymphedema patient-reported outcome instrument. Our results suggest that doxycycline may be of use in patients with breast cancer-related lymphedema; however, larger and more rigorous studies are needed. [ABSTRACT FROM AUTHOR]

Purpose: While vascularized lymph node transplant (VLNT) has gained popularity, there are a lack of prospective long-term studies and standardized outcomes. The purpose of this study was to evaluate the safety and efficacy of VLNT using all available outcome measures. Methods: This was a prospective study on all consecutive patients who underwent VLNT. Outcomes were assessed with 2 patient-reported outcome metrics, limb volume, bioimpedance, need for compression, and incidence of cellulitis. Results: There were 89 patients with the following donor sites: omentum (73%), axilla (13%), supraclavicular (7%), groin (3.5%). The mean follow-up was 23.7±12 months. There was a significant improvement at 2 years postoperatively across all outcome measures: 28.4% improvement in the Lymphedema Life Impact Scale, 20% average reduction in limb volume, 27.5% improvement in bioimpedance score, 93% reduction in cellulitis, and 34% of patients no longer required compression. Complications were transient and low without any donor site lymphedema. Conclusions: VLNT is a safe and effective treatment for lymphedema with significant benefits fully manifesting at 2 years postoperatively. Omentum does not have any donor site lymphedema risk making it an attractive first choice. [ABSTRACT FROM AUTHOR]

Lymphedema is a chronic disease that results in swelling and decreased function due to abnormal lymphatic fluid clearance and chronic inflammation. In Western countries, lymphedema most commonly develops following an iatrogenic injury to the lymphatic system during cancer treatment. It is estimated that as many as 10 million patients suffer from lymphedema in the United States alone. Current treatments for lymphedema are palliative in nature, relying on compression garments and physical therapy to decrease interstitial fluid accumulation in the affected extremity. However, recent discoveries have increased the hopes of therapeutic interventions that may promote lymphatic regeneration and function. The purpose of this review is to summarize current experimental pharmacological strategies in the treatment of lymphedema. [ABSTRACT FROM AUTHOR]

Background: Upper extremity transplantation is a quality-of-life enhancing treatment for select patients with upper extremity loss. This article reviews the preoperative, intraoperative, and postoperative challenges in the upper extremity transplantation process and the lessons learned from the first 2 decades of hand transplantation. Methods: Key components of the author's hand transplantation protocol including patient selection, donor screening, surgical rehearsal, donor procurement, transplantation, immunosuppression, and patient outcome reporting/follow-up are reported to assist other teams who wish to establish a hand transplantation program. Results: There have been many advancements in the first 20 years of hand transplantation including better patient selection criteria, the recent addition of pediatric patients, improved surgical techniques such as the use of virtual surgical planning, and improved immunosuppression protocols. Improvement has also taken place in the tracking and reporting of hand transplant outcomes, but more work is clearly needed to fully define the benefits of transplantation, especially for pediatric patients. Conclusions: Over the past 20 years, significant progress has been made in upper extremity transplantation although a number of challenges remain including how to best document and share outcome measures, optimize immunosuppression, and diagnose/treat rejection. The authors encourage upper extremity transplant programs to report their experience and protocols to advance hand transplantation as standard of care for properly selected individuals. [ABSTRACT FROM AUTHOR]

Ramadan is the ninth month of the Islamic lunar calendar and is observed by Muslims as a month of fasting. All Muslim adults are expected to fast; nevertheless certain subgroups, including sick, frail subjects, and pregnant women, among others, are exempted. Ramadan fasting has been shown to impact on body systems in different manners. The influence of Ramadan fasting on immune system regulation remains elusive; however, immune system changes, such as the modulation of body response to various infectious, stressful, and other harmful events, are of great interest during fasting. In this paper, we performed an extensive systematic literature review of different scholarly databases (ISI/Web of Science, Scopus, PubMed,/MEDLINE, Google Scholar, Directory of Open Access Journals, EbscoHOST, Scirus, Science Direct, the Cochrane Library, and ProQuest), using the following key words: “fasting,” “Ramadan,” “Islam,” and “immunity.” Conclusions drawn from these findings included: (1) Ramadan fasting has been shown to only mildly influence the immune system and the alterations induced are transient, returning to basal pre-Ramadan status shortly afterward. (2) Ramadan fasting during the second trimester of pregnancy was shown to be safe and did not result in negative fetal outcomes, or maternal oxidative status alterations. (3) In cardiac patients, Ramadan fasting can have beneficial effects including lipid profile improvement and alleviation of oxidative stress. (4) In asthmatic patients as well as in patients with human immunodeficiency virus/acquired immunodeficiency syndrome and autoimmune disorders, fasting was safe. (5) In psychiatric patients, such as those suffering from schizophrenia, fasting could increase immunologic markers. (6) Fasting Muslim athletes who maintain intensive training schedule during Ramadan showed fluctuations of immunologic markers. [ABSTRACT FROM AUTHOR]

Acute health care environments can be stressful settings with clinicians experiencing deleterious effects of burnout and compassion fatigue affecting their mental health. Subsequently, the quality of patient care and outcomes may be threatened if clinicians experience burnout or compassion fatigue. Therefore, the aim of this descriptive, cross-sectional study was to evaluate the prevalence of burnout and compassion fatigue among burn clinicians in Israel. Fifty-five clinicians from Burns, Plastics and Reconstruction Surgery and Intensive Care completed four validated surveys to assess burnout (Maslach Burnout Inventory), depression (PRIME-MD), health- related quality of life (SF-8), and compassion fatigue (Professional Quality of Life version 5). Burn clinicians were compared with Plastics and Reconstruction Surgery and Intensive Care clinicians. This study identified a high prevalence of burnout (38.2%) among Intensive Care, Plastics and Reconstruction and Burns clinicians, with Burns clinicians having a greatly increased prevalence of burnout compared to Intensive Care clinicians (OR =24.3, P=0.017). Additional factors contributing to compassion fatigue were those without children (P=0.016), divorced (P=0.035), of a younger age (P=0.019), and a registered nurse (P=0.05). Burnout increased clinicians' risk of adverse professional and personal outcomes and correlated with less free time (P<0.001), increased risk of experiencing work-home disputes (P=0.05), increased depression (P=0.001) and decreased career satisfaction (P=0.01). Burnout was also associated with higher physical (mean difference =3.8, P,0.001) and lower mental (mean difference =-3.5, P<0.001) Quality of Life scores. Caring for burn survivors can lead to burnout, compassion fatigue, and vicarious trauma. Identifying strategies to abate these issues is essential to ensure improved clinicial environments and patient outcomes. [ABSTRACT FROM AUTHOR]

The tropical fig borer, Batocera rufomaculata De Geer, is a large beetle that is a pest on a number of fruit trees, including fig and mango. Adults feed on the leaves and twigs and females lay their eggs under the bark of the tree. The larvae bore into the tree trunk, causing substantial damage that may lead to the collapse and death of the host tree. We studied how larval development under inferior feeding conditions (experienced during development in dying trees) affects flight endurance in the adult insect. We grew larvae either in their natural host or on sawdust enriched with stale fig tree twigs. Flight endurance of the adults was measured using a custom-built flight-mill. Beetles emerging from the natural host were significantly larger but flew shorter distances than beetles reared on less favourable substrates. There was no difference in the allometric slope of wing area with body mass between the beetles groups; however flight muscle mass scaled with total body mass with an exponent significantly lower than 1.0. Hence, smaller beetles had proportionally larger flight muscles. These findings suggest that beetles that developed smaller as a result from poor nutritional conditions in deteriorating hosts, are better equipped to fly longer distances in search of a new host tree. [ABSTRACT FROM AUTHOR]

The autoimmune/inflammatory syndrome induced by adjuvants (ASIA), presented by Shoenfeld and Agmon-Levin in 2011, is an entity that incorporates diverse autoimmune conditions induced by the exposure to various adjuvants. Adjuvants are agents that entail the capability to induce immune reactions. Adjuvants are found in many vaccines and used mainly to increase the response to vaccination in the general population. Silicone has also been reported to be able to induce diverse immune reactions. Clinical cases and series of heterogeneous autoimmune conditions including systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis have been reported to be induced by several adjuvants. However, only a small number of cases of autoimmune thyroid disorder have been included under the umbrella of ASIA syndrome. Indeed, clinical cases of Hashimoto's thyroiditis and/or subacute thyroiditis were observed after the exposure to vaccines as well as silicone implantation. In our review, we aimed to summarize the current knowledge on ASIA syndrome presented as endocrinopathies, focusing on autoimmune thyroid disorders associated with the various adjuvants. [ABSTRACT FROM AUTHOR]