The Effect of Vascular Endothelial Growth Factor C and Adipose-Derived Stem Cells on Lymphatic Regeneration in a Rat Vascularized Lymph Node Transfer Model.

BACKGROUND: Lymphedema is a chronic condition characterized by progressive edema with complicated treatment. Recently, new treatment strategies inducing lymphangiogenesis were proposed. The aim of our study was to examine the effect of vascular endothelial growth factor C (VEGF-C) and adipose-derived stem cells (ADSCs) on lymphatic regeneration and drainage re-establishment in vascularized lymph node transfer (VLNT) model using a pedicled vascularized lymph node (VLN) groin flap. METHODS: Female Lewis rats with groin VLN flaps were utilized as a lymphedema model. Group A served as the control. Group B received VEGF-C. Group C received both VEGF-C and ADSCs. Group D received ADSCs only. Lymphatic drainage re-establishment was evaluated by ultrasound-photoacoustic imaging (US-PAI) after indocyanine green (ICG) injection. RESULTS: The fastest regeneration of elevated flaps was observed in Groups B and C in all monitored periods. After the first month, ICG positivity was detected in 14.3% of animals in Group A, 71.43% of animals in Group B (odds ratio [OR] = 15; p = 0.048), and 83.33% in Group C (OR = 30; p = 0.027). On the contrary, the difference between control group and Group D (16.67%; p = 0.905) was statistically insignificant. Administration of VEGF-C, ADSC + VEGF-C, and ADSC led to full flap regeneration after 6 months. The control group had the lowest percentage of ICG positivity at all monitored time points. CONCLUSION: We found that the fastest regeneration occurred with the combination of the VLN flap and VEGF-C. The addition of ADSC had an insignificant effect in our study. Furthermore, we proved the feasibility of PAI as an assessment tool of the lymphatic drainage recovery in a VLNT model.

Bilateral Prophylactic Nipple-Sparing Mastectomy: Analysis of the Risk-Reducing Effect in BRCA1/2 Mutation Carriers.

BACKGROUND: Mutations in the BRCA1 or BRCA2 genes increase the lifetime risk of developing breast cancer to 68-72% by the age of 80. One of the modalities to manage the risk is a prophylactic mastectomy. Bilateral nipple-sparing mastectomy specifically offers the most favorable esthetic outcomes but the evidence for its oncological safety remains limited. Thus, we aimed to compare the occurrence of breast cancer between nipple-sparing mastectomy and surveillance groups of BRCA1 or BRCA 2 mutations carriers. MATERIALS AND METHODS: BRCA1 or BRCA2-positive patients undergoing bilateral prophylactic nipple-sparing mastectomy at our department were identified. Only those unaffected by breast cancer were eligible. Each patient was pair-matched with a BRCA1 or BRCA2-positive patient of equal age from the surveillance group. Breast cancer incidence in both groups was recorded and the results were compared. RESULTS: None of 105 patients who underwent NSM between 2009 and 2019 at a single institution with a mean follow-up time of 50 months developed breast cancer over this time period. One patient in this group died of an unrelated cause. Nine patients from 105 in the match-paired surveillance group were diagnosed with breast cancer during a mean follow-up time of 58.3 months, however, none of them died. CONCLUSION: To the best of our knowledge, this is the largest single-center study of risk-reducing bilateral NSM in healthy BRCA1 or BRCA2 mutation carriers. Based on our results and those of other series, we conclude that NSM in its current form appears to be at least equally as safe as other types of mastectomy for preventing breast cancer in BRCA1 or BRCA2 mutation carriers. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Animal Models Used in the Research of Vascularized Lymph Node Transfer: A Systematic Review.

BACKGROUND: Lymphedema is a common adverse consequence of breast cancer therapy, while still relatively little is known about its pathophysiology. Several treatment options emerged over the past decades, and among them, vascularized lymph node transfer (VLNT) seems to be particularly promising. Animal models are indispensable to improve our understanding of the underlying processes surrounding the transplantation of a vascularized lymph node. This review aimed to systematically evaluate animal models of VLNT and compare their advantages and disadvantages. MATERIALS AND METHODS: A systematic review of literature in the Scopus, Web of Science, and Ovid MEDLINE databases was conducted according to the PRISMA guidelines to identify all studies on animal models used for the research of VLNT. The algorithm used in search of articles was "Vascularized Lymph Node Transfer" AND "Model". Articles were manually verified for relevance to the topic. The resulting models were assessed for their suitability for VLNT research. RESULTS: The literature search yielded a total of 233 studies after duplicates removal. Of those, 217 were excluded based on title and abstract review. Another study was excluded after reviewing the full-text article leaving 15 eligible studies to be included in this review article. CONCLUSIONS: Rats were found to be the most dominantly used animal model in the VLNT research, although other models had their benefits. The main areas of study were the functionality of VLNT within or without a preinduced lymphedema, its response to ischemia, and clarification of lymphatic pathways reestablishment following VLNT.

The Swedish cause of death register.

Sweden has a long tradition of recording cause of death data. The Swedish cause of death register is a high quality virtually complete register of all deaths in Sweden since 1952. Although originally created for official statistics, it is a highly important data source for medical research since it can be linked to many other national registers, which contain data on social and health factors in the Swedish population. For the appropriate use of this register, it is fundamental to understand its origins and composition. In this paper we describe the origins and composition of the Swedish cause of death register, set out the key strengths and weaknesses of the register, and present the main causes of death across age groups and over time in Sweden. This paper provides a guide and reference to individuals and organisations interested in data from the Swedish cause of death register.

Pregnancy outcome in more than 5000 births to women with viral hepatitis: a population-based cohort study in Sweden.

Previous studies have shown inconsistent results with respect to hepatitis B (HBV), hepatitis C (HCV) and pregnancy outcome. The aim of this study was to investigate pregnancy outcome in women with HBV or HCV. In a nationwide cohort of births between 2001 and 2011 we investigated the risks of adverse pregnancy outcomes in 2990 births to women with HBV and 2056 births to women with HCV using data from Swedish healthcare registries. Births to women without HBV (n = 1090 979), and births without HCV (n = 1091 913) served as population controls. Crude and adjusted relative risks (aRR) were calculated using Poisson regression analysis. Women with HCV were more likely to smoke (46.7 vs. 8.0%) and to have alcohol dependence (18.9 vs. 1.3%) compared with population controls. Most women with HBV were born in non-Nordic countries (91.9%). Maternal HCV was associated with a decreased risk of preeclampsia (aRR: 0.39, 95% CI: 0.24-0.64), but an increased risk of preterm birth (aRR: 1.32, 95% CI: 1.08-1.60) and late neonatal death (7-27 days: aRR: 3.79, 95% CI: 1.07-13.39) Preterm birth were also more common in mothers with HBV, aRR: 1.21 (95% CI: 1.02-1.45). Both HBV and HCV are risk factors for preterm birth, while HCV seems to be associated with a decreased risk for preeclampsia. Future studies should corroborate these findings.

Antibiotic exposure in the first year of life and later treated asthma, a population based birth cohort study of 143,000 children.

Several epidemiological studies reported an association between antibiotic consumption in the first year of life and later asthma, but results are conflicting and affected by potential biases. We examined this controversial issue in a population-based birth cohort. Using administrative data, we identified 143,163 children born in 1995-2011 in Friuli-Venezia Giulia (Italy) (median follow-up 5.25 years, 927,350 person-years). Antibiotic prescriptions in the first year of life and subsequent treated asthma (defined as ≥2 anti-asthmatic drug prescriptions within a 12-month period) were retrieved from drug prescription records. We estimated incidence rate ratios (IRR) using Poisson regression models, adjusted for perinatal variables and for hospitalizations for infections in the first year of life. We identified 34,957 new-onset asthma cases. Antibiotic consumption in the first year of life increased the risk of new-onset asthma [IRR 1.51, 95% confidence interval (CI) 1.48-1.54] with a dose-response relationship (p-trend <0.001). The risk was highest for asthma identified at 13-35 months of life (IRR 2.07, 95% CI 2.00-2.14), but remained statistically significant for asthma identified at 36-71 months (IRR 1.17, 95% CI 1.14-1.21) and at ≥72 months (IRR 1.15, 95% CI 1.08-1.22). Antibiotics increased the risk of current asthma at ≥6 years (IRR 1.35, 95% CI 1.30-1.41) and at ≥13 years of age (IRR 1.19, 95% CI 1.08-1.33). Antibiotic exposure in infancy is associated with an increased risk of asthma up to adolescence. The association detected at older ages is not explained by reverse causation; however, confounding by respiratory infections not leading to hospital admission cannot be excluded.