Explore the vast range of titles available.

IgG antibodies cause inflammation and organ damage in autoimmune diseases such as systemic lupus erythematosus (SLE). We investigated the metabolic profile of macrophages isolated from inflamed tissues in immune complex (IC)-associated diseases, including SLE and rheumatoid arthritis, and following IgG Fcγ receptor cross-linking. We found that human and mouse macrophages undergo a switch to glycolysis in response to IgG IC stimulation, mirroring macrophage metabolic changes in inflamed tissue in vivo. This metabolic reprogramming was required to generate a number of proinflammatory mediators, including IL-1β, and was dependent on mTOR and hypoxia-inducible factor (HIF)1α. Inhibition of glycolysis, or genetic depletion of HIF1α, attenuated IgG IC-induced activation of macrophages in vitro, including primary human kidney macrophages. In vivo, glycolysis inhibition led to a reduction in kidney macrophage IL-1β and reduced neutrophil recruitment in a murine model of antibody-mediated nephritis. Together, our data reveal the molecular mechanisms underpinning FcγR-mediated metabolic reprogramming in macrophages and suggest a therapeutic strategy for autoantibody-induced inflammation, including lupus nephritis.

PurposeBreast cancer is the most common malignancy among young women of reproductive age. Adjuvant treatment with tamoxifen reduces the risk of recurrence in hormone-sensitive breast cancer. However, the use of tamoxifen is considered contraindicated during pregnancy, because of a limited number of case reports demonstrating potential adverse effects on the fetus. The objective of this report is to give a more broad overview of the available data on the effect of tamoxifen exposure during pregnancy.MethodsA literature review was performed using PubMed and the databases of the Netherlands Pharmacovigilance Centre Lareb and of the International Network on Cancer, Infertility, and Pregnancy.ResultsA total of 238 cases of tamoxifen use during pregnancy were found. Of the 167 pregnancies with known outcome, 21 were complicated by an abnormal fetal development. The malformations described were non-specific and the majority of cases concerned healthy infants despite exposure to tamoxifen.ConclusionThere seems to be an increased risk of fetal abnormalities when taking tamoxifen during pregnancy (12.6% in contrast to 3.9% in the general population), but the evidence is limited and no causal relationship could be established. The possible disadvantage of postponing or discontinuing tamoxifen for the maternal prognosis is unclear. Patients should be counseled about the use of tamoxifen during pregnancy instead of presenting it as being absolutely contraindicated.

The nested regional climate/mesoscale modelling system developed by the authors is applied to the Hadley Centre Global Environment Model version 2-Earth System global model outputs to project future changes of landfalling tropical cyclone (TC) activity in the South China region. Results show that the modelling system is capable of reproducing the current TC landfall climatology, although it exhibits a noticeable southward bias of TC activity of in the western North Pacific. Future projections show a continuous northward migration of TC activity in the western North Pacific throughout the twenty-first century. Fewer TCs making landfall in South China are projected in the late century, but these landfalling TCs tend to be more intense. Investigations in the large-scale environment suggest that despite warmer sea surface temperature and weaker vertical wind shear, the drier and less cyclonic lower atmosphere all-season is responsible for the reduced TC activity. However, once a TC is formed, the environment it stays in is as wet as today and so it can intensify further than the present-day TCs. Inter-annual variability is also explored, and the influence of the ENSO variation appears to be smaller.

BackgroundSafety of sentinel lymph node (SLN) biopsy for breast cancer during pregnancy is insufficiently explored. We investigated efficacy and local recurrence rate in a large series of pregnant patients.Patients and methodsWomen diagnosed with breast cancer who underwent SLN biopsy during pregnancy were identified from the International Network on Cancer, Infertility and Pregnancy, the German Breast Group, and the Cancer and Pregnancy Registry. Chart review was performed to record technique and outcome of SLN biopsy, locoregional and distant recurrence, and survival.ResultsWe identified 145 women with clinically N0 disease who underwent SLN during pregnancy. The SLN detection techniques were as follows: 99mTc-labeled albumin nanocolloid only (n = 96; 66.2%), blue dye only (n = 14; 9.7%), combined technique (n = 15; 10.3%), or unknown (n = 20; 13.8%). Mapping was unsuccessful in one patient (0.7%) and she underwent an axillary lymph node dissection (ALND). Mean number of SLNs was 3.2 (interquartile range 1-3; missing n = 15). Positive SLNs were found in 43 (29.7%) patients and 34 subsequently underwent ALND. After a median follow-up of 48 months (range 1–177), 123 (84.8%) patients were alive and free of disease. Eleven patients experienced a locoregional relapse, including 1 isolated ipsilateral axillary recurrence (0.7%). Eleven (7.6%) patients developed distant metastases, of whom 9 (6.2%) died of breast cancer. No neonatal adverse events related to SLN procedure during pregnancy were reported.ConclusionsSLN biopsy during pregnancy has a comparably low axillary recurrence rate as in nonpregnant women. Therefore, this method can be considered during pregnancy instead of standard ALND for early-stage, clinically node-negative breast cancer.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main out-comes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.

Summary Fractures are common in chronic kidney disease (CKD). We determined if bone mineral density testing by dual energy X-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HR pQCT) could discriminate fracture status in CKD patients. Both tests were able to discriminate fracture status. Further, the addition of HR pQCT measurements to DXA measurements did not improve fracture discrimination. Introduction The optimal method to identify individuals with CKD at high fracture risk is unknown. Methods We determined if bone mineral density (BMD) by DXA and HR pQCT could discriminate fracture status in 211 adult men and women with stages 3 to 5 CKD, attending predialysis clinics in Toronto Canada, using logistic regression. Results are expressed as the odds ratio (OR) of fracture (prevalent vertebral and/or low trauma since age 40 years) per standard deviation decrease in the predictor adjusted for age, weight, sex, and CKD stage. We constructed receiver operating characteristic curves to examine the discriminative ability of BMD measures for fracture. Results Most participants were Caucasian men with a mean age of 63.3 ± 15.5 years. There were 77 fractures in 74 participants. Decreases in BMD were associated with increased fracture risk: OR = 1.56 (95% confidence interval (CI), 1.41 to 1.71) for BMD by DXA at the ultradistal radius, and OR = 1.24 (95% CI, 1.12 to 1.36) for cortical area by HR pQCT. Further, while both tests were able to discriminate fracture status, the addition of HR pQCT measures to BMD by DXA did not improve fracture discrimination ability. Conclusions Among CKD patients not yet requiring renal replacement therapy, BMD by DXA is able to discriminate fracture status.

A numerical method is developed using a regional climate model (RegCM3) and the Weather Forecast and Research (WRF) model to predict seasonal tropical cyclone (TC) intensities at landfall for the South China region. In designing the model system, three sensitivity tests have been performed to identify the optimal choice of the RegCM3 model domain, WRF horizontal resolution and WRF physics packages. Driven from the National Centers for Environmental Prediction Climate Forecast System Reanalysis dataset, the model system can produce a reasonable distribution of TC intensities at landfall on a seasonal scale. Analyses of the model output suggest that the strength and extent of the subtropical ridge in the East China Sea are crucial to simulating TC landfalls in the Guangdong and Hainan provinces. This study demonstrates the potential for predicting TC intensities at landfall on a seasonal basis as well as projecting future climate changes using numerical models.

PurposeTo assess the primary safety and oncological outcome of percutaneous cryoablation in patients with non-visceral metastases of the abdominal cavity after prior surgery.MethodsAll patients with non-visceral metastases after prior abdominal surgery, treated with percutaneous cryoablation, and at least one year of follow-up were retrospectively identified. Technical success was achieved if the ice-ball had a minimum margin of 10 mm in three dimensions on the per-procedural CT images. Complications were recorded using the Society of Interventional Radiology (SIR) classification system. Time until disease progression was monitored with follow-up CT and/or MRI. Local control was defined as absence of recurrence at the site of ablation.ResultsEleven patients underwent cryoablation for 14 non-visceral metastases (mean diameter 20 ± 9 mm). Primary tumor origin was renal cell (n = 4), colorectal (n = 3), granulosa cell (n = 2), endometrium (n = 1) and appendix (n = 1) carcinoma. Treated metastases were localized retroperitoneal (n = 8), intraperitoneal (n = 2), or in the abdominal wall (n = 4). Technical success was achieved in all procedures. After a median follow-up of 27 months (12–38 months), all patients were alive. Local control was observed in 10/14 non-visceral metastases, and the earliest local progression was detected after ten months. No major adverse events occurred. One patient suffered a minor asymptomatic adverse event.ConclusionThis proof-of-concept study suggests that cryoablation can be a minimal invasive treatment option in a selected group of patients with non-visceral metastases in the abdominal cavity after prior surgery.

Studying the emotional disorders of perimenopausal women and their influencing factors from a psychological perspective is essential for developing targeted psychological interventions and support strategies. Such efforts can help middle-aged and elderly women better cope with the challenges of perimenopause and improve their overall quality of life. This study aimed to explore the chain mediating effect of self-esteem and psychological resilience on the relationship between illness perception and emotional disorders in perimenopausal women in Macau. A total of 617 postmenopausal women completed the Brief Illness Perception Questionnaire, Psychological Resilience Scale, Self-Esteem Scale, and Hospital Anxiety and Depression Scale. Results revealed a significant positive correlation between illness perception and emotional disorders. Illness perception was found to have a significant direct effect on emotional disorders and an indirect effect through the mediating roles of self-esteem and psychological resilience, both independently and sequentially. These findings indicate that illness perception directly influences emotional disorders in postmenopausal women in Macau and indirectly impacts them through self-esteem and psychological resilience, offering valuable insights for psychological intervention strategies.

Opinion statement Epithelial ovarian cancer (EOC) is the fourth most common gynecologic cancer in Europe and is the leading cause of death among women with gynecologic malignancies. This is due to the fact that the majority of the patients are diagnosed with advanced stage disease. In these stages, extensive intraperitoneal metastases are often present, making therapy more difficult. The current standard treatment involves primary or interval cytoreductive surgery and chemotherapy. However, many patients develop intraperitoneal (IP) recurrences despite complete surgery and chemotherapy. Therefore, alternative ways to deliver chemotherapy have been examined. Administration of the chemotherapy directly into the peritoneal cavity allows high doses of the cytotoxic agent at the site of the cancer, while minimizing the occurrence of systemic side effects. Theoretically, IP administration is most beneficial when only microscopic disease is present since penetration of the drug is limited to a few millimeters. IP chemotherapy can be administered during surgery under hyperthermic conditions (HIPEC) or during regular chemotherapy courses through a catheter placed into the abdominal cavity. IP administration results in an improved survival, although catheter-related morbidity is reported. Hyperthermia potentiates the cytotoxic effect of chemotherapy and may therefore have an additional positive effect on prognosis. Although recent observational studies show encouraging results with respect to effect on survival and rate of complications, it remains a challenge to identify those patients who would benefit most from adding HIPEC to the standard treatment. In this respect, age and timing of HIPEC during treatment might be important factors, although no convincing evidence is available yet. Currently, a total of 18 clinical trials are open and to answer the above-mentioned questions, it is adamant to complete these trials, especially the randomized phase III trials. Accrual is hampered by the fact that HIPEC is currently offered as standard treatment in some centers even though convincing evidence is not yet available. If these phase III trials show positive results in favor of HIPEC, subsequent trials comparing surgery and postoperative IP chemotherapy with surgery and HIPEC seem a logical next step.