Predictors of Blood Transfusion in Patients Undergoing Cytoreductive Surgeries for Ovarian Malignancy.

OBJECTIVES: The aims of this study were to describe the baseline estimated blood loss (EBL) in surgery and transfusion rate in patients undergoing cytoreductive surgeries for ovarian malignancy, and identify perioperative variables associated with blood loss and transfusion. METHODS: A retrospective cohort study at a single institution was performed that included patients with known or suspected ovarian malignancy undergoing cytoreductive surgery between 2016 and 2021. t tests, χ2 tests, and multiple logistic regression analyses were used. RESULTS: Among 44 patients meeting inclusion criteria, 61% received perioperative blood transfusion. There were significant differences in EBL and preoperative hemoglobin levels between patients who did and did not receive transfusion (EBL 442.6 vs 236.8 mL, P = 0.0008; preoperative hemoglobin 10.2 vs 11.2 g/dL, P = 0.049). After adjusting for preoperative hemoglobin, the risk of transfusion increased for each additional 200 mL of EBL (odds ratio [OR] 3.8, 95% confidence interval [CI] 1.5-9.5). Stratified by race, the association between EBL and transfusion risk remained statistically significant only for non-Latinx White patients (OR 6.1, 95% CI 1.7-21.9), who made up 77% of the study population, but not for patients of other races and ethnicities (OR 1.0, 95% CI 0.16-6.42). CONCLUSIONS: Perioperative blood transfusion is common in patients undergoing cytoreductive surgery. In this study, EBL and preoperative hemoglobin levels were significantly associated with transfusion receipt. Clinicians should optimize hemoglobin levels and intraoperative blood conservation strategies to reduce the need for transfusion. The results also highlight the importance of considering racial and ethnic differences when developing strategies to reduce transfusion risk.

Adipose tissue-selective ablation of ADAM10 results in divergent metabolic phenotypes following long-term dietary manipulation.

A Disintegrin And Metalloproteinase domain-containing protein 10 (ADAM10), is involved in several metabolic and inflammatory pathways. We speculated that ADAM10 plays a modulatory role in adipose tissue inflammation and metabolism. To this end, we studied adipose tissue-specific ADAM10 knock-out mice (aKO). While young, regular chow diet-fed aKO mice showed increased insulin sensitivity, following prolonged (33 weeks) high-fat diet (HFD) exposure, aKO mice developed obesity and insulin resistance. Compared to controls, aKO mice showed less inflammatory adipokine profile despite the significant increase in adiposity. In brown adipose tissue, aKO mice on HFD had changes in CD8+ T cell populations indicating a lesser inflammatory pattern. Following HFD, both aKO and control littermates demonstrated decreased adipose tissue pro-inflammatory macrophages, and increased anti-inflammatory accumulation, without differences between the genotypes. Collectively, our observations indicate that selective deletion of ADAM10 in adipocytes results in a mitigated inflammatory response, leading to increased insulin sensitivity in young mice fed with regular diet. This state of insulin sensitivity, following prolonged HFD, facilitates energy storage resulting in increased fat accumulation which ultimately leads to the development of a phenotype of obesity and insulin resistance. In conclusion, the data indicate that ADAM10 has a modulatory effect of inflammation and whole-body energy metabolism.

Differences in single gene expression patterns and signaling pathways between Black and White patients in high grade endometrioid endometrial cancer independent of BMI.

Objective: Endometrial cancer (EC) incidence and mortality are increasing with striking racial disparities. Race and obesity are known risk factors for EC, however, their relationship and impact on tumor biology in higher grade endometrioid EC are unclear. The objective of this pilot study was to identify gene- and pathway-level changes in tumors from Black patients compared to White, both in general and in the context of dichotomized BMI. Methods: A single institution retrospective convenience sample was obtained for grade 2 or 3 endometrioid EC, equally distributed amongst Black and White patients. Tumor samples were analyzed with the Tempus Laboratories xT NGS-based genome profiling test. DESeq2 was applied to identify differentially expressed genes, and then subjected to ingenuity pathway analysis (IPA). Continuous variables were analyzed using unpaired t-tests, and categorical using Chi-squared and Fisher exact tests. Results: 39 representative cases were identified and analyzed from 2006 to 2021. Baseline clinicopathologic characteristics were similar. 157 genes were differentially expressed in tumors from Black patients compared to White regardless of BMI. IPA identified 81 significantly different pathways between Black and White patients with a BMI < 40 kg/m2, and 117 with a BMI ≥ 40 kg/m2. Of these, eleven pathways were consistently and significantly activated or deactivated regardless of BMI. Conclusion: Differences in gene expression and pathway activation in EC exist between race and BMI, which highlights the need for further research to better understand the implications of these differences on endometrioid EC progression, outcomes, and treatment in this historically underserved patient population.

Metastatic Uterine Leiomyosarcoma presenting as small bowel intussusception at two independent visits.

•Metastatic disease to the small bowel may present with intussusception.•Clinical decision making for malignant bowel obstruction is difficult and individual specific.•Malignant bowel obstruction due to metastatic year has an average life expectancy of less than 200 days.

Weight Gain After Thyroidectomy: A Systematic Review and Meta-Analysis.

CONTEXT: Weight gain is a major driver of dissatisfaction and decreased quality of life in patients with hypothyroidism. Data on the changes in body weight following thyroidectomy are conflicting. OBJECTIVE: To perform a systematic review of the literature and a meta-analysis of weight changes following total thyroidectomy. DATA SOURCES: Literature search on PubMed. STUDY SELECTION: Studies in English published between September 1998 and May 2018 reporting post-thyroidectomy weight changes. DATA EXTRACTION: Data were reviewed and compared by 3 investigators; discrepancies were resolved by consensus. Meta-analyses were performed using fixed and random effect models. Univariable and multivariable meta-regression models for weight change were implemented against study follow-up, gender, and age. Exploratory subgroup analyses were performed for indication for surgery. DATA SYNTHESIS: Seventeen studies (3164 patients) with 23.8 ± 23.6 months follow-up were included. Severe heterogeneity across studies was observed. Using a random effect model, the estimated overall weight change was a gain of 2.13 kg, 95% confidence interval (CI; 0.95, 3.30). Age was negatively associated with weight change (ß = -0.238, P < 0.001). In subgroup analyses, weight gain was more evident in patients undergoing thyroidectomy for hyperthyroidism: 5.19 kg, 95% CI (3.21, 7.17) vs goiter or malignancy 1.55 kg, 95% CI (0.82, 2.27) and 1.30 kg, 95% CI (0.45, 2.15), respectively. CONCLUSIONS: Patients undergoing thyroidectomy experience possible mild weight gain, particularly younger individuals and those with hyperthyroidism as the indication for surgery. Prospective studies directed to assess the pathophysiology of weight gain post-thyroidectomy, and to test novel treatment modalities, are needed to better characterize post-thyroidectomy weight changes.

Association of a Pediatric Gynecology eLearning Module With Resident Knowledge and Clinical Skills: A Randomized Controlled Trial.

OBJECTIVE: To assess whether a pediatric and adolescent gynecology electronic learning (eLearning) module improves knowledge and clinical performance among obstetrics and gynecology residents. METHODS: We conducted a multi-institutional, single-blinded, randomized controlled trial across four university programs; three had pediatric and adolescent gynecology rotations, and two had pediatric and adolescent gynecology fellowship-trained faculty. Applying permutated block randomization, residents were randomized to no intervention or completion of a validated eLearning module on prepubertal bleeding. All residents subsequently completed a pediatric and adolescent gynecology-related knowledge assessment that queried understanding of prepubertal bleeding and an objective structured clinical examination that assessed history collection, performance of a prepubertal genital examination, vaginal culture, and vaginoscopy for a pediatric patient. Objective structured clinical examinations were videotaped and reviewed by two faculty, blinded to randomization group; interrater reliability score was 97%. We calculated descriptive frequencies and compared randomization groups using χ analyses and Fisher exact tests for categorical variables, and median tests for continuous variables; a value of P<.05 was considered significant. RESULTS: From July 2018 to June 2019, we invited 115 residents to participate; 97 (83%) completed both objective structured clinical examination and follow-up knowledge assessments. Most were female (91%) and the majority reported limited pediatric and adolescent gynecology didactic or clinical experience, with 36% reporting prior didactics on prepubertal vaginal bleeding and 33% reporting prior exposure to the prepubertal genital examination. Forty-five participants (46%) were randomized to the module and groups were similar across training levels. Residents assigned to the module scored significantly higher on the knowledge assessment (4/5 vs 2/5, P<.001) and objective structured clinical examination (13/16 vs 7/16, P<.001) and were more likely to avoid a speculum in the examination of a pediatric patient (95.6% vs 57.7%, P<.001). CONCLUSION: Our pediatric and adolescent gynecology eLearning module resulted in improved short-term resident knowledge and simulated clinical skills among obstetrics and gynecology residents. Applying this learning technique in other programs may help address deficiencies in pediatric and adolescent gynecology education and training.

Adipocyte ADAM17 plays a limited role in metabolic inflammation.

The role of ADAM17, its substrates, and its natural inhibitor has been well studied in the context of inflammation, including metabolic inflammation, with mixed results. Previous studies examining global Adam17 knockdown models and ADAM17 inhibition using overexpression of endogenous ADAM17 inhibitors have shown improved metabolic health and decreased metabolic inflammation. However, there have been no studies examining the role of adipocyte ADAM17 using in vivo models. In this study, we developed an adipocyte-specific Adam17 knockout model using Adipoq-Cre-expressing mice crossed with Adam17-floxed mice. Using this model, we show that loss of adipocyte ADAM17 plays no evident role in baseline metabolic responses. Surprisingly, in a state of metabolic stress using high-fat diet (HFD), we observed that adipocyte ADAM17 had little effect overall on the metabolic phenotype as well as inflammatory cell populations. Using whole-body metabolic phenotyping, we show that loss of ADAM17 has no effect on energy utilization both at a baseline state as well as following HFD. However, lastly, using high-parameter flow cytometry, we show that loss of adipocyte ADAM17 alters macrophage and eosinophil populations following HFD. Overall, the studies presented here give more insight into the role of ADAM17 in metabolic responses and metabolic inflammation, specifically in adipocytes.

An appraisal of whole-room indirect calorimeters and a metabolic cart for measuring resting and active metabolic rates.

Whole-room indirect calorimeters (WRICs) have traditionally been used for real-time resting metabolic rate (RMR) measurements, while metabolic rate (MR) during short-interval exercises has commonly been measured by metabolic carts (MCs). This study aims to investigate the feasibility of incorporating short-interval exercises into WRIC study protocols by comparing the performance of WRICs and an MC. We assessed the 40-min RMR of 15 subjects with 2-day repeats and the 10-15 min activity MR (AMR) of 14 subjects at three intensities, using a large WRIC, a small WRIC, and an MC. We evaluated the biases between the instruments and quantified sources of variation using variance component analysis. All three instruments showed good agreement for both RMR (maximum bias = 0.07 kcal/min) and AMR assessment (maximum bias = 0.53 kcal/min). Moreover, the majority of the variability was between-subject and between-intensity variation, whereas the types of instrument contributed only a small amount to total variation in RMR (2%) and AMR (0.2%) data. In Conclusion, the good reproducibility among the instruments indicates that they may be used interchangeably in well-designed studies. Overall, WRICs can serve as an accurate and versatile means of assessing MR, capable of integrating RMR and short-interval AMR assessments into a single protocol.

E0771 and 4T1 murine breast cancer cells and interleukin 6 alter gene expression patterns but do not induce browning in cultured white adipocytes.

Breast cancer remains a substantial clinical problem worldwide, and cancer-associated cachexia is a condition associated with poor prognosis in this and other malignancies. Adipose tissue is involved in the development and progression of cancer-associated cachexia, but its various roles and mechanisms of action are not completely defined, especially as it relates to breast cancer. Interleukin 6 has been implicated in several mechanisms contributing to increased breast cancer tumorigenesis, as well as a net-negative energy balance and cancer-associated cachexia via adipose tissue remodeling in other models of cancer; however, its potential role in breast cancer-associated white adipose browning has not been explored. In this study, we demonstrate localized white adipose tissue browning in a spontaneous model of murine mammary cancer. We then used an in vitro murine adipocyte culture system with the E0771 and 4T1 cell lines as models of breast cancer. We demonstrate that while the E0771 and 4T1 secretomes and cross-talk with white adipocytes alter white adipocyte mRNA expression, they do not directly induce white adipocyte browning. Additionally, we show that neither exogenous administration of interleukin 6 alone or with its soluble receptor directly induce white adipocyte browning. Together, these results demonstrate that neither the E0771 or 4T1 murine breast cancer cell lines, nor interleukin 6, directly cause browning of cultured white adipocytes. This suggests that their roles in adipose tissue remodeling are more complex and indirect in nature.