Lifestyle Intervention in Pregnant Women With Obesity Impacts Cord Blood DNA Methylation,Which Associates With Body Composition in the Offspring

Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring. Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the Treatment of Obese Pregnant women (TOP)-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus control subjects (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus control subjects (false discovery rate [FDR] <5%) when using the Houseman reference-free method to correct for cell composition, and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms, including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared with control subjects. Methylation at 17 sites, annotated to, for example, DISC1, GBX2, HERC2, and HUWE1, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR <5%). Moreover, 22 methylation sites were associated with offspring BMI z scores during the first 3 years of life (P < 0.05). Overall, lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring’s lean mass and early growth.     

Weightbearing and Activity Restriction Treatments and Quality of Life in Patients with Perthes Disease

BackgroundWeightbearing and activity restrictions are commonly prescribed during the active stages of Perthes disease. These restrictions, ranging from cast or brace treatment with nonweightbearing to full weightbearing with activity restrictions, may have a substantial influence on the physical, mental, and social health of a child. However, their impact on the patient’s quality of life is not well-described.Questions/purposesAfter controlling for confounding variables, we asked (1) are restrictions on weightbearing and activity associated with physical health measures (as expressed by the Patient-Reported Outcome Measurement Information System [PROMIS] mobility, PROMIS pain interference, and PROMIS fatigue) of children in the active stages of Perthes disease? (2) Are these restrictions associated with poorer scores for mental health measures (PROMIS depressive symptoms and PROMIS anxiety)? (3) Are these restrictions associated with poorer scores for social health measures (PROMIS peer relationships)?MethodsBetween 2013 and 2020, 211 patients with Perthes disease at a single institution were assigned six PROMIS measures to assess physical, mental, and social health. Patients who met the following eligibility criteria were analyzed: age 8 to 14 years old, completion of six PROMIS measures, English-speaking, and active stage of Perthes disease (Waldenstrom Stage I, II, or III). Weightbearing and activity restrictions were clinically recommended to patients in the initial through early reossification stages of Perthes disease when patients had increasing pain, loss of hip motion, loss of hip containment, progression of femoral head deformity, increased hip synovitis, and femoral head involvement on MRI or as a postoperative regimen. Patients were categorized into four intervention groups based on weightbearing and activity regimen. We excluded 111 patients who did not meet the inclusion criteria. The following six pediatric self-report PROMIS measures were assessed: mobility, pain interference, fatigue, depressive symptoms, anxiety, and peer relationships. Of the 100 patients, 36 were categorized into the no-restriction regimen, 27 into the mild-restriction regimen, 25 into the moderate-restriction regimen, and 12 into the severe-restriction regimen at the time of PROMIS administration. The median (range) age at diagnosis was 8 years old (range 2 to 13 years). There were 85 boys and 15 girls. Eleven patients had hips in Waldenstrom Stage I, 10 were in Stage II, and 79 were in Stage III. Forty-four patients had hips classified as lateral pillar B and 47 patients as lateral pillar C. Nine patients had not reached the mid-fragmentation stage for appropriate lateral pillar classification by the time they took the PROMIS survey. ANOVA was used to compare differences between the mean PROMIS T-scores of these weightbearing/activity regimens. Results were assessed with a significance of p < 0.05 and adjusted for Waldenstrom stage, gender, age at diagnosis, and history of major surgery using multivariate regression analysis.ResultsAfter controlling for confounding variables, the mild- (β regression coefficient -15 [95% CI -19 to -10]; p < 0.001), moderate- (β -19 [95% CI -24 to -14]; p < 0.001), and severe- (β -25 [95% CI -30 to -19]; p < 0.001) restriction groups were associated with worse mobility T-scores compared with the no-restriction group, but no association was detected for the pain interference or fatigue measures. Weightbearing and activity restrictions were not associated with mental health measures (depressive symptoms and anxiety). Weightbearing and activity restrictions were not associated with social health measures (peer relationships). Earlier Waldenstrom stage was associated with worse pain interference (β 10 [95% CI 2 to 17]; p = 0.01) and peer relationships scores (β -8 [95% CI -15 to -1]; p = 0.03); female gender was linked with worse depressive symptoms (β 7 [95% CI 2 to 12]; p = 0.005) and peer relationships scores (β -6 [95% CI -12 to 0]; p = 0.04); and earlier age at diagnosis was associated with worse peer relationships scores (β 1 [95% CI 0 to 2]; p = 0.03). History of major surgery had no connection to any of the six PROMIS measures.ConclusionWe found that weightbearing and activity restriction treatments are associated with poorer patient-reported mobility in the active stages of Perthes disease after controlling for Waldenstrom stage, gender, age at diagnosis, and history of surgery. Weightbearing/activity restrictions, however, are not associated with pain interference, fatigue, depressive symptoms, anxiety, and peer relationships. Understanding how these treatments are associated with quality of life in patients with Perthes disease can aid in decision-making for providers, help set expectations for patients and their parents, and provide opportunities for better education and preparation. Because of the chronic nature of Perthes disease, future studies may focus on longitudinal trends in patient-reported outcomes to better understand the overall impact of this disease and its treatment.Level of EvidenceLevel III, therapeutic study.     

A comparative study of portal vein embolization versus radiation lobectomy with Yttrium-90 micropheres in preparation for liver resection for initially unresectable hepatocellular carcinoma

BackgroundPortal vein embolization before liver resection is considered the therapy of choice for patients with inadequate future liver remnants. The concept of radioembolization with Yttrium-90 to achieve the same goal has limited data.MethodsWe retrospectively compared patients who underwent portal vein embolization and Yttrium-90 lobectomy before resection of hepatocellular carcinoma in patients with chronic liver disease.ResultsSeventy-three patients underwent portal vein embolization and 22 patients underwent Yttrium-90. Forty-seven percent of patients before portal vein embolization required additional procedures for tumor control, and 27% of patients after Yttrium-90 required additional procedure to mainly induce further hypertrophy. Both therapies achieved the goal of future liver remnants >40%, but the degree of hypertrophy was significantly higher in Yttrium-90 patients (63% for Yttrium-90, 36% for portal vein embolization, P < .01). Tumor response was significantly better with Yttrium-90, achieving complete response in 50% of patients. Resectability rate was higher after portal vein embolization (85% for portal vein embolization, 64% for Yttrium-90, P = .03). Tumor progression was the most common reason precluding surgery. Complete tumor control was the reason not to pursue surgery in 18% of patients after Yttrium-90.ConclusionBoth preoperative portal vein embolization and Yttrium-90, increases liver resectability rates by inducing hypertrophy of future liver remnants in patients with hepatocellular carcinoma and chronic liver disease. Yttrium-90 lobectomy achieved better tumor control and provided more time to assess therapy response, optimizing the indication for surgery.     

Clinical Significance of De Novo Malignancy After Liver Transplant: A Single-Center Study

BackgroundSeveral studies have reported that solid organ transplant recipients have a high risk for malignant tumors because the suppressed immune system fails in preventing malignant transformations. De novo malignancy after transplantation is the most common cause of death in the late period after liver transplant (LT). This study investigated the clinical significance of de novo malignancy after LT, and it is the largest study based in Korea to report long-term follow-up results associated with de novo malignancy after LT.MethodsData of 1793 adults who underwent LT in Seoul National University Hospital were retrospectively collected, and medical charts and data from the Ministry of Public Administration and Security were reviewed to examine the causes of death and de novo malignancy status. The Fisher exact test and Kaplan-Meier survival analysis were used to analyze the data.ResultsOf the 1793 recipients, 27 died of de novo malignancies. Of 875 hepatocellular carcinoma (HCC) patients, 12 died, and of 918 non-HCC patients, 15 died. De novo malignancy was the main cause of death at 5 years after LT but was not in the initial 5 years. In Korea the most common cancers that developed after LT were gastric cancer (21.4%) and lymphoma (14.3%). De novo HCC in non-HCC cases was found in 2 patients.ConclusionDe novo malignancy is a key factor affecting long-term survival after LT. Therefore, regular screening and education are important for improving long-term survival and quality of life in these patients after LT.     

Clinical Characteristics and Risk Factors of Early-Onset Tuberculosis After Liver Transplantation

BackgroundWe encountered some cases of early-onset tuberculosis (TB) after liver transplant (LT), leading to further transmission to other immunocompromised patients. Therefore, we investigated the clinical characteristics and risk factors of early-onset TB after LT.MethodsAll adult patients with TB after LT from 1996 to 2019 were retrospectively enrolled. Our hospital did not screen for latent TB infection (LTBI) in LT recipients because of concerns regarding the potential hepatotoxicity of anti-TB medication. Patients were categorized into 2 groups based on the TB onset time after LT: early-onset TB (≤2 months) and late-onset TB (>2 months).ResultsOf 4301 LT recipients, 91 patients developed TB after LT (2.1%). The median time from LT to TB development was 9.4 months. Of these 91 patients, 11 were classified as having early-onset TB (12.1%). Patients with early-onset TB had a greater pretransplant TB history than patients with late-onset TB (36.4% vs 11.3%, P = .048).ConclusionThis unusual early-onset TB was more common in patients with a pretransplant TB history, suggesting the possibility of missed TB or full manifestation of the indolent course of TB after LT. Therefore, LT recipients with a pretransplant TB history should undergo thorough screening for active TB and consider prophylaxis.     

Measuring patient perceptions of surgeon communication performance in the treatment of thyroid nodules and thyroid cancer using the communication assessment tool

BackgroundThyroid surgeons are offering their patients less aggressive diagnostic and therapeutic management strategies for thyroid nodules and low-risk thyroid cancer in an effort to decrease overdiagnosis and overtreatment of indolent disease. Explaining the rationale for less aggressive management plans requires physicians to be effective communicators. We aimed to assess the communication skills of thyroid surgeons with the Makoul Communication Assessment Tool and to identify risk factors for poor communication.MethodsNew adult patients with thyroid nodules or thyroid cancer presenting to a single tertiary-referral endocrine surgery clinic were enrolled from July 2018 through December 2019. Patients were administered the Communication Assessment Tool immediately after their clinical encounter. Outlier communication scores were identified, and clinical characteristics were compared between outlier and nonoutlier groups.ResultsA total of 107 patients completed the Communication Assessment Tool. Mean (standard deviation) total and top box scores were 67 (6) and 86% (29%), respectively. Twenty-five patients (23%) were in the low-outlier group, defined by a total score below 67.5/70 or top box score below 82.25%. Other race and non-Hispanic patients (versus white race) were more likely low outliers (odds ratio 3.58, P = .048). The lowest scoring Communication Assessment Tool item overall was “the doctor encouraged me to ask questions” (78.5% top box).ConclusionWe found communication to be perceived as excellent in the majority of patients; however, an opportunity for improvement was identified in 29% of participants. Significant differences in race and ethnicity between low outlier and nonoutlier communication score patients were observed, which warrants additional investigation. These findings support the utility of the Communication Assessment Tool in studying the effectiveness of communication improvement initiatives.     

Berberine plays a cardioprotective role by inhibiting macrophage Wnt5a/β-catenin pathway in the myocardium of mice after myocardial infarction

Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/β-catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/β-catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI.     

Wound outcomes and factors associated with wound healing after first-time femoropopliteal artery intervention in patients with ischemic tissue loss

Background/objectiveThis study’s goal is to describe wound outcomes at 2 years following intervention for atherosclerotic femoropopliteal lesions in patients with ischemic tissue loss.MethodsA retrospective review of 135 first-time endovascular procedures for chronic femoropopliteal atherosclerotic lesions related to ischemic tissue loss was performed. The final wound outcomes were categorized according to the initial wound healing, recurrence and the need of major/minor amputation.ResultsAt 2-years of follow up, 76 limbs (56.3%) showed complete wound healing without recurrence, however, wound development occurred at other sites on the same foot following complete primary healing in 11 limbs (8.1%). Tolerable wounds persisted or wounds recurred at the same site in 30 limbs (22.2%), and 18 limbs (13.3%) needed major amputations. Independent factors that prevented wound healing without recurrence at 2 years were renal insufficiency (HR = 0.225, 95% C.I. = 0.091–0.556, p = 0.001), ankle pressure < 50 mmHg or flat forefoot PVR (HR = 0.328, 95% C.I. = 0.124–0.867, p = 0.025) and functional performance < 4 metabolic equivalents (MET) (HR = 0.150, 95% C.I. = 0.063–0.360, p < 0.001).ConclusionWound outcome classifications showed detailed information regarding clinical outcomes in patients with ischemic tissue loss. Renal insufficiency, ischemia grade 3 and poor functional performance were independent risk factors that prevented wound healing.