Ductal carcinoma in situ (DCIS) is a precursor lesion of invasive ductal carcinoma (IDC) of the breast. To understand the dynamics of genomic alterations in this progression, we used four multicolor fluorescence in situ hybridization probe panels consisting of the oncogenes COX2, MYC, HER2, CCND1, and ZNF217 and the tumor suppressor genes DBC2, CDH1, and TP53 to visualize copy number changes in 13 cases of synchronous DCIS and IDC based on single-cell analyses. The DCIS had a lower degree of chromosomal instability than the IDC. Despite enormous intercellular heterogeneity in DCIS and IDC, we observed signal patterns consistent with a nonrandom distribution of genomic imbalances. CDH1 was most commonly lost, and gain of MYC emerged during progression from DCIS to IDC. Four of 13 DCISs showed identical clonal imbalances in the IDCs. Six cases revealed a switch, and in four of those, the IDC had acquired a gain of MYC. In one case, the major clone in the IDC was one of several clones in the DCIS, and in another case, the major clone in the DCIS became one of the two major clones in the IDC. Despite considerable chromosomal instability, in most cases the evolution from DCIS to IDC is determined by recurrent patterns of genomic imbalances, consistent with a biological continuum.

Summary To assess the effectiveness of liraglutide 3.0 mg in post‐bariatric surgery patients, and to determine whether this would differ based on the type of bariatric surgery. One hundred seventeen post‐bariatric surgery patients from the Wharton Medical Clinic were analysed. Changes in weight while taking liraglutide 3.0 mg were examined for all patients, and by three types of bariatric surgery—Roux‐en‐Y gastric bypass, gastric banding and gastric sleeve. Patients primarily underwent Roux‐en‐Y gastric bypass (n = 53, 45.3%) or gastric banding (n = 50, 42.7%). Over 7.6 ± 7.1 months taking liraglutide 3.0 mg, patients lost a statistically significant amount of weight (−6.3 ± 7.7 kg, P < .05) regardless of the type of surgery they had (P > .05). This decrease in weight remained significant after 1‐year of taking liraglutide 3.0 mg (P < .05). Nausea was the most prevalent side effect, reported by 29.1% patients. While options for excess weight management in post‐bariatric surgery patients are limited, results of this study suggest that post‐bariatric surgery patients can lose a significant amount of weight while taking liraglutide 3.0 mg regardless of the type of surgery they had. Further, similar to non‐surgical populations, post‐bariatric surgery patients taking liraglutide 3.0 mg may experience gastrointestinal side effects such as nausea and can continue to lose weight up to 1 year.

Objective Real‐world clinical effectiveness of liraglutide 3.0 mg, in combination with diet and exercise, was investigated 4 and 6 months post initiation. Changes in absolute and percent body weight were examined from baseline. Methods A cohort of liraglutide 3.0 mg initiators in 2015 and 2016 was identified from six Canadian weight‐management clinics. Post initiation values at 4 and 6 months were compared with baseline values using a paired t test. Results The full cohort consisted of 311 participants, with 210 in the ≥ 4‐month persistence group and 167 in the ≥ 6‐month persistence group. Average baseline BMI was 40.7 kg/m2, and weight was 114.8 kg. There was a significant change in body weight 6 and 4 months after initiation of treatment in persistent subjects (≥ 6‐month: −8.0 kg, P < 0.001; ≥ 4‐month: −7.0 kg, P < 0.001) and All Subjects, regardless of persistence (−7.3 kg; P < 0.001). Percentage change in body weight from baseline was −7.1% in the ≥ 6‐month group and −6.3% in the ≥ 4‐month group, and All Subjects lost 6.5% body weight. Of participants in the ≥ 6‐month group, 64.10% and 34.5% lost ≥ 5% and > 10% body weight, respectively. Conclusions In a real‐world setting, liraglutide 3.0 mg, when combined with diet and exercise, was associated with clinically meaningful weight loss.

BackgroundThe cause of the obesity epidemic is multifactorial, but may, in part, be related to medication-induced weight gain. While clinicians may strive to do their best to select pharmacotherapy(ies) that has the least negative impact on weight, the literature regarding the weight effects of medication is often limited and devoid of alternative therapies.ResultsAntipsychotics, antidepressants, antihyperglycemics, antihypertensives and corticosteroids all contain medications that were associated with significant weight gain. However, there are several medication alternatives within the majority of these classes associated with weight neutral or even weight loss effects. Further, while not all of the classes of medication examined in this review have weight-favorable alternatives, there exist many other tools to mitigate weight gain associated with medication use, such as changes in dosing, medication delivery or the use of adjunctive therapies.ConclusionMedication-induced weight gain can be frustrating for both the patient and the clinician. As the use of pharmaceuticals continues to increase, it is pertinent for clinicians to consider the weight effects of medications prior to prescribing or in the course of treatment. In the case where it is not feasible to make changes to medication, adjunctive therapies should be considered.

Background It has been suggested that cardiorespiratory fitness (CRF) may be used to identify those at greatest risk for severe COVID-19 illness. However, no study to date has examined the association between CRF and COVID-19. The objectives of this study were to determine whether CRF is independently associated with testing positive with or dying from COVID-19. Methods This is a prospective cohort study of 2,690 adults from the UK Biobank Study that were followed from March 16th, 2020 to July 26th, 2020. Participants who were tested for COVID-19 and had undergone CRF assessment were examined. CRF was estimated (eCRF) and categorized as low (<20th percentile), moderate (20th to 80th percentile) and high (≥80th percentile) within sex and ten-year age groups (e.g. 50–60 years). Participants were classified as having COVID-19 if they tested positive (primarily PCR tests) at an in-patient or out-patient setting as of July 26, 2020. Participants were classified as having died from COVID-19 if the primary or underlying cause of death was listed ICD-10 codes U071 or U072 by June 30th, 2020. Adjusted risk ratios (aRR) and 95% confidence intervals (CI) were estimated and a forward model building approach used to identify covariates. Findings There was no significant association between eCRF and testing positive for COVID-19. Conversely, individuals with moderate (aRR = 0.43, 95% CI: 0.25, 0.75) and high fitness (aRR = 0.37, 95% CI: 0.16, 0.85) had a significantly lower risk of dying from COVID-19 than those with low fitness. Conclusions While eCRF was not significantly associated with testing positive for COVID-19, we observed a significant dose-response between having higher eCRF and a decreased risk of dying from COVID-19. This suggests that prior gains in CRF could be protective against dying from COVID-19 should someone develop the virus.