Concurrent Use of Statins in Patients Undergoing Curative Intent Treatment for Triple Negative Breast Cancer: A Systematic Review and Meta-Analysis.

Pre-clinical studies in triple negative breast cancer (TNBC) suggest that statins may inhibit cell proliferation, promote cell-cycle arrest, induce apoptosis, change the tumor microenvironment, and improve effectiveness of other therapies. Observational studies have demonstrated variable effects from statin therapy on oncologic outcomes in these patients. As such, we aimed to pool previous data via a systematic review and meta-analysis to elucidate the impact of concurrent statin use on oncologic outcomes for patients with TNBC. Medline, EMBASE, CENTRAL, and PubMed were systematically searched from inception through to June 2022. Studies were included if they compared patients with TNBC receiving and not receiving statin therapy concurrently with oncologic treatment for curative intent in terms of recurrence and survival in a non-metastatic setting. The primary outcomes were 5-year disease-free survival (DFS) and 5-year overall survival (OS). A pairwise meta-analyses was performed using inverse variance random effects. Risk of bias was assessed with the ROBINS-I and the GRADE approach was conducted to assess quality of evidence. From 4014 citations, 5 studies with 625 patients on statin therapy and 2707 patients not on statin therapy were included. There was a significant increase in 5-year DFS for patients on statin therapy compared to patients not on statin therapy (OR 1.44, 95% CI 1.04-1.98, P = .03). No significant difference was noted in 5-year OS between the 2 groups (OR 1.12, 95% CI 0.86-1.47, P = .40). Included studies were at moderate-to-high risk of bias. The GRADE quality of evidence was very low. This review presents very low-quality evidence that concurrent use of statins with oncologic treatment may potentially improve long-term DFS for patients with TNBC undergoing curative intent therapy. Future research by way of large, prospective study is required to further clarify the clinical utility of statins on patients undergoing treatment for TNBC.

Residual Risk of Breast Cancer After Bariatric Surgery.

Importance: Excess adiposity confers higher risk of breast cancer for women. For women who have lost substantial weight, it is unclear whether previous obesity confers residual increased baseline risk of breast cancer compared with peers without obesity. Objectives: To determine whether there is a residual risk of breast cancer due to prior obesity among patients who undergo bariatric surgery. Design, Setting, and Participants: Retrospective matched cohort study of 69 260 women with index date between January 1, 2010, and December 31, 2016. Patients were followed up for 5 years after bariatric surgery or index date. Population-based clinical and administrative data from multiple databases in Ontario, Canada, were used to match a cohort of women who underwent bariatric surgery for obesity (baseline body mass index [BMI] ≥35 with comorbid conditions or BMI ≥40) to women without a history of bariatric surgery according to age and breast cancer screening history. Nonsurgical controls were divided into 4 BMI categories (<25, 25-29, 30-34, and ≥35). Data were analyzed on October 21, 2021. Exposures: Weight loss via bariatric surgery. Main Outcomes and Measures: Residual hazard of breast cancer after washout periods of 1, 2, and 5 years. Comparisons were made between the surgical and nonsurgical cohorts overall and within each of the BMI subgroups. Results: In total, 69 260 women were included in the analysis, with 13 852 women in each of the 5 study cohorts. The mean (SD) age was 45.1 (10.9) years. In the postsurgical cohort vs the overall nonsurgical cohort (n = 55 408), there was an increased hazard for incident breast cancer in the nonsurgical group after washout periods of 1 year (hazard ratio [HR], 1.40 [95% CI, 1.18-1.67]), 2 years (HR, 1.31 [95% CI, 1.12-1.53]), and 5 years (HR, 1.38 [95% CI, 1.21-1.58]). When the postsurgical cohort was compared with the nonsurgical cohort with BMI less than 25, the hazard of incident breast cancer was not significantly different regardless of the washout period, whereas there was a reduced hazard for incident breast cancer among postsurgical patients compared with nonsurgical patients in all high BMI categories (BMI ≥25). Conclusions and Relevance: Findings suggest that bariatric surgery was associated with a reduced risk of developing breast cancer for women with prior obesity equivalent to that of a woman with a BMI less than 25 and a lower risk when compared with all groups with BMI greater than or equal to 25.

Safety and Accuracy of Sentinel Lymph Node Biopsy Alone in Clinically Node-Positive Patients Undergoing Upfront Surgery for Invasive Breast Cancer: A Systematic Review.

Landmark trials (Z0011 and AMAROS) have demonstrated that axillary lymph node dissection (ALND) can be safely omitted in patients with breast cancer and 1-2 positive sentinel nodes. Extrapolating from these and other cardinal studies such as NSABP B-04, guidelines state that patients with 1-2 needle biopsy-proven positive lymph nodes undergoing upfront surgery can have sentinel lymph node biopsy (SLNB) alone. The purpose of this study is to systematically review the literature to identify studies examining the direct application of SLNB in such patients. EMBASE and Ovid MEDLINE were searched from inception to 3 May 2022. Studies including patients with nodal involvement confirmed on pre-operative biopsy and undergoing SLNB were identified. Studies with neoadjuvant chemotherapy were excluded. Search resulted in 2518 records, of which 68 full-text studies were reviewed, ultimately yielding only 2 studies meeting inclusion criteria. Both studies used targeted axillary surgery (TAS) with pre-operative localization of the biopsy-proven positive node in addition to standard SLNB techniques. In a non-randomized single-center prospective study, Lee et al. report no regional recurrences in patients undergoing TAS or ALND, and no difference in distant recurrence or mortality at 5 years. In the prospective multicenter TAXIS trial by Webber et al., the median number of positive nodes retrieved with TAS in patients undergoing upfront surgery was 2 (1, 4 IQR). Within the subset of patients who underwent subsequent ALND, 61 (70.9%) had additional positive nodes, with 26 (30.2%) patients having ≥4 additional positive nodes. Our review demonstrates that there is limited direct evidence for SLNB alone in clinically node-positive patients undergoing upfront surgery. Available data suggest a high proportion of patients with residual disease in this setting. While the totality of the data, mostly indirect evidence, suggests SLNB alone may be safe, we call on clinicians and researchers to prospectively collect data on this patient population to better inform decision-making.

A Canadian survey of medical students and undergraduate deans on the management of patients living with obesity.

BACKGROUND: With over 26% of Canadian adults living with obesity, undergraduate medical education (UGME) should prepare medical students to manage this chronic disease. It is currently unknown how the management of patients living with obesity is taught within UGME curricula in Canada. This study (1) examined the knowledge and self-reported competence of final-year medical students in managing patients living with obesity, and (2) explored how this topic is taught within UGME curricula in Canada. METHODS: We distributed two online surveys: one to final-year medical students, and another to UGME deans at 9 English-speaking medical schools in Canada. The medical student survey assessed students' knowledge and self-reported competence in managing patients living with obesity. The dean's survey assessed how management of patients living with obesity is taught within the UGME curriculum. RESULTS: One hundred thirty-three (6.9%) and 180 (9.3%) out of 1936 eligible students completed the knowledge and self-reported competence parts of the survey, respectively. Mean knowledge score was 10.5 (2.1) out of 18. Students had greatest knowledge about etiology of obesity and goals of treatment, and poorest knowledge about physiology and maintenance of weight loss. Mean self-reported competence score was 2.5 (0.86) out of 4. Students felt most competent assessing diet for unhealthy behaviors and calculating body mass index. Five (56%) out of 9 deans completed the survey. A mean of 14.6 (5.0) curricular hours were spent on teaching management of patients living with obesity. Nutrition and bariatric surgery were most frequently covered topics, with education delivered most often via large-group sessions and clinical activities. CONCLUSIONS: Canadian medical students lack adequate knowledge and feel inadequately prepared to manage patients living with obesity. Changes to UGME curricula may help address this gap in education.

Bariatric Surgery and Breast Cancer Incidence: a Population-Based, Matched Cohort Study.

PURPOSE: Obesity is associated with increased breast cancer risk in women. Bariatric surgery induces substantial weight loss. However, the effects of such weight loss on subsequent breast cancer risk in women with obesity are poorly understood. To examine breast cancer incidence and related outcomes in women with obesity undergoing bariatric surgery. MATERIALS AND METHODS: This was a population-based matched cohort study of breast surgery outcomes utilizing linked clinical databases in Ontario, Canada. Women with obesity who underwent bariatric surgery were 1:1 matched using a propensity score to non-surgical controls for age and breast cancer screening history. The main outcomes were incidence of breast cancer after lag periods of 1, 2, and 5 years. Additional outcomes included tumor hormone receptor status, cancer stage, and treatments undertaken. Time-varying Cox proportional hazard models accounting for screening during follow-up were used to model cancer incidence. RESULTS: A total of 12,724 women per group were included, average age 45.09. After a 1-year lag, breast cancer incidence occurred in 1.09% and 0.79% of the control and surgery groups, respectively (adjusted hazard ratio, 0.81 [95%CI 0.69-0.95]; p = 0.01). This association was maintained after lag periods of 2 and 5 years. Women in the surgical cohort diagnosed with breast cancer were more likely to have low-grade tumors and less likely to have high-grade tumors (overall p < 0.01). No association was found for tumor hormone receptor status, although the surgical group was more likely to have her2neu-negative tumors (p = 0.01). CONCLUSION: Bariatric surgery was associated with a lower incidence of breast cancer and lower tumor grade in women with obesity. Further evaluation of outcomes, including mortality, is required.

Improvement of kidney function in patients with chronic kidney disease and severe obesity after bariatric surgery: A systematic review and meta-analysis.

The general management for chronic kidney disease (CKD) includes treating reversible causes, including obesity, which may be both a driver and comorbidity for CKD. Bariatric surgery has been shown to reduce the likelihood of CKD progression and improve kidney function in observational studies. We performed a systematic review and meta-analysis of patients with at least stage 3 CKD and obesity receiving bariatric surgery. We searched Embase, MEDLINE, CENTRAL and identified eligible studies reporting on kidney function outcomes in included patients before and after bariatric surgery with comparison to a medical intervention control if available. Risk of bias was assessed with the Newcastle-Ottawa Risk of Bias score. Nineteen studies were included for synthesis. Bariatric surgery showed improved eGFR with a mean difference (MD) of 11.64 (95%CI: 5.84 to 17.45, I2  = 66%) ml/min/1.73m2 and reduced SCr with MD of -0.24 (95%CI -0.21 to -0.39, I2  = 0%) mg/dl after bariatric surgery. There was no significant difference in the relative risk (RR) of having CKD stage 3 after bariatric surgery, with a RR of -1.13 (95%CI: -0.83 to -2.07, I2  = 13%), but there was reduced likelihood of having uACR >30 mg/g or above with a RR of -3.03 (95%CI: -1.44 to -6.40, I2  = 91%). Bariatric surgery may be associated with improved kidney function with the reduction of BMI and may be a safe treatment option for patients with CKD. Future studies with more robust reporting are required to determine the feasibility of bariatric surgery for the treatment of CKD.

Risk factors and protective measures for healthcare worker infection during highly infectious viral respiratory epidemics: A systematic review and meta-analysis.

OBJECTIVE: To investigate risk factors for healthcare worker (HCW) infection in viral respiratory pandemics: severe acute respiratory coronavirus virus 2 (SARS-CoV-2), Middle East respiratory syndrome (MERS), SARS CoV-1, influenza A H1N1, influenza H5N1. To improve understanding of HCW risk management amid the COVID-19 pandemic. DESIGN: Systematic review and meta-analysis. METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL databases from conception until July 2020 for studies comparing infected HCWs (cases) and noninfected HCWs (controls) and risk factors for infection. Outcomes included HCW types, infection prevention practices, and medical procedures. Pooled effect estimates with pathogen-specific stratified meta-analysis and inverse variance meta-regression analysis were completed. We used the GRADE framework to rate certainty of evidence. (PROSPERO no. CRD42020176232, 6 April 2020.). RESULTS: In total, 54 comparative studies were included (n = 191,004 HCWs). Compared to nonfrontline HCWs, frontline HCWs were at increased infection risk (OR, 1.66; 95% CI, 1.24-2.22), and the risk was greater for HCWs involved in endotracheal intubations (risk difference, 35.2%; 95% CI, 21.4-47.9). Use of gloves, gown, surgical mask, N95 respirator, face protection, and infection training were each strongly protective against infection. Meta-regression showed reduced infection risk in frontline HCWs working in facilities with infection designated wards (OR, -1.04; 95% CI, -1.53 to -0.33, P = .004) and performing aerosol-generating medical procedures in designated centers (OR, -1.30; 95% CI, -2.52 to -0.08; P = .037). CONCLUSIONS: During highly infectious respiratory pandemics, widely available protective measures such as use of gloves, gowns, and face masks are strongly protective against infection and should be instituted, preferably in dedicated settings, to protect frontline HCW during waves of respiratory virus pandemics.

Outcomes of bariatric surgery in elderly patients: a registry-based cohort study with 3-year follow-up.

BACKGROUND: Elderly patients undergo bariatric surgery less frequently than younger patients. Short- and medium-term outcomes after bariatric surgery in the elderly population remain largely unknown. The objective of the present retrospective, registry-based cohort study was to compare short- and medium-term outcomes between patients <65 and ≥65 years undergoing bariatric surgery, hypothesizing similar outcomes between groups. METHODS: In this retrospective, registry-based cohort study, the Ontario Bariatric Registry was used to compare data of patients <65 and ≥65 years who underwent Roux-en-Y gastric bypass and sleeve gastrectomy between January 2010 and August 2019 in all accredited bariatric centers of excellence in Ontario, Canada. Primary outcomes were overall postoperative complications. Secondary outcomes included early (<30 days) complications, readmissions, reoperations, mortality, weight loss and comorbidities improvement at 1 and 3 year after surgery. RESULTS: Data of 22,981 patients <65 and 532 patients ≥65 years were analyzed. Overall postoperative complications were similar between patients <65 and ≥65 years (3388/22,981 [14.7%] vs. 73/532 [13.7%], p = 0.537). Early (<30 days) postoperative complications, readmissions, reoperations, and mortality rates were also similar between groups. Both groups had significant weight loss and comorbidities improvement at 1- and 3-year follow-up. Patients <65 years had superior weight loss (+3.5%, 95% CI: 1.6-5.4, p < 0.001) and higher rates of remission for diabetes mellitus (63.8% vs. 39.3%, p < 0.001), hypertension (37.9% vs. 14.5%, p < 0.001), dyslipidemia (28.2% vs. 9.5%, p < 0.001) and gastroesophageal reflux (65.1% vs. 24.0 %, p < 0.001) compared to patients ≥65 years at 3 year. CONCLUSIONS: Patients <65 and ≥65 years had similar perioperative morbidity and mortality after bariatric surgery. Even though patients <65 years had overall better medium-term outcomes, bariatric surgery is safe and yields significant weight loss and comorbidities improvement in patients ≥65 years.

The role of bariatric surgery on kidney transplantation: A systematic review and meta-analysis.

INTRODUCTION: Obesity (body mass index [BMI] >35 kg/m2) remains a relative contraindication for kidney transplant, while patients after kidney transplantation (KTX) are predisposed to obesity. The present study aims to investigate the role of bariatric surgery in improving transplant candidacy in patients prior to KTX, as well its safety and efficacy in KTX patients postoperatively. METHODS: A systematic search was conducted up to March 2020. Both comparative and non-comparative studies investigating the role of bariatric surgery before or after KTX were considered. Outcomes included change in BMI, rates of mortality and complications, and the rate of patients who underwent KTX following bariatric surgery. Pooled estimates were calculated using the random effects meta-analysis of proportions. RESULTS: Twenty-one studies were eligible for final review; 11 studies investigated the role of bariatric surgery before KTX. The weighted mean BMI was 43.4 (5.7) kg/m2 at baseline and 33.9 (6.3) kg/m2 at 29.1 months followup. After bariatric surgery, 83% (95% confidence interval [CI] 57-99) were successfully listed for KTX and 83% (95% CI 65-97) of patients subsequently received successful KTX. Ten studies investigated the role of bariatric surgery after kidney transplant. Weighted mean baseline BMI was 43.8 (2.2) kg/m2 and mean BMI at 19.5 months followup was 34.2 (6.7) kg/m2. Overall, all-cause 30-day mortality was 0.5% for both those who underwent bariatric surgery before or after receiving a KTX. The results of this study are limited by the inclusion of only non-randomized studies, limited followup, and high heterogeneity. CONCLUSIONS: Bariatric surgery may be safe and effective in reducing weight to improve KTX candidacy in patients with severe obesity and can also be used safely following KTX.

A population-based study of treatment patterns, 10-year recurrence and breast cancer-specific mortality in a cohort of elderly patients with breast cancer.

BACKGROUND: We compared disease characteristics, therapies offered and received, and outcomes between older (>75 years) and younger (60-75 years) women with breast cancer (BC) from a regional database in Ontario, Canada. METHODS: BC surgical cases from 12 hospitals were included. Younger (60-75 years) and older (>75 years) groups were compared. Cox proportional hazards regression with competing risk analyses assessed the relationship between predictor variables, 10-year recurrence and BC-specific mortality. RESULTS: Our sample comprised 774 women; 33.5% were older. Older women had larger tumours, were more likely to have positive nodes, had more comorbidities, were more likely to undergo mastectomy, had less nodal surgery, were less likely to receive adjuvant therapies, and experienced more recurrences and BC-specific deaths (p < 0.05). Significant predictors of recurrence were older age, higher grade and disease stage, and omission of nodal surgery. Older age, higher grade, and stage were predictors of BC-specific mortality. CONCLUSION: Older BC patients (>75 years) received less treatment and experienced increased recurrence and BC-specific mortality.

Bariatric surgery before, during, and after liver transplantation: a systematic review and meta-analysis.

Morbid obesity is considered a relative contraindication for liver transplantation (LTX) because of increased risk of complications. The aim of this study was to investigate the role of bariatric surgery before, during, and after LTX. A systematic review of MEDLINE, EMBASE, CENTRAL, and PubMed databases was performed for studies investigating bariatric surgery in patients before, during, or after LTX. Random-effects meta-analysis of proportions was used to calculate pooled effect estimates. One hundred eighty-seven patients underwent bariatric surgery before LTX (8 studies). After surgery, 82% (95% confidence interval, 62%-97%) of patients were successfully listed for LTX and 70% (95% confidence interval, 40%-93%) successfully received LTX. The 30-day mortality rate was 0%. The graft survival rate after 1 year was 70% (95% confidence interval, 30%-99%). Thirty-day minor and major complications rate was 4% and 1%, respectively. Thirty-two patients underwent bariatric surgery during LTX (2 studies). The 30-day mortality rate after surgery was 0% and 1-year graft survival was 100%. Sixty-four patients underwent bariatric surgery after LTX (9 studies). The 30-day mortality was 0%, but 5 deaths occurred beyond 30 days (7.8%). Bariatric surgery may be safe and feasible as a bridge to LTX for patients who would otherwise be ineligible and post-LTX patients for weight loss.

Metabolic outcomes after bariatric surgery for Indigenous patients in Ontario.

BACKGROUND: In 2013, 18% of Canadian adults had obesity (body mass index [BMI] >30 kg/m2), compared with 25.7% of Canada's Indigenous population. Bariatric surgery is an effective treatment for obesity, but has not been studied in Canadian Indigenous populations. OBJECTIVES: To determine the effects of bariatric surgery in the Indigenous Ontario population. SETTING: Multicenter data from the publicly funded Ontario bariatric program and registry. METHODS: Prospectively collected data using all surgical patients between March 2010 and 2018 was included in initial analysis and included the following postoperative outcomes: diabetes, hypertension, and gastroesophageal reflux disease. Demographic characteristics, baseline characteristics, and univariate outcomes were assessed using Pearson Χ2 or t tests. Multivariable regression for BMI change was used with complete case analysis and multiple imputation. RESULTS: Of 16,629 individuals initially identified, 338 self-identified as Indigenous, 13,502 as Non-Indigenous, and 2789 omitted ethnicity and were excluded. Baseline demographic characteristics were not statistically different; rates of hypertension (P = .03) and diabetes (P < .001) were higher in the Indigenous population. Univariable analysis showed similar 1-year BMI change (Indigenous: 15.8 ± 6.0 kg/m2; Non-Indigenous: 16.1 ± 5.6 kg/m2, P = .362). After adjustment, BMI change was not different between groups at 6 months (effect size = .07, 95% confidence interval -.45 to .58, P = .803) and 1 year (effect size = -.24, 95% confidence interval -.93 to .45, P = .489). Rates of co-morbidities were similar at 1 year between the 2 populations, despite differences at baseline. Six-month and 1-year follow-up rates were higher in the Non-Indigenous population (P < .001, P = .005, respectively). CONCLUSIONS: Weight loss and resolution of obesity-related co-morbidities are similar in Indigenous and Non-Indigenous patients. Access to surgery, patient selection, and long-term results merit further investigation.