Selective internal radiation therapy of metastatic breast cancer to the liver: A meta-analysis.

Introduction: The aim of this study is to conduct a meta-analysis to assess the efficacy of yttrium-90 selective internal radiation therapy (SIRT) in treating patients with breast cancer with hepatic metastasis. Method: PubMed and The Cochrane Library were queried from establishment to January 2021. The following keywords were implemented: "breast", "yttrium", and "radioembolization". The following variables and outcomes were collected: publication year, region, sample size, study design, presence of extrahepatic disease, tumor burden, infused radioactivity, breast cancer subtype, previous treatment, median survival time (MST), length of follow-up, adverse events, and radiographical response such as Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Results: A total of 24 studies from 14 institutions were included in the present meta-analysis. On the basis of the data from 412 patients, post-embolization MST was 9.8 [95% confidence interval (CI): 9.0-11.6] months. Patients with additional extrahepatic metastasis had a poorer survival rate compared with those with localized hepatic metastasis only (MST: 5.3 vs. 15 months, p < 0.0001). Patients with <25% liver tumor burden exhibited more promising survival than those with >25% (MST: 10.5 vs. 6.8 months, p < 0.0139). On the basis of RECIST, mRECIST, and PERCIST criteria, tumor response rate was 36% (95% CI: 26%-47%), 49% (95% CI: 34%-65%), and 47% (95% CI: 17%-78%), respectively, whereas tumor control rate was 85% (95% CI: 76%-93%), 73% (95% CI: 59%-85%), and 97% (95% CI: 91%-100%), respectively. Conclusion: On the basis of the available published evidence, SIRT is feasible and effective in treating patients with breast cancer with liver metastasis. Patients with lower hepatic tumor burden and without extrahepatic metastasis demonstrated more survival benefit. Future randomized controlled trials are warranted.

Defining Global Benchmarks in Elective Secondary Bariatric Surgery Comprising Conversional, Revisional, and Reversal Procedures.

OBJECTIVE: To define "best possible" outcomes for secondary bariatric surgery (BS). BACKGROUND: Management of poor response and of long-term complications after BS is complex and under-investigated. Indications and types of reoperations vary widely and postoperative complication rates are higher compared to primary BS. METHODS: Out of 44,884 BS performed in 18 high-volume centers from 4 continents between 06/2013-05/2019, 5,349 (12%) secondary BS cases were identified. Twenty-one outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of centers. Benchmark cases had no previous laparotomy, diabetes, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, thromboembolic events, BMI> 50 kg/m2 or age> 65 years. RESULTS: The benchmark cohort included 3143 cases, mainly females (85%), aged 43.8 ±â€Š10 years, 8.4 ±â€Š5.3 years after primary BS, with a BMI 35.2 ±â€Š7 kg/m2. Main indications were insufficient weight loss (43%) and gastro-esophageal reflux disease/dysphagia (25%). 90-days postoperatively, 14.6% of benchmark patients presented ≥1 complication, mortality was 0.06% (n = 2). Significantly higher morbidity was observed in non-benchmark cases (OR 1.37) and after conversional/reversal or revisional procedures with gastrointestinal suture/stapling (OR 1.84). Benchmark cutoffs for conversional BS were ≤4.5% re-intervention, ≤8.3% re-operation 90-days postoperatively. At 2-years (IQR 1-3) 15.6% of benchmark patients required a reoperation. CONCLUSION: Secondary BS is safe, although postoperative morbidity exceeds the established benchmarks for primary BS. The excess morbidity is due to an increased risk of gastrointestinal leakage and higher need for intensive care. The considerable rate of tertiary BS warrants expertise and future research to optimize the management of non-success after BS.

Chronic treatment with clenbuterol modulates endothelial progenitor cells and circulating factors in a murine model of cardiomyopathy.

The purpose of this study was to determine the effects of chronic treatment with the beta 2 adrenergic receptor agonist clenbuterol on endothelial progenitor cells (EPC) in a well-characterized model of heart failure, the muscle LIM protein knockout (MLP(-/-)) mouse. MLP(-/-) mice were treated daily with clenbuterol (2 mg/kg) or saline subcutaneously for 6 weeks. Clenbuterol led to a 30% increase in CD31(+) cells in the bone marrow of MLP(-/-) heart failure mice (p < 0.004). Clenbuterol did not improve ejection fraction. Clenbuterol treatment in MLP(-/-) mice was associated with significant changes in the following circulating factors: tissue inhibitor of metalloproteinase-type 1, leukemia inhibitory factor 1, C-reactive protein, apolipoprotein A1, fibroblast growth factor 2, serum glutamic oxaloacetic transaminase, macrophage-derived chemokine, and monocyte chemoattractant protein-3. Clenbuterol treatment in the MLP(-/-) model of heart failure did not rescue heart function, yet did increase CD31(+) cells in the bone marrow. This is the first evidence that a beta 2 agonist increases EPC proliferation in the bone marrow in a preclinical model of heart failure.

Iso-osmolar radio contrast iodixanol in patients with chronic kidney disease.

BACKGROUND: Although radio contrast volume has been associated with worsening post-procedural kidney function, this relationship has not been extensively studied using an iso-osmolar contrast agent in chronic kidney disease patients. METHODS: We retrospectively studied patients undergoing cardiac catheterization at the University of Minnesota from 2000 to 2004, using the iso-osmolar contrast agent, iodixanol. All patients were included who had calculated creatinine clearance (CCR) < 60 mL/min, not on dialysis, and serum creatinine measured on the same day and within 7 days after the procedure. Comparison of a subgroup with severe chronic kidney disease and diabetes mellitus was compared to a similar historical control group that used the low-osmolar contrast agent, iohexol. RESULTS: Serum creatinine and CCR were 2.9 +/- 1.5 mg/dL and 33.4 +/- 12.0 mL/min (mean +/- standard deviation), respectively, at baseline in 117 cases. Peak creatinine increased by 0.03 +/- 0.7 mg/dL after 84.3 +/- 67.3 mL of iodixanol was used. Contrast-induced nephropathy definition was fulfilled in 22 (18.8%) cases. A non-significant negative correlation was found between the volume of iodixanol and the change in creatinine (r2 = 0.0011, p = 0.7254). A subgroup with severe chronic kidney disease and diabetes mellitus with iodixanol had a significantly lower creatinine increase (n = 25, 0.09 +/- 0.5 mg/dL), compared to historical controls (n = 42, 0.7 +/- 0.8 mg/dL) with iohexol (p < 0.001). A non-significant positive correlation between volume of contrast and change in creatinine was found in this subgroup who received iodixanol (n = 25, r2 = 0.0756, p = 0.1835), but was significant in the historical controls who received iohexol (n = 42, r2 = 0.135, p = 0.017). CONCLUSIONS: The volume of iso-osmolar radio contrast does not affect the incidence of contrast-induced nephropathy in patients with chronic kidney disease. A randomized trial evaluating the incidence of contrast nephropathy would verify the safety of ad hoc versus staged angiographic procedures in this population.

Effects of sarcoplasmic reticulum Ca2+-ATPase overexpression in postinfarction rat myocytes.

Previous studies in adult myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) demonstrated abnormal contractility and intracellular Ca(2+) concentration ([Ca(2+)](i)) homeostasis and decreased sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) expression and activity, but sarcoplasmic reticulum Ca(2+) leak was unchanged. In the present study, we investigated whether SERCA2 overexpression in MI myocytes would restore contraction and [Ca(2+)](i) transients to normal. Compared with sham-operated hearts, 3-wk MI hearts exhibited significantly higher left ventricular end-diastolic and end-systolic volumes but lower fractional shortening and ejection fraction, as measured by M-mode echocardiography. Seventy-two hours after adenovirus-mediated gene transfer, SERCA2 overexpression in 3-wk MI myocytes did not affect Na(+)-Ca(2+) exchanger expression but restored the depressed SERCA2 levels toward those measured in sham myocytes. In addition, the reduced sarcoplasmic reticulum Ca(2+) uptake in MI myocytes was improved to normal levels by SERCA2 overexpression. At extracellular Ca(2+) concentration of 5 mM, the subnormal contraction and [Ca(2+)](i) transient amplitudes in MI myocytes (compared with sham myocytes) were restored to normal by SERCA2 overexpression. However, at 0.6 mM extracellular Ca(2+) concentration, the supernormal contraction and [Ca(2+)](i) transient amplitudes in MI myocytes (compared with sham myocytes) were exacerbated by SERCA2 overexpression. We conclude that SERCA2 overexpression was only partially effective in ameliorating contraction and [Ca(2+)](i) transient abnormalities in our rat model of ischemic cardiomyopathy. We suggest that other Ca(2+) transport pathways, e.g., Na(+)-Ca(2+) exchanger, may also play an important role in contractile and [Ca(2+)](i) homeostatic abnormalities in MI myocytes.

Percutaneous coronary intervention in chronic kidney disease patients.

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). The increased prevalence of CVD in patients with renal dysfunction has been attributed to lack of effective prevention and low utilization of effective therapy. The optimal treatment of ischemic heart disease in ESRD patients before renal transplantation is controversial. Although no meta-analysis or pooled analysis of the data from small trials exists, it appears that percutaneous coronary intervention (PCI) provides excellent angiographic success but is associated with increased restenosis and the need for revascularization and that coronary artery bypass grafting (CABG), while associated with higher in-hospital morbidity and mortality, provides better overall long-term results and freedom from angina. Despite suboptimal results for percutaneous interventions in comparison with bypass surgery, PCI remains a viable option, especially for patients who are not candidates for surgery and those with disabling angina despite anti-anginal therapy. Regardless of the revascularization strategy used, outcomes of CABG or PCI in these patients are significantly worse than outcomes in the general population. The long-term benefit after revascularization and adjunctive medical therapy should be an area of intense future research. Studies should also be conducted to investigate the benefit and safety of therapies such as the long-term use of beta-blockers, statins, and renin-angiotensin-aldosterone axis inhibition in patients with CKD.

Clinical predictors of 30-day cardiac events in patients with acute coronary syndrome at a community hospital.

OBJECTIVE: We sought to determine predictors of coronary events (cardiac death, acute myocardial infarction, and urgent revascularization) within 30 days after admission. METHODS: We prospectively collected data on 400 patients admitted through our emergency room for unstable angina and acute coronary syndromes. Patients with ST-segment elevation myocardial infarction and those who required thrombolysis were excluded. RESULTS: Of 383 patients who were eligible, 120 patients had coronary events within 30 days. Statistically significant variables associated with coronary events were advanced age, male sex, family history of premature coronary artery disease (CAD), diabetes mellitus, tobacco abuse, prior congestive heart failure, prior myocardial infarction, and history of CAD. Symptoms at presentation associated with cardiac events were typical angina and shortness of breath. Objective measures of ischemia associated with cardiac events were elevated troponin T, elevated creatine kinase MB, and ischemic electrocardiographic changes. Using forward stepwise regression analysis, we generated a model to predict 30-day major adverse cardiac events. The strongest predicting variable was serum troponin T (accounting for 33% of predicting r2, P < 0.001) followed by typical angina (r2 increasing to 37%), ischemic electrocardiographic changes (40%), prior CAD (42%), family history of premature CAD (44%), shortness of breath (46%), and positive creatine kinase MB (48%). The positive predictive power of the complete model was r2 = 48%, P < 0.001. CONCLUSION: Our model incorporating elements from the patient's demographic, medical history, presentation, and ischemic assessment identified 48% of patients presenting with unstable angina and acute coronary syndromes who will suffer a major adverse cardiac event within 30 days of admission. Although the strongest predictor was identified as serum troponin T, other clinical criteria offered improvement in our predictive abilities. Therefore, good initial clinical evaluation in addition to simple tests such as serum cardiac markers and electrocardiography are valuable in risk stratification of patients presenting with acute coronary syndromes and cardiac chest pain. Additional testing may be necessary to improve the positive predictive value of the model. Cardiac enzymes and electrocardiographic changes have the highest negative predictive value for occurrence of major adverse cardiac events. Identification of high-risk patients is essential to direct resources toward these patients and to avoid unnecessary costs and risk to the low-risk population.

Prevention of radiocontrast-induced nephropathy with N-acetylcysteine in patients undergoing coronary angiography.

OBJECTIVES: Acetylcysteine in patients undergoing computerized tomography with intravenous contrast reduces the incidence of acute renal dysfunction. We examined the effect of N-acetylcysteine in patients undergoing coronary angiography. METHODS: Fifty-five consecutive patients receiving 3 doses of N-acetylcysteine prior to cardiac catheterization were compared to 55 historical controls. All patients in both groups had baseline serum creatinine > 1.2 mg/dl and received intravenous hydration before and after the procedure. Serum creatinine levels at baseline and 48 hours after the procedure were compared. RESULTS: Univariate analysis of clinical variables revealed no significant differences between the groups except for a higher baseline creatinine in the treatment group (2.0 0.7 vs. 1.8 0.4 mg/dl; p = 0.04). There was no difference in the amount or type of contrast used. The mean change in creatinine after 48 hours was -0.4 0.3 versus +0.1 0.3 mg/dl for treatment and control groups (p < 0.001). In patients with baseline creatinine > 2 mg/dl, the benefit was larger (-0.4 0.4 vs. +0.5 0.3 mg/dl; p < 0.001). Multivariate analysis confirmed pre-treatment with N-acetylcysteine as an independent predictor of renal protection (p < 0.001). CONCLUSIONS: Prophylactic use of acetylcysteine prevented reduction of renal function after coronary angiography. The benefit was greater in patients with baseline serum creatinine > 2 mg/dl.

Effects of Na(+)/Ca(2+) exchanger downregulation on contractility and [Ca(2+)](i) transients in adult rat myocytes.

Postmyocardial infarction (MI) rat myocytes demonstrated depressed Na(+)/Ca(2+) exchange (NCX1) activity, altered contractility, and intracellular Ca(2+) concentration ([Ca(2+)](i)) transients. We investigated whether NCX1 downregulation in normal myocytes resulted in contractility changes observed in MI myocytes. Myocytes infected with adenovirus expressing antisense (AS) oligonucleotides to NCX1 had 30% less NCX1 at 3 days and 66% less NCX1 at 6 days. The half-time of relaxation from caffeine-induced contracture was twice as long in ASNCX1 myocytes. Sarcoplasmic reticulum (SR) Ca(2+)-ATPase abundance, SR Ca(2+) uptake, resting membrane potential, action potential amplitude and duration, L-type Ca(2+) current density and cell size were not affected by ASNCX1 treatment. At extracellular Ca(2+) concentration ([Ca(2+)](o)) of 5 mM, ASNCX1 myocytes had significantly lower contraction and [Ca(2+)](i) transient amplitudes and SR Ca(2+) contents than control myocytes. At 0.6 mM [Ca(2+)](o), contraction and [Ca(2+)](i) transient amplitudes and SR Ca(2+) contents were significantly higher in ASNCX1 myocytes. At 1.8 mM [Ca(2+)](o), contraction and [Ca(2+)](i) transient amplitudes were not different between control and ASNCX1 myocytes. This pattern of contractile and [Ca(2+)](i) transient abnormalities in ASNCX1 myocytes mimics that observed in rat MI myocytes. We conclude that downregulation of NCX1 in adult rat myocytes resulted in decreases in both Ca(2+) influx and efflux during a twitch. We suggest that depressed NCX1 activity may partly account for the contractile abnormalities after MI.

Intragastric gallstone-induced bezoar: an unusual cause of acute gastric outlet obstruction.

Bezoars are an uncommon cause of acute gastric outlet obstruction. To our knowledge, this is the first report of a bezoar formed around a gallstone that migrated to the stomach via a cholecystogastric fistula. Our patient was a 42-year-old African American woman with long-standing type 2 diabetes. We suspect that diabetic diathesis was the major factor responsible for producing the pathologic derangement of the gallbladder and stomach, which led to development of the bezoar and serious complications.