Single-session versus two-session placement of chest port and gastrostomy tube in patients with head and neck cancer: Is there any difference in the device-related early infection rates?

BACKGROUND: It is unknown whether placement of a chest port (port) and a gastrostomy tube (G-tube) in a single session increases the risk of the early device infections in patients with head and neck cancer (HNC) undergoing chemoradiation. PURPOSE: To compare the incidence of early (≤30 days) port and G-tube infections placed in a single session compared to two separate sessions in patients with HNC. MATERIAL AND METHODS: Between January 2012 and December 2019, 169 patients with HNC undergoing chemoradiation had a port and a G-tube placed in a single session (single-session group), while 25 had both devices placed in two separate sessions (two-session group) within 30 days of each other. The incidence of early device infections was compared between groups. Logistic regression analysis was conducted to determine if the number of sessions was a variable affecting device infections. RESULTS: A total of 6 (3%) early port infections and 13 (6.7%) early G-tube infections were identified. The two groups did not significantly differ in the incidence of early port infections (3.0%, 5/169 and 4.0%, 1/25, p = 0.59) nor early G-tube infections (7.1%, 12/169 and 4.0%, 1/25, p = 1.0). The number of sessions for device placement was not a variable affecting overall device infections in logistic regression analyses (odds ratio: 1.24, 95% confidence interval: 0.20-7.82, p = 0.82) after controlling for potential confounding variables. CONCLUSIONS: The risk of early device infections in single-session placement appeared to be the same as two-session placement in patients with HNC undergoing chemoradiation.

Progression to Cirrhosis Leads to Improvement in Atherogenic Milieu.

INTRODUCTION: The prevalence of coronary artery disease (CAD) is high among patients with cirrhosis; however, the impact of it on cardiovascular disease (CVD) is not known. The aim of the current study was to evaluate CVD events in patients with cirrhosis and impact of cirrhosis on biomarkers of atherogenesis. METHODS: The study included 682 patients with decompensated cirrhosis referred for liver transplantation (LT) evaluation between 2010 and 2017. All patients were followed until they experienced a CVD event, non-cardiac death, liver transplantation or last follow-up. To evaluate mechanistic link, patients with NASH cirrhosis were propensity matched 1:2 to non-cirrhosis NASH patients and biomarkers of atherogenic risk were compared. RESULTS: The composite CVD outcome occurred in 23(3.4%) patients after a median follow-up period of 585 days (IQR 139, 747). A strong association between presence of any CAD and CVD event was noted (HR = 6.8, 95% CI 2.9, 15.9) that was independent of age, gender, BMI, and MELD score. In competing risk model, the combined rate of LT and non-cardiac was significantly higher when compared to the rate of CVD events. Marker of insulin resistance and inflammation-related markers were similar in patients with and without cirrhosis. Patients with cirrhosis were more likely to have reduced VLDL, sdLDL-C, LDL-C, and triglycerides. Interestingly, patients with cirrhosis had an increase in serum HDL-2, the anti-atherogenic lipoprotein, and adiponectin, a protective serum adipokine. CONCLUSION: The risk of CVD events in patients with cirrhosis is low and may potentially be due to improvement in markers of atherogenic risk.

Association Between Lipoprotein Particles and Atherosclerotic Events in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease,1 is independently associated with increased risk of cardiovascular disease (CVD), which is the leading cause of mortality in patients with NAFLD.2 This is likely caused by the centrality of the liver in lipid homeostasis. Prior cross-sectional studies have shown that NAFLD is associated with perturbations in lipid profile and atherogenic lipoprotein subparticles.3 Although statins improve lipid profile and CVD-associated mortality, residual CVD risk has been demonstrated in major statin trials.4,5 A key contributor to this residual risk is the limited ability of the standard lipid profile to precisely quantify atherogenic lipoprotein subparticles, such as small dense low-density lipoprotein (sdLDL), which might confer higher atherogenic risk. There are currently no studies evaluating the longitudinal impact of sdLDL on atherosclerotic events in NAFLD. Thus, we conducted a prospective study in patients with histologically confirmed NAFLD to better define the relationship among NAFLD, residual CVD risk, and sdLDL.

Office-Based Weight Loss Counseling Is Ineffective in Liver Transplant Recipients.

BACKGROUND: Weight gain after liver transplantation (LT) is a predictor of major morbidity and mortality post-LT; however, there are no data regarding weight loss following LT. The current study evaluates the effectiveness of standard lifestyle intervention in LT recipients. METHODS: All adult LT recipients with body mass index (BMI) ≥ 25 kg/m2 who followed up in post-LT clinic from January 2013 to January 2016 were given standard lifestyle advice based on societal recommendations which was reinforced at 24 weeks. Patients were followed for a total of 48 weeks to assess the impact of such advice on weight. Primary outcome was achieving weight loss ≥ 5% of the body weight after 48 weeks of follow-up. RESULTS: A total of 151 patients with 86 (56.0%) overweight and 65 (44.0%) obese patients were enrolled in the study. The mean BMI at baseline increased from 30.2 ± 3.7 to 30.9 ± 4.3 kg/m2 at 48-week follow-up (p = 0.001). Over the course of study, 58 (38.4%) patients lost any weight and weight loss greater than 5% and 10% occurred in only 18 (11.9%) and 8 (5.3%) of the entire cohort, respectively. Higher level of education was associated with increased likelihood of weight loss (OR 9.8, 95% CI 2.6, 36.9, p = 0.001), while nonalcoholic steatohepatitis as etiology of liver disease (HR 3.7, 95% CI 1.4, 9.7, p = 0.007) was associated with weight gain. CONCLUSION: The practice of office-based lifestyle intervention is ineffective in achieving clinically significant weight loss in LT recipients, and additional strategies are required to mitigate post-LT weight gain.

The Impact of Coronary Artery Disease and Statins on Survival After Liver Transplantation.

Cardiovascular disease (CVD) is a major contributor to longterm mortality after liver transplantation (LT) necessitating aggressive modification of CVD risk. However, it is unclear how coronary artery disease (CAD) and the development of dyslipidemia following LT impacts clinical outcomes and how management of these factors may impact survival. Patients undergoing LT at Virginia Commonwealth University from January 2007 to January 2017 were included (n = 495). CAD and risk factors in all potential liver transplantation recipients (LTRs) over the age of 50 years were evaluated via coronary angiography. The impact of pre-LT CAD after transplantation was evaluated via a survival analysis. Additionally, factors associated with new-onset dyslipidemia, statin use, and mortality were assessed using multiple logistic regression or Cox proportional hazards models. The mean age of the cohort was 55.3 ± 9.3 years at the time of LT, and median follow-up was 4.5 years. CAD was noted in 129 (26.1%) patients during the pre-LT evaluation. The presence or severity of pre-LT CAD did not impact post-LT survival. Dyslipidemia was present in 96 patients at LT, and 157 patients developed new-onset dyslipidemia after LT. Statins were underused as only 45.7% of patients with known CAD were on therapy. In patients with new-onset dyslipidemia, statin therapy was initiated in 111 (71.1%), and median time to initiation of statin therapy was 2.5 years. Statin use conferred survival benefit (hazard ratio, 0.25; 95% confidence interval, 0.12-0.49) and was well tolerated with only 12% of patients developing an adverse event requiring the cessation of therapy. In conclusion, pre-LT CAD did not impact survival after LT, potentially suggesting a role of accelerated atherosclerosis that may not be captured on pre-LT testing. Although statin therapy confers survival benefit, it is underused in LTRs.

Clinical Predictors of Port Infections in Adult Patients with Hematologic Malignancies.

PURPOSE: To identify clinical predictors of port infections in adult patients with hematologic malignancies. MATERIALS AND METHODS: A retrospective chart review identified 223 adult patients (age ≥ 18 y) with hematologic malignancies, including lymphoma (n = 163), leukemia (n = 49), and others (n = 11), who had a port placed from 2012 to 2015. Early (< 30 d after port placement) and overall port infections (bloodstream and site infections) were recorded. To elucidate clinical predictors for early and overall port infections, proportional subdistribution hazard regression (PSHREG) analyses were conducted with variables including patients' demographics, medications used, laboratory data, and port characteristics. RESULTS: Total duration of follow-up was 83,722 catheter-days (median per patient, 274 catheter-days). Early and overall port infections were identified in 8 (3.6%) and 26 (11.7%) patients, respectively. Early and overall infection rates were 1.2 and 0.3 infections/1,000 catheter-days, respectively. Backward stepwise multivariate PSHREG analyses identified hypoalbuminemia (< 3.5 mg/dL) at the time of port placement (hazard ratio = 5.03; 95% confidence interval, 1.14-22.16; P = .03) and steroid use (> 30 d cumulatively during follow-up period) (hazard ratio = 3.41; 95% confidence interval, 1.55-7.47; P = .002) as independent risk factors for early and overall port infections, respectively. CONCLUSIONS: In adult patients with hematologic malignancies, hypoalbuminemia at the time of port placement was a clinical predictor for early port infections, whereas steroid use was a clinical predictor for overall port infections.

Transfer of PAMAM dendrimers across human placenta: prospects of its use as drug carrier during pregnancy.

Dendrimers offer significant potential as nanocarriers for targeted delivery of drugs and imaging agents. The objectives of this study were to evaluate the transplacental transport, kinetics and biodistribution of PAMAM dendrimers ex-vivo across the human placenta in comparison with antipyrine, a freely diffusible molecule, using dually perfused re-circulating term human placental lobules. The purpose of this study is to determine if dendrimers as drug carriers can be used to design drug delivery systems directed at selectively treating either the mother or the fetus. The transplacental transfers of fluorescently (Alexa 488) tagged PAMAM dendrimer (16 kDa) and antipyrine (188 Da) from maternal to fetal circulation were measured using HPLC/dual UV and fluorescent detector (sensitivity of 10 ng/mL for dendrimer and 100 ng/mL for antipyrine respectively). C(max) for the dendrimer-Alexa (DA) in maternal perfusate (T(max)=15 min) was 18 times higher than in the fetal perfusate and never equilibrated with the maternal perfusate during 5.5 h of perfusion (n=4). DA exhibited a measurable but low transplacental transport of 2.26±0.12 µg/mL during 5.5h, where the mean transplacental transfer was 0.84±0.11% of the total maternal concentration and the feto-maternal ratio as percent was 0.073%±0.02. The biochemical and physiological analysis of the placentae perfused with DA demonstrated normal function throughout the perfusion. The immunofluorescence histochemistry confirmed that the biodistribution of DA in perfused placenta was sparsely dispersed, and when noted was principally seen in the inter-villous spaces and outer rim of the villous branches. In a few cases, DA was found internalized and localized in nuclei and cytoplasm of syncytiotrophoblast and inside the villous core; however, DA was mostly absent from the villous capillaries. In conclusion, the PAMAM dendrimers exhibited a low rate of transfer from maternal to the fetal side across the perfused human placenta, which is similar to other investigations of large macromolecules, e.g., IgG. These overall findings suggest that entry of drugs conjugated to polymers, i.e., dendrimers, would be limited in their transfer across the human placenta when compared to smaller drug molecules alone, suggesting novel methods for selectively delivering therapeutics to the pregnant woman without significant transfer to the fetus, especially since the half life of the dendrimer in blood is relatively short.