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Background US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. Purpose To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). Materials and Methods In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1-4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. Results Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature ( P = .31), heart rate ( P = .92), diastolic pressure ( P = .31), or systolic pressure ( P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE ( P > .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE ( P = .02). Conclusion The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response. © RSNA, 2020.

Background: Switching antiretroviral therapy (ART) in people with HIV (PWH) can influence their risk for drug-drug interactions (DDIs). The purpose of this study was to assess changes in the incidence and severity of DDIs among PWH who switched their ART to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF)., Methods: This was a multicenter retrospective cohort study of PWH on ART and at least 1 concomitant medication (CM) who switched to BIC/FTC/TAF between 3/2018 and 6/2019. Using the University of Liverpool's HIV Drug Interaction Database, 2 DDI analyses were performed for each patient. The first assessed patients' preswitch ART regimens with their CM list. The second assessed the same CM list with BIC/FTC/TAF. Each ART-CM combination was given a score of 0 (no or potential weak interaction), 1 (potential interaction), or 2 (contraindicated interaction). A paired t test analyzed changes in total DDI scores following ART switches, and linear regression examined factors contributing to DDI score reductions., Results: Among 411 patients, 236 (57%) had at least 1 DDI present at baseline. On average, baseline DDI scores (SD) were 1.4 (1.8) and decreased by 1 point (95% CI, -1.1 to -0.8) after patients switched to BIC/FTC/TAF ( P < .0001). After adjusting for demographics, baseline ART, and CM categories, switching to BIC/FTC/TAF led to significant DDI score reductions in patients receiving CMs for cardiovascular disease, neurologic/psychiatric disorders, chronic pain, inflammation, gastrointestinal/urologic conditions, and conditions requiring hormonal therapy., Conclusions: Treatment-experienced PWH eligible to switch their ART may experience significant declines in number and severity of DDIs if switched to BIC/FTC/TAF., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer. Clinicians commonly refer to surgical therapy as resection with curative intent. However, PDA cure rates after resection remain unknown and the definition of cure remains vague. We investigated how patients (the majority undergoing resection), family members, and clinicians understand the concept of cure, to better inform discussions with patients regarding PDA prognosis., Methods: In a prospective survey, cohorts were asked to indicate the best definition of cure from three choices: 5-year survival endpoint (typically used in the literature), a biological endpoint without biochemical or radiographic signs of disease (similar to the NCI definition), or a practical endpoint where life span approximates similarly aged patients without PDA. Fleiss' kappa statistic was calculated to measure inter-rater agreement., Results: Patients, family members, and health care professionals (N = 200) agreed that renormalization of life expectancy was the preferred definition of cure in the context of pancreatic cancer. Inter-rater agreement was highest for the patient and family member groups (Fleiss' kappa 0.27 and 0.40, respectively, P < 0.001), while variability was observed between health care professionals (Fleiss' kappa 0.11, P < 0.001)., Conclusions: In all groups surveyed, the probability for a normal life expectancy is the preferred long-term metric in patients with early-staged pancreatic cancer. Renormalization of life expectancy appears to be an important therapy goal for PDA patients and it is advisable to address this topic during clinical discussions.

In the Local Health Authority (LHA) of Parma, Emilia Romagna, Italy, 16 medical homes were established between 2011 and 2014. The authors implemented a 1-year (January 1, 2015, to December 31, 2015) cross-sectional population-based design to compare utilization and processes of care between medical homes and comparison practices using the Parma LHA administrative health care database. Residents (n = 372 396) attributed to a primary care physician practicing in a medical home as of January 1, 2015, were considered exposed to medical homes. Adjusted rates of emergency department (ED) use (incidence rate ratio [IRR] = 0.86; 95% CI = 0.82-0.90), potentially avoidable ED use (IRR = 0.78; 95% CI = 0.72-0.84), and hospitalization for chronic ambulatory care sensitive conditions (ACSCs; IRR = 0.87, 95% CI = 0.78-0.97) were lower among patients in medical homes. Performance on process of care measures favored the medical home group; however, associations were generally weak. Receipt of care in medical homes in Parma LHA was associated with lower rates of avoidable ED visits and hospitalizations for chronic ACSCs.

Objectives: Polypharmacy (≥5 concurrent medications) is common among older patients with cancer (48%-80%) and associated with increased frailty, morbidity, and mortality. This study examined the relationship between polypharmacy and inpatient hospitalization among older adults with cancer treated with intravenous (IV) chemotherapy., Materials and Methods: The main data source was the Surveillance, Epidemiology, and End Results-Medicare linked files. Patients (≥65 years) were included if they were diagnosed with prostate (n = 1430), breast (n = 5490), or lung cancer (n = 7309) in 1991-2013 and received IV chemotherapy in 2011-2014. The number of medications during the six-month window pre-IV chemotherapy initiation determined polypharmacy status. Negative binomial models were used to assess the association between polypharmacy and post-chemotherapy inpatient hospitalization. The results were presented as incidence rate ratios., Results: We identified 13,959 patients with prostate, breast, or lung cancer treated with IV chemotherapy. The median number of prescription medications during the six-month window pre-IV chemotherapy initiation was high: ten among patients with prostate cancer, nine among patients with breast cancer, and eleven among patients with lung cancer. Compared to patients taking <5 prescriptions, post-chemotherapy hospitalization rate for patients with prostate cancer was 42%, 75%, and 114% higher among those taking 5-9, 10-14, and 15+ medications, respectively. Patients with breast and lung cancer demonstrated similar patterns., Conclusion: This large population-based study found that polypharmacy during the six-month window pre-IV chemotherapy is highly predictive of post-chemotherapy inpatient hospitalization. Further studies are needed to evaluate whether medication management interventions can reduce post-chemotherapy inpatient hospitalization among older patients with cancer., Competing Interests: Declaration of Competing Interest Author Name: Wm. Kevin Kelly. Research Funding for Self from Janssen, Bayer, Novartis, Genentech, Seattle Genetics, Constellation. No other authors have any conflict of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

What Is Known and Objective: Observational clinical studies of metformin for prevention and treatment of several cancer types have reported mixed findings. Although preclinical studies have suggested metformin may reduce head and neck cancer (HNC) proliferation, clinical evidence is limited. The objective of this large population-based study was to evaluate the relationship between metformin exposure following HNC diagnosis and all-cause mortality., Methods: We conducted a retrospective cohort study using the Italian Emilia-Romagna Regional administrative healthcare database, which includes demographic, hospital and outpatient prescription information for ~4.5 million residents. Included patients were followed from the first hospital discharge (index) during the study period (01/2003-12/2012) with a diagnosis of HNC. Metformin exposure and select covariates were operationalized in a time-dependent manner during follow-up. Cox proportional hazards models estimated the covariate-adjusted time-dependent association between metformin exposure and all-cause mortality., Results and Discussion: Among 7872 patients diagnosed with HNC, 708 (9.0%) were exposed to metformin after HNC diagnosis, and 3626 (46.1%) died during follow-up (median follow-up: 35.2 months). In the covariate-adjusted model, the all-cause mortality rate appeared lower (HR: 0.81, 95% CI: 0.61-1.09) among metformin exposed patients during the 2 years post-diagnosis, while the all-cause mortality rate appeared higher (HR: 1.20, 95% CI: 0.94-1.53) among exposed patients after 2 years post-diagnosis. Metformin was protective among patients ≤60 years of age (HR for the period of 0-2 years post-diagnosis: 0.22, 95% CI 0.09-0.56; HR for the period ≥2 years post-diagnosis: 0.56, 95% CI 0.26-1.22) but not in those >60 years., What Is New and Conclusion: In this population-based study of metformin in HNC, we found a modest protective association between metformin exposure and all-cause mortality in the 2-year post-diagnosis period. Age appeared to modify the association between metformin and HNC survival., (© 2019 John Wiley & Sons Ltd.)

Objective: Enhanced recovery pathways reduce length of stay and costs following lung resection. However, many fear that early discharge may lead to increased hospital readmissions. In this study, we aimed to determine whether early discharge was associated with increased readmission following anatomic lung resection., Methods: Using the lung resection database approved by our institutional review board, we identified all patients undergoing minimally invasive lobectomy and segmentectomy between January 2010 and March 2017 at our institution, where an enhanced recovery pathway is well established. Thirty-day readmissions were compared between patients with short- and average length of stay, defined as 1 to 2 days and 3 to 5 days, respectively. Multivariable logistic regression analysis of patients matched by propensity scores was performed to determine odds of 30-day readmission for each group. Significance was set at P < 0.05., Results: A total of 296 patients met inclusion criteria. Unadjusted analysis revealed a 3-fold increased rate of readmission in the group with average length of stay (9%, n = 12) versus the group with short length of stay (3%, n = 5; P < 0.01). At baseline, patients with average length of stay had increased rates of preoperative chemotherapy (13%, n = 18 vs. 4%, n = 6; P < 0.01) and radiation (12%, n = 16 vs. 3%, n = 5). Patients with average length of stay also had higher rates of lobectomy (95%, n = 127 vs. 86%, n = 140; P = 0.02) and postoperative complications (31%, n = 41 vs. 4%, n = 7; P < 0.01). On multivariable analysis, patients with average length of stay had a 2.3-fold greater odds of readmission, which was not statistically significant (OR = 2.33; 95% CI, 0.60 to 9.02; P = 0.22)., Conclusions: Early discharge following minimally invasive anatomic lung resection does not increase the risk of hospital readmission in patients treated within an enhanced recovery pathway.

Purpose: No consensus exists regarding the most effective form of pancreaticojejunostomy (PJ) following pancreaticoduodenectomy (PD). Methods: Data were gathered through the American College of Surgeons-National Surgical Quality Improvement Program, Pancreatectomy Demonstration Project. A total of 1781 patients underwent a PD at 43 institutions. After appropriate exclusions, 890 patients were analyzed. Patients were divided into duct-to-mucosa ( n  = 734, 82%) and invagination ( n  = 156, 18%) groups and were compared by unadjusted analysis. Type of PJ was included in eight separate morbidity and mortality multivariable analyses. Results: Invagination patients had higher serum albumin ( p  < 0.01) and lower body mass index ( p  < 0.01), were less likely to have a preoperative biliary stent ( p  < 0.01), and were more likely to have a soft gland ( p  < 0.01). PJ anastomosis type was not associated with morbidity but was associated with mortality (duct-to-mucosa vs. invagination, odds ratio = 0.22, p  < 0.01). Among patients who developed a clinically relevant pancreatic fistula, none of the 119 duct-to-mucosa, compared with 5 of 21 invagination, patients died ( p  < 0.01). Conclusion: Patients who undergo a PJ by duct-to-mucosa or invagination differ with respect to preoperative and intraoperative variables. When an invagination PJ leaks, there may be a greater influence on mortality than when a duct-to-mucosa PJ leaks., Competing Interests: The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) and the hospitals participating in the ACS-NSQIP are the source of the data used herein; they have not verified and are not responsible for the statistical validity of the data or the conclusions.

Background: Pulmonary infarction is an infrequent complication of pulmonary embolism. Traditionally, it has been regarded as a sign of worse outcome because ischemia can only occur by the simultaneous failure of all oxygenation sources to the area of infarct, but supporting evidence is limited., Methods: We identified 74 cases of pulmonary infarction over 5 years at a single academic center via review of radiographic reports. Contrast-enhanced chest CT scans were examined to confirm evidence of pulmonary infarction, and patient clinical characteristics and imaging results were studied., Results: Survival to discharge was high (97%). Patients most commonly presented with dyspnea (69%), chest pain (46%), and swelling or pain in the lower extremities (31%), while underlying risk factors included history of malignancy (41%) and surgery within 30 days (24%). Many patients had concurrent cardiovascular (59%) and pulmonary disease (22%). Infarction disproportionately affected the lower lobes., Conclusions: Survival after diagnosis of pulmonary infarction is comparable to uncomplicated pulmonary embolism, suggesting that outcome is not worse. While emboli occurred in multiple lobar sites, pulmonary infarction occurred most commonly in the lower lobes, suggesting unique underlying physiological mechanisms in pulmonary infarction development., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and study aims  Dietary restrictions are integral to colonoscopy preparation and impact patient satisfaction. Utilizing split-dose, lower-volume polyethylene glycol 3350-electrolyte solution (PEG-ELS), this study compared colon preparation adequacy of a low-residue diet to clear liquids using a validated grading scale. Patients and methods  This was a prospective, randomized, single-blinded, single-center non-inferiority study evaluating diet the day prior to outpatient colonoscopy. Subjects were randomized to a Low-Residue diet for breakfast and lunch, or Clears only. All subjects received split dose PEG-ELS. The primary endpoint was preparation adequacy using the Boston Bowel Preparation Scale (BBPS), with adequate defined as a score > 5. Secondary endpoints included mean BBPS scores for the entire colon and individual segments, satisfaction, adverse events, polyp and adenoma detection rates, and impact on sleep and daily activities. Results  Final analysis included 140 subjects, 72 assigned to Clears and 68 to Low-Residue. The Low-Residue diet was non-inferior to Clears (risk difference = - 5.08 %, P  = 0.04) after adjusting for age. Mean colon cleansing scores were not significantly different overall and for individual colonic segments. Satisfaction with the Low-Residue diet was significantly greater ( P  = 0.01). The adenoma detection rate was not statistically significantly different between study groups, but the number of adenomas detected was significantly greater with Clears ( P  = 0.01). Adverse events and impact on sleep and activities did not differ significantly between diet arms. Conclusions  A low-residue diet for breakfast and lunch the day prior to colonoscopy was non-inferior to clear liquids alone for achieving adequate colon cleansing when using split dose PEG-ELS.

Background/objective: Post-transplant diabetes mellitus (PTDM) is both common and associated with poor outcomes after kidney transplantation. Our objective was to examine relationships of uremia-associated inflammation and adiponectin with PTDM., Methods: Nondiabetic kidney transplant patients were enrolled with donor controls. Inflammatory cytokines and adiponectin were measured before and after transplantation. Adipose tissue was obtained for gene expression analysis. Glucose transport was quantified in vitro in C2C12 cells following cytokine exposure. The patients were monitored up to 12 months for PTDM., Results: We studied 36 controls and 32 transplant patients, of whom 11 (35%) developed PTDM. Compared to controls, plasma TNFα, IL-6, MCP-1, and CRP levels were higher in transplant patients (p < 0.01). In multivariable analysis, TNFα plasma levels before transplantation were associated with development of PTDM (OR = 2.03, p = 0.04). Visceral adipose tissue TNFα mRNA expression was higher in transplant patients than controls (fold change 1.33; p < 0.05). TNFα mRNA expression was also higher in patients who developed PTDM than in those who did not (fold change 1.42; p = 0.05), and adiponectin mRNA expression was lower (fold change 0.48; p < 0.05). The studies on the C2C12 cells demonstrated an increase in glucose uptake following exposure to adiponectin and no significant change after exposure to TNFα alone. Concomitant TNFα and adiponectin exposure blunted adiponectin-induced glucose uptake (11% reduction; p < 0.001)., Conclusion: Our in vitro and clinical observations suggest that TNFα could contribute to PTDM through an effect on adiponectin. Our study proposes that inflammation is involved in glucose regulation after kidney transplantation.

Background: Primary pancreatic lymphoma (PPL) is a rare disease, accounting for only 0.5% of all pancreatic masses. A paucity of literature exists on the epidemiology and outcomes of PPL. Here, we present a series of 523 cases of PPL obtained from the Surveillance, Epidemiology, and End Results database., Methods: Patients diagnosed with a PPL from 1973 to 2007 were identified. Data on patient and tumor characteristics as well as initial treatment with surgery or radiation were extracted. Survival rates were calculated using the Kaplan-Meier method. A multivariate analysis was performed to determine independent prognostic factors predicting mortality hazard ratios using Cox proportional hazards modeling., Results: Fifty-eight percent of patients identified were male. The median age range at diagnosis was 65 to 69 years. The most common histologic subtype in the present series was diffuse large B-cell lymphoma, which accounted for 56% of all patients. The 5-year overall survival for the group was 45%. Multivariate analysis suggests that age more than 60 years at diagnosis, race of "other" (compared with "white"), and marital status of single or widowed were predictive of increased all-cause mortality (P<0.05)., Conclusions: This represents the largest published series of patients with PPL. Age more than 60 years, female sex, and marital status of married were identified as independent prognostic factors predicting for decreased all-cause mortality.

The effect of weight loss on mortality rate is widely studied and of importance in the field of obesity. Separating the effects of intentional weight loss (IWL) from unintentional weight loss (UWL) has been a challenge. Most studies addressing this issue have used weight loss among people intending to lose weight as a surrogate of IWL. Coffey et al. (2005) [1] showed that these were not equivalent and developed a preliminary model to separate the effects of IWL from those of UWL. In this study we construct and implement Bayesian latent-variable linear models that allow the separation of the effects of IWL and UWL. The key idea of our method is to augment the unobserved UWL by using the information of observed weight loss among individuals not intending to lose weight. This data augmentation approach offers a way to estimate the effects of IWL and UWL as well as any parameters of interest. We applied our method to a real data set of rodent caloric restriction studies: our results suggest that IWL has a beneficial effect on mouse lifespan in contrast to UWL. Extensions to human data involving censored outcomes are discussed.

Studies that explore the link between weight loss among obese individuals and mortality have met with mixed results. One possible explanation is that total weight loss may have contributions from weight loss that is intentional and weight loss that is unintentional. The latter may be due to some underlying condition that has a deleterious effect on subsequent mortality. Some studies have then focused on subjects who intend to lose weight. However, in a population there is no guarantee that weight loss among these individuals is due only to their intention. This paper extends the work of Coffey et al., (2005) who treated intentional weight loss as a latent variable. In particular, the problem is reformulated using potential outcomes. This formulation more clearly identifies a nonestimable correlation that arises because of the latent variable, and it allows for the incorporation of covariate information that can tighten estimable bounds for this correlation. We show in a data set from an experiment on mice that substantial tightening of bounds is possible with a covariate that is predictive of weight loss. These bounds can then, in turn, be used to estimate bounds on a causal parameter in a linear model.

The purpose of this article is to review and project treatment procedures for areas of esthetic concern. The authors were participants in a consensus conference sponsored by ITI and held in August 2003 in Gstaad, Switzerland. This article deals with the basic prosthetic/restorative aspects in implant esthetics. It is based on a literature review performed by 16 participants from Group 2 (Buser et al) in this section of the Journal.