bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute-on-chronic liver failure: management and prognosis
Authors: Olson Jody C. 
Published: January 2019

Purpose of review
Hospitalizations due to complications of cirrhosis continue to rise. Patients with chronic liver disease who suffer acute decompensation [acute-on-chronic liver failure (ACLF)] often require intensive care support and are at high risk for short-term mortality. Given the high mortality rate associated with this condition is incumbent on intensive care providers who care for this patient population to have a working knowledge of ACLF with its associated complications, management strategies and prognosis.

Recent findings
Recognizing ACLF as a distinct clinical entity has gained international attention in recent years though a consensus does not exist. There has been progress on better defining this clinical entity and recent studies have begun to address the critical care needs of these patients. Additional studies are required to define the best care practices for patients with ACLF.

Summary
ACLF is a condition occurring in patients with chronic liver disease which is commonly associated with a need for intensive care support and carries a high risk of short-term mortality. Intensive care specialists must be familiar with diagnosis and management of this condition.
Implementation of Value-based Medicine (VBM) to Patients With Chronic Hepatitis C (HCV) Infection
Authors: Bush Haley , Rafiq Nila , Younossi Zobair M. 
Published: January 2019

Introduction:
With the significant clinical and economic burden of chronic HCV, effective treatment must be provided efficiently and appropriately. VBM is predicated upon improving health outcomes (clinical and quality) while optimizing the cost of delivering these outcomes. This review explores the concepts of VBM and how it can be used as a strategy for HCV eradication, using the United States as a case example. Once treated with interferon-based regimens, patients with HCV experienced low cure rates, very poor health-related quality of life (HRQoL), decreased work productivity and significant costs. In this context, the old treatment of HCV produced little value to the patient and the society. However, the development of new antiviral regimens for HCV which are free of interferon, has greatly improved treatment success rates as documented with very high cure rates and by improving patient-reported outcomes (PROs), including HRQoL. However, the short-term economic investment to deliver this curative treatment to all HCV-infected patients can be sizeable. In contrast, if one takes the long-term view from the societal perspective, these new treatment regimens can lead to savings by reducing the costs of long-term complications of HCV infection.

Conclusions:
All of the necessary tools are now available to implement strategies to eradicate HCV. The new all oral direct acting antivirals brings value to the patients and the society because it leads to improvements of clinically important outcomes. Furthermore, the costs associated with these treatment regimens can be recovered by preventing the future economic burden of HCV-complications.
Triglycerides and triglyceride-rich lipoproteins in the development and progression of atherosclerosis
Authors: Generoso Giuliano , Janovsky Carolina C.P.S. , Bittencourt Marcio S. 
Published: January 2019

Purpose of review
In this review, we intend to show the heterogenicity of the triglyceride group, including the triglyceride-rich lipoproteins and its subparticles, apolipoproteins, and its role in atherogenesis through epidemiological and genetic studies, observing the association of these various components and subclasses with subclinical atherosclerosis and cardiovascular events. Also, we reevaluated the moment of blood collection for the triglyceride measurement and its repercussion in atherosclerosis. Finally, we present the current scenario and new insights about the pharmacologic treatment of hypertriglyceridemia.

Recent findings
Recent studies have been observed, a correlation between cardiovascular disease and triglyceride components (as apolipoproteins A-V, C-I, C-III) as well as proteins involved in the metabolism pathway, such as the angiopoietin-like proteins. Also, the triglyceride-rich lipoproteins, also known as remnants, were recently associated with atherogenesis. Another important topic addressed is about nonfasting triglyceride level, which has been postulated as a better predictor of cardiovascular events than fasting collection.

Summary
Regarding hypertriglyceridemia treatment, the drug therapy was updated, as the omega-3 polyunsaturated fatty acids were tested in primary prevention as eicosapentaenoic acid and docosahexaenoic acid combination resulted in no benefit, whereas the administration of icosapent ethyl in secondary prevention and high-risk patients showed a robust decrease of the cardiovascular outcomes.
Rationally designed small molecules to prevent type 1 diabetes
Authors: Ostrov David A. , Gottlieb Peter A. , Michels Aaron W. 
Published: January 2019

Purpose of review
To review the recent findings that small ‘drug-like’ compounds block disease-specific human leukocyte antigen (HLA) molecules in type 1 diabetes (T1D).

Recent findings
The predominant genetic risk for developing T1D, the immune-mediated form of diabetes, is conferred through HLA genes. One such gene, termed HLA-DQ8, is present in 50–60% of patients with T1D and those at-risk. DQ8 presents disease-relevant peptides to T cells, which mediate tissue-specific destruction of pancreatic islets. Using a structure-based approach to evaluate the ‘druggability’ of the DQ8 molecule, methyldopa, a clinically well-established oral antihypertensive agent, was discovered to bind DQ8. Methyldopa blocked the activation of DQ8-specific T cells responding to self-antigens such as insulin but not influenza. In a proof-of-concept clinical trial (NCT01883804), methyldopa was administered to recent-onset T1D patients with the DQ8 gene that confirmed the mechanism of action and diminished inflammatory T cell responses toward insulin.

Summary
Methyldopa blocks the diabetes-specific function of HLA-DQ8, which represents a personalized medicine approach to treat the underlying autoimmunity in T1D. Clinical trials are warranted and underway to evaluate methyldopa in potentially preserving residual β-cell function in those with new onset and at risk for T1D.
Systemic treatment in elderly head and neck cancer patients: recommendations for clinical practice
Authors: Szturz Petr , Bossi Paolo , Vermorken Jan B. 
Published: January 2019

Purpose of review
Despite the constantly growing number of elderly patients with squamous cell carcinoma of the head and neck (SCCHN), the majority of clinical trials have been focusing on their younger counterparts. However, because of age-related changes and the resulting higher prevalence of frailty, senior people need an adapted evidence-based approach.

Recent findings
Recommendations presented in this article proceed from those relevant for the general patient population taking into consideration the individual process of aging. In this respect, categorization into fit, vulnerable and frail elderly patients was used to guide systemic treatment.

Summary
The fit and vulnerable subgroups with locoregionally advanced SCCHN may still benefit from curative treatment, whereas for the remaining cases only palliative measures are usually appropriate. Advanced calendar age is not a contraindication for cisplatin making part of the standard regimens in locally advanced (high-dose 3-weekly schedule concurrent with radiotherapy) and recurrent/metastatic disease (in combination with 5-fluorouracil and cetuximab). In the latter setting, modern immunotherapy with immune checkpoint inhibitors, particularly the antiprogrammed cell death protein-1 (anti-PD-1) agents nivolumab and pembrolizumab, changed clinical practice. These drugs have a favourable toxicity profile making them good candidates even for management of vulnerable patients. Regardless of the chosen strategy, attentive supportive care is of paramount importance.
Living donor liver transplantation
Authors: Goldaracena Nicolas , Barbas Andrew S. 
Published: January 2019

Purpose of review
As experience grows, living donor liver transplantation (LDLT) has become an effective treatment option to overcome the deceased donor organ shortage.

Recent findings
Donor safety is the highest priority in LDLT. Strict donor selection according to structured protocols and center experience are the main factors that determine donor safety. However, with increased experience, many centers have explored increasing organ availability within living donation by means of ABO incompatible LDLT, dual graft LDLT, and anonymous living donation. Also, this growing experience in LDLT has allowed the transplant community to cautiously explore the role of liver transplantation for hepatocellular carcinoma outside of Milan criteria and patients with unresectable colorectal liver metastases.

Summary
LDLT has become established as a viable strategy to ameliorate the organ shortage experienced by centers around the world. Improved understanding of this technique has allowed the improved utilization of live donor graft resources, without compromising donor safety. Moreover, LDLT may offer some advantages over deceased donor liver transplantation and a unique opportunity to assess the broader applicability of liver transplantation.
Understanding and managing cardiovascular outcomes in liver transplant recipients
Authors: Izzy Manhal , VanWagner Lisa B. , Lee Samuel S. , Altieri Mario , Angirekula Mounika , Watt Kymberly D. 
Published: January 2019

Purpose of review
Cardiovascular disease (CVD) is a common cause of mortality after liver transplantation. The transplant community is focused on improving long-term survival. Understanding the prevalence of CVD in liver transplant recipients, precipitating factors as well as prevention and management strategies is essential to achieving this goal.

Recent findings
CVD is the leading cause of death within the first year after transplant. Arrhythmia and heart failure are the most often cardiovascular morbidities in the first year after transplant which could be related to pretransplant diastolic dysfunction. Pretransplant diastolic dysfunction is reflective of presence of cirrhotic cardiomyopathy which is not as harmless as it was thought. Multiple cardiovascular risk prediction models have become available to aid management in liver transplant recipients.

Summary
A comprehensive prevention and treatment strategy is critical to minimize cardiovascular morbidity and mortality after liver transplant. Weight management and metabolic syndrome control are cornerstones to any prevention and management strategy. Bariatric surgery is an underutilized tool in liver transplant recipients. Awareness of ‘metabolic-friendly’ immunosuppressive regimens should be sought. Strict adherence to the cardiology and endocrine society guidelines with regard to managing metabolic derangements post liver transplantation is instrumental for CVD prevention until transplant specific recommendations can be made.
Enhanced Recovery in Mild Acute Pancreatitis
Authors: Dong Elizabeth , Chang Jonathan I. , Verma Dhruv , Butler Rebecca K. , Villarin Cecia K. , Kwok Karl K. , Chen Wansu , Wu Bechien U. 
Published: January 2019

Objectives
Acute pancreatitis (AP) is a leading cause of hospitalization for a gastrointestinal illness in the United States. We hypothesized that enhanced recovery approaches may lead to earlier time to refeeding in patients with AP.

Methods
We performed a double-blind, randomized controlled trial of patients admitted with mild AP from July 2016 to April 2017 at a tertiary medical center. Participants were randomly assigned to receive either enhanced recovery consisting of nonopioid analgesia, patient-directed oral intake, and early ambulation versus standard treatment with opioid analgesia and physician-directed diet. Primary study end point was time to oral refeeding on an intent-to-treat basis. Secondary end points included differences in pancreatitis activity scores, morphine equivalents, length of stay, and 30-day readmissions.

Results
Forty-six participants enrolled. Median age was 53.1 years, and 54.3% were female. There was significant reduction in time to successful oral refeeding in the enhanced recovery versus standard treatment group (median, 13.8 vs 124.8 hours, P < 0.001). Pancreatitis activity scores trended lower at 48 to 96 hours among patients assigned to enhanced recovery (mean, 43.6 vs. 58.9, P = 0.32). No differences found in length of stay or 30-day readmissions.

Conclusion
In this randomized controlled trial, enhanced recovery was safe and effective in promoting earlier time to refeeding in patients hospitalized with AP.
Comparative Accuracy of Tumor Size Assessment and Stage Analysis by Imaging Modalities Versus Gross Examination for Pancreatic Ductal Adenocarcinoma
Authors: Kassardjian Ari , Stanzione Nicholas , Wang Hanlin L. 
Published: January 2019

Objectives
Tumor size has been shown to be a strong predictor of patient survival in pancreatic ductal adenocarcinoma (PDAC). The aims of this study were to assess the consistency of preoperative imaging and gross examination for PDAC tumor size measurement and to evaluate the impact on T and overall tumor staging when size measurements by imaging and gross examination were different.

Methods
Patients diagnosed with PDAC who underwent pancreaticoduodenectomy or distal pancreatectomy from 2007 to 2017 were retrospectively reviewed. A total of 268 cases were included.

Results
Imaging studies underestimated tumor size in comparison with gross examination. Staging the tumors based on imaging size using the eighth edition American Joint Committee on Cancer resulted in an altered T stage in 106 cases (39.6%). There was no T-stage change in the remaining 162 cases (60.4%) despite the presence of variable size discrepancies (0.1–1.7 cm). When nodal metastases were also considered, there was no change in the overall tumor stage in most cases.

Conclusions
Although discrepancies exist between tumor size measurements by imaging modalities and gross examination, which may result in an altered T stage in a substantial number of cases, the overall tumor stage is only rarely altered.
The Benefit-Risk Balance of Nab-Paclitaxel in Metastatic Pancreatic Adenocarcinoma
Authors: Péron Julien , Giai Joris , Maucort-Boulch Delphine , Buyse Marc 
Published: January 2019

Objectives
The benefit-risk balance of 5-fluorouracil, oxaliplatin, irinotecan, and leucovorin versus gemcitabine assessed using generalized pairwise comparison was strongly positive. We sought to assess the benefit-risk balance of nab-paclitaxel plus gemcitabine using the data of the MPACT trial, as it is an alternative to 5-fluorouracil, oxaliplatin, irinotecan, and leucovorin.

Methods
This statistical method allows for the simultaneous analysis of several prioritized outcomes. The first priority outcome was survival time (overall survival). The second priority outcome was toxicity. The overall treatment effect was quantified using the overall net benefit. Multiple sensitivity analyses were performed to assess the consistency of the results according to possible patients' preferences.

Results
In this trial, 861 patients received nab-paclitaxel plus gemcitabine or gemcitabine alone. The overall net benefit favored strongly and significantly the combination group. When only large survival differences were considered clinically relevant, the net benefit was not in favor of the combination group.

Conclusions
The overall net benefit is a clinically intuitive way of comparing patients with respect to all important efficacy and toxicity outcomes. The nab-paclitaxel plus gemcitabine combination has a positive benefit-risk balance, but it might not be suitable for patients who would consider losing several months of survival to avoid a significant toxic event.
Microvessel Density and Impact of Angiogenesis on Survival of Resected Pancreatic Cancer Patients
Authors: Ntellas Panagiotis , Dadouli Katerina , Perivoliotis Konstantinos , Sogka Eleni , Pentheroudakis Georgios , Ioannou Maria , Hadjichristodoulou Christos , Tepetes Konstantinos , Mauri Davide 
Published: January 2019

Objectives
Angiogenesis plays a major role in tumor progression and metastasis; however, its role in pancreatic cancer (PC) remains unclear. The aim of the study was to explore the cumulative evidence concerning the impact of microvessel density (MVD), an estimator of angiogenesis, on resected PC patients.

Methods
A systematic review of literature and a meta-analysis of relevant reports were performed. Overall survival and disease-free survival were scrutinized.

Results
One thousand five hundred patients were analyzed. Overall survival (hazard ratio, 2.0; 95% confidence interval, 1.57–2.54; P < 0.001) and disease-free survival (hazard ratio, 1.99; 95% confidence interval, 1.24–3.2; P = 0.004) were in favor of the low-MVD group. Use of CD105 antibody and of a computerized image analysis system was found to significantly reduce the heterogeneity. Disease staging, tumor location, and grading showed significant effect on survival.

Conclusions
High-MVD expression was strongly associated with poorer survival and recurrence among resected PC patients, demonstrating a negative prognostic value. Use of CD105 antibody and of a computerized image analysis system is recommended in future studies because they reduce heterogeneity of results. The potential role of MVD as a marker to select PC patients who would benefit from antiangiogenetic treatment should be further explored in clinical trials.
Closing the Disparity in Pancreatic Cancer Outcomes
Authors: Vick Alexis D. , Hery Danielle N. , Markowiak Stephen F. , Brunicardi F. Charles 
Published: January 2019

Objectives
African Americans (AAs) have disproportionately higher incidence and lower survival rates from pancreatic cancer compared with whites. Historically, this disparity has been attributed to modifiable risk factors. Recent studies suggest that nonmodifiable aspects may also play an important role. We review these new contributions as potential targets for closing the disparity.

Methods
A PubMed search was conducted to review studies of nonmodifiable elements contributing to pancreatic cancer disparities in AAs.

Results
Several nonmodifiable risks are associated with the racial disparity in pancreatic cancer. SSTR5 P335L, Kaiso, and KDM4/JMJD2A demonstrate differential racial expression, increasing their potential as therapeutic targets. Many social determinants of health and their associations with diabetes, obesity, and the microbiome are partially modifiable risk factors that significantly contribute to outcomes in minorities. Barriers to progress include the low minority inclusion in research studies.

Conclusions
Genomics, epigenetics, the microbiome, and social determinants of health are components that contribute to the pancreatic cancer disparity in AAs. These factors can be researched, targeted, and modified to improve mortality rates. Closing the disparity in pancreatic cancer will require an integrated approach of personalized medicine, increased minority recruitment to studies, and advanced health care/education access.
Contribution of Inhibition of Protein Catabolism in Myeloma
Authors: Bianchi Giada , Anderson Kenneth C. 
Published: January 2019

AbstractMultiple myeloma (MM) is a cancer of plasma cells, characterized by abundant synthesis of monoclonal immunoglobulins and/or free light chains. Although MM remains incurable, median overall survival has considerably improved over the past 2 decades largely due to the introduction of novel agents, including proteasome inhibitors (PIs) and immunomodulatory drugs. Bortezomib, a reversible boronate PI, was the first Food and Drug Administration–approved PI in MM and subsequently mantle cell lymphoma. Carfilzomib and ixazomib, the former an irreversible epoxyketone and the latter an orally bioavailable reversible PI, have been subsequently approved in MM. Altogether, these drugs represent the first effort to disrupt protein homeostasis as a therapeutic strategy in MM. Although effective, de novo resistance is a recognized phenomenon, and acquired resistance to PI is common, prompting the development of biology-based combination therapies. Based on laboratory evidence of increased, constitutive proteotoxic stress, targeting protein catabolism with single or combination therapies is an effective strategy in MM. In this article, we review the scientific rationale and bases for therapeutic application and effectiveness of Food and Drug Administration–approved and investigational drugs targeting protein homeostasis in MM.
Smoldering Multiple Myeloma
Authors: Kapoor Prashant , Rajkumar S. Vincent 
Published: January 2019

Abstract
Smoldering multiple myeloma (SMM) is an asymptomatic, intermediate stage positioned between the plasma cell disorders of monoclonal gammopathy of undermined significance and overt multiple myeloma (MM). Although the patients with SMM have a higher risk of progression to MM in comparison to their counterparts with monoclonal gammopathy of undermined significance, their clinical course can be highly variable. The standard of care for SMM, irrespective of the risk status, continues to be observation due to paucity of high-level evidence demonstrating survival or quality-of-life benefit with early intervention. With the expanded 2014 criteria for MM utilizing biomarkers, the subset of SMM patients with 70% to 80% risk of progression at 2 years (ultra-high risk SMM) is now categorized as active MM and treated prior to the development of end-organ damage. After exclusion of this group, patients with approximately 50% risk of progression in 2 years are now considered high-risk SMM, and the value of early treatment in this subset can be established only through clinical trials. Despite its limitations, a recent phase III trial (QuiRedex) has shown survival advantage to using lenalidomide and dexamethasone doublet over observation in high-risk SMM. In this article, we review the evolving concepts in the diagnosis, risk stratification, and management of SMM.
Are 4-Drug Regimens Here to Stay? Role in Induction and Salvage Therapies
Authors: Richter Joshua , Jagannath Sundar 
Published: January 2019

Abstract
With 10 novel therapies approved across the decade, the multiple myeloma (MM) treatment paradigm continues to evolve in breadth and complexity. The current gestalt of the day has been the emergence of data to support 3-drug combinations over their 2-drug counterparts. Current guidelines and consensus statements support this approach. With the recent incorporation of monoclonal antibodies into the fray of myeloma therapy, we have begun to ask what the roles of 4-drug combinations are in both the upfront and the relapsed and refractory settings. The recent approval of daratumumab in combination with bortezomib, melphalan, and prednisone (Dara-VMP/ALCYONE) supports the role of quadruplet therapy in some patients with newly diagnosed disease who do not plan to proceed toward autologous transplant. There are a number of ongoing studies evaluating this type of strategy in both transplant-eligible and non–transplant-eligible newly diagnosed MM patients and in relapsed and refractory MM patients. Many of these seek to enhance standard-of-care treatments with the addition of monoclonal antibodies. We evaluate the historical and current data supporting the role of quadruplet- versus triplet-based therapies in MM.